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A. Pneumococcal Pneumonia

  1. S. pneumoniae is a highly virulent, lancet shaped, Gram positive diplococcus
    1. Teichoic acids on surface appear major induce much inflammation
    2. Polysaccharide (mucous) coat make organisms resistant to phagocytosis
  2. Most common cause of community acquired pneumonia (CAP), in :>30% of cases [1]
    1. Other streptococcal species can cause pneumonia as well
    2. Frequent cause of sinusitis, otitis media, bronchitis, bacteremia, other infections
  3. Predisposing Factors
    1. Splenectomy (patients should be on Penicillin prophylaxis)
    2. Hypogamma-globulinemia
    3. Nephrotic syndrome
    4. HIV (5X increased risk)
    5. Narcotic abuse
  4. Pneumonia
    1. Leading cause of pneumonia: nearly 500,000 cases per year
    2. Most common cause of CAP
    3. Rapidly progressive in most patients if untreated
    4. Fevers usually with rigors, up to 102-103°F
    5. Patients are toxic appearing, with severe malaise, diaphoresis
    6. Bacteremia common (positive blood cultures) - 5-10% of cases
    7. Cough common with copious sputum production - thick, yellow, diagnose with Gram stain
    8. Chest radiograph (CXR) shows consolidation, usually unilobar, though may progress
    9. Leukocytosis with marked immature neutrophil predominance (left shift)
  5. Diagnosis may require special antigen stains or genetic analyses [2]
  6. Treatment [3,4]
    1. Penicillin (PCN) is no longer the drug of choice for pneumococcal pneumonia
    2. At least 20% of all isolates are PCN resistant; not related to ß-lactamase
    3. Penicillin-resistant pneumococcal pneumonia has same mortality as sensitive disease
    4. For outpatients, oral macrolide, doxycycline, or fluoroquinolone is recommended
    5. For inpatients, most PCN-resistant pneumonical pneumonia is sensitive to cefotaxime or ceftriaxone (but not to ceftazadime) or to newer fluoroquinolones
    6. Vancomycin is drug of choice for hospitalized patients with penicillin and 3° cephalosporin resistance
    7. New fluoroquinolones include levofloxacin, gatifloxacin, moxifloxacin
    8. Intravenous levofloxacin or gatifloxacin can also be used for inpatients
  7. Antibiotic monotherapy is suboptimal for severe bactermic pneumococcal pneumonia [5]
    1. Quinolones and macrolides and/or vancomycin are generally part of the regimen
    2. Third generation cephalosporins are probably less clinically effective [5]
  8. Vaccination is highly effective and underused

B. Hemophilus Pneumonia

  1. Characteristics
    1. Non-typable hemophilus species are second most common cause of bacterial pneumonia
    2. Non-typable strains frequently colonize patients with COPD
    3. Type B Common in children <6 years and in elderly
    4. Overall causes ~10% of CAP, particularly in elderly persons and COPD
  2. Symptoms
    1. Onset acute (children and elderly) or gradual (COPD)
    2. Moderate to high fever
    3. Sputum production
  3. Chest Radiograph
    1. Scattered or no infiltrates in COPD
    2. Children and immune compromised adults may show rapid progression
    3. Consolidation may occur in these patients
  4. Invasive H. influenzae pneumonia occurs fairly frequently in adults
    1. Majority (~80%) of the patients were women
    2. Risk factors for invasion: chronic lung disease, pregnancy, HIV infection, neoplasia
    3. Many isolates were ampicillin resistant
  5. Treatment [3,4]
    1. Standard therapies must cover H. influenzae
    2. Cefuroxime covers H. influenzae well including ß-lactamase positive strains
    3. COPD prophylaxis is usually not recommended, but TMP/SMX (Bactrim®) may be used
    4. Outpatient: newer fluoroquinolones or second generation macrolides recommended
    5. For inpatients, 3° cephalosporin or newer fluoroquinolones are recommended
  6. Vaccination
    1. Vaccine only for serotype B is available
    2. Strongly recommended for children and in immunocompromised patients
    3. Vaccine for non-typable strains not yet available

