Penetration of moxifloxacin into bone in patients undergoing total knee arthroplasty

Malincarne, Lisa; Ghebregzabher, Michele; Moretti, Michael; Egidi, Ada Maristella; Canovari, Benedetta; Tavolieri, Gabriele; Francisci, Daniela; Cerulli, Giuliano Giorgio; Baldelli, Franco

doi:10.1093/jac/dkl091

Cited by 49 publications

(32 citation statements)

References 30 publications

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“…The maintenance dose in treating bone infections should be selected based on the AUC in bone. Average bone/ plasma concentration ratios for moxifloxacin in bone ranged from 0.3 to 0.54 between 1 h and 5 h after the end of infusion in various patient groups (30,34,35).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

“…Good penetration into bone has been reported for several quinolones. The average bone/serum concentration ratio in humans at approximately 2 to 5 h postdosing was 0.33 to 0.54 for moxifloxacin (30,34,35).Resistance to the older quinolones has been emerging, and they do not show sufficient microbiological efficacy against S. aureus and coagulase-negative staphylococci and streptococci (28). Moxifloxacin has improved activity against gram-positive and anaerobic pathogens frequently encountered as causative agents in osteomyelitis (28), such as staphylococci, enterobacteriaceae, streptococci, and Haemophilus influenzae (19).…”

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confidence: 99%

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Penetration of Moxifloxacin into Bone Evaluated by Monte Carlo Simulation

Landersdorfer

Kinzig

Hennig

et al. 2009

Antimicrob Agents Chemother

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Moxifloxacin is a fluoroquinolone with a broad spectrum of activity and good penetration into many tissues, including bone. Penetration of moxifloxacin into bone has not yet been studied using compartmental modeling techniques. Therefore, we determined the rate and extent of bone penetration by moxifloxacin and evaluated its pharmacodynamic profile in bone via Monte Carlo simulation. Twenty-four patients (10 males, 14 females) undergoing total hip replacement received 400 mg moxifloxacin orally 2 to 7 h prior to surgery. Blood and bone specimens were collected. Bone samples were pulverized under liquid nitrogen by a cryogenic mill, including an internal standard. Drug concentrations were analyzed by high-performance liquid chromatography. We used ADAPT II (results reported), NONMEM, and WinBUGS for pharmacokinetic analysis. Quinolones are established in the treatment of osteomyelitis. Most clinical experience has been gained with ciprofloxacin and ofloxacin (28). Oral administration of quinolones was efficacious in surgical prophylaxis, even after a single dose (6, 39), and also facilitates prolonged therapy. In in vitro studies, Staphylococcus aureus penetrates and survives in bone cells, i.e., osteoblasts (25); therefore, quinolones, which penetrate intracellularly, might be of advantage.Moxifloxacin achieves high concentrations in many tissues. Good penetration into bone has been reported for several quinolones. The average bone/serum concentration ratio in humans at approximately 2 to 5 h postdosing was 0.33 to 0.54 for moxifloxacin (30,34,35).Resistance to the older quinolones has been emerging, and they do not show sufficient microbiological efficacy against S. aureus and coagulase-negative staphylococci and streptococci (28). Moxifloxacin has improved activity against gram-positive and anaerobic pathogens frequently encountered as causative agents in osteomyelitis (28), such as staphylococci, enterobacteriaceae, streptococci, and Haemophilus influenzae (19).Moxifloxacin has lower MICs than do levofloxacin, ciprofloxacin, ofloxacin, and norfloxacin for S. aureus (51), which is the most common pathogen of osteomyelitis. The main causative bacteria for osteomyelitis are S. aureus (methicillin susceptible or resistant), coagulase-negative staphylococci, propionibacteria, streptococci, and Pseudomonas aeruginosa (27). P. aeruginosa can cause osteomyelitis due to nosocomial infections or chronic unresolved middle ear infections in children.Studying the time course and extent of bone penetration before investigating the agent in a clinical trial is important (17,51). Bone penetration studies most often report the ratio of concentrations in bone and serum. However, the ratio of tissue concentrations to serum concentrations of a drug changes with time, a phenomenon known as system hysteresis, and therefore, the concentration ratio depends on the sampling time. Like in the present study, bone penetration of antimicrobials is most often studied in patients undergoing joint replacement, where only one bone sample can...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Penetration of Moxifloxacin into Bone Evaluated by Monte Carlo Simulation

