scholarly journals Rifampin-Based Combination Therapy Is Active in Foreign-Body Osteomyelitis after Prior Rifampin Monotherapy

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Cassandra L. Brinkman ◽  
Suzannah M. Schmidt-Malan ◽  
Jayawant N. Mandrekar ◽  
Robin Patel

ABSTRACT Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.

2013 ◽  
Vol 57 (10) ◽  
pp. 5080-5086 ◽  
Author(s):  
Jared A. Niska ◽  
Jonathan H. Shahbazian ◽  
Romela Irene Ramos ◽  
Kevin P. Francis ◽  
Nicholas M. Bernthal ◽  
...  

ABSTRACTTreatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in whichStaphylococcus aureuswas inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention.In vivobioluminescence imaging,ex vivoCFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuablein vivopreclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.


2014 ◽  
Vol 58 (9) ◽  
pp. 5576-5580 ◽  
Author(s):  
Cristina El Haj ◽  
Oscar Murillo ◽  
Alba Ribera ◽  
Mireia Vivas ◽  
Dolors Garcia-Somoza ◽  
...  

ABSTRACTWe compared the efficacies of daptomycin (doses equivalent to 8 to 10 mg/kg of body weight/day in humans) and cloxacillin alone with those of cloxacillin-rifampin and cloxacillin-daptomycin combinations, using a tissue cage methicillin-susceptibleStaphylococcus aureus(MSSA) infection model. Monotherapies were less effective than combinations (P< 0.05), and daptomycin resistance emerged. Cloxacillin-daptomycin proved as effective as cloxacillin-rifampin and prevented the appearance of resistance; this combination may be an alternative anti-MSSA therapy, which may offer greater benefits in the early treatment of prosthetic joint infections (PJI).


Author(s):  
Natalia E Castillo Almeida ◽  
Ryan W Stevens ◽  
Pooja Gurram ◽  
Christina G Rivera ◽  
Gina A Suh

Abstract Purpose To identify risk factors that may predispose patients to rifampin- and cefazolin-induced coagulopathy. Summary An 86-year-old man with a history of rheumatoid arthritis on chronic prednisone and stage 3 chronic kidney disease, notably not on warfarin, presented to the hospital with a 10-day history of right hip pain, swelling, and drainage after a recent right total-hip arthroplasty. The patient underwent a combination of surgical intervention and medication therapy with rifampin and ceftriaxone. After discharge and at postoperative day 9, ceftriaxone was changed to cefazolin due to increasing alkaline phosphatase levels. Four weeks after the initial debridement, antibiotics, and implant retention, the patient underwent a second irrigation and debridement due to persistent infection. Cefazolin and rifampin therapy was extended. Three days later, the patient presented to the emergency room with significant bleeding at the surgical site and a profoundly elevated prothrombin time and international normalized ratio (INR). No potential contributors were identified. The Naranjo adverse drug reaction probability scale identified cefazolin and rifampin as the probable cause of elevated INR. The Liverpool adverse drug reaction avoidability assessment tool classified this adverse event as “definitely avoidable.” Conclusion Rifampin-containing regimens are often recommended to treat staphylococcal prosthetic joint infections when the implant is retained. In methicillin-susceptible staphylococcal infections, cefazolin is routinely employed as the β-lactam backbone of definitive antimicrobial regimens. Although rifampin- and cefazolin-induced hypoprothrombinemia seems to be rare, adverse consequences of its occurrence may be prevented with appropriate monitoring.


Author(s):  
Emeli Månsson ◽  
Thor Bech Johannesen ◽  
Åsa Nilsdotter-Augustinsson ◽  
Bo Söderquist ◽  
Marc Stegger

There is increased awareness of the worldwide spread of specific epidemic multidrug-resistant (MDR) lineages of the human commensal Staphylococcus epidermidis . Here, using bioinformatic analyses accounting for population structure, we determined genomic traits (genes, SNPs and k-mers) that distinguish S. epidermidis causing prosthetic-joint infections (PJIs) from commensal isolates from nares, by analysing whole-genome sequencing data from S. epidermidis from PJIs prospectively collected over 10 years in Sweden, and contemporary S. epidermidis from the nares of patients scheduled for arthroplasty surgery. Previously suggested virulence determinants and the presence of genes and mutations linked to antimicrobial resistance (AMR) were also investigated. Publicly available S. epidermidis sequences were used for international extrapolation and validation of findings. Our data show that S. epidermidis causing PJIs differed from nasal isolates not by virulence but by traits associated with resistance to compounds used in prevention of PJIs: β-lactams, aminoglycosides and chlorhexidine. Almost a quarter of the PJI isolates did not belong to any of the previously described major nosocomial lineages, but the AMR-related traits were also over-represented in these isolates, as well as in international S. epidermidis isolates originating from PJIs. Genes previously associated with virulence in S. epidermidis were over-represented in individual lineages, but failed to reach statistical significance when adjusted for population structure. Our findings suggest that the current strategies for prevention of PJIs select for nosocomial MDR S. epidermidis lineages that have arisen from horizontal gene transfer of AMR-related traits into multiple genetic backgrounds.


Materials ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3144
Author(s):  
David Romera ◽  
Beatriz Toirac ◽  
John-Jairo Aguilera-Correa ◽  
Amaya García-Casas ◽  
Aránzazu Mediero ◽  
...  

Fungal prosthetic-joint infections are rare but devastating complications following arthroplasty. These infections are highly recurrent and expose the patient to the development of candidemia, which has high mortality rates. Patients with this condition are often immunocompromised and present several comorbidities, and thus pose a challenge for diagnosis and treatment. The most frequently isolated organisms in these infections are Candida albicans and Candida parapsilosis, pathogens that initiate the infection by developing a biofilm on the implant surface. In this study, a novel hybrid organo–inorganic sol–gel coating was developed from a mixture of organopolysiloxanes and organophosphite, to which different concentrations of fluconazole or anidulafungin were added. Then, the capacity of these coatings to prevent biofilm formation and treat mature biofilms produced by reference and clinical strains of C. albicans and C. Parapsilosis was evaluated. Anidulafungin-loaded sol–gel coatings were more effective in preventing C. albicans biofilm formation, while fluconazole-loaded sol–gel prevented C. parapsilosis biofilm formation more effectively. Treatment with unloaded sol–gel was sufficient to reduce C. albicans biofilms, and the sol–gels loaded with fluconazole or anidulafungin slightly enhanced this effect. In contrast, unloaded coatings stimulated C. parapsilosis biofilm formation, and loading with fluconazole reduced these biofilms by up to 99%. In conclusion, these coatings represent a novel therapeutic approach with potential clinical use to prevent and treat fungal prosthetic-joint infections.


2015 ◽  
Vol 21 (8) ◽  
pp. 786.e9-786.e17 ◽  
Author(s):  
E. Tornero ◽  
L. Morata ◽  
J.C. Martínez-Pastor ◽  
G. Bori ◽  
C. Climent ◽  
...  

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