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Streptococcus pneumoniae
Eric Nuermberger, M.D.
02-04-2008
- No good incidence/prevalence data for S. pneumoniae carriage or infection from Zambia, but carriage rates decline with age in other African cohorts.
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S. pneumoniae shown to be common cause of bacterial meningitis in HIV+ pts in southern Africa.
- Dx in Zambia by Gram stain of sterile fluids as urinary antigen testing not available and Cx rarely performed.
- Respiratory fluoroquinolones not generally available in Zambia; activity of ciprofloxacin poor against S. pneumoniae.
- Most antibiotics listed below available in Zambia with exception of respiratory fluoroquinolones and vancomycin.
- Increasing incidence of antibiotic resistance in invasive pneumococci from neighboring Zimbabwe (Gwanzura L, Pasi C, Nathoo KJ, et al. reference), and resistance was more common in HIV+ pts.
Zambia Information Author: David Riedel, M.D.
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Streptococcus pneumoniae (pneumococcus): Gram-positive diplococcus with polysaccharide capsule
- Grows well on standard media, but prior antibiotics may preclude growth
- Definite pathogen when isolated from sterile site (blood, CSF, joint fluid, etc); Probable pathogen in respiratory specimens (Gram stain or Cx) or when urinary antigen positive in pt w/pneumonia
- Rapid urinary antigen test (Binax): 70-90% sensitive, 90% specific for bacteremic pneumonia; lower yield in non-bacteremic pneumonia; little data for HIV+ pts
- Blood Cx more sensitive for Dx of pneumonia in HIV+ vs. HIV- pts
- Ecologic niche is nasopharynx, colonizes 5-10% of adults, 20-40% of children
- Incidence of invasive disease 150-300x higher in HIV+ vs. controls; although may be lower (~35x) in HAART era
- Risk of invasive disease inversely proportional to CD4 count
- HIV does not clearly affect treatment response or increase mortality, but pneumonia recurs in 8-25% within 6 mo (usually reinfection)
- Classical presentation: abrupt onset of fever, rigors, productive cough, pleurisy; Exam: tachycardia, increased resp rate, hypoxia, findings c/w lung consolidation, maybe pleural rub; CXR: typically lobar pneumonia +/- effusion, but multilobar, even diffuse infiltrates possible
- Pts without vital sign abnormalities unlikely to have pneumococcal pneumonia
- HIV infection is risk factor for infection with drug-resistant pneumococci
- Lung: pneumonia, pleural effusion, empyema, acute exacerbation of chronic bronchitis (AECB)
- Sinuses: sinusitis
- Middle ear: otitis media
- CNS: meningitis
- Joints: septic arthritis
- Peritoneum: spontaneous bacterial peritonitis
- Heart: purulent pericarditis, endocarditis
- Skin: cellulitis
- Eye: conjunctivitis
- For empiric therapy of pneumonia, see Pneumonia, bacterial. Recommendations below are for pathogen-directed therapy unless otherwise specified (adapted from IDSA/ATS guidelines).
- Pneumonia, (PCN sens, MIC <2), ICU patient, parenteral: penicillin G 2-4 MU q4h or ampicillin 1-2g q6h (preferred) OR ceftriaxone 1g IV qd or bid or cefotaxime 1-2 g IV q6-8h (alternatives). Addition of a macrolide or fluoroquinolone (levofloxacin, moxifloxacin) may be beneficial in severe pneumonia until improvement noted.
- Pneumonia, (PCN sens, MIC <2), ward patient, parenteral: penicillin G 2-4 MU q4h or ampicillin 1-2g q6h (preferred) OR ceftriaxone 1g IV qd or bid or cefotaxime 1-2 g IV q6-8h (alternatives). Moxifloxacin 400 mg IV/PO qd, levofloxacin 500-750 mg IV/PO qd or clindamycin 600 mg IV q8h (IgE-mediated beta-lactam allergy)
- Pneumonia, (PCN sens), oral: amoxicillin 2-3 g/d (preferred), cefpodoxime 200 mg bid, cefprozil 500 mg bid, cefuroxime 500 mg bid, cefdinir 300 mg bid, clarithromycin 1 g qd (XL) or 500 mg bid, azithromycin 500 mg once, then 250-500 mg qd, doxycycline 100 mg bid
- Pneumonia, PCN resist (MIC >2): ceftriaxone or cefotaxime (as above) if MIC to either agent is <2 mg/L OR fluoroquinolone IV/PO qd (levofloxacin 500-750 mg, moxifloxacin 400 mg)
- Sinusitis, empiric: amoxicillin 500 mg tid or 750 mg bid, doxycycline 100 mg bid (ACP guidelines, Ann Intern Med 2001;134:479)
- Acute exac. chr. bronchitis: same as for sinusitis above (ACP guidelines, Ann Intern Med 2001;134:595)
- For empiric therapy of presumed bacterial meningitis, see Bacterial Meningitis, Acute, Community-Acquired . Recommendations below are for pathogen-directed therapy unless otherwise specified (adapted from IDSA guidelines)
- PCN sens (MIC <0.1): penicillin G 4 MU IV q4h or ampicillin 2g IV q4h (preferred); ceftriaxone 2g IV q12h or cefotaxime 2-3 g IV q4-6h (alternatives).
- PCN non-susceptible (MIC 0.1-1): ceftriaxone or cefotaxime (as above) (preferred); cefepime 2 g IV q8h or meropenem 2 g IV q8h (alternatives)
- PCN resist (MIC >2): vancomycin 15 mg/kg q8-12h PLUS ceftriaxone or cefotaxime (as above) (preferred); moxifloxacin 400 mg IV q24h (alternative)
- HAART decreases risk of pneumonia; TMP/SMX and azithromycin prophylaxis do not, but may increase risk that pneumococcal infections will be with resistant strains
- Pneumovax recommended for pts with CD4 >200, optional if CD4 <200 (2002 USPHS/IDSA guidelines MMWR 51[RR-8]:1). No data to suggest Prevnar is more effective in HIV+ pts.
- Revaccinate every 3-5 yrs and when CD4 >200 if initial vaccination was given when <200
- Annual influenza vaccination may decrease risk of pneumococcal superinfection of influenza
| Drug | Recommendations/Comments |
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Amoxicillin
| Oral-beta-lactam of choice. More potent in vitro activity and better absorption than PCN. Less expensive than oral cephalosporins and more potent than many. |
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Azithromycin
| Unbeatable convenience. In vitro activity comparable to other macrolides. Comparable efficacy to other drug classes in clinical trials of CAP. Low serum concentrations and anecdotal reports of breakthrough bacteremia with resistant pneumococci have raised concerns about its use for severely ill or overtly bacteremic patients. Avoid empiric use in patients on macrolide prophylaxis for MAC infection. |
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Cefaclor
| Inferior activity among oral cephalosporins. Avoid use in adults. |
| Cefdinir | With cefpodoxime, cefditoren, cefuroxime and cefprozil, one of 5 most active oral cephalosporins. |
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Cefditoren
| With cefpodoxime, cefprozil,cefdinir and cefuroxime, one of 5 most active oral cephalosporins. |
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Cefotaxime
| With ceftriaxone, the preferred parenteral cephalosporins. Active against 95% of pneumococcal strains. More convenient than PCN or ampicillin. |
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Cefpodoxime Proxetil
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With cefprozil, cefditoren, cefdinir and cefuroxime, one of 5 most active oral cephalosporins.
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Cefprozil
| With cefpodoxime, cefditoren, cefdinir and cefuroxime, one of 5 most active oral cephalosporins. |
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Ceftriaxone
| With cefotaxime, the preferred parenteral cephalosporins. Active against 95% of pneumococcal strains. More convenient than PCN or ampicillin. Ceftriaxone's once daily dosing schedule makes outpatient administration possible. |
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Cefuroxime axetil
| With cefpodoxime, cefditoren,cefdinir and cefprozil, one of 5 most active oral cephalosporins. |
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Clarithromycin
| Most potent macrolide from standpoint of serum pharmacokinetics. Once daily oral form now makes it more convenient. Clinical significance of low-level in vitro macrolide resistance caused by efflux pump (MICs 2-8 g/mL), which accounts for 2/3 of resistance in US, remains uncertain. Avoid empiric use in pts on macrolide prophylaxis for MAC infection. |
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Clindamycin
| More reliable in vitro activity than the macrolides (i.e., <5-10% resistance). Susceptibility and low-level resistance (MICs 2-16 g/mL) to erythromycin predicts clindamycin activity. |
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Doxycycline
| Seldom used, despite good in vitro activity. Paucity of clinical trials data. Resistance in 6-16%. Start with 200 mg loading dose. |
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Ertapenem
| New carbapenem with more limited spectrum than imipenem, meropenem that is now approved for CAP therapy. Active against 2/3 of PCN-resistant pneumococci and has convenient, qd dosing schedule, similar to that of ceftriaxone. Questions remain regarding its ability to promote carbapenem resistance among Gram-negative pathogens. |
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Erythromycin
| No good reason to use this over azithromycin or clarithromycin except for its low cost. Many drug interactions and high rate of GI intolerance (may be an issue with PI co-administration) |
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Gemifloxacin
| New respiratory available only in oral form. Reversible maculopapular rash occurred in 2%, 12%, 15%, and 23% of young women after 5, 7, 10 and 14 days of therapy, but occurred in <2% of men over 40. Risk of rash unknown in HIV+ pts and 2 other respiratory fluoroquinolones on the market should limit use for now. |
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Levofloxacin
| With moxifloxacin and gemifloxacin, one of 3 "respiratory" fluoroquinolones w/ improved potency against Gram-positive organisms. Active against 97-99% of strains, although resistant mutants may be selected by prior administration. Abuse of this class for mild infections of the upper and lower respiratory tract may limit its longevity. |
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Linezolid
| Active against all pneumococci. Highly bioavailable oral form, but should be reserved for unusual cases due to concerns about promoting resistance and its very high cost. |
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Moxifloxacin
| With levofloxacin and gemifloxacin, one of 3 "respiratory" fluoroquinolones w/ improved potency against Gram-positive organisms. Active against 97-99% of strains, although resistant mutants may be selected by prior administration. Abuse of this class for mild infections of the upper and lower respiratory tract may limit its longevity. |
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Penicillin
| Good drug for susceptible strains, though amoxicillin preferred for oral therapy due to increased potency and absorption. |
| Telithromycin | New ketolide antibiotic active in vitro against most macrolide-resistant pneumococci (<1% of all pneumococci are telithromycin-resistant). Convenient once-daily oral dosing. Unusual side effect is impaired visual accommodation. FDA removed indications for sinusitis and exacerbations of chronic bronchitis due to risk-benefit concerns, but pneumonia indication was preserved. Drug interactions may make it difficult to use in pts on PIs. |
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Vancomycin
| Active against all pneumococci strains, but published experience in severe pneumonia and meningitis is limited. Should be used in empiric regimens for meningitis. |
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