Pneumonia causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hamid Qazi, MD, BSc [2], Priyamvada Singh, M.D. [3]; Alejandro Lemor, M.D. [4]; Ogheneochuko Ajari, MB.BS, MS [5]

Overview

Pneumonia can result from a variety of causes, including infection with bacteria, viruses, fungi, parasites, and chemical or physical injury to the lungs. The etiology will depend upon various factors such as age, immune status, geographical area, and comorbidities.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Anthrax

Common Causes

• Cryptococcus neoformans
• Flu
• Histoplasmosis
• Hospital-acquired pneumonia
• Mycoplasma pneumonia
• Pneumocystis jiroveci
• Respiratory syncytial virus
• Rhinovirus
• Streptococcus pneumoniae

Causes by Pathogen

Click here for bacterial pneumonia

Click here for viral pneumonia

Click here for fungal pneumonia

Infants

Source of Infection

• Aerosol
• Aspiration of amniotic fluid
• Blood-borne infection across the placenta

Newborn

• Most common cause is Streptococcus agalactiae (Group B Streptococcus)
• GBS causes at least 50% of cases of CAP in the first week of life.
• Other bacterial causes in the newborn period include Listeria monocytogenes and tuberculosis
• Viral causes like herpes simplex virus (most common) adenovirus, mumps, and enterovirus

Children

• For the most part, children older than one month are at risk for the same microorganisms as adults.
• However, children less than five years are much less likely to have pneumonia caused by mycoplasma pneumoniae, chlamydophila pneumoniae, or legionella pneumophila.
• In contrast, older children and teenagers are more likely to acquire mycoplasma pneumoniae and chlamydophila pneumoniae than adults.
• A unique cause of CAP in this group is chlamydia trachomatis, which is acquired during birth but does not cause pneumonia until 2-4 weeks later.
• Common viruses include respiratory syncytial virus (RSV), metapneumovirus, adenovirus, parainfluenza, influenza, and rhinovirus.
• RSV in particular is a common source of illness and hospitalization.
• Fungi and parasites are not typically encountered in otherwise healthy infants, though maternally-derived syphilis can be a cause of CAP in this age group.

Microbiological Etiology

Typical Bacteria	Atypical Bacteria	Viruses
Streptococcus pneumoniae Haemophilus influenzae Staphylococcus aureus Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa	Mycoplasma pneumoniae Chlamydophila pneumoniae Legionella pneumophila	Influenza Parainfluenza Respiratory syncytial virus (RSV) Metapneumovirus Adenovirus

Most Common Etiologies for Community-Acquired Pneumonia

Outpatient	Inpatient (non-ICU)	Inpatient (ICU)
Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Influenza A and B, adenovirus, respiratory syncytial virus, parainfluenza	Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Legionella Aspiration Influenza A and B, adenovirus, respiratory syncytial virus, parainfluenza Yersinia enterocolitica	Streptococcus pneumoniae Staphylococcus aureus Legionella Gram-negative bacilli Haemophilus influenzae Acinetobacter baumannii

Community Acquired Pneumonia

Most Common Etiologies for Community-Acquired Pneumonia

Outpatient	Inpatient (non-ICU)	Inpatient (ICU)
Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Influenza A and B, adenovirus, respiratory syncytial virus, parainfluenza	Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Legionella Aspiration Influenza A and B, adenovirus, respiratory syncytial virus, parainfluenza Yersinia enterocolitica	Streptococcus pneumoniae Staphylococcus aureus Legionella Gram-negative bacilli Haemophilus influenzae Acinetobacter baumannii

Common Causes by Age Group

Age Group	Neonates	Children	Adults
Bacteria	Listeria monocytogenes Mycobacterium tuberculosis	Mycoplasma pneumoniae Chlamydophila pneumoniae Legionella pneumophila Chlamydia trachomatis	Typical Bacteria Streptococcus pneumoniae Haemophilus influenzae Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa Atypical Bacteria Mycoplasma pneumoniae Chlamydophila pneumoniae Legionella pneumophila
Virus	Herpes simplex virus Adenovirus Mumps Enterovirus	Respiratory syncytial virus (RSV) Metapneumovirus Adenovirus Parainfluenza Influenza Rhinovirus	Influenza Parainfluenza Respiratory syncytial virus (RSV) Metapneumovirus Adenovirus

• Newborn infants, children, and adults are at risk for different spectrums of disease causing microorganisms.

