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Barbara E. Murray - One of the best experts on this subject based on the ideXlab platform.
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in vivo effects of Cefazolin daptomycin and nafcillin in experimental endocarditis with a methicillin susceptible staphylococcus aureus strain showing an inoculum effect against Cefazolin
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Esteban C Nannini, Kavindra V Singh, Barbara E. Murray, Cesar A AriasAbstract:Several reports have implicated the inoculum effect that some strains of type A beta-lactamase (Bla)-producing, methicillin-susceptible Staphylococcus aureus (MSSA) show against Cefazolin as the cause for clinical failures in certain serious deep-seated infections. Here, using a previously reported MSSA strain displaying this phenotype (TX0117), we obtained a Bla-cured derivative (TX0117c) with a combination of novobiocin and high temperature. Both isolates were then used in a rat endocarditis model and treated with Cefazolin, nafcillin, and daptomycin, given to simulate human dosing. Animals were treated for 3 days and either sacrificed at 24 h after the last antibiotic dose (standard group) or left untreated for an additional 3 days (relapse group). With TX0117 in the standard treatment group, daptomycin and nafcillin were both significantly better than Cefazolin in reducing CFU/g of vegetations, achieving mean log10 reductions compared to levels in untreated rats of 7.1, 5.3, and 1.8, respectively (Cefazolin versus daptomycin, P < 0.0001; Cefazolin versus nafcillin, P = 0.005; daptomycin versus nafcillin, P = 0.053). In addition, Cefazolin was significantly more effective in reducing vegetation titers of TX0117c than of TX0117 (mean log10 reduction of 1.4 versus 5.5, respectively; P = 0.0001). Similar results were observed with animals in the relapse group. Thus, these data show that there can be an in vivo consequence of the in vitro inoculum effect that some MSSA strains display against Cefazolin and indicate a specific role for Bla production using a Bla-cured derivative strain against which Cefazolin regained both in vitro and in vivo activity.
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inoculum effect with Cefazolin among clinical isolates of methicillin susceptible staphylococcus aureus frequency and possible cause of Cefazolin treatment failure
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: Esteban C Nannini, Martin E Stryjewski, Agathe Bourgogne, Tom H Rude, Ralph G Corey, Vance G Fowler, Kavindra V Singh, Barbara E. MurrayAbstract:Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A β-lactamase (Bla) have been associated with Cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The Cefazolin MIC90 was 2 μg/ml for a standard inoculum and 32 μg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of ≥16 μg/ml with 107 CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher Cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced Cefazolin failure showed a Cefazolin inoculum effect, while none from the six patients successfully treated with Cefazolin showed an inoculum effect, suggesting an association between these strains and Cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with Cefazolin, a phenomenon that could explain the cases of Cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with Cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.
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relapse of type a β lactamase producing staphylococcus aureus native valve endocarditis during Cefazolin therapy revisiting the issue
Clinical Infectious Diseases, 2003Co-Authors: Esteban C Nannini, Kavindra V Singh, Barbara E. MurrayAbstract:Our experience with a patient with methicillin-susceptible Staphylococcus aureus aortic native valve endocarditis, who had a relapse involving fever and positive blood culture results while receiving Cefazolin, led us to evaluate this organism's ability to hydrolyze Cefazolin at high inocula, a previously well-documented phenomenon. Analysis of the infecting strain disclosed a high minimum inhibitory concentration of Cefazolin when a large inoculum was used, as well as rapid and complete Cefazolin degradation, which was associated with regrowth in a time-kill experiment. DNA sequencing of the β-lactamase gene showed that it was identical to that of the S. aureus type A β-lactamase, known to efficiently inactivate Cefazolin. A word of caution is given regarding the use of this antibiotic for treatment of endocarditis caused by this type of S. aureus isolate.
Kristi A. Traugott - One of the best experts on this subject based on the ideXlab platform.
