Are all beta-lactams similarly effective in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia?

Abstract

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.

Is Cefazolin Inferior to Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia?

“…First, we could not find any difference in clinical efficacy between cefazolin and nafcillin for the treatment of MSSA bacteremia, although few endocarditis cases were included in the study. This finding is compatible with recently reported retrospective clinical study data (11,13) and with an earlier experimental study that showed that cefazolin was as effective as nafcillin in reducing bacterial titers in vegetations using a rabbit endocarditis model (3). Second, treatment failure was significantly associated with the site of MSSA infection in our study, especially for endocarditis and pneumonia, rather than with cefazolin use.…”

“…To our knowledge, there have also been no prospective studies that have compared cefazolin with antistaphylococcal penicillin for the treatment of MSSA bacteremia. A recent retrospective study suggested that there was no significant difference between cefazolin and cloxacillin treatments of MSSA bacteremia (11). However, the data could be skewed because physicians tend to use antistaphylococcal penicillin for more serious infections and cefazolin for less serious infections.…”

2015 ESC Guidelines for the management of infective endocarditis

“…4. Podawanie kloksacyliny/cefazoliny w leczeniu empirycznym IZW/bakteriemii spowodowanych MSSA wiąże się z niższym współczynnikiem śmiertelności w porównaniu z innymi b-laktamami, w tym amoksycyliną z kwasem klawulonowym i ampicyliną z sulbaktamem [203] oraz wankomycyną [159]. Sugerowane schematy leczenia empirycznego u pacjentów w ostrym stadium choroby podsumowano w tabeli 20.…”

Predictors of Mortality in Staphylococcus aureus Bacteremia

“…No randomized control trial comparing these agents has been performed to definitively answer questions regarding relative efficacies. A single-center cohort study comparing cloxacillin (n ϭ 281) with cefazolin (n ϭ 71) for MSSA-B infections detected no mortality or outcome difference between the two agents (222). Baseline patient characteristics differed significantly between the two groups, and this probably influenced the clinicians' initial antibiotic selections, thus limiting possible conclusions.…”

“…For the treatment of MSSA-B infections, the 30-day mortality rate was higher for patients receiving empirical treatment (i.e., van Hal et al commenced within the first 48 h) with a third-generation cephalosporin (OR, 2.24; 95% CI, 1.23 to 4.08; P ϭ 0.008) or ␤-lactam-␤-lactamase inhibitor combinations (OR, 2.68; 95% CI, 1.23 to 5.85; P ϭ 0.013) than for patients receiving cloxacillin or cefazolin (222). In that same study, no conclusions could be made for definitive MSSA-B therapy (given from days 3 to 9, i.e., the first week after the receipt of blood culture results), as the numbers of patients treated with broad-spectrum ␤-lactam agents were too small compared to the numbers of patients treated with cloxacillin or cefazolin.…”