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community-acquired pneumonia (CAP)

Pneumonia acquired in the community. (also see pneumonia) Etiology: 1) adults a) pathogen identified in 38% of cases [52] - viruses in 23% - bacteria in 11% - both bacteria & virus in 3% - fungus or mycobacterium in 1% b) most commonly detected pathogens (% of cases) - rhinovirus (9%) - influenza virus (6%)* - S. pneumoniae (5%) - human metapneumovirus (4%) - respiratory syncytial virus (3%) c) common bacteria - Streptococcus pneumoniae, most common in adults [52] - 90% of identified bacterial isolates in adults - 95% of identified isolates in preantibiotic era [43] - 10-15% of inpatient cases in the United States [43]* - 20-60% of hospitalized patients in U.S. [51] - 20% of hospitalized patients [100] - risk increases following influenza [48,49] - Haemophilus influenzae (most commonly with chronic pulmonary disease) [16] - Moraxella catarrhalis (most commonly with chronic pulmonary disease) [16] - Staphylococcus aureus [16] (< 10%), < 1% [68] - risk increases following influenza [16,48,49] & with hemodialysis - MRSA more common with nosocomial pneumonia, or nursing home setting - also see Staphylococcal pneumonia - bacterial pathogens detected by multiplex PCR assay [99] - Hemophilus influenzae in 33% - Streptococcus pneumoniae in 20% - Staphylococcus aureus in 20% - gram-negative bacilli in 18% - Moraxella catarrhalis in 12% d) atypical bacteria in 20-30% [12] - Mycoplasma pneumoniae (12%) (most commonly age 20-40 years) [16] - Chlamydophilq pneumoniae (7%) (most commonly age 20-40 years) [16] - Legionella pneumophila (5%) e) other bacteria (aspiration pneumonia) [16] - gram negative enteric pathogens - oral anaerobes f) risk factors - older age - 25-fold more common among the elderly than younger adults [52] - pulmonary disease: COPD, bronchietasis, smoking - common variable immunodeficiency - poor dentition - aspiration due to GI or neurologic disease - injection drug use - antibiotic therapy within 3 months - alcoholism g) > 50% of older veterans hospitalized & treated for pneumonia have discordant diagnosis from initial presentation to hospital discharge [107] 2) children a) viral pneumonia (66%) [47]; 80% [52] - respiratory syncytial virus (28%) - rhinovirus (27%) - adenovirus - metapneumovirus - influenza is not a common cause of pneumonia [48,49] b) bacterial pneumonia (8%) - Mycoplasma pneumoniae (most common) [81] - Streptococcus pneumoniae - Staphylococcus aureus c) both (7%) 3) other pathogens (see see pathogens in community-acquired pneumonia) - bacterial pneumonia - pertussis - pulmonary tuberculosis - atypical Mycobacterium: Mycobacterium kansasii - psittacosis (exposure to birds) - Pseudomonoas aeruginosa - COPD, smokers, cystic fibrosis, bronchiectasis, glucocorticoid - Coxiella burnetti - Burkholderia pseudomallei, Burkholderia cepacia - inhalation anthrax (bioterrorism) - plague (bioterrorism) - tularemia (bioterrorism) - Acinetobacter - fungal pneumonia - histoplasmosis (exposure to bat or bird droppings) - coccidiodomycosis - apspergillosis - viral pneumonia - influenza - hantavirus pulmonary syndrome - SARS-CoV - MERS-CoV 4) other causes - aspiration pneumonia - eosinophilic pneumonia - interstitial pneumonia - postobstructive pneumonia - bronchial neoplasm, foreign body, bronchial stricture 5) idiopathic > 50% [100] * the 10-15% estimate is at odds with the 90% of isolates largely because in most cases no pathogen is identified [52] * ref [16] suggests influenza viruses most common viruses contributing to development of CAP Epidemiology: - 60% of hospitalizations for community-acquired pneumonia are in patients > 65 years of age - most children hospitalized with pneumonia are < 5 years of age with underlying conditions, such as asthma or premature birth [47] History: 1) travel history - southwestern USA (coccidioidomycosis, Hantavirus) - southeast Asia or China (meliodosis, SARS) 2) occupational history - exposure to birds (psittacosis, cryptococcus), bats (SARS-like coronavirus), farm animals (anthrax), rabbits (tularemia) Clinical manifestations: 1) typical CAP a) rapid onset b) high fever c) productive cough (sputum production) d) pleuritic chest pain e) dyspnea f) tachypnea (esp in elderly) [16] g) pulmonary crackles, consolidation 2) atypical CAP a) low-grade fever b) non productive cough c) no chest pain [16] d) may present as delirium, confusion, & falls in the elderly [102] 3) influenza-like syndrome that seems to be improving, suddenly becoming worse suggests Staphylococcus aureus [16] 4) signs/symptoms of severe CAP a) confusion, disorientation b) hypothermia: core temperature < 36.0 C c) tachypnea: respiratory rate > 30/min d) hypotension [16] Laboratory: 1) sputum gram stain & sputum culture - may not be cost-effective for outpatient treatment [16] - patients not responding to outpatient antibiotic therapy [16] - all patients admitted to ICU - patients with cavitary lung lesions [16] - patients with structural lung disease - consider lung abscess if sputum is foul smelling - multiplex PCR assay may become the new standard 2) blood cultures prior to IV antibiotics [16] - not cost-effective for outpatient treatment [7] - all patients admitted to ICU - patients treated empirically for MRSA or Pseudomonas aeruginosa - culture may direct different specific antibiotic therapy 3) sputum culture & blood culture are recommended for patients with severe CAP, all ICU patients & for inpatients receiving empirical treatment for MRSA or Pseudomonas aeruginosa. - multiplex PCR assay may become the new standard 4) rapid antigen testing for influenza A & influenza B - all hospitalized patients with CAP during influenza season 5) urine antigen testing in hospitalized patients - Legionella pneumophila antigen in urine (positive for serotype 1) - Streptococcus pneumoniae antigen in urine* - all patients admitted to ICU & probably all hospitalized patients with CAP [16] 6) complete blood count (CBC) a) leukopenia: WBC < 4000/uL suggests severe CAP [16] b) thrombocytopenia: platelet count < 100,000/uL suggests severe CAP [16] 7) basic metabolic panel a) serum glucose - patients without preexisting diabetes mellitus with hyperglycemia have increased risk of mortality b) serum urea nitrogen: BUN > 20 mg/dL suggests severe CAP [16] 8) arterial blood gas: pO2/FiO2 <= 250 suggests severe CAP [16] 9) serum CRP, CRP Whole Blood, - cut-point of 20 mg/L may be of value in ruling out a diagnosis of CAP if probability of CAP >10%, typically in emergency departments - in primary care, CRP testing is unlikely to be of value [14] - useful in primary care when used in combination with serum procalcitonin [36] - low serum CRP helpful to rule out pneumonia [36] - serum CRP > 150 mg/L at hospital admission may be indication for glucocorticoids [46] - point of CRP reduces antibiotic use in primary care [90] 10) serum procalcitonin > 0.1-0.25 ng/mL suggests bacterial pneumonia rather than heart failure [56,60] - high levels (>10 ng/mL) associated with need for intensive care but clinical relevance uncertain [66] - PCT Assay FDA-approved Feb 2017 [71] - reduces antibiotic use (26%) in primary care without safety concern [89] - not recommended by the Infectious Diseases Society of America to guide initiation of antimicrobial therapy in community-acquired pneumonia 11) no threshold for WBC, serum CRP or serum procalcitonin that reliably rules in or rules out community-acquired pneumonia [85] 12) see ARUP consult [25] * sensitivity 70% not affected by prior antibiotic administration [16] Special laboratory: - endotracheal aspirate for gram stain & culture for hospitalized patients [16,32] - fiberoptic bronchoscopy with bronchoalveolar lavage &/or bronchoscopic biopsy is generally performed as indicated after CT [16] - failure to improve after 3 days of initial empiric therapy [16] - failure of 2 courses appropriate antibiotics [96] * computed tomgraphy of the chest is the initial diagnostic test of choice [16] Radiology: - chext X-ray a) pulmonary