Surgical Antibiotic Prophylaxis in Children Undergoing Surgery: A Systematic Review and Meta-Analysis

Abstract

Background:

To establish the role of surgical antibiotic prophylaxis (SAP) in the prevention of surgical site infection (SSI) in children undergoing surgery.

Design:

A systematic review and meta-analysis of six databases: MEDLINE (PubMed), EMBASE, CINAHL Plus, Cochrane Library, Web of Science, and Scopus.

Study Selection:

Included studies (irrespective of design) compared outcomes in children undergoing surgery, aged 0 to 21 years who received SAP with those who did not, with SSI as an outcome, using the U.S. Centers for Disease Control and Prevention (CDC) definitions for SSI.

Data Extraction:

Two independent reviewers applied eligibility criteria, assessed the risk of bias, and extracted data.

Results:

A total of six randomized control trials and 26 observational studies including 202,593 surgical procedures among 202,405 participants were included in the review. The pooled odds ratio of SSI was 1.20; (95% confidence interval [CI], 0.91–1.58) comparing those receiving SAP with those not receiving SAP, with moderate heterogeneity in effect size between studies (τ² = 0.246; χ² = 69.75; p < 0.001; I² = 57.0%). There was insufficient data on many factors known to be associated with SSI, such as cost, length of stay, re-admission, and re-operation; it was therefore not possible to perform subanalyses on these.

Conclusions:

This review and metanalysis did not find a preventive action of SAP against SSI, and our results suggest that SAP should not be used in surgical wound class (SWC) I procedures in children. However, considering the poor quality of included studies, the principal message of this study is in highlighting the absence of quality data to drive evidence-based decision-making in SSI prevention in children, and in advocating for more research in this field.

International infection prevention and control (IPC) guidelines provide standardized recommendations for health-care–associated infection (HAI) prevention in adults, but often lack specific information about children. Guidelines in healthcare are important because they inform local implementation of evidence-based measures.¹

Surgical site infection (SSI) is the second most common cause of HAI in high-income countries (HICs),² and the most common cause of HAI in low- and middle-income countries (LMICs).³ Surgical site infection is also the most common complication of surgery in children, representing one-third of all post-operative complications.⁴ Zingg et al.⁵ found that among children, SSIs were more frequent with increasing age, and suggested that age-adapted strategies for IPC in pediatric settings were needed to combat HAIs, of which SSIs form an important and largely preventable portion. Surgical site infections range in severity, complexity, and effect. Superficial SSIs involve only the skin or subcutaneous tissue; deep SSIs involve primarily fascia and muscle, whereas organ/space SSIs involve specific organs or body cavities.⁶

Adults who develop an SSI are twice as likely to die, 60% more likely to stay in an intensive care unit, and five times more likely to be re-admitted to the hospital.⁷ These statistics are not available for children; nevertheless, SSIs are a major cause of morbidity and mortality in the pediatric patient, resulting in a substantial burden on the health and well-being of affected children and their families.⁸ Surgical site infections lead to increased need for re-operation, and increase hospital stays by an average 10.6 days, hence to loss of work productivity for parents and guardians.^9–12

Surgical site infection is the costliest type of HAI with an estimated annual cost of $3.3 billion and is associated with nearly one million additional inpatient-days annually in the United States.¹³ In the United States, the Affordable Care Act has led to a focused interest in quality and value initiatives aimed at preventing SSIs because of their attendant financial burden.^14,15

Strategies to reduce SSIs have focused on pre-operative patient optimization, operative factors such as surgical antibiotic prophylaxis (SAP), post-operative care, and infection surveillance programs.¹⁶ Standardized SSI prevention protocols utilizing care bundles have been shown to reduce SSI rates in adults irrespective of resource setting,^17,18 a strategy that may be as effective in children; SAP is included in every such care bundle.^19–22 Surgical antibiotic prophylaxis administered within two hours prior to the surgical incision is an established practice for SSI prevention in adults.^3,23,24 The goal of SAP is to prevent SSIs by using safe, cost-effective antibiotic agents that have the appropriate spectrum of activity.^25,26

Although the effect of SAP has been well investigated and documented in adults, data on children are limited and SAP use poorly characterized.²⁷ Araujo da Silva et al.¹ reviewed international IPC guidelines and recommendations for prevention of HAIs, and found that pediatric-specific recommendations for SSI prevention were either totally omitted, or based on a limited number of intervention studies in specific conditions, such as spinal surgery and ventriculo-spinal shunts, and could not therefore be generalized to other conditions.

The most recent World Health Organization (WHO) SSI prevention guidelines highlighted the lack of data in children and thus recommendations were limited to adults only.^3,23,28 A combination of low-quality studies in children, a dearth of pediatric SSI data, and an abundance of high-quality adult studies means that the current practice of SAP administration in children is informed entirely by adult data, similar to many other practices in the IPC world.^1,29,30 There are many diagnostic and therapeutic differences between children and adults, therefore, the standard IPC practices designed for adults may not be effective or need modifications when applied to a pediatric population.^31,32 Neonates for example, are at high risk of infection because of factors such as immunologic immaturity and microbiota implantation; also, antibiotic pharmacokinetics are different compared with older children and adults.^33,34 Additionally, although appropriate antibiotic use may be protective for this patient population, inappropriate use exposes them to deleterious adverse effects.³⁵ Therefore, risk factors for SSI in children derived from studies in adult populations are potentially misleading because of differences in pathophysiology and management.^30,36

There exists, nevertheless, a body of evidence across different pediatric surgical specialties investigating the effect of SAP on SSI. However, no systematic review has yet summarized data evaluating the effectiveness of SAP in children. This systematic review and meta-analysis sought to establish the role of SAP in the prevention of SSI in children undergoing surgery.