C. Mycoplasma

  1. Characteristics
    1. Mycoplasma pneumoniae is an atypical organism
    2. Common cause of CAO; most common cause of CAP in young adults
    3. Also called "Walking Pneumonia"
    4. Rarely occurs in mechanically ventilated patients
  2. Symptoms
    1. Cough with pleurisy, usually non-productive of sputum
    2. Fever common; but chills uncommon
    3. Myalgias, arthralgias, malaise common
    4. Bullous myringitis (tympanic membrane inflammation) occurs occasionally
    5. Long prodrome (usually with non-productive cough) common
    6. Variety of rashes (eg. maculopapular) not uncommon
    7. Rarely severely ill
  3. Extrapulmonary manifestations
    1. Hemolytic anemia - due to cold agglutinins: IgM Abs against red blood cell I antigens
    2. CNS complications - transverse myelitis
    3. Myopericarditis
    4. Erythema multiforme
    5. Stevens-Johnson Syndrome
    6. Pharnyngitis with cervical lymphadenopathy
    7. Sinusitis
  4. Chest Radiograph
    1. Often very faint or no infiltrates
    2. Diffuse, patchy interstitial infiltrates
    3. Pleural effusions are uncommon
  5. Diagnosis
    1. Mycoplasma titers are used
    2. Cold agglutinins elevated in ~50% of cases (may be elevated in other infections)
    3. Cold agglutinins are anti-erythrocyte antibodies that can cause hemolysis, clumping
    4. Antibodies are directed against the I antigen on erythrocytes
    5. Deep sputum sample, bronchealveolar lavage (BAL) or biopsy specimen may be needed
    6. Immunofluorescence test now available for staining specimens
    7. Polymerase chain reactions are being developed
  6. Treatment
    1. Inpatient: macrolide IV, doxycycline 100mg bid IV, or IV fluoroquinolone
    2. Outpatient (or tolerating po): Erythromycin, Clarithromycin, Azithromycin, Doxycycline, Fluoroquinolone
    3. Symptoms may persist up to ~2 weeks despite therapy
    4. Untreated patients have symptoms persist >4 weeks
  7. Respiratory Complications
    1. Intractable cough (despite adequate therapy)
    2. Bullous myringitis, Sinusitis
    3. Pharyngitis with cervical lymphadenopathy

D. Chlamydophila Pneumonia

  1. Introduction
    1. Organism previously called Chlamydia pneumoniae now Chlamydophila pneumoniae
    2. C. pneumoniae previously called the "TWAR" agent (initials of first two patients)
    3. Obligate intracellular gram negative organism
    4. Distinct from Chylamydia trachomatis and C. psittici (<10% DNA homology)
    5. Causes ~10% of CAP
    6. Reported in nursing home outbreaks with high morbidity and some mortality
  2. Clinical Presentation
    1. Prolonged, mild to moderate pneumonia
    2. Fever and cough very common, often with rales (crackles)
    3. Pharyngitis ± hoarseness in ~50% of patients (may precede pneumonia by 1-3 weeks)
    4. Up to 5% of bronchitis and sinusitis cases may be caused by C. pneumoniae
    5. This syndrome is much less severe than that seen with C. psittici
  3. Laboratory
    1. Chest radiograph usually shows single subsegmental lesions with bronchopneumonia
    2. Air space consolidation occurs in ~30% of cases
    3. Serum microimmunofluorescence most useful diagnostic test (IgM versus IgG)
    4. Antibody rise occurs 1 month (IgM) or 2 months (IgG) post infection (symptom onset)
  4. Treatment
    1. Erythromycin may actually prolong the infection
    2. Tetracycline or doxycycline for 2 weeks is recommended treatment

