Category: Pneumonia

Abstract

Streptococcus pneumoniae is a bacteria (major one) that causes deadly disease named pneumonia. It majorly affects the lung portion. Alveoli is an air sac present in the lungs where the exchanging of oxygen from the lung to the body and exhaling carbon dioxide (CO2) takes place first. The air sac gets filled with fluids, pus, etc which causes inflammation that leads to difficulty in breathing. Nearly a million adults were suffered from this deadly disease. Most of the developed countries also get panicked due to this disease. The initial step in treating pneumonia is to take an x-ray of the chest region. Only minor symptoms are visible in X-ray which is very difficult to interpret. So, it is done only by experts, not by ordinary physicians. The present world gets automated day by day so this problematic pneumonia detection requires automation. Applying deep learning in pneumonia detection will help to get rid off this problem. The proposed idea is to use a deep learning approach called Faster region convolutional neural network (Faster RCNN) instead of analyzing the whole chest x-ray image only the lung region is analyzed.

Keywords—FASTER RCNN; deep learning; Pneumonia; x-ray

I. Introduction

Pneumonia is a deadly lung disease caused by bacteria, fungi, and viruses. The main part of the lung is alveoli which is responsible for the exchanging oxygen (O2) from lung to body and exhaling carbon dioxide (CO2). This alveoli an air sac gets infected by this pneumonia diseases. The air sac gets filled with fluid and also suffers from inflammation. Rising in body temperature (fever), cold, repetitive cough, difficulty in breathing, and frequent tiredness are indications of pneumonia. The indications along with colored sputum i.e., green, bloody sputum or yellowish confirm pneumonia infection. Sputum color indicates the severity of the disease. Based on NCBI pneumonia comes under two types namely community-acquired pneumonia (disease acquired in the home) and nosocomial pneumonia (disease acquired in the hospital). Treating pneumonia mainly involves taking an x-ray of the chest area further diagnosis may require CT scan, MRI scan, ultrasound of the chest depending upon physician treating techniques. Mostly x-rays were used because it is cost-effective and affordable for all class of people. The main obstacle involved here is interpreting x-ray which is not as easy as normal x-rays taken from non-complicated body parts.

So the interpretation of x-ray requires experts not by all physicians. Already previous works were done on using convolutional neural network but all those were implemented using traditional CNN techniques which require high computational cost and involves analyzing unwanted x-ray portions. The proposed idea is to automate pneumonia detection using a deep learning approach named FASTER RCNN which analyses only the desired portion using region of interest (ROI) avoids unnecessary portions in a chest x-ray.

II. Related works

The deep learning technique was mainly used for object detection, facial recognition related applications. The previous related work was done on CNN (convolutional neural network) using Xception and vgg16 network by Enes AYAN and Halil Murat ÜNVER. A comparative research study was done by them. Parameters like training time, speed, and accuracy were measured in previous work.

But theses CNN techniques were replaced by new methods presently. The previous work was not produced notable results only comparative research was done. Layers used in previous work were increased not concentrated new logic. The dataset was classified as only two classes namely pneumonia affected and not pneumonia affected no deeper analysis was done. Pneumonia x-ray shows only slight variations like opaqueness, inflammation and not normal these variations help in accurate detection. The CNN major limitation is that it does not encode object position and orientation. So it leads to a waste of computational cost because x-ray image contains neck, shoulder portion these were not required for analyzing pneumonia.

III. Materials and methods

A. Dataset and data preprocessing

In this research, the pneumonia x-ray image dataset was collected from the Kaggle platform consists of around 26000 images in DCM format and a CSV file with a bounding box and patient information. This dataset was published under RSNA pneumonia detection challenge in Kaggle platform. Around 4000 images were used for this study and these images were classified as three classes namely 1. Lung opacity 2. Normal 3. Not normal. Figures (Fig.1, Fig.2, Fig.3) for respective categories were mentioned for some images, bounding boxes were drawn manually using the LabelImg tool. The XML file produced by LabelImg tool was converted to CSV file using python xml_to_csv program. All x-ray images were in DCM format and these images were converted to JPG format using DICOM converter software. Dataset images were in 1024 X 1024 dimension and the desired region for each image was available in the Kaggle platform and for some images desired bounding coordinates were drawn manually and those bounding box values were updated in CSV file to train images.

Fig.1. Normal

Fig.2. Not normal Fig.3. Lung opacity

B. Faster RCNN architecture

One of the deep learning techniques is FASTER RCNN (Region convolutional neural network) that this method has an important advantage i.e., uses RPN (Region proposal network). The normal CNN layers (Convolutional, ReLu, Pooling, and Fully connected layer) were involved in this method followed by some additional features that play a major role here. RPN is a major player produces a number of proposals from the feature map which was the output of CNN layers. RPN uses classifier and regressor which tells whether the particular proposal is the desired one or background. The proposals are called anchors. After ROI (region of interest) pooling was applied to produce a fixed-size feature map and then the SoftMax layer and regressor suggest bounding boxes. The pros of this method are it avoids selective search and avoids feeding of 2000 regions for each layer. In this study, a faster RCNN inception v2 coco model were used to train the dataset. Pneumonia analysis mainly insists on the lung portion where only major interpretation takes place so RCNN plays a major role by taking only the desired area or region for analysis. Usually, an x-ray of chest contains neck, shoulder region those all are not required in the analysis. This method is an apt one for analyzing pneumonia by using all parameters efficiently. Figure 4 represents architecture of faster RCNN. In figure 4 four CNN layers were involved namely convolutional, ReLu, pooling, and fully connected layer. All these layers produce a feature by interpreting from the input x-ray image and RPN suggests proposals from the input image and then region of interest pooling applied to make all proposals to a fixed size. After that classifier tells whether the particular part infected with pneumonia or not.

Fig.4.FASTER RCNN ARCHITECTURE

C. Model and device

In this study, a faster RCNN inception v2 coco model were used to train the dataset. TensorFlow library was used along with a faster RCNN pretrained model to train the dataset. TensorFlow has its pros such as easy error debugging, graph notations, easy library management, ease to extend and pipelining support were tremendous. The library was updated regularly so it will be fruitful for developing projects. Google colab a free cloud service that offers free GPU to develop deep learning projects with major library support. The specifications were followed by 1xTesla K80 12GB GDDR5 VRAM with CUDA support. Dataset was trained using Google colab to avoid unnecessary training problems.

D. Experimentation results

In this part, training and techniques were discussed. The dataset was trained using faster RCNN inception v2 coco which is an open-source model and the TensorFlow library was used. All images were in 1024 X 1024 dimensions to avoid low-quality image problems the images were used as it is and no images were compressed and the images used are taken from RSNA pneumonia detection challenge. The threshold value for training was set to around 20000 steps to maintain a decent loss percentage. Training loss and RPN loss were illustrated graphically using tensorboard. To reduce the loss percentage number of iterations were carried out until the loss value comes under 0.099. Faster RCNN requires training time a little more compared with other deep learning techniques. The main problem faced was more training time required. Training images around 4000 were used and test images were around 1000 randomly picked from the dataset. Images were classified into three classes lung opacity, normal and not normal. Lung opacity and not normal indicates pneumonia infection and normal represents free from pneumonia infection. Random images were tested and checked whether it correctly classifies or not. Figure 5 represents lung opacity i.e., pneumonia affected and figure 6 represents normal i.e., free from pneumonia.

Fig.5. This image was classified by Faster RCNN shows that person affected by pneumonia (Lung opacity class).

Fig.6. This image was classified by Faster RCNN shows that person free from pneumonia (Normal class).

IV. Conclusion

This paper provided a solution to automate pneumonia detection from x-ray images using faster RCNN without depending on physician analysis. This work not fully replace the need for physician analysis but helps in analyzing the pneumonia. The results were obtained using the Faster RCNN inception v2 coco model. Future work is based on analyzing pneumonia using x-ray along with person-environment and body physical conditions.

V. References

1. E. Ayan and H. M. Ünver, ‘Diagnosis of Pneumonia from Chest X-Ray Images Using Deep Learning,’ 2019 Scientific Meeting on Electrical-Electronics & Biomedical Engineering and Computer Science (EBBT), Istanbul, Turkey,2019, pp.1-5.
2. B. Li, G. Kang, K. Cheng, and N. Zhang, ‘Attention-Guided Convolutional Neural Network for Detecting Pneumonia on Chest X-Rays,’ 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Berlin, Germany, 2019, pp. 4851-4854.
3. S. R. Islam, S. P. Maity, A. K. Ray and M. Mandal, ‘Automatic Detection of Pneumonia on Compressed Sensing Images using Deep Learning,’ 2019 IEEE Canadian Conference of Electrical and Computer Engineering (CCECE), Edmonton, AB, Canada, 2019, pp. 1-4.
4. Stephen, Okeke & Sain, Mangal & Maduh, Uchenna & Jeong, Doun. (2019). An Efficient Deep Learning Approach to Pneumonia Classification in Healthcare. Journal of Healthcare Engineering. 2019. 1-7. 10.1155/2019/4180949.
5. D. Varshni, K. Thakral, L. Agarwal, R. Nijhawan and A. Mittal, ‘Pneumonia Detection Using CNN based Feature Extraction,’ 2019 IEEE International Conference on Electrical, Computer and Communication Technologies (ICECCT), Coimbatore, India, 2019, pp. 1-7.
6. Jaiswal, Amit & Tiwari, Prayag & Gupta, Deepak & Khanna, Ashish & Rodrigues, Joel. (2019). Identifying Pneumonia in Chest X-Rays: A Deep Learning Approach. Measurement. 145. 10.1016/j.measurement.2019.05.076.

Chapter 1. Introduction

1.1 Background

Acute Respiratory Infections (ARTIs) in infants and young children, mostly under 5 is one of the most distinct and dominant causes of mortality worldwide. Evidently, a significant portion of these casualties are caused by pneumonia which is a lower respiratory tract infection. According to a recent estimation, approximately 2 million children die every year globally (Levine, Foundation, & Dinleyici, 2010) on account of this detrimental condition and that is almost 19% of total children mortality rate. Nevertheless, this enumeration is more protrusive for Sub-Saharan Africa and South Asia (Nga Tong, BA, 2013)

Figure 1: Global Distribution of cause-specific mortality in children. (Ranganathan & Sonnappa, 2009)

Pneumonia generally occurs in lungs and it is basically the inflammation of lungs sac due to infection. A person having pneumonia suffer from relentless chest pain while breathing or coughing and the fluid or pus build up in alveoli of lungs causes some complications including limitations in oxygen intake which originates shortness of breath followed by fever, chills, and fatigue. However, more severe and life threatening conditions include sepsis, empyema, and pleural effusion or para-pneumonic effusion.

1.2 Types of Pneumonia Infection

Pneumonia is primarily categorized either as community or nosocomial pneumonia. The community-acquired pneumonia is the most common one and it generally occurs in the non-hospital patients. On the other hand, nosocomial infection is contracted by hospitalized patients in healthcare settings which involves ‘Hospital Acquired Pneumonia (HAP)’ and ‘Ventilator acquired pneumonia (VAP)’. Pneumonia is also classified based on the affected area and the way through which the inflammation occurs. These usually comprises of – bronchopneumonia (develops in bronchi), lobar pneumonia (emanates intra-alveolar space), interstitial pneumonia (permeate interstitial tissue in alveoli), lipoid pneumonia (augmentation of fat or lipid particles into the lungs), and aspiration pneumonia (due to insufflating toxic substances). Notably, a broad range of microbes including virus, bacteria, and fungi are held accountable for varying types of pneumonia and on this ground pneumonia are of three types- bacterial, viral, and fungal pneumonia.

1.2.1 General Classification

The most common classification of Pneumonia is based on exposure to pathogens which involves Community-acquired Pneumonia (CAP) and Nosocomial (Arshad, Fasanya, Cheema, & Singh, 2016).

1.2.1.1 Community-Acquired Pneumonia

CAP is infection of pulmonary parenchyma and commonly occurs in patients not residing in hospital facility. It is the most prevailing form of pneumonia and incurred from community. A current assessment shows that every 40 out of 1000 cases of pneumonia infection is caused by CAP (America, America, & McIntosh, 2002) Patients develops CAP mostly because of bacterial infection. However, some atypical pathogens also give rise to CAP.