Patients and Methods

Search strategy and selection criteria

The systematic review protocol was registered with PROSPERO (CRD42019111791),³⁷ and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement.^38,39 We searched the following databases: MEDLINE (PubMed), EMBASE, CINAHL Plus, Cochrane Library, Web of Science, and Scopus, for studies published in English between January 1993 and August 2020, to ensure included studies were consistent with the U.S. Centers for Disease Control and Prevention (CDC) SSI definitions, first published in 1992.⁶

We used a compound search strategy using a comprehensive list of search terms that included exploded Medical Subject Headings (MESH terms) with the following search concepts: surgical antibiotic prophylaxis; children; and surgical site infection, and with synonyms for each search concept. The full search strategy is available in Supplementary Table S1–S3. Included studies, irrespective of design, compared outcomes in children undergoing surgery, aged 0 to 21 years who received SAP (SAP group) with those who did not (no SAP group), with SSI as an outcome, using the CDC definitions for SSI.^6,14

The search was conducted independently by two reviewers (P.M.N. and Y.H.). All references identified by the search were imported into Endnote 20 (Clarivate Analytics, Philadelphia, PA); duplicates were removed, and titles and abstracts screened. Full-text articles were reviewed for eligibility; the reviewers compared and agreed on a list of eligible studies. Any disagreements were resolved by discussion between the two authors or, when necessary, via consultation with the senior author (K.K.).

Data extraction

Two authors (P.M.N. and Y.H.) independently reviewed each eligible article and extracted relevant data using a pre-specified data extraction form. Data collection included publication date, country in which study was conducted, country-income status, number of participants, age, gender, degree of contamination according to CDC wound classification, SAP administration, post-operative antibiotic use, and outcomes (SSI, allergy, and other morbidities, or mortality). The Newcastle-Ottawa Quality Assessment Scale⁴⁰ was used to assess the quality of included observational studies, while RCTs were assessed using RevMan 5.4. Odds ratios for all included studies comparing SSIs between participants who received SAP, and those who did not, were extracted or computed from reported data, and used to derive the effect size in the meta-analyses.

Risk of bias assessment

Two authors (P.M.N. and Y.H.) independently assessed the risk of bias of included studies using the Cochrane Collaboration's tool for assessing risk of bias in RCTs,^41,42 and the Newcastle-Ottawa Scale for Observational Studies.⁴² The Newcastle-Ottawa scales were converted to the U.S. Agency for Healthcare Research and Quality (AHRQ) standard thresholds (good, fair, and poor) for interpretation.⁴³ Results were displayed as tables for both RCTs and observational studies. The possibility of publication bias was assessed visually with a funnel plot.

Data analysis

Meta-analyses of available comparisons from the included studies were performed using STATA, version 17 (StataCorp LLC, College Station, TX). A random effects model assuming a different underlying effect for each study was used to calculate pooled odds ratios, along with 95% confidence intervals. The I² and a L'Abbe plot were used to assess heterogeneity and dispersion of effects sizes. Meta-analyses were performed for all included studies, with subgroup analysis of RCTs and observational studies. Pooled proportions of SSIs in those who received SAP (SAP group), and those who did not receive SAP (no SAP group) were calculated. Subgroup analyses were performed on type of study, resource setting, surgical specialty, and surgical wound class (SWC).

Results

Database and hand searches yielded 6,901 titles and abstracts; 2,950 duplicates were removed. A further 3,791 were excluded after screening; 160 full-text articles were assessed for eligibility, of which 123 were excluded. Five studies were excluded during data abstraction; 32 studies were included in the meta-analysis (Fig. 1).

FIG. 1.

Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram. SAP = surgical antibiotic prophylaxis

General characteristics of included studies

Thirty-two studies met the study criteria for inclusion: six RCTs^44–49 and 26 observational studies^50–75 including a total of 202,953 children, aged between 0 and 21 years. Five studies used the number of incisions as denominator,^{44,51,54,73,74} whereas the rest reported individual participant outcomes (Table 1). Overall, more males than females were recruited, with the proportion of boys ranging between 43% and 100%; three studies involved only boys.^53,63,69 The 32 studies originated from 17 countries: 12 from the United States,^{52–54,56–58,60,61,63,65,67,71} three from Canada,^59,64,69 two each from Nigeria^44,46 and The Netherlands,^70,72 and one study each from Switzerland,⁵⁰ New Zealand,⁵¹ Germany,⁵⁵ Mexico,⁶² Estonia,⁶⁶ Kenya,⁶⁸ India,⁴⁵ Nepal,⁴⁷ Tunisia,⁷⁴ Bangladesh,⁷⁵ Sweden,⁴⁸ Italy,⁴⁹ and the United Kingdom.⁷³ Twenty-three studies from HICs comprised 98.3% (n = 199,245) of the study participants,^{48–61,63–65,67,69–73} with the United States contributing the majority (n = 187,106). The six RCTs included a total of 1,825 participants, whereas the 26 observational studies had 201,302 participants. Because of the small number of RCTs, and the limited number of abstractable data for subanalyses from the included studies, the authors present combined analysis of the observational and RCT studies.