E. Psittacosis / Ornithosis [6]

  1. Introduction
    1. Chlamydia psittaci is an obligate intracellular parasite with no cell wall
    2. Inhaled into the lungs
    3. Ubiquitous zoonosis, carried primarily by birds (mainly parrots) and animals
    4. 80% of patients have contact with some species of bird prior to illness
  2. Clinical Presentation
    1. Systemic illness, may begin suddenly with high fever
    2. Progressive fever over 2-4 days
    3. Headache, myalgia, pharyngitis (no exudate), epistaxis
    4. Persistent cough in many cases, may be productive
    5. Splenomegaly, skin lesions (erythematous spots) may occur
    6. Can affect many organs: endocarditis, hepatitis, meningitis, rash, etc.
    7. Acute renal failure (glomerulonephritis) with hematuria can occur
    8. Fulminant toxic syndrome resembling typhoid or sepsis also described
  3. Laboratory
    1. Leukopenia, possibly severe, in ~25% of cases
    2. Antibody titer 1:32 or higher in appropriate clinical setting is diagnostic
    3. Antibodies often cross-react with Chlamydia pneumoniae
    4. Organism generally not cultured (requires tissue culture)
    5. Patchy infiltrate on chest radiograph, often hilar or in lower lobes
    6. Polymerase chain reaction tests are being developed
    7. Legionella infection should be ruled out
  4. Treatment
    1. Tetracycline or doxycycline 10-21 days
    2. Second generation macrolides also have activity
    3. Diagnosis should be reported to public health service
    4. Treat infected birds

F. Legionella [7]

  1. Properties of Legionella pneumophilia
    1. Intracellular pathogen
    2. >30 known species; >50 serotypes; serologies 1, 4, 6 most common in humans
    3. Ingested by macrophages and neutrophils, inhibits lysosomal fusion
    4. Gram negative cell wall
    5. Mainly found in wet (humidified) sources
    6. Monochloramine disinfection is effective for reducing risk of transmission [8]
  2. Risk Factors
    1. Smoking
    2. Immunocompromise
    3. Head / Neck surgery
    4. Recent plumbing repairs
    5. Hospitalization in building with contamined ventilation system
  3. Symptoms, Signs and Laboratory
    1. Fever
    2. Pleuritic pain (~30%)
    3. Hyponatremia (~45%) - not specific for Legionella pneumonia
    4. Major change in vital signs: hypotension, tachypnea (hypoxemia), bradycardia
    5. Very often associated with gastrointestinal upset
    6. Often not accompanied by sputum production
    7. Overall increased incidence of hyponatremia (but not very useful for individual patient)
  4. Chest Radiograph (CXR)
    1. Pleural effusion (~50%)
    2. Multilobar involvement common
    3. Interstitial pattern often seen early
    4. Cavitation is not uncommon
  5. Diagnosis [9]
    1. Legionella Direct Fluorescence Antigen (DFA) is usual test
    2. DFA - rapid way to make diagnosis (90-100% specificity) but ~35% sensitivity
    3. Urine antigen detection with RIA or ELISA is not sufficiently sensitive
    4. New indirect immunofluorescent serum antibody: titer at least 1:256 is significant
    5. However, seroconversion may not be reliable indicator of early infection
    6. Polymerase chain reaction testing may become gold standard, highly sensitive [9]
  6. Treatment [10]
    1. High dose erythromycin 1g q6 hour IV was previous optimal therapy
    2. This therapy is poorly tolerated, and probably not as effective as newer agents
    3. Intravenous once daily azithromycin 500mg IV is as effective and much better tolerated
    4. "Respiratory" fluoroquinolones such as levofloxacin, moxifloxacin also very effective
    5. Rifampin 300mg bid x 21 days may be added for severe cases
    6. Oral antibiotics when patient stabilizes (new macrolides or quinolones)
    7. For many CAP, second generation macrolides or "repiratory" flouroquinolones are the clear agents of choice prior to definitive identification of organism

G. Staphylococcal Pneumonia

  1. Clinical Setting
    1. Usually occurs in compromised (hospitalized) host
    2. Up to 15% of in hospital pneumonia cases
    3. Classically described as either during or following influenza (less common now)
    4. Diabetes mellitus
    5. Neoplastic disease / Chemotherapy
    6. Hypogammaglobulinemia
    7. Alcoholism
    8. Less than 5% of CAP; more common in children <3 years old and elderly
    9. May be secondary to bacteremia or endocarditis
  2. Symptoms
    1. High fever (105°F) and chills
    2. Cough with blood stained, thick sputum
    3. Tachypnea and cyanosis
  3. Chest Radiograph (CXR)
    1. Early consolidation (organism destroys alveolar cell walls)
    2. Multiple lobes usually involved
    3. Multiple abscess and empyema formation
    4. Residual necrosis / fibrosis
    5. Pneumatocele formation, mainly in children
  4. Diagnosis
    1. Clinical setting - patient's age, hospitalization, general health
    2. Gram Stain: grape-like clusters of Gram positive cocci
    3. Culture: usually grows S. aureus
  5. Therapy
    1. Supportive care very important
    2. May require constant oximetry monitoring and intubation
    3. Double antibiotic coverage is recommended for severely ill patients
    4. Oxacillin (or Cefazolin) and Gentamicin, Unasyn® and Gentamicin
    5. Vancomycin or linezolid for methicillin resistant staphylococci
    6. Outpatient: dicloxacillin, first generation cephalosporin, TMP/SMX (Bactrim®)

