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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Diagnosis>Opportunistic Infections>
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Pneumonia, bacterial

Eric Nuermberger, M.D.
02-05-2008

  • Pulmonary TB is most common serious lower respiratory infection in much of Africa
  • Bacterial pneumonia (most commonly pneumococcal) also common & may occur along with pulmonary TB
  • PCP, pulmonary KS, and cryptococcal pneumonia less common (10% of pulmonary disease), but can occur along with TB or bacterial pneumonia
  • Treat suspected bacterial pneumonia with amoxicillin or cotrimoxazole 800/160 bid
  • If no improvement within 1 week or worsening Sx, evaluate for TB & consider empiric treatment for TB (or PCP, KS, or cryptococcus if evidence suggests these infections)

REFERENCES

Zambia Information Author: Christopher Hoffmann, MD, MPH

PATHOGENS

CLINICAL

  • Invasive pneumococcal, H. influenzae infections 100x more common in HIV+ pts vs. HIV-, and may mimic PCP.
  • Risk of legionellosis may be 40x higher in pts with AIDS vs. general population.
  • Suspect P. aeruginosa when CD4 <50, esp. if bronchiectasis, neutropenia, or steroid therapy. Radiographic findings may include consolidation, patchy interstitial infiltrates, and cavitary disease.
  • Suspect S. aureus (and MRSA) if IDU, cavitary pneumonia, hemoptysis, concomitant influenza, prior history of MRSA colonization or infection in patient or close contact.
  • Suspect TB with Sx >2 wks duration, past +PPD, Hx of TB exposure or residence in endemic country, hemoptysis, apical cavitary disease, hilar adenopathy, miliary or reticulonodular infiltrates. Empiric FQ therapy for CAP may delay appropriate Dx of TB and select for resistance to this important second-line drug class.

DIAGNOSIS

  • Hx: cough, fever +/- sputum production, dyspnea, pleurisy
  • PE: fever, tachycardia, tachypnea, rales or signs of consolidation
  • CXR showing infiltrate, although CXR pattern not always predictive of etiology
  • Good quality sputum gram stain obtained before Abx may establish probable etiology. Any isolation of Pneumocystis, M. tuberculosis, Legionella, Cryptococcus, or Histoplasma should be considered definitive Dx, but a co-pathogen could also be present.
  • Blood Cx have higher yield in HIV+ pts with bacterial pneumonia (obtain for inpts). Other rapid tests include Legionella and pneumococcal urinary antigens, cryptococcal serum antigen.

TREATMENT

OUTPATIENT (EMPIRIC)

  • PORT prediction rule, used to support hospitalization decision in immunocompetent pts (see Ref 20), is not validated for HIV+ pts and should not be used.
  • Consider PCP if CD4 <250, no prophylaxis, indolent course, dry cough, diffuse interstitial infiltrates, hypoxemia/desaturation with exercise out of proportion to CXR findings, thrush. Empiric PCP treatment not recommended, pursue diagnosis with induced sputum +/- BAL and treat accordingly.
  • Recommendations for empiric treatment of bacterial pneumonia listed in no particular order.
  • Azithromycin 500 mg PO x1, then 250-500 mg PO qd x 5d or clarithromycin 500 mg PO bid or 1g  (XL formulation) PO qd x 7-10d.
  • Cephalosporin (cefuroxime 500 mg, cefpodoxime 400 mg, cefprozil 500 mg, cefditoren 400 mg, cefdinir 300 mg) PO bid x 7-10d.
  • Doxycycline 100 mg PO bid x 7-10d
  • FQ (moxifloxacin 400 mg, or levofloxacin 500-750 mg) PO qd x 5-7d.
  • Avoid macrolide if pt receiving macrolide prophylaxis for MAC.
  • When alternatives exist, consider avoiding gemifloxacin in all pts (risk of rash unclear in HIV+ pts) and telithromycin in pts on PIs (adverse interactions).
INPATIENT (EMPIRIC)

