Antimicrobial resistance threatens the safety of contemporary surgery. Appropriately timed prophylaxis can prevent SSI; unnecessarily broad or prolonged antimicrobial exposure can create selective pressure without additional clinical benefit.

Paediatric surgical patients include neonates with congenital anomalies, children requiring complex cardiac operations, transplant recipients, and patients needing postoperative intensive care. Prior hospitalisation, invasive devices, parenteral nutrition and repeated antibiotics can change bacterial ecology.

Antibiotic exposure may suppress susceptible commensal organisms and permit expansion of resistant Enterobacterales, enterococci and non-fermenting Gram-negative organisms. Colonisation may precede wound infection, catheter-associated infection or bloodstream infection.

It is essential to distinguish newly acquired resistance from pre-existing carriage. Children may enter surgery already colonised with ESBL-producing or carbapenem-resistant organisms; postoperative infection may represent progression from carriage rather than resistance newly created by prophylaxis.

This review evaluates the pathway from antibiotic exposure through MDRO carriage to postoperative infection, while separately examining inappropriate prophylaxis as a modifiable selection pressure.

Study design and review question

This systematic review was structured according to PRISMA 2020. The review question was: among children undergoing surgery, how does antimicrobial exposure—duration, spectrum, cumulative use or targeted prophylaxis—relate to subsequent MDRO colonisation or infection? The protocol was not prospectively registered.

PECO framework

Information sources and search

The search covered MEDLINE/PubMed, Embase, Scopus, Web of Science, CINAHL, CENTRAL and citation tracking for January 2000 through June 2026. Search terms: (child* OR pediatric OR paediatric OR neonate OR adolescent) AND (surgery OR surgical OR perioperative OR postoperative OR cardiac surgery OR appendicitis OR transplantation) AND (antibiotic OR antimicrobial OR prophylaxis OR carbapenem OR cephalosporin) AND (multidrug-resistant OR ESBL OR CRE OR carbapenem-resistant OR MRSA OR VRE).

Eligibility and outcomes

Eligible reports concerned paediatric surgical or perioperative patients with identifiable antimicrobial exposure, duration/spectrum of prophylaxis, relevant preoperative carriage or subsequent resistant infection. Adult-only studies, reviews, guidelines without original data, non-surgical studies without separable surgical data, and reports without usable outcomes were excluded. Reviews were used for context rather than primary study counts.

MDRO encompassed ESBL-producing Enterobacterales, carbapenem-resistant Enterobacterales and other resistant Gram-negative organisms, MRSA, VRE and study-defined MDR bacterial pathogens. Outcomes were extracted as defined by each primary study.

Data extraction, bias and synthesis

Extracted items included design, country, population, sample, antibiotic class and duration, baseline carriage, resistant phenotype, postoperative infection, SSI, length of stay and mortality. Observational studies were considered using ROBINS-I domains and randomised studies, where applicable, using RoB 2 principles. Confounding by indication, baseline colonisation, illness severity and surveillance intensity were prioritised. Heterogeneity precluded a defensible pooled estimate; findings are presented narratively.

Study selection

The selection dataset identified 2,418 database records and 64 additional records. After removing 612 duplicates, 1,870 records were screened and 1,647 excluded. Of 223 reports sought, nine were unavailable. Full-text assessment covered 214 reports, with 199 exclusions and 15 studies retained for qualitative synthesis.

Full-text exclusions

Characteristics of included studies

The evidence spanned cardiac surgery, abdominal surgery, transplantation-associated populations and multispecialty paediatric surgery. Some studies were perioperative antibiotic stewardship cohorts; others were high-risk paediatric resistance studies in which prior surgery was a major exposure. Their inferential relevance differs and is addressed in the discussion.

Antibiotic duration as a modifiable exposure

Álvarez et al. found that prophylaxis extending beyond 48 hours after paediatric cardiac surgery did not provide measurable nosocomial infection protection and was associated with increased infection [2]. Salas et al. described 12,895 paediatric surgical procedures, 11% with prophylaxis exceeding 24 hours and approximately 5,733 potentially excess antibiotic-days [8]. Each additional antibiotic day extends selection pressure on commensal flora.

Postoperative prophylaxis and surgical-site infection

A large multicentre cohort reported substantial hospital variation in postoperative prophylaxis without lower SSI rates at hospitals using more postoperative antibiotics [11]. This suggests opportunities to reduce unnecessary postoperative doses while preserving correctly indicated pre-incisional prophylaxis.

Broad-spectrum and inappropriate prophylaxis

Anandalwar et al. documented inappropriate prophylaxis in more than half of paediatric operations [12]. Procedure-level analysis found that unindicated, excessively broad and prolonged prophylaxis were concentrated in selected surgical categories [13]. Antimicrobial stewardship should therefore be procedure-specific.

Carbapenem and antipseudomonal exposure

Aktürk et al. identified previous carbapenem use and previous surgery as independent correlates of progression from CRKP colonisation to systemic infection [3]. Chiotos et al. reported recent antipseudomonal exposure (OR 5.20) and prior surgery (OR 6.30) as risk factors for CRE [5]. Ruvinsky et al. associated prior meropenem with CRE bloodstream infection in a high-risk paediatric population [9]. These studies do not establish that every resistant isolate newly emerged after the index operation.

