Post-antibiotic suppressive effect of ciprofloxacin against gram-positive and gram-negative bacteria

The post-antibiotic suppressive effect (PAE) of different antibacterial agents against gram-positive bacteria has been known since the 1940s. Recently, it has been demonstrated that quinolone antimicrobial agents exert a PAE against gram-negative bacteria. In this study, the PAEs of ciprofloxacin against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens, Staphylococcus aureus, and Streptococcus faecalis were determined. The differences in PAE determined by three different techniques--filtration, centrifugation, and dilution--were assessed for S. aureus and E. coli. Ciprofloxacin had a PAE by all three methods, and filtration was used in the majority of studies. A ciprofloxacin concentration of 3 micrograms/ml in Mueller-Hinton broth, pH 7.4, with two hours of exposure produced a PAE of three to four hours for gram-negative bacilli, and 1.9 hours for S. aureus, but had no effect on S. faecalis. Exposure of organisms in urine to 300 micrograms/ml of ciprofloxacin for two hours produced a two- to six-hour PAE for E. coli, S. marcescens, P. aeruginosa, and K. pneumoniae. Use of Mueller-Hinton broth with a magnesium concentration of 8 mM, pH 5.5, yielded similar results. Using human serum, a four-hour PAE was found for P. aeruginosa. There was a progressive increase in the PAE as the duration of ciprofloxacin exposure was increased from 0.9 hours to three hours. Increasing the ciprofloxacin concentration from two to eight times the minimal bactericidal concentration (MBC) for P. aeruginosa or from four to 16 times the MBC for E. coli did not cause a significant difference in the PAE using a two-hour exposure. Overall, ciprofloxacin produced an excellent PAE for most gram-negative bacteria and for S. aureus, but not for S. faecalis. A PAE caused by ciprofloxacin can be demonstrated in broth supplemented with magnesium, in urine, in serum, and in broth with the pH adjusted to an acidic level and with the increased magnesium concentration found in urine. These results support less frequent dosing programs for ciprofloxacin in the treatment of tissue and urinary infections.