Table 1. Microbial Pathogens Responsible for CAP

Microbial agents/

Cause

Prevalence (%)

North American Studies

Prevalence (%)

British Thoracic Society Studies

Bacteria

Streptococcus pneumoniae

Haemophilus influenzae

Staphylococcus aureus

Gram-negative bacilli

Klebsiella Pneumoniae

Miscellaneous

20–60

3–10

3–5

3–10

15-20

3–5

60–75

4–5

1–5

Rare

—

—

Atypical agents

Legionella

Mycoplasma pneumoniae

Chlamydia pneumonia

Chlamydia trachomatis

Chlamydia psittaci

Coxiella brunette

10–20

2–8

1–6

4–6

—

2–5

5–18

—

Viruses

Ureplasma urealyticum

Pnumocistic carinii

Herpes Simplex virus

Hantavirus

Rhinovirus

Adenovirus

Haemophilus influenza type B

Respiratory syncytial virus

2-15

8-16

Aspiration

6-10

—

Collected from: (New, Journal, & Medicine, 1995) & (America et al., 2002)

1.2.1.2 Nosocomial Pneumonia

Nosocomial pneumonia infection on the other hand is caused by residence in long term care hospital facility. Patients generally get contracted by nosocomial infection within 48-72 hours after being admitted. Nosocomial pneumonia infection are of two types – Ventilator-Associated Pneumonia (VAP) and Hospital Acquired/ Healthcare-Associated Pneumonia (HAP) and both the types are generally caused by bacteria.

1.2.1.2.1 Ventilator Acquired Pneumonia

VAP- the patients admitted into the Intensive Care Unit (ICU) are at great risk for acquiring VAP. Depending on the ICU setting, etiology varies from patients to patients. Nonetheless, demographics shows that almost 28% patients receiving Mechanical Ventilation (MV) or any other respiratory support including endotracheal intubation and nasogastric tubes are contracted with VAP frequently (Asensio et al., 2000), (Chastre & Fagon, 2002).

1.2.1.2.2 Hospital-Acquired Pneumonia

HAP is the highest leading cause of death among the other nosocomial infections – Urinary Tract Infection (UTI), Surgical Site Infection (SSI), Blood Stream Infection (BSI), etc. (Gaynes & Edwards, n.d.). Several factors are associated with HAP, including, invasive medical or surgical procedures, peripheral venous catheterization, single-room stay of patients of multiple pathological conditions, roll boards, contact with healthcare workers, etc. (Asensio et al., 2000),(Gaynes & Edwards, nd.), (Lautenbach et al., 2001).

1.2.2 Anatomical Classification

Considering the location of infection, pneumonia is subdivided into three categories- lobar pneumonia, bronchopneumonia, and interstitial pneumonia.

1.2.2.1 Lobar Pneumonia

Lobar Pneumonia is characterized by accumulation of exudates in the intra-alveolar space, especially in one distinct lobe. It is also recognized as non-segmental pneumonia or focal non-segmental pneumonia. Most probable causative agent of lobar pneumonia is Streptococcus pneumonia known otherwise as pneumococcus. In lobar pneumonia we can see fluid-filled spaces that move from alveoli to alveoli until it occupies the whole lobe essentially. Therefore, it starts distally and spreads throughout the lobe. The progression of lobar pneumonia occurs in four stages- first congestion- which is alveolar edema followed by bacterial proliferation, then red hepatization- inflation of hemorrhagic exudates, grey hepatization- that is the accretion of suppurative alveolar exudates containing fibrin and finally resolution which is the processing of residual exudates. Severe complications of this class of pneumonia includes bacteremia and multi-organ infection.(Urinary & Dis-, 1930)

1.2.2.2 Bronchopneumonia

The term bronchopneumonia is generally used for the pneumonia infection that is significantly located in bronchi. It can infect in patches throughout the respiratory tract. Here, the congestion begins proximally from bronchioles and move toward the alveoli. Due to the pathophysiological similarities of bronchopneumonia with the lobar pneumonia, it is often leads to misdiagnosis or significant error in treatment plan. (Adolescence, 1933)

1.2.2.3 Interstitial Pneumonia

Interstitial pneumonia is characterized by progressive scarring in lungs. It permeates interstitial tissue in alveoli. The symptoms of infection includes fibrosis and inflammation. It is also termed as ‘cryptogenic fibrosing alveolitis’ (Turner-Warwick, Burrows, & Johnson, 1980). Interstitial pneumonia is only diagnosed when more acute disease supervenes and bring the patient to medical attention.(Inoue et al., 2003)

1.2.3 Etiological classification

Etiologically pneumonia is classified into – bacterial, viral and fungal pneumonia depending on the causative agents. However, the bacterial infections are more prevalent.

1.2.3.1 Bacterial Pneumonia

In bacterial pneumonia, bacteria causes the lung’s air sacs to become inflate and filled with pus, fluid and cellular debris. Bacterial pneumonia can be both mild and serious and it can eventually lead to total respiratory failure and even death. The severity of this type of pneumonia depends on the strength of the bacteria and how quickly the patient is diagnosed and treated. A cough with thick yellow, green or blood tinged mucus, severe chest pain along with fever can be the primary symptoms suggestive to bacterial infection (Virkki et al., 2002)

Streptococcus pnemoniae, Staphylococcus aureus, Mycobacterium tuberculosis, Haemophilus influnzae (type B) and Klebsiella pneumoniae are some of the common bacterial causative agents. (America et al., 2002)

Figure 2. Invading bacteria rate. Collected from:(Jones, 2010)

1.2.3.2 Viral Pneumonia

According to a recent study about 200 million cases of viral pneumonia occur every year. (Ruuskanen, Lahti, Jennings, & Murdoch, 2011). Viral pneumonia as suggested by the name is caused by virus. It occurs mostly on the immuno-compromised patients. Viral pneumonia is induced by rhinovirus, adenovirus, parainfluenza viruses1,2,3, influenza virus (A and B) and respiratory syncytial virus mostly (America et al., 2002). However, some other significant agents includes-

• Human meta-pneumovirus
• Human bocavirus
• Coronavirus types 229E, OC43, NL63, HKU1, SARS
• Enteroviruses
• Varicella-zoster virus
• Hantavirus
• Parechoviruses
• Epstein-Barr virus
• Human herpesvirus 6 and 7
• Herpes simplex virus
• Mimivirus
• Cytomegalovirus
• Measles etc. (Ruuskanen et al., 2011)

1.2.3.3 Fungal Pneumonia

Fungal pneumonia is mediated by fungus. In individuals with a normal immune system, fungi are a rare cause of pneumonia and often it’s regional. It is induced by Cryptococcus, Histoplasma, and coccidioides predominantly.

1.3 Clinical Symptoms and risk factors of Pneumonia

Usually the symptoms of pneumonia includes cough with or without bloody sputum which is the colored mucus. Again, as lungs are filled with exudates due to fluid buildup, oxygen intake by the lungs become significantly lower which ultimately causes dyspnea-shortness of breath followed by chest pain. Also, often there are systematic symptoms including fever and fatigue. Some generalized and well known risk factors of pneumonia are- being hospitalized, having a history of smoking and also, use of proton pump inhibitors has been recently associated with development of pneumonia (Gulmez et al., 2007). Additionally, having pulmonary diagnosis such as COPD (Chronic Obstructive Pulmonary Disorder) is a big risk factor. Impaired immune system, alcohol abuse, IV drug use and some neurological injuries also have great impact.

1.4 [Diagnosis of Pneumonia

Entrenched upon the symptoms, general diagnosis of pneumonia is usually done. Typical ways of diagnosing are- chest x-ray, differential diagnosis, having an ultrasound of lungs, microbiological diagnosis through blood culture etc. The most trivial form diagnosis is the chest x-ray and a usual chest x-ray of bronchopneumonia typically shows patchy areas that are spread out throughout the lungs. In atypical or interstitial pneumonia the pattern is also often spread throughout the lungs. However, in this case, it is often concentrated in the perihilar region of lungs and looks reticular, meaning there will be more line shaped opacities visible in a chest x-ray. In a lobar pneumonia, the fluid is localized to a single lobe or a set of lobes. Another way to detect lobar pneumonia, though, is to look for dullness to percussion which suggests that there is a lung consolidation. There is also tactile vocal fremitus which is when you feel more vibrations from a patient’s chest after they repeat certain phrases which is because sound travels better through the fluid filled consolidate tissue than air-filled healthy tissues. Late inspiratory crackles can also be heard along with bronchial breath sounds, bronchophony, and egophony.

References

1. Adolescence, B. I. N. (1933). Epidemic Hemolytic.
2. America, N., America, N., & McIntosh, K. (2002). in C Hildren. The New England Journal of Medicine, 346(6), 429–437. https://doi.org/10.1056/NEJMra011994
3. Arshad, H., Fasanya, A., Cheema, T., & Singh, A. C. (2016). Acute pneumonia. Critical Care Nursing Quarterly, 39(2), 148–160. https://doi.org/10.1097/CNQ.0000000000000108
4. Asensio, A., Oliver, A., González-Diego, P., Baquero, F., Claudio Pérez-Díaz, J., Ros, P., … Cantó, R. (2000). Outbreak of a Multiresistant Klebsiella pneumoniae Strain in an Intensive Care Unit: Antibiotic Use as Risk Factor for Colonization and Infection. In Clinical Infectious Diseases (Vol. 30). Retrieved from https://academic.oup.com/cid/article-abstract/30/1/55/323745
5. Chastre, J., & Fagon, J. (2002). State of the Art Ventilator-associated Pneumonia. Am J Respir Crit Care Med, 165(23), 867–903. https://doi.org/10.1164/rccm.2105078
6. Gaynes, R., & Edwards, J. R. (n.d.). Overview of Nosocomial Infections Caused by Gram-Negative Bacilli. Retrieved from https://academic.oup.com/cid/article-abstract/41/6/848/2022258
7. Gulmez, S. E., Holm, A., Frederiksen, H., Jensen, T. G., Pedersen, C., & Hallas, J. (2007). Use of proton pump inhibitors and the risk of community-acquired pneumonia: A population-based case-control study. Archives of Internal Medicine, 167(9), 950–955. https://doi.org/10.1001/archinte.167.9.950
8. Inoue, A., Saijo, Y., Maemondo, M., Gomi, K., Tokue, Y., Kimura, Y., … Nukiwa, T. (2003). Severe acute interstitial pneumonia and gefitinib. Lancet, 361(9352), 137–139. https://doi.org/10.1016/S0140-6736(03)12190-3
9. Jones, R. N. (2010). Microbial Etiologies of Hospital‐Acquired Bacterial Pneumonia and Ventilator‐Associated Bacterial Pneumonia. Clinical Infectious Diseases, 51(S1), S81–S87. https://doi.org/10.1086/653053
10. Lautenbach, E., Strom, B. L., Bilker, W. B., Baldus Patel, J., Edelstein, P. H., & Fishman, N. O. (2001). Epidemiological Investigation of Fluoroquinolone Resistance in Infections Due to Extended-Spectrum b-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae. Retrieved from https://academic.oup.com/cid/article-abstract/33/8/1288/345145
11. Levine, O. S., Foundation, M. G., & Dinleyici, E. C. (2010). Pneumonia : The Forgotten Killer Review / Derleme Pneumonia : The Forgotten Killer Pnömoni : Unutulmuş Katil. (January 2014), 2–4.
12. New, T. H. E., Journal, E., & Medicine, O. F. (1995). Current concepts community-acquired pneumonia. 222, 1618–1624.
13. Nga Tong, BA, M. (2013). Background Paper 6.22 Pneumonia. “A Public Health Approach to Innovation,” (May), 7–8. Retrieved from http://www.who.int/medicines/areas/priority_medicines/BP6_22Pneumo.pdf
14. Ranganathan, S. C., & Sonnappa, S. (2009). Pneumonia and Other Respiratory Infections. Pediatric Clinics of North America, 56(1), 135–156. https://doi.org/10.1016/j.pcl.2008.10.005
15. Ruuskanen, O., Lahti, E., Jennings, L. C., & Murdoch, D. R. (2011). Viral pneumonia. The Lancet, 377(9773), 1264–1275. https://doi.org/10.1016/S0140-6736(10)61459-6
16. Turner-Warwick, M., Burrows, B., & Johnson, A. (1980). Cryptogenic fibrosing alveolitis: Clinical features and their influence on survival. Thorax, 35(3), 171–180. https://doi.org/10.1136/thx.35.3.171
17. Urinary, I. N. T. H. E., & Dis-, H. (1930). Patients Suffering. 409–421.
18. Virkki, R., Rikalainen, H., Svedström, E., Juven, T., Mertsola, J., & Ruuskanen, O. (2002). Differentiation of bacterial and viral pneumonia in children. Thorax, 57(5), 438–441. https://doi.org/10.1136/thorax.57.5.438

Learning objectives:

On completion of this case study, the student/reader will be able to:

• Describe the etiology of Streptococcus pneumonia infection.
• Explain the clinical manifestations of Streptococcus pneumonia infections.
• Identify available treatment options and interventions to prevent Streptococcus pneumonia.

