Novel Therapeutic Combinations for Methicillin-Resistant Staphylococcus aureus Bacteremia and Prosthetic Joint Infection With Evolving Multidrug Resistance

2012 ◽  
Vol 20 (2) ◽  
pp. 157-160 ◽  
Author(s):  
Howard Miller ◽  
Lynn Nolan ◽  
Pamela A. Moise
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Prosthetic Joint Infection ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Prosthetic Joint ◽  
Novel Therapeutic

scholarly journals Salvage Bacteriophage Therapy for a Chronic MRSA Prosthetic Joint Infection

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 241 ◽  
Author(s):  
James B. Doub ◽  
Vincent Y. Ng ◽  
Aaron J. Johnson ◽  
Magdalena Slomka ◽  
Joseph Fackler ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Prosthetic Joint Infection ◽  
Chronic Infection ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Intravenous Dose ◽  
Bacteriophage Therapy ◽  
Methicillin Resistant ◽  
The Third ◽  
Prosthetic Joint

This is a case of a 72 year old male with a chronic methicillin-resistant Staphylococcus aureus prosthetic joint infection. After the third intravenous dose of bacteriophage therapy, an unusual, reversible transaminitis prompted stoppage of bacteriophage therapy. Nevertheless, treatment was successful and the patient’s severe chronic infection was eradicated.

scholarly journals Adjunctive Rifampin Is Crucial to Optimizing Daptomycin Efficacy against Rabbit Prosthetic Joint Infection Due to Methicillin-Resistant Staphylococcus aureus

2011 ◽  
Vol 55 (10) ◽  
pp. 4589-4593 ◽  
Author(s):  
Azzam Saleh-Mghir ◽  
Claudette Muller-Serieys ◽  
Aurélien Dinh ◽  
Laurent Massias ◽  
Anne-Claude Crémieux
Keyword(s):  
Staphylococcus Aureus ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Detection Threshold ◽  
High Dose ◽  
Prosthesis Infection ◽  
Methicillin Resistant ◽  
Prosthetic Joint ◽  
Mutant Strains

ABSTRACTDaptomycin is an attractive option for treating prosthetic joint infection, but the 6-mg/kg of body weight/day dose was linked to clinical failure and emergence of resistance. Using a methicillin-resistantStaphylococcus aureus(MRSA) knee prosthesis infection in rabbits, we studied the efficacies of high-dose daptomycin (22 mg/kg given intravenously [i.v.] once daily [o.d.]; equivalent to 8 mg/kg/day in humans) or vancomycin (60 mg/kg given intramuscularly [i.m.] twice daily [b.i.d.]), both either alone or with adjunctive rifampin (10 mg/kg i.m. b.i.d.). After partial knee replacement with a silicone implant, 107MRSA CFU was injected into the knees. Treatment started 7 days postinoculation and lasted 7 days. Positive cultures were screened for the emergence of mutant strains, defined as having 3-fold-increased MICs. Althoughin vivomean log10CFU/g of daptomycin-treated (4.23 ± 1.44;n= 12) or vancomycin-treated (4.63 ± 1.08;n= 12) crushed bone was significantly lower than that of controls (5.93 ± 1.15;n= 9) (P< 0.01), neither treatment sterilized bone (2/12 and 0/12 rabbits with sterile bone, respectively). Daptomycin mutant strains were found in 6/12, 3/12, and 2/9 daptomycin-treated, vancomycin-treated, and control rabbits, respectively; no resistant strains emerged (MIC was always <1 mg/liter). Adjunctive rifampin with daptomycin (1.47 ± 0.04 CFU/g of bone [detection threshold]; 11/11 sterile bones) or vancomycin (1.5 ± 0.12 CFU/g of bone; 6/8 sterile bones) was significantly more effective than monotherapy (P< 0.01) and prevented the emergence of daptomycin mutant strains. In this MRSA joint prosthesis infection model, combining rifampin with daptomycin was highly effective. Daptomycin mutant strains were isolatedin vivoeven without treatment, but adjunctive rifampin prevented this phenomenon, previously found after monotherapy in humans.

scholarly journals 390. Treatment and Outcome of Methicillin-Resistant Staphylococcus aureus Hip and Knee Prosthetic Joint Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S201-S201
Author(s):  
Michael Henry ◽  
Alberto V Carli ◽  
Milan Kapadia ◽  
Yu-fen Chiu ◽  
Barry Brause ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Surgical Treatment ◽  
Treatment Failure ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Infection Type ◽  
Joint Infection ◽  
Methicillin Resistant ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Implant Retention