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β lactam therapy for methicillin susceptible staphylococcus aureus bacteremia a comparative review of Cefazolin versus antistaphylococcal penicillins
Pharmacotherapy, 2017Co-Authors: Kelly Echevarria, Kristi A. TraugottAbstract:Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with high morbidity and mortality. Traditionally, antistaphylococcal penicillins (ASPs) have been considered the agents of choice for the treatment of MSSA bacteremia. Vancomycin has been demonstrated to have poorer outcomes in several studies and is only recommended for patients with severe penicillin allergies. Although Cefazolin is considered as an alternative to the ASPs for patients with nonsevere penicillin allergies, Cefazolin offers several pharmacologic advantages over ASPs, such as more convenient dosing regimens, and antimicrobial stewardship programs are increasingly using Cefazolin as the preferential agent for MSSA infections as part of cost-saving initiatives. Concerns about susceptibility to hydrolysis by type A β-lactamases, particularly at high inocula seen in deep-seated infections such as endocarditis; selective pressures from unnecessary gram-negative coverage; and lack of comparative clinical data have precluded recommending Cefazolin as a first-line therapy for MSSA bacteremia. Recent clinical studies, however, have suggested similar clinical efficacy but better tolerability, with lower rates of discontinuation due to adverse drug reactions, of Cefazolin compared with ASPs. Other variables, such as adequate source control (e.g., intravascular catheter removal, debridement, or drainage) and enhanced pharmacodynamics through aggressive Cefazolin dosing, may mitigate the role of Cefazolin inoculum effect and factor into determining improved clinical outcomes. In this review, we highlight the utility of Cefazolin versus ASPs in the treatment of MSSA bacteremia with a focus on clinical efficacy and safety.
Esteban C Nannini - One of the best experts on this subject based on the ideXlab platform.
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in vivo effects of Cefazolin daptomycin and nafcillin in experimental endocarditis with a methicillin susceptible staphylococcus aureus strain showing an inoculum effect against Cefazolin
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Esteban C Nannini, Kavindra V Singh, Barbara E. Murray, Cesar A AriasAbstract:Several reports have implicated the inoculum effect that some strains of type A beta-lactamase (Bla)-producing, methicillin-susceptible Staphylococcus aureus (MSSA) show against Cefazolin as the cause for clinical failures in certain serious deep-seated infections. Here, using a previously reported MSSA strain displaying this phenotype (TX0117), we obtained a Bla-cured derivative (TX0117c) with a combination of novobiocin and high temperature. Both isolates were then used in a rat endocarditis model and treated with Cefazolin, nafcillin, and daptomycin, given to simulate human dosing. Animals were treated for 3 days and either sacrificed at 24 h after the last antibiotic dose (standard group) or left untreated for an additional 3 days (relapse group). With TX0117 in the standard treatment group, daptomycin and nafcillin were both significantly better than Cefazolin in reducing CFU/g of vegetations, achieving mean log10 reductions compared to levels in untreated rats of 7.1, 5.3, and 1.8, respectively (Cefazolin versus daptomycin, P < 0.0001; Cefazolin versus nafcillin, P = 0.005; daptomycin versus nafcillin, P = 0.053). In addition, Cefazolin was significantly more effective in reducing vegetation titers of TX0117c than of TX0117 (mean log10 reduction of 1.4 versus 5.5, respectively; P = 0.0001). Similar results were observed with animals in the relapse group. Thus, these data show that there can be an in vivo consequence of the in vitro inoculum effect that some MSSA strains display against Cefazolin and indicate a specific role for Bla production using a Bla-cured derivative strain against which Cefazolin regained both in vitro and in vivo activity.
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inoculum effect with Cefazolin among clinical isolates of methicillin susceptible staphylococcus aureus frequency and possible cause of Cefazolin treatment failure
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: Esteban C Nannini, Martin E Stryjewski, Agathe Bourgogne, Tom H Rude, Ralph G Corey, Vance G Fowler, Kavindra V Singh, Barbara E. MurrayAbstract:Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A β-lactamase (Bla) have been associated with Cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The Cefazolin MIC90 was 2 μg/ml for a standard inoculum and 32 μg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of ≥16 μg/ml with 107 CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher Cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced Cefazolin failure showed a Cefazolin inoculum effect, while none from the six patients successfully treated with Cefazolin showed an inoculum effect, suggesting an association between these strains and Cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with Cefazolin, a phenomenon that could explain the cases of Cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with Cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.
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relapse of type a β lactamase producing staphylococcus aureus native valve endocarditis during Cefazolin therapy revisiting the issue
Clinical Infectious Diseases, 2003Co-Authors: Esteban C Nannini, Kavindra V Singh, Barbara E. MurrayAbstract:Our experience with a patient with methicillin-susceptible Staphylococcus aureus aortic native valve endocarditis, who had a relapse involving fever and positive blood culture results while receiving Cefazolin, led us to evaluate this organism's ability to hydrolyze Cefazolin at high inocula, a previously well-documented phenomenon. Analysis of the infecting strain disclosed a high minimum inhibitory concentration of Cefazolin when a large inoculum was used, as well as rapid and complete Cefazolin degradation, which was associated with regrowth in a time-kill experiment. DNA sequencing of the β-lactamase gene showed that it was identical to that of the S. aureus type A β-lactamase, known to efficiently inactivate Cefazolin. A word of caution is given regarding the use of this antibiotic for treatment of endocarditis caused by this type of S. aureus isolate.