  • Give Abx within 4hrs.
  • Preferred: [ceftriaxone 1-2 g IV qd or cefotaxime 1-2 g IV q8h] PLUS [azithromycin 500 mg IV/PO qd or erythromycin 500-1000 mg IV q6h or clarithromycin 500 mg PO bid or 1 g (XL formulation) PO qd].
  • Preferred: FQ (moxifloxacin 400 mg, or levofloxacin 750 mg) IV/PO qd.
  • Aspiration: clindamycin 600 mg IV q8h, FQ as above.
  • Add PCP coverage (preferably TMP-SMX 5mg/kg IV/PO q8h +/- corticosteroids) if CD4 <250, no PCP prophylaxis, indolent course, dry cough, diffuse interstitial infiltrates, hypoxemia/desaturation with exercise out of proportion to CXR findings.
  • If Pseudomonas suspected (CD4 <50 with bronchiectasis, neutropenia, or steroid therapy): [ceftazidime 2 g IV q8h, cefepime 2 g IV q12h, or piperacillin/tazobactam 4.45 g IV q6h or 3.375 g IV q4h] PLUS ciprofloxacin 400 mg IV q12h or [gentamicin/tobramycin 5 mg/kg IV qd + azithromycin 500 mg IV qd].
  • Duration of therapy determined by etiology or suspected etiology and/or by clinical response. S. pneumoniae, H. influenzae:7-10d; Enterobacteriaceae, Legionella: 14d; S. aureus, P. aeruginosa: 21d.