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) total hip and knee prosthetic joint infections (PJI) can be highly morbid and difficult to treat. Other clinical factors notwithstanding, explantation is usually recommended, although comparative treatment data are lacking. We sought to compare the success of implant retention to two-stage exchange in MRSA-infected PJI to better understand treatment options in this difficult cohort. Methods A retrospective cohort of hip and knee PJIs from 2009 to 2016 were identified by ICD code and surgical treatment. All cases met MSIS criteria for PJI, and had culture-confirmed MRSA from synovial or intra-articular tissue culture. PJIs were either treated with exchange arthroplasty or debridement with antibiotic and implant retention (DAIR). Success was defined as no further surgical treatment for infection at two years. Kaplan–Meier estimates were used to calculate the 2-year survival rate free from treatment failure. Univariate logistic regression was performed to identify risk factors associated with treatment failure. Results 65 MRSA PJIs were identified with 42 undergoing explantation and 23 undergoing DAIR. Demographics, Charlson comorbidities, infection type (early post-operative, hematogenous or late chronic), and history of prior PJI were not significantly different between treatment groups. Survivorship at two years was 75% (95% confidence interval [CI] 61–88%) for exchange compared with 29% (95% CI 10–48%) for DAIR, P = 0.0002. Within the exchange group, knee PJIs were more likely to fail than hip PJI (odds ratio [OR] 7.1, CI 1.3–38, P = 0.02), and patients with diabetes were more likely to fail (OR 17, CI 1.6–178, P = 0.02). Conclusion MRSA PJIs treated with DAIR have worse outcomes than those treated with prosthesis exchange. Further investigation is needed to identify predictors of DAIR success, to optimize surgical treatment choice, and to improve outcomes of these difficult infections. Disclosures All authors: No reported disclosures.

scholarly journals Ceftaroline-Fosamil Efficacy against Methicillin-Resistant Staphylococcus aureus in a Rabbit Prosthetic Joint Infection Model

2014 ◽  
Vol 58 (11) ◽  
pp. 6496-6500 ◽  
Author(s):  
Laure Gatin ◽  
Azzam Saleh-Mghir ◽  
Jason Tasse ◽  
Idir Ghout ◽  
Frédéric Laurent ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Infection Model ◽  
Ceftaroline Fosamil ◽  
Methicillin Resistant ◽  
Prosthetic Joint ◽  
Intramedullary Canal

ABSTRACTCeftaroline (CPT), the active metabolite of the prodrug ceftaroline-fosamil (CPT-F), demonstratesin vitrobactericidal activity against methicillin-resistantStaphylococcus aureus(MRSA) and is effective in rabbit models of difficult-to-treat MRSA endocarditis and acute osteomyelitis. However, itsin vivoefficacy 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 × 107MRSA 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 thein vivomean log10CFU/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 log10CFU/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.

scholarly journals Evaluation of Oritavancin Combinations with Rifampin, Gentamicin, or Linezolid against Prosthetic Joint Infection-Associated Methicillin-ResistantStaphylococcus aureusBiofilms by Time-Kill Assays

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Qun Yan ◽  
Melissa J. Karau ◽  
Yash S. Raval ◽  
Robin Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Antibiofilm Activity ◽  
Methicillin Resistant ◽  
Content Type ◽  
Prosthetic Joint ◽  
Time Kill

ABSTRACTThe antibiofilm activity of oritavancin in combination with rifampin, gentamicin, or linezolid was evaluated against 10 prosthetic joint infection (PJI)-related methicillin-resistantStaphylococcus aureus(MRSA) isolates by time-kill assays. Oritavancin combined with rifampin demonstrated statistically significant bacterial reductions compared with those of either antimicrobial alone for all 10 isolates (P≤ 0.001), with synergy being observed for 80% of the isolates. Oritavancin and rifampin combination therapy may be an option for treating MRSA PJI.

scholarly journals Intestinal methicillin-resistant Staphylococcus aureus causes prosthetic infection via ‘Trojan Horse’ mechanism: Evidence from a rat model

2020 ◽  
Vol 9 (4) ◽  
pp. 152-161
Author(s):  
Hongyi Zhu ◽  
Hanqiang Jin ◽  
Changqing Zhang ◽  
Ting Yuan
Keyword(s):  
Staphylococcus Aureus ◽  
Intravenous Injection ◽  
Rat Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Fluorescent Protein ◽  
Joint Infection ◽  
Trojan Horse ◽  
Methicillin Resistant ◽  
Prosthetic Joint ◽  
Green Fluorescent

Aims Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown. Methods Rats underwent intestinal colonization with green fluorescent protein (GFP)-tagged MRSA by gavage and an intra-articular wire was then surgically implanted. After ten days, the presence of PJI was determined by bacterial cultures of the distal femur, joint capsule, and implant. We excluded several other possibilities for PJI development. Intraoperative contamination was excluded by culturing the specimen obtained from surgical site. Extracellular bacteraemia-associated PJI was excluded by comparing with the infection rate after intravenous injection of MRSA or MRSA-carrying neutrophils. To further support this theory, we tested the efficacy of prophylactic membrane-permeable and non-membrane-permeable antibiotics in this model. Results After undergoing knee surgery eight or 72 hours after colonization, five out of 20 rats (25.0%) and two out of 20 rats (10.0%) developed PJI, respectively. Strikingly, 11 out of 20 rats (55.0%) developed PJI after intravenous injection of MRSA-carrying neutrophils that were isolated from rats with intestinal MRSA colonization. None of the rats receiving intravenous injections of MRSA developed PJI. These results suggest that intestinal MRSA carried by neutrophils could cause PJI in our rat model. Ten out of 20 (50.0%) rats treated with non-membrane-permeable gentamicin developed PJI, whereas only one out of 20 (5.0%) rats treated with membrane-permeable linezolid developed PJI. Conclusion Neutrophils as carriers of intestinal MRSA may play an important role in PJI development. Cite this article: Bone Joint Res. 2020;9(4):152–161.

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