History:

A 54-year-old white male was seen in the emergency department. He gave a history of homelessness and chronic alcoholism. His symptoms included fever, chills, and a deep productive cough. The patient was hospitalized for 3 days. The patient possibly has a bacterial infection due to the high white blood count along with neutrophilia, and lymphocytopenia and the observed toxic changes in the white blood cells. The patient also has low red blood cell count and observed macrocytosis morphology, indicating possible anemia caused by chronic alcoholism.

Table 1 – Blood Analysis Results

CBC RESULTS

VALUE

REFERENCE RANGE1

WBC, μL

18,300 ↑↑

3,600 -10,600

RBC, x106/μL

3.9 ↓↓

4.7 – 6.1

Hemoglobin, g/dL

11.0 ↓↓

13.5 – 18.0

Hematocrit, %

34.0 ↓↓

40.0 – 54.0

MCV, μm3

108 ↑↑

80.0 – 100.0

MCH, pg

35.0 ↑↑

26.0 – 32.0

MCHC, g/dL

34.0

32.0 – 36.0

RDW-CV, g/L

16.0 ↑↑

11.5 – 14.5

Platelets, 106/L

237,000

150,000 – 450,000

DIFFERENTIAL

Neutrophil, %

75 ↑ ↑

50 – 70

Lymphocytes, %

15 ↓↓

18 – 42

Monocytes, %

0 ↓↓

2 – 11

Eosinophils

1 – 3

Basophils

0 – 2

MORPHOLOGY

Macrocytes

1+

Target cell

Occasional

Toxic granulation

Observed

Vacuolization

Observed

Döhle bodies

Observed

Abbreviations: WBC, white blood cell; RBC, red blood cell; MCV, mean corpuscular volume; MCH, mean hemoglobin value; MCHC, mean corpuscular hemoglobin volume, RDW-CV, red blood cell distribution width.

Table 2 – Bacterial Culture Results

Gram Stain

Gram-positive lancet-shaped diplococci

Culture/Colony Morphology

Alpha-hemolytic round, glistening, dome-shaped appearance

Biochemical Test

Bile Solubility – positive

Optochin susceptibility sensitive 5.0

Discussion

Clinical Manifestations and Etiology

Streptococcus pneumoniae is one of the major pathogens infecting humans worldwide. S. pneumoniae most commonly affects children, the elderly, and other people with weakened immune systems. It is the most common cause of community-acquired bacterial pneumonia.2 Streptococcus pneumonia can cause many types of illness including pneumonia, ear infections, sinus infections but can also lead to severe cases of meningitis and sepsis.2,3

Pneumococcal infection is spread from respiratory droplets from the nose or mouth of an infected person. Droplets in the air may be inhaled by those nearby. Contact with hands, tissues, and other articles contaminated by infected nasal and oropharyngeal secretions also spreads the infection.3,4

S. pneumoniae is normally found in the nasopharynx approximately 5-10% of healthy adults and approximately 20- 40% of healthy children.4 Crowded environments (e.g. daycare centers, army barracks, etc.) increase the potential for exposure to S. pneumonia. The pneumococcus attaches to the nasopharyngeal cells through interaction of bacterial surface adhesins. This normal colonization can become infectious if the organism is carried into areas such as the canal that connect the middle ear to the nasopharynx or nasal sinuses, where it can cause otitis media and sinusitis.2,4

[bookmark: _Hlk3490018]S. pneumonia produces a variety of virulence factors, including the polysaccharide capsule, surface-associated proteins and enzymes, and the toxin pneumolysin (PLY). The most important virulence factor of the pneumococcus is the polysaccharide capsule. The capsule enhances the ability of bacteria to prevent phagocytosis by preventing complement C3b opsonization of the bacterial cells.5,6 The capsule and surface protein that interfere with phagocytosis help the microorganism attack the host immune’s defense. The infection causes inflammation, one of the main symptoms of S. pneumonia. Autolysis causes lysing of bacteria producing inflammation which involves complements of the cell wall and the toxin pneumolysin.5,6

Streptococcus pneumonia symptoms include shaking, fever, low blood pressure, shortness of breath, and rapid breathing, symptoms similar to those observed in the patient.2 (Refer to patient history). The patient’s CBC (Table 1), indicated elevated white count, decreased lymphocytes, and increased neutrophils with toxic changes. These are all indicators of a bacterial infection such as S. pneumonia. Neutrophil’s primary function is phagocytosis of organisms and other infectious agents. A “left shift” to more immature neutrophil forms occurs as precursors are released from the bone marrow during infection.1,7

Toxic granules, Döhle bodies, and vacuoles noted in the patient’s peripheral blood smear most likely result from the activation of increased cytokine activity and shortened activity of neutrophils during infection (Table 1). In many infections or toxic stimulations, neutrophils respond with large dark blue intracytoplasmic azurophil granules.1,7 The toxic granules may be present within metamyelocytes, band, and segmented neutrophils in such cases. Toxic granulation would appear in the neutrophil’s cytoplasm which reflects an increase in lysosomal enzyme and primary azurophilic granules. Toxic granulation is seen in cases of severe infection, as a result of phagocytosis. Infection is the most frequent cause of toxic granulation. 1,7 Toxic granulation may be observed in the band neutrophil shown in Image 1.9 Döhle bodies are small, light blue-gray irregular staining patches of cytoplasm seen near the edge of the cell in granulocytes in certain conditions. Associated with infections, burns, leukemia, chemotherapy, inflammatory state. Döhle bodies are present when the body is responding to unusually severe stress or stimulus. This stress may cause the cytoplasm of some cells to mature improperly. When present, they are typically observed in the outer periphery of the cytoplasm, close to the cell wall. Döhle bodies are composed of RNA from rough endoplasmic reticulum, which is left over from previous maturation stages. Their presence does not aid in the diagnosis of the disorders in which they are found, but they are frequently seen along with toxic granulation and/or vacuoles in cases of infections or burns. (7,8) Döhle bodies are indicated by the arrows in Image 2.7 Vacuoles are clear, unstained areas in the cytoplasm of neutrophils and seen in conditions such as infection when toxic granulation and Döhle bodies are present. Toxic vacuolization is indicated by the arrows in the cell of Image 3.7 Toxic vacuolation and toxic granulation are classified as reactive and not pathologic since the body is responding normally in an effort to rid itself of the infection caused by bacteria.1,7

The observed decrease in red blood cells, hemoglobin, hematocrit, and increase in MCV, MCH, and RDW can be associated with the patient’s history of alcoholism (Table 1). Chronic excessive alcohol ingestion reduces the number of blood cell precursors in the bone marrow and causes characteristic structural abnormalities in these cells, resulting in fewer-than-normal or nonfunctional mature blood cells.8 For example, enlarged RBCs can occur in the blood – a condition called macrocytosis — as well as oddly shaped RBCs that are subject to premature or accelerated destruction because of their structural abnormalities. As a result, alcoholics frequently are diagnosed with anemia.8 Macrocytosis is used to describe erythrocytes that are larger than normal, typically reported as mean cell volume (MCV) greater than 100fL. The amount of hemoglobin increases proportionately with the increase in cell size. Increased MCV is an indication of macrocytic anemia when:9

• In nonpregnant females, hemoglobin < 12g/dL or hematocrit < 36%
• In pregnant females, hemoglobin < 11g/dL
• In males, hemoglobin < 13 g/dL or hematocrit < 41%.

A history of alcohol abuse is an important indication to the cause of the increased mean cell volume (MCV) and red cell distribution (RDW). Target cells are often observed in macrocytic anemia.9 Although the macrocytosis of alcoholism may be secondary to poor nutrition with a resulting folate or vitamin B-12 deficiency, it is more often due to direct toxic effect of the alcohol on the marrow.8,9 Those who drink excessive amounts of alcohol can develop macrocytosis even in the absence of other factors associated with RBC enlargement, such as alcoholic liver disease or folic acid deficiency. Alcohol abuse is the disorder most commonly associated with macrocytosis: Up to 80% of men and 46% of women with macrocytosis have been found to be alcoholics. The exact mechanism is unknown, however, alcoholism appears to interfere directly with RBC development, because macrocytosis is reversed in the abstinence of alcohol.8

Laboratory Methods for Detection and Identification

Presumptive identification is made by traditional physiological and biochemical methods. On microscopic examination, S. pneumonia bacteria appear as gram-positive cocci arranged in chains and pairs (diplococci). A green, α-hemolytic, zone surrounds S. pneumonia colonies on blood-agar plates. Pneumococci produce pneumolysin, which breaks down hemoglobin into a green pigment that can be observed as a large green zone surrounding S. pneumoniae colonies growing on blood agar plates (Table 2). S. pneumoniae colonies vary in appearance depending on the degree of encapsulation of the organism.10

The opacity variance of S. pneumoniae colonies appears to reflect differences in the organism’s pathogenesis and virulence. For example, transparent variants are associated with increased amounts of cell-wall-associated teichoic acid, while opaque variants are associated with enhanced production of capsular polysaccharides.11 Optochin susceptibility test is used to differentiate Streptococci pneumonia from Streptococci viridian’s because of its ability to selectively inhibit the growth of S. pneumoniae on blood agar plates at very low concentrations. A zone of inhibition greater than 14 mm with a 6-mm disk or a zone of inhibition or greater than 16 mm with a 10-mm disk is considered susceptible and a presumptive identification of S. pneumoniae. Isolates producing smaller zones should be tested for bile solubility to confirm their identity.10

The test for bile solubility takes advantage of the S. pneumoniae autocatalytic enzyme amidase. The addition of the bile salts or detergent accelerates the natural lytic reaction observed in pneumococcal cultures by increasing the activation of autolytic enzymes produced by Streptococcus pneumoniae. S. pneumoniae in a bile salt solution lyses, and the solution becomes clear. Other α-hemolytic organisms do not undergo autolysis, and the solution remains cloudy.10,11 Additional testing, by serology, may occasionally be necessary, since not all pneumococcal strains lyse completely with the addition of bile salts.11

The Quellung reaction (swelling of the capsule) is considered the “gold standard” technique for serotyping Streptococcus pneumonia and is another means of identification. This microscopic “precipitin test” can be used to identify pneumococci or to determine the capsular serotype of individual pneumococcal isolates. There are over 90 different capsular serotypes of S. pneumoniae. This technique utilizes a high-quality microscope and specific pneumococcal antisera. This method involves testing a pneumococcal cell suspension with pooled and specific antisera directed against the capsular polysaccharide. The antigen-antibody reactions are observed microscopically. A positive Quellung reaction is the result of the binding of the capsular polysaccharide of pneumococci with type specific antibody contained in the typing antiserum.12

Treatment and Vaccination

Pneumococcal infections are usually managed with penicillin however, a growing number of penicillin-resistant S. Pneumoniae strains have caused concern. The organism has developed antibiotic resistance due to its ability to genetically recombine and reproduce rapidly. Other antibiotics that have been show to work well on penicillin-resistant bacteria include erythromycin and chloramphenicol. Physicians have started to use a ‘broad spectrum of antibiotics to treat first and then an antibiotic sensitivity test is performed to identify the best antibiotic. The susceptibility and resistance of S. pneumonia to various antibiotic depends on the geographic region, country, and time.10

Two vaccines are available for prevention of S. pneumoniae and are recommended for infant, elderly or immunocompromised people. The vaccines currently offer protection against the most common strains, but due to the large antigenic variety of the S. pneumoniae, which has more than 90 capsular serotypes identified based on capsular polysaccharides, a universal vaccine has not been developed.10

The pneumococcal conjugate vaccine (PCV13 or Prevnar 13®) protects against 13 types of pneumococcal bacteria. The recommendation by the Center for Disease Control is “PCV13 for use in infants and young children and adults 65 years or older. Older children and adults younger than 65 years old who are at increased risk for getting pneumococcal disease may also need a dose of PCV13.”11,15 The pneumococcal polysaccharide vaccine (PPSV23 or Pneumovax®) protects against 23 types of pneumococcal bacteria. The Center for Disease control recommends it “for all the patient adults 65 years or older and for those 2 years or older at increased risk for disease.”10,13

Even with treatment, some people with pneumonia, especially those in high-risk groups, may experience complications, including bacteremia or sepsis, difficulty breathing, pleural effusion, or lung abscess. Bacteria that enters the bloodstream from the lungs can spread the infection to other organs, potentially causing organ failure. If the pneumonia is severe or if there is chronic underlying lung diseases, the patient may have trouble breathing in enough oxygen. This could lead to hospitalization and use of a breathing machine while the lung heals. Pneumonia may cause fluid to build up in the thin space between layers of tissue that line the lungs and chest cavity. If the fluid becomes infected, it may be necessary to drain it through a chest tube or remove it surgically. An abscess occurs if pus forms in a cavity in the lung. An abscess is usually treated with antibiotics.1,3,13

Summary

Streptococcus pneumoniae is one of the most common organisms causing upper respiratory, lower respiratory, and invasive infections in children and adults. The patient in this case exhibited fever, chills, and deep productive cough, all typical symptoms associated with S. pneumonia. In this case, the increase in white bloods cells, decrease in lymphocytes and increase in neutrophils in addition to the presence of toxic granulation, Döhle bodies, and vacuoles serve as indicators for bacterial-induced infection, such as Streptococcus pneumonia. Additionally, bacterial testing that includes colony morphology, Gram stain, catalase reaction, alpha-hemolytic activity on 5% sheep blood agar, optochin susceptibility, and bile solubility (Table 2) all assist in identification of S. pneumonia as the causative organism for the patient’s fever, chills, and deep productive cough.3,10, More than 90 serotypes have been identified, based on capsular polysaccharides. The Quellung test is another means of identification. Employing all the tests described above can provide a clear identification of S. pneumoniae. Treatment for S. pneumonia is usually penicillin or a “broad spectrum” of antibiotics.

