Failure of Macrolide Antibiotic Treatment in Patients with Bacteremia Due to Erythromycin-Resistant Streptococcus pneumoniae

• Published in: Clinical infectious diseases 2002-09, Vol.35 (5), p.556-564
• Main Authors: Lonks, John R., Garau, Javier, Gomez, Lucía, Xercavins, Mariona, de Echagüen, Anna Ochoa, Gareen, Ilana F., Reiss, Philip T., Medeiros, Antone A.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteremia; Bacteremia - drug therapy; Bacteremia - microbiology; Bacterial diseases; Bacterial sepsis; Biological and medical sciences; Blood; Case-Control Studies; Child; Child, Preschool; Drug Resistance - physiology; Erythromycin - pharmacology; Female; Human bacterial diseases; Humans; Infant; Infections; Infectious diseases; Macrolides; Major Articles; Male; Medical sciences; Middle Aged; Penicillin; Pharmacology. Drug treatments; Pneumococcal meningitis; Pneumococcal pneumonia; Streptococcus pneumoniae; Teaching hospitals; Treatment Failure
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/341978

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.