Carriage of ESBL-PE May Increase the Risk of Colorectal Surgical Site Infections

Although the 2013 Infectious Diseases Society of America¹ and 2017 US Centers for Disease Control and Prevention (CDC) guidelines² recommend a combination of oral antimicrobials, mechanical bowel preparation (MBP), and intravenous (IV) cephalosporin and metronidazole for colorectal surgical prophylaxis, screening for extended-spectrum β-lactamase—producing Enterobacteriaceae (ESBL-PE) in high-risk patients and coverage are not included. Despite the high rates of morbidity and mortality with ESBL-PE infections, little is known about the prevalence of ESBL-PE fecal carriage and its effect on rates of surgical site infections (SSIs) after colorectal surgery.^3-6

Dubinsky-Pertov et al conducted a prospective multicenter cohort study comparing SSI rates following elective colorectal surgery in ESBL-PE carriers to noncarriers when given standard cephalosporin plus metronidazole prophylaxis. They excluded appendectomies, minor ano-rectal procedures, and documented infections (eg, diverticulitis and peritonitis).⁷ Extended-spectrum β-lactamase (ESBL) carriers were identified via positive rectal swab taken 14 days to 1 hour before surgery, with growth on blood agar for species identification and ESBL production confirmation via Vitek 2 and double discs diffusion, according to Clinical & Laboratory Standards Institute guidelines. Data were collected on patient and surgery characteristics and SSI outcomes.

The primary endpoint was SSI diagnosis within 30 days of surgery, and secondary endpoints were type of SSI and causative organisms. For all analyses, a mixed-effects model with the study site as a random effects variable was used, and likelihood ratio to select confounders and bivariate mixed-effects logistic regression was applied for ESBL-pathogen analysis.

Among the 3 international study sites, differences were seen in carriage rates (P<.0001), indication for surgery (P<.001), and mechanical bowel preparation (P<.0001). Carriers were more likely to have cardiovascular disease (P = .01) and previous colorectal surgery (P = .03) and less likely to have had rectal resection (P = .03) or drains (P = .02). The National Nosocomial Infections Surveillance (NNIS) risk score did not differ significantly between groups (P = .20).

Of the 3600 patients screened, 222 ESBL-PE carriers and 440 noncarriers met inclusion. The overall SSI incidence was 15.7%, with rates more than double in ESBL-PE carriers (24.8%) than noncarriers (11.1%; P<.001). Carriers had higher rates of deep SSIs (odds ratio [OR], 2.25; 95% CI, 1.27-3.99) and more ESBL-PE SSIs (7.2%) than noncarriers (1.6%; OR, 4.23; 95% CI, 1.70-10.56).

Although the trial was not blinded, and the carrier group was not randomized, these findings indicate a potentially higher failure rate when standard prophylactic antimicrobials are given to carriers of ESBL-PE. Because ESBL rectal swab cultures have a reported sensitivity of 80%,^5,7 some underdetection may have underestimated the effect of carriage on SSI incidence. The results were pooled across the 3 sites, and so it is unclear how SSI rates differ across various prevalence ranges. In addition, outcomes for the different classes of cephalosporins and types of MBP were not disclosed.

Further research is needed to assess the diagnostic accuracy of gram-negative multidrug-resistant organism screening, including detection of resistance genes, the effect of other extended-spectrum β-lactamases, particularly Ambler class C presence on ESBL detection, non—β-lactamase resistance mechanisms, and prevalence thresholds that will require routine preoperative screening and targeted antimicrobial prophylaxis.

At this time, evidence is limited around the clinical utility of rectal swab screening for predicting SSIs. However, this study highlights the need for better understanding of gram-negative surveillance screening tools and their prediction performance (ie, sensitivity, specificity, positive and negative predictive values, negative and positive likelihood ratios, diagnostic odd ratios). It is unknown whether screening would be of more value than gram-negative multidrug-resistant organism risk assessment (eg, history or colonization of gram-negative multidrug-resistant organisms, recent use of broad-spectrum antimicrobials, origin of infection and comorbidities) and whether any of these should be included in future NNIS scoring.

Although a recent report by the CDC described a 7% national decrease in colorectal SSIs from 2015 to 2016, there is large heterogeneity in reporting (microbiology laboratory interpretation and SSI surveillance reported to National Healthcare Safety Network), and the prevalence rate of ESBL SSIs with current antibiotic prophylaxis guidelines remains unclear ^8-10.

The investigators describe a second phase trial R-GNOSIS to determine benefit of targeted pre-surgical prophylaxis with carbapenems for ESBL-PE carriers versus induction of carbapenem resistance.⁷ Until there are more robust clinical trials, validated screening or risk stratification tools with supporting consensus guidelines, antimicrobial stewardship and infection prevention teams should review their institutional SSI outcomes and report any gram-negative multidrug-resistant organism outbreaks to their locate state authority. Providers should assess multidrug-resistant organism risk factors prior to surgery and consult with infectious disease experts for guidance on antimicrobial prophylaxis.

References:

1. Bratzler DW, Dellinger EP, Olsen KM, et al; American Society of Health-System Pharmacists; Infectious Disease Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283. doi: 10.2146/ajhp120568.
2. Berríos-Torres SI, Umscheid CA, Bratzler DW, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg. 2017;152(8):784—791. doi:10.1001/jamasurg.2017.0904.
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4. Leistner R, Schröder C, Geffers C, Breier A-C, Gastmeier P, Behnke M. Regional distribution of nosocomial infections due to ESBL-positive Enterobacteriaceae in Germany: data from the German National Reference Center for the Surveillance of Nosocomial Infections (KISS). Clin Microbiol Infect. 2015;21(3):255.e1-5. doi: 10.1016/j.cmi.2014.07.015.
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6. Kluytmans-van den Bergh MF, Verhulst C, Willemsen LE, Verkade E, Bonten MJM, Kluytmans JAJW. 2015. Rectal carriage of extended-spectrum-betalactamase- producing Enterobacteriaceae in hospitalized patients: selective preenrichment increases yield of screening. J Clin Microbiol. 2015;53(8):2709-2712. doi: 10.1128/JCM.01251-15.
7. Dubinsky-Pertzov B, Temkin E, Harbarth S, et al; R-GNOSIS WP4 study group. Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae and the risk of surgical site infection after colorectal surgery: a prospective cohort study [published online September 10, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy768.
8. Jazmati N, Jazmati T, Hamprecht A. Importance of pre-enrichment for detection of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) from rectal swabs. Eur J Clin Microbiol Infect Dis. 2017;36(10):1847-1851. doi: 10.1007/s10096-017-3000-1.
9. US Centers for Disease Control and Prevention. 2016 National and State Healthcare-Associated Infections Progress Report. cdc.gov/hai/data/portal/progress-report.html. Updated October 25, 2018. Accessed November 1, 2018.
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