Staphylococcal osteomyelitis—a comparison of co-amoxiclav with clindamycin and flucloxacillin in an experimental rat model

Gisby, J; Beale, A S; Bryant, Joanna; Toseland, C. D. N.

doi:10.1093/jac/34.5.755

Cited by 15 publications

(3 citation statements)

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“…Although its efficacy has been established in several experimental models [9,10], only a few series on the clindamycin treatment of human bone and joint infections have been reported [11][12][13]. The current recommendation for the dosage of oral clindamycin is 150-300 mg every 6 h for moderately severe infection and 300-450 mg every 6 h for severe infection [14].…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis

Bouazza

Pestre

Jullien

et al. 2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Clindamycin pharmacokinetics have been studied in adult patients. Rifampicin co-administration could decrease clindamycin exposure. WHAT THIS STUDY ADDS• This clindamycin population analysis in patients with osteomyelitis provides useful insight into the fate of this drug and shows that clindamycin clearance increases with body weight. Moreover, this study shows a potential effect of combined rifampicin on clindamycin clearance and addresses sub-therapeutic clindamycin concentrations in heavier patients. AIMSThis study was performed to describe clindamycin, administered either orally or intravenously, concentration-time courses to patients with osteomyelitis, to study the effects of different covariates on clindamycin pharmacokinetics and to simulate an optimized administration scheme. METHODSClindamycin concentrations were measured in 50 patients. A total of 122 plasma concentrations were available (58 from oral administration and 64 from i.v. infusion). A population pharmacokinetic model was developed with MONOLIX 4 software. RESULTSA one compartment model adequately described the data. Clindamycin clearance increased significantly with body weight (BW). The typical population estimates (interindividual variability) for clearance, volume of distribution and absorption rate constant were 16.2 l h -1 (0.39), 70.2 l and 0.92 h -1, respectively. The bioavailability of the oral form was estimated to be 87.6%. According to BW, theoretical doses needed to reach a Cmin of 2 mg l -1 were then calculated. CONCLUSIONSThe current recommendation of 600 mg three times daily seems to be effective up to 75 kg but the dose should be raised to 900 mg three times daily thereafter. These assumptions should be prospectively confirmed.

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Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis

Bouazza

Pestre

Jullien

et al. 2012

Brit J Clinical Pharma

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“…Clindamycin (7-chloro-7-deoxy-lincomycin) is a valuable option, because this lincosamide antibiotic is active against staphylococci, streptococci, and anaerobic bacteria (25); has high levels of joint and bone penetration (7,9,11,21,22,23,27); inhibits biofilm formation and bacterial adherence (6,18,19); and is well tolerated (11,12). Its efficacy has been established in several experimental models (13,16), but only a few series on the clindamycin treatment of human bone and joint infections have been reported (10)(11)(12).…”

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confidence: 99%

Continuous Clindamycin Infusion, an Innovative Approach to Treating Bone and Joint Infections

Zeller

Dzeing-Ella

Kitzis

et al. 2010

Antimicrob Agents Chemother

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The feasibility, safety, and efficacy of prolonged, continuous, intravenous clindamycin therapy were retrospectively evaluated for 70 patients treated for bone and joint infections, 40% of whom were treated as outpatients. The median treatment duration was 40 days, the median daily clindamycin dose was 2,400 mg, and three moderate-grade adverse events occurred. The median serum clindamycin concentrations on days 3 to 14 and days 8 to 28 were 5 and 6.2 mg/liter, respectively; the median concentration was significantly lower (P < 0.02) in patients treated with rifampin (5.3 mg/liter) than in those not treated with rifampin (8.9 mg/liter). Among 53 patients with a median follow-up of 30 months (range, 24 to 53 months), 49 (92%) were considered cured (1 patient had a relapse, and 3 patients had reinfections).The optimization of antibiotic regimens remains a major issue in the management of bone and joint infections, because no consensus guidelines are currently available (15,26). Clindamycin (7-chloro-7-deoxy-lincomycin) is a valuable option, because this lincosamide antibiotic is active against staphylococci, streptococci, and anaerobic bacteria (25); has high levels of joint and bone penetration (7,9,11,21,22,23,27); inhibits biofilm formation and bacterial adherence (6,18,19); and is well tolerated (11,12). Its efficacy has been established in several experimental models (13, 16), but only a few series on the clindamycin treatment of human bone and joint infections have been reported (10-12).In our Referral Center for the Treatment of Bone and Joint Infections, clindamycin is a drug of choice for the treatment of susceptible staphylococcal, streptococcal, and gram-positive anaerobic bacterial infections. To optimize the efficacy of the drug (14), we administer clindamycin via continuous intravenous infusion, because its antibacterial activity is time dependent (1, 5).The aim of this study was to evaluate retrospectively the feasibility, tolerability, and efficacy of prolonged administration of continuous intravenous clindamycin in our cohort of patients and to determine the serum clindamycin concentrations. Because serum clindamycin concentrations were frequently low in patients also receiving rifampin, we compared the serum concentrations of patients receiving combined therapy with and without rifampin. MATERIALS AND METHODSPatients. This retrospective cohort study included all the patients treated in our center for a bone and/or joint infection with continuous intravenous clindamycin for Ն1 week and for whom at least one clindamycin concentration determination was performed. All the patients gave written informed consent before inclusion.All the pathogens were clindamycin susceptible, as determined by the standard disk diffusion method of the Société Française de Microbiologie (MIC Ͻ 2 mg/liter), and none of them had inducible resistance to clindamycin. All the Staphylococcus strains were erythromycin susceptible.Drug administration. Clindamycin, administered intravenously through a central venous catheter, was...

