Pharmacokinetic/pharmacodynamic based dosing of ciprofloxacin in complicated urinary tract infections
DOI:
https://doi.org/10.3329/bjp.v10i3.23604Keywords:
Ciprofloxacin, Complicated urinary tract infections, Pharmacokinetics, Pharmacodynamics,Abstract
Ciprofloxacin is often used in treatment of complicated urinary tract infections in areas with high rates of resistance to first line agents. The aim of this study was to evaluate efficacy of ciprofloxacin in standard dosing regimens in treatment of complicated urinary tract infections. Plasma concentration curves were simulated and minimum inhibitory concentration (MIC) and post-antibiotic effect were determined. Ciprofloxacin MIC ranged from 0.0156 for Gram-negative and to 0.125-0.5 µg/mL for Gram-positive bacteria. Both dosing regimens were suitable for eradication of Gram-negative bacteria, with slight supremacy of 750 mg/12 hours over 500 mg/12 hours dosing regimen. Even though all strains were fully susceptible to ciprofloxacin, pharmaco-kinetic/pharmacodynamic parameters did not meet target thresholds for pathogens with MIC over 0.1-0.2 µg/mL regardless of the administered dose. Ciprofloxacin remains an excellent choice for treatment of complicated urinary tract infections caused by Gram-negative bacteria, but in infection caused by Gram-positive strains, deeper analysis is necessary in order to achieve optimal results.
Downloads
References
Ambrose PG. Antimicrobial susceptibility breakpoints: PK-PD and susceptibility breakpoints. Treat Respir Med. 2005; 4(Suppl 1): 5-11.
Barber A, Norton J, Spivak A, Mulvey M. Urinary tract infections: Current and emerging management strategies. Clin Infect Dis. 2013; 57: 719-24.
Blondeau J, Hansen G, Metzler K, Hedlin P. The role of PK/PD parameters to avoid selection and increase of resistance: Mutant prevention concentration. J Chemother. 2004; 16(Suppl 3): 1-19.
Chen YH, Ko WC, Hsueh PR. Emerging resistance problems and future perspectives in pharmacotherapy for complicated urinary tract infections. Expert Opin Pharmacother. 2013; 14: 587-96.
Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: Approved standard. 7th ed. Clinical and Laboratory Standards Institute document M7-A7. Clinical and Laboratory Standards Institute, 2006.
Craig WA. Does the Dose Matter? Clin Infect Dis. 2001; 33(Suppl 3): 233-37.
Craig WA, Gudmundsson S: Postantibiotic effect. In: Antibiotics in laboratory medicine. 4th ed. Baltimore MD, Williams & Wilkins, 1996, pp 296329.
Daoud Z, Sokhn ES, Azar E, Masri K, Doron S. Mutant prevention concentrations of ciprofloxacin against urinary isolates of Escherichia coli and Klebsiella pneumonia. J Infect Dev Ctries. 2014; 8: 154-59.
Drusano G L, Preston S, Fowler C, Corrado M, Weisinger B, Kahn J: Relationship between fluoroquinolone area under the curve: Minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia. J Infect Dis. 2004; 189: 1590-97.
Finch R. Ciprofloxacin: Efficacy and indications. J Chemother . 2000; 12 Suppl: 15-17.
Firsov A, Vostrov S, Lubenko I, Drlica K, Portnoy Y, Zinner S: In vitro pharmacodynamic evaluation of the mutant selection window hypothesis using four fluoroquinolones against Staphylococcus aureus. Antimicrob Agents Chemother. 2003; 47: 1604-13.
Forrest A, Nix DE, Ballow CH, Goss TF, Birmingham MC, Schentag JJ. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother. 1993; 37: 1073-81.
Jacobs MR. Optimisation of antimicrobial therapy using pharmacokinetic and pharmacodynamic parameters. Clin Microbiol Infect. 2001; 7: 589-96.
