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Neurogenic heterotopic ossifications (NHO) are heterotopic bones that develop in periarticular muscles after severe central nervous system (CNS) injuries. Several retrospective studies have shown that NHO prevalence is higher in patients who suffer concomitant infections. However, it is unclear whether these infections directly contribute to NHO development or reflect the immunodepression observed in patients with CNS injury. Using our mouse model of NHO induced by spinal cord injury (SCI) between vertebrae T 11 to T 13 , we demonstrate that lipopolysaccharides (LPS) from gram-negative bacteria exacerbate NHO development in a toll-like receptor-4 (TLR4)-dependent manner, signaling through the TIR-domain-containing adapter-inducing interferon-β (TRIF/TICAM1) adaptor rather than the myeloid differentiation primary response-88 (MYD88) adaptor. We find that T 11 to T 13 SCI did not significantly alter intestinal integrity nor cause intestinal bacteria translocation or endotoxemia, suggesting that NHO development is not driven by endotoxins from the gut in this model of SCI-induced NHO. Relevant to the human pathology, LPS increased expression of osteoblast markers in cultures of human fibro-adipogenic progenitors isolated from muscles surrounding NHO biopsies. In a case-control retrospective study in patients with traumatic brain injuries, infections with gram-negative Pseudomonas species were significantly associated with NHO development. Together these data suggest a functional association between gram-negative bacterial infections and NHO development and highlights infection management as a key consideration to avoid NHO development in patients. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Objective: To establish international recommendations for the management of spastic equinovarus foot deformity., Design: Delphi method., Setting: International study., Participants: A total of 24 international experts (N=24) in neuro-orthopedic deformities, from different specialties (Physical and Rehabilitation Medicine physicians, neurologists, geriatricians, orthopedic surgeons, neurosurgeons, plastic surgeons)., Interventions: Experts answered 3 rounds of questions related to important aspects of diagnosis, assessment, and treatment of spastic equinovarus foot deformity., Main Outcome Measures: A consensus was established when at least 80% of experts agreed on a statement RESULTS: A total of 52 items reached consensus. Experts recommend assessing effect of the deformity on functional activities before treatment. Before treatment, it is crucial to differentiate spastic muscle overactivity from soft tissue contractures, identify which muscles are involved in the deformity, and evaluate the activity of antagonist muscles. Motor nerve blocks, 2-dimensional video analysis, and radiologic examinations are often required to complement a clinical examination. The treatment of equinovarus foot depends on the correctability of the deformity and the patient's ability to stand or walk. The preoperative assessment should include an interdisciplinary consultation that must finalize a formal agreement between physicians and the patient, which will define personalized attainable goals before surgery., Conclusion: The establishment of guidelines on managing equinovarus foot will help physicians and surgeons, specialists, and nonspecialists to diagnoses and assess the deformity and direct patients to a network of experts to optimize patient functional recovery and improve their autonomy., (Copyright © 2022. Published by Elsevier Inc.)

