RESUMEN
PURPOSE: To compare the effectiveness and safety of cefazolin versus cloxacillin for the treatment of infective endocarditis (IE) due to methicillin-sensitive Staphylococci (MSS). METHODS: Data were retrospectively collected on patients treated for a definite MSS endocarditis who received cefazolin or cloxacillin for at least 10 consecutive days in six French hospitals between January-1 2014 and December-31 2020. The primary endpoint was treatment failure defined as a composite of death within 90 days of starting antibiotherapy, or embolic event during antibiotherapy, or relapse of IE within 90 days of stopping antibiotherapy. We used Cox regression adjusted for the inverse probability of treatment weighting of receiving cefazolin. RESULTS: 192 patients were included (median age 67.8 years). IE was caused by S.aureus in 175 (91.1%) and by coagulase-negative staphylococci in 17 (8.9%). Ninety-four patients (48.9%) received cefazolin, and 98 (51%) received cloxacillin. 34 patients (34.7%) with cefazolin and 26 (27.7%) with cloxacillin met the composite primary endpoint, with no significant differences between groups (adjusted HR = 1.13, 95% CI 0.63 to 2.03). There were no significant differences in secondary efficacy endpoints or biological safety events. CONCLUSION: The effectiveness of cefazolin did not significantly differ from cloxacillin for the treatment of MSS endocarditis.
Asunto(s)
Antibacterianos , Cefazolina , Cloxacilina , Endocarditis Bacteriana , Infecciones Estafilocócicas , Humanos , Cefazolina/uso terapéutico , Cloxacilina/uso terapéutico , Cloxacilina/efectos adversos , Anciano , Masculino , Femenino , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Estudios Retrospectivos , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/mortalidad , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad , Persona de Mediana Edad , Resultado del Tratamiento , Staphylococcus/efectos de los fármacos , Puntaje de Propensión , Francia , Anciano de 80 o más AñosRESUMEN
OBJECTIVES: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). METHODS: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. RESULTS: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. CONCLUSION: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective.
Asunto(s)
Bacteriemia , Endocarditis Bacteriana , Insuficiencia Renal , Infecciones Estafilocócicas , Humanos , Cefazolina/efectos adversos , Estudios Prospectivos , Estudios Retrospectivos , Infecciones Estafilocócicas/tratamiento farmacológico , Resultado del Tratamiento , Bacteriemia/tratamiento farmacológico , Antibacterianos/efectos adversos , Cloxacilina/efectos adversos , Endocarditis Bacteriana/tratamiento farmacológico , Staphylococcus aureus , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/tratamiento farmacológico , RecurrenciaRESUMEN
Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 µg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 µg/mL compared to strains with MIC of oxacillin < 1 µg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 µg/mL and 176 isolates with an MIC < 1 µg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 µg/mL and an MIC < 1 µg/mL (16.4% versus 15.9%, P = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P = 0.86) or cefazolin (10.3% versus 11.9%, P = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 µg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.
Asunto(s)
Antibacterianos , Bacteriemia , Cefazolina , Staphylococcus aureus Resistente a Meticilina , Oxacilina , Infecciones Estafilocócicas , Oxacilina/efectos adversos , Oxacilina/farmacología , Oxacilina/uso terapéutico , Cefazolina/efectos adversos , Cefazolina/farmacología , Cefazolina/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Bacteriemia/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
OBJECTIVES: We compared the effectiveness of cefazolin and cloxacillin as definitive antibiotic therapy for methicillin-susceptible Staphylococcus aureus (MSSA) spinal epidural abscess (SEA). METHODS: This retrospective cohort study included patients with MSSA SEA from two academic hospitals in Hamilton, Ontario, Canada, between 2014 and 2020. Patients treated with cefazolin were compared to those treated with cloxacillin. Co-primary outcomes included 90-day mortality, antibiotic failure, adverse reactions and recurrence. Inverse probability of treatment weighting using propensity scores was used to balance important prognostic factors and to estimate an adjusted risk difference. RESULTS: Of 98 patients with MSSA SEA, 50 and 48 patients were treated with cefazolin and cloxacillin, respectively. Mortality at 90 days was 8% and 13% in the cefazolin and cloxacillin groups, respectively (P = 0.52). The antibiotic failure rate was 12% and 19% in the cefazolin and cloxacillin groups, respectively (P = 0.41). The serious adverse reactions rate was 0% and 4% in the cefazolin and cloxacillin groups, respectively (P = 0.24). The recurrence rate was 2% and 8% in the cefazolin and cloxacillin groups, respectively (P = 0.20). The adjusted risk difference for mortality at 90 days was -1% [95% confidence interval (CI) -10% to 8%] favouring cefazolin. The adjusted risk differences for antibiotic failure, adverse reactions and recurrence were 1% (95% CI -12% to 14%), -5% (95% CI -11% to 2%) and -18% (-36% to -1%) respectively. CONCLUSION: Cefazolin is likely as effective as an antistaphylococcal penicillin and may be considered as a first-line treatment for MSSA SEA.