Krcmery S, Naber KG. Ciprofloxacin once versus twice daily in the treatment of complicated urinary tract infections. Int J Antimicrob Agents. 1999; 11: 133-38.
Licata L, Smith C, Goldschmidt R, Barrett J, Frosco M. Comparison of the postantibiotic and postantibiotic sub-MIC effects of levofloxacin and ciprofloxacin on Staphylococcus aureus and Streptococcus pneumoniae. Antimicrob Agents Chemother. 1997; 41: 950-55.
Minguez F, Ramos C, Barrientos S, Loscos A, Prieto J. Postantibiotic effect of ciprofloxacin compared with that of five other quinolones. Chemotherapy 1991; 37: 420-25.
Mouton JW, Brown DF, Apfalter P, Cantón R, Giske CG, Ivanova M, MacGowan AP, Rodloff A, Soussy CJ, Steinbakk M, Kahlmeter G. The role of pharmacokinetics/pharmaco-dynamics in setting clinical MIC breakpoints: The EUCAST approach. Clin Microbiol Infect. 2012; 18: E37-E45.
Mueller M, de la Pena A, Derendorf H. Issues in pharmacokinetics and pharmacodynamics of anti-infective agents: Kill curves versus MIC. Antimicrob Agents Chemother. 2004; 48: 369377.
Nicolau P. Optimizing outcomes with antimicrobial therapy through pharmacodynamic pro?ling. J infect Chemother. 2003; 9: 292-96.
Nicolle LE: Complicated urinary tract infections in adults. Can J Infect Dis Med Microbiol. 2005; 16: 349-60.
Olofsson S, Marcusson L, Komp Lindgren P, Hughes D, Cars O. Selection of ciprofloxacin resistance in Escherichia coli in an in vitro kinetic model: Relation between drug exposure and mutant prevention concentration. J Antimicrob Chemother. 2006; 57: 1116-21.
Navarro SM, Coloma Milano C, Zarzuelo Castañeda A, Sayalero Marinero ML, Sánchez-Navarro A. Pharmacokinetics of ciprofloxacin as a tool to optimise dosage schedules in community patients. Clin Pharmacokinet. 2002a; 41: 121320.
Navarro SM, Sayalero Marinero M, Sánchez Navarro A. Pharmacokinetic/pharmacodynamic modeling of ciprofloxacin 250 mg/12 h versus 500 mg/24 h for urinary infections. J Antimicrob Chemother. 2002b; 50: 67-72.
Scaglione F, Mouton J, Mattina R, Fraschini F: Pharmacodynamics of levofloxacin and ciprofloxacin in a murine pneumonia model: Peak concentration/MIC versus area under the curve/MIC ratios. Antimicrob Agents Chemother. 2003; 47: 2749-55.
Schentag J. Clinical pharmacology of the fluoroquinolones: Studies in human dynamic/kinetic models. Clin Infect Dis. 2000; 31(Suppl 2): 40-44.
Spangler SK, Lin G, Jacobs MR, Appelbaum PC. Postantibiotic effect and postantibiotic sub-MIC effect of levofloxacin compared to those of ofloxacin, ciprofloxacin, erythromycin, azithromycin, and clarithromycin against 20 Pneumococci. Antimicrob Agents Chemother. 1998; 42: 1253.
Van Bambeke F, Michot J, Van Eldere J, Tulkens P. Quinolones in 2005: An update. Clin Microbiol Infect. 2005; 11: 256-80.
Wispelwey B. Clinical implications of pharmacokinetics and pharmacodynamics of fluoroquinolones. Clin Infect Dis. 2005; 41(Suppl 2): 127-35.
Zelenitsky S, Ariano R, Iacovides H, Sun S, Harding G. AUC(0-t)/MIC is a continuous index of fluoroquinolone exposure and predictive of antibacterial response for Streptococcus pneumoniae in an in vitro infection model. J Antimicrob Chemother. 2003; 51: 905-11.
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