Background: Optimal treatment of carbapenemase-producing Enterobacterales (CPE) bone infections is poorly defined. This study evaluated the efficacy of the novel beta-lactam-beta-lactamase inhibitor-ceftazidime-avibactam (CAZ-AVI)-with different antibiotic combinations in an experimental model of CPE osteomyelitis., Methods: KPC-99YC is a clinical strain of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae with intermediate susceptibility to meropenem (MIC 4 mg/L), gentamicin (MIC 0.25 mg/L), colistin (MIC 0.25 mg/L), fosfomycin (MIC 4 mg/L) and ceftazidime-avibactam (MIC 1 mg/L). Time-kill curves were performed at 4x MIC. Osteomyelitis was induced in rabbits by tibial injection of 2×10 8 CFU of KPC-99YC. Six groups started treatment 14 days later for 7 days: control, colistin, CAZ-AVI, CAZ-AVI plus gentamicin, CAZ-AVI plus colistin and CAZ-AVI plus fosfomycin. Antibiotic dosages were selected to simulate plasma concentrations obtained in humans. Treatment was evaluated according to bone cultures quantified in log 10 CFU., Results: In vitro, CAZ-AVI plus colistin or gentamicin were rapidly bactericidal in contrast with CAZ-AVI plus fosfomycin. In vivo, compared with controls, colistin alone (P = 0.045) and CAZ-AVI alone or in combination significantly lowered bone bacterial counts (P < 0.001). Bone sterilisation was achieved in 67% and 100% of animals with combinations of CAZ-AVI plus colistin or gentamicin (P = 0.001 and P < 0.001, respectively) whereas other treatments were no different from controls. CAZ-AVI plus gentamicin provided greater bone bacterial reduction than CAZ-AVI plus colistin (P = 0.033). No CAZ-AVI-resistant strains emerged in treated rabbits, regardless of combination., Conclusions: CAZ-AVI plus gentamicin was the best effective combination therapy. Combinations with CAZ-AVI appear to be a promising treatment of KPC-producing Klebsiella pneumoniae osteomyelitis., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

For breast cancer patients, surgery remains the cornerstone in treatment. Perioperative and postoperative period is associated with impaired immune function that can have profound implications for cancer patients in terms of tumor recurrence and metastases. The three main factors include surgery and related neuroendocrine stress response, anesthetic drugs, including opioid analgesics and postoperative pain. The most investigated immune cells are natural killer (NK) cells that are affected by both anesthesia and surgery. It has been demonstrated that ketamine, thiopental, volatile anesthetics, fentanyl and morphine, but not propofol, remifentanil or tramadol reduce the number of circulating NK cells and depress their toxicity. The level of NK cells' cytotoxicity is inversely proportional to the stage and spread of cancer. Regional anesthesia and its potential beneficial effects on the perioperative immune response and long-term outcome after surgery has been investigated as an alternative to general anesthesia in patients undergoing breast cancer surgery. In this paper, we present a review of literature aimed to assess the impact of regional anesthesia techniques on the immune response in patients undergoing breast cancer surgery and how it compares to general anesthesia.

Neuro-orthopedic surgery is an alternative to the conservative treatment of spastic equinovarus foot (SEF) in adults. The objective of the present narrative review was to summarize current practice with regard to patient assessment, the choice of treatment, the various neuro-orthopedic procedures, and the latter's outcomes. We searched literature databases (MEDLINE, EMBASE, Cochrane) for original articles or opinion papers on surgical treatment of spastic equinovarus foot in adults. Neuro-orthopedic approaches require a careful analysis of the patient's and/or his/her caregiver needs and thus relevant treatment goals. Surgical planning requires detailed knowledge of impairments involved in the spastic equinovarus foot deformity based on a careful clinical examination and additional information from diagnostic nerve blocks and/or a quantitative gait analysis. Procedures mainly target nerves (neurotomy) and tendons (lengthening, transfer, tenotomy). These procedures reduce impairments (spasticity, range of motion, and foot position), improve gait and walking function, but their impact on participation and personalized treatment goals remains to be demonstrated. Neuro-orthopedic surgery is an effective treatment option for spastic equinovarus foot in adults. However, practice is still very heterogeneous and there is no consensus on the medical strategies to be applied before, during and after surgery (particularly the type of anesthesia, the need for immobilization, rehabilitation procedures)., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

The clinical assessment of a hypertonic upper limb in central neurological diseases should be analytical, systematic (shoulder, elbow, extrinsic and intrinsic hand) and focused on the patient or caregiver's wishes and on the expected objectives (esthetic, hygienic, functional). Nerve blocks can help to separate mixed contractures, show the existence of antagonist muscles or find a starter muscle in dystonia patterns. The etiology (especially the evolving nature of the disease), general health condition (especially in older adults), associated deficits (cerebellar, sensory and cognitive; hemineglect) are considered together to arrive at a contract with patients and/or caregivers., (Copyright © 2021. Published by Elsevier Masson SAS.)

