scholarly journals Rifampin Combination Therapy for Nonmycobacterial Infections

2010 ◽  
Vol 23 (1) ◽  
pp. 14-34 ◽  
Author(s):  
Graeme N. Forrest ◽  
Kimberly Tamura
Keyword(s):  
Combination Therapy ◽  
Prosthetic Heart Valve ◽  
Case Series ◽  
Source Control ◽  
Retrospective Case ◽  
Coagulase Negative Staphylococci ◽  
Joint Infections ◽  
Prosthetic Joint Infections

SUMMARY The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

scholarly journals Antimicrobial Activity of Dalbavancin and Comparator Agents Tested against Gram-Positive Clinical Isolates Causing Bone and Joint Infections in United States (US) Medical Centers (2011–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S373-S373
Author(s):  
Helio S Sader ◽  
Rodrigo E Mendes ◽  
Robert K Flamm ◽  
Michael A Pfaller
Keyword(s):  
Active Agent ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Joint Infections ◽  
Bone And Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Viridans Group Streptococci ◽  
Research Grant

Abstract Background Bone and joint infections (BJI) comprise a series of disorders, including septic arthritis, osteomyelitis, and prosthetic joint infections. We evaluated the activity of dalbavancin (DALBA) against pathogens isolated from BJI in US hospitals. Methods A total of 744 organisms collected from 55 hospitals in 2011–2016 were evaluated, including 463 S. aureus, 88 coagulase-negative staphylococci (CoNS), 104 β-haemolytic streptococci (BHS), 60 E. faecalis, and 29 viridans group streptococci (VGS). Bacteria were identified by standard algorithms and MALDI-TOF-MS. Susceptibility testing was performed by CLSI methods (M07-A10); interpretation of MIC results used CLSI (2017) and EUCAST (2017) criteria. Results S. aureus (62.2%) was the most common pathogen associated with BJI, followed by BHS (14.0%) and CoNS (11.8%). All S. aureus (41.5% methicillin-resistant [MRSA]) isolates were susceptible (S) to DALBA, linezolid (LNZ), teicoplanin (TEI) and vancomycin (VAN), while daptomycin (DAPTO) and clindamycin (CLI) showed susceptibility rates of 99.8% and 87.7% (CLSI), respectively. DALBA MIC results (MIC50/90, ≤0.03/0.06 μg/mL) were ≥8-fold lower compared with DAPTO (MIC50/90, 0.25/0.5 μg/mL) against all S. aureus. Among CoNS, (61.4% MRSA), DALBA (MIC50/90, ≤0.03/0.06 μg/mL) was the most potent agent, followed by DAPTO (MIC50/90, 0.25/0.5 μg/mL), LNZ (MIC50/90, 0.5/1 μg/mL), and VAN (MIC50/90, 1/2 μg/mL). DALBA inhibited all E. faecalis isolates at ≤0.25 μg/mL (FDA S breakpoint), except for 3 VAN-resistant (VanA) isolates. High susceptibility rates for ampicillin (98.3%; CLSI), DAPTO (100.0%), LNZ (100.0%), TEI (93.3%) and VAN (93.3%) were obtained against E. faecalis. DALBA, DAPTO, LNZ, ceftriaxone, penicillin, and VAN were active against all BHS (100.0%S), while DALBA (MIC50/90, ≤0.03/0.06 μg/mL; 100.0%S) was the most active agent against VGS, inhibiting all isolates at ≤0.06 μg/mL. Ceftriaxone, LNZ, DAPTO, and VAN were also active against VGS (93.1 – 100.0%S; CLSI), whereas CLI (82.8%S) had marginal activity. Conclusion DALBA demonstrated potent in vitro activity against common gram-positive isolates causing BJI (2011–2016) and appears to be a viable candidate for treating BJI/osteomyelitis caused by gram-positive cocci. Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; M. A. Pfaller, Allergan: Research Contractor, Research grant

scholarly journals Impact of the Combination of Daptomycin and Trimethoprim-Sulfamethoxazole on Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Infections

2015 ◽  
Vol 59 (4) ◽  
pp. 1969-1976 ◽  
Author(s):  
Kimberly C. Claeys ◽  
Jordan R. Smith ◽  
Anthony M. Casapao ◽  
Ryan P. Mynatt ◽  
Lisa Avery ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Case Series ◽  
Signs And Symptoms ◽  
Retrospective Case ◽  
Methicillin Resistant ◽  
Content Type ◽  
Hospital Stays ◽  
Prolonged Hospital

ABSTRACTComplicatedStaphylococcus aureusinfections, including bacteremia, are often associated with treatment failures, prolonged hospital stays, and the emergence of resistance to primary and even secondary therapies. Daptomycin is commonly used as salvage therapy after vancomycin failure for the treatment of methicillin-resistantS. aureus(MRSA) infections. Unfortunately, the emergence of daptomycin resistance, especially in deep-seated infections, has been reported, prompting the need for alternative or combination therapy. Numerous antibiotic combinations with daptomycin have been investigated clinically andin vitro. Of interest, the combination of daptomycin and trimethoprim-sulfamethoxazole (TMP-SMX) has proved to be rapidly bactericidalin vitroto strains that are both susceptible and nonsusceptible to daptomycin. However, to date, there is limited clinical evidence supporting the use of this combination. This was a multicenter, retrospective case series of patients treated with the combination of daptomycin and TMP-SMX for at least 72 h. The objective of this study was to describe the safety and effectiveness of this regimen in clinical practice. The most commonly stated reason that TMP-SMX was added to daptomycin was persistent bacteremia and/or progressive signs and symptoms of infection. After the initiation of combination therapy, the median time to clearance of bacteremia was 2.5 days. Microbiological eradication was demonstrated in 24 out of 28 patients, andin vitrosynergy was demonstrated in 17 of the 17 recovered isolates. Further research with this combination is necessary to describe the optimal role and its impact on patient outcomes.

scholarly journals Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection

2013 ◽  
Vol 57 (10) ◽  
pp. 5080-5086 ◽  
Author(s):  
Jared A. Niska ◽  
Jonathan H. Shahbazian ◽  
Romela Irene Ramos ◽  
Kevin P. Francis ◽  
Nicholas M. Bernthal ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Mouse Model ◽  
Antibiotic Therapy ◽  
Joint Infection ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Implant Retention

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.

