Risk prediction for Staphylococcus aureus surgical site infection following cardiothoracic surgery; A secondary analysis of the V710-P003 trial

PLoS One. 2018 Mar 21;13(3):e0193445. doi: 10.1371/journal.pone.0193445. eCollection 2018.

Abstract

Background: Identifying patients undergoing cardiothoracic surgery at high risk of Staphylococcus aureus surgical site infection (SSI) is a prerequisite for implementing effective preventive interventions. The objective of this study was to develop a risk prediction model for S. aureus SSI or bacteremia after cardiothoracic surgery based on pre-operative variables.

Materials/methods: Data from the Merck Phase IIb/III S. aureus vaccine (V710-P003) clinical trial were analyzed. In this randomized placebo-controlled trial, the effect of preoperative vaccination against S. aureus was investigated in patients undergoing cardiothoracic surgery. The primary outcome was deep/superficial S. aureus SSI or S. aureus bacteremia through day 90 after surgery. Performance, calibration, and discrimination of the final model were assessed.

Results: Overall 164 out of 7,647 included patients (2.1%) developed S. aureus infection (149 SSI, 15 bacteremia, 28 both). Independent risk factors for developing the primary outcome were pre-operative colonization with S. aureus (OR 3.08, 95% confidence interval [CI] 2.23-4.22), diabetes mellitus (OR 1.87, 95% CI 1.34-2.60), BMI (OR 1.02 per kg/m2, 95% CI 0.99-1.05), and CABG (OR 2.67, 95% CI 1.91-3.78). Although vaccination had a significant (albeit modest) protective effect, it was omitted from the model because its addition did not significantly change the coefficients of the final model and V710-vaccine development has been discontinued due to insufficient efficacy. The final prediction model had moderate discriminative accuracy (AUC-value, 0.72).

Conclusion: Pre-operative S. aureus colonization status, diabetes mellitus, BMI, and type of surgical procedure moderately predicted the risk of S. aureus SSI and/or bacteremia among patients undergoing cardiothoracic surgery.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Surgical Procedures / adverse effects*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Staphylococcal Infections / diagnosis*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / prevention & control
  • Staphylococcal Vaccines / therapeutic use
  • Staphylococcus aureus / pathogenicity*
  • Surgical Wound Infection / diagnosis*
  • Surgical Wound Infection / microbiology
  • Surgical Wound Infection / prevention & control
  • Vaccination

Substances

  • Staphylococcal Vaccines
  • V710 vaccine

Grants and funding

Commercial organizations participating in this project are Merck & Co., Inc., Kenilworth, NJ, USA; AstraZeneca, LP; MedImmune. This research project has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115523 resources which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. The commercial organizations AstraZeneca and MedImmune partly funded the subsidies that came from IMI. This project used data collected earlier in a randomized-controlled study sponsored and funded by Merck & Co. Inc., Kenilworth, NJ, USA. Merck & Co., provided salary support for MDN and grant support for VF, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. The funder (IMI) provided support in the form of salaries for authors KrO, MW, SH, MB, FP, JK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. The funder (AstraZeneca) provided support in the form of salaries for authors FS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. The funder (MedImmune) provided support in the form of salaries for authors HJ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.