Antibiotic resistance: learning from animal feeds and animal experimentation  P. Moreillon, J.M. Entenza  Clinical Microbiology and Infection  Volume 7, Pages 13-18 (January 2001) DOI: 10.1046/j.1469-0691.2001.00068.x Copyright © 2001 European Society of Clinical Infectious Diseases Terms and Conditions

Figure 1 Outcome of 3-day treatment of experimental endocarditis due to strain MRSA P8 with either levofloxacin (equivalent to 500 mg of oral levofloxacin once a day in humans) or ciprofloxacin (equivalent to 750 mg of oral ciprofloxacin twice a day in humans). Each dot in the figure represents the bacterial density in the vegetation of a single animal. Control animals were killed at the start of therapy, i.e. 12 h after inoculation. Treated rats were killed 12 h after the trough serum level of the last antibiotic dose. The two open dots in the ciprofloxacin treatment group represent two animals in which bacteria with increased (eight times) MICs of ciprofloxacin were isolated from the valve. P < 0.05 indicates statistically significant differences between the incidence of valve infection, determined by the Fisher's exact test. Clinical Microbiology and Infection 2001 7, 13-18DOI: (10.1046/j.1469-0691.2001.00068.x) Copyright © 2001 European Society of Clinical Infectious Diseases Terms and Conditions

Figure 2 Selection of levofloxacin (LEVO)- and ciprofloxacin (CIPRO)-resistant derivatives by exposure of a methicillin-susceptible (MSSA 112, left panel) and a methicillin-resistant (MRSA P8, right panel) strain of S. aureus to stepwise increasing concentrations of antibiotics. Series of tubes containing 2-fold serial dilutions of either test drug were inoculated with a final concentration of 105 CFU/mL of the test organisms and further incubated for 24 h at 35°C, as for MIC tests. On the next day, the tube with the highest antibiotic concentration still showing turbidity was used to inoculate a new series of antibiotic-containing tubes. The procedure was repeated and the increase in MIC was followed over time. Both quinolones selected for derivatives with progressive increase in their MICs. However, resistance developed more slowly with levofloxacin than with ciprofloxacin. Clinical Microbiology and Infection 2001 7, 13-18DOI: (10.1046/j.1469-0691.2001.00068.x) Copyright © 2001 European Society of Clinical Infectious Diseases Terms and Conditions

Figure 3 Population analysis profile of the ciprofloxacin-resistant laboratory mutant P8/128 (closed squares) and a ciprofloxacin-resistant clinical isolate of S. aureus (closed triangles) grown on agar plates containing increasing concentrations of Y-688. Large bacterial numbers (up to 1010 CFUs) were spread on plates containing 2-fold-increasing concentrations of the drug. Resistant variants able to grow in the presence of increased concentrations of Y-688 were counted after 48 h of incubation at 35°C. Clinical Microbiology and Infection 2001 7, 13-18DOI: (10.1046/j.1469-0691.2001.00068.x) Copyright © 2001 European Society of Clinical Infectious Diseases Terms and Conditions