In addition to the S. pneumonia infection the patient also has a macrocytic anemia, based on a history of alcoholism and CBC results (Table 1). In cases of macrocytosis related to alcoholism, the elevated MCV may be due to the direct effect of the alcohol, liver disease, and/or folate deficiency.8,9 Macrocytosis due to alcoholism usually reverses only after a few months of abstinence from alcohol.8

Questions

1. How does pneumonia present in patients with S. pneumoniae infection?

• a. Chills, diarrhea, fatigue
• b. Fever, chills, deep cough
• c. Fever, diarrhea, loss of appetite
• d. Abdominal pains, vomiting, fatigue

1. 2. A high white blood count with increased in neutrophils indicates what type of infection

• a. Viral infection
• b. Bacterial infection
• c. Fungal infection
• d. Protozoan infection

1. 3. What leukocyte cytoplasmic inclusion is composed of ribosomal RNA?

• a. Primary granules
• b. Toxic granules
• c. Döhle bodies
• d. Howell-Jolly bodies

1. 4. What is the “gold standard” test for Streptococcus pneumonia?

• a. Optochin sensitive test
• b. Bile Solubility test
• c. Quellung test
• d. Catalase Test

1. 5. Which of the following is the drug of choice for treating most streptococcal infections?

• a. Erythromycin
• b. Cephalothin
• c. Penicillin
• d. Gentamicin

Figures

1. [image: https://www.medialabinc.net/courses/imgs/970-326139.jpg] [image: https://p5759554.vo.llnwd.net/e1/courses/imgs/600-663991.jpg] [image: https://www.medialabinc.net/courses/imgs/970-326140.jpg]Image 2 – Döhle Bodies 7

• Image 3 –Vacuoles 7
• Image 1 – Toxic Granulation 7

1. References
2. Keohane Elaine M, Smith Larry J, and Walenga Jeanine M. Rodak’s Hematology: Clinical Principles and Applications. 5th ed. St. Louis: Elsevier; 2016.
3. Grayson Kristina M, Blevins Lance K, Oliver Melisa B, Ornelles David A, Swords W Edwards, Alexander-Miller Marth A. ‘Activation-dependent modulation of Streptococcus pneumonia- mediated death in human lymphocytes.’ Pathogens and Disease, 2015;75:1-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827582/pdf/ftx008.pdf.
4. Ortqvist Ake, Hedlund Jonas, Kalin Mats. Streptococcus pneumoniae: Epidemiology, Risk Factors, and Clinical Features. Semin Respir Crit Care Med. 2005;26(6):563-574.
5. [bookmark: _Hlk3562561]Skovsted Ian C. Textbook in Diagnosis, Serotyping, Virulence Factors and Enzyme-linked Immunoassay (ELISA) for Measuring Pneumococcal Antibodies: Streptococcus Pneumonia, 4th ed. Denmark: SSI Diagnostics; 2017.
6. Mitchell AM, Mitchell TJ. Streptococcus pneumonia: virulence factors and variation. Clin Microbiol Infect. 2010;16: 411–418
7. Velasco Alonsod Streptococcus pneumoniae: Virulence Factors, Pathogenesis, and Vaccines. American Society for Microbiology. 1995 Dec; 59(4): 591-603. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC239389/pdf/590591.pdf
8. Reiqua C. William, Koneman Elmer W. Lab CE MediaLab – White Cell and Platelet Disorders: Peripheral Blood Clues to Nonneoplastic Conditions; c2018 [cited: 2019 March 14]. Available from: https://www.labce.com/white-cell-morphology.aspx
9. Ballard Harold S. The Hematological Complication of Alcoholism. Alcohol Health & Research World. 1997; 21(1): 42-52.
10. Herrin Vincent E. Emedicine – Medscape Macrocytosis; c2018 [cited: 2019 March 13]. Available from: htps://emedicine.medscape.com/article/203858-overview
11. Mahon Connie R, Lehman Donald C. Textbook of Diagnostics Microbiology. 6th ed. St. Louis: Elsevier; 2019.
12. Bakdash Suzanne, Couce Marta, Nichols Larry, Pasculle William. Case 349- A man in His 40s with Severe Headaches after a fall; c2003 [cited 2019 March 14] Available from: https://path.upmc.edu/cases/case349.html
13. Habib Maha, Porter Barbara D, Satzke Catherine. Capsular Serotyping of Streptococcus pneumonia Using the Quellung Reaction. J Vis Exp Feb 2014; 84; 1-4.
14. National Center for Immunization and Respiratory Diseases, Division of Bacterial Diseases. Pneumococcal Vaccination Center for Disease Control. US Department of Health and Human Services. c2017 [cited: 2019 March 14]. Available from: https://www.cdc.gov/pneumococcal/vaccination.html

Question Answers

1. – b. Fever, chills, deep cough
2. – b. Bacterial infection
3. – c. Döhle bodies
4. a. Howell-Jolly bodies
5. c. Quellung test
6. – c. Penicillin

Introduction:

Due to minimal development of new treatments since antibiotics in 1950s. There have neither been any new drugs developed targeting Community-Acquired Pneumonia. Therefore, the purpose of the topic for this diploma thesis is to find the significance of corticosteroid treatment applied to community-acquired pneumonia, after new studies has emerged providing scientific evidence of potential positive effects of corticosteroid treatment. The goal is to compare this treatment with the treatment we use today and see if there are any significant improvements. Compare the studies with both positive and negative outcomes, and weigh if the results overweigh the side effects. In the first part of my thesis, we will be introduced and educated about Community-Acquired pneumonia and corticosteroids. On the second part I will focus on a review provided by the research based on the results of corticosteroid treatment on individuals with community-acquired pneumonia.

Method:

A review based on available open access internet sources, books, and articles.

Conclusion:

Some newly published randomized clinical studies have shown some potentially positive effect of short use of corticosteroids in Community-acquired pneumonia with fast clinical and radiological improvement in addition to one day’s shorter hospitalization. (Stern et al., 2017) (Blum et al., 2015) On the other hand, it is not observed any secure effect in accordance to mortality, and corticosteroid treatment increase the risk of hyperglycemia. Also, other studies have shown no significant effect in this kind of supplementary treatment. (Snijders, Daniels, de Graaff, van der Werf, & Boersma, 2010) Too summarize, its most likely a subgroup of pneumonia patients that can have benefits of corticosteroid treatment, but there is no international consensus. (Wan et al., 2016)

Preface

I choose to write about the topic “Role of corticosteroids in treatment of community-acquired pneumonia” because it is a very important subject in modern medicine, which in a way has stood still in evolving specific and targeted treatment for several decades. It’s a disease where mortality rates are high, and more attention should be shed to find an adequate solution. It’s a very interesting topic that I wanted to learn more about a topic that for sure will follow me after the studies.

My goal is to learn more about community-acquired pneumonia, incidences, todays treatments, the effect corticosteroids has and together gather this information to try to find a solution. It is a big threat for in care patients and thus attracted my attention to write about this topic for my diploma thesis.

I would like to thank my tutor and advisor doc. MD. Robert Vyšehradský, PhD for assigning this topic for my diploma thesis. It has been very interesting and educational.

Also, it is important for me to thank all my family and friends for supporting me though the medical studies in Martin, Slovakia

1 Literary review

1.1 Community-Acquired Pneumonia

1.1.1 Pneumonia

Pneumonia is a lower respiratory tract infection associated with respiratory symptoms and signs of acute infection, most often presenting with lower general condition and fever >38C. Pneumonia affects the lung parenchyma, most commonly with exudation of alveoli’s, but can also involve the bronchi’s, bronchioles, pleura, and interstitial.

Pneumonia is one of the most common causes of hospitalization and still a leading consequence of morbidity and death. Pneumococci used to be one of the most leading causes of pneumonia. Epidemiologic studies in the 19’ hundreds have shown a gradual reduction of pneumococci as a result for pneumonia, and introduction of the pneumococci vaccine in the western world from 2006 has shown an obvious reduction in occurrence in systemic pneumococci disease.

Gene technological methods has the last year been introduced as a routine microbiological diagnostic, as well as culture from airways and blood. Some hospitals also use antigen-based analysis in urine for detecting antigen from pneumococci and legionella bacteria. On the other side, we can see that serologic analysis is in less use due to being in less benefit in acute situations.

Pneumonia can be divided based after its pathological path into Broncho-, lobar- and interstitial/atypical pneumonia. Or based on where it is acquired: Community or Hospital-acquired pneumonia. Community-acquired pneumonia is pneumonia in patients that has not been admitted to the hospital or any other kind of health-related institution last 14 days. Suspicion of this should be present in newly onset of radiological infiltrative and at least 2 of these: Fever, productive cough, or increased inflammation parameters. In addition, we also have aspiration pneumonia which is due to aspiration of food, gastric content to the airways. A common cause is vomiting of someone unconscious. Leading to pneumonia from both the infection and chemic reaction followed by HCl from the stomach.

Even though the vaccination has led to a significant decrease in pneumococci, it is still the highest detected microbe in pneumonia. A new combination of traditional and modern gene techonological microbiologic methods gives new knowledge of causes of pneumonia. Newer studies has shown that viral- and mixed infections are more commen (20-30%) and this is knowledge for how pneumonia should be understood and treated.

Etiology

Risk factors:

1. Congenital disease: Primary ciliary dyskinesia and Cystic fibrosis
2. Impared local imunity: Smoking (inhibits cilia and macrophage activity), impared coughing reflex ( Alcoholism, increased age..), Viral respiratory infections, COPD, Lung malignancies, and Bronchiectasis
3. Immunodeficiencies: Primary: CVID (hypogammaglobulinemia and recurrent infection) and Secondary: HIV
4. From other organs systems: Nevrologic defect in swallowing and cough reflex after stroke, urami and reduced function of spleen.

1.2 Pathogen

Pneumonia is the one of the most infectious causes of hospitalization and death, especially in elderly and immunocompromised.

Bronchopneumonia/Lobar pneumonia: The lungs are constantly exposed to particles. The lower airways is able to stay sterilized due to defense mechanisms, but due to an defect in the defense mechanism or exposure to an virulent microorganism that travels to the lungs due to micro-, macro aspiration or hematogenous route can cause pneumonia. The pathogen microorganism attaches to the respiratory epithelium, causes necrosis, interstitial inflammation, and exudation in the alveoli.

Atypical pneumonia: The reason of dyspnea is so severe in atypical pneumonia is because the gas exchange between the alveoli’s and capillaries is blocked due to interstitial inflammation. With viral pneumonia, a secondary bacterial infection might occur due to the epithelium being damaged from the virus of inhibition of mucocillary transport. Often hard to identify etiologic agent.

Aspiration pneumonia: Gastric acid causes chemical pneumonia which again leads to Acute respiratory distress syndrome. The factors leading to hypoxemia is edema, decreased activity of surfactant, alveolar bleeding, and production of hyaline membrane.