H. Gram Negative Pneumonia

  1. Typically hospital and nursing-home acquired infections
  2. Ventilated and immunocompromised patients are usual hosts
  3. Increased risks in patients with immunocompromise, particularly neutropenia
  4. Alcoholics have higher rates of K. pneumoniae and other gram negative species
  5. Very high mortality, antibiotic resistance, and lung destruction
    1. Pseudomonas aurugenosa has ~61% mortality
    2. Klebsiella pneumoniae and others ~35% mortality
    3. Escherichia coli ~35% mortality
    4. Neutropenic patients with pneumonia are at particularly high risk for death
  6. Double antibiotic coverage for serious infections
    1. Extended spectrum ß-lactam + aminoglycoside preferred
    2. Aztreonam or Imipenem with an aminoglycoside also acceptable

I. Aspiration Pneumonitis and Pneumonia [11]

  1. Aspiration Syndromes
    1. Aspiration pneumonitis (Mendelson's Syndrome) - chemical injury
    2. Aspiration pneumonia - infection with oropharyngeal bacteria
    3. Airway obstruction - mucus plugging
    4. Lung abscess
    5. Exogenous lipoid pneumonia
    6. Chronic interstitial fibrosis
    7. Mycobacterium fortuitum pneumonia
  2. Clinical Setting
    1. Impaired gag reflex
    2. Comatose patients
    3. Alcoholics (often post-binge)
    4. Stroke
    5. Mechanical Ventilation
  3. Aspiration Pneumonia - Organisms
    1. Oral anaerobes (Peptococcus, Peptostreptococcus, Fusobacterium)
    2. Non-oral anaerobes - Bacteroides ssp., especially in recurrent infection
    3. Superinfection with gram negative rods - common in chronically ill patients
    4. Klebsiella pneumoniae superinfection quite common, especially in alcoholics
  4. Chest Radiograph
    1. Site of consolidation depends on position of aspiration
    2. Usually patient lying down, and middle or upper lobes involved
    3. Bibasilar pneuomonias not uncommon, especially in semi-conscious patients
  5. Anaerobic Pneumonia
    1. Common in chronic aspiration, nursing home patients, etc.
    2. Bacteroides species (including B. fragilis) often involved
    3. Pleural exudates, empyema, lung abscess not uncommon
  6. Treatment
    1. Aspiration precautions - raise head of bed, encourage solid foods
    2. Broad spectrum antibiotics are generally indicated
    3. Timentin® or Unasyn® - excellent pan-coverage including B. fragilis
    4. Clindamycin - B. fragilis may be resistant, no Gram negative coverage
    5. Metronidazole - excellent Gram negative anaerobic coverage (do not use alone)
    6. Penicillin - Bacteroides species often resistant, and no Gram negative coverage
  7. Post-obstructive (such as tumor) pneumonias have similar organisms and treatment

