Oral ciprofloxacin biofilm activity in a catheter-associated urinary tract infection model

Abstract

Background: Catheter-associated urinary tract infections (CA-UTIs) are a common hospital-acquired infection. We examined ciprofloxacin activity in a novel CA-UTI in vitro model. Methods: Three ATCC strains [Escherichia coli (ECO)-25922, Klebsiella pneumoniae (KPN)-700721, Pseudomonas aeruginosa (PAE)-27853] and 45 clinical urinary isolates were assessed. Biofilm mass and planktonic bacterial density were quantified during drug-free incubation (72h) and following ciprofloxacin exposure (equivalent 750mg orally q12h, 3days). Results: ECO produced smaller biofilms (6.3±1.1log10cfu/cm2) compared with KPN (7.1±0.7log10cfu/cm2) and PAE (7.0±1.2log10cfu/cm2), which extended along the entire catheter length. Following ciprofloxacin, all isolates with MIC>4mg/L had minimal biofilm disruption or planktonic kill. Ciprofloxacin resistance was most common in PAE isolates (10/16 isolates), compared with ECO (3/16 isolates) and KPN (6/16 isolates). Greater ciprofloxacin exposure (AUC0-24/MIC) was required for a 3log10 biofilm kill for KPN (5858; R2=0.7774) compared with ECO (2117; R2=0.7907) and PAE (2485; R2=0.8260). Due to persistent growth in the bladder, ECO required greater ciprofloxacin exposure for a 3log10 planktonic kill (5920; R2=0.8440) compared with KPN (2825; R2=0.9121) and PAE (1760; R2=0.8781). Monte Carlo simulation supported a 95% PTA for both a 3log10 biofilm and planktonic kill for ECO and KPN isolates with MIC≤0.5mg/L and PAE isolates with MIC≤1mg/L. Conclusions: In a novel CA-UTI model, following simulated ciprofloxacin therapy, KPN biofilms were comparatively more difficult to disrupt, ECO planktonic growth frequently persisted in the bladder, and PAE had greater propensity for emergence of ciprofloxacin resistance.