Table 1.

Characteristics and Included Studies

Study characteristics						Participants
Study ID, year, country	Economy	Specialties	Procedures	Risk factors	Design, scope	Population	Age	SWC	SAP+post-opAb	SAP use conclusion	Total
RCTs
Osuigwe 2006, Nigeria	LMIC	Gen	General surgery, urology, otolaryngology	NS	SC	Ind	NS	1	√	^‡	278
Usang 2008, Nigeria	LMIC	Gen	Inguinal herniotomies	Use of diapers, SWC	SC	Inc	0–15 y	1	X	^ⴕ	104
Vaze 2014, India	LMIC	Gen	Inguinal herniotomies	Weight	SC	Ind	34.02 m	1	√	^‡	251
Khanal 2020, Nepal	LMIC	ENT	Myringoplasty	NS	SC	Ind	11.3 y	1	X	^‡	55
Söderquist-Elinder 1995, Sweden	HIC	Gen	Uncomplicated appendicitis	NS	SC	Ind	NS	2–3	X	^ⴕ	544
Monaco 2009, Italy	HIC	Dental	Mandibular third molar extraction	NS	SC	Inc	15 y	2	X	^ⴕ	59
Observational studies
Horwitz 1997, US	HIC	All	All pediatric surgical procedures	SWC	3C	Ind	3.48 ± 0.14 y	1–4	NS	NS	846
Porras-Hernández, 2003, Mexico	UMIC	Gen, Card, Neuro	Neurosurgical, cardiovascular, and general surgical patients	Procedure duration (>90 min), and use of open drains	SC	Ind	27.5 mo	1–4	X	^ⴕ	428
Bucher^* 2011, US	HIC	All	SWC I/II procedures	Race, postoperative location, skin preparation, urinary catheter, procedure duration, and implantable device	SC	Ind	NS	1, 2	X	NS	16031
Katz 2011, US	HIC	Gen	Laparoscopic pyloromyotomy	Not identified	SC	Ind	39.4 ± 19.8 d	1	X	^‡	195
Bansal, 2012, Switzerland	HIC	Gen	Acute appendectomies	Perforated appendicitis	SC	Ind	3–15 y	1–4	NC	^‡	200
Formaini 2012, US	HIC	Ortho	Minimally invasive orthopedic procedures	NS	SC	Ind	NS	1	X	NS	2330
Smith 2017, Canada	HIC	Uro	Stented hypospadias repair	NS	SC	Ind	NS	1	X	^‡	224
Krom 2020, Netherlands	HIC	Gen	Percutaneous endoscopic gastrostomy	NS	SC	Ind	2.9y (med)	2	X	^‡	297
Ladd 2005, US	HIC	Gen	Supraumbilical pyloromyotomy	Umbilicus	SC	Ind	36.7 d	1	X	^ⴕ	384
Wood^** 2012, Kenya	LMIC	All	Neurosurgery, general surgery, orthopedics, urology, plastic surgery, and gynecology	Not identified	SC	Ind	0–18 y	1–3	X	NS	940
Segal 2014, Canada	HIC	All	Infants admitted to the Neonatal Intensive Care Unit	SWC	SC	Ind	12 m (med)	1–4	NS	NS	724
Shah 2014, US	HIC	Gen, card, spine	General surgery, cardiac surgery, and spinal surgery	Inappropriately administered SAP had a 1.7-fold increased risk of SSIs.	SC	Ind	4.16 ± 5.5 y	1–4	X	^ⴕ	5023
Ellett 2015, US	HIC	Uro	SWC I/II urologic procedures	NS	SC	Inc	3.7 ± 4.4y	1, 2	NS	NS	1192
Engelmann 2015, Germany	HIC	Gen	Percutaneous endoscopic gastrostomy	NS	SC	Ind	2.42 y (med)	2	X	^ⴕ	103