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“…Successful treatment of infections with amoxicillin-clavulanic acid after molar extraction (22), peri-implantitis (52), osteomyelitis due to diabetic foot infections (40), prophylaxis of infections after orthognathic surgery (6), and staphylococcal osteomyelitis in a rat model (23) has been reported. The combination was recommended for the treatment of osteomyelitis caused by mixed anaerobic and aerobic pathogens (39).…”

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confidence: 99%

Bone Penetration of Amoxicillin and Clavulanic Acid Evaluated by Population Pharmacokinetics and Monte Carlo Simulation

Landersdorfer

Kinzig

Bulitta

et al. 2009

Antimicrob Agents Chemother

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Amoxicillin (amoxicilline)-clavulanic acid has promising activity against pathogens that cause bone infections. We present the first evaluation of the bone penetration of a beta-lactam by population pharmacokinetics and pharmacodynamic profiling via Monte Carlo simulations. Twenty uninfected patients undergoing total hip replacement received a single intravenous infusion of 2,000 mg/200 mg amoxicillin-clavulanic acid before surgery. Blood and bone specimens were collected. Bone samples were pulverized under liquid nitrogen with a cryogenic mill, including an internal standard. The drug concentrations in serum and total bone were analyzed by liquid chromatography-tandem mass spectrometry. We used NONMEM and S-ADAPT for population pharmacokinetic analysis and a target time of the non-protein-bound drug concentration above the MIC for >50% of the dosing interval for near-maximal bactericidal activity in serum. The median of the ratio of the area under the curve (AUC) for bone/AUC for serum was 20% (10th to 90th percentile for betweensubject variability [variability], 16 to 25%) in cortical bone and 18% (variability, 11 to 29%) in cancellous bone for amoxicillin and 15% (variability, 11 to 21%) in cortical bone and 10% (variability, 5.1 to 21%) in cancellous bone for clavulanic acid. Analysis in S-ADAPT yielded similar results. The equilibration half-lives between serum and bone were 12 min for amoxicillin and 14 min for clavulanic acid. For a 30-min infusion of 2,000 mg/200 mg amoxicillin-clavulanic acid every 4 h, amoxicillin achieved robust (>90%) probabilities of target attainment (PTAs) for MICs of <12 mg/liter in serum and 2 to 3 mg/liter in bone and population PTAs above 95% against methicillin-susceptible Staphylococcus aureus in bone and serum. The AUC of amoxicillin-clavulanic acid was 5 to 10 times lower in bone than in serum, and amoxicillin-clavulanic acid achieved a rapid equilibrium and favorable population PTAs against pathogens commonly encountered in bone infections.Osteomyelitis is difficult to diagnose and treat and may cause irreversible damage. Antibiotic treatment over weeks to months is required, often in addition to surgical debridement. To reduce the incidence of infections after orthopedic surgery, perioperative prophylaxis is standard practice. Each year more than a million hip replacements are done worldwide. Prosthetic devices are particularly susceptible to infections, more than 50% of which are due to Staphylococcus aureus or coagulase-negative staphylococci, such as S. epidermidis (38). It is vitally important that adequate surgical prophylaxis be used and that sufficient concentrations of antibiotic with activity against frequently encountered pathogens in bone be achieved.Amoxicillin (amoxicilline) in combination with clavulanic acid is active against pathogens commonly found in prosthesisrelated bone infections (MICs at which 90% of bacteria are inhibited [MIC 90 s], 1 mg/liter for methicillin-susceptible S. aureus [MSSA] and 8 mg/liter for S. epidermidis [28]). Successful treat...

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Staphylococcal osteomyelitis—a comparison of co-amoxiclav with clindamycin and flucloxacillin in an experimental rat model

Cited by 15 publications

References 0 publications

Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis

Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis

Continuous Clindamycin Infusion, an Innovative Approach to Treating Bone and Joint Infections

Bone Penetration of Amoxicillin and Clavulanic Acid Evaluated by Population Pharmacokinetics and Monte Carlo Simulation

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