infiltrate required for diagnosis - a negative chest X-ray does not rule out pneumonia esp. in elderly [16] b) cavities with air-fluid levels suggest pulmonary abscess - abscesses may be due to Staphylococcus aureus, Klebsiella pneumoniae, Nocardia, Actinomyces, Rhodococcus, mycobacteria, fungi - cavities without air-fluid levels suggest tuberculosis or pulmonary mycosis - cavitary infiltrate can result from Staphylococcus aureus [16] c) enlargement of mediastinal or hilar lymph nodes suggest tuberculosis or pulmonary mycosis [16] d) lobar pneumonia suggests Streptococcus pneumoniae [16] e) right lower lobe pneumonia suggests aspiration pneumonia (anaerobes) f) interstitial infiltrate suggests virus vs atypical bacteria (Legionella, Chlamydiphila, Mycoplasma) - bronchiolitis & bronchopneumonia suggest viral infection g) pleural effusion/empyema suggests oral anaerobes, Staphylococcus aureus, Streptococcus pneumoniae & other Streptococci h) multilobar infiltrates suggests severe CAP [16] - follow-up chest X-ray in 2-3 months [13] - not necessary if symptoms have resolved in 5-7 days [16] - routine follow-up chest X-ray not recommended because radiographic findings may linger after clinical improvement [16,83] - if rapid resolution, 6 week follow-up [14] - to show resolution & absence of underlying lung cancer - may not be necessary in younger non-smokers [16,22] - ultrasound may be appropriate for children & young adults [28,89] - sensitivity 86%, specificity 89% relative to chest X-ray - CT of thorax is gold standard - improves diagnostic accuracy - unknown whether routine use would improve outcomes [55] - significant radiation exposure - no direct comparison with ultrasound [55] - initial diagnostic test of choice for treatment failure [16] - no resolution of chest X-ray pathology * cases of chest X-ray negative, but chest CT positive community acquired pneumonia with similar distribution of bacterial & viral pathogens, similar rates of requiring intensive care, & similar hospital stays [77] Complications: 1) pulmonary - lung abscess - empyema - ARDS - underlying lung cancer ? [14] 2) hematology - leukopenia - thrombocytopenia 3) cardiac - acute coronary syndrome - cardiac arrhythmias - hospitalization for pneumonia in middle-aged & older adults is associated with increased risk for cardiovascular disease (RR=4.1, risk greatest within 30 days) [44] - increased risk for heart failure (RR=1.6-1.7); 12% vs 7.4% within 10 years [72] 4) other - delirium - acute renal failure - adrenal insufficiency - CAP due to Staphylococcus aureus is associated with higher mortality & prolonged hospitalizations than CAP due to Streptococcus pneumoniae [16] - male sex & older age associated with higher risk for treatment failure [91] - C difficile colitis: - patients without history of C difficle colitis - 30 day risk 0.7%, similar for azithromycin & doxycycline [101] - patients with prior history of C difficle colitis - 30 day risk 12%, greater for azithromycin than doxycycline (RR=1.8) [101] - among older veterans, high-risk of hospitalization, facilty variation, no relationship to 30-day mortality [106] Differential diagnosis: - influenza A or influenza B - tuberculosis or other Mycobacterial pulmonary infection - pulmonary mycosis a) Histoplasma capsulatum b) coccidioidomycosis - cryptogenic organizing pneumonia (no response to antibiotics) - whooping cough (Bordetella pertussis) - pulmonary abscess (foul smelling sputum) - psittacosis (Chlamydophilia psittaci) - tularemia (Francisella tularensis) - Hantavirus pulmonary syndrome - Q fever (Coxiella burnetii) - bronchiectasis - cystic fibrosis (Burkholderia cepacia, Pseudomonas aeruginosa, Staphylococcus aureus) - anthrax (Bacillus anthracis) - pneumonic plague (Yersinia pestis) - endobronchial obstruction - heart failure Management: also see pneumonia === general === 1) pneumonia severity index, CURB-65 criteria or other criteria for severe pneumonia should be used in assessment of need for hospitalization [16] 2) diagnostic measures (sputum gram stain & culture) prior to empiric antibiotics [16] 3) antibiotic initiation within 4-8 hours of hospital arrival associated with lower mortality [65] 4) early mobilization [26] 5) objective criteria for switching from intravenous to oral antibiotics [26] 6) predefined criteria for deciding on hospital discharge [26] 7) a clinical decision support embedded in the electronic medical record may reduce practice variation & improve care [93] 8) if patients test positive for influenza, treat [16] - see viral pneumonia &/or influenza === empiric antimicrobial therapy in adults === 1) outpatient community-acquired pneumonia in patients < 60 years of age without comorbidity a) etiology: most likely: 1] Streptococcus pneumoniae 2] Moraxella catarrhalis 3] respiratory viruses 4] Chlamydia pneumoniae 5] Haemophilus influenzae 6] Mycoplasma pneumoniae b) empiric therapy: 1] amoxicillin [83] (MKSAP19) 2] doxycycline: efficacy equivalent to macrolide or fluoroquinolone [94] 3] macrolide a] erythromycin b] clarithromycin or azithromycin in smokers because of their activity against Haemophilus influenzae c] azithromycin for patients without risk factors for drug-resistant Streptococcus pneumoniae (M-phenotype) [16,29]; older age, immunosuppression, alcoholism, beta-lactam within past 3 months, exposure to child in day care d] azithromycin provides coverage for atypical organisms; Chlamydia pneumoniae, Mycoplasma pneumoniae [16,29] e] solithromycin non-inferior to moxifloxacin [57] f] base on local resistance [83] g] NOT for patients recently treated with antibiotics (use fluoroquinolone) [1,16] 4] respiratory fluoroquinolone* - recent treatment with beta-lactam antibiotic [16] 5] do not use same class of antibiotic patients has received within last 3 months [16] 6] no follow-up necessary unless failure to improve within 3 days of a 5 day cours of antibiotics [16] 2) outpatient community-acquired pneumonia in patients > 60 years of age or with comorbidity a) etiology: most likely: 1] Streptococcus pneumoniae (30% PCN resistant) 2] respiratory viruses 3] Haemophilus influenzae 4] aerobic gram negative bacilli 5] Staphylococcus aureus (< 1%) [68] (also see Staphylococcal pneumonia) b) empiric therapy: 1] oral 2nd generation cephalosporin 2] amoxicillin or Augmentin 3] add macrolide or doxycycline to cover: a] Legionella b] Mycoplasma c] Chlamydia 4] respiratory fluoroquinolone* (alone) 5] add vancomycin if suspecting Staphylococcus aureus [16] 6] Bactrim not recommended [14] a] increased Streptococcus pneumoniae resistance b] no coverage of Mycoplasma, Chlamydia 7] do not use same class of antibiotic patients has received within last 3 months [16] 3) patients with community-acquired pneumonia that require hospitalization (see pneumonia severity index) a) increased likelihood of polymicrobial infection b) risk factors 1] age > 65 or < 2 years 2] coexisting illnesses 3] immunosuppression 4] altered mental status 5] aspiration 6] malnutrition 7] alcohol abuse 8] tachypnea (respiratory rate > 30/min) 9] systolic blood pressure < 90 mm Hg 10] hypoxemia 11] multilobular involvement 12] exposure to a child in a day care center c) etiology: most likely: 1] Streptococcus pneumoniae 2] respiratory viruses 3] Haemophilus influenzae 4] aerobic gram negative bacilli 5] Staphylococcus aureus (< 1%) [68] (also see Staphylococcal pneumonia) 6] anaerobes 7] Legionella 8] Chlamydia 9] Klebsiella pneumoniae d) empiric therapy 1] 3rd generation cephalosporin plus a macrolide or doxycycline [1,105] a] ceftriaxone, cefotaxime, or ceftizoxime b] erythromycin, azithromycin, or clarithromycin covers Legionella [5], Mycoplasma & Chlamydia frequently complicating bacterial pneumonia c] doxycycline alternative to macrolide - may be better choice if prior history of C difficile colitis - may be better choice if prolonged PR interval d] benefits of azithromycin in the elderly outweigh risks [41] e] beta-lactam antibiotic plus macrolide more effective than beta-lactam antibiotic alone [42] f] evidence favors empiric beta-lactam/macrolide vs empiric beta-lactam/fluoroquinolone [83] 2] fluoroquinolone* (alone) - oral fluoroquinolone as effective as IV [67] 3] tigecycline (Tygacil) FDA-approved in 2009 for CAP 4] Lefamulin FDA-approved in 2019 for CAP 5] add vancomycin or linezolid if MRSA suspected [16] 6] coverage with 2 effective antibiotics if Pseudomonas suspected (ex ceftazidime or cefepime + fluroquinolone) 7] beta-lactam-macrolide combination or fluoroquinolone vs beta-lactam monotherapy - no better [50,75] - shorter time to clinical stability & lower mortality (1.5%) [103] 8] macrolide resistance in pneumococcal pneumonia does not affect outcomes [51] e) switch from IV to oral antibiotics once symptoms improve & patients becomes afebrile [58] f) observation of patients for 24 hours in hospital after switch from IV to oral antibiotics unecessary [10,16,31] 4) patients with community-acquired pneumonia that require hospitalization in an intensive care unit (ICU) a) indications 1] heart rate > 125/min 2] respiratory rate > 30/min 3] diastolic blood pressure < 60 mm Hg 4] systolic blood pressure < 90 mm Hg 5] temperature < 35 C (95 F) or > 40 C (104 F) [16] 6] sepsis syndrome b) empiric therapy 1] vancomycin, ceftriaxone or ampicillin sulbactam or Zosyn or meropenem plus a macrolide or fluoroquinolone* [16] 2] vancomycin if critically ill or risk factor for MRSA [16] a] increased nephrotoxicity when vancomycin used in combination with piperacillin tazobactam [79] - discontinue piperacillin tazobactam but continue vancomycin if evidence of nephrotoxicity [79] b] coverage for MRSA + dual coverage for Pseudomonas if hospitalized & treated with parenteral antibiotics in past 3 months [16] 3] Cefepime, imipenem, meropenem, or Zosyn plus an aminoglycoside plus a fluoroquinolone (dual Pseudomonas coverage for COPD, smokers, bronchiectasis, cystic fibrosis, glucocorticoid use) [16] - dual Pseudomonas coverage if growth from respiratory culture in past year - single agent appropriate if antibiotic sensitivity known [104] 4] coverage for Legionella in patients with COPD (macrolide or fluroquinolone) 5] treat aspiration pneumonia with Zosyn plus azithromycin for failed fluoroquinolone treatment in an alcoholic [16] 6] older regimens a] erythromycin, azithromycin or a fluoroquinolone* plus cefotaxime, ceftriaxone or penicillin/beta-lactamase inhibitor** b] macrolide plus beta-lactamase inhibitor may confer advantage over fluoroquinolone [18] c] fluoroquinolone* plus clindamycin, vancomycin or aminoglycoside [2] d] fluoroquinolone* plus aztreonam c) corticosteroids 1] patients with possible adrenal insufficiency [16] 2] may shorten hospital stay (1 day) in patients with refractory septic shock [16,19] 3] may reduce mortality in patients with severe disease if started early [98] 5) presence of cavitary lesion(s) requires treatment for Staphylococcus aureus, including MRSA (also see Staphylococcal pneumonia) - add vancomycin to initial empiric therapy [16,30] 6) low-risk patients may be safely treated as outpatients [5] 7) length of therapy (outpatient) a) 5 days of outpatient therapy [16,87] - as good as 10 days [16] - better than 3 days in a pediatric patient population [38] b) 3 days of outpatient antibiotic therapy as effective as 8 days [8,88] 8) 5 days of inpatient antibiotics if good response to treatment [16,69,73,87] a) afebrile for 48-72 hours b) no more than 1 sign of clinical instability 1] pulse > 100/min 2] respiratory rate > 24/min 3] systolic blood pressure < 90 mm Hg 4] arterial oxygen saturation < 90% or pO2 < 60 mm Hg on room air c) previously 7-10 days, 14 days if severe 9) exceptions to 5 days of therapy a) cavitary lesion, lung abscess, empyema b) sepsis or other extrapulmonary infection c) instability (persistent fever, abnormal vital signs, or hypoxia) === failure to improve === - fiberoptic bronchoscopy with bronchoalveolar lavage &/or bronchoscopic biopsy is generally performed after CT* [16] - failure to improve after 3 days of initial empiric