Improving Clinical Outcomes in Patients With Methicillin-Sensitive Staphylococcus aureus Bacteremia and Reported Penicillin Allergy

Abstract

Background: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection. First-line MSSA therapies (nafcillin, oxacillin, cefazolin) are generally avoided in the 10% of patients reporting penicillin (PCN) allergy, but most of these patients are not truly allergic. We used a decision tree with sensitivity analyses to determine the optimal evaluation and treatment for patients with MSSA bacteremia and reported PCN allergy.

Methods: Our model simulates 3 strategies: (1) no allergy evaluation, give vancomycin (Vanc); (2) allergy history-guided treatment: if history excludes anaphylactic features, give cefazolin (Hx-Cefaz); and (3) complete allergy evaluation with history-appropriate PCN skin testing: if skin test negative, give cefazolin (ST-Cefaz). Model outcomes included 12-week MSSA cure, recurrence, and death; allergic reactions including major, minor, and potentially iatrogenic; and adverse drug reactions.

Results: Vanc results in the fewest patients achieving MSSA cure and the highest rate of recurrence (67.3%/14.8% vs 83.4%/9.3% for Hx-Cefaz and 84.5%/8.9% for ST-Cefaz) as well as the greatest frequency of allergic reactions (3.0% vs 2.4% for Hx-Cefaz and 1.7% for ST-Cefaz) and highest rates of adverse drug reactions (5.2% vs 4.6% for Hx-Cefaz and 4.7% for ST-Cefaz). Even in a "best case for Vanc" scenario, Vanc yields the poorest outcomes. ST-Cefaz is preferred to Hx-Cefaz although sensitive to input variations.

Conclusions: Patients with MSSA bacteremia and a reported PCN allergy should have the allergy addressed for optimal treatment. Full allergy evaluation with skin testing seems to be preferred, although more data are needed.

Keywords: Staphylococcus aureus; allergy; decision analysis; penicillin; vancomycin.

Figure 1.

Simplified decision tree for patients with methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia and reported penicillin (PCN) allergy. The decision tree, read from left to right, displays the 12-week course of a patient with MSSA bacteremia and reported PCN allergy. Squares represent decision nodes; circles represent the chance nodes where the probabilities are defined by the input parameters. The tree's 3 prominent branches are the strategies evaluated by the model: (1) no allergy evaluation, give vancomycin (Vanc); (2) allergy history–guided treatment: if history excludes anaphylactic features, give cefazolin (Hx-Cefaz); and (3) complete allergy evaluation with history-appropriate PCN skin testing; if skin test negative, give cefazolin (ST-Cefaz). In each branch, therapy can be altered based on allergic or adverse drug reactions (ADRs); no patient in the tree is treated with >3 drugs in his/her 12-week course. Once a definitive antibiotic course is identified, the patient experiences cure, recurrence, or death, represented by the rightmost part of the figure.

Figure 2.

One-way sensitivity analyses for the composite outcome for patients with methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia and reported penicillin (PCN) allergy, comparing Vanc to Hx-Cefaz (see Figure 1 for decision tree). This tornado diagram summarizes the results of all influential 1-way sensitivity analyses on the composite outcome (cure, +50; recurrence of infection, −20; death, −50; major allergic reactions, −10; minor allergic reactions, −2; adverse drug reactions [ADRs], −6) with the variables examined within the probabilities described on the vertical axis. Each horizontal bar represents the range of expected values generated by varying the related variable across its plausible range, as indicated at opposite ends of each bar. A wide bar indicates that the associated variable has a large potential effect on the composite outcome. The vertical dotted lines represent the expected value of the composite outcome for Vanc (21.3) and Hx-Cefaz (35.9). Because there is no overlap between bars in Vanc and Hx-Cefaz, there is no plausible input parameter change that could result in the Vanc strategy having a higher composite outcome than the Hx-Cefaz strategy. Abbreviations: Hx-Cefaz, allergy history–guided treatment: if history excludes anaphylactic features, give cefazolin; Vanc, no allergy evaluation, give vancomycin.

Figure 3.

Optimal strategy selection in Monte Carlo simulation of 100 000 patients with methicillin-sensitive Staphylococcus aureus bacteremia and reported penicillin allergy using probabilistic sensitivity analysis, comparing Vanc to Hx-Cefaz (see Figure 1 for decision tree). The bars (horizontal axis) display the frequency (vertical axis) with which a strategy is optimal for each clinical outcome defined, allowing variability in all input parameters simultaneously in probabilistic sensitivity analyses. Hx-Cefaz is the optimal choice for all outcomes, except minimizing iatrogenic allergic reactions where the Vanc strategy is preferred. Abbreviations: ADR, adverse drug reaction; Hx-Cefaz, allergy history–guided treatment: if history excludes anaphylactic features, give cefazolin; Vanc, no allergy evaluation, give vancomycin.