Identification of factors affecting in vivo aminoglycoside activity in an experimental model of gram-negative endocarditis

Potel, G.; Caillon, Jocelyne; Gallou, F. Le; Bugnon, Denis; Conte, Philippe Le; Raza, J; Lepage, Jean-Yves; Baron, D.; Drugeon, H

doi:10.1128/aac.36.4.744

Cited by 20 publications

(16 citation statements)

References 23 publications

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“…The specific aminoglycoside used is a critical variable and cannot be totally predicted from MIC data alone because pharmacodynamic characteristics differ markedly in animal models of IE caused by Gram-negative aerobic bacilli. 152,153 Thus, determinations of tube-dilution MBC often are necessary to guide therapy (Class IIb, Level of Evidence: C).…”

Section: Non-hacek Gram-negative Bacillimentioning

confidence: 99%

Infective Endocarditis

Baddour¹,

Wilson²,

Bayer³

et al. 2005

Circulation

1,277

436

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Background-Despite advances in medical, surgical, and critical care interventions, infective endocarditis remains a disease that is associated with considerable morbidity and mortality. The continuing evolution of antimicrobial resistance among common pathogens that cause infective endocarditis creates additional therapeutic issues for physicians to manage in this potentially life-threatening illness. Methods and Results-This work represents the third iteration of an infective endocarditis "treatment" document developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It updates recommendations for diagnosis, treatment, and management of complications of infective endocarditis. A multidisciplinary committee of experts drafted this document to assist physicians in the evolving care of patients with infective endocarditis in the new millennium. This extensive document is accompanied by an executive summary that covers the key points of the diagnosis, antimicrobial therapy, and management of infective endocarditis. For the first time, an evidence-based scoring system that is used by the American College of Cardiology and the American Heart Association was applied to treatment recommendations. Tables also have been included that provide input on the use of echocardiography during diagnosis and treatment of infective endocarditis, evaluation and treatment of culture-negative endocarditis, and short-term and long-term management of patients during and after completion of antimicrobial treatment. To assist physicians who care for children, pediatric dosing was added to each treatment regimen. Conclusions-The recommendations outlined in this update should assist physicians in all aspects of patient care in the diagnosis, medical and surgical treatment, and follow-up of infective endocarditis, as well as management of associated complications. Clinical variability and complexity in infective endocarditis, however, dictate that these guidelines be used to support and not supplant physician-directed decisions in individual patient management. (Circulation. 2005; 111:e394-e433.)

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Section: Non-hacek Gram-negative Bacillimentioning

confidence: 99%

Infective Endocarditis

Baddour¹,

Wilson²,

Bayer³

et al. 2005

Circulation

1,277

436

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“…They were kept in individual cages and allowed free access to food and water throughout the experiment. A polyethylene catheter was positioned in the left ventricle of each rabbit, with the tip passing through the aortic valve, as previously described (1,21). The catheter was left in place throughout the study.…”

Section: Methodsmentioning

confidence: 99%

Comparative efficacies of ciprofloxacin and pefloxacin alone or in combination with fosfomycin in experimental endocarditis induced by multidrug-susceptible and -resistant Pseudomonas aeruginosa

Xiong

Potel

Caillon

et al. 1995

Antimicrob Agents Chemother

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The in vivo efficacy of ciprofloxacin or pefloxacin alone or in combination with fosfomycin was evaluated in experimental aortic valve endocarditis induced in 133 rabbits by a multidrug-susceptible or multidrugresistant strain of Pseudomonas aeruginosa. Therapy was initiated early (12 h after infection), when bacterial counts in aortic valve vegetations were relatively low, or late (48 h after infection), when vegetations contained a larger inoculum. Antibiotics were administered as a continuous 24-h intravenous infusion. Mean steady-state levels of ciprofloxacin (64 mg/kg), pefloxacin (64 mg/kg), and fosfomycin (300 mg/kg) in serum were 2.5, 4.2, and 63.9 mg/liter, respectively. For the multidrug-susceptible strain, all regimens except pefloxacin alone significantly reduced the number of CFU per gram of vegetation versus controls, whether treatment was performed early or late. For the multidrug-resistant strain, none of the regimens showed differences from untreated controls, except ciprofloxacin-fosfomycin, which significantly reduced bacterial counts in vegetations compared with controls when therapy was begun early (4.1 ؎ 1.1 log 10 CFU/g of vegetation; P < 0.001 versus the control). These data suggest that combination of fosfomycin with ciprofloxacin or pefloxacin is more effective than ciprofloxacin or pefloxacin alone for the therapy of severe infections caused by multidrugsusceptible P. aeruginosa.Severe infections caused by Pseudomonas aeruginosa are a major problem in hospitalized patients who often fail to respond to medical therapy alone (2, 23). Fluoroquinolones are frequently used in the treatment of severe gram-negative infectious diseases, and ciprofloxacin and pefloxacin have proved effective against certain P. aeruginosa infections (10). However, clinical failures have occurred because of the development of resistance during therapy (22, 23) and there has also been a worldwide emergence of P. aeruginosa strains resistant to multiple older antimicrobial agents. These events indicate a need for experimental animal studies with newer antipseudomonal regimens. Antimicrobial combinations have been proposed as a means of increasing bactericidal activity in vivo, and some data suggest a possible synergy of fluoroquinolones with other antimicrobial agents (5,14,20). Moreover, fosfomycin, a drug with remarkable activity against P. aeruginosa, has shown a synergistic bactericidal effect in vitro against multidrug-resistant P. aeruginosa when combined with ciprofloxacin (12,20).The present study was designed to evaluate the efficacy of ciprofloxacin or pefloxacin alone versus association with fosfomycin. Experiments were conducted with a rabbit model of aortic valve endocarditis induced by a multidrug-susceptible or multidrug-resistant strain of P. aeruginosa. MATERIALS AND METHODSMicroorganisms. Two clinical strains of P. aeruginosa isolated from the blood of burn unit patients with septicemia were found to be susceptible (PA1) or resistant (PA2) to multiple antibiotics. Both proved resistant to rabbit s...