Community-acquired pneumonia is mostly caused from (the 3 first accounts for 80%):

• S.pneumoniae (50%)
• H.influenzae (w/ COPD)
• M.catarrhalis
• C.pneumoniae
• Respiratory viruses

Atypical Pneumonia:

• Virus
• Mycoplasma pneumoniae
• Chlamydophilia Pneumoniae
• Pneumocysties jerovecii (fungi)
• Legionella

In a population-based study from January 2010 to July 2012, was all hospitalized patients over 18 years old admitted with pneumonia in 5 hospitals registered within Chicago and Nashville. Nosocomial pneumonia and immunocompromised patients were excluded from the study. Patients from a general practitioner in Nashville, without symptoms of respiratory tract infections, worked as a control group to find out the prevalence of respiratory pathogens in the healthy population.

Of the 2500 patients in the study, 90% of them had radiologic findings indicating pneumonia. Of these 90%, there was done bacterial and virologic testing. Pathogens was only detected in 38%. The most abundant was Rhinovirus (9%), followed by influensa (6%). Pneumococci was detected in 5%. The yearly admission of pneumonia was 25 cases per 10000 adults. The incidents increased by age, and for the patiants admitted over 80 years old it was 165 incidents per 10000.

The low incidents of Pneumococci can be explained by vaccination the last decade.

• Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 2015. E-publisert 14.7. 2015.
• https://tidsskriftet.no/2015/10/fra-andre-tidsskrifter/hva-er-arsakene-til-pneumoni#reference-1
• https://oslo-universitetssykehus.no/Documents/Medisinsk%20klinikk/Bj%C3%B8rn%20Skrede%20-%20Pneumoni.pdf

1.2.1 Bacteria

As we know, pneumonia is caused by both virus and bacteria. Bacterial infection occurs less frequently then virus infections but are the most serious kind of infection. Bacterial pneumonia is one of the most common serious infections in children but are usually easily treated with antibiotics.

A bacterial pneumonia can occur rather spontaneously but is most commonly seen after a cold lasting a few days with fever, rhinorrhea, and cough. The common cold impairs the immune system and injures the muco-cillary transport making it easier for the bacteria to travel down to the lungs causing an infection. There are several bacteria’s causing pneumonia but the most common especially with children is Pneumococci. In 2006 the pneumococcal vaccine was introduced to the vaccination program that protects against some of these pneumococci, but not all. Older children and adolescent are more likely to get pneumonia caused by mycoplasma and chlamydia. Mycoplasma and Chlamydia are contagious.

1.2.1.1 Streptococcus Pneumoniae

Is a Gram-positive cocci in diplo or chains. It gives upper respiratory tract infections, pneumonia, Meningitis, and Sepsis. It’s a polysaccharide capsule and pneumolysin are the most important virulent factors.

The infection occurs normally in the upper respiratory. It’s a frequent cause of opportunistic infections disease of the airways. The highest carrier effect is found in 2-year-old children. Highest incidens in the winter and early spring. The disease normally occurs when normal functions has changed such as during a viral infection, chemical irritation or absent cough reflex. People with low spleen function or has underwent a splenectomy has a high risk of a serious pneumococci infection. It is together with N.menigitidis the most common cause of meningitis.

The infection occurs after the airway virus has damaged the mucosa. The most common cause of disease strains from the capsule. The capsule inhibits phagocytosis of the bacteria and is therefore an important virulent factor. The cell wall of the bacteria contains adhesions that bind to the epithelial cells. The pneumolysin which resembles streptolysin in S.pyogenes, gives cell lysis thru pore production. It destroys ciliated epithelial cells and phagocytes. Activation of the complement system with migration of innflamatory cells and release of cytokines leads to fever and tissue damage. IgA secration causes the bacteria to bind and get captured in the mucus of the airways, then getting transported away via cilia activity. The IgA protease inhibits this interaction. Phorphorylcholine binds platelets, leucocytes, endothelial cells and tissue cells making it accessible for the bacteria to invade the cells. This gives the bacteria protection against detection and phagocytosis. The bacteria can also be transported intracellularly to other areas such as into the blood and central nervous system. This facilitates spread of the infection.

Diagnostics

• Nasal swab is important to prove pneumococci in the airways.
• Blood culture Grows with alpha hemolysis on blood agar.
• Optochin Sensitivity Test is the most used test to identify pneumococci.
• Treatment and prevention

See 1.2.22 and 1.2.2.3

1.2.1.2 H.influenzae

Is a gram negative rod bacteria. The bacteria act in a acapsular and capsular form. The capsule form has several serotypes (a-f). The most important serotype is type b (Hib). People with chronic lung diseases such as COPD is exposed to Hu-infections with worsening of their lung disease. With such non systemic infections it is often caused without a capsule. Systemic (invasive) Hi infections are cause by the capsular variant. Hib was a important cause of systemic disease in small children before the introduction of the vaccine. Which has caused a strong reduction of incidents of Hib infection. The transmission of the infection occurs thru close droplet transmission. The incubation time is 2-4 days (Hib).

Diagnostics

1. Nasal and throat swab
2. Agenspåvisning i blod eller spinalvæske ved dyrkning, antigen- eller ved nukleinsyreamplifiseringstest. Bærertilstand kan eventuelt påvises ved hals- eller neseprøve.
3. Ampicilin treatment.

• https://www.fhi.no/nettpub/smittevernveilederen/sykdommer-a-a/haemophilus-influenzae-invasiv-sykd/

1.2.2 Virus

1.2.2.1 Influenza virus

Is a single-stranded RNA virus with serotypes A, B, and C. It gives the classis influenza disease. It’s important virulent factors are Hemagglutinin-antigen and Neuraminidase-antigen.

The virus is transmitted thru droplets and contact. Low infectious dose is enough. It takes approximately 3-5 days from transmission till symptoms first starts. The season for influenza starts normally between December and lasts for 3 months. The Influenza A-epidemy occurs every 1-3 years because new variants of influenza type 1 shows up which causes most people to lose their immunity. The influenza A-pandemic occurs every 10-40 years because it has a new virus type that large parts of the world don’t have immunity to. Incubation period is 1-4 days dependent on the inoculums size.

Human influenza virus is divided into 3 serotypes A, B and C. The division is based on the antigenic properties of the nucleoprotein. The virus is round shaped. The genome is single stranded RNA which I put together by 8 parts in influenza A- and B-virus. The virus is membrane encoded, with an inner protein heath and a other lipid membrane. The surface of the virus has 2 types of protein particles:

• Hemagglutinin which binds the virus to receptors on host cell membranes. After binding to the host cell, it’s taken up to the endocytosis. Red blood cells also has receptors for the influenza virus, so the virus can agglutinate the RBC (this is used in diagnostics).
• Neuraminidase an enzyme which causes destruction of receptors. Its enzymatic activity cleaves syaline acid from glycoporteins in mucus and from glycoproetins that are receptors for host cell. It cleaves bindings of hemagglutinin in syaline acid containing receptors.

Replication of the virus RNA undergoes in the nucleus of the host cell, while the virus protein I produced in the cytoplasm.

When the virus reaches the airways thru droplet infection, there is a primary replication of the virus in the mucus of the pharynx and trachea. Ciliary epithelium with receptors for H id invaded at first by the virus. Mucus producing cells is also attacked which leads to cassation in mucus production in affected areas. Leucocytes infiltrate the area and causes edema and bronchospasm. Alveolar macrophages are recruited which leads to reduction of phagocytose of secondary infection of bacteria. Under the infection large amount of interferon is produced. This induces production f protein MxA which administrates antiviral activity. The virus quantity in the airways is reduced with increased interferon quantity. When the infection goes down the lower airways it will lead to primary influenza pneumonia. This can lead to necrosis of alveolar cells, capillary thrombosis and interstitial edema. Immunity against influenza arises from IgG antibody against H- and N-antigen. Local IgA antibody against the virus hemagglutinin is also produced. IgA antibodies last some monthes while IgG stays for years to prevent infection from same disease.

The infection can be asymptomatic or arise as a mild airway infection. More serious causes can lead to more life-threatening pneumonia. The disease last around 7 till 10 days and its incubation period is 1-2 days. Typical symptoms are shivers, fever, myalgia, dry cough, dysphagia, tiredness and reduced general condition.

Complications from this infection may be primary acute influenza pneumonia or secondary bacterial superinfection with yellow staphylococcus, S.pyogenes or H.influenzae which can present as pneumonia and other diseases. Death may occur especially in elderly and patients with reduced immunity. Reyes syndrome, which is a rare, acute encephalitis with liver failure, seen in children with influenza type B infection.

Diagnostics

1. A swab from the nasopharynx can be used. The virus can be detected thru cell culture, under fluoroscopic microscopy or PCR.
2. Treatment
3. Antiviral treatment shortens the disease time and has healing effects if started within 2 days of the first symptoms. Oseltamivir and Zanamivir is used.

• https://legeforeningen.no/PageFiles/26765/Foreldreinformasjon%20Lungebetennelse.pdf
• http://meddev.uio.no/elaring/lcms/indremedisin/infeksjonsmedisin/nl-streptococcus-pneumonia.xml?menuItemIndex=17
• http://meddev.uio.no/elaring/lcms/indremedisin/infeksjonsmedisin/nl-influensavirus.xml?menuItemIndex=11

1.2.2.2 Respiratory Syncytial virus

Respiratory Syncytial virus is a infection from the paramyxoviridae. RSV is divided into two groups (A and B), but its uncertain if this has any clinical difference. Clinically it’s difficult to differentiate between infection with asthma. RSV is the main cause of bronchopulmonary obstruction in children under 2 years. In older children and adults, the infection is a cold. RSV causes outbreak every winter. Like influenza there is a variation between the time and size of the outbreaks. The RSV seaseon is normally from November till May. Most likely the spread of the virus in older children, often with sibling that are not sick themselves. Numbers from US shows that 1,7% of childran under 6 monthes gets hospitalized due to RSV. 60-70% of all children har within their first year gone thru a RSV infection with a high between 2 till 5 monthes old. The disease is a important cause of death in underdeveloped countries.

The infection is transmited thru direct contact thru infectiousus material such as snot and droplets. The person is the most infectious in the early stages of the disease, but children can spread the disease within 1-2 weeks after the symptoms. Reinfections are common. The incubation period is 3-6 days.

Normally only symptomatic treatment is needed, with obstruction an inhalationtreatment is recired. To prevent spread good hand hygene is the most important preventive measure against RSV infection at home or the hospital. Childran that wants to be protected agains the RSV-infection has to keep away from possible carriers. Palivizumab is available as a prophylaxis to vaurnable children. In these children palivizumab is show to prevent RSv infections causing hospitalization, but has noe documented affect against death. Its given before season start. Its given to children under 2 years with congential diseases, immundeficency, serious pulmonary-heart diseases and extremely premature children.

Diagnostics

1. Nasopharynx swab with immunoflourecent tecnic or PCR-test.

• https://www.fhi.no/nettpub/smittevernveilederen/sykdommer-a-a/rs-virusinfeksjon—veileder-for-he/

1.4 Symptoms

(Bacterial pneumonia: Fever, reduced general condition and very often, but not always; cough and dyspnea. Sometimes also abdominal pain. Young children show unspecific symptoms such as fatigue, anorexia and sometimes vomiting. – These are symptoms usually seen in acute viral infections such as cold. If the symptoms get stronger over time with rising fever and tachypnoea and dyspnea, bacterial infection might be suspected.)

People with Pneumonia often present symptoms of sickness, reduced appetite, sweating, shivers, muscle/joint pain and headache (many has previously had an upper respiratory tract infection. Following its typical with cough, fever and in many dyspnea. With bacterial etiology it is often seen purulent exporant. The frequency of respiration is an important indicator of the seriousness of the infection. Elderly often present with little or diffuse symptoms. Cough and fever can be absent. Sometimes reduced general condition or delirium can be the only clinical signs.

1.5 Diagnosis

Clinical findings

The frequency of respiration is increased but can also be normal. Reduced respiratory sound above the affected section of the lung in pleural effusion. Gliding sound if presents of pleuritis. Attenuation in lobar pneumonia. Peripheral cyanosis as a consequence of type 2 respiratory failure. The oxygen saturation is usually normal.

In children to differ pneumonia from bronchitis, you look if tachypnea is present, then its most likely pneumonia. Tachypnea is defined as a respiratory rate over 60 in 2 months old children, over 50 in children between 2-12m, over 40 in 1 year old’s. High fever and tachycardia can give tachypnea. In children, COPD patients and in respiratory failure we can see localized intercostal retraction.

To score the severity of pneumonia we use CURB65

1. C: Confusion
2. U: Urea >7 mmol/l
3. R: Respiratory rate >30/min
4. B: Blood pressure 100 (S.Pneumoniae often >300), in atypical pneumonia 20-40 in pneumonia lasting over >1 week.