Koshbin 2015, Canada	HIC	All	Children undergoing surgery: in cardiovascular surgery, general surgery, neurosurgery, orthopedic surgery, otolaryngology, plastic surgery, and urology.	Non-compliance with SAP guidelines, gender, age, weight, ASA class, procedure duration, SWC, post-operative location, cardiovascular surgery	SC	Ind	6.8 ± 5.7 y	1–4	NS	NS	9465
Battin 2016, New Zealand	HIC	Gen	Neonatal abdominal procedures	None identified	SC	Inc	0–28 d	1–4	NS	NS	60
Nuzzi 2016, US	HIC	Plast	Excision of skin lesions	None identified	SC	Ind	9.1 ± 5. 2y	1	X	^‡	872
Chan 2017, US	HIC	Uro	Circumcision	NS	43C	Ind	2 y (med)	1	X	^‡	84226
Perotti 2018, US	HIC	Ortho	Soft-tissue procedures without a groin incision, in patients with cerebral palsy	NS	SC	Ind	10 ± 4.8 y	1	X	^‡	125
Rensing, 2018, US	HIC	Uro, Gen	Pediatric orchiopexy	None identified	43C	Ind	4.6 y	1	X	^‡	71676
Van Els 2016, Netherlands	HIC	Gen	Percutaneous endoscopic gastrostomy	NS	SC	Ind	4.9 ± 4.8 y	2	X	^‡	129
Varik 2018, Estonia	UMIC	Gen, Uro, Ortho	General surgical, orthopedic and urological	SWC, operation related complications	SC	Ind	NS	1–4	NS	NS	589
Williams 2018, US	HIC	Gen	Pyloromyotomy	NS	49C	Ind	36.2 ± 17.4 m	1	X	^‡	4206
Kaabachi 2006, Tunisia	LMIC	Ortho	Orthopedic procedures	Talipes equina varus	SC	Inc	5.4 ± 3.5 y	1–3	X	NS	503
Hassan 2013, Bangladesh	LMIC	All	Elective day cases	NS	3C	Ind	NS	1	√	^‡	200
Jones 2019, UK	HIC	Ortho	Elective non-spinal orthopedic procedures	Surgical incisions >10 cm, procedure duration >1 h	SC	Ind	NS	1–3	X	NS	334

US = United States; UK = United Kingdom; SWC = surgical wound class; SSI = surgical site infection; SAP = surgical antibiotic prophylaxis; RCTs = randomized controlled trials; LMIC = low- and-middle income country; UMIC = upper middle income country (included in LMIC for analysis); HIC = high income country; post-opAb = post-operative antibiotic agents; √ = given; X = not given; NS = not stated; NC = not clear; Ind = individual participant counted; Inc = each incision included as individual participant; Gen = general pediatric surgery; ENT = ear, nose, and throat; Card = cardiothoracic; Neuro = neurosurgery; Ortho = orthopedic surgery; Plast = plastic; C = centers; SC = single center; med = median.

ⴕ

Advocated for SAP use.

‡

No evidence for use of SAP.

Bucher, Patients who did not return for review were logged in as negative for SSI.

Wood, Numbers did not add up.

Three studies from the United States used the Pediatric Health Information System (PHIS) database, containing data from more than 45 not-for-profit, tertiary care pediatric hospitals. These accounted for 80% of the total study participants; they reported data on three different procedures: circumcision, orchiopexy, and pyloromyotomy, respectively.^53,63,67 The nine studies from LMICs (including four of the six RCTs) had a total of 3,348 participants.^{44–47,62,66,68,74,75} Twenty-seven studies^{44–52,54–56,58–62,64–66,68–74} were conducted in single centers, whereas five were multicenter studies.^{53,57,63,67,75} Twelve studies involved general pediatric surgical patients^{44–46,48,50,51,55,58,67, 70–72}; four studies were focused on pediatric orthopedic surgery,^56,61,73,74 three were conducted in urology,^53,54,69 and one each in plastic surgery, dental surgery, and otolaryngology, respectively^47,49,60; four studies included combinations of two or three specialties each,^62,63,65,66 whereas six studies involved patients from all specialties.^{52,57,59,64,68,75}

Risk factors for SSI

Five studies^{44,57,59,64,66} found a positive association between SWC and SSI. Other factors associated with SSI among study participants were length of surgical procedure and non-compliance with SAP guidelines (underuse and overuse).^{50,51,57,59,62,64–66} Varik et al.⁶⁶ reported a positive association between SSI and length of hospital stay (p = 0.001). Three studies did not find an association between age and SSI,^51,57,59 and two of these did not find an association between weight and SSI.^51,59 The risk factors identified by the different studies were varied and the data as reported could not be abstracted for subanalyses (Table 1).

Surgical antibiotic prophylaxis-related morbidity

Four studies reported SAP-related allergies,^53,60,63,66 two of which found statistically significant higher odds (1.2 and 1.5) of allergic reactions among the SAP group compared with the no SAP group (p < 0.005).^53,63 Varik et al.⁶⁶ did not comment on whether the allergies reported in their study were attributable to SAP. No SSI- or SAP-related deaths were reported in the included studies. Meta-analysis of the 32 included studies^44–75 on the effect of SAP on SSI yielded an odds ratio (OR) of 1.20 (95% confidence interval [CI], 0.91–1.58), comparing children receiving SAP with those who did not (Fig. 2). Meta-analysis of observational studies revealed an OR of 1.34 (95% CI, 1.01–1.79; p = 0.04); meta-analysis of the RCTs favored the use of SAP, but this was not statistically significant (OR, 0.57; 95% CI, 0.26–1.24; p = 0.157).

FIG. 2.

Meta-analysis of all studies. OBS = observational studies; MC = multi-center; RCT = randomized clinical trial; SC = single center; CI = confidence interval.

Usang et al.⁴⁴ did not record any SSI in the SAP group, but follow-up was short (7 days) resulting in an OR of 0.08, (95% CI, 0.00–1.41); although this study was a relative outlier, a sensitivity analysis excluding this study did not change the overall pooled results.

