Molecular characterization and differential effects of levofloxacin and ciprofloxacin on the potential for developing quinolone resistance among clinical Pseudomonas aeruginosa isolates.

Background: Fluoroquinolones are some of the most used antimicrobial agents for the treatment of Pseudomonas aeruginosa. This study aimed at exploring the differential activity of ciprofloxacin and levofloxacin on the selection of resistance among P. aeruginosa isolates at our medical center. Methods: 233 P. aeruginosa clinical isolates were included in this study. Antimicrobial susceptibility testing (AST) was done using disk diffusion and broth microdilution assays. Random Amplification of Polymorphic DNA (RAPD) was done to determine the genetic relatedness between the isolates. Induction of resistance against ciprofloxacin and levofloxacin was done on 19 isolates. Fitness cost assay was done on the 38 induced mutants and their parental isolates. Finally, whole genome sequencing was done on 16 induced mutants and their 8 parental isolates. Results: AST results showed that aztreonam had the highest non-susceptibility. RAPD results identified 18 clusters. The 19 P. aeruginosa isolates that were induced against ciprofloxacin and levofloxacin yielded MICs ranging between 16 and 256 µg/mL. Levofloxacin required fewer passages in 10 isolates and the same number of passages in 9 isolates as compared to ciprofloxacin to reach their breakpoints. Fitness cost results showed that 12 and 10 induced mutants against ciprofloxacin and levofloxacin, respectively, had higher fitness cost when compared to their parental isolates. Whole genome sequencing results showed that resistance to ciprofloxacin and levofloxacin in sequenced mutants were mainly associated with alterations in gyrA, gyrB and parC genes. Conclusion: Understanding resistance patterns and risk factors associated with infections is crucial to decrease the emerging threat of antimicrobial resistance.

Clinical predictors of mortality in patients with pseudomonas aeruginosa infection.

BACKGROUND: Infections caused by Pseudomonas aeruginosa are difficult to treat with a significant cost and burden. In Lebanon, P. aeruginosa is one of the most common organisms in ventilator-associated pneumonia (VAP). P. aeruginosa has developed widespread resistance to multiple antimicrobial agents such as fluoroquinolones and carbapenems. We aimed at identifying risk factors associated for P. aeruginosa infections as well as identifying independent risk factors for developing septic shock and in-hospital mortality. METHODS: We used a cross-sectional study design where we included patients with documented P. aeruginosa cultures who developed an infection after obtaining written consent. Two multivariable regression models were used to determine independent predictors of septic shock and mortality. RESULTS: During the observed period of 30 months 196 patients were recruited. The most common predisposing factor was antibiotic use for more than 48 hours within 30 days (55%). The prevalence of multi-drug resistant (MDR) P. aeruginosa was 10%. The strongest predictors of mortality were steroid use (aOR = 3.4), respiratory failure (aOR = 7.3), identified respiratory cultures (aOR = 6.0), malignancy (aOR = 9.8), septic shock (aOR = 18.6), and hemodialysis (aOR = 30.9). CONCLUSION: Understanding resistance patterns and risk factors associated with mortality is crucial to personalize treatment based on risk level and to decrease the emerging threat of antimicrobial resistance.