title: Suboptimal clinical response to ciprofloxacin in patients with enteric fever due to Salmonella spp. with reduced fluoroquinolone susceptibility: a case series.
abstract: BACKGROUND
  Salmonella spp. with reduced susceptibility to fluoroquinolones have higher than usual MICs to these agents but are still considered "susceptible" by NCCLS criteria. Delayed treatment response to fluoroquinolones has been noted, especially in cases of enteric fever due to such strains. We reviewed the ciprofloxacin susceptibility and clinical outcome of our recent enteric fever cases.
  
  
  METHODS
  Salmonella enterica Serotype Typhi (S. Typhi) and Serotype Paratyphi (S. Paratyphi) blood culture isolates (1998-2002) were tested against nalidixic acid by disk diffusion (DD) and agar dilution (AD) and to ciprofloxacin by AD using NCCLS methods and interpretive criteria. Reduced fluoroquinolone susceptibility was defined as a ciprofloxacin MIC of 0.125-1.0 mg/L. The clinical records of patients treated with ciprofloxacin for isolates with reduced fluoroquinolone susceptibility were reviewed.
  
  
  RESULTS
  Seven of 21 (33%) S. Typhi and S. Paratyphi isolates had reduced susceptibility to fluoroquinolones (MIC range 0.125-0.5 mg/L). All 7 were nalidixic acid resistant by DD (no zone) and by AD (MIC 128- >512 mg/L). The other 14 isolates were nalidixic acid susceptible and fully susceptible to ciprofloxacin (MIC range 0.015-0.03 mg/L). Five of the 7 cases were treated initially with oral ciprofloxacin. One patient remained febrile on IV ciprofloxacin until cefotaxime was added, with fever recurrence when cefotaxime was discontinued. Two continued on oral or IV ciprofloxacin alone but had prolonged fevers of 9-10 days duration, one was switched to IV beta-lactam therapy after remaining febrile for 3 days on oral/IV ciprofloxacin and one was treated successfully with oral ciprofloxacin. Four of the 5 required hospitalization.
  
  
  CONCLUSIONS
  Our cases provide further evidence that reduced fluoroquinolone susceptibility of S. Typhi and S. Paratyphi is clinically significant. Laboratories should test extra-intestinal Salmonella spp. for reduced fluoroquinolone susceptibility.
authors.affiliation: Division of Infectious Disease, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, ON, Canada. slinger@cheo.on.ca.
authors.forename: Robert
authors.initials: R
authors.lastname: Slinger
authors.forename: Marc
authors.initials: M
authors.lastname: Desjardins
authors.forename: Anne E
authors.initials: AE
authors.lastname: McCarthy
authors.forename: Karam
authors.initials: K
authors.lastname: Ramotar
authors.forename: Peter
authors.initials: P
authors.lastname: Jessamine
authors.forename: Christiane
authors.initials: C
authors.lastname: Guibord
authors.forename: Baldwin
authors.initials: B
authors.lastname: Toye
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D002939:Ciprofloxacin / Q000494:pharmacology / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000494:pharmacology; D010284:Paratyphoid Fever / Q000188:drug therapy* / Q000382:microbiology; D012189:Retrospective Studies; D012482:Salmonella paratyphi A / Q000187:drug effects* / Q000235:genetics; D012485:Salmonella typhi / Q000187:drug effects* / Q000235:genetics; D014435:Typhoid Fever / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D009268:Nalidixic Acid; D002939:Ciprofloxacin