Neuro-orthopedic complications of the upper limb affect all of its joints and lead to a multitude of clinical pictures. The clinical assessment, which should be multidisciplinary, will have to answer basic questions to define the goal(s) and the appropriate surgical strategy. What is the patient's and family's complaint? What is the possible utility of the deformities? What is the type of deformity? Is it reducible or not? What is the contribution of the upper limb deformities versus that of any associated injuries to the discomfort? Several difficulties exist in the clinical assessment: evaluation of the antagonists especially the wrist extensor muscles; the intrinsic deformity component, which can be masked by the extrinsic component when retracted, the muscles responsible for a wrist flexion contracture and the complex shoulder deformities. Many patients have multiple deformities, which creates a problem for the hierarchy of corrections depending on the objectives. The answer to these questions helps to define a clear objective that will be formalized in a contract with the patient and subsequently to define the surgical strategy. Surgery is based on a simple principle: relax the muscles on the side of the deformity, either by selective neurotomy if there is a simple hypertonia, or by a tendon procedure if the muscle is retracted; compensate for the antagonists if they are deficient, and potentially stabilize the joint. Conservative procedures are preferred to preserve the possibility of functional recovery in the future. The wide range of medical and surgical solutions allows the patient's care to be personalized. In the upper limb, the results are better for hygienic, positioning, and analgesic objectives. They remain more difficult to obtain for functional objectives, due to the biomechanical complexity of gripping., (Copyright © 2021 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Neurogenic heterotopic ossifications (NHOs) are periarticular ectopic ossifications that frequently develop after a central nervous system injury, most often a traumatic one. They limit range of motion and cause pain, interfering with limb positioning and function, whether active or passive. Highly described in the lower limbs, NHOs can also develop in the upper limb, with specific characteristics depending on their location. This article provides a summary of the diagnostic and therapeutic management of NHOs in the upper limb, based on the current literature., (Copyright © 2021 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Background: Neurogenic heterotopic ossification (NHO) is a frequent complication, often involving the hip. The functional impact may require surgical management and pre-surgical imaging assessment is necessary, usually by computed tomography (CT). We aimed to compare the performances of magnetic resonance imaging (MRI) and CT for bone assessment on pre-surgical imaging of the heterotopic ossifications and their features in NHO of the hip., Methods: This single-center prospective preliminary study included all patients who underwent surgery for NHO with joint limitation from July 2019 to March 2020. All patients had a CT after biphasic iodinated solution injection and an MRI including T1-weighted, STIR and ZTE sequences. Standardized reports were completed for both exams for each patient, evaluating location, implantation and fragmentation of NHO, relation to the joint capsule and bone mineralization, then were compared., Results: Seven patients from 32 to 70 years old (mean = 50.2 ± 17.2 years) were evaluated. NHO were bilateral in 2 patients, for a total of nine hips: six right hips and three left hips. Observed concordance rates between MRI and CT were, respectively, 94.4% for location, 100% for circumferential extension, 87.3% for implantation 88.9% for fragmentation, 77.8% for relation to the joint capsule and 66.7% for bone mineralization. It was 100% for femoral neck fracture and osteonecrosis of the femoral head., Conclusion: This preliminary study suggests that pre-surgical MRI imaging should be considered as effective as CT for bone assessment of NHO and their features., Trial Registration: ClinicalTrials.gov, NCT03832556. Registered February 6, 2019, https://clinicaltrials.gov/ct2/show/NCT03832556 ., (© 2021. The Author(s).)

Guidelines for the management of carbapenemase-producing Enterobacterales (CPE) infections recommend a combination of two active agents, including meropenem if the minimum inhibitory concentration (MIC) is ≤8 mg/L. The therapeutic equivalence of meropenem generics has been challenged. We compared the bactericidal activity of meropenem innovator (AstraZeneca) and four generic products (Actavis, Kabi, Mylan and Panpharma), both in vitro and in vivo, in association with colistin. In vitro time-kill studies were performed at 4 × MIC. An experimental model of KPC-producing Klebsiella pneumoniae osteomyelitis was induced in rabbits by tibial injection of a sclerosing agent followed by 2 × 10 8 CFU of K. pneumoniae KPC-99YC (meropenem MIC = 4 mg/L; colistin MIC = 1 mg/L). At 14 days after inoculation, treatment for 7 days started in seven groups of ≥10 rabbits, including a control group, a colistin group, and one group for each meropenem product (i.e. the innovator and four generics), in combination with colistin. In vitro, meropenem + colistin was bactericidal with no viable bacteria after 6 h, and this effect was similar with all meropenem products. In the osteomyelitis model, there was no significant difference between meropenem generics and the innovator when combined with colistin. Colistin-resistant strains were detected after treatment with colistin + meropenem innovator (n = 3) and generics (n = 3). The efficacy of four meropenem generics did not differ from the innovator in vitro and in an experimental rabbit model of KPC-producing K. pneumoniae osteomyelitis in terms of bactericidal activity and the emergence of resistance., (Copyright © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Carbapenemase-producing Enterobacteriaceae (CPE) are emerging multidrug-resistant bacteria responsible for invasive infections, including prosthetic joint infections (PJIs). Local administration of colistin may provide bactericidal concentrations in situ. This study evaluated the efficacy of a colistin-impregnated cement spacer, alone and in combination with systemic antibiotics, in a rabbit model of CPE-PJI. Elution of 3 MIU of colistimethate sodium (CMS) in 40 g of poly(methyl methacrylate) cement was studied in vitro. In vivo, 5 × 10 8 CFU of KPC-producing Klebsiella pneumoniae (colistin and meropenem MICs of 1 mg/L and 4 mg/L, respectively) were injected close to a prosthetic knee. Surgical debridement and prosthesis removal were performed 7 days later, and rabbits were assigned to six treatment groups (11-13 rabbits each): drug-free spacer; colistin-loaded spacer; colistin intramuscular (i.m.); colistin i.m. + colistin spacer; colistin i.m. + meropenem subcutaneous (s.c.); and colistin i.m. + meropenem s.c. + colistin spacer. Systemic treatment was administered at doses targeting pharmacokinetics in humans, and rabbits were euthanised 7 days later to evaluate bacterial counts in infected bones. In vitro, CMS elution was low (<0.1% at 24 h) but reached a local concentration of ≥20 mg/L (>20 × MIC). In vivo, combinations of local and systemic colistin, with or without meropenem, were the only regimens superior to the control group (P ≤ 0.05) in terms of viable bacterial counts and the proportion of rabbits with sterile bone, with no emergence of colistin-resistant strains. Colistin-loaded cement spacer in combination with systemic antibiotics were the most effective regimens in this CPE-PJI model., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Soft tissue surgery for upper extremity contractures can improve hygiene, pain, and appearance in adults with central nervous system lesions. The goal of such interventions is highly individual; thus, goal attainment scaling (GAS; a method of scoring the extent to which patient's individual goals are achieved [5 levels] in the course of intervention and using T score values) is pertinent to evaluate outcome. The objective of this study was to assess the effect of soft tissue surgery for upper extremity muscle contractures in patients with central nervous system lesions using GAS., Methods: Retrospective data from 70 interventions were included (63 patients; 23 women). The mean age was 51.3 ± 16.2 years (range, 24.2-87.0 years). The primary goal was to improve hygiene (n = 58), pain (n = 10), or appearance (n = 2). The etiologies were stroke (n = 35), traumatic brain injury (n = 16), cerebral anoxia (n = 4), neurodegenerative disease (n = 6), and cerebral palsy (n = 2). The GAS score was calculated before surgery and 3 months after surgery., Results: The T score (which took into account the weight of each goal) was 52.3 at 3 months (38.5 before surgery), corresponding to a "better than expected" outcome. The mean of the differences of the GAS score for each goal before and after surgery increased by 1.27 for hygiene, 1.06 for pain, and 1.00 for appearance., Conclusions: Soft tissue surgery can safely and effectively improve hygiene, pain, and appearance in