The studies exhibited a high degree of heterogeneity (I² = 95.15%) in SSI prevalence; 2% (95% CI, 2%–3%) of SAP recipients developed SSI, whereas 1% (95% CI, 1%–1%) of those not receiving SAP developed SSI (Table 2). Subanalysis by specific SWC procedures did not show a statistically significant effect of SAP, albeit with huge heterogeneity (except for the studies focused on SWC I procedures). The pooled odds ratio comparing participants receiving and those not receiving SAP limited to studies including combined SWC I–IV procedures was 2.00 (95% CI, 1.44–2.79) with considerable heterogeneity across studies. Pooled proportions by SWC classes are reported in Table 2. Surgical antibiotic prophylaxis did not decrease the odds of SSI in children managed in general pediatric surgery (OR, 0.72; 95% CI, 0.47–1.18).^{44–46,48,50,51,55,58,67,70–72} Eight studies reported a positive association between length of surgery and SSI occurrence; in these studies, SAP recipients had 1.82 times higher odds of developing an SSI than those in the no SAP group (OR, 1.82; 95% CI, 1.27–2.63).^{50,51,57,59,62,66,68,73}

Table 2.

Summary of Findings

		Total with			ES			Favors		Meta-proportion
	Participants	SAP (SSI/N)	No SAP (SSI/N)	Heterogeneity (I²)	OR	95% CI	Test for overall effect (p)	SAP	No SAP	SAP with SSI % (95% CI)	No SAP with SSI % (95% CI)
1	All studies	559/53,497	600/144,910	56.9%	1.199	0.909–1.582	0.198		√	2 (2–3)	1 (1–1)
Subgroups
2	Observational	538/52,770	569/144,346	57.0%	1.342	1.010–1.785	0.043		√	2 (2–2)	1 (1–1)
3	RCTs	21/727	31/564	30.9%	0.570	0.262–1.242	0.157	√		3 (2–4)	5 (3–8)
4	HIC studies	414/5,1703	509/143,356	57.3%	1.060	0.769–1.460	0.722		√	2 (1–2)	1 (0–1)
5	Non-HIC studies	145/1794	91/1554	44.8%	1.649	0.983–2.768	0.058		√	7 (4–10)	6 (2–9)
6	Wound class I studies	41/34,989	201/125,951	0.0%	0.85	0.577–1.256	0.416	√		0 (0–0)	0 (0–0)
	Wound class II studies	39/605	69/527	40.8%	0.653	0.311–1.370	0.259	√		8 (2–15)	11 (4–17)
7	Wound class I–IV studies	314/9,535	199/7,800	57.6%	1.870	1.255–2.786	0.002		√	4 (2–5)	1 (1–2)
8	Studies from the US	219/45672	312/137,248	65%	1.257	0.751–2.106	0.384		√	1 (1–1)	0 (0–1)

SAP = surgical antibiotic prophylaxis; SSI = surgical site infection; OR = odds ratio; 95% CI = 95% confidence interval; RCTs = randomized controlled trials; HIC = high income country; US = United States; N = total number of participants in the group.

Subanalysis by resource setting did not show any effect of SAP in studies performed in HICs^{48–61,63–65,67,69–73} (OR, 1.06; 95% CI, 0.77–1.46), whereas patients receiving SAP in studies conducted in LMICs had higher odds of developing SSI^{44-47,62,66,68,74,75} (OR, 1.65; 95% CI, 0.99–2.76; I² = 48.3%). Pooled prevalence of SSI in those not receiving SAP was 6% (95% CI, 2%–9%) in LMICs and 1% (95% CI, 1%–1%) in HICs (Table 2).

There was no difference in effect when investigating the effect of SAP in single versus multicenter studies. There were insufficient data on many factors known to be associated with SSI, such as cost, length of stay, re-admission, and re-operation; it was therefore not possible to perform subanalyses on these.

Heterogeneity and publication bias

The included studies were conducted across 17 countries, involved different pediatric surgical specialties and SWC procedures as well as age groups, creating substantial clinical heterogeneity. Statistical heterogeneity is reflected in the generally wide confidence intervals of the effect sizes and high I² of pooled estimates. Meta-analysis of proportions of SSI in the two comparison groups yielded high heterogeneity (>38% to 96%). Figure 3 shows that most studies are located along the no effect line, with some outliers indicating heterogeneity.

FIG. 3.

L'Abbe plot.

Publication bias

The funnel plot of all included studies was asymmetrical suggesting publication bias (Fig. 4). There was no evidence against small study effects on both Egger's test (p = 0.622), and Begg's test (p = 0.793).⁷⁶

FIG. 4.

Funnel plot. OBS = observational studies; MC = multi-center; RCT = randomized clinical trial; SC = single center; CI = confidence interval.

Quality of included studies

The overall quality of the six randomized clinical trials^44–49 was low with a placebo being used in only trial one⁴⁶ (Table 3). None of the RCTs included a sample size calculation and almost all were underpowered to detect a clinically relevant difference. One RCT⁴⁴ followed patients for only seven days likely resulting in outcome misclassification, and ascertainment bias.

