Ofloxacin Clinical Pharmacokinetics

The pharmacodynamic properties of levofloxacin (an optically active isomer of ofloxacin), ofloxacin, and ciprofloxacin, alone and in combination with rifampin, were evaluated over 24 to 48 h against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA 1199 and MRSA 494, respectively) energy-dependent efilux process mediated by the norA gene appeared to be responsible for the resistance observed. Our data suggest that with levofloxacin there is a more rapid onset of bactericidal activity than with ofloxacin or ciprofloxacin against MSSA 1199 and that the activity of levofloxacin is similar to that of ofloxacin but better than that of ciprofloxacin against MRSA 494. Resistance was noted only after exposure to the low dose of ciprofloxacin. Resistance to ofloxacin did not develop even when the pharmacokinetics of the drug were set to equal those of ciprofloxacin, suggesting that ofloxacin differs from ciprofloxacin irrespective of time of exposure. The resistance to ciprofloxacin that developed in our in vitro model may be mediated by the cfxc-ofr locus, which has been shown to be associated with low-level fluoroquinolone resistance. Overall, levofloxacin demonstrated potent bactericidal activity against S. aureus, without the emergence of resistance in our infection model. Quinolones dosed once daily were more effective than equivalent dosages administered twice daily. The addition of rifampin was not synergistic but prevented the emergence of ciprofloxacin resistance.

Section: Materuils and Methodssupporting

confidence: 81%

“…The emergence of resistance to ofloxacin has been reported only in Japan (11,19,28). This difference may be due to the longer half-life of ofloxacin than that of ciprofloxacin (6 versus 3 h), providing prolonged exposure to the drug and a possible secondary mechanism of action against nondividing organisms (21,24).…”

mentioning

confidence: 99%

Pharmacodynamics of levofloxacin, ofloxacin, and ciprofloxacin, alone and in combination with rifampin, against methicillin-susceptible and -resistant Staphylococcus aureus in an in vitro infection model

Kang

Rybak

McGrath

et al. 1994

“…Ofloxacin (OFL), a pyridonecarboxylic acid derivative of nalidixic acid, has an asymmetric center at the C-3 position of the oxazine ring (12). This fluoroquinolone exists as a racemic mixture (12).…”

mentioning

confidence: 99%

“…This fluoroquinolone exists as a racemic mixture (12). Levofloxacin (LEV), the l-enantiomer, has twoto fourfold greater in vitro activity than OFL against a variety of gram-positive and gram-negative pathogens (3,16,20).…”

mentioning

confidence: 99%

Activity of levofloxacin in a murine model of tuberculosis

Klemens

Sharpe

Rogge

et al. 1994

The activity of levofloxacin (LEV) Ofloxacin (OFL), a pyridonecarboxylic acid derivative of nalidixic acid, has an asymmetric center at the C-3 position of the oxazine ring (12). This fluoroquinolone exists as a racemic mixture (12). Levofloxacin (LEV), the l-enantiomer, has twoto fourfold greater in vitro activity than OFL against a variety of gram-positive and gram-negative pathogens (3,16,20). It is also more active than OFL in murine models of systemic infection with Staphylococcus aureus and Pseudomonas aeruginosa (2).The MICs of OFL for Mycobacterium tuberculosis determined radiometrically in 7H12 broth range from 0.5 to 2.0 ,ug/ml (6). The dose-dependent activity of OFL has been demonstrated in a murine model of tuberculosis (19). OFL at 300 mg/kg of body weight has good activity, but OFL at 150 mg/kg has only modest activity (19). The area under the concentration-time curve for OFL in mice receiving the drug at 150 mg/kg is similar to that in humans receiving a single 600-mg dose (8). Although OFL dosages of as high as 800 mg given once per day have been well tolerated (22), the role of OFL in the treatment of tuberculosis has not yet been defined (7,10,23).The MICs of LEV for M. tuberculosis (n = 12) determined radiometrically are twofold lower than those of OFL (range, 0.25 to 1.0 ,ug/ml) (14). The purpose of the present study was to evaluate the activity of LEV in a murine model of tuberculosis. The activity of LEV was compared with those of the first-line antituberculosis agents and those of OFL and sparfloxacin (SPA).

“…During separate in vivo investigations, the pharmacokinetics of the quinolone agents, cefazolin, and vancomycin were determined by obtaining 0.5 ml of intracardiac blood at various intervals up to 12 h from the time the subcutaneous or intraperitoneal dose was administered. The quinolones were evaluated by using different doses (measured in milligrams per kilogram) to determine which of them yielded peak levels in serum comparable to values obtained with the same agents in humans (2,12,28,46). Concentrations of the quinolones and cefazolin in serum were determined by using disk diffusion bioassay techniques (23,27) and the following media, indicator strains, and lower limits of detection: for ciprofloxacin and ofloxacin, antibiotic medium 2 (Difco), Klebsiella pneumoniae ATCC 10031, and 0.25 ,ug/ml; and for cefazolin, antibiotic medium 1 (Difco), S. aureus ATCC 6538P, and 2 ,ug/ml.…”

mentioning

confidence: 99%

Comparative prophylactic efficacies of ciprofloxacin, ofloxacin, cefazolin, and vancomycin in experimental model of staphylococcal wound infection

Kernodle

Kaiser

1994

Recent shifts in the species and antibiotic resistance patterns of bacteria causing nosocomial infections present new challenges for providing effective prophylaxis in surgery. Traditional regimens lack activity against methicillin-resistant staphylococci and many gram-negative species causing nosocomial infections. The new fluoroquinolones exhibit in vitro activity against many emerging surgical wound pathogens. To determine the potential of this class of antimicrobial agents for use in surgery, we compared the prophylactic efficacies of ciprofloxacin and ofloxacin with those of cefazolin and vancomycin in a guinea pig model of abscess formation. Four Staphylococcus aureus strains, one Staphylococcus epidermidis strain, and one Staphylococcus haemolyticus strain were evaluated. Vancomycin was the most effective prophylactic agent, exhibiting in vivo activity against all strains which was superior or equivalent to those of all other agents tested. Cefazolin was the least effective agent and surpassed the two quinolones in prophylactic efficacy against only one organism, a quinolone-and methicillin-resistant strain of S. aureus. The two quinolones provided excellent protection against infection with all but the quinolone-resistant isolate. The in vivo emergence of quinolone resistance among quinolonesusceptible isolates was not detected. The methicillin-resistant, quinolone-susceptible S. epidermidis and S. haemolyticus isolates were extremely susceptible to prophylaxis, exhibiting 50% infective doses above 4 x 106 CFU for seven of the eight antibiotic-strain combinations. We conclude that ciprofloxacin and ofloxacin may be effective antistaphylococcal agents in surgery. The role of these agents remains to be defined, and the definition should include consideration of an adverse effect upon antibiotic resistance patterns of organisms causing nosocomial infections.The magnitude of the problem of surgical wound infections in the United States, as many as 920,000 infections annually (45), underscores the need for improved perioperative prophylaxis. While most surgeons use cephalosporins, the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci as surgical wound pathogens in many institutions (34, 38) has prompted a search for alternative prophylactic regimens. Although vancomycin use in neurologic, cardiothoracic, and vascular surgery (5,16,18,19,29,41,44)