Baseline colonisation and postoperative infection

Cheikh et al. found ESBL carriage in 17 of 111 screened cardiac surgery patients. Four of 17 carriers developed ESBL postoperative infection compared with one non-carrier; the authors reported a markedly elevated relative risk [4]. Preoperative screening therefore informs infection-control measures, but positive carriage does not automatically justify broadening routine prophylaxis.

Targeted prophylaxis for known carriers

Cies et al. evaluated targeted prophylaxis among MDRO-colonised paediatric cardiothoracic patients and did not demonstrate a significant reduction in postoperative infection [6]. Small sample sizes limit conclusions about benefit or equivalence. A targeted approach requires an explicit risk-benefit framework.

Abdominal surgery and resistance

In complicated appendicitis, therapeutic antibiotic selection differs from clean-procedure prophylaxis. Kwok et al. documented resistant pathogens in paediatric appendicitis [7]. Management should prioritise source control, appropriate empirical treatment, microbiological reassessment and evidence-based treatment duration.

Progression from colonisation to infection

Darda et al. observed progression to infection among colonised neonates and children and identified longer broad-spectrum antibiotic exposure as a correlate [10]. Although not exclusively surgical, these findings matter for neonates and children receiving intensive postoperative care.

Postoperative sepsis and resistant pathogens

Bhende et al. reported postoperative sepsis among children after cardiac surgery; all eight culture-positive bacterial bloodstream infections in the cohort were MDR [14]. This demonstrates the clinical importance of resistant infection but does not prove that prophylaxis caused resistance.

Quantitative signals

Risk of bias and evidence certainty

The most important threat was confounding by indication. Disease severity, device use and duration of hospitalisation can independently increase both antibiotic exposure and MDRO risk. Confidence in the association between prior broad-spectrum exposure and resistant infection is greater than confidence in direct proof of new resistance emergence following an individual perioperative course.

The evidence supports three conclusions. First, potentially unnecessary antibiotic exposure is common in paediatric surgical care. Second, broad-spectrum and carbapenem exposure are repeatedly associated with resistant Gram-negative colonisation or infection in high-risk children. Third, preoperative carriage is an important predictor of postoperative infection and must be distinguished from de novo resistance emergence.

The literature seldom measures true emergence prospectively. An ideal study would obtain preoperative surveillance cultures, quantify antibiotic-days and spectrum, repeat surveillance, and use molecular typing to distinguish persistence, selection and transmission. Without these measurements, observational associations should not be interpreted as proof that prophylaxis created a resistant strain.

Prophylaxis is intended to provide tissue concentrations during operative contamination, not to treat an established infection. Extending it solely because drains, catheters or a chest tube remain in place can create ecological exposure without proven benefit. By contrast, perforated appendicitis or postoperative sepsis may require therapeutic courses; stewardship must distinguish these indications.

Carbapenems remain essential when severe infection or resistance patterns warrant them. The goal is not indiscriminate restriction, but early cultures, appropriate initial therapy, prompt review, and de-escalation when narrower treatment is safe.

Screening of selected high-risk children can support infection-control precautions and inform empirical therapy if postoperative sepsis occurs. However, universal escalation of prophylaxis for all carriers could increase selection pressure. Local epidemiology, procedure risk, previous isolates and clinical condition should guide individual decisions.

In lower-resource settings, resistant-organism burden and limited rapid diagnostics make stewardship especially challenging. Local antibiograms, microbiological surveillance, hand hygiene, environmental cleaning and prompt laboratory reporting are necessary complements to prescribing interventions.

Strengths and limitations

This review separates antibiotic overexposure, pre-existing MDRO carriage, postoperative acquisition and invasive resistant infection, rather than treating all resistant isolates as evidence of new emergence. However, most available studies are observational, surgical subgroups are sometimes not separable, cardiac surgery and ICU cohorts are overrepresented, and MDRO definitions vary. Risk-based rather than universal screening can bias detection.

Future research

Prospective multicentre studies should enrol children before surgery, measure baseline carriage, quantify days of therapy and spectrum, repeat surveillance after antibiotics and apply genomic typing. Outcomes should include SSI, acquisition, bloodstream infection, antibiotic adverse events, hospital stay, readmission and mortality. Procedure-specific trials are needed in neonatal gastrointestinal, cardiac, transplant and complex abdominal surgery.

Antibiotic exposure and antimicrobial resistance are closely linked in paediatric surgical care. Prolonged or broad-spectrum exposure is a modifiable risk marker, while baseline MDRO carriage and critical-care exposure substantially influence postoperative infection. Prolonged prophylaxis has not consistently improved SSI prevention. Precision antimicrobial use—correct indication, timely prophylaxis, appropriate spectrum, limited duration, microbiology-guided treatment and de-escalation—is therefore essential. Prospective surveillance studies are needed to determine how much unnecessary exposure can be avoided and whether that reduction prevents new MDRO acquisition.

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