title: Do piperacillin/tazobactam and other antibiotics with inhibitory activity against Clostridium difficile reduce the risk for acquisition of C. difficile colonization?
abstract: BACKGROUND
  Systemic antibiotics vary widely in in vitro activity against Clostridium difficile. Some agents with activity against C. difficile (e.g., piperacillin/tazobactam) inhibit establishment of colonization in mice. We tested the hypothesis that piperacillin/tazobactam and other agents with activity against C. difficile achieve sufficient concentrations in the intestinal tract to inhibit colonization in patients.
  
  
  METHODS
  Point-prevalence culture surveys were conducted to compare the frequency of asymptomatic rectal carriage of toxigenic C. difficile among patients receiving piperacillin/tazobactam or other inhibitory antibiotics (e.g. ampicillin, linezolid, carbapenems) versus antibiotics lacking activity against C. difficile (e.g., cephalosporins, ciprofloxacin). For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups.
  
  
  RESULTS
  Of 250 patients, 32 (13 %) were asymptomatic carriers of C. difficile. In comparison to patients receiving non-inhibitory antibiotics or prior antibiotics within 90 days, patients currently receiving piperacillin/tazobactam were less likely to be asymptomatic carriers (1/36, 3 versus 7/36, 19 and 15/69, 22 %, respectively; P = 0.024) and more likely to have fecal suspensions with in vitro inhibitory activity against C. difficile (20/28, 71 versus 3/11, 27 and 4/26, 15 %; P = 0.03). Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics.
  
  
  CONCLUSIONS
  Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve, University School of Medicine, Cleveland, Ohio, USA.|Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Sirisha
authors.initials: S
authors.lastname: Kundrapu
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve, University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Venkata C K
authors.initials: VC
authors.lastname: Sunkesula
authors.affiliation: Geriatric Research Education and Clinical Center, Cleveland VA Medical Center, 10701 East Blvd, 44106, Cleveland, Ohio, USA.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Jury
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve, University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cadnum
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve, University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Nerandzic
authors.affiliation: Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Jackson S
authors.initials: JS
authors.lastname: Musuuza
authors.affiliation: Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Sethi
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve, University School of Medicine, Cleveland, Ohio, USA. curtis.donskey@va.gov.|Geriatric Research Education and Clinical Center, Cleveland VA Medical Center, 10701 East Blvd, 44106, Cleveland, Ohio, USA. curtis.donskey@va.gov.
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Donskey
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016360:Clostridioides difficile / Q000187:drug effects / Q000502:physiology; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy* / Q000209:etiology; D005243:Feces / Q000382:microbiology; D006761:Hospitals; D006801:Humans; D007422:Intestines / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010878:Piperacillin / Q000008:administration & dosage* / Q000494:pharmacology; D012307:Risk Factors; D000078142:Tazobactam
chemical_list: D000900:Anti-Bacterial Agents; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin
keywords: Clostridium difficile; Colonization; Piperacillin/tazobactam