The Six S’s of Surgical Antibiotic Prophylaxis in Pediatrics: A Pragmatic Approach

Surgical site infections (SSIs) cause substantial morbidity with delayed healing, patient distress, increased length of stay and emergency department re-presentations, as well as higher mortality.1–3 They are among the most common and costly hospital-acquired infections, accounting for up to 20% of cases.4,5 In Australia, for example, in 2018–2019, SSIs cost public hospitals $323.5 million. The prevention of SSIs involves a comprehensive approach known as the “SSI prevention bundle.” Surgical antimicrobial prophylaxis (SAP) is a key component of this bundle, providing antibiotic cover during potential iatrogenic introduction of bacteria. Other components include preoperative, intraoperative and postoperative strategies6 designed to optimize patients’ health before surgery, maintain surgical asepsis during the procedure and measures for wound care and infection surveillance postoperatively. Appropriately implemented SAP significantly reduces the risk of SSIs and leads to better patient outcomes and lower healthcare costs, yet practice varies widely. High-quality evidence to support recommendations in pediatrics is scarce due to the lack of comparative studies in children7 and an absence of evidence in neonates.8 This is despite SSI rates being high in some pediatric settings, for example, up to 13% in neonatal abdominal surgery.9 Most major guidelines for preventing SSI do not include specific recommendations for SAP in neonates or children.10 Pediatric SAP guidelines that exist are often extrapolated from adult practice, with dosing adjusted from adult doses. Alarmingly, studies consistently show that SAP is among the highest contributors to inappropriate antibiotic prescribing, particularly in neonatal settings where antibiotic use is already high.8,11,12 In Australian tertiary children’s hospitals, for example, more than a third of SAP prescriptions were inappropriate. Of these, 32% were prescriptions continued for longer than 24 hours and 17% involved an incorrect choice of antibiotic for the procedure.12 Additionally, while there is growing awareness of the problem of antibiotic resistance, there is insufficient focus on how SAP practices can contribute to or mitigate this challenge, particularly in high-risk pediatric settings, such as neonatal intensive care units and pediatric intensive care units. Given the already high antibiotic exposure in these vulnerable populations, inappropriate SAP practices exacerbate the development of multidrug-resistant pathogens.8 Reducing unnecessary variation and inappropriate prescribing improves patient care and reduces unnecessary antibiotic use. Simplifying key concepts, as illustrated by the global success of the World Health Organization’s “5 Moments for Hand Hygiene” program, can improve adherence to best practice. Here, we introduce the “6 S’s of SAP” (Figs. 1 and 2) as a structured framework to ensure the fundamental principles of SAP are met: Specific procedures, Suitable antibiotics, Start at optimal time, Severe antibiotic allergy, Single dose and Stop.FIGURE 1.: Summary of key points of the 6 S’s of surgical antimicrobial prophylaxis.FIGURE 2.: Examplar guideline incorporating the 6 S’s of surgical antimicrobial prophylaxis.The “6 S’s of SAP” framework provides the basis for other antimicrobial stewardship strategies to improve adherence and implementation, such as electronic decision support, education, auditing, interdisciplinary engagement and prescriber feedback.2,8,13 Until more evidence is available, efforts should focus on improving adherence to existing guidelines and refining local protocols to ensure consistent adoption. SPECIFIC PROCEDURES The decision to use SAP depends on several factors, including the surgical site’s risk of contamination, the patient’s underlying conditions and the potential for postoperative infection. While SAP is important in higher-risk surgeries, it is not universally required for all procedures. Correct classification is key to selecting appropriate antibiotic prophylaxis and ensuring that SAP is reserved for procedures with an infection risk, thus reducing unnecessary use. In general, procedures that do not substantially increase the risk of bacterial contamination into a sterile space do not need SAP. This includes procedures that do not breach anatomical barriers (such as closed fracture repair without fixation), procedures involving only nonsterile spaces (such as endoscopic procedures into the gastrointestinal lumen) and localized clean procedures with minimal mucosal or skin breach (such as tonsillectomy, vascular access, minor skin procedures and simple hernia repair). The American College of Surgeons deems these procedures to have an SSI risk of less than 2% and the American Academy of Pediatrics does not recommend SAP in these settings.14,15 However, there are exceptions to the list of procedures for which SAP is generally not indicated. For example, in immunocompromised children, even minimal bacterial introduction may overwhelm the immune system’s defenses. In such cases, procedures like the insertion of central venous catheters, especially when expected to remain in place for prolonged durations (such as during chemotherapy), may require SAP. One important difference between adults and children is the use of SAP for urinary tract cystoscopy. In adults, SAP is not recommended for simple cystoscopy as it does not usually breach the mucosa. However, in children, SAP is recommended due to the higher prevalence of urological abnormalities, which increase the risk of infection from even minimal bacterial introduction into this otherwise sterile site. For more extensive surgeries involving prolonged mucosal or skin breach or those with a high risk of contamination, prophylactic antibiotics are recommended. This includes clean-contaminated surgeries, such as appendicectomies, where there is a risk of contamination from enteric bacteria as the appendix can become contaminated with fecal matter.16 Pediatric cardiothoracic surgeries, such as for complex congenital heart disease correction, are an example of high-risk procedures appropriate for SAP. They have multiple risk factors for SSIs, including severe underlying health issues, the complexity of the surgery, delayed sternal closure and prolonged postoperative critical care management.17 SUITABLE ANTIBIOTIC For procedures where SAP is recommended, the selection of the correct antibiotic(s) involves consideration of the surgical procedure and the child’s individual risk factors, including colonization with resistant bacteria.18 The appropriate antibiotic depends on the likely pathogens associated with the specific type of surgery. For the majority of operations, this involves cover for skin flora that may enter as the scalpel