<i>In Vitro</i>
            Efficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

Tang, Hung Jen; Chen, Chi Chung; Cheng, Kuo Chen; Wu, Kuan Ying; Lin, Yi Chung; Zhang, Chun Cheng; Weng, Tzu Chieh; Yu, Wen Liang; Chiu, Yu Hsin; Toh, Han Siong; Chiang, Shyh Ren; Su, Bo; Ko, Wen Chien; Chuang, Yin Ching

doi:10.1128/aac.01236-13

Cited by 45 publications

(30 citation statements)

References 18 publications

(23 reference statements)

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“…(90), and minocycline (87%) (163). Lower synergy was reported with rifampin (50%) (164). It is also noteworthy that antagonism was not reported for any of the above combinations.…”

Section: Newer Studiesmentioning

confidence: 89%

Fosfomycin

et al. 2016

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SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

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“…(90), and minocycline (87%) (163). Lower synergy was reported with rifampin (50%) (164). It is also noteworthy that antagonism was not reported for any of the above combinations.…”

Section: Newer Studiesmentioning

confidence: 89%

Fosfomycin

et al. 2016

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“…Alternatively, rifampin in combination with another antibiotic, like vancomycin, is commonly regarded as a critical treatment strategy against implant-associated Staphylococcal infections [1, 37]. This is based on the notion that rifampin is efficacious against Staphylococci in biofilm [38, 39]; however, rifampin is incompatible with PMMA spacers because this antibiotic impairs the polymerization of PMMA [6]. Future studies of alternative antimicrobial therapies in this mouse model with implant retention will likely require successful treatment of the biofilm in order to realize complete eradication of the infection.…”

Section: Discussionmentioning

confidence: 99%

A novel murine model of established Staphylococcal bone infection in the presence of a fracture fixation plate to study therapies utilizing antibiotic-laden spacers after revision surgery

Inzana

Schwarz

Kates

et al. 2015

Bone

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Mice are the small animal model of choice in biomedical research due to the low cost and availability of genetically engineered lines. However, the devices utilized in current mouse models of implant-associated bone infection have been limited to intramedullary or trans-cortical pins, which are not amenable to treatments involving extensive debridement of a full-thickness bone loss and placement of a segmental antibiotic spacer. To overcome these limitations, we developed a clinically faithful model that utilizes a locking fracture fixation plate to enable debridement of an infected segmental bone defect (full-thickness osteotomy) during a revision surgery, and investigated the therapeutic effects of placing an antibiotic-laden spacer in the segmental bone defect. To first determine the ideal time point for revision following infection, a 0.7 mm osteotomy in the femoral mid-shaft was stabilized with a radiolucent PEEK fixation plate. The defect was inoculated with bioluminescent Staphylococcus aureus, and the infection was monitored over 14 days by bioluminescent imaging (BLI). Osteolysis and reactive bone formation were assessed by X-ray and micro-computed tomography (micro-CT). The active bacterial infection peaked by 5 days post-inoculation, however the stability of the implant fixation became compromised by 10–14 days post-inoculation due to osteolysis around the screws. Thus, day 7 was defined as the ideal time point to perform the revision surgery. During the revision surgery, the infected tissue was debrided and the osteotomy was widened to 3 mm to place a poly-methyl methacrylate spacer, with or without vancomycin. Half of the groups also received systemic vancomycin for the remaining 21 days of the study. The viable bacteria remaining at the end of the study were measured using colony forming unit assays. Volumetric bone changes (osteolysis and reactive bone formation) were directly measured using micro-CT image analysis. Mice that were treated with local or systemic vancomycin did not display gross pathology at the end of the study. While localized vancomycin delivery alone tended to decrease the bacterial burden and osteolysis, these effects were only significant when combined with systemic antibiotic therapy. This novel mouse model replicates key features of implant-associated osteomyelitis that make treatment extremely difficult, such as biofilm formation and osteolysis, and imitates the clinical practice of placing an antibiotic-laden spacer after infected tissue debridement. In addition, the model demonstrates the limitations of current PMMA spacers and could be an invaluable tool for evaluating alternative antimicrobial treatments for implant-associated bone infection.

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“…Rifampicin is probably the antimicrobial agent that demonstrated the best activity on staphylococcal biofilm [54,[59][60][61][62][63]. When in combination, fosfomycin has been found to enhance the antimicrobial activities of many antibiotics in meticillin-resistant S. aureus (MRSA) biofilm [64].…”

Section: Choice Of Antibioticsmentioning

confidence: 99%

Medical treatment of prosthetic vascular graft infections: Review of the literature and proposals of a Working Group

Revest¹,

Camou²,

Senneville³

et al. 2015

International Journal of Antimicrobial Agents

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More than 400000 vascular grafts are inserted annually in the USA. Graft insertion is complicated by infection in 0.5-4% of cases. Vascular graft infections (VGIs) are becoming one of the most frequent prosthesis-related infections and are associated with considerable mortality, ranging from 10 to 25% within 30 days following the diagnosis. Treatment of VGI is based on urgent surgical removal of the infected graft followed by prolonged antibiotherapy. Data regarding the best antibiotherapy to use are lacking since no well designed trial to study antimicrobial treatment of VGI exists. Moreover, since VGIs demonstrate very specific pathophysiology, guidelines on other material-related infections or infective endocarditis treatment cannot be entirely applied to VGI. A French multidisciplinary group gathering infectious diseases specialists, anaesthesiologists, intensivists, microbiologists, radiologists and vascular surgeons was created to review the literature dealing with VGI and to make some proposals regarding empirical and documented antibiotic therapy for these infections. This article reveals these proposals.

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In Vitro Efficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

Cited by 45 publications

References 18 publications

Fosfomycin

Fosfomycin

A novel murine model of established Staphylococcal bone infection in the presence of a fracture fixation plate to study therapies utilizing antibiotic-laden spacers after revision surgery

Medical treatment of prosthetic vascular graft infections: Review of the literature and proposals of a Working Group

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