• Arterial bloodgas
• Nasal swab, PCR – Used to identify Mycoplasma pneumoniae, Clamydophila pneumoniae and viruses.
• Cultivation
• Pneumococci antigen test (urine, quick test) – Sensitivity 70%, Spesifisity 96%
• Blood Culture

In patient with poor therapy response and clinical worsening after 2-3 days, you have to think about the possibilities of infection from Legionella, resistant pathogens or metastasis. Always have TB in mind.

Microbiological diagnostics

Two set of bloodculture is reccomende in patients which are hospitalized due to pneumonia. Exporants/sputumtest from the airways is also very beneficial.

Bronchoscopy with bronchoalveolar lavage is costly but most beneficial in critically ill or difficult infections. One nasopharynx test is enough for both PCR and culture. Antigen in urine is beneficial for pneumococci and legionella.

Blood culture: two sets of blood culture is recommended in patients that is hospitalized for CAP. A positive finding of a typical airway bacteria can be in significant clinical importance. On the other side, there are a majority of negative results and atypical bacteria cannot grow the normal way.

Airway test

Exporant/sputum: Microbiological analysis of exporatory induced sputum is in the routine testing, low cost efficant with good microbiological results.

Bronchoscopy w bronchoalveolar lavage: This diagnostic method is costly but Is used in crityclly ill or immunocompirmized patients.

Transthoracale airway sample: Is a costly method with radiological guided fine needle aspiration of contaminated lung parenchyma. Pneumothorax is a complication. But this method is of strong clinical beneficial.

Infection serology: serological analysis has in the western world been replaced with PCR, but can still be benefical in epidemiological studies(5,6) or in suspicion of more chronic path in atypical microbes such as bordella pertussis(11,12)

Urine antigen: Urin-antigen analysis is used to detect pneumococci and legionella pneumophila serotype 1 are fast and easy analysis with high spesifisity (>95%), but with low sensitivity for both microbes (50-80%). Another problem is that pneumococci antigen can still be in the urine several weeks after an infecition and a postitive finding can be misleading.

Biomarkers

C-reactive protein is a polypeptide produced in the liver. CRP is increased during inflammation such as pneumonia. Excpecially an high increase in this marker can be seen in bacterial pneumonia(14), while infections from viral microbes and atypical bacteria gives less of an increase. Many studies has shown that CRP has a limited benefit in providing information of the inflammation being of bacterial or viral etiology.(15,16). But what is know is that the CRP is of correlation in the size of the infiltration of the lung(17) and that limited fall in CRP after some days of treatment is correlated to a bad prognosis(18,19).

Procalcitonin is a precursor of the thyroid hormone calcitonin and is produced in the tissues of the thyroid gland. Secration of the this precursor is correspondant to the innflamatory process of pneumonia. Procalcitonin is primarily increased in bacterial infections. High value of procalcitonin is also correlated to a bad prognosis.

Leukocytes’ increase of neutrophilic granulucytes and low value of lymphocytes can indicate bacterial pneumonia. Therfor an ration of 10-20 between this two can draw us towards an bacterial pneumonia (22).

1.7 Vaccination

Pneumococci infection

The introduction of Hib vaccine in the vaccination program in children I many countries has caused a significant reduction in Hib infections. In 2016 the EU/EØS-area rapported of 3379 causes of systemic Hi infection. Most cases per 100 000 of the population was reported in the Nordic countries, Irland, Great Britain, and the Netherlands. Hib-vaccine is from 2017 introduced in 191 countries, and the global vaccination coverage with 3 doses vaccine is from WHO calculated to be 72%.

1.8 Complications

1. Sepsis (expecioally people with splenectomy)
2. Sterile pleural effusion
3. Emphysema
4. Lung abscess
5. Risk factors for complicated course of disease is elderly, preexisting lung disease, immunodeficiency/AIDS, and nosocomial infection.

1.9 Differential diagnosis

• Acute Bronchitis: Better general condition, faster fall in temperature and CRP
• Bronchiolitis: Generally, within first year of living. Tachypnea and retraction.
• Asthma: Obstruction dominates
• COPD: Obstructive, excarbation can develop to pneumonia
• Heart failure: Dyspnea is the main symptom, afebrile, CRP is normal or slightly increased.
• Lung cancer: Afebril, can be impossible to devide from pneumonia in acute state.

Pneumonia is an infection that causes the tissue in either 1 or both lungs to become inflamed, this can be caused by different types of organisms, but is most commonly caused by a bacterial infection in the upper respiratory tract. When pneumonia affects both of the lungs this is known as bilateral lobular pneumonia. This in turn causes a build-up of fluid within the alveoli and the bronchiole of the lungs. This causes a pneumococcal infection which is caused by the streptococcus pneumoniae bacteria, and although bacterial pneumonia is the most common, it can also be present in other forms. Streptococcus pneumoniae is accountable for causing approximately 70-80% of all cases of pneumonia. This is treated with a course of antibiotics which allows for the pneumococcus bacterium to clear up and out of the lungs. Here are some other examples of how pneumonia can appear:

1. Viral pneumonia – caused by the respiratory syncytial virus (RSV).
2. Aspiration pneumonia – caused by inhaling a foreign substance (e.g. vomit, or harmful substances).
3. Ventilator Associated Pneumonia – caused by a colonisation of bacteria which causes an aspiration of the microorganism to enter directly into the lungs e.g. through an ET tube.

When a patient contracts pneumonia they can experience a range of symptoms that can either be present from the start of the infection, or symptoms can develop slowly over a course of several days. There are different risk factor groups that are more susceptible to contracting pneumonia. Some of these groups are:

• Babies/young children – as they have an underdeveloped immune system making them more likely to pick up pathogens.
• People who are immunocompromised e.g. HIV/AIDS / undergoing chemotherapy.
• Patients with pre-existing respiratory disease e.g. chronic bronchitis/bronchiectasis.
• Smoking/excessive alcohol users as this increases risk of pneumonia attacks.

Epidemiology

Pneumonia affects people of all ages, and only affects 1% of the population each year. Approximately 50% of all pneumonia cases affect those under the age of 50 years old. This common disease is more prevalent in the winter months due to the rapid decrease in temperature, as well as in the spring months, again due to the sudden contrast of temperatures. Issues regarding overcrowding also contribute to the spread of bacteria and viruses which becomes responsible for causing pneumonia in the lower socio-economic groups. This is due to the fact that many people are confined to a small space which allows for the pathogens that cause pneumonia to spread very quickly. Also, the ratio of the number of people to the space that they are all living in means that this can allow bacteria to multiply quickly therefore contributing to the growth of bacteria/viruses present that cause pneumonia. Mortality rates for this disease is 5-10% of all cases, however this is most common in young children and the elderly. Young children are more susceptible due to the fact that they have narrow airways which can become blocked easily by mucus secretions which they are unable to clear. They also have very weak immune systems due to being under developed which means they have not built up the immunity within their white blood cells that is needed to fight off the pathogens that cause pneumonia.

Mechanism and pathophysiology

Whilst pneumonia can be caused by a range of microorganisms, the most common is a bacteria called streptococcus pneumoniae. However pneumonia can also be caused by virus and uncommonly, fungi.

Bacterial pneumonia typically affects just 1 part of the lung, often what is known as ‘a lobe’. This form of pneumonia often occurs in patients who have recently had a viral cold/flu, and this specific form of pneumonia is known as lobular pneumonia.

Some bacteria are able to cause atypical pneumonia, which is a strain that is caused initially by a pathogen that is not commonly associated with the disease. For example the most common bacteria that causes atypical pneumonia is mycoplasma pneumoniae. This is a contagious respiratory infection which in severe cases can cause damage to the vital organs. This form affects people usually under 40 years old, and particularly those who live in crowded living/working conditions.

In terms of viral infections relating to pneumonia, the influenza virus is the biggest cause of pneumonia in adults whereas in children the respiratory syncytial virus is the lead cause of viral pneumonia. With viral forms of pneumonia they are typically short lived and don’t tend to cause too much disruption to the bodies ‘normal’ daily functions. However they can be severe and result in a hospital admission for the patient. This is due to the virus invading the lungs and multiplying therefore causing more of an impact and needing a higher response from the body’s immune system to fight the virus. Viral pneumonias can also be made more complex due to a secondary bacterial infection build up in the lungs also, which again puts more strain on the immune response systems resulting in the patient having more prolonged severe symptoms.

Fungal pneumonias aren’t common however they can be caused by candida albicans. This form of pneumonia typically affects those with immunological disorders.

Diagnosis

In terms of diagnosing pneumonia (regardless of the microorganism that caused the infection) several tests may be necessary. An initial assessment carried out by a health professional will be the first step to diagnosing pneumonia, and this may be performed by a GP, or a doctor in a hospital setting. This is where the patient will be asked questions relating to the symptoms they may be experiencing, and the patient’s initial observations will be taken – temperature, listening to patients chest for any crackles, blood pressure reading, possible echocardiogram trace, oxygen saturations. From these readings a clinical decision will be made whether to refer the patient for any diagnostic tests such as a chest x-ray, and alternatively whether they need any immediate treatment such as oxygen or Ventolin nebulisers to help aid the patient with breathing less erratically and to increase oxygen levels. They may also require some blood tests to look at inflammation markers, or possible sputum samples to understand what type of infection a patient may have in order for the appropriate antibiotics to be issued.

Screening and prevention

The majority of pneumonia cases are caused by bacterial infections and are not typically transmitted from one person to the next. However personal hygiene levels of those close to affected person, and the patient themselves, should be kept to a high standard. This is to prevent the microorganisms from spreading, which in turn reduces the chances of a pneumonia outbreak. This is essential in a healthcare setting to ensure that no risks to the public health through outbreaks are created.

As smoking and alcohol misuse also increases a person’s chance of developing pneumonia, it should be a conscious decision for those at greater risk to cut down/stop these habits. Alcohol misuse particular weakens the pulmonary systems natural defence against infections, therefore making a person more vulnerable to the infection.

Disease management

Pneumonia is typically treated with antibiotics as the pneumococcus is very sensitive to these drugs, therefore making the treatment more effective. The antibiotics chosen to treat pneumonia can vary depending on the severity of the case, and in turn this can affect the dose also. The most appropriate antibiotic can be investigated for via blood tests/sputum samples where staff can analyse what microorganism is present. This would in turn affect treatment methods for the patient. However with the use of antibiotics there is always a concern with patients developing antibiotic resistance in relation to superbugs i.e. MRSA. This is why many tests may be carried out to properly identify the pathogen before any long term treatment will be issued.

Often with pneumonia the oxygen saturation levels can drop and can partly be because it causes the efficiency of O2 diffusion from the lungs into the bloodstream to decrease. Therefore oxygen can be issued as part of the treatment plan. With issuing acute oxygen therapy this helps to increase the oxygen levels, however there is potential risk of CO2 retention which could lead to hypercapnic respiratory failure (type II respiratory failure). Therefore people who have acute oxygen therapy may have regular capillary/arterial blood gas samples taken to assess their levels whilst on treatment. Also with O2 saturations, they can drop if a person is changing their breathing pattern very rapidly. For example if a patient with pneumonia is finding it difficult to breathe they may start hypo ventilating. This is where the body’s ventilator system becomes inadequate to carry out the gas exchange between O2 and CO2. This process causes an increase in the CO2 levels, which in turn will lower the O2 levels due to the fact that the CO2 is not getting blown off meaning that CO2 gets retained.

Patient outlook

After an inpatient stay a follow with the GP will be made within 6 weeks of the discharge date, and this is to ensure that any symptoms have relieved. A follow up chest x-ray may be arranged also to check the resolution of any consolidation within the lungs. If after the 6 weeks, the symptoms are still prevalent then further tests will be carried out to check whether the infection is still present. If the patient has had aspiration pneumonia then it may be necessary to have a bronchoscopy to remove the foreign body that has been inhaled.

History / Subjective

The subjective diagnosis highlights that the patient has the symptoms and background of pneumonia (Jarvis 618). It was revealed previously that Helen was treated from pneumonia and hypertension, but the prescribed antibiotics did not contribute to any positive results. Speaking of her medical history, the woman has type II diabetes, hypertension, hyperlipidemia, and osteoarthritis.

The presence of these chronic diseases increases the possibilities of the development of pneumonia. To support this hypothesis, some researchers highlight that patients with diabetes II are more vulnerable to cardiovascular diseases and respiratory illnesses (Liu 268). In this case, the medical history underlines the possibility of the occurrence of pneumonia, as the woman has heart problems and diabetes, which are viewed as favorable conditions for the progress of this illness. Lastly, her family history and current lifestyle do not contribute to the development of many chronic diseases.

