Increasing Rates of Penicillin Sensitivity in Staphylococcus aureus

LETTER

Recent publications have reported on the rise of penicillin-sensitive Staphylococcus aureus (PSSA). This trend has now been observed on several continents (1) and has been shown to involve bloodstream infections and other serious infections (2). This increase in the incidence of PSSA infections has also been mirrored by a decrease in methicillin-resistant S. aureus (MRSA) infection rates (3), which raises two important questions. First, over what time period has PSSA been reemerging, and perhaps more importantly, how can we capitalize on this susceptibility renaissance?

To address these knowledge gaps, we evaluated all unique adult cases of methicillin-sensitive Staphylococcus aureus bacteremia at the McGill University Health Centre (832 beds) (Montreal, Quebec, Canada) from January 2006 to April 2016 and obtained penicillin MICs using the Vitek 2 AST-gp67 cards (bioMérieux, France). Susceptibility was confirmed by using the combination of Vitek 2-estimated MIC with a negative nitrocefin-based chromogenic assay (4). There were 682 unique methicillin-sensitive S. aureus (MSSA) isolates and 182 unique PSSA isolates. Quarterly mean MICs during this period demonstrate that penicillin MICs have been decreasing over a decade within methicillin-sensitive strains (Fig. 1).

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FIG 1

(Top) Quarterly mean MICs for methicillin-sensitive Staphylococcus aureus (including penicillin-sensitive strains). P = 0.007 for temporal trend. (Bottom) Quarterly mean MICs for penicillin-sensitive Staphylococcus aureus alone. P = 0.367 for temporal trend.

The reemergence of penicillin susceptibility has been occurring for more than 12 years in North America, and an increasing proportion of MSSA isolates now show penicillin susceptibility. Nonetheless, the optimal treatment for this phenotype remains unknown, and clinical practice has not been altered by this change in susceptibility landscape. Penicillin therapy offers advantages compared to other first-line therapies. First, for susceptible strains, penicillin's time above MIC is greater than for other antibiotics, and it targets a narrower spectrum than first-generation cephalosporins do. Second, the mechanism of methicillin resistance (through the mecC gene and staphylococcal cassette chromosome mec element [SCCmec]) is less likely to be selected by use of penicillin (5), potentially resulting in decreased selection pressure for methicillin resistance.

Despite these advantages, there remains skepticism toward the use of penicillin for the treatment of serious S. aureus infections, owing to the possibility of a clinical laboratory's inability to detect penicillinase-producing strains. The chromogenic beta-lactamase test is a rapid test to detect blaZ-carrying S. aureus; however, it has poor sensitivity compared to PCR methods (4). Nonetheless, when performed in combination with automated determination of the MIC, its performance improves substantially (4). While also imperfect, penicillin disc diffusion tests are currently recommended by both North American (10-U penicillin discs) and European (1-U penicillin discs) guidelines. The clinical significance of phenotypic-test-negative, PCR-positive isolates remains to be determined.

Inappropriate antibiotic use has led to an alarming prevalence of drug-resistant organisms, but the reemergence of PSSA offers a novel antimicrobial stewardship opportunity. Given these new data, a trial comparing penicillin to other first-line options in the treatment of PSSA infections seems warranted. If molecular and phenotypic tests were performed on all isolates, this would also help determine the preferred method for detecting clinically relevant penicillin susceptibility among S. aureus isolates. If such a change in the resistance landscape of one of the most commonly isolated human pathogen does not change our practice, then what will?