• In addition, adults with chronic illnesses, who live in certain parts of the world, who reside in nursing homes, who have recently been treated with antibiotics, or who are alcoholics are at risk for unique infections.

Infants and Newborns

• GBS causes at least 50% of cases of CAP in the first week of life.
• Other bacterial causes in the newborn period include Listeria monocytogenes and Mycobacterium tuberculosis.
• Viral causes like herpes simplex virus (most common), adenovirus, mumps, and enterovirus.

Children

• For the most part, children older than one month are at risk for the same microorganisms as adults.
• Children less than five years are much less likely to have pneumonia caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae, or Legionella pneumophila.
• In contrast, older children and teenagers are more likely to acquire Mycoplasma pneumoniae and Chlamydophila pneumoniae than adults.
• A unique cause of CAP in this group is Chlamydia trachomatis, which is acquired during birth but does not cause pneumonia until 2-4 weeks later.
• Common viruses include respiratory syncytial virus (RSV), metapneumovirus, adenovirus, parainfluenza, influenza, and rhinovirus.
• RSV in particular is a common source of illness and hospitalization.
• Fungi and parasites are not typically encountered in otherwise healthy infants, though maternally-derived syphilis can be a cause of CAP in this age group.

Adults

The causes of CAP in adults are outlined in the following categories:

Viruses

• Viruses account for about 20% cases of CAP.
• Common viruses are influenza, parainfluenza, respiratory syncytial virus, metapneumovirus, and adenovirus.
• Less common viruses include chicken pox, SARS, avian flu, and hantavirus.

Streptococcus pneumoniae

• Streptococcus pneumoniae is the most common cause of community-acquired pneumonia.
• Aspiration pneumonia is most commonly caused by anaerobic organisms.
• Prior to the development of antibiotics and vaccination, it was a leading cause of death.
• Traditionally, it was highly sensitive to penicillin, but during the 1970s resistance to multiple antibiotics began to develop.
• Current strains of drug resistant Streptococcus pneumoniae (DRSP) are common, accounting for twenty percent of all streptococcal infections.
• Risk factors for DRSP in adults include being older than 65, having exposure to children in day care, alcoholism, other severe underlying disease, or recent treatment with antibiotics; individuals exposed to these risk factors should initially be treated with antibiotics effective against DRSP.

Atypical Organisms

• Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila are often grouped as atypical pneumonia. Community-acquired pneumonia caused by these agents present insidiously, with a non-productive cough and prominent extra-pulmonary complaints, such as myalgias and diarrhea (lack the typical pneumonia symptoms of fever, cough, and sputum).

• Mycoplasma pneumoniae is often referred to as "walking pneumonia." It is transmitted via respiratory droplets and is common among healthy individuals in close contact with one another in settings such as dormitories or military barracks.

• Atypical organisms are more difficult to grow and respond to different antibiotics; they were discovered more recently than the typical bacteria discovered in the early twentieth century.

Haemophilus influenzae

• Haemophilus influenzae used to be a common bacterial cause of CAP.
• First discovered in 1892, it was initially believed to be the cause of influenza because it commonly causes CAP in people who have suffered recent lung damage from viral pneumonia.

Enteric Gram-Negative Bacteria

• Enteric bacteria such as Escherichia coli and Klebsiella pneumoniae may cause commnity-acquired penumonia.
• Risk factors in adults for infection include: living in a nursing home, serious heart and lung disease, and recent antibiotic use; these individuals should initially be treated with antibiotics effective against enteric Gram-negative bacteria.

Pseudomonas aeruginosa

• Pseudomonas aeruginosa is an uncommon cause of CAP, but it is a particularly difficult bacteria to treat.
• Individuals who are malnourished, have bronchiectasis, are on corticosteroids, or have recently had strong antibiotics for a week or more, should initially be treated with antibiotics effective against Pseudomonas aeruginosa.

