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      The Safety and Economic Impact of Cefazolin versus Nafcillin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections

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          Abstract

          Introduction

          Anti-staphylococcal penicillins are generally accepted as first-line therapy for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, but their use may be limited by interstitial nephritis and acute kidney injury. Alternatives include first-generation cephalosporins including cefazolin.

          Methods

          We conducted a retrospective cohort study to compare adverse effects and clinical outcomes among patients with MSSA bacteremia treated with cefazolin or nafcillin. The primary endpoint was acute kidney injury (AKI), defined as a 0.3 mg/dL or 50% increase from baseline.

          Results

          Incidence of AKI was 27/82 (33%) versus 9/68 (13%) ( p = 0.007) in the nafcillin and cefazolin arms, respectively. After adjusting for endocarditis and intensive care unit admission in multivariate logistic regression, nafcillin was an independent predictor of AKI [adj odds ratio (OR) = 2.74; 95% (CI) 1.1–6.6]. Patients who experienced AKI were more likely to have a prolonged intensive care unit stay.

          Conclusion

          Risk of nephrotoxicity is increased with nafcillin compared with cefazolin. Cefazolin should considered as a safer alternative to nafcillin for select patients with MSSA bacteremia.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s40121-017-0148-z) contains supplementary material, which is available to authorized users.

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          Outcome of vancomycin treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia.

          Myoung-don Oh, Hai-Joong Kim, Hong Bin Kim … (2007)
          Limited data on the clinical outcome of vancomycin treatment compared with that of beta-lactam treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B) are available. We used different and complementary approaches: (i) a retrospective cohort study using a propensity score to adjust for confounding by treatment assignment and (ii) a matched case-control study. Of all patients with S. aureus bacteremia (SAB) in two university-affiliated hospitals over a 7-year period, 294 patients with MSSA-B were enrolled in the cohort study. The cases for the case-control study were defined as patients who received vancomycin treatment for MSSA-B; the controls, who were patients that received beta-lactam treatment for MSSA-B, were selected at a 1:2 (case:control) ratio according to the objective matching scoring system and the propensity score system. In the cohort study, SAB-related mortality in patients with vancomycin treatment (37%, 10/27) was significantly higher than that in those with beta-lactam treatment (18%, 47/267) (P = 0.02). In addition, multivariate analysis revealed that vancomycin treatment was associated with SAB-related mortality when independent predictors for SAB-related mortality and propensity score were considered (adjusted odds ratio of 3.3, 95% confidence interval of 1.2 to 9.5). In the case-control study using the objective matching scoring system and the propensity score system, SAB-related mortality in case patients was 37% (10/27) and in control patients 11% (6/54) (P < 0.01). Our data suggest that vancomycin is inferior to beta-lactam in the treatment of MSSA-B.
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            Outcome and attributable mortality in critically Ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

            Eric Hoste, Koenraad H D K Vandewoude, F Colardyn … (2002)
            Staphylococcus aureus bacteremia carries high mortality rates. The clinical impact of methicillin resistance remains controversial: outcome comparisons between patients with bacteremia involving methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) S aureus are difficult to perform because of important differences in severity of illness. A retrospective cohort analysis and 2 independent case-control analyses were performed to determine and compare outcomes and attributable mortality rates of MSSA (n = 38) and MRSA bacteremia (n = 47) in critically ill patients. For the case-control studies, matching (1:2 ratio) was based on the APACHE (Acute Physiology and Chronic Health Evaluation) II classification: APACHE II score (+/-1 point) and diagnostic category. Patients with MRSA bacteremia had more acute renal failure and hemodynamic instability than patients with MSSA bacteremia. They had a longer intensive care unit stay and ventilator dependency. Patients with MRSA bacteremia had a higher 30-day mortality rate (53.2% vs 18.4%) and in-hospital mortality rate (63.8% vs 23.7%) (P<.05). Multivariate survival analysis demonstrated acute renal failure, length of mechanical ventilation, age, and methicillin resistance to be independently associated with mortality (P<.05). The attributable mortality rate for MSSA bacteremia was 1.3%: mortality rates for cases and controls were respectively 23.7% and 22.4% (P =.94). The attributable mortality rate for MRSA bacteremia was 23.4%: mortality rates for cases and controls were respectively 63.8% and 40.4% (P =.02). The difference (22.1%) between both attributable mortality rates was significant (95% confidence interval, 8.8%-35.3%). In critically ill patients, after accurate adjustment for disease severity and acute illness, we found MRSA bacteremia to have a higher attributable mortality than MSSA bacteremia.
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              Are all beta-lactams similarly effective in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia?

