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 β-Lactamase Inhibitors Enhance the Synergy between β-Lactam Antibiotics and Daptomycin against Methicillin-Resistant Staphylococcus aureus

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Karl Evans R. Henson ◽  
Juwon Yim ◽  
Jordan R. Smith ◽  
George Sakoulas ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Time Kill ◽  
Lactamase Inhibitor

ABSTRACT The evidence for using combination therapy for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections is growing. In this study, we investigated the synergistic effect of daptomycin (DAP) combined with piperacillin-tazobactam and ampicillin-sulbactam against MRSA in time-kill experiments. Six of eight strains demonstrated synergy between DAP and the β-lactam–β-lactamase inhibitor (BLI) combination. In 5/8 strains, the synergy occurred only in the presence of the BLI, highlighting a role for BLIs in peptide–β-lactam synergy.

scholarly journals In VitroPharmacodynamics of Vancomycin and Cefazolin Alone and in Combination against Methicillin-Resistant Staphylococcus aureus

2011 ◽  
Vol 56 (1) ◽  
pp. 202-207 ◽  
Author(s):  
Mao Hagihara ◽  
Dora E. Wiskirchen ◽  
Joseph L. Kuti ◽  
David P. Nicolau
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Synergistic Effects ◽  
Bacterial Density ◽  
Bacterial Killing ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Mics ◽  
Time Kill

ABSTRACTPrevious studies employing time-kill methods have observed synergistic effects against methicillin-resistantStaphylococcus aureus(MRSA) when a β-lactam is combined with vancomycin. However, these time-kill studies have neglected the importance of human-simulated exposures. We evaluated the effect of human simulated exposures of vancomycin at 1 g every 8 h (q8h) in combination with cefazolin at 1 g q8h against various MRSA isolates. Four clinical isolates (two MRSA isolates [vancomycin MICs, 0.5 and 2.0 μg/ml], a heterogeneous vancomycin-intermediateS. aureus[hVISA] isolate [MIC, 2.0 μg/ml], and a vancomycin-intermediateS. aureus[VISA] isolate [MIC, 8.0 μg/ml]) were evaluated in anin vitropharmacodynamic model with a starting inoculum of 106or 108CFU/ml. Bacterial density was measured over 48 to 72 h. Time-kill curves were constructed, and the area under the bacterial killing and regrowth curve (AUBC) was calculated. During 106CFU/ml studies, combination therapy achieved greater log10CFU/ml changes than vancomycin alone at 12 h (−4.31 ± 0.58 versus −2.80 ± 0.59,P< 0.001), but not at 48 h. Combination therapy significantly reduced the AUBC from 0 to 48 h (122 ± 14) compared with vancomycin alone (148 ± 22,P= 0.017). Similar results were observed during 108CFU/ml studies, where combination therapy achieved greater log10CFU/ml changes at 12 h than vancomycin alone (−4.00 ± 0.20 versus −1.10 ± 0.04,P< 0.001) and significantly reduced the AUBC (275 ± 30 versus 429 ± 37,P< 0.001) after 72 h of incubation. In this study, the combination of vancomycin and cefazolin at human-simulated exposures improved the rate of kill against these MRSA isolates and resulted in greater overall antibacterial effect, but no differences in bacterial density were observed by the end of the experiments.

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 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 Microbiological Aetiology, Epidemiology, and Clinical Profile of Prosthetic Joint Infections: Are Current Antibiotic Prophylaxis Guidelines Effective?

2012 ◽  
Vol 56 (5) ◽  
pp. 2386-2391 ◽  
Author(s):  
Trisha N. Peel ◽  
Allen C. Cheng ◽  
Kirsty L. Buising ◽  
Peter F. M. Choong
Keyword(s):  
Antibiotic Prophylaxis ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Surgical Antibiotic Prophylaxis

ABSTRACTProsthetic joint infections remain a major complication of arthroplasty. At present, local and international guidelines recommend cefazolin as a surgical antibiotic prophylaxis at the time of arthroplasty. This retrospective cohort study conducted across 10 hospitals over a 3-year period (January 2006 to December 2008) investigated the epidemiology and microbiological etiology of prosthetic joint infections. There were 163 cases of prosthetic joint infection identified. From a review of the microbiological culture results, methicillin-resistantStaphylococcus aureus(MRSA) and coagulase-negative staphylococci were isolated in 45% of infections. In addition, polymicrobial infections, particularly those involving Gram-negative bacilli and enterococcal species, were common (36%). The majority (88%) of patients received cefazolin as an antibiotic prophylaxis at the time of arthroplasty. In 63% of patients in this cohort, the microorganisms subsequently obtained were not susceptible to the antibiotic prophylaxis administered. The results of this study highlight the importance of ongoing reviews of the local ecology of prosthetic joint infection, demonstrating that the spectrum of pathogens involved is broad. The results should inform empirical antibiotic therapy. This report also provokes discussion about infection control strategies, including changing surgical antibiotic prophylaxis to a combination of glycopeptide and cefazolin, to reduce the incidence of infections due to methicillin-resistant staphylococci.

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.

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