European Society of Clinical Microbiology and Infectious Diseases/European Committee on infection control clinical guidelines on pre-operative decolonization and targeted prophylaxis in patients colonized by multidrug-resistant Gram-positive bacteria before surgery.

SCOPE: The aim of these guidelines is to provide recommendations for decolonization and perioperative antibiotic prophylaxis (PAP) in multidrug-resistant Gram-positive bacteria (MDR-GPB) adult carriers before inpatient surgery. METHODS: These European Society of Clinical Microbiology and Infectious Diseases/European Committee on Infection Control guidelines were developed following a systematic review of published studies targeting methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, methicillin-resistant coagulase-negative Staphylococci, and pan-drug-resistant-GPB. Critical outcomes were the occurrence of surgical site infections (SSIs) caused by the colonizing MDR-GPB and SSIs-attributable mortality. Important outcomes included the occurrence of SSIs caused by any pathogen, hospital-acquired infections, all-cause mortality, and adverse events associated with the interventions, including resistance development to the agents used and the incidence of Clostridioides difficile infections. The last search of all databases was performed on 1 November 2023. The level of evidence and the strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included. RECOMMENDATIONS: The guideline panel reviewed the impact of decolonization, targeted PAP, and combined interventions (e.g. decolonization and targeted PAP) on the risk of SSIs and other outcomes in MDR-GPB carriers, according to the type of bacteria and type of surgery. We recommend screening for S. aureus before high-risk operations, such as cardiothoracic and orthopaedic surgery. Decolonization with intranasal mupirocin with or without a chlorhexidine bath is recommended in patients colonized with S. aureus before cardiothoracic and orthopaedic surgery and suggested in other surgeries. The addition of vancomycin to standard prophylaxis is suggested for MRSA carriers in cardiothoracic surgery, orthopaedic surgery, and neurosurgery. Combined interventions (e.g. decolonization and targeted prophylaxis) are suggested for MRSA carriers undergoing cardiothoracic and orthopaedic surgery. No recommendation could be made regarding screening, decolonization and targeted prophylaxis for vancomycin-resistant enterococci because of the lack of data. No evidence was retrieved for methicillin-resistant coagulase-negative Staphylococci and pan-drug-resistant-GPB. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship and infection control teams are warranted before implementing screening procedures or performing changes in PAP policy. Future research should focus on novel decolonizing techniques, on the monitoring of resistance to decolonizing agents and PAP regimens, and on standardized combined interventions in high-quality studies.

Colonisation with Extended-Spectrum Cephalosporin-Resistant Enterobacterales and Infection Risk in Surgical Patients: A Systematic Review and Meta-analysis.

INTRODUCTION: Limited evidence has been reported for surgical site infections (SSIs) in patients undergoing surgery who are carriers of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E). A systematic review and meta-analysis were conducted to evaluate the risk of postoperative infections in adult inpatients colonised with ESCR-E before surgery. METHODS: The Medline, Embase and Cochrane databases were searched between January 2011 and April 2022, following PRISMA indications. Random effects meta-analysis was used to quantify the association between ESCR-E colonisation and infection. RESULTS: Among the 467 articles reviewed, 9 observational studies encompassing 7219 adult patients undergoing surgery were included. The ESCR-E colonisation rate was 13.7% (95% CI 7.7-19.7). The most commonly reported surgeries included abdominal surgery (44%) and liver transplantation (LT; 33%). The SSI rate was 23.2% (95% CI 13.2-33.1). Pooled incidence risk was 0.36 (95% CI 0.22-0.50) vs 0.13 (95% CI 0.02-0.24) for any postoperative infection and 0.28 (95% CI 0.18-0.38) vs 0.17 (95% CI 0.07-0.26) for SSIs in ESCR-E carriers vs noncarriers, respectively. In ESCR-E carriers, the ESCR-E infection ratio was 7 times higher than noncarriers. Postoperative infection risk was higher in carriers versus noncarriers following LT. Sources of detected heterogeneity between studies included ESCR-E colonisation and the geographic region of origin. CONCLUSIONS: Patients colonised with ESCR-E before surgery had increased incidence rates of post-surgical infections and SSIs compared to noncarriers. Our results suggest considering the implementation of pre-surgical screening for detecting ESCR-E colonisation status according to the type of surgery and the local epidemiology.