              Sarah M Paul, N Zemer-Wassercug, O Talker … (2011)
              Methicillin-sensitive Staphylococcus aureus (MSSA) is susceptible to many beta-lactams. We compared cloxacillin and cefazolin, the first-line recommended antibiotics, and other beta-lactams in the treatment of MSSA bacteraemia. This was a retrospective cohort study. Included were adult patients with clinically-significant MSSA bacteraemia treated with a beta-lactam that was started within 48 h after blood cultures were taken. We separated between empirical treatment administered to the patient before receipt of final blood culture results and definitive treatment administered thereafter. Univariate and multivariable analyses for 30-day (empirical treatment) and 90-day (definitive treatment) mortality were conducted, including the type of beta-lactam administered to the patient. Five-hundred and forty-one patients were included for the analysis of empirical treatment and 498 patients alive at 7 days were evaluable for definitive treatment. Empirical treatment with cloxacillin or cefazolin (n = 131) was associated with lower 30-day mortality as compared with cefuroxime (n = 98, p 0.058), ceftriaxone or cefotaxime (n = 194, p 0.008) and beta-lactam-beta-lactamase combinations (n = 61, p 0.013), with adjusted odds ratios (OR) for death ranging from 1.98 to 2.68. Definitive treatment with cefazolin (n = 72) was not significantly different from cloxacillin (n = 281); adjusted OR for 90-day mortality 0.91 (95% confidence interval 0.47-1.77). Treatment with cefazolin both in the empirical and definitive periods was not significantly different from cloxacillin; adjusted OR 0.81 (95% confidence interval 0.18-3.62). Treatment of MSSA bacteraemia with cefazolin is not significantly different from treatment with cloxacillin, while treatment with other beta-lactams, including second and third generation cephalosporins, might be associated with higher mortality.
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                Author and article information

                Contributors
                Susan L. Davis: sldavis@wayne.edu
                Journal
                Journal ID (nlm-ta): Infect Dis Ther
                Journal ID (iso-abbrev): Infect Dis Ther
                Title: Infectious Diseases and Therapy
                Publisher: Springer Healthcare (Cheshire )
                ISSN (Print): 2193-8229
                ISSN (Electronic): 2193-6382
                Publication date (Electronic): 6 March 2017
                Publication date PMC-release: 6 March 2017
                Publication date (Print): June 2017
                Volume: 6
                Issue: 2
                Pages: 225-231
                Affiliations
                [1 ]ISNI 0000 0001 2160 8953, GRID grid.413103.4, , Henry Ford Hospital, ; Detroit, MI USA
                [2 ]ISNI 0000 0001 1456 7807, GRID grid.254444.7, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, , Wayne State University, ; Detroit, MI USA
                Article
                Publisher ID: 148
                DOI: 10.1007/s40121-017-0148-z
                PMC ID: 5446361
                PubMed ID: 28265972
                SO-VID: cd66bc1c-a9dc-41b8-8adc-b316c230d754
                Copyright © © The Author(s) 2017
                History
                Date received : 22 November 2016
                Categories
                Subject: Original Research
                Custom metadata
                issue-copyright-statement © Springer Healthcare 2017

                Keywords: cost-effective,methicillin-susceptible staphylococcus aureus (mssa),nephrotoxicity
                Data availability:
                Keywords: cost-effective, methicillin-susceptible staphylococcus aureus (mssa), nephrotoxicity

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