Table 3.

Risk of Bias of RCTs

RCT author, year	A–Random sequence generation (selection bias)	B–Allocation concealment (selection bias	C–Blinding of participants and personnel (performance bias)	D–Blinding of outcome assessment (detection bias)	E–Incomplete outcome data (attrition bias)	F–Selective reporting (reporting bias)
Söderquist-Elinder, 1995	Unclear	Unclear	Unclear	Unclear	Low risk	Low risk
Osuigwe, 2006	Low risk	Low risk	Low risk	Low risk	Low risk	High risk
Usang, 2008	Low risk	Low risk	Unclear	Low risk	Low risk	Low risk
Monaco, 2009	Unclear	High risk	Unclear	Unclear	Unclear	Unclear
Vaze, 2014	Unclear	Unclear	High risk	Low risk	Low risk	Low risk
Khanal, 2020	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk

RCT = randomized controlled trial

The average Newcastle-Ottawa Scale scores for the 26 observational studies^50–75 was 6.8 (Tables 4 and 5); these scores were converted to the AHRQ⁷⁷ standard thresholds: 25 studies were of good quality, whereas one was of fair quality.⁵⁵

Table 4.

Risk of Bias of Observational Studies

Quality assessment criteria		Acceptable (^*)	Bansal 2012	Battin 2016	Bucher 2011	Chan 2017	Ellet 2015	Engelmann 2015	Formaini 2012	Hasan 2013	Horwitz 1997	Jones 2019	Kaabachi 2005	Katz 2011	Khoshbin 2011	Krom 2020	Ladd 2005	Nuzzi 2016	Perotti 2018	Porras-Hernandez 2003	Rensing 2018	Sega 2014	Shah 2014	Smith 2017	van Els 2016	Varik 2018	Williams 2018	Wood 2012
Selection	1) Representativeness	c) Selected group of users	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
	2) Selection of non-exposed cohort	a) Drawn from the same community as the exposed cohort^*	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
	3) Ascertainment of exposure	a) Use of a secure record^*	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
	4) Demonstration that outcome of interest was not present at start of study?	a) Yes^*	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
Comparability	1) Comparability of cohorts on the basis of the design or analysis	b) Study controls for any additional factor (age)^*	√	√	√	√	√		√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
Comparability		c) Cohorts are not comparable based on design or analysis controlled for confounders						√
Outcome	1) Assessment of outcome	b) Record linkage^*	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
	2) Was follow-up long enough for outcomes to occur (30-d follow up)?	a) Yes (majority of population at least 30 d)^*	√	√	√	√	√	√	√	X	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
	3) Adequacy of follow-up of cohorts	a) Complete follow-up–all subjects accounted for^*	√	√	√	√	√	√		√		√	√		√	√	√	√	√	√	√	√	√	√	√	√	√	√
		b) Subjects lost to follow-up unlikely to introduce bias–small number lost -							√		√
		>80% follow-up, or description provided of those lost, providing a non-selective loss to follow-up^*
		c) Follow up rate <80% and no description of those lost, or a selective loss to follow up												√
Total			7	7	7	7	7	6	6	5	6	7	7	6	7	7	7	7	7	7	7	7	7	7	7	7	7	7

Newcastle-Ottawa Quality Assessment Scale: A study is awarded a maximum of one star (^*) for each numbered item within the Selection and Exposure categories. A maximum of two stars can be given for Comparability. The total number of stars within each study give an aggregate (total) score, which reflects the quality of the study.

Table 5.

AHRQ Standard Thresholds for Risk of Bias of Observational Studies

	Domain
Quality	Selection	Comparability	Outcome
Good	3 or 4 stars	1 or 2 stars	2 or 3 stars
Fair	2 stars	1 or 2 stars	2 or 3 stars
Poor	0 or 1 star	0 stars	0 or 1 stars

Discussion

This systematic review and meta-analysis found no evidence of a preventive effect of SAP on SSI in children overall and in subanalyses conducted across SWC procedures, resource setting, and study design. Meta-analysis of the observational studies favored the no SAP group (OR, 0.342; p = 0.043), whereas RCTs favored the SAP group (OR, 0.570; p = 157), and a pooled OR of 1.199, p = 0.198, in favor of the no SAP group. Meta-analysis of proportions of SSI in the two comparison groups yielded high heterogeneity (38% to 96%).

Surgical wound classification was introduced by the National Academy of Sciences in 1964; it divides surgical wounds into four categories based on the potential bacterial load of the wound, and therefore increasing risk of SSI: clean (SWC I), clean-contaminated (SWC II), contaminated (SWC III), and dirty (SWC IV).⁷⁸ Surgical wound classification in adults is an important determinant of SSI risk, with SSI guidelines indicating increasing SSI rates with increasing wound contamination (1%–5% for SWC I; 3%–11% for SWC II; 10%–17% for SWC III; and over 27% for SWC IV)⁷⁹; SWC is also one of the three components that make up the National Nosocomial Infections Surveillance (NNIS) risk index, the most commonly used SSI risk stratification index in adults.⁸⁰