Special Situations

• Coccidioides spp. are common in southwestern area of the United States.
• Anaerobic infection is common in alcoholics. Pneumococcal pneumonia remains the most common cause of CAP in alcoholics.
• Psittacosis (caused by Chlamydophila psittaci) should be considered in the patient with exposure to birds or bird droppings.
• Anaerobes are common in patients with poor dental hygiene and a suspected large volume of aspiration.
• Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Legionella species are the common causes of community acquired pneumonia in those with chronic obstructive pulmonary disorders and smokers.
• Streptococcus pneumoniae, Gram-negative bacilli, Haemophilus influenzae, Staphylococcus aureus, anaerobes, and Chlamydophila pneumoniae are more common in nursing home residents.
• Streptococcus pneumoniae, Haemophilus influenzae, and Mycobacterium tuberculosis are common pathogens in early stages of HIV, whereas, Pneumocystis jiroveci, Histoplasma, and Cryptococcus are commonly seen in late stages HIV.
• In patients with structural lung disease such as bronchiectasis and cystic fibrosis, Pseudomonas aeruginosa, Burkholderia cepacia, and Staphylococcus aureus are the common pathogens involved.

Aspiration Pneumonia

• Incompetent swallowing mechanism, as can be found in neurological disease (a common cause being strokes) or while a person is intoxicated.
• Iatrogenic causes such as general anaesthesia for an operation. Patients are therefore instructed to be nil per os (NPO) for at least four hours before surgery.
• Whether aspiration pneumonia represents a true bacterial infection or a chemical inflammatory process remains the subject of significant controversy.

Hospital Acquired Pneumonia

The causes of hospital acquired pneumonia are as follows:

Aerobic Gram Negative Pathogens

• Commonly polymicrobial
• Common microbial agents include:
  • Pseudomonas aeruginosa
  • Escherichia coli
  • Klebsiella pneumoniae
  • Acinetobacter

Gram-Positive Pathogens

• Staphylococcus aureus
• Methicillin resistant staphylococcus aureus (common in patients with diabetes mellitus, head trauma, and in ICU)

Elderly Population

• S. aureus
• Enteric gram-negative rods
• Streptococcus pneumoniae
• Pseudomonas

Ventilator-associated Pneumonia (VAP)

• The microbiologic flora responsible for VAP is different from that of the more common community-acquired pneumonia (CAP). In particular, viruses and fungi are uncommon causes in people who do not have underlying immune deficiencies.
• Though any microorganism that causes CAP can cause VAP, there are several bacteria which are particularly important causes of VAP because of their resistance to commonly used antibiotics. These bacteria are referred to as multidrug resistant (MDR).
• VAP has been classified into either early-onset pneumonia (EOP), if pneumonia develops within 96 hours of the patient’s admission to an ICU or intubation for mechanical ventilation, and late-onset pneumonia (LOP), if pneumonia develops after 96 hours of the patient’s admission to an ICU or intubation for mechanical ventilation.
• This categorization can be helpful to clinicians in initiating empiric antimicrobial therapy for cases of pneumonia, when the results of microbiologic diagnostic testing are not yet available.
• EOP has been associated usually with non-multi-antimicrobial-resistant microorganisms such as Escherichia coli, Klebsiella spp., Proteus spp., S. pneumoniae, H. influenzae, and oxacillin-sensitive S. aureus.
• On the other hand, LOP has been associated with Pseudomonas aeruginosa, oxacillin-resistant S. aureus, and Acinetobacter spp (strains that are usually multi-antibiotic-resistant).

The following is a list of the most MDR common pathogens associated with ventilator-associated pneumonia:

• Pseudomonas aeruginosa is the most common MDR gram-negative bacterium causing VAP. Pseudomonas has natural resistance to many antibiotics and has been known to acquire resistance to every antibiotic except for polymixin B. Resistance is typically acquired through upregulation or mutation of a variety of efflux pumps which pump antbiotics out of the cell. Resistance may also occur through loss of an outer membrane porin channel (OprD).
• Klebsiella pneumoniae has natural resistance to some beta-lactam antibiotics such as ampicillin. Resistance to cephalosporins and aztreonam may arise through induction of a plasmid-based extended spectrum beta-lactamase (ESBL) or plasmid-based ampC-type enzyme.
• Serratia marcescens has an ampC gene which can be induced by exposure to antibiotics such as cephalosporins. Thus, culture sensitivities may initially indicate appropriate treatment which fails due to bacterial response.
• Enterobacter as a group also have an inducible ampC gene. Enterobacter may also develop resistance by acquiring plasmids.
• Citrobacter also has an inducible ampC gene.
• Stenotrophomonas maltophilia often colonizes people who have endotracheal tubes or tracheostomies but can also cause pneumonia. It is often resistant to a wide array of antibiotics but is usually sensitive to co-trimoxazole.
• Acinetobacter are becoming more common and may be resistant to carbapenems such as imipenem and meropenem.
• Burkholderia cepacia is an important organism in people with cystic fibrosis and is often resistant to multiple antibiotics.
• Methicillin-resistant Staphylococcus aureus is an increasing cause of VAP. As many as fifty percent of Staphylococcus aureus isolates in the intensive care setting are resistant to methicillin. Resistance is conferred by the mecA gene.

