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Clin Infect Dis. 2002 Sep 1;35(5):556-64. Epub 2002 Aug 9.

Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae.

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Miriam and Rhode Island Hospitals and Brown Medical School, Providence, RI 02906, USA.


The rate of macrolide resistance among Streptococcus pneumoniae is increasing, but some investigators have questioned its clinical relevance. We conducted a matched case-control study of patients with bacteremic pneumococcal infection at 4 hospitals to determine whether development of breakthrough bacteremia during macrolide treatment was related to macrolide susceptibility of the pneumococcal isolate. Case patients (n=86) were patients who had pneumococcal bacteremia and an isolate that was either resistant or intermediately resistant to erythromycin. Controls (n=141) were patients matched for age, sex, location, and year that bacteremia developed who had an erythromycin-susceptible pneumococcus isolated. Excluding patients with meningitis, 18 (24%) of 76 case patients and none of 136 matched controls were taking a macrolide when blood was obtained for culture (P=.00000012). Moreover, 5 (24%) of 21 case patients with the low-level-resistant M phenotype and none of 40 controls were taking a macrolide (P=.00157). These data show that development of breakthrough bacteremia during macrolide or azalide therapy is more likely to occur among patients infected with an erythromycin-resistant pneumococcus, and they also indicate that in vitro macrolide resistance resulting from both the efflux and methylase mechanisms is clinically relevant.

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