ESCMID/EUCIC clinical practice guidelines on perioperative antibiotic prophylaxis in patients colonized by multidrug-resistant Gram-negative bacteria before surgery.

SCOPE: The aim of the guidelines is to provide recommendations on perioperative antibiotic prophylaxis (PAP) in adult inpatients who are carriers of multidrug-resistant Gram-negative bacteria (MDR-GNB) before surgery. METHODS: These evidence-based guidelines were developed after a systematic review of published studies on PAP targeting the following MDR-GNB: extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), aminoglycoside-resistant Enterobacterales, fluoroquinolone-resistant Enterobacterales, cotrimoxazole-resistant Stenotrophomonas maltophilia, carbapenem-resistant Acinetobacter baumannii (CRAB), extremely drug-resistant Pseudomonas aeruginosa, colistin-resistant Gram-negative bacteria, and pan-drug-resistant Gram-negative bacteria. The critical outcomes were the occurrence of surgical site infections (SSIs) caused by any bacteria and/or by the colonizing MDR-GNB, and SSI-attributable mortality. Important outcomes included the occurrence of any type of postsurgical infectious complication, all-cause mortality, and adverse events of PAP, including development of resistance to targeted (culture-based) PAP after surgery and incidence of Clostridioides difficile infections. The last search of all databases was performed until April 30, 2022. The level of evidence and strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included in the recommendation development. RECOMMENDATIONS: The guideline panel reviewed the evidence, per bacteria, of the risk of SSIs in patients colonized with MDR-GNB before surgery and critically appraised the existing studies. Significant knowledge gaps were identified, and most questions were addressed by observational studies. Moderate to high risk of bias was identified in the retrieved studies, and the majority of the recommendations were supported by low level of evidence. The panel conditionally recommends rectal screening and targeted PAP for fluoroquinolone-resistant Enterobacterales before transrectal ultrasound-guided prostate biopsy and for extended-spectrum cephalosporin-resistant Enterobacterales in patients undergoing colorectal surgery and solid organ transplantation. Screening for CRE and CRAB is suggested before transplant surgery after assessment of the local epidemiology. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship teams before implementing the screening procedures or performing changes in PAP are warranted. High-quality prospective studies to assess the impact of PAP among CRE and CRAB carriers performing high-risk surgeries are advocated. Future well-designed clinical trials should assess the effectiveness of targeted PAP, including the monitoring of MDR-GNB colonization through postoperative cultures using European Committee on Antimicrobial Susceptibility Testing clinical breakpoints.

Induction of contact-dependent CD8(+) regulatory T cells through stimulation with staphylococcal and streptococcal superantigens.

The bacterial superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes are potent stimulators of polyclonal T-cell proliferation. They are the causes of toxic shock syndrome but also induce CD25(+) FOXP3(+) regulatory cells in the CD4 compartment. Several studies have recently described different forms of antigen-induced regulatory CD8(+) T cells in the context of inflammatory diseases and chronic viral infections. In this paper we show that bacterial superantigens are potent inducers of human regulatory CD8(+) T cells. We used four prototypic superantigens of S. aureus (toxic shock syndrome toxin-1 and staphylococcal enterotoxin A) and Str. pyogenes (streptococcal pyrogenic exotoxins A and K/L). At concentrations below 1 ng/ml each toxin triggers concentration-dependent T-cell receptor Vß-specific expression of CD25 and FOXP3 on CD8(+) T cells. This effect is independent of CD4(+) T-cell help but requires antigen-presenting cells for maximum effect. The cells also express the activation/regulatory markers cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumour necrosis factor receptor-related protein and skin homing adhesins CD103 and cutaneous lymphocyte-associated antigen. Superantigen-induced CD25(+) FOXP3(+) CD8(+) T cells were as potent as freshly prepared naturally occurring CD4(+) regulatory T cells in suppressing proliferation of CD4(+) CD25(-) T cells in response to anti-CD3 stimulation. Although superantigen-induced CD8(+) CD25(+) FOXP3(+) express interleukin-10 and interferon-γ their suppressive function is cell contact dependent. Our findings indicate that regulatory CD8(+) T cells may be a feature of acute bacterial infections contributing to immune evasion by the microbe and disease pathogenesis. The presence and magnitude of regulatory CD8(+) T-cell responses may represent a novel biomarker in such infections. Superantigen-induced regulatory CD8(+) T cells also have therapeutic potential.