PE Findings / Objective

At the same time, it is essential to conduct a physical examination to determine the diagnosis and prescribe relevant medication and treatment to the patient (Jarvis 787; Forbes and Watt 413). The typical signs of pneumonia include high breath rate, pain, chills, and the absence of high fever (Boltz et al. 32). These atypical symptoms of pneumonia are often present among the adults since the changes in their bodies modify the responsiveness of the organism to the illness (Boltz et al. 33).

To support the presumptive diagnosis, the woman has increased blood pressure (162/90), insignificant fever (37.8C), and an intensified respiratory rate (28 breaths per minute). At the same time, Helen complains about the pain in the chest, and physical examination depicts bibasilar clackers, bilateral expiratory wheezes, and dullness over the right base. In turn, it was also highlighted that the bilateral anterior cervical and supraclavicular lymphadenopathy takes place. It could be said that physical examination highlights the symptoms of pneumonia, and additional laboratory testing such as erythrocyte sedimentation rate could be provided to reveal the progress of the intervention.

Assessment / Differential Diagnosis

A combination of objective and subjective examination helps understand the nature of the patient’s condition (Jarvis 618). In the first place, Helena complains about the pain in the chest, increased breathing rates, and coughing. At the same time, the presumptive diagnosis highlights the potential development of pneumonia. Meanwhile, the woman’s chronic cardiovascular disease and type II diabetes increase the possibility of the progression of this illness (Liu 268).

In turn, the changes like the symptoms due to the age, and the physical examination underlines tachypnea, bibasilar crackles, and bilateral expiratory wheezes. It could be said that all of the information depicted previously emphasizes that pneumonia is the appropriate diagnosis. Nonetheless, one has to pay high attention to type II diabetes, hypertension, hyperlipidemia, osteoarthritis, and prescribed medication while designing the nursing care plan.

Plan / Diagnostic Work-up

As for the nursing plan, in the first place, the woman has to be informed about her condition, as it will help her prepare for the required medical intervention (Bastable 25). It will assist in avoiding ethical issues. The next step is to conduct testing to identify the initial cause of pneumonia. This approach will help adjust treatment and determine whether azithromycin and hydrochlorothiazide are appropriate in this case.

CT scans would be used to add details to the diagnosis and highlight the nature of the disease (Webb, Brant, and Major 175). The respiratory treatments will continue to minimize the shortness of breath. At the same time, pain relievers (Tylenol) and cough medications will be prescribed to determine the effectiveness of interventions to the patient. The condition of the patient will be monitored regularly to see the progress of the treatment.

Works Cited

Bastable, Susan. Essentials of Patient Education. Burlington: Jones & Bartlett Learning, 2016. Print.

Boltz, Marie, Elizabeth Capezuti, Terry Fulmer, and Diane Zwicker. Evidenced-Based Geriatric Nursing Protocols for Best Practice. New York, Springer Publishing Company, LLC, 2015. Print.

Forbes, Helen, and Elizabeth Watt. Jarvis’s Physical Examination and Health Assessment. St. Louis: Elsevier, 2015. Print.

Jarvis, Caroline. Physical Examination and Health Assessment. St. Louis: Elsevier, 2016. Print.

Liu, Jian. “Impact of Diabetes Mellitus on Pneumonia Mortality in a Senior Population: Results from the NHANES III Follow-Up Study.” Journal of Geriatric Cardiology 10.3 (2013), 267-271. Print.

Webb, Richard, William Brant, and Nancy Major. Fundamentals of Body CT. Philadelphia: Elsevier, 2016. Print.

Pneumonia is a severe condition that has to be treated immediately to avoid possible complications. Pletz, Rohde, Welte, Kolditz, and Ot (2016) state that it is an “infectious disease with the highest number of deaths worldwide” (p. 300). A nursing professional can help a patient deal with the condition by identifying a nursing diagnosis and providing further interventions. According to Gulanick and Myers (2014), the concept of nursing diagnosis reflects a patient’s response to an identified health issue. This paper aims to examine pneumonia from a nursing perspective and offer four possible interventions for the condition.

Nursing diagnosis in the case of pneumonia would include aspects such as blocked airways and coughing. Additionally, a patient may cough, have a fever, and feel exhausted. Pertinent pathophysiology of pneumonia consists of several primary symptoms, but mainly high temperature, which would indicate inflammation in a patient’s body. Gulanick and Myers (2014) state that primary symptoms are pleuritic chest pain, fever, chills, changes in sputum, cough, and dyspnea. Based on these factors, a primary care provider would diagnose an individual with pneumonia.

It is crucial to carry out tests that would determine the primary causes of the condition. According to Li, An, Fu, and Li (2016), pneumonia is a “lung inflammation caused by different pathogens or other factors” (p. 2145). Risk factors may vary, for instance, an intubated patient may develop the disease. At the same time, another person may acquire community-based pneumonia while having little contact with healthcare establishments. Thus, both patients who have been in a hospital for a while and those who are newly admitted are at risk of contracting the disease. Additionally, Gulanick and Myers (2014) state that other contributing factors include substance use, exposure to other illnesses, immobility, or chronic conditions. Immunization is another aspect to consider in regards to pneumonia.

The etiology of the disease is reflected in microorganisms from the external environment that contaminates one’s body. According to Gulanick and Myers (2014), viruses or bacteria can cause pneumonia. Additionally, sometimes fungi or other factors can cause the condition. Cooper and Haut (2013) state that patients who require lung ventilation are at risk as well because they may be infected easily. Considering the factors mentioned above, several nursing interventions might be applied:

• Antibiotics;
• Therapy aimed at reducing fever symptoms;
• Respiratory physiotherapy for airways;
• Proper diet and fluid intake.

The primary objective of treating pneumonia is to ensure that the patient is prescribed medication and is receiving it. Antibiotics should be suggested within four hours of arriving at the hospital (Cooper & Haut, 2016). Both parenteral and oral medication can be prescribed, depending on the severity of a case. Cooper and Haut (2016) distinguish concurrent viral and bacterial pneumonia. In the case of a viral illness, antibiotics would not be sufficient; thus, antiviral drugs should be prescribed instead. Therapy, together with medication, should be applied to counteract significant fever symptoms that a patient has.

In some cases, patients may require lung ventilation due to complications. Li et al. (2016) suggest respiratory physiotherapy for airways to ensure they are not blocked. Also, oxygen therapy treatment aimed at the prevention of respiratory failure might be another nursing intervention. Additionally, nursing professionals should focus on preventing possible comorbid conditions. In less severe cases, ensuring that proper nutrition and fluid intake is in place can help the patient get better. Measures such as a humidifier can help relieve some symptoms as well.

Overall, pneumonia is a severe condition that affects many people around the world. A nursing professional should focus on the primary symptoms of the disease, such as blocked airways and difficulty of breathing. The interventions would include ensuring proper medication is taken by an individual, fever symptoms reduction, respiratory physiotherapy for airways, and adequate nutrition. Additionally, a nurse may install a humidifier to relieve breathing difficulty for a patient.

References

Cooper, V. B., & Haut, C. (2013). Preventing ventilator associated pneumonia in children: An evidence based protocol. Critical Care Nurse, 33, 21-29. Web.

Gulanick, M., & Myers, J. L. (2014). Nursing care plans: Diagnoses, interventions, and outcomes (8th ed.). Philadelphia, PA: Elsevier.

Li, W., An, X., Fu, M., & Li, C. (2016). Emergency treatment and nursing of children with severe pneumonia complicated by heart failure and respiratory failure: 10 case reports. Experimental and Therapeutic Medicine, 12(4), 2145–2149. Web.

Pletz, M. W., Rohde, G. G., Welte, T., Kolditz, M., & Ot, S. (2016). Advances in the prevention, management, and treatment of community-acquired pneumonia. F1000 Research, 5, 300. Web.

Introduction

Pneumonia is a major healthcare problem that causes a high level of mortality and morbidity in both children and adults (Shan, Tunik, & Tsung, 2013). Therefore, it is necessary to understand epidemiological, diagnostic, and treatment implications of the disease in order to inform clinical decisions of healthcare practitioners. The paper will discuss pediatric pneumonia and an educational program on respiratory viral infections.

Discussion

Children and Adults

It is much harder to diagnose pneumonia in children when compared to adults because the presenting symptoms of pediatric pneumonia overlap with other respiratory conditions (Nelson, 2015). The following signs are suggestive of the disease in children: increased respiratory rate, grunting, audible wheeze, and indrawing of the lower chest wall (Nelson, 2015). It is also necessary to conduct bacterial studies and run the complete blood count (CBC) test. The diagnostic process for pediatric pneumonia is complicated by the fact that respiratory rates of children differ with age. Furthermore, even though ultrasonography allows to accurately identify the condition in both children and adults, it is more effective for diagnosing adult patients (Shan et al., 2013). When it comes to differences in the treatment of the disease, children require hospitalization more often. Also, young children more commonly have viral pneumonia, which does not require antibiotic therapy (Nelson, 2015). Adults, on the other hand, are more vulnerable to bacterial pneumonia; therefore, their treatment revolves around the antibiotic administration.

Epidemiology and Etiology

The key etiological agents that cause the disease are Streptococcus pneumonia, haemophilus influenza type b, respiratory syncytial virus (RSV) and influenza virus (Rudan et al., 2013). It is worth mentioning that RSV is the agent which is associated with the majority of pneumonia episodes—29 percent (Rudan et al., 2013). The findings of a study on community-acquired childhood pneumonia point to the improvement of the epidemiological burden of the disease over the last decade. Specifically, whereas in 2000, the estimated global incidence of pneumonia fell in the range between 0.21 to 0.71 per child, the range of the average incidence has substantially narrowed in 2010—from 0.11 to 0.51 (Rudan et al., 2013). A reduction of the median incidence of the disease constitutes almost 25 percent, which is evidence of the substantial progress achieved by the global healthcare community (Rudan et al., 2013).

Educational Program

A ‘play-station’ should emphasize the importance of regular and frequent hand washing as a means of reducing the risk of contracting the disease. Therefore, the use of bath-inspired visual themes, as well as toy basins and soaps, can reinforce the health message. A program has to ensure that children’s education is tailored to their cognitive needs and age. Parents should also be provided with basic pneumonia information (Abolwafa & Mohamed, 2017). To this end, the program has to address the signs and symptoms of the disease specific to children, temperature-taking, fever management, and prevention by using bullet points and visual aids. It is of utter importance to inform families that newborns do not necessarily exhibit signs of infection such as cough and vomiting (Nelson, 2015). The program should also remind parents of the need to regularly vaccinate their children. To reinforce the information at home, parents can be provided with printed booklets and web-based resources on the prevention and management of pneumonia.

Conclusion

The paper has discussed the specifics of pediatric pneumonia. It has been argued that the condition is associated with the substantial healthcare burden; therefore, it necessitates efficient health promotion and disease prevention activities. The paper has also outlined the educational program that can be used to reduce the incidence of pneumonia among children.

References

Abolwafa, N. F., & Mohamed, A. H. (2017). Effect of educational program on mothers knowledge about prevention of pneumonia for their children under five years. IOSR Journal of Nursing and Health Science, 6(5), 5-12.

Nelson, B. D. (2015). Essential clinical global health. Hoboken, NJ: John Wiley & Sons.

Rudan, I., O’Brien, K. L., Nair, H., Liu, L., Theodoratou, E., Qazi, S.,… Campbell, H. (2013). Epidemiology and etiology of childhood pneumonia in 2010: Estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries. Journal of Global Health, 3(1), 1-19.

Shan, V. P., Tunik, M. G., & Tsung, J. W. (2013). Prospective evaluation of point-of-care ultrasonography for the diagnosis of pneumonia in children and young adults. JAMA Pediatrics, 167(2), 119-125.

My primary diagnosis at this point

My primary diagnosis leads to a condition known as Community-Acquired Pneumonia (CAP). CAP is one of the respiratory conditions that are closely related to Hospital Acquired Pneumonia (HAP). While HAP affects individuals in healthcare facilities, CAP is common amongst individuals outside medical facilities. Some of the factors that substantiate my diagnosis espouse the symptoms associated with CAP.

Prina, Ranzani, and Torres (2015) allude that tachypnea, crackles, and high fever are signed, which indicate that the patient is suffering from CAP. In this regard, the symptoms presented by Leroy on his second visit to the clinic are similar to those associated with CAP. The symptoms advanced by Leroy are linked to respiratory issues, a phenomenon that guides medical practitioners to the conclusion that he is suffering from CAP. As such, the conclusion that Leroy suffers from CAP emanates from the similarity of his experiences and the symptoms of CAP.

