title: Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae.
abstract: 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.
authors.affiliation: Miriam and Rhode Island Hospitals and Brown Medical School, Providence, RI 02906, USA. John_Lonks@brown.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Lonks
authors.forename: Javier
authors.initials: J
authors.lastname: Garau
authors.forename: Lucía
authors.initials: L
authors.lastname: Gomez
authors.forename: Mariona
authors.initials: M
authors.lastname: Xercavins
authors.forename: Anna
authors.initials: A
authors.lastname: Ochoa de Echagüen
authors.forename: Ilana F
authors.initials: IF
authors.lastname: Gareen
authors.forename: Philip T
authors.initials: PT
authors.lastname: Reiss
authors.forename: Antone A
authors.initials: AA
authors.lastname: Medeiros
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000502:physiology; D004917:Erythromycin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D013296:Streptococcus pneumoniae; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin