title: Pharmacodynamic profiling of commonly prescribed antimicrobial drugs against Escherichia coli isolates from urinary tract.
abstract: Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections. Minimum inhibitory concentration determination by Etest was performed for 205 Brazilian community urinary tract infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream strains recovered from a surveillance study. Pharmacodynamic exposure was modeled via a 5000 subject Monte Carlo simulation. All isolates were susceptible to ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%, 75.7% and 64.3% among inpatient isolates, respectively. Against outpatient isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in conservative scenarios) achieved high cumulative fraction of response: carbapenems and piperacillin/tazobactam cumulative fraction of responses were close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar results were observed against inpatients isolates for carbapenems (100%) and piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9% bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive scenario) and 56.7% (conservative scenario) respectively. Based on this model, standard doses of beta-lactams were predicted to deliver sufficient pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided for inpatients and ciprofloxacin empirical prescription should be avoided in both inpatients and outpatients with complicated urinary tract infection.
authors.affiliation: Laboratório Especial de Microbiologia Clínica, Department of Infectology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address: gbtrova@gmail.com.
authors.forename: Gabriel Trova
authors.initials: GT
authors.lastname: Cuba
authors.affiliation: Laboratório Especial de Microbiologia Clínica, Department of Infectology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Antonio Carlos Campos
authors.initials: AC
authors.lastname: Pignatari
authors.affiliation: Laboratório Especial de Microbiologia Clínica, Department of Infectology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Katya Silva
authors.initials: KS
authors.lastname: Patekoski
authors.affiliation: Laboratório Especial de Microbiologia Clínica, Department of Infectology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Lucimila Jorge
authors.initials: LJ
authors.lastname: Luchesi
authors.affiliation: Laboratório Especial de Microbiologia Clínica, Department of Infectology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Carlos Roberto Veiga
authors.initials: CR
authors.lastname: Kiffer
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002443:Ceftriaxone / Q000493:pharmacokinetics / Q000494:pharmacology; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology; D000077727:Ertapenem; D004926:Escherichia coli / Q000187:drug effects* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests / Q000379:methods; D009010:Monte Carlo Method; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D010878:Piperacillin / Q000493:pharmacokinetics / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D011704:Pyelonephritis / Q000382:microbiology; D012720:Severity of Illness Index; D013845:Thienamycins / Q000493:pharmacokinetics / Q000494:pharmacology; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology; D047090:beta-Lactams / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D002939:Ciprofloxacin; D002443:Ceftriaxone; D010397:Penicillanic Acid; D000077731:Meropenem; D000077727:Ertapenem; D010878:Piperacillin
keywords: Escherichia coli; Monte Carlo method; Pharmacodynamics; Urinary tract infection
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