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.

scholarly journals Novel Use of Rifabutin and Rifapentine to Treat Methicillin-Resistant Staphylococcus aureus in a Rat Model of Foreign Body Osteomyelitis

2020 ◽  
Vol 222 (9) ◽  
pp. 1498-1504
Author(s):  
Melissa J Karau ◽  
Suzannah M Schmidt-Malan ◽  
Mariana Albano ◽  
Jayawant N Mandrekar ◽  
Christina G Rivera ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Rat Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Kirschner Wire ◽  
Methicillin Resistant ◽  
Joint Infections ◽  
Single Animal ◽  
K Wires

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

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 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 Is intracellular Staphylococcus aureus associated with recurrent infection in a rat model of open fracture?

2020 ◽  
Vol 9 (2) ◽  
pp. 71-76
Author(s):  
Tao Gao ◽  
Junqing Lin ◽  
Changqing Zhang ◽  
Hongyi Zhu ◽  
Xianyou Zheng
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Marrow ◽  
Green Fluorescent Protein ◽  
Rat Model ◽  
Open Fracture ◽  
Fluorescent Protein ◽  
Kirschner Wire ◽  
Recurrent Infection ◽  
Host Immune System ◽  
Green Fluorescent

Aims The purpose of this study was to determine whether intracellular Staphylococcus aureus is associated with recurrent infection in a rat model of open fracture. Methods After stabilizing with Kirschner wire, we created a midshaft femur fracture in Sprague-Dawley rats and infected the wound with green fluorescent protein (GFP)-tagged S. aureus. After repeated debridement and negative swab culture was achieved, the isolation of GFP-containing cells from skin, bone marrow, and muscle was then performed. The composition and viability of intracellular S. aureus in isolated GFP-positive cells was assessed. We suppressed the host immune system and observed whether recurrent infection would occur. Finally, rats were assigned to one of six treatment groups (a combination of antibiotic treatment and implant removal/retention). The proportion of successful eradication was determined. Results Green fluorescent protein-containing cells were successfully isolated after the swab culture was negative from skin (n = 0, 0%), muscle (n = 10, 100%), and bone marrow (n = 10, 100%) of a total of ten rats. The phagocytes were predominant in GFP-positive cells from muscle (73%) and bone marrow (81%) with a significantly higher viability of intracellular S. aureus (all p-values < 0.001). The recurrent infection occurred in up to 75% of rats after the immunosuppression. The proportion of successful eradication was not associated with implant retention or removal, and the efficacy of linezolid in eradicating intracellular S. aureus is significantly higher than that of vancomycin. Conclusion Intracellular S. aureus is associated with recurrent infection in the rat model of open fracture. Usage of linezolid, a membrane-permeable antibiotic, is an effective strategy against intracellular S. aureus. Cite this article: Bone Joint Res. 2020;9(2):71–76.

scholarly journals Comparison of Methicillin-Resistant Staphylococcus aureus Isolates from Cellulitis and from Osteomyelitis in a Taiwan Hospital, 2016–2018

2019 ◽  
Vol 8 (6) ◽  
pp. 816 ◽  
Author(s):  
Kuo-Ti Peng ◽  
Tsung-Yu Huang ◽  
Yao-Chang Chiang ◽  
Yu-Yi Hsu ◽  
Fang-Yi Chuang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Sccmec Type ◽  
Multidrug Resistant ◽  
Chang Gung Memorial Hospital ◽  
Methicillin Resistant ◽  
Mrsa Strains ◽  
Resistance Rates

Methicillin-resistant Staphylococcus aureus (MRSA) causes superficial infections such as cellulitis or invasive infections such as osteomyelitis; however, differences in MRSA isolates from cellulitis (CL-MRSA) and from osteomyelitis (OM-MRSA) at the same local area remain largely unknown. A total of 221 MRSA isolates including 106 CL-MRSA strains and 115 OM-MRSA strains were collected at Chang-Gung Memorial Hospital in Taiwan between 2016 and 2018, and their genotypic and phenotypic characteristics were compared. We found that OM-MRSA isolates significantly exhibited higher rates of resistance to multiple antibiotics than CL-MRSA isolates. Genotypically, OM-MRSA isolates had higher proportions of the SCCmec type III, the sequence type ST239, and the spa type t037 than CL-MRSA isolates. Besides the multidrug-resistant lineage ST239-t037-SCCmecIII more prevalent in OM-MRSA, higher antibiotic resistance rates were also observed in several other prevalent lineages in OM-MRSA as compared to the same lineages in CL-MRSA. Furthermore, when prosthetic joint infection (PJI) associated and non-PJI-associated MRSA strains in osteomyelitis were compared, no significant differences were observed in antibiotic resistance rates between the two groups, albeit more diverse genotypes were found in non-PJI-associated MRSA. Our findings therefore suggest that deep infections may allow MRSA to evade antibiotic attack and facilitate the convergent evolution and selection of multidrug-resistant lineages.

Sign in / Sign up

Export Citation Format

Share Document