title: Failure of clindamycin to eradicate infection with beta-hemolytic streptococci inducibly resistant to clindamycin in an animal model and in human infections.
abstract: Inducible clindamycin resistance in beta-hemolytic streptococci remains an underrecognized phenomenon of unknown clinical significance. We performed an evaluation of inducible clindamycin resistance using an animal model as well as retrospectively reviewing the charts of patients treated with clindamycin monotherapy who were infected with beta-hemolytic streptococci inducibly resistant to clindamycin. The neutropenic mouse thigh model of infection was used to evaluate the in vivo activity of clindamycin against beta-hemolytic streptococci, including isolates susceptible, inducibly resistant, or constitutively resistant to clindamycin. The clinical microbiology laboratory information system and pharmacy databases were cross-referenced to identify patients with infections due to inducibly clindamycin-resistant beta-hemolytic streptococci who were treated with clindamycin monotherapy. Medical records of these patients were reviewed to evaluate microbiologic and clinical outcomes. Inducible clindamycin resistance resulted in impaired killing of beta-hemolytic streptococci in the animal model. Though suppressed initially, compared to those with constitutive resistance (P=0.0429), by 48 h, colony counts of inducibly clindamycin-resistant organisms were similar to those of constitutively resistant isolates (P=0.1142). In addition, we identified 8 patients infected with inducibly clindamycin-resistant beta-hemolytic streptococci who experienced clinical and microbiologic failure when treated with clindamycin monotherapy. These patients either improved initially and subsequently failed or never responded to clindamycin therapy. We have demonstrated in a murine model of infection and from human cases that inducible clindamycin resistance in beta-hemolytic streptococci is clinically significant. Routine testing and reporting by clinical laboratories should be encouraged and alternative antimicrobial agents considered when these organisms are encountered in clinical care.
authors: Department of Pharmacy, University Health System, San Antonio, Texas, USA.
authors: James S
authors: JS
authors: Lewis
authors: Alex J
authors: AJ
authors: Lepak
authors: George R
authors: GR
authors: Thompson
authors: William A
authors: WA
authors: Craig
authors: David R
authors: DR
authors: Andes
authors: Kathryn E
authors: KE
authors: Sabol-Dzintars
authors: James H
authors: JH
authors: Jorgensen
mesh_terms: D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002981:Clindamycin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008875:Middle Aged; D012189:Retrospective Studies; D013290:Streptococcal Infections / Q000188:drug therapy*; D013291:Streptococcus / Q000187:drug effects*; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin