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Review: antibiotics active against atypical pathogens do not improve community acquired pneumonia more than β lactam antibiotics
  1. Thomas J Marrie, MD
  1. University of Alberta
 Edmonton, Alberta, Canada

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 Q In patients with community acquired pneumonia (CAP), how do antibiotics active against atypical pathogens (AAAAPs) compare with β lactam antibiotics for effectiveness?

    Clinical impact ratings GP/FP/Primary care ★★★★★★☆ Internal medicine ★★★★★★☆ Infectious disease ★★★★★★☆


    Embedded ImageData sources:

    Cochrane Central Controlled Trials Register, Medline, and EMBASE/Excerpta Medica (to December 2003); conference proceedings; registration authorities; reference lists of review articles and retrieved studies; and pharmaceutical companies conducting trials on AAAAPs.

    Embedded ImageStudy selection and assessment:

    randomised, blinded (investigators, patients, and outcome assessors), controlled trials (RCTs) that compared AAAAPs (fluoroquinolones, macrolides, and ketolides) with β lactam antibiotics (penicillins and cephalosporins) in patients with radiographically confirmed CAP.

    Embedded ImageOutcomes:

    failure to achieve clinical cure or improvement and all cause mortality.


    18 RCTs (n = 6749) met the selection criteria. The trials evaluated 9 different fluoroquinolones, 2 macrolides, and 1 ketolide. Time of outcome assessment ranged from the end of treatment to 38–42 days after commencement of antibiotics. No RCT showed a difference between groups in failure to achieve clinical cure or improvement and no significant heterogeneity existed between studies. Pooled analysis showed no overall difference between groups for failure to achieve cure or improvement and no difference when analyses were done separately on type of AAAAP (table). No treatment effect was seen in patients with Mycoplasma pneumoniae (13 RCTs) (relative risk [RR] 0.60, 95% CI 0.31 to 1.17) or Chlamydia pneumoniae (7 RCTs) (RR 2.32, CI 0.67 to 8.03), but a reduction in failure to achieve cure or improvement with AAAAPs was seen in patients with Legionella species (10 RCTs) (RR 0.40, CI 0.19 to 0.85). AAAAPs and β lactam antibiotics did not differ for all cause mortality (RR 1.20, CI 0.84 to 1.71).

    Antibiotics active against atypical pathogens (AAAAPs) v β lactam antibiotics in community acquired pneumonia*


    In patients with community acquired pneumonia, antibiotics active against atypical pathogens and β lactam antibiotics do not differ for achieving clinical cure or improvement.


    There are 2 ways in which one can interpret the results of the meta-analysis by Mills et al. One is that patients with pneumonia of mild to moderate severity (apart from those with Legionnaire’s disease) do not need to receive AAAAPs (mainly Mycoplasma pneumoniae and Chlamydia pneumoniae) because the host response is sufficient to contain this infection. The second interpretation is that the wrong outcome measures were used in the clinical trials. Time to resolution of symptoms and time to return to work are more likely to be responsive to the intervention in patients with very low mortality caused by pneumonia. I suspect that both interpretations may be correct.

    2 previous trials suggest a shorter time to resolution of fever in patients with M pneumoniae and Coxiella burnetii infection treated with AAAAPs.1,2 Since such outcomes were not addressed in the review, the question of benefit with AAAAPs remains unresolved.

    Despite its limitations, this review confirms the findings of observational studies dating back to the original outbreak of Legionnaire’s disease3,4 that indicated that treatment of Legionnaire’s disease with AAAAPs improved outcomes. The issue of whether AAAAPs offer an advantage over β lactam antibiotics in patients with CAP needs to be addressed in an RCT using appropriate outcomes.


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    • For correspondence: Dr G D Mills, Waikato Hospital, Hamilton, New Zealand.

    • Source of funding: Waikato District Health Board.