Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Surgical site infection (SSI) is the most common postoperative complication, causing substantial patient morbidity, costs, and potential catastrophic expenditure, particularly in low- and middle-income countries (LMICs). Despite its importance, prospective, standardized, internationally comparable data on SSI incidence and related adverse events are scarce, hindering resource allocation and policy in LMICs. Recently published WHO guidelines provide recommendations for SSI prevention but rely largely on evidence from high-income settings and may not fully translate to resource-limited environments. Microbiological data on antimicrobial resistance and the likely source of causative organisms are also needed to refine prevention strategies. This study aimed to determine global SSI incidence after gastrointestinal surgery across countries stratified by the Human Development Index (HDI) and to identify associated risk factors, including antibiotic resistance patterns.

Evidence before this study: Systematic searches (PubMed, MEDLINE, Google Scholar, ClinicalTrials.gov; Jan 1, 1997–June 1, 2017) for multinational research on SSI after abdominal surgery in LMICs identified numerous small single-centre studies of low-to-medium quality, with SSI incidence ranging widely (0.4%–30.9% overall; clean-contaminated 1.5%–81.0%, contaminated 0.5%–65.5%, dirty 0.2%–100%). High heterogeneity precluded meta-analysis. One multinational study since 2010 included a limited range of countries and reported low SSI incidence, potentially due to passive 30-day follow-up; lowest-income countries and children were underrepresented. Added value of this study: Provides standardized, validated, prospective, contemporaneous global data on SSI after gastrointestinal surgery across HDI strata, demonstrating higher SSI rates in LMICs even after casemix adjustment, with the highest incidence after dirty surgery. A substantial proportion of SSIs involved organisms resistant to the prophylactic antibiotic, with the greatest burden in LMICs. Implications: SSI burden is disproportionately greater in LMICs. WHO-preferred measures lack robust high-quality interventional evidence from LMICs; pragmatic randomized trials are urgently needed to guide prevention and antibiotic stewardship.

Design: International, multicentre, prospective cohort study following a published protocol, coordinated via the GlobalSurg network. Ethical/audit approvals were obtained locally; UK NHS ethics deemed the study exempt from formal registration. Participants and sampling: Any hospital worldwide could participate. Local teams prospectively enrolled all consecutive patients undergoing elective or emergency gastrointestinal resection (oesophagus, stomach, small bowel, colon, rectum, appendix, gallbladder; including stoma formation/reversal) during at least one pre-selected 2-week period. Open and minimally invasive approaches were eligible; no age restriction. Exclusions: primary vascular, gynaecological, obstetric, urological, or transplant indications where the GI tract is typically not opened. Variables and data collection: Predefined, objective, standardized variables included demographics (age, sex), ASA class, immune suppression (e.g., HIV, malaria, diabetes, steroids/chemotherapy/other immunosuppressants), smoking; disease/treatment variables (diagnostic category, elective vs emergency, WHO surgical safety checklist use, laparoscopy, epidural, prophylactic antibiotics, intraoperative contamination classified as clean-contaminated, contaminated, or dirty per operative surgeon). Antibiotic use before/after surgery and duration were recorded. Microbiology (wound cultures per local protocols) categorized organisms as bowel-derived, skin-derived, or mixed; antimicrobial resistance defined as resistance to the prophylactic antibiotic administered. Data were entered into REDCap; site leads verified records; central checks queried missing data. Vetted but incomplete records were excluded from analysis. Outcomes: Primary—30-day SSI incidence (CDC criteria for superficial and deep incisional SSI). Organ-space infections (intra-abdominal/pelvic) were recorded separately. Secondary—30-day mortality; perioperative antibiotic use; 30-day reintervention (operative/radiologic/endoscopic); prevalence of antimicrobial resistance among SSIs with cultures; in-hospital SSI incidence; overall 30-day SSI incidence assessed at 30 days (in person, phone, or record review). Validation: Three-part validation across a representative sample: self-reported processes; independent validation of case ascertainment and sampled data accuracy; qualitative assessment of engagement and data collection. Sample size: Assuming 15% baseline SSI, 550 patients per HDI group (~1,350 total allowing for missing data) would detect a 6.5 percentage-point difference with 80% power at alpha=0.05. Statistical analysis: Countries stratified into HDI tertiles. Differences tested using Pearson’s chi-squared (categorical) and Kruskal–Wallis (continuous). Bayesian multilevel logistic regression accounted for casemix, with hospital and country random effects; non-informative priors with sensitivity analyses; first-order interactions assessed; model selection via WAIC and discrimination via c-statistic. Results reported as odds ratios (ORs) with 95% credible intervals (CrIs). A restricted cubic spline for continuous HDI rank assessed non-linearity (generalized additive model) with posterior predictions and 95% intervals. Analyses in R 3.1.1 and Stan 2.10.0. Trial registration: NCT02662231. Data sharing: http://ssi.globalsurg.org. Role of funder: No role in design, data collection, analysis, interpretation, or writing.