The tests that I will perform

To ascertain fully that the patient suffers from CAP, I will need to undertake several tests. Some of the tests comprise CBC that represents a complete blood count, chest X-ray, and sputum. By testing the blood count, I will be in a position of analyzing and assessing whether Leroy’s blood has additional white blood cells. It is fundamental to explain that the presence of additional or extra blood cells is one of the predisposing factors, which confirm that the patient has CAP. Consequently, a chest X-ray helps reveal whether the lungs have fluids that lead to CAP (Feldman & Anderson, 2015). To get near precise results, I will use Computed Tomography (CT) X-ray because the common x rays may not give clear results. Furthermore, I will test Leroy’s sputum and the amount of oxygen in his blood.

Sputum tests are very important in examining the presence of bacteria or other causatives that may have initiated the eventuality of the disease. Besides, sputum tests help in establishing the presence of fluids in the respiratory system of the patient. For a clear examination of the bacteria or fungi that may have triggered the infection, I will undertake blood tests through the process referred to as blood culture.

Another important test that I will engage in is auscultation. Wunderink and Waterer (2014) explain that auscultation tests help medical practitioners listen keenly to the internal process of the body such as heartbeat rate and breathing using a stethoscope. Through the test, I will be in a better place to reaffirm the presence of pulmonary crackles and tachypnea that indicate the presence of the CAP.

Pharmacological treatment and its mechanism of action

Since Leroy appears fit and UT infections have diminished, I will provide medication that he will take at home. It is important to state that CAP is a condition that is treated using antibiotics. Some of the antibiotics that are useful in treating CAP include Doxycycline, Macrolide, and Quinolone. Therefore, with knowledge of Leroy’s health and age, I will use an antibiotic that best suits his condition. I will choose azithromycin, a macrolide, which addresses CAP by ensuring that mRNA translation does not materialize.

Musher and Thorner (2014) highlight that azithromycin is an antibiotic that interferes with the growth of bacteria because it hampers the synthesis of proteins that are vital in bacterial development. The dosage that I will prescribe espouses an oral intake of the antibiotic for five days. The patient will commence his medication by taking a single dose of 500mg and then proceed with a regular intake of 250mg per day for four days. Besides advising Leroy to continue taking water about eight glasses per day, I will also have him visit the clinic after 3 days so that I can check his progress.

References

Feldman, C., & Anderson, R. (2015). Community-acquired pneumonia: Pathogenesis of acute cardiac events and potential adjunctive therapies. CHEST journal, 148(2), 523-532.

Musher, D., & Thorner, A. (2014). Community-acquired pneumonia. New England journal of medicine, 371(17), 1619-1628.

Prina, E., Ranzani, O., & Torres, A. (2015). Community-acquired pneumonia. The lancet, 386(9998), 1097-1108.

Wunderink, R., & Waterer, G. (2014). Community-acquired pneumonia. New England journal of medicine, 370(6), 543-551.

Hospital-acquired diseases are frequent incidents as the conditions in which patients are located contribute to their development significantly. Most patients have weakened immunity due to injuries or illnesses that are the causes of their hospitalization. At the same time, they are surrounded by hundreds of other people with other ailments. Even patients who cannot leave their rooms are also exposed to external factors because medical personnel carries germs and bacteria on their clothes and hand. Ventilator-associated pneumonia (VAP) is a leader in hospital-acquired infections as respiration devices create an environment for the growth of bacteria and this disease is especially dangerous (Lyons & Kollef, 2018). Nowadays, the cases of VAP are significantly lower than decades ago because nurses use preventive measures to decrease the risks of infection. However, the problem of inappropriate care for patients who need artificial ventilation of lungs still exists and causes pneumonia, which has to be eliminated.

There are many diseases that a patient can get in the hospital, but some of them are easily transmitted, while others are less spreadable. Ventilator-associated pneumonia arises due to the wrong use of medical devices, such as catheters, improper oral cleaning, and non-compliance with hygiene rules by patients and medical personnel (Boev & Kiss, 2017). The consequences of infection can be a more prolonged treatment of the patient and their depressed state, as well as the occurrence of injuries and even death.

However, there is still a lag in the literature about the prevention of these diseases. Scientists study pneumonia as part of hospital-acquired infections, for example, Salem (2019) and Bashar (2019), or evaluate the knowledge of nurses on this topic as Rafieia, Rahimia, Shafaeia, and Ommatmohammadi (2020). Lyons and Kollef (2018) study the preventive measures of VAP in detail; however, they emphasize direct care but not a general strategy. Thus, there is a need to identify health strategies that reduce the incidence of VAP, since this disease can be avoided mostly by professional skills and the care of nurses.

The role of nurses is crucial in preventing ventilator-associated pneumonia as they perform primary care for patients and should monitor the risks and treatment of patients. For this reason, every advanced nurse has to know and use strategies that can improve his or her direct care and performance of his or her colleagues and subordinates. Consequently, competencies of advanced nurses are necessary for this purpose, since their work is vital for the treatment and rehabilitation of patients and organizational skills are sufficient and useful for building collaboration within the staff.

Possible Strategies for VAP Prevention

There are several strategies for reducing the number of hospital-acquired VAP cases that advanced nurses can apply by using their professional skills. According to the Royal College of Nursing (2018), the core competencies of an advanced nurse are direct care, leadership, and collaborative practice, improving quality and developing practice, developing self and others. Consequently, the strategies can include refreshing and gaining knowledge through collaboration, developing new methods of prevention and control, leading subordinates, and testing nurses’ skills for the prevention of VAP.

The first strategy is justified by the fact that most of the nurses are not familiar with the basic rules for taking care of patients who need artificial ventilation of lungs. According to a study by Rafieia et al. (2020), not a single nurse answered all questions about preventing VAP correctly. In addition, Salem (2018) his study, determined that although most nurses had a good understanding of such simple methods of preventing infection as washing hands and using sterile gloves, most of them neglected the rules for various reasons. Consequently, the participation of medical personnel in seminars on this topic is a necessity to reduce the incidence of hospital-acquired diseases.

Hospital management and advanced nurses also should encourage colleagues to improve prevention methods by helping them to promote their ideas and share them at medical conferences. The promotion of collaborative work of different specialists is also a beneficial strategy, since it creates conditions in which representatives of different healthcare areas and levels develop a better way for patient care. Leadership also is the most effective and convenient way of influence, since senior professional nurse can encourage her or his colleagues to be more responsible in their direct care and interaction with patients (Royal College of Nursing, 2018). Training should also be provided for junior staff by advanced nurses to ensure their knowledge of the necessary measures to prevent infections, including pneumonia.

Senior nurses also need to monitor the implementation of hygiene rules and the use of medical instruments to help fill up the knowledge of newcomers. In addition, Salem (2018) emphasized that some employees know the rules but ignore them due to negligence, limited time, or other reasons; thus, implementation fines for the violation of standards can be useful. No-pay policy for hospital-acquired infection also can be beneficial, since the same method for hospital-acquired falls had a positive impact on nurses’ work (Fehlberg et al., 2017). However, these changes are beyond advanced nurse’s authorities; hence she or he can only initiate them and control other nurses by warnings or administrative measures.

Strategic Focus

The most appropriate strategy for the elimination of hospital-acquired cases of ventilator-associated pneumonia is conducting seminars and training for nurses. This method is available for any advances nurses, since it requires only attention and interest of personal but do not bring additional costs. It also ensures that staff is familiar with the rules of patient care for the prevention of VAP, and these seminars provide an opportunity to exchange observations and discus unclear nuances.

The obligatory program of these seminars is to identify the main steps of patient care and understand their needs. Patients are admitted to a hospital with various diseases and different states of health; hence, it is impossible to write a uniquely clear guide for all nurses. However, there are general steps and recommendations that must be followed to protect patients from ventilator-associated pneumonia.

The first step after hospitalization, in any case, is an examination of a patient by a doctor and determination of diagnosis and treatment. The nurse should use the information provided by the physician and his or her prescriptions, as well as evaluate the patient’s behavior according to general and individual characteristics. Based on these characteristics, the nurse can assess the risks of developing complications and acquiring diseases. For example, a history of lung infections or a weakened immune system due to other disorders or age can reduce the body’s resistance to new conditions. Thus, these features have to be considered for the determination of preventive procedures. This step is necessary to anticipate all possible complications, but at the same time not to overload the patient’s body with unnecessary means and medicines.

The next step is the selection of the necessary preventive measures appropriate to certain risks. First, the nurse should advocate using non-invasive methods of ventilation as this change reduces the likelihood of infection (Bashar, 2019). Enteral feeding is also more beneficial for the patient than parenteral, so the nurse should offer the physician alternative method if possible (Bashar, 2019). However, if these options are not available, then several procedures can help reduce the likelihood of bacteria spreading. Among them, the location of the patient’s head on the bed at an angle of 30-45 degrees, daily oral cleaning with chlorhexidine, digestive antibiotics, regular bathing, prevention of wounds, and ulcers (Boev & Kiss, 2017). All these basic methods should be explained to nurses and discussed by them.

In addition, there are general guidelines for patient safety. Among basic rules are washing hands, using sterile instruments, disinfecting punctures, wearing a medical uniform and mask, and avoiding work if a nurse has infectious and respiratory diseases (Boev & Kiss, 2017). These steps are the most important in the treatment of patients and almost completely depends on the competence and professional skills of a nurse.

Therefore, regular seminars at which senior and junior nurses will discuss preventive measures will allow them to obtain and refresh knowledge. In addition, not only theory should be presented at trainings but also practical aspects, for example, catheter change, as well as colleagues can share their unusual cases. This practice will improve both collaboration and quality of direct patient care, but it does not take much working time.

Outcome of Strategy in the Prevention of Hospital-Acquired VAP

There are several methods to evaluate the usefulness of training for reducing the incidence of VAP. The first method is to check the theoretical knowledge of nurses by using questionnaires. This method is easy to implement, since nurses can use ready-made questions for tests from scientific research. For example, Rafieia et al. (2020) create nine categories of items for their study that cover necessary preventive measures. These tests can also be expanded and improved for more detailed assestment.

Another method is to check patients who need ventilation and their prescriptions and compare them with basic preventive measures and steps. This method is more accurate as it directly shows the work of a nurse; however, it requires considerable time for understanding each case and daily monitoring. Therefore, the main indicator of the success of the methods is the statistics on hospital-acquired VAP. The ratio of data on patients who need ventilation and cases of acquired pneumonia gives a clear idea of ​​the current situation, and its comparisons with data from previous months show the progress. Consequently, the success of such short-term strategy as conducting medical seminars can be measured simply, and an assessment of knowledge will help to determine the gap between theory and practice.

Conclusion

Therefore, the role of an advanced nurse in reducing the cases of ventilator-associated pneumonia in a hospital is one of the most significant among all medical personnel. The rehabilitation of the patients and the likelihood of their effective treatment depend on the responsibility and skills of this employee, since she or he performs practical care and affects theoretical medical knowledge. Consequently, the primary strategy for prevention VAP is conducting training and seminars for staff by advanced nurses, since it ensures their understanding of preventive measures. This strategy is also easy to implement and measure its success; thus, it is available for any hospital. In addition, seminars help to improve the quality of care of all nurses, regardless of their qualifications and professional experience, through collaborative discussion and decrease the level of hospital-acquired diseases.

References

Bashar, F. J. (2019). Methods of Preventing Hospital Acquired Infection. Advances in Bioscience and Clinical Medicine, 7(3), 13-19.

Boev, C., & Kiss, E. (2017). Hospital-Acquired Infections. Critical Care Nursing Clinics of North America, 29(1), 51–65.

Fehlberg, E. A., Lucero, R. J., Weaver, M. T., Mcdaniel, A. M., Chandler, M., Richey, P. A., … Shorr, R. I. (2017). Impact of the CMS no-pay policy on hospital-acquired fall prevention related practice patterns. Innovation in Aging, 1(3), 1-8.

Lyons, P. G., & Kollef, M. H. (2018). Prevention of hospital-acquired pneumonia. Current Opinion in Critical Care, 24(5), 370–378.

Rafieia, H., Rahimi, S., Shafaei, M., & Ommatmohammadi, M. (2020). Emergency nurses’ knowledge about ventilator-associated pneumonia. International Emergency Nursing, 48(2020), 1-4.

Royal College of Nursing. (2018). Advanced level nursing practice. Section 2: Advanced level nursing practice competencies. London, England: Royal College of Nursing.

Salem, O. A. (2019). Knowledge and practices of nurses in infection prevention and control within a tertiary care hospital. Annals of Medical & Health Science Research, 9, 422-425.