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Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections.

ABSTRACT: Fluoroquinolones are a guideline-recommended therapy for complicated urinary tract infections, including pyelonephritis. Elevated drug concentrations of fluoroquinolones in the urine and therapy with high-dose levofloxacin are believed to overcome resistance and effectively treat infections caused by resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.gov, NCT01345929 and NCT01345955 , both registered April 28, 2011) provided an opportunity to test this hypothesis by examining the clinical and microbiological outcomes of high-dose levofloxacin treatment by levofloxacin minimum inhibitory concentration.Patients were randomly assigned 1:1 to ceftolozane/tazobactam (1.5 g intravenous every 8 h) or levofloxacin (750 mg intravenous once daily) for 7 days of therapy. The ASPECT-cUTI study provided data on 370 patients with at least one isolate of Enterobacteriaceae at baseline who were treated with levofloxacin. Outcomes were assessed at the test-of-cure (5-9 days after treatment) and late follow-up (21-42 days after treatment) visits in the microbiologically evaluable population (N?=?327).Test-of-cure clinical cure rates above 90% were observed at minimum inhibitory concentrations ?4 ?g/mL. Microbiological eradication rates were consistently >90% at levofloxacin minimum inhibitory concentrations ?0.06 ?g/mL. Lack of eradication of causative pathogens at the test-of-cure visit increased the likelihood of relapse by the late follow-up visit.Results from this study do not support levofloxacin therapy for complicated urinary tract infections caused by organisms with levofloxacin minimum inhibitory concentrations ?4 ?g/mL.ClinicalTrials.gov, NCT01345929 and NCT01345955.

SUBMITTER: Armstrong ES

PROVIDER: S-EPMC5124239 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections.

Armstrong Eliana S ES Mikulca Janelle A JA Cloutier Daniel J DJ Bliss Caleb A CA Steenbergen Judith N JN

BMC infectious diseases 20161125 1

<h4>Background</h4>Fluoroquinolones are a guideline-recommended therapy for complicated urinary tract infections, including pyelonephritis. Elevated drug concentrations of fluoroquinolones in the urine and therapy with high-dose levofloxacin are believed to overcome resistance and effectively treat infections caused by resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.gov, NCT01345929 and NCT01345955 , both registered April 28, 2011) provided an opportunity to test this ...[more]

PMID: 27887579

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Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections.

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Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections.

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