therapy - may be due to misdiagnosis, a resistant pathogen, lung abscess, empyema, pulmonary embolism, fungal infection, or aspiration pneumonia [16] - aspiration pneumonia most common in right lower lobe in patients with reduced level of consciousness (alcoholism, drug abuse, seizures) - piperacillin-tazobactam + azithromycin [16] - anaerobic coverage for lung abscess or empyema [16] - thoracentesis to determine need for chest tube drainage [16] - failure to improve after 2 courses appropriate antibiotics [96] * computed tomgraphy of the chest is the initial diagnostic test of choice [16] === CAP in children === 1) parenteral penicillin or ampicillin works as well as ceftriaxone or cefotaxime [37] 2) 5-day antibiotic strategy was superior to a 10-day strategy for outpatient treatment of children [92] - 5 days of oral amoxicillin (80 mg/kg/day; divided TID) for outpatient therapy [38] 3) for children discharged from the hospital with complicated pneumonia (pneumonia with pleural effusion), IV antibiotics offers no advantage over oral antibiotics [70] 4) antibiotic therapy broader than ampicillin should be avoided in otherwise healthy, immunized, hospitalized patients with uncomplicated CAP [78] * see refs [23,37,38,70,78,92] === glucocorticoid adjunct to antibiotics === 1) considered in patients with refractory septic shock [83] 2) dexamethasone 5 mg IV QD for 4 days; adjunct to antibiotics a) may shorten hospital stay [27] b) not ready for routine use [20,21,27] 3) prednisone 20-60 mg QD for 3-7 days [45,54,76] - shortens time to clinical stability & hospital discharge - lowers risk of ARDS [100] - lowers in-hospital mortality [54]; NNT = 38 - mortality benefit may only occur for patients with severe pneumonia [54]; NNT = 7 - mortality benefit only in patients admitted directly to ICU [100] - increase risk of in-hospital hyperglycemia requiring insulin 4) methylprednisolone 0.5 mg/kg IV every 12 hours [46] 5) serum CRP > 150 mg/L at hospital admission may be indication for glucocorticoids [46] 6) may be beneficial for patients hospitalized with severe pneumonia [53,54,76] 7) oral glucocorticoids of no benefit to adults without chronic obstructive pulmonary disease [74] 8) a bundled protocol than included 50 mg of prednisolone for 7 days does not improve 90 day mortality, length of stay or hospital readmission but does increase gastrointestinal bleeding [82] 9) no mortality benefit but does reduce need for mechanical ventilation [97] === follow-up === - evaluate for bronchiectasis with recurrent pneumonia a) immunodeficiency b) unusual pathogen - routine follow-up chest X-ray not recommended because radiographic findings may linger after clinical improvement [16] - transitional care programs for home care after hospitalization can reduce readmissions [1] === prevention === 1) influenza vaccine annually 2) PCV13 & PPSV23 [16] - decline in pneumococcal pneumonia due to: - widespread use of pneumovax in adults - use of pneumococcal conjugate vaccine in children - decreased rates of cigarette smoking [43] 3) effective & consistent oral hygiene may reduce incidence of pneumonia in nursing home residents [86] Notes: * Most fluoroquinolones are not recommended for empiric antimicrobial activity in pneumonia because of unreliable activity against Streptococcus pneumoniae. Fluoroquinolones with enhanced activity against Streptococcus pneumonia include: 1) levofloxacin (750 mg QD) [11] 2) sparfloxacin 3) trovafloxacin 4) grepafloxacin 5) moxifloxacin 6) gatifloxacin 7) gemifloxacin * oral fluoroquinolones as effective as IV [67] ** penicillin/beta lactamase inhibitor: 1) ampicillin sulbactam (Augmentin) 2) piperacillin tazobactam (Zosyn) 3) ticarcillin clavulanate (Timentin)

Related

criteria for hospitalization of patients with pneumonia CURB-65 criteria outpatient management of HIV related pneumonia pathogens in community-acquired pneumonia pneumonia severity index; PORT score (PSI)

General

pneumonia (PNA)

References

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