Aspiration Pneumonia Causes

• Incompetent swallowing mechanism, such as in neurological disease (a common cause being strokes) or while a person is intoxicated.
• Iatrogenic causes such as general anaesthesia for an operation. Patients are therefore instructed to be nil per os (NPO) for at least four hours before surgery.
• Whether aspiration pneumonia represents a true bacterial infection or a chemical inflammatory process remains the subject of significant controversy.

Drug Side Effect

• Blinatumomab
• Belimumab
• Boceprevir
• Ceritinib
• Dornase Alfa
• Enfuvirtide
• ethanolamine oleate
• Felbamate
• Iloperidone
• interferon alfacon-1
• Pegylated interferon alfa-2b

Causes in Aphabetical Order

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Causes by Organ System

Cardiovascular	No underlying causes
Chemical/Poisoning	No underlying cause
Dental	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Blinatumomab, belimumab, boceprevir, ceritinib, dornase alfa, enfuvirtide, ethanolamine oleate, felbamate, iloperidone, interferon alfacon-1, pegylated interferon alfa-2b
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	No underlying cause
Gastroenterologic	No underlying cause
Genetic	No underlying cause
Hematologic	No underlying causes
Iatrogenic	No underlying cause
Infectious Disease	Acinetobacter baumannii, actinomycosis, adenovirus (serotype 1, 2, 3, 4, 5, 7, 14, 21, 35), AIDS-related opportunistic infections, aspergillosis, aspiration, bacillus anthracis, bird flu (avian influenza), blastomycosis, burkholderia cepacia, burkholderia pseudomallei, chlamydophila pneumoniae, chickenpox, coccidioides immitis, coronavirus, coxiella burnetii (Q fever), cryptococcus neoformans, cytomegalovirus, escherichia coli, enterovirus, francisella tularensis, gram-negative bacilli, haemophilus influenzae, H1N1 flu, hantavirus, herpes simplex virus, Histoplasma capsulatum, histoplasmosis, human bocavirus, Human parechovirus types 1, 2, and 3, influenza, klebsiella pneumoniae, legionella micdadei, legionella pneumophila (Legionnaires' disease), listeria monocytogenes, mycoplasma pneumoniae, measles, melioidosis, metapneumovirus, Middle East respiratory syndrome coronavirus, moraxella catarrhalis, mumps, mycobacterium avium-intracellulare, mycobacterium haemophilum, mycobacterium kansasii, neisseria meningitidis, New Haven coronavirus, nocardia, paragonimiasis, parainfluenza, pneumocystis jiroveci, pneumonic plague, proteus, pseudomonas aeruginosa, chlamydophila psittaci (psittacosis), rat-bite fever, respiratory syncytial virus (RSV), rhinovirus, rhodococcus equi, streptococcus pneumoniae (pneumococcus), SARS, serratia, severe acute respiratory syndrome, sporotrichosis , staphylococcus aureus, streptococcus agalactiae (group B streptococcus), streptococcus pyogenes (group A streptococcus), streptococcus pneumoniae, swine flu, toxocariasis , toxoplasma gondii, trichosporon , trypanosomiasis, typhus, varicella-zoster virus, yersinia enterocolitica, yersinia pestis, zygomycosis
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	No underlying causes
Nutritional/Metabolic	No underlying cause
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying cause
Ophthalmologic	No underlying causes
Overdose/Toxicity	No underlying cause
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal/Electrolyte	No underlying causes
Rheumatology/Immunology/Allergy	No underlying cause
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Miscellaneous	No underlying cause