Investigation of ciprofloxacin antibacterial combinations.

Ciprofloxacin, one of the most active fluoroquinolone antimicrobial agents, is bactericidal against a broad spectrum of Gram-positive and Gram-negative microorganisms, including Staphylococcus aureus and Pseudomonas aeruginosa. However, reports of decreased susceptibility to ciprofloxacin during monotherapy in clinical studies of previously susceptible organisms have led to concerns over the future success of the fluoroquinolone class of antibacterials. Therefore, the present study was undertaken to determine whether combining ciprofloxacin with trimethoprim and or a sulphonamide could prove clinically beneficial. The microbiological activity of the antibacterials used either alone or in combination was studied using in vitro techniques, against cultures of P. aeruginosa, S. aureus and Burkholderia cepacia. The antibacterials were used at concentrations either equal to or below those clinically achievable in plasma. In a number of cases, potentially important synergistic interactions were demonstrated. S. aureus and P. aeruginosa mutants resistant to the antibacterials alone or in combination were selected in vitro. Stably resistant mutants of both organisms were isolated. The greatest propensity for the development of resistance was demonstrated when ciprofloxacin was used alone. The development of resistance was markedly reduced when ciprofloxacin, trimethoprim and a sulphonamide (either sulphamethoxazole or sulphadiazine) were used in combination. Killing curve determinations provided additional evidence of the prevention or delay of the emergence of drug-resistant subpopulations of P. aeruginosa and S. aureus. Two separate HPLC methods were developed to obtain a separation between ciprofloxacin and sulphadiazine, and between ciprofloxacin and trimethoprim in Iso-sensitest broth. Each method was capable of quantitating each compound within the microbiological matrix and no pre-treatment processes were required. Bacterial uptake studies involving HPLC assay and dry weight determinations indicated that ciprofloxacin and sulphadiazine were able to enhance the uptake of the other by log phase P. aeruginosa cultured in the presence of the antibacterials. The combination of ciprofloxacin and trimethoprim indicated no marked difference in the drug uptakes by log phase P. aeruginosa compared with drug uptakes from broth containing either antibacterial alone.

Grantor dc:publisher.institution

Robert Gordon University

Year dc:date.issued

1997

Author dc:creator

• Hamilton, Vivienne E.S.

Advisor dc:contributor.advisor

• R.M.E. Richards and R.G. Reid

• Ciprofloxacin
• Antibacterial combinations
• Trimethoprim
• Sulphonamide
• Synergistic interactions
• Gram-positive
• Gram-negative
• Microorganisms

Language dc:language

en

Identifier

oai:rgu-repository.worktribe.com:2807405
https://doi.org/10.48526/rgu-wt-2807405

OAI identifier oai:identifier

oai:rgu-repository.worktribe.com:2807405