Fourteen studies that exclusively focused on SWC I procedures comprised 81.5% of all participants in the included studies. Many authorities hold the view that the risk of SSI in SWC I is so low that SAP does not provide any additional benefit to patients.^81,82 Whereas SSI prevention guidelines are unanimous on SAP administration for SWC II to IV for adults,^83–85 the management of SWC I remains contentious. Current guidelines on SAP in adults do not recommend SAP for SWC I procedures, except for patients undergoing surgery with placement of prostheses or implants, and the occasional specialty-specific, patient-specific, or institution-specific recommendations.⁸³ Surgical antibiotic prophylaxis may also be justified for any procedure if the patient has an underlying medical condition associated with a high risk of SSI.^83–85 The WHO and CDC SSI prevention guidelines do not provide guidance on SWC-specific SAP, but rather have left it to local or specialty guidelines to determine local practice.^24,28

The incidence of SSI in pediatric patients in HICs is estimated at 2% to 5%.⁸⁶ In this study, the incidence of SSI in all included studies ranged between 0% and 18.7%; in 10 studies, all from HICs, the SSI incidence was below 1%.^{52–54,56,60,61,63} The incidence of SSIs in studies conducted in LMICs (1.19%–18.7%) was higher compared with studies from HICs. The pooled SSI proportion among children who did not receive SAP was 1% and 6% in HIC and LMIC studies, respectively. High SSI rates have been reported among adults in LMIC,^17,87 but have not yet been systematically reviewed in children.^68,88 Our findings are consistent with a WHO SSI estimate of 12.7%, (95% CI, 6.7–20.3) among children in LMIC settings.²⁸ Although children in LMICs experience higher rates of SSI than those in HICs, there is no evidence that SAP prevents SSIs in LMICs, and multimodal interventions are more likely to lead to successful reduction of SSI rates even in this setting.¹⁷ Surgical antibiotic prophylaxis administration in studies including combined SWC I–IV procedures^{50,51,57,59,62 64–66} was paradoxically associated with a 1.87 increased odds of SSI among SAP recipients, compared with the no SAP group; inappropriate use of SAP (under- or overuse), allocation bias (if SAP recipients received SAP because of a perceived higher risk of infection), and residual confounding are possible explanations for this result.

A number of authors have not found an association between SAP administration and SSI in children, across different resource settings.^86,88,89 Their findings of no benefit of SAP in children are consistent with the results of this review and meta-analysis.

The incidence of SSI in children across all procedures in this review was low: 1% to 2%, with an even lower incidence in children undergoing SWC I procedures (<0.01%). Studies performing only SWC I procedures had limited heterogeneity (I² = 0%), a statistically non-significant SSI reduction in the SAP group compared with the no SAP group (OR, 0.85; 95% CI, 0.577–1.256; p = 0.416), and equivalent metaproportions between the SAP and no SAP groups with SSI (<0.001%; Table 2). Thus, in SWC I procedures, excluding cardiovascular, spine, and neurosurgic procedures, with such a low SSI incidence, the number needed to treat with antibiotic agents to prevent an SSI would be vast even if SAP were to provide 100% protection, and therefore, the benefit of SAP would be questionable even if a protective effect existed. Unfortunately, except for SWC I studies, the number of patients receiving SAP by SWC was not reported in studies with mixed surgical wound classes, therefore stratified SWC analyses could not be performed to determine the effect of SAP for the different SWC procedures (Table 1).

Although five studies included in this review reported a positive association between SWC and SSI,^{44,57,59,64,66} two large studies have questioned the utility of the current surgical wound classification in children, arguing that it does not reflect SSI risk in children.^15,90 Furthermore, significant inter-observer differences in pediatric surgical wound classification have been reported.⁹¹ Similarly, a number of authors have questioned the value of NNIS risk index among children,^32,92 with some proposing either local adaptation of the NNIS index, or even the creation of a new SSI risk index.^92,93

Although SAP may be the most important SSI prevention measure in adults, it is not without complications. Surgical antibiotic prophylaxis-related adverse effects include allergic reactions ranging from minor skin rashes to anaphylaxis, Clostridium difficile infection, the emergence of resistant organisms, and mortality. Antimicrobial stewardship is an essential component of SSI prevention, in ensuring appropriate use of SAP, because inappropriate use (both under- and overuse), may increase the rate of SAP-related adverse events including the occurrence of preventable SSIs, the development of multi-drug resistance, and allergies, among other undesirable outcomes; overuse is more frequent among pediatric patients.^27,94–97 These complications often lead to increased length of hospital stay, and an increase in health care costs at individual, and the population level.^63,94,95,98 Of the 32 included studies, only four reported adverse effects^{53,60,63 66}; it was therefore not possible to perform a subgroup analysis of adverse events.