Determining Optimal Current Intensity and Duration for Electrically Activated Silver-Based Prophylactic Hip Implant Prototype Design

2013 ◽  
Author(s):  
Zhuo Tan ◽  
Rohan A. Shirwaiker ◽  
Paul E. Orndoff
Keyword(s):  
Joint Infections ◽  
Main Challenge ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Optimal Current ◽  
Actual Design ◽  
Potential Benefits ◽  
The Cost

Infections associated with medical prostheses result in notable morbidity, and traditional osteomyelitis treatments are often accompanied by high risk and cost. The probability of prosthetic joint infections is 1–2.5 % for primary hip or knee replacements and 2.1–5.8 % for revision surgeries, and the cost of treating such an infection is estimated to be over $50,000 per episode. [1] While the potential benefits of silver surfaces stimulated by low intensity direct current (LIDC) have been discussed in literature, we have recently utilized that concept in the actual design of prophylactic indwelling residual hardware prostheses for the very first time. [2–4] A modular titanium hip stem coated with silver at the anode (and titanium as the cathode) and activated by a watch battery encapsulated within the two electrode modules (Figure 1) will result in oligodynamic iontophoresis (OI) in the soft tissue surrounding the implant which is prone to infections. Preliminary in vitro and in vivo results have demonstrated the potency of silver-based OI as an effective local antibacterial therapy in osteomyelitis treatment with advantages over various antibiotics. However, the main challenge here is achieving the antibacterial potency while minimizing any potential toxic effects on local tissues. [4]

scholarly journals Controlling Antibiotic Release from Polymethylmethacrylate Bone Cement

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 26
Author(s):  
Victoria Wall ◽  
Thi-Hiep Nguyen ◽  
Nghi Nguyen ◽  
Phong A. Tran
Keyword(s):  
Bone Cement ◽  
Joint Infections ◽  
Current State ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Bone Void

Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the implanted prosthesis. High antibiotic concentrations are, on the other hand, often associated with tissue toxicity. Controlling antibiotic release from ALBCS is key to achieving effective infection control and promoting prosthesis integration with the surrounding bone tissue. However, current ALBCs still need significant improvement in regulating antibiotic release. In this review, we first provide a brief introduction to prosthetic joint infections, and the background concepts of therapeutic efficacy and toxicity in antibiotics. We then review the current state of ALBCs and their release characteristics before focusing on the research and development in controlling the antibiotic release and osteo-conductivity/inductivity. We then conclude by a discussion on the need for better in vitro experiment designs such that the release results can be extrapolated to predict better the local antibiotic concentrations in vivo.

scholarly journals 1070. In vitro Activity of PLG0206 Against Isolates Commonly Found in Periprosthetic Joint Infections (PJI)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S627-S628
Author(s):  
David Huang ◽  
Jonathan Steckbeck ◽  
Chris Pillar ◽  
Bev Murray ◽  
David Huganfel ◽  
...  
Keyword(s):  
Culture Collection ◽  
Multi Drug Resistance ◽  
Broth Microdilution ◽  
Coagulase Negative Staphylococci ◽  
Cationic Antimicrobial Peptide ◽  
Gram Negative ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Abstract Background PLG0206 is a novel engineered cationic antimicrobial peptide being evaluated for treatment of prosthetic joint infections. In this study, the activity of PLG0206 was evaluated by broth microdilution against 104 isolates of Staphylococcus epidermidis, 53 other coagulase-negative staphylococci (CoNS), 3 S. aureus, and 66 Gram-negative isolates consisting of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Methods Imipenem, levofloxacin, tigecycline, linezolid, vancomycin, oxacillin, ceftazidime, colistin, and amikacin were tested as comparators. Testing was conducted in accordance with guidelines from the Clinical and Laboratory Standards Institute (CLSI; M7 and M100). Test organisms consisted of reference strains from the American Type Culture Collection, the Centers for Disease Control Antibiotic Reference Bank and clinical isolates from the Micromyx repository. The media employed for testing in the broth microdilution MIC assay for all organisms were cation-adjusted Mueller Hinton Broth and for PLG0206 only included RPMI-1640 medium supplemented with 0.002% P-80. Results Activity of PLG0206 in RPMI against CoNS, S. aureus, and resistant Gram-negative* pathogens are shown in Table. Activity of PLG0206 in RPMI against CoNS, S. aureus and resistant Gram-negative* pathogens Activity of PLG0206 in RPMI against CoNS, S. aureus and resistant Gram-negative* pathogens Conclusion PLG0206 was found to have potent antimicrobial activity when evaluated in RPMI against S. epidermidis, CoNS non-epidermidis, S. aureus, Enterobacterales, P. aeruginosa, and A. baumannii, including isolates with multi-drug resistance. Disclosures David Huang, MD, PhD, Peptilogics (Employee) Jonathan Steckbeck, PhD, Peptilogics (Employee) Chris Pillar, PhD, Micromyx (Employee) Bev Murray, BS, Micromyx (Employee) David Huganfel, BS, Micromyx (Employee) Dean Shinabanger, PhD, Micromyx (Employee)

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