Methicillin-resistant Staphylococcus Aureus Osteomyelitis Research Articles

Anti-glucosaminidase monoclonal antibodies as a passive immunization for methicillin-resistant Staphylococcus aureus (MRSA) orthopedic infections

Recently, methicillin-resistant Staphylococcus aureus (MRSA) has surpassed HIV as the most deadly pathogen in the United States, accounting for over 100,000 deaths per year. In orthopedics, MRSA osteomyelitis has become the greatest concern in patient care, despite the fact that improvements in surgical technique and aggressive antibiotic prophylaxis have decreased the infection rate for most procedures to less than 5%. This great concern is largely due to the very poor outcomes associated with MRSA osteomyelitis, which includes 30-50% failure rates for revision surgery. Thus, there is a need to develop additional therapeutic interventions such as passive immunization, particularly for immunocompromised patients and the elderly who are typically poor responders to active vaccines. Using a novel murine model of implant-associated osteomyelitis in which a stainless steel pin is coated with bioluminescent S. aureus and implanted transcortically through the tibial metaphysis, we discovered that mice protect themselves from this infection by mounting a specific IgG2b response against the peptidoglycan hydrolase, glucosaminidase (Gmd), an enzyme involved in cell wall digestion during binary fission. Since this subunit of S. aureus autolysin is essential for bacterial growth, and no genetic variation has been identified among clinical strains, we propose that monoclonal antibodies against this enzyme would have multiple mechanisms of action, including promotion of opsonophagocytosis and direct inhibition of enzyme function. Here we review the field of MRSA osteomyelitis and our research to date on the development of an anti-Gmd passive immunotherapy.

TMP-SMX Is Another Option for Treatment of Acute Osteomyelitis

Transitioning from intravenous (IV) to oral antibiotic therapy for acute hematogenous osteomyelitis hastens the return to normal activities in children. However, emergence of methicillin-resistant Staphylococcus aureus (MRSA) limits the choice of an oral agent. Clindamycin has a good track record for treatment of MRSA osteomyelitis, but its use …

Efficacy of the new cephalosporin ceftaroline in the treatment of experimental methicillin-resistant Staphylococcus aureus acute osteomyelitis

To evaluate the activity of a new cephalosporin, ceftaroline, in comparison with other antistaphylococcal drugs (linezolid and vancomycin) at projected human therapeutic doses against methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains. Using a rabbit experimental model of acute osteomyelitis, efficacy was assessed following 4 days of treatment by colony counts of infected bone tissues (joint fluid, femoral bone marrow and bone). Although vancomycin remains the standard treatment for MRSA osteomyelitis, it was ineffective against the MRSA strain and poorly active against GISA infections in this model. Ceftaroline and linezolid demonstrated significant activity in bone marrow and bone, and were significantly better than vancomycin treatment. However, ceftaroline was the only drug to exhibit significant activity against MRSA in infected joint fluid. The present study supports ceftaroline as a promising therapeutic option for the treatment of severe MRSA infections, including osteomyelitis.

Decal bone matrix as a local antibiotic delivery vehicle in a MRSA-infected bone model: An experimental study

Background:Polymethyl methacrylate (PMMA) antibiotic beads though have proved their utility as a local antibiotic delivery system, however, there are limitations. Decalcified bone matrix (DBM) as a vehicle of antibiotics can serve the purpose, provided a minimum inhibitory concentration is sustained. Healing of the defect and avoiding the second surgery is another advantage. We studied the DBM as the delivery vehicle for vancomycin in controlling the methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis as well as healing of the cavity simultaneously in an experimental study.Materials and Methods:An in vitro study was conducted to optimize vancomycin impregnation in the DBM. For the in vivo study, a unicortical defect was created in the metaphysis of the distal femur in 18 rabbits. After contaminating the defect with MRSA, rabbits were divided into three groups. Group I (eight limbs) received no graft. Defects in group II (11 limbs) were filled with plain DBM chips and in group III (14 limbs), cavities were implanted with vancomycin-impregnated decal bone chips. Rabbits were assessed by clinical, radiological, histological, gross examination and bacterial load assay. High Performance Liquid Chromatography HPLC analysis of vancomycin in group III was done to assess the concentration in DBM chips.Results:In group I, the infection persisted throughout the period of the study. Group II showed the fulminated infection at the grafted site with DBM chips sequestrating out. Vancomycin-impregnated decal chips in group III did not show any sign of infection and eventually incorporated. The bacterial load study showed a progressive load change and HPLC revealed an effective antibiotic concentration up to 3 weeks in both in vitro and in vivo.Conclusion:Decal bone chips were effective as the local antibiotic delivery vehicle in preventing the MRSA osteomyelitis model. It eluted vancomycin significantly and the graft uptake was also excellent. Allogeneic decal grafts eliminated the need for second surgery and acted as an excellent delivery vehicle for antibiotics.

Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections

Objective: Higher vancomycin concentrations are thought necessary for treatment of deep-seated methicillin-resistant Staphylococcus aureus (MRSA) infection, yet this may result in greater risk of nephrotoxicity. We evaluated the relationship of serum vancomycin trough concentration with clinical outcomes and nephrotoxicity for patients with deep-seated MRSA infection.Methods: A retrospective cohort study evaluated adults with MRSA pneumonia, endocarditis or osteomyelitis who received vancomycin for ≥ 5 days from June 2005 to June 2007. Patients were stratified by mean vancomycin trough level [low (< 15 mg/l), high (≥ 15 mg/l)]. Outcomes were clinical response, mortality, length of stay (LOS) and nephrotoxicity. Three definitions of nephrotoxicity were used: i) rise in serum creatinine (SCr) ≥ 0.5 mg/dl; ii) 50% increase in SCr; and iii) 25% decrease in estimated creatinine clearance.Results: Fifty-five patients experiencing MRSA pneumonia (n = 28), endocarditis (n = 9), osteomyelitis (n = 20) and multiple infections (n = 2) were stratified into low (n = 39) and high (n = 16) groups. High group patients were more likely to be septic (p = 0.01) and have a higher APACHE II score (p = 0.01). After adjustment for APACHE II score, clinical response rates among survivors did not differ significantly. Risk of death was not significantly different between the high (19%) and low (5%) group patients (p = 0.1). LOS did not differ significantly between groups (p = 0.7). Nephrotoxicity occurred in the low and high groups, respectively, for 10 and 31% (p = 0.04) with definition 1, 10 and 31% (p = 0.04) with definition 2, and 13 and 25% (p = 0.1) with definition 3. After adjustment for APACHE II score, odds of nephrotoxicity based on definitions 1 or 2 were increased among the high versus low groups (OR = 3.27, 95% CI: 0.7 – 15.25, p = 0.1), although not statistically significant.Conclusions: Clinical outcomes did not differ significantly between high and low trough groups for deep-seated MRSA infections. Nephrotoxicity was consistently higher in the high trough group, regardless of the definition used.

In Vitro and In Vivo Efficacies of Teicoplanin-Loaded Calcium Sulfate for Treatment of Chronic Methicillin-Resistant Staphylococcus aureus Osteomyelitis

The in vitro and in vivo therapeutic efficacies of teicoplanin-loaded calcium sulfate (TCS; 10% [wt] teicoplanin) were investigated in a rabbit model of chronic methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. The in vitro elution characteristics of teicoplanin from TCS pellets were realized by carrying out an evaluation of the release kinetics, recovery rate, and antibacterial activity of the released teicoplanin. Chronic osteomyelitis was induced by inoculating 10(7) CFU of a MRSA strain into the tibial cavity of rabbits. After 3 weeks, the animals were treated by debridement followed by implantation of TCS pellets in group 1, calcium sulfate (CS) pellets alone in group 2, and intravenous (i.v.) teicoplanin (6 mg/kg of body weight every 12 h for three doses and then every 24 h up to 4 weeks) in group 3. Animals in group 4 were left untreated. After 6 weeks, the efficacy of the osteomyelitis treatment was evaluated by hematological, radiological, microbiological, and histological examinations. In vitro elution studies showed sustained release of teicoplanin at a therapeutic level over a time period of 3 weeks. The released teicoplanin maintained its antibacterial activity. In vivo, the best therapeutic effect was observed in animals treated with TCS pellets, resulting in significantly lower radiological and histological scores, lower positive rates of MRSA culture and bacterial load, and excellent bone regeneration compared with those treated by CS alone or i.v. teicoplanin, without any local or systemic adverse effects. TCS pellets are an effective alternative to i.v. teicoplanin for the treatment of chronic MRSA osteomyelitis, particularly because teicoplanin is delivered locally while the TCS pellets simultaneously promote bone defect repair.

Methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis of the mandible

Methicillin-resistant Staphylococcus aureus (MRSA) is a type of Staphylococcus that is resistant to certain antibiotics, such as methicillin, oxacillin, penicillin, and amoxicillin. This nosocomial pathogen has become a great threat in hospitals globally. Up to 40% of the normal population carries S. aureus in the anterior nares, and this rate is often higher in hospitalized patients and their attendants. This case report presents a patient with serious MRSA osteomyelitis of the mandible demonstrating purulent discharge. The patient failed to recover despite prolonged postoperative treatment and the administration of several antibiotics. There was a resulting nonunion along with chronic MRSA infection. The treatment protocol involved a multimodal approach with parenteral clindamycin infusion, local rifampicin irrigation, and intermaxillary fixation of the jaws.

Are diabetic foot ulcers complicated by MRSA osteomyelitis associated with worse prognosis? Outcomes of a surgical series

The aim of this study was to compare the outcomes of surgical treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) with cases caused by methicillin-sensitive Staphylococcus aureus (MSSA). We abstracted data of a series of 185 consecutive patients with diabetes and foot osteomyelitis undergoing surgery within the first 12 h after admission at a single hospital. Bone infection was confirmed by histopathological studies. Only cases where Staphylococcus aureus was isolated from bone specimens were included in this analysis. We analysed several variables between the two groups: MRSA vs. MSSA. MRSA bone infection was associated with higher body temperature (P = 0.02) and white blood cell count (P = 0.02) than MSSA. Patients with MRSA infections underwent a greater number of surgical procedures (P = 0.03). Limb salvage was achieved in 93.6% of the patients, with no statistically significant difference in limb salvage rates between MRSA and MSSA-related osteomyelitis. From our experience, where treatment is based on early and aggressive surgical treatment, MRSA bone infections are not associated with worse prognosis.

Daptomycin in bone and joint infections: a review of the literature

IntroductionTo review the pharmacology, pharmacokinetics, efficacy, and safety of daptomycin, a novel antibiotic for the treatment of bone and joint infections, a literature search of relevant articles was conducted.Materials and methodsA PubMed/MEDLINE search (1990–April 2008) to identify relevant English-language literature was conducted. Search terms included bone and joint infection, osteomyelitis, daptomycin, and methicillin-resistant Staphylococcus aureus (MRSA). Additional articles were identified by reviewing the bibliographies of articles cited. Programs and abstracts from infectious disease meetings were searched, and prescribing information of antibiotics indicated for bone and joint infections consulted. All articles identified from data sources published in English were evaluated.ResultsCaused primarily by Gram-positive pathogens such as S. aureus and, to a lesser extent, Enterococcus faecalis, bone and joint infections are difficult to treat successfully. Surgical intervention and prolonged courses of antibiotics are frequently required, and failure of first-line antibiotic therapy is common. The emergence of S. aureus strains with reduced susceptibility to vancomycin, the longstanding gold standard for bone and joint infections, has complicated the clinical scenario. Few randomized trials comparing the efficacy of different antibiotics for bone and joint infections exist. Daptomycin, a novel intravenous lipopeptide antibiotic, has shown potent in vitro activity against a broad spectrum of Gram-positive bacteria, including many resistant pathogens commonly associated with bone and joint infections such as MRSA and vancomycin-resistant E. faecalis. Early clinical investigation of daptomycin in bone and joint infections unresponsive to antibiotics, such as vancomycin, has found a cure rate of approximately 80%, with a low incidence of adverse events and drug resistance.ConclusionFurther studies are warranted to determine if limited clinical evidence, described in individual case reports and a daptomycin-specific retrospective registry, suggests daptomycin is a promising option for patients with bone and joint infections such as MRSA osteomyelitis.

Treatment of experimental osteomyelitis by Methicillin Resistant Staphylococcus Aureus with bone cement system releasing grepafloxacin

The authors examined the effectiveness of the local anti-microbial treatment on methicillin resistant Staphylococcus aureus (MRSA) experimental osteomyelitis. Thirty-six rabbits with chronic MRSA osteomyelitis of the right femur were treated with local grepafloxacin delivery system prepared by a mixture of acrylic bone cement (polymethyl methacrylate, PMMA) plus 4% grepafloxacin. Osteomyelitis was induced by inoculating MRSA (100 microl of cultured bacteria; 10(7)) and the local insertion of a needle, serving as a foreign body, at the upper third of the femur. The course of the infection was followed by clinical, radiographic and microbiological examination. In the third week, all animals were re-operated, needles were removed, and antibiotic containing acrylic cement was implanted. Thereafter, one control and five treated animals were sacrificed per week, within 6 weeks. Osteomyelitis was found in all rabbits. In vitro grepafloxacin levels remained high throughout the 6 weeks of the experiment. Histologically tissue reaction against the cement was not observed. Osteomyelitis lesions and bone structure were progressively repaired after cement implantation. Biomechanical analysis showed no significant influence on the mechanical properties of acrylic cement due to grepafloxacin. The above mixture could prove to be an important supplementary method for the treatment of bone infections. Such a system could replace the use of gentamycin PMMA beads in the treatment of patients with chronic osteomyelitis due to MRSA. Furthermore, the proposed method could be used as a spacer after removal septic loosened prostheses in combination with systemic administration of antibiotics.

In vivo comparison of Dhvar-5 and gentamicin in an MRSA osteomyelitis prevention model

The continued rise in drug-resistant pathogens has led to global research efforts into new antimicrobial agents. A promising class of new agents are the antimicrobial peptides. The aim of the study was to investigate the efficacy of the antimicrobial peptide Dhvar-5 in a prophylactic, methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model. Dhvar-5 (12 mg or 24 mg/rabbit) was incorporated into polymethyl methacrylate (PMMA) beads as a local drug delivery system. For comparison, plain beads (control) and beads containing gentamicin as a sulphate (10 mg or 24 mg per rabbit) were also prepared. The beads were inserted into the inoculated femoral cavity of 36 rabbits, and 1 week later they were killed. The presence and severity of MRSA osteomyelitis was assessed by culture and histology. Both the 24 mg Dhvar-5 beads and the 24 mg gentamicin sulphate beads significantly reduced the bacterial load of the inoculated femora compared with the control chain. Although a 24 mg Dhvar-5 dose inhibited MRSA growth, it did not completely sterilize the femora. Sterilization occurred only in some of the gentamicin-treated specimens. We conclude that both the gentamicin beads and the Dhvar-5 beads were only partially effective at preventing MRSA infection in this model.

Vascularized fibular grafting in the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis and infected nonunion.

Twenty patients with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and bone infection were treated with vascularized fibular grafts. There were 16 males and four females, and the patient ages at operation ranged from 17 to 73 years. Nine of the lesions affected the femur, eight the tibia, and there were three others. All of the patients were treated with extensive debridement of the lesions and local antibiotic therapy. Continuous local irrigation was applied in two patients, antibiotic-formulated bone cement in five, and both in 10 patients. Recurrence of local infection occurred in six patients, including one failed graft. Eventually, 18 of the 20 cases attained successful subsidence of the inflammation. The mean period required to obtain radiographic bone union was 7 months in the femoral reconstruction group, 6.1 months in the tibial reconstruction group, and 6 months in the remaining patients. The authors believe that vascularized fibular grafting is the most reliable procedure for the treatment of MRSA osteomyelitis and infected nonunion.

Methicillin-resistant Staphylococcus Aureus Osteomyelitis

In five patients, the diagnosis of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis was made by clinical and roentgenographic methods and confirmed by bone biopsy cultures. The treatment was staged according to the anatomic setting of the infection and the systemic and local competence of the host. Seven episodes of osteomyelitis were encountered in the five patients. Two patients had persistence of their infection and were successfully treated by additional surgical debridement, antibiotics, and adjunctive hyperbaric oxygen. Vancomycin was administered to all patients. The daily dosage of vancomycin ranged between 100 mg and 2.0 gm. The length of vancomycin therapy ranged from 19 to 56 days. Five of seven biopsy specimens grew bacterial organisms in addition to MRSA. The MIC of vancomycin for MRSA ranged between 0.39 and 1.56 micrograms/ml. Osteomyelitis was arrested in five of seven episodes, and follow-up evaluations ranged from two to 35 months. Two of five (40%) patients receiving the combination of vancomycin and tobramycin developed signs of renal toxicity. Renal function returned to normal after discontinuation of the antibiotics. MRSA osteomyelitis is usually acquired by spread from a contiguous focus of infection and is often polymicrobic in nature. Treatment with vancomycin or vancomycin plus tobramycin when the infection was polymicrobic was effective. The combination of vancomycin plus tobramycin is potentially nephrotoxic.