Drug Comments

DrugRecommendations/Comments
Amoxicillin Probably oral drug of choice for pneumococcal infections once etiology established. Dosing up to 4g per day provides serum concentrations to inhibit isolates with MICs as high as 2. Lacks activity against atypical agents and nearly half of H. influenzae infections.
Amoxicillin + Clavulanate Has all features of amoxicillin and reliable activity against H. influenzae, but more expensive. New XR formulation (1000/62.5 mg) allows increase in amoxicillin dose to 2000bid to inhibit pneumococci with MICs as high as 2 mcg/mL without increasing the dose of clavulanate (125 mg bid), the diarrhea-causing component.
Ampicillin + Sulbactam Good activity against S. pneumoniae and H. influenzae but lacks atypical activity and activity vs. P. aeruginosa. Third-generation cephalosporins are favored parenteral beta-lactams for empiric threapy unless aspiration suspected.
Azithromycin Has activity against all major pathogens causing CAP in immunocompetent pts, but not P. aeruginosa, and has proven efficacy as monotherapy. Major advantages are convenience of once daily dosing and the tissue pharmacokinetics, which permit shorter duration of therapy. Up to 35% of pneumococci are resistant in vitro, but clinical significance of low-level resistance (MIC < 8) is debated. Clarithromycin may have better PK profile, but may not be as well tolerated.
Cefaclor A poor choice given low potency against S. pneumoniae and lack of atypical activity.
Cefepime Adds pseudomonal activity to spectrum of third-generation cephalosporins, so most useful when P. aeruginosa suspected or confirmed. Should be paired with macrolide used in an empiric regimen due to lack of activity against atypical pathogens.
Cefotaxime With ceftriaxone, the parenteral beta-lactam of choice for empiric therapy unless aspiration or P. aeruginosa are suspected. Should be combined with a macrolide or FQ in seriously ill pts.
Ceftazidime Third-generation cephalosporin with enhanced activity against P. aeruginosa, but reduced activity against S. pneumoniae, H. influenzae compared to ceftriaxone, cefotaxime. Use should be limited to suspected or confirmed pseudomonal pneumonia.
Ceftriaxone With cefotaxime, the parenteral beta-lactam of choice for empiric therapy unless aspiration or P. aeruginosa suspected. Should be combined with macrolide or FQ in seriously ill pts.
Cefuroxime axetil With cefprozil, cefpodoxime and cefditoren, these are the oral cephalosporins of choice. Cefuroxime should generally not be used parenterally for empiric therapy of pneumonia due to poor pharmacodynamic target attainment against pneumococci relative to third-generation cephalosporins.
Clarithromycin Like azithromycin has activity against all major pathogens in immunocompetent pts. New XL formulations permits once daily oral dosing. Main disadvantage is lack of IV formulation. Up to 35% of pneumococci are resistant in vitro, but clinical significance of low-level resistance (MIC < 8) is debated. Has best PK profile of macrolides, but may not be as well tolerated as azithromycin.
Clindamycin Treatment of choice for aspiration pneumonia, but may also be useful against multi-drug resistant pneumococci (resistance rates <10%) and against MRSA. For the latter however, must rule out inducible clinda resistance with a D-test if isolate erythromycin-resistant.
 Daptomycin Do not use to treat pneumonia: shown to be inferior to ceftriaxone in clinical trial of CAP treatment, presumably because it achieves low concentrations in broncho-alveolar lining fluid and may be bound to pulmonary surfactant.
Doxycycline A rational choice for outpts due to low cost and activity against all major pathogens of CAP in immunocompetent pts. Resistance rates vary among pneumococci, but are generally less than 20%.
Levofloxacin Has activity against all major pathogens of bacterial pneumonia and advantages of once-daily dosing and high oral bioavailability. Major concern is overuse of this class and promotion of resistance. Avoid empiric use in pts recently treated with a FQ. Although ciprofloxacin remains the FQ of choice for pseudomonal infections, the 750 mg daily dose of levofloxacin likely has similar activity.
Linezolid New agent with reliable activity against all gram-positive bacteria and excellent oral bioavailability, but no activity against gram-negative or atypical pathogens. Very expensive. Retrospective analysis of 2 clinical trials for nosocomial pneumonia suggest it is as good or better than vancomycin for staphylococcal pneumonia, but randomized clinical trial is in progress. It is probably the preferred agent against strains with vancomycin MICs >1 mcg/ml. Use should generally be limited to MRSA pneumonia, especially when oral therapy is preferred and other drugs (TMP-SMX, clindamycin, FQ) are not options.
Moxifloxacin Has activity against all major pathogens of bacterial pneumonia and has advantages of once-daily dosing and high oral bioavailability. Major concern is overuse of this class and promotion of resistance. Avoid empiric use in pts recently treated with a FQ. Ciprofloxacin remains the FQ of choice for pseudomonal infections.
Piperacillin + Tazobactam Broad-spectrum beta-lactam most useful when infection with P. aeruginosa suspected or confirmed. May be used without the tazobactam if susceptibility confirmed.
 Telithromycin New ketolide that is active against virtually all S. pneumoniae, including macrolide-resistant isolates. Unusual side effect is impaired visual accommodation. Avoid in pts on PIs, as it may interact adversely. Of concern is risk of fulminant hepatic failure that prompted FDA to remove indication for acute sinusitis and AECB.
Trimethoprim + Sulfamethoxazole Unreliable activity vs. S. pneumoniae and H. influenzae make this a poor empiric choice for CAP, but it remains treatment of choice for PCP and should be added when this Dx suspected. Has also become an option for MRSA infections.
Vancomycin Predictable activity against virtually all S. pneumoniae and S. aureus strains, but limited activity against other common CAP pathogens. Little rationale for use in empiric treatment of pneumonia unless MRSA suspected. Emerging evidence suggests vancomycin has poor activity against MRSA strains with MICs >1 mcg/ml. Consider use of linezolid for pneumonia caused by such strains.
Tigecycline  Broad-spectrum tetracycline derivative active against resistant MRSA, drug-resistant pneumococcus, ESBL+ bacilli, some multidrug-resistant Acinetobacter, anaerobes, and atypicals. Not active against P. aeruginosa. Non-inferior to levofloxacin in immunocompetent patients with CAP, however given its extremely broad-spectrum and lack of oral formulation, its use should be restricted to pathogen-directed therapy for resistant organisms in hospitalized patients when other options are not available. It may have a role in nosocomial pneumonia, although this has yet to be defined.

FOLLOW UP

  • IV to PO switch when clinically improved, T <100, RR <24, PO2 >90, tolerating PO.
  • For pts not responding to empiric therapy targeting routine bacterial pathogens, consider MRSA, P. aeruginosa, PCP, TB and other mycobacterial infections, cryptococcosis & other fungal infections, KS, lymphoid interstitial pneumonitis.
  • Counsel re: smoking cessation.
  • Vaccinate for influenza (all pts) and pneumococcus (if CD4 >200). No perceived benefit to vaccination against H. influenzae.

OTHER INFORMATION

  • Recommendations are those of the author and editorial staff, largely compiled from the available literature.

Pathogen Specific Therapy

REFERENCES

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