Landersdorfer

Kinzig

Hennig

et al. 2009

Antimicrob Agents Chemother

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“…26 Moxifloxacin shows good bioavailability and penetration into both cortical and cancellous bone. 39 Moxifloxacin also diffuses well in inflammatory fluids and has a similar pharmacokinetic profile to that in human serum after a single oral dose. 40,41 Teicoplanin has a similar antibacterial spectrum similar to that of vancomycin, but a longer half-life and a lower risk of serious side effects.…”

Section: Discussionmentioning

confidence: 97%

“…30 However, doubledose oral administration of moxifloxacin produces mean plasma and bone concentrations of >2.5 mg/L, which were higher than the MIC 90 values for moxifloxacin in MSSA and MRSA models. 39 As both oral and intravenous moxifloxacin administration produce similar tissue concentrations, osteomyelitis therapy may begin with oral moxifloxacin or be converted to oral therapy after a period of intravenous application. In this study, moxifloxacin was injected intraperitoneally to facilitate simultaneous drug administration in equal doses to all animals.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of moxifloxacin compared to teicoplanin in the treatment of implant‐related chronic osteomyelitis in rats

Özturan

Yücel

Koçoğlu

et al. 2010

Journal Orthopaedic Research

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Treatment of implant-related chronic osteomyelitis is often difficult and usually consists of implant removal, extensive surgical debridement, and prolonged antibiotic use. This study was performed to assess the efficacy of moxifloxacin compared to a glycopeptide, teicoplanin in chronic implant-related methicillin-sensitive Staphylococcus aureus (MSSA) osteomyelitis. The left femoral medullar cavities of 60 Wistar male rats were contaminated with 100 l of 10 8 cfu/ml methicillin-sensitive S. aureus (ATCC 29213) and Kirschner wires were placed into the medulla of the femur. After 6 weeks, rats were randomly divided into five groups. In two groups, the Kirschner wires were removed. Experimental groups were as follows: group 1: contaminated, Kirschner wire inside, received teicoplanin; group 2: contaminated, Kirschner wire removed, received teicoplanin; group 3: contaminated, Kirschner wire inside, received moxifloxacin; group 4: contaminated, Kirschner wire removed, received moxifloxacin; group 5: contaminated, Kirschner wire inside, no antibiotics (control group). Groups 1 and 2 received teicoplanin (20 mg/kg once daily), whereas groups 3 and 4 received moxifloxacin (10 mg/kg twice daily) intraperitoneally for 28 days. At the end of the treatment, animals were sacrificed by inhalation anesthesia with ether and femora were retrieved and bacterial counts (cfu/g) were determined. Bacterial counts in all study groups were significantly reduced relative to the control. The decrease of bacterial counts was more prominent in group 4 compared to group 1 (p = 0.001) and group 2 (p = 0.003). Moxifloxacin therapy is an effective alternative to teicoplanin for chronic implant-related MSSA osteomyelitis.

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Pharmacokinetics and Pharmacodynamics of Antibiotics in Bone

Landersdorfer

Bulitta

Sörgel

2015

Bone and Joint Infections

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Chronic osteomyelitis requires prolonged antibiotic treatment, has a high recurrence rate, and can cause irreversible damage. Also, the number of orthopedic device-related infections continues to increase [1]. Therefore, adequate antibiotic treatment and surgical prophylaxis are critical. Therapeutic success is primarily determined by the antimicrobial activity against the infecting pathogen and the rate and extent of antibiotic penetration into bone. Adequate bone penetration has to be ensured as antibiotics need to reach effective concentrations at the infection site to kill bacterial pathogens. Therefore studying the time course and extent of bone penetration before launching a clinical effectiveness trial is important. The aim of this chapter is to review the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics in bone and present methods that support optimized evidence-based selection of antibiotic dosage regimens.

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Penetration of moxifloxacin into bone in patients undergoing total knee arthroplasty

Abstract: These data show a good penetration of moxifloxacin into both cancellous and cortical bone, with concentrations, after double dosing, exceeding the MIC90 for most pathogens involved in osteomyelitis and the clinic susceptibility breakpoint for Mycobacterium tuberculosis.

Cited by 49 publications

References 30 publications

Penetration of Moxifloxacin into Bone Evaluated by Monte Carlo Simulation

Penetration of Moxifloxacin into Bone Evaluated by Monte Carlo Simulation

Efficacy of moxifloxacin compared to teicoplanin in the treatment of implant‐related chronic osteomyelitis in rats

Pharmacokinetics and Pharmacodynamics of Antibiotics in Bone

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