Discussion

In this study, we found that most of the 80 studied hepatobiliary SSIs demonstrated organisms nonsusceptible to standard prophylaxis regimens but that receipt of prophylaxis with either enterococcal or pseudomonal spectrum-of-activity was not associated with reduced risk of SSI. These findings regarding the microbiology of hepatobiliary SSI agree with studies that have demonstrated resistance rates of >50% in culture isolates implicated in infections after hepatobiliary procedures.Reference Fong, McMillan and Marchegiani ^{9 ,} Reference Gavazzi, Ridolfi and Capretti ¹⁰

While most SSI cases demonstrated an organism nonsusceptible to the prophylaxis received, we found only patient and procedure-specific factors to be predictive of SSI, rather than antimicrobial spectrum of activity. Patient-specific predictors of SSI included male gender, which has been identified as a risk factor for SSI after hepatobiliary procedures previously.Reference Morikane ¹¹ Having a listed β-lactam allergy was also predictive of SSI. Documentation of a β-lactam allergy has been associated with worse outcomes in hospitalized patients,Reference Charneski, Deshpande and Smith ^{12 ,} Reference Macy and Contreras ¹³ but conclusions regarding its association with the development of SSI are mixed.Reference Trinh, Chen, Sexton and Anderson ^{14 ,} Reference Tan, Springer, Ruder, Ruffolo and Chen ¹⁵ A recent large retrospective cohort investigation found that having a listed penicillin allergy resulted in a 50% increased odds of SSI, which was largely attributable to the receipt of second-line perioperative regimens.Reference Blumenthal, Ryan, Li, Lee, Kuhlen and Shenoy ¹⁶ Indeed, the increased risk of SSI in our population may also be attributable to the receipt of nonstandard prophylaxis regimens, as 32% of patients with a β-lactam allergy received a nonstandard regimen, as opposed to 11% without a listed allergy. This finding emphasizes the importance of obtaining an accurate allergy history and considering the use of alternate agents only when patients report a history of an IgE-mediated or severe reaction such as Stevens-Johnson syndrome/toxic epidermal necrolysis to β-lactams.

Procedure-specific predictors of SSI included undergoing an open procedure and procedure duration >4 hours. These findings correlate with other studies that have demonstrated an association between open procedure and increased procedure duration and the development of an SSI in hepatobiliary procedures.Reference Morikane ^{11 ,} Reference Mu, Edwards, Horan, Berrios-Torres and Fridkin ¹⁷ These findings may suggest the importance of intraoperative re-dosing of antimicrobial agents with relatively short half-lives in procedures of prolonged duration.

Providers may consider the administration of broad-spectrum or extended-duration prophylaxis to be potentially advantageous in reducing SSI.Reference Donald, Sunjaya and Lu ^{6 ,} Reference Bull, Worth, Spelman and Richards ¹⁸ We did not find this to be the case, however, as receipt of antimicrobials for >24 hours and receipt of a regimen with expanded gram-negative or anti-enterococcal coverage was not associated with reduced risk of SSI. These results suggest that, in hepatobiliary procedures, patient and procedure specific factors are more associated with the outcome of SSI rather than the spectrum or duration of prophylaxis received.

The strengths of our study include the use of a nationally recognized NHSN definition to select cases and controls. Given the robustness of our electronic medical record, missing data was minimal. Indeed, 98% of cases had accompanying culture results. In addition, risk factors traditionally associated with SSI in prior studies were found to be predictive of SSI in our cohort suggesting external validity of our findings.

The limitations of this study include the retrospective design, which prohibits randomization and, therefore, introduces the possibility of unmeasured confounding. The ascertainment process of cases and controls created a significant difference between the groups in baseline comorbidities and procedure characteristics. We attempted to correct both limitations by performing a regression analysis to control for factors believed to be most associated with SSI. We did not directly assess the timing of intraoperative re-dosing of prophylaxis. However, additional doses were received at similar frequencies in both case and control patient procedures, making differences in re-dosing an unlikely confounder in the relationship between antimicrobial and SSI. While we did not find receipt of a regimen with expanded gram-negative or enterococcal activity to be protective of SSI, we cannot exclude the possibility that this is a false-negative finding due to a lack of power, as the retrospective nature of our design inherently limited our sample size. It is a reasonable hypothesis that specific patient groups, such as those with a history of MDRO, or certain high-risk procedures may benefit from broad-spectrum antimicrobial prophylaxis, but this could not be assessed due to limited sample size. This should be the focus of future investigation.

In conclusion, most hepatobiliary SSI cases at our institution demonstrated pathogens nonsusceptible to standard prophylaxis regimens. Our analysis suggests that patient-specific and procedure-specific risk factors may be more predictive of SSI than the spectrum or duration of prophylaxis administered. Practitioners should strive to obtain an accurate allergy history, as the documentation of a β-lactam allergy was predictive of SSI in this cohort and was potentially mediated by receipt of a non-β-lactam prophylaxis regimen.