J. Ventilator Associated Pneumonia (VAP) [2]

  1. Nosocomial bacterial pneumonia in patients on mechanical ventilation
    1. Due to bacterial colonization of aerodigestive tract
    2. Also usually involves aspiration of contaminated secretions into lower areas
  2. Early Onset
    1. Within 72 hours of endotracheal intubation
    2. Usually due to relatively sensitive bacteria
    3. Oxacillin-sensitive Staphylococcus (Staph) aureus
    4. Haemophilus influenzae
    5. Streptococcus pneumonia
  3. Late Onset
    1. More than 72 hours after endotracheal intubation
    2. Usually due to resistant pathogens
    3. Oxacillin-resistant Staph aureus (MRSA)
    4. Pseudomonas aeruginosa
    5. Acinetobacter species
    6. Enterobacter species
    7. Mortality rate 10-30%
  4. Treatment
    1. Supportive care
    2. Antibiotics - initially with focused spectrum, then taper to specific organisms
  5. Reducing Antibiotic Resistance in ICU [12]
    1. Antibiotic resistance in the intensive care unit (ICU) is an increasing problem
    2. Most commonly seen in mechanically ventilated patients
    3. The following should be instituted to reduce development of antibiotic resistance:
    4. Limit unnecessary antibiotic administration
    5. Antibiotics for VAP for 8 days as effective as 15 days with less antibiotic use and less development of resistance [13]
    6. Optimize antimicrobial effectiveness
    7. Reduce length of mechanical ventilation (use noninvasive ventilation whenever possible)
    8. Increase vaccination of adults to pneumococcus, influenza virus, and H. influenzae
  6. Prophylaxis [14]
    1. Remove endotracheal (ET) and naso(oro-)gastric tubes as soon as possible
    2. Formal infection control program including hand washing
    3. Semirecumbant positioning of patient
    4. Provide adequate nutritional support
    5. Avoid gastric overdistension
    6. Noninvasive (positive pressure) or oral, non-nasal, intubation whenever possible
    7. Continuous subglotic suctioning
    8. Maintain adequate pressure in ET tube cuff
    9. Chest physiotherapy of no proven benefit, not recommended
    10. Prophylactic systemic or inhaled antibiotics are not effective and should not be used
    11. Selective digestive tract decontamination is of questionable benefit [15]
    12. Sucralfate is generally preferred over H2-blockers ro reduce risk of VAP but clear data are not available [15]
  7. Sucralfate generally preferred over H2-antagonists for stress ulcer prophylaxis

K. Pneumocystis jiroveci (PCP) [16,17]

  1. Formerly called Pneumocystis carinii
    1. Fungal Organism (formerly classified as a protozoan)
    2. Lives in many animals, in alveolar space
    3. Lower respiratory organism in all normal humans
    4. Universal exposure to organism as children
    5. Most commonly occurs in HIV disease
    6. Also occurs in patients on immunosuppressive agents
    7. May occur during glucocorticoid tapers as well
    8. Not uncommon in cancer patients
  2. Diagnosis
    1. Clinical suspicion, usually in HIV infected patients (CD4 <250 cells/µL)
    2. Usually acute, diffuse interstitial pneumonia on chest radiograph (CXR)
    3. However, may present with any abnormality on CXR
    4. For example, upper lobar PCP is not uncommon in patients on pentamidine prophylaxis
    5. Sputum for analysis (india ink) or Bronchiolar lavage (BAL)
    6. Serum LDH: highly sensitive, relatively specific for PCP
    7. High A-a gradient (>10mm): insensitive and nonspecific
  3. Therapeutic Options
    1. Selection usually depends on severity of disease and comorbid conditions
    2. Many patients develop allergies or other intolerance to one or more of these agents
    3. Side effects / reactions must be monitored closely
  4. Trimethoprim-Sulfamethoxazole (TMP-SMX, Bactrim®)
    1. Most effective drug; may be given intravenously or orally
    2. Of all agents, poorest tolerability in HIV+ patients
  5. Other Agents
    1. Pentamidine
    2. Clindamycin + Primaquine
    3. Atovaquone (Mepron®)
    4. Dapsone + trimethoprim
    5. Trimetrexate (NeuTrexin®) - qd injections with leucovorin, 21 days, 45mg/m2
    6. TMP-SFX, Dapsone-TMP, and Clindamycin + Primaquine equal efficacy in mild disease
  6. Prophylaxis
    1. TMP/SMX (Bactrim®, Septra®) 1 SS (double strength) po qd or bid 3 times/week
    2. Dapsone 100mg + Pyramethamine 50mg po 2-3 times / week (now second line)
    3. Pentamidine (300mg), aerosolized, q month (now third line for prophylaxis)
    4. Overall, TMP/SMX most effective but with poorest tolerability
    5. TMP/SMX and Dapsone/Pyramethamine also prevent Toxoplasmososis
    6. Despite prophylaxis, PCP occurs in ~15% of patients with CD4<75/µl over 2 years
    7. G6PD levels should be checked before using dapsone or pyramethamine

