DOI: 10.36347/sjams.2015.v03i04.046

Pages: 1818-1825

Background: Complicated urinary tract infections (cUTIs) caused by multidrug-resistant (MDR) organisms represent a significant clinical challenge requiring precise pharmacokinetic (PK)/pharmacodynamic (PD) optimization. Inadequate drug concentrations at the site of infection contribute to therapeutic failure and resistance emergence. Objective: To quantify and compare serum and urinary drug concentrations of ciprofloxacin, piperacillin-tazobactam, and meropenem in hospitalized patients with cUTIs and to delineate their implications for Therapeutic Drug Monitoring (TDM) protocols. Methods: A prospective observational study was conducted across two tertiary care centers in South India (Bhaskar Medical College, Hyderabad and DR B.R. Ambedkar Medical College, Bangalore) from January 2014 to March 2015. A total of 140 adult patients diagnosed with cUTI were enrolled and allocated to three antibiotic regimen groups. Serial blood samples at steady state (pre-dose and 1-hour post-dose) and mid-stream urine samples were collected. Drug concentrations were determined using validated High-Performance Liquid Chromatography (HPLC) assays. Pharmacokinetic parameters including Cmax, Cmin, AUC, t½, and %T>MIC were computed. Results: Mean serum Cmax values were 4.82 ± 0.91 µg/mL, 298.6 ± 42.3 µg/mL, and 52.4 ± 8.7 µg/mL for ciprofloxacin, piperacillin-tazobactam, and meropenem, respectively. Urinary concentrations exceeded minimum inhibitory concentrations (MICs) by factors of 1250, 301, and 623 for the respective antibiotics. Clinical cure rates at Day 7 were 78.3%, 80.9%, and 82.9% for the three groups. The %T>MIC for piperacillin-tazobactam (68.2%) and meropenem (72.8%) met the PK/PD targets for beta-lactams, whereas 13.0% of the ciprofloxacin cohort had sub-therapeutic serum levels. Conclusion: Substantial interpatient variability in serum antibiotic concentrations was observed among cUTI patients. Routine serum TDM is especially critical for ciprofloxacin-treated patients and t