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Indian Journal of Medical Microbiology, Vol. 28, No. 1, January-March, 2010, pp. 84-85 Correspondence Activities of fourth generation cephalosporins alone and in combination with gentamicin, amikacin, ciprofloxacin and levofloxacin against bloodstream Pseudomonas aeruginosa isolate *B Ozbek, G Otuk Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Istanbul, 34116 Beyazit, Istanbul, Turkey Correspondence Address: *Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Istanbul, 34116 Beyazit, Istanbul, Turkey, bernaozbek@hotmail.com Date of Submission: 06-Mar-2009 Code Number: mb10029 PMID: 20061781 DOI: 10.4103/0255-0857.58746 Dear Editor, Pseudomonas aeruginosa infection has been related to life-threatening bacteremia and high mortality. Treatment of P. aeruginosa infections is often complicated by resistant phenotypes. On the other hand, emergence of resistance has been observed when any of the newer anti-pseudomonal antibiotics is used alone against this organism. [1] As P. aeruginosa infections often progress rapidly, patients with Pseudomonas infections might receive empirical antibiotics that are inactive against Pseudomonas, especially before antibiotic susceptibility results become available. [2] For these reasons, P. aeruginosa has been an important consideration in the development of an effective combination therapy in order to produce rapid enhancement of bactericidal activity and to help prevent or delay the emergence of resistance. Anti-pseudomonal cephalosporins are frequently used for empirical therapy in severely ill patients in intensive care, oncology and transplantation units. Therefore, using the time-kill curve technique, we studied the in-vitro comparative activities of fourth generation cephalosporins and ceftazidime, in combination with gentamicin, amikacin, ciprofloxacin and levofloxacin against P. aeruginosa strains that were isolated from patients with bacteremia. Fifteen non-duplicates, nosocomially acquired P. aeruginosa strains isolated from blood specimens between January and June 2004 were obtained from the Department of Infectious Diseases and Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul. As a reference strain, P. aeruginosa ATCC 27853 (American Type Culture Collection, Rockville, Md.) was used. Mueller-Hinton Broth (Difco Laboratories, Detroit, Michigan) supplemented with divalent cations was used for Minimum inhibitory concentration (MIC) determinations and for time-kill curve studies. MICs were determined by the microbroth dilution technique, as described by the Clinical and Laboratory Standards Institute (CLSI). [3] The time-kill curve method was used for synergy testing and was performed using the broth macrodilution technique described by the NCCLS M26-A method. [4] For each strain, antibiotics were studied both alone and in combination, at MIC concentrations. The inoculum was prepared spectrophometrically and was added to the flasks in order to yield a final concentration of 1 × 10 6 cfu/mL. The final inoculum was determined at time zero; viable counts were performed after 4, 8, 12 and 24 hours of incubation, at 35°C. The MIC values of the five antibiotics were ranked as follows: amikacin > cefepime > cefpirome > ceftazidime > gentamicin > ciprofloxacin = levofloxacin. The activities of fourth generation cephalosporins or ceftazidime with gentamicin, amikacin, ciprofloxacin or levofloxacin are summarized in [ Figure - 1]. Synergy was evaluated at 8, 12 and 24 hours. All cephalosporins plus aminoglycoside or fluoroquinolone combinations yielded synergistic activity against ≥ 60% of strains at 24 hours. The combination of fourth generation cephalosporins plus ciprofloxacin resulted in synergistic activity against 66% of the tested strains, whereas, synergistic activity was noted against 60% of strains with combinations of fourth generation cephalosporins plus levofloxacin, at 24 hours. Antagonism was not observed with any combination. Results of this study indicate good synergistic activity with cefepime or cefpirome combinations that include aminoglycosides or fluoroquinolones. No significant differences were found in synergistic effects between the fourth generation cephalosporins or ceftazidime or between the tested fluoroquinolones or aminoglycosides. These results support the potential role of the fourth generation cephalosporins as an alternative to ceftazidime in combination therapy with the studied aminoglycosides or fluoroquinolones in the treatment of severe P. aeruginosa infections. Although the synergy was apparent when the strains were susceptible to all agents tested (60 of 96), antibiotic combinations tested in the present study showed most frequent synergy in 74 of the 84 cases (88%) at 24 hours, when the strains were resistant to at least one agent. Similar results have been obtained previously. [5] The potential for tested cephalosporins to act synergistically with studied aminoglycosides or fluoroquinolones against resistant isolates may provide an alternative when selecting empirical antibiotic therapy in institutions that have high rates of drug resistance among P. aeruginosa. This work was supported by a grant from the research Fund of The University of Istanbul. Project number: T - 415/08032004. References
Copyright 2010 - Indian Journal of Medical Microbiology The following images related to this document are available:Photo images[mb10029f1.jpg] |
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