L. Other Atypical Organisms

  1. Mycobacterial infections
    1. Increased incidence in HIV disease and intravenous drug abusers
    2. Increasing incidence of drug resistant infections
    3. Atypical mycobacterial infections (non-tuberculosis) may also occur
    4. Atypical mycobacteria nearly always occur in immunocompromised patients
  2. Fungal Pneumonia
    1. Usually occur in immunocompromised hosts
    2. Bronchoalveolar lavage (or biopsy specimen) is often required for diagnosis
    3. Typical Fungal Pneumonias: Aspergillis, Cryptococcus, Histoplasma
    4. Unusual: Zygomycetes, Fusarium, Candida, Coccidioides
  3. Organizing Pneumonia (OP) [18]
    1. Also called "cryptogenic OP" or bronchiolitis obliterans with OP (BOOP)
    2. Non-specific response to infectious and other types of lung injury
  4. SARS - human coronavirus
  5. Metapneumovirus [19]

M. Treatment Considerations [3,4]

  1. Antibiotic Selection
    1. If sputum strongly suggests single organism in appropriate clinical setting, treat that organism
    2. Otherwise obtain cultures and begin therapy covering most likely organisms
    3. Adjust therapy based on clinical course and microbiology
    4. In CAP, pneumococcus should always be covered
  2. CAP - Outpatients Age <60 Years with No Comorbidities [3]
    1. Newer macrolide or fluoroquinolone is preferred [3,21,22]
    2. Erythromycin may be used, but is poorly tolerated and often stopped
    3. Therefore, clarithromycin or azithromycin are now strongly recommended [7]
    4. "Respiratory" fluoroquinolones include levofloxacin, moxifloxacin or grepafloxin [3,4]
    5. Doxycycline is an effective, inexpensive alternative [3,23]
  3. CAP - Outpatients >60 years old or with comorbidities [3,21,22]
    1. Antipneumococcal fluoroquinolone alone may be sufficient
    2. Second generation macrolide is generally recommended (caution drug interactions)
    3. Amoxicillin+clavulanate (Augmentin®) ± Macrolide
    4. Cefuroxime axetil (Ceftin®) + Macrolide or doxycycline
    5. Doxycycline is also inexpensive and reasonable, particularly in non-smokers
    6. Avoid first generation quinolones or erythromycin; TMP/SMX less well tolerated
  4. CAP - Empiric Inpatient Treatment [3]
    1. Intravenous azithromycin or newer fluoroquinolones cover nearly all organisms
    2. Double coverage with ceftriaxone or cefotaxime + macrolide or fluoroquinolone is recommended [21,22]
    3. Resistant, typical: ticarcillin+clavulanate (Timentin®) or piperacillin+sulbactam (Zosyn®) or a penam + tobramycin (or amikacin) + metronidazole
    4. If staphylococcus suspected (severe disease, cavitary lesions, previous infection), vancomycin should be added
    5. Prognostic rules for elderly patients with CAP have been developed [24]
    6. Patients with severe pneumonia treated with parenteral antibiotics for 48 hours regardless of fever status then switched to oral agents do well [25]
  5. Hospital Acquired Pneumonias [4]
    1. Aminoglycoside + one of the following to cover Gram positive organisms:
    2. Ceftriaxone, cefotaxime, cefepime, Timentin®, Zosyn®, meropenem or imipenem
    3. If Pseudomonas is suspected, ceftazidime can be used
    4. Vancomycin must be used if staphylococci are supsected pending identification
    5. Anaerobic coverage may include metronidazole (or Timentin® or Zosyn®)
    6. Atypical organisms can be covered by second generation macrolide or fluoroquinolone
  6. Atypical Pneumonias [10]
    1. Treatment: High dose clarithromycin or azithromycin or "respiratory" fluoroquinolones
    2. Doxycyline can often be used in patients intolerant to macrolides or fluoroquinolones
  7. Pneumonias Acquired in Nursing Homes / Chronic Care Facilities
    1. S. pneumonia ~ 20%
    2. Klebsiella pneumonia ~15%
    3. Staphylococcus aureus ~10% (may be methicillin / erythromycin resistant)
    4. H. influenza ~8%
    5. Aspiration Pneumonias (mouth flora): ~15%
    6. Others: Moraxella catarrhalis, E. coli, Group B Streptococcus, other gram negatives

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