adults with cerebral damage. The preoperative evaluation should be multidisciplinary. The GAS is a useful tool to assess the effectiveness of orthopedic surgery for these patients., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Neurogenic heterotopic ossification (NHO) is usually treated by surgical excision. Postoperative infection (POI) is a possible complication, whose epidemiology, causative organisms, and risk factors are poorly known. We therefore conducted a case-control study to (1) identify the risk factors for POI after surgical excision of NHO at the hip, (2) determine the frequency of POI, (3) and identify the causative organisms., Hypothesis: Risk factors for POI after NHO excision at the hip can be identified., Material and Methods: In this retrospective case-control study, the BANKHO database for patients with NHO at our centre was used to identify risk factors by comparing patients with and without POI after NHO excision at the hip. To this end, odds ratios (ORs) with their 95% confidence intervals (95%CIs) were computed for each main criterion. Postoperative follow-up was at least 6 months., Results: Between 1993 and 2013, 411 hip NHO excisions were performed. Among them, 42 (10%) were followed by POI. The American Society of Anesthesiologists (ASA) score was I in 2/42 (5%) patients with vs. 74/369 (20%) patients without POI, II in 30/42 (71%) patients with vs. 258/369 (70%) patients without POI, and III in 10/42 (24%) patients with vs. 37/369 (10%) patients without POI (P<0.01). Mean age was 31±11 years (range, 17-79years) in the group with POI and 39±14 years (range, 15-77years) in the group without POI (P<0.01). The NHO was related to spinal cord injury in 26/42 (62%) patients with POI compared to 92/369 (25%) patients without POI (P<0.01). ORs indicated a significant risk increase in patients with an ASA score of III (2.84; 95%CI, 1.28-6.31), age younger than 30 years (1.85; 95%CI, 1.03-3.32), and spinal cord injury as the cause of NHO (4.89; 95%CI, 2.67-8.98). The predominant organisms were staphylococci (skin flora) in the patients with spinal cord injury and bacteria commonly found in intensive care units in the other patients., Discussion: A higher ASA score, younger age, and spinal cord injury as the cause of NHO at the hip are risk factors for POI. The proportion of patients with POI after hip NHO excision was 10%, in accordance with previous reports. POI was more common among patients with spinal cord injury (22% vs. 5% in the other patients). Neither changes in prophylactic antibiotic therapy regimens nor the institution of a detailed skin preparation protocol affected the frequency of POI. Skin pH alterations may deserve to be investigated with the goal of diminishing the risk of POI, most notably in spinal cord injury patients., Level of Evidence: III, case-control study., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: In bone and joint infections (BJIs), bacterial toxins are major virulence factors: Panton-Valentine leukocidin (PVL) expression leads to severe local damage, including bone distortion and abscesses, while α-hemolysin (Hla) production is associated with severe sepsis-related mortality. Recently, other toxins, namely phenol-soluble modulins (PSMs) expressed by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300 (LAC WT) were shown to have ex vivo intracellular cytotoxic activity after S. aureus invasion of osteoblasts, but their in vivo contribution in a relatively PVL-sensitive osteomyelitis model remains poorly elucidated., Materials and Methods: We compared the outcomes of experimental rabbit osteomyelitises induced with pvl+hla+psms+ LAC WT and its isogenic Δpsm derivatives (LAC Δpsmα and LAC Δpsmαβhld) using an inoculum of 3 × 108 CFUs. Mortality, hematogenous spread (blood culture, spleen and kidney), lung and bone involvements were assessed in two groups (non-survivors of severe sepsis and survivors sacrificed on day (D) 14)., Results: Severe sepsis-related mortality tended to be lower for Δpsm derivatives (Kaplan-Meier curves, P = .06). Non-survivors' bone LAC-Δpsmα (6.9 log10 CFUs/g of bone, P = .04) or -Δpsmαβhld (6.86 log10 CFUs/g of bone, P = .014) densities were significantly higher than LAC WT (6.43 log10 CFUs/g of bone). Conversely, lung Δpsmαβhld CFUs were significantly lower than LAC WT (P = .04). LAC Δpsmα, Δpsmαβhld and WT induced similar bone damage in D14 survivors, with comparable bacterial densities (respectively: 5.89, 5.91, and 6.15 log10 CFUs/g of bone). Meanwhile, pulmonary histological scores of inflammation were significantly higher for LAC Δpsmα- and Δpsmαβhld-infected rabbits compared to LAC WT (P = .04 and .01, respectively) but with comparable lung bacterial densities., Conclusion: Our experimental results showed that deactivating PSM peptides significantly limited bacterial dissemination from bone during the early phase of infection, but did not affect local severity of USA300 rabbit osteomyelitis.