breaches the skin, primarily Staphylococcus aureus and streptococci.6 A first-generation cephalosporin, such as cefazolin, is commonly recommended for this. However, some procedures are at risk of introducing infection with additional pathogens, necessitating broader cover. In surgeries involving the gastrointestinal tract, abdominal or pelvic organs, deep wound debridement, ischemic limb or open fracture, the risk of anaerobic bacterial infection warrants the addition of metronidazole.19 While cefazolin usually provides adequate prophylactic cover for Escherichia coli, SAP for an abdominopelvic infection involving a bowel lumen breach requires broader Gram-negative cover with, for example, a third-generation cephalosporin. Similarly, for complicated urinary tract surgery, including stent insertion, although cefazolin has activity against E. coli, the increasing prevalence of extended-spectrum beta-lactamases-producing urinary pathogens means broader Gram-negative cover may be needed with, for example, an aminoglycoside. Evidence from adult studies suggests that SAP usually does not need to be modified based on local antimicrobial resistance patterns. Even with relatively high rates of methicillin-resistant S. aureus (MRSA) in the community, for example, cefazolin remains the preferred antibiotic for SAP.20 However, individual patient factors should always be considered, particularly for high-risk procedures or surgeries with severe consequences. For example, a child having cardiac surgery with known MRSA colonization or who belongs to a population with specific risk factors (eg, certain Indigenous populations) should receive vancomycin in addition to cefazolin, as this improves both MRSA and MSSA cover.20,21 Similarly, in gastrointestinal/abdominal surgery, a child known to be colonized with an extended-spectrum beta-lactamases-producing enteric pathogen should have SAP tailored to that pathogen’s susceptibility profile. Antibiotic dosing in children depends on age and weight, and it is also important to consider developmental pharmacokinetics in children, as hepatic and renal functions mature over time.22 Additionally, certain procedures can alter antibiotic pharmacokinetics, necessitating dose adjustments. For instance, during cardiac bypass surgery, cefazolin pharmacokinetic modeling studies indicate that higher doses may be required to achieve target plasma concentrations.23 However, further research is needed to better understand the impact of these factors on SAP dosing in pediatrics. START AT OPTIMAL TIME The optimal time to start SAP is generally agreed to be 15–60 minutes before incision to minimize the risk of SSI.24 This timing aims to achieve high tissue levels of the antibiotic at the time of incision, aligning peak concentrations in the bloodstream with knife-to-skin and potential bacterial contamination. However, some research indicates a wider window of up to 120 minutes preincision may still be effective.25 This may be particularly appropriate for young children, especially neonates and infants, who have altered pharmacokinetics. For antibiotics with long infusion times, such as vancomycin, earlier administration is necessary to achieve adequate levels at the time of incision.26 In contrast, administering SAP after skin incision or more than 120 minutes before surgery significantly increases the risk of SSI.25 SEVERE ANTIBIOTIC ALLERGY The presence of a severe antibiotic allergy, in practice anaphylaxis, necessitates the use of an alternative antibiotic with a similar spectrum. In children, severe beta-lactam allergy is the most common reason for choosing an alternative antibiotic for SAP.27 For most procedures, vancomycin is an adequate substitute to cover skin flora, including S. aureus and Streptococcus pyogenes. In procedures in which anaerobes are also a risk, such as ear, nose and throat surgery, clindamycin might be a more appropriate choice, although there are rising rates of clindamycin resistance in S. aureus globally. In procedures in which Gram-negative pathogens are a risk (such as Klebsiella pneumoniae in cardiac surgery or enteric pathogens in gastrointestinal surgery), an aminoglycoside should be added. SINGLE DOSE Multiple studies, primarily done in adults, have shown that single-dose antimicrobial prophylaxis is as effective as multiple-dose regimens in preventing SSIs for most surgical procedures.28 Single-dose prophylaxis reduces unnecessary antibiotic exposure and is associated with reduced healthcare costs, lower risk of antibiotic resistance and lower risk of drug-related adverse effects.28 However, for surgeries lasting more than 3 hours, additional intraoperative doses may be necessary. Intraoperative redosing is specifically recommended for procedures lasting more than 4 hours and the usual recommendation is to re-dose after 2 half-lives of the antibiotic have passed.26 STOP For the vast majority of procedures, SAP should be discontinued immediately following surgery.29 There is no definitive evidence to support ongoing antibiotic prophylaxis after surgery in reducing the risk of SSI. There is also no evidence to justify ongoing prophylaxis while catheters or drains are in situ, including cerebrospinal fluid drains.30 In fact, prolonged antibiotic use has been associated with increased patient harm, including the risk of antibiotic resistance, adverse drug reactions and disruption of the microbiome.31 There are only a few procedures in children for which recommendations are to continue SAP up to 24 hours postsurgery before discontinuation, including complex cardiac and orthognathic operations. CONCLUSIONS Despite the availability of both international and institutional guidelines, adherence to the recommended SAP choice and duration for pediatric procedures remains inconsistent between institutions and surgical departments. This variability is due to multiple factors, including limited pediatric-specific evidence and the complexity around tailoring SAP for different and often rare procedures for congenital anomalies. In addition, nuances around SAP have not traditionally been a high priority for surgeons. Implementing SAP recommendations through education, regular audits and feedback can improve adherence to timing and antibiotic selection.17,28 The lack of child-specific evidence on SAP highlights a key gap in antimicrobial stewardship knowledge.7 High-quality randomized controlled trials in both resource-rich and resource-poor settings are needed. The high number of children having surgery every day means this is not beyond our reach. In the meantime, simplifying SAP prescribing to the fundamental principles embodied by the “6 S’s of SAP” framework can help standardize appropriate antibiotic use, reduce inappropriate prescribing and play a crucial role in hospital-based antimicrobial stewardship programs.