Marin L Schweizer - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of nafcillin or Cefazolin versus vancomycin in methicillin susceptible staphylococcus aureus bacteremia
BMC Infectious Diseases, 2011Co-Authors: Marin L Schweizer, Jon P Furuno, Anthony D Harris, Kristie J Johnson, Michelle Shardell, Jessina C Mcgregor, Kerri A Thom, Sara E Cosgrove, George SakoulasAbstract:The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics nafcillin and Cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality. This retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received nafcillin, Cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing nafcillin or Cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to nafcillin or Cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin. 267 patients were included; 14% (38/267) received nafcillin or Cefazolin, 51% (135/267) received both vancomycin and either nafcillin or Cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving nafcillin or Cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to nafcillin or Cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin. Receipt of nafcillin or Cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of nafcillin or Cefazolin in the treatment of MSSA bacteremia.
Sandra B Nelson - One of the best experts on this subject based on the ideXlab platform.
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comparative evaluation of the tolerability of Cefazolin and nafcillin for treatment of methicillin susceptible staphylococcus aureus infections in the outpatient setting
Clinical Infectious Diseases, 2014Co-Authors: Ilan Youngster, Erica S Shenoy, David C Hooper, Sandra B NelsonAbstract:Background. Nafcillin and Cefazolin are considered first-line therapy for most infections with methicillin-susceptible Staphylococcus aureus (MSSA), and recent studies have suggested similar clinical efficacy. Limited data are available on the comparative tolerability of these agents. Methods. In this retrospective cohort analysis of patients treated with either nafcillin or Cefazolin for MSSA infection in the outpatient parenteral antimicrobial therapy clinic at Massachusetts General Hospital from 2007 to 2011, the frequency of premature antimicrobial discontinuation (PAD) and drug-emergent events (DEEs) was calculated. Results. Three hundred sixty-six and 119 patients were treated with nafcillin or Cefazolin, respectively. The median anticipated duration of therapy was comparable at 28 (interquartile range [IQR], 16–37) and 29 (IQR, 24–39) days, respectively, for those treated with nafcillin and Cefazolin. Fewer patients completed the prespecified treatment course with nafcillin than with Cefazolin (PAD rate, 33.8% vs 6.7%; P < .0001). The hazard ratio for PAD in the nafcillin vs Cefazolin groups was 2.81 (95% confidence interval [CI], 1.26–3.68). More patients in the nafcillin group developed rash (13.9% vs 4.2%; P = .002), renal dysfunction (11.4% vs 3.3%; P = .006), and liver function abnormalities (8.1% vs 1.6%; P = .01). Overall rates of DEEs per 1000 patient-days were 16.9 (95% CI, 10.4–27.3) and 4.8 (95% CI, 1.1–10.2), respectively. In 9 cases of nafcillin discontinuation, treatment was changed to Cefazolin; all 9 completed treatment with no further observed DEEs. Conclusions. Nafcillin treatment was associated with higher rates of both PAD as well as DEEs compared with Cefazolin treatment. This difference in tolerability, in addition to efficacy and cost, should be considered when decisions for outpatient parenteral MSSA treatment are made.
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tolerability of Cefazolin after immune mediated hypersensitivity reactions to nafcillin in the outpatient setting
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Kimberly G Blumenthal, Ilan Youngster, Erica S Shenoy, Aleena Banerji, Sandra B NelsonAbstract:ABSTRACT The objective of the present study was to assess the safety and tolerability of Cefazolin therapy among patients with methicillin-sensitive Gram-positive bacterial infections who develop non-IgE-mediated hypersensitivity reactions (HSRs) to nafcillin. In this retrospective cohort analysis of the Outpatient Parenteral Antimicrobial Therapy program at the Massachusetts General Hospital from 2007 through 2013, we identified patients switched from nafcillin to Cefazolin after an immune-mediated HSR. We reviewed patient demographics, details about the original HSR, and outcomes after the switch to Cefazolin therapy. HSRs were classified by reaction type and likely mechanism. There were 467 patients treated with nafcillin, of which 60 (12.8%) were switched to Cefazolin during their prescribed course. Of the 60 patients who transitioned to Cefazolin, 17 (28.3%) were switched because of non-IgE-mediated HSRs. HSRs included maculopapular rash ( n = 10), immune-mediated nephritis ( n = 3), isolated eosinophilia ( n = 2), immune-mediated hepatitis ( n = 1), and a serum sickness-like reaction ( n = 1). All but one patient (94.1%) who switched to Cefazolin tolerated the drug with resolution of the HSR and completed their therapy with Cefazolin. No patient experienced worsening of their rash or progressive organ dysfunction. With appropriate monitoring, therapy with Cefazolin after non-IgE-mediated HSRs to nafcillin appears to be safe.