Unlabelled: Possibilities for bone reconstruction in osteonecrosis of the femoral head in sickle cell hemoglobinopathies before the end of growth have not been assessed. The aim of our study was to evaluate the morphological and functional results in 11 osteonecrosis of the femoral head because of homozygous sickle cell disease. Surgical treatment consisted of a triple acetabular osteotomy in seven cases, femoral varus osteotomy in two cases and a combination of both in two cases. The severity of the osteonecrosis was evaluated on radiographs and magnetic resonance imaging (MRI), pre- and postoperative, and function of the hip joint was assessed by Harris and Postel Merle d'Aubigné scores. The anesthetic part (pre- and postoperative) and eventual complications were collected and analyzed. The maximum follow-up was between 1 to 9.6 years. All patients were considered to be satisfactory at maximum follow-up. The severity of the initial damage was not associated with any morphological or functional outcome at maximum follow-up. All patients had an objective functional gain. We found no general complications. We proposed a decision tree for the patient's management of avascular necrosis of the femoral head in sickle cell hemoglobinopathies before bone maturity, and with an Arlet and Ficat's stage of 3 or 4. The results of this study confirmed the interest of conservative surgical treatment in children with homozygous sickle cell anemia in case of osteonecrosis of the femoral head., Level of Evidence: IV (cases series of our department).

Purpose: Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the determinants of plasma clindamycin trough concentration, C min, especially the effect of co-treatment with rifampicin, and the consequences on clinical outcome., Methods: An observational study was performed, involving patients hospitalized for a bone and joint infection who received clindamycin as part of their antibiotic treatment. Target C min was 1.7 mg/L, to reach the desired bone concentration/MIC >2, assuming a 30% diffusion into bone and MIC = 2.5 mg/L., Results: Sixty one patients (mean age: 56.8 years, 57.4% male) were included between 2007 and 2011. 72.1% underwent a surgery on a foreign material, and 91.1% were infected by at least a Gram-positive micro-organism. Median C min value was 1.39 mg/L, with 58% of the values below the threshold value of 1.7 mg/L. Median C min was significantly lower for patients taking rifampicin (0.46 vs 1.52 mg/L, p = 0.034). No patient with rifampicin co-administration reached the target concentration (maximal C min: 0.85 mg/L). After a median follow-up of 17 months (1.5-38 months), 4 patients relapsed, 2 died and 47 (88.7% of the patients with known outcome) were cured, independently of association with rifampicin., Conclusions: This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.

Ceftaroline (CPT), the active metabolite of the prodrug ceftaroline-fosamil (CPT-F), demonstrates in vitro bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and is effective in rabbit models of difficult-to-treat MRSA endocarditis and acute osteomyelitis. However, its in vivo efficacy in a prosthetic joint infection (PJI) model is unknown. Using a MRSA-infected knee PJI model in rabbits, the efficacies of CPT-F or vancomycin (VAN) alone and combined with rifampin (RIF) were compared. After each partial knee replacement with a silicone implant that fit into the tibial intramedullary canal was performed, 5 × 10(7) MRSA CFU (MICs of 0.38, 0.006, and 1 mg/liter for CPT, RIF, and VAN, respectively) was injected into the knee. Infected animals were randomly assigned to receive no treatment (controls) or CPT-F (60 mg/kg of body weight intramuscularly [i.m.]), VAN (60 mg/kg i.m.), CPT-F plus RIF (10 mg/kg i.m.), or VAN plus RIF starting 7 days postinoculation and lasting for 7 days. Surviving bacteria in crushed tibias were counted 3 days after ending treatment. Although the in vivo mean log10 CFU/g of CPT-treated (3.0 ± 0.9, n = 12) and VAN-treated (3.5 ± 1.1, n = 12) crushed bones was significantly lower than those of controls (5.6 ± 1.1, n = 14) (P < 0.001), neither treatment fully sterilized the bones (3/12 were sterile with each treatment). The mean log10 CFU/g values for the antibiotics in combination with RIF were 1.9 ± 0.5 (12/14 were sterile) for CPT-F and 1.9 ± 0.5 (12/14 were sterile) for VAN. In this MRSA PJI model, the efficacies of CPT-F and VAN did not differ; thus, CPT appears to be a promising antimicrobial agent for the treatment of MRSA PJIs., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)