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“…Moreover, early bactericidal activity in an antibiotic regimen is potentially important for the treatment of life-threatening infections. In a previous study (13), we defined the critical concentration of aminoglycosides in serum in an experimental model of Serratia marcescens endocarditis in rabbits. This in vivo parameter was defined by the lowest steady-state concentration in serum that was able to achieve a 2-log-unit reduction in CFU in endocarditis vegetations versus those in controls 24 h after the beginning of a continuous intravenous (i.v.)…”

mentioning

confidence: 99%

“…Left ventricular endocarditis was induced as described previously (11,13). Twenty-four hours after the insertion of a catheter through the left carotid artery, the aseptic vegetations were colonized by injecting a single i.v.…”

mentioning

confidence: 99%

In vivo bactericidal activities of ciprofloxacin and pefloxacin in an experimental model of Serratia marcescens endocarditis

Juvin

Potel

Caillon

et al. 1994

Antimicrob Agents Chemother

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The critical concentrations of pefloxacin and ciprofloxacin in serum, corresponding to the lowest concentration in serum able to achieve a 2-log-unit reduction in the CFU in vegetations after a 24-h exposure at a steady-state concentration obtained by a continuous intravenous infusion, were determined in an experimental model of Serratia marcescens endocarditis in rabbits. In vitro data showed that the MICs of ciprofloxacin and pefloxacin were 0.06 and 0.25 mg/liter, respectively. The killing curves indicated a maximum killing rate at a concentration four times that of the MICs. In vivo, the critical concentrations of pefloxacin and ciprofloxacin in serum were 0.4 and 0.24 mg/liter, respectively, corresponding to a concentration of four times the MICs.The fluoroquinolones are often used for the treatment of severe gram-negative infectious diseases. Although in vitro studies have suggested that their bactericidal activities are concentration dependent (2, 15), many in vivo factors (protein binding, serum half-life, local activity conditions such as pH, anaerobiosis, etc.) may also be involved (10). Moreover, early bactericidal activity in an antibiotic regimen is potentially important for the treatment of life-threatening infections. In a previous study (13), we defined the critical concentration of aminoglycosides in serum in an experimental model of Serratia marcescens endocarditis in rabbits. This in vivo parameter was defined by the lowest steady-state concentration in serum that was able to achieve a 2-log-unit reduction in CFU in endocarditis vegetations versus those in controls 24 h after the beginning of a continuous intravenous (i.v.) infusion. The critical concentration in serum (CCS), which defines the intrinsic activity of each antibiotic in vivo, is more relevant than the in vitro MIC for studying the in vivo concentration-activity relationship. The purpose of the present study was to investigate the CCSs of two fluoroquinolones in the same model of S. marcescens endocarditis.S. marcescens HN229 was used to induce experimental endocarditis. It was isolated from the urine of a hospitalized patient. This strain was resistant to rabbit serum. The two fluoroquinolones used were pefloxacin (Roger-Bellon, Paris, France) and ciprofloxacin (Bayer, Paris, France). The MIC of each antibiotic was determined by a Mueller-Hinton broth dilution technique (supplemented with Ca2' and Mg2+) (8), which was defined as the lowest concentration that produced no visible growth after 18 h of incubation in a 96-well microplate. The MBC corresponded to the lowest concentration that was able to achieve 0.1% surviving bacteria (8). A quinolone inhibitor (magnesium sulfate) was used to avoid a carryover phenomenon (6). By using the dynamic checkerboard method (4, 5), time-kill curves were drawn for each antibiotic at 11 concentrations (from 0.03 to 32 and from 0.015 to 16 mg/liter for pefloxacin and ciprofloxacin, respectively) in Mueller- surviving bacteria were counted after 0, 1.5, 3, 6, and 24 h of incubation by a semiautom...

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Identification of factors affecting in vivo aminoglycoside activity in an experimental model of gram-negative endocarditis

Cited by 20 publications

References 23 publications

Infective Endocarditis

Infective Endocarditis

Comparative efficacies of ciprofloxacin and pefloxacin alone or in combination with fosfomycin in experimental endocarditis induced by multidrug-susceptible and -resistant Pseudomonas aeruginosa

In vivo bactericidal activities of ciprofloxacin and pefloxacin in an experimental model of Serratia marcescens endocarditis

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