- Cohort: 12,539 patients from 343 hospitals in 66 countries (7,339 high-HDI; 3,918 middle-HDI; 1,282 low-HDI). Children (≤16 years): 10.3% (n=1,291). Most common operations: cholecystectomy 35.2% (4,412/12,539), appendicectomy 33.3% (4,179/12,539). Emergency: 48.8%; open approach: 46.9%; WHO checklist used: 70.5%. - Contamination class: clean-contaminated 79.1%, contaminated 12.3%, dirty 7.9%; dirty classifications more frequent in low-HDI settings (14.1%). - Primary outcome: Overall 30-day SSI 12.3% (1,538/12,539). By HDI: high 9.4% (691/7,339), middle 14.0% (549/3,918), low 23.2% (298/1,282), p<0.001. - Highest SSI incidence after dirty surgery in all HDI groups: high 17.8% (102/574), middle 31.4% (74/236), low 39.8% (72/181). - Adjusted analyses: Low-HDI independently associated with higher SSI risk vs high-HDI (adjusted OR 1.60, 95% CrI 1.05–2.37; p=0.030); middle-HDI not significantly different (OR 1.12, 0.77–1.61; p=0.539). Laparoscopic approach associated with lower SSI risk (OR 0.36, 0.30–0.42; p<0.001). Increasing contamination associated with higher SSI. Failure to use a surgical safety checklist was associated with higher SSI. - Mortality: 30-day mortality 1.9% (235/12,539), higher in low-HDI (4.8%) than middle (1.6%) or high (1.5%). SSI associated with worse outcomes: mortality 4.7% with SSI vs 1.5% without; higher reintervention and organ-space infection rates; other HCAIs more frequent with SSI. - Length of stay: Median 7.0 days (IQR 11.0) with SSI vs 2.0 days (IQR 4.0) without; p<0.001. - Antibiotic use: Preoperative/prophylactic antibiotics used in 88.2% overall; higher in low-HDI (95.5%) vs middle (86.6%) and high (87.8%); p<0.001. Postoperative antibiotics used more in LMICs: high 46.0%, middle 80.0%, low 85.6%; p<0.001. After adjustment (including contamination), low-HDI associated with increased postoperative antibiotic use (adjusted OR 4.37, 95% CrI 1.65–11.85; p=0.002). Courses ≥5 days: high 24.9%, middle 46.9%, low 50.7%; p<0.001. - Microbiology and resistance: Cultures available in 610/1,538 (39.7%) SSIs. Among 472 with classified origin, 63.8% bowel-derived, 20.6% skin-derived, 11.2% mixed. Resistance to the prophylactic antibiotic in 21.6% (132/610), varying by HDI: high 16.6% (49/295), middle 19.8% (37/187), low 35.9% (46/128); p<0.001. - Validation: 93% case ascertainment in validation sample; high agreement for continuous and categorical predictors and mortality.

This study demonstrates a substantial global burden of SSI after gastrointestinal surgery, with a clear gradient across development levels: patients in low-HDI countries have significantly higher SSI risk than those in middle- or high-HDI countries, independent of casemix and intraoperative contamination. Dirty procedures carry the highest absolute risk everywhere, but HDI remains an independent risk factor. SSI substantially prolongs hospital stay and is associated with higher mortality, reinterventions, organ-space infections, and other health-care–associated infections, underscoring its clinical and system-level impact. The findings also link SSI to antimicrobial resistance: bowel-derived organisms predominate, and over one-fifth of cultured SSIs were resistant to the prophylactic antibiotic, with the highest resistance in low-HDI settings. Postoperative antibiotic use and duration were greater in LMICs, not explained by casemix, highlighting potential targets for stewardship. The association between failure to use a surgical safety checklist and higher SSI may reflect broader safety culture deficits. These results address key knowledge gaps by providing standardized, prospective, multinational data that enable meaningful comparisons across settings. They support prioritizing SSI prevention in LMICs and inform the design of context-appropriate interventions and stewardship policies.

SSI after gastrointestinal surgery is common worldwide and disproportionately affects patients in low-HDI countries, independent of patient, disease, and procedural factors. Dirty surgery carries the highest risk, and antimicrobial resistance to prophylactic antibiotics is frequent, particularly in LMICs. Given the prolonged hospital stays and adverse outcomes associated with SSI, targeted prevention and antibiotic stewardship are urgent priorities. High-quality, pragmatic randomized trials in LMICs are needed to evaluate effective, scalable SSI prevention strategies and optimize antibiotic use.

- Follow-up: Not all patients could be directly assessed at 30 days; mixed follow-up methods (in-person, phone, records) may under-ascertain SSIs compared with proactive follow-up in trials. A sensitivity analysis using in-hospital SSI showed similar patterns across HDI groups. - Microbiology: Specimen collection, laboratory methods, and resistance definitions were not standardized across centres; cultures were available in only 39.7% of SSIs, potentially underestimating resistance. - Observational design: Potential for residual confounding and missed cases despite protocolized data collection, validation, and local coordination; causal inferences cannot be made. - Data quality: Although validation showed high accuracy and 93% case ascertainment, some variables (e.g., 30-day reintervention) had lower agreement.