Asunto(s)
Antibacterianos/uso terapéutico , Cefazolina/uso terapéutico , Cloxacilina/uso terapéutico , Absceso Epidural/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Anciano , Antibacterianos/efectos adversos , Canadá , Cefazolina/efectos adversos , Cloxacilina/efectos adversos , Absceso Epidural/microbiología , Femenino , Humanos , Masculino , Meticilina/farmacología , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Infecciones Estafilocócicas/mortalidad , Resultado del TratamientoRESUMEN
OBJECTIVES: Current guidelines recommend cefazolin as an alternative to antistaphylococcal penicillins (ASPs) in methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis despite the lack of comparative study. The objective of this study was to evaluate the comparative outcomes of cefazolin vs. ASPs in MSSA infective endocarditis. METHODS: This was a retrospective analysis of an observational multicentre cohort study using prospectively collected data from patients with MSSA endocarditis confirmed by endocarditis team and treated either with cefazolin or ASPs between July 2013 and December 2018. Patients were excluded if they received both treatments. The primary outcome was 90-day all-cause mortality. RESULTS: Of 210 patients included, 53 patients (25.2%) received cefazolin and 157 (74.8%) received ASPs. The overall 90-day mortality rate was 27.6% (58/210 patients), 24.5% (13/53) in the cefazolin group vs. 28.7% (45/157) in the ASP group (p 0.561). Premature antimicrobial discontinuation due to adverse events occurred less frequently with cefazolin than with ASPs (0/53 vs. 13/157 patients; p 0.042). In multivariate analysis, there was no difference in 90-day mortality between cefazolin and ASPs (adjusted odds ratio (aOR), 1.2; 95% confidence interval (CI), 0.49-2.91; p 0.681), while age (aOR, 1.06; 95% CI, 1.03-1.09; p < 0.001), Charlson comorbidity index (aOR, 1.18; 95% CI, 1.02-1.36 p 0.023), cerebral embolism (aOR, 2.83; 95% CI, 1.33-6.14; p 0.007) and intensive care unit admission (aOR, 4.16; 95% CI, 1.89-9.59; p 0.001) were factors significantly associated with higher mortality. CONCLUSIONS: Cefazolin seems to be a possible alternative to ASPs in MSSA endocarditis. More studies are needed to confirm these results and determine which treatment should be recommended as first-line therapy.
Asunto(s)
Antibacterianos/uso terapéutico , Cefazolina/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Penicilinas/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Anciano , Endocarditis Bacteriana/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Infecciones Estafilocócicas/microbiología , Resultado del TratamientoRESUMEN
BACKGROUND: Studies have shown that the prognosis of the treatment of methicillin-susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment with ß-lactam. However, there are only few studies comparing treatment with antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin, with that of glycopeptides as a definitive therapy for MSSA bacteremia. METHODS: Patients with MSSA bacteremia recruited from a tertiary referral hospital were enrolled in this retrospective cohort study. Demographic characteristics, laboratory data, and clinical outcome of the treatment were compared between a group receiving nafcillin and a group receiving glycopeptides. RESULTS: A total of 188 patients with MSSA bacteremia were included in this study. The glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p < 0.001) and proportion of healthcare-associated infections (47.3 vs. 72.2%, p < 0.001) compared to the nafcillin group. The ratio of skin and soft tissue infections (30.0 vs. 16.7%, p = 0.037) and bone and joint infections (17.8 vs. 6.3%, p = 0.022), as well as levels of C-reactive protein (139.60 vs. 107.61 mg/dL, p = 0.022) were higher in the nafcillin group. All-cause 28-day mortality was significantly high in the glycopeptide group (7.7 vs. 20.6%, p = 0.013). CONCLUSION: In patients with MSSA bacteremia, all-cause 28-day mortality rate was higher in a group treated with glycopeptides than in a group treated with nafcillin. Therefore, the use of nafcillin should be considered as a definitive therapy for MSSA bacteremia.
Asunto(s)
Antibacterianos/uso terapéutico , Glicopéptidos/uso terapéutico , Nafcilina/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Adulto , Anciano , Antibacterianos/farmacología , Bacteriemia/tratamiento farmacológico , Proteína C-Reactiva/análisis , Estudios de Cohortes , Infección Hospitalaria/complicaciones , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Masculino , Meticilina/farmacología , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Centros de Atención TerciariaRESUMEN
Staphylococcus aureus bacteraemia (SAB) is a frequent and deadly disease. Given the lack of a randomized trial, optimal first-line antibiotic treatment is still debated. Our aim was to identify prognostic factors in SAB patients and to analyse the impact of first-line antibiotics. The VIRSTA prospective cohort study was conducted in eight tertiary care centres in France. Consecutive incident adults in whom a blood culture drawn in participating centres grew S. aureus between April 2009 and October 2011 were prospectively followed for 12 weeks. Factors associated with 12-week case-fatality were identified by multivariate logistic regression. We enrolled 2091 patients and analysed survival in 1972 (median age 67.8 years, interquartile range 55.5-78.9; females 692/1972, 35.1%). SAB was nosocomial or healthcare-related in 1372/1972 (69.6%) of cases and the primary focus was unknown in 414/1972 (21.0%) of cases. Week 12 case-fatality rate was 671/1972 (34.0%). The main independent prognostic factors on multivariate analysis were age (adjusted OR by 10-year increment 1.56; 95% CI 1.44-1.69), septic shock (OR 5.11; 95% CI 3.84-6.80), metastatic cancer (OR 4.28; 95% CI 2.88-6.38), and unknown primary focus (OR 2.62; 95% CI 2.02-3.41). In the 1538 patients with methicillin-sensitive S. aureus (MSSA) bacteraemia, first-line empiric antistaphylococcal penicillins (OR 0.40; 95% CI 0.17-0.95) and vancomycin (OR 0.37; 95% CI 0.17-0.83), alone or combined with an aminoglycoside, were associated with better outcome compared with other antibiotics. There are few modifiable prognostic factors for SAB. Initiating empiric antibiotics with antistaphylococcal penicillins or vancomycin may be associated with better outcome in MSSA bacteraemia.