Given the heterogeneity of the included studies, the absence of a clear benefit of SAP for SSI prevention, and the potential adverse effects resulting from SAP administration, well-designed studies are needed to determine the value and effectiveness of SAP in SWC II to IV, whereas guidelines should at least recommend against SAP administration in SWC I procedures in children, with appropriate exceptions.³⁰

Surgical antibiotic prophylaxis use and SSI prevention in children

The notion that “children are not just small adults”^99–101 is an important consideration in applying SSI prevention measures. These should not be borrowed from adults and applied directly to children: “absence of evidence is not evidence of absence.”¹⁰² This review and meta-analysis presents evidence on pediatric SSIs that suggests the need for a re-analysis of SSI risk factors and therefore preventive interventions in this patient population. Currently, the risk factors are not well defined, whereas SWC and the NNIS risk index are under contention.^15,32,90 In adults, the hierarchy of SSI risk factors is well established, allowing for an ethically acceptable and achievable evidence-based prioritization of preventive measures in any resource setting,^3,17,23 a situation that is desirable for children as well.

This review and meta-analysis has a number of limitations: included studies had to be in English and only six fairly small RCTs were retrieved, whereas observational studies were heterogenous, with limited abstractable data for subgroup analyses; the bulk of the studies were from HICs, with a disproportionately large contribution from the United States.

This review nevertheless has a number of strengths. It included studies from all types of economies, geographical locations, surgical wound classes, and pediatric specialties. In addition, the study identified a number of gaps in SAP and SSIs in children that will hopefully stimulate research and help improve patient outcomes.

Conclusions

This review and metanalysis did not find a preventive action of SAP against SSI, however, in general, it is to be noted that because of the low-quality RCTs and preponderance of observational studies, residual confounding likely affected the direction of the effect estimates. Furthermore, allocation bias may have led to patients with a high risk of SSI receiving SAP leading to the observed paradoxical higher SSI rates among SAP recipients; these results should therefore be interpreted with caution.

The principal message of this study is in highlighting the absence of quality data to drive evidence-based decision-making in SSI prevention in children, and in advocating for more research in this field. Our results suggest that SAP should not be used in SWC I procedures in children.

Footnotes

Acknowledgments

Part of this work was presented by P.M.N. as a thesis at the London School of Hygiene and Tropical Medicine.

Authors' Contributions

P.M.N. and K.K. designed the study. P.M.N. and Y.H. screened records, extracted data, and assessed risk of bias. P.M.N. performed the statistical analysis. P.M.N., Y.H., G.P., and K.K. analyzed and interpreted the data. P.M.N. drafted the manuscript. All authors provided critical conceptual input, interpreted the data analysis, and critically revised the manuscript, and read and approved the final manuscript.

Funding Information

No funding was received.

Author Disclosure Statement

All authors declare that there are no competing financial interests.

Supplementary Material

References

Araujo da Silva

, Zingg

, Dramowski

, et al. Most international guidelines on prevention of healthcare-associated infection lack comprehensive recommendations for neonates and children. J Hosp Infect, 2016; 94:159–162.

Kizilcan

, Tanyel

, Buyukpamukcu

, Hicsonmez

. The necessity of prophylactic antibiotics in uncomplicated appendicitis during childhood. J Pediatr Surg, 1992; 27:586–588.

Allegranzi

, Zayed

, Bischoff

, et al. New WHO recommendations on intraoperative and postoperative measures for surgical site infection prevention: An evidence-based global perspective. Lancet Infect Dis, 2016; 16:e288–e303.

Raval

, Dillon

, Bruny

, et al. American College of Surgeons National Surgical Quality Improvement Program Pediatric: A phase 1 report. J Am Coll Surg, 2011; 212:1–11.

Zingg

, Hopkins

, Gayet-Ageron

, et al. Health-care-associated infections in neonates, children, and adolescents: An analysis of paediatric data from the European Centre for Disease Prevention and Control point-prevalence survey. Lancet Infect Dis, 2017; 17:381–389.

Horan

, Gaynes

, Martone

, et al. CDC definitions of nosocomial surgical site infections, 1992: A modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol, 1992; 13:606–608.

Kirkland

, Briggs

, Trivette

, et al. The impact of surgical-site infections in the 1990s: Attributable mortality, excess length of hospitalization, and extra costs. Infect Control Hosp Epidemiol, 1999; 20:725–730.

Taylor

, Shekerdemian

. Avoidance of hospital-acquired infections in pediatric cardiac surgical patients. Pediatr Crit Care Med, 2016; 17:S279–286.

Harrod

, Boykin

, Hedequist

. Complications of infection in pediatric spine surgery. Pediatric Health, 2009; 3:579–592.

10.

, Vittinghoff

, Nobuhara

, et al. Surgical site infections in neonates and infants: Is antibiotic prophylaxis needed for longer than 24 h?. Pediatr Surg Int, 2014; 30:587–592.

11.

Salsgiver

, Crotty

, LaRussa

, et al. Surgical site infections following spine surgery for non-idiopathic scoliosis. J Pediatr Orthop, 2017; 37:e476–e483.

12.

Knerlich-Lukoschus

, Messing-Junger

. Prophylactic antibiotics in pediatric neurological surgery. Childs Nerv Syst, 2018; 34:1859–1864.

13.

Zimlichman

, Henderson

, Tamir

, et al. Health care–associated infections. JAMA Intern Med, 2013; 173:2039.

14.

Centers for Disease Control and Prevention; National Healthcare Safety

Network

. Surgical site infection event (SSI). Atlanta

: Centers for Disease Control and

Prevention

, 2021. https://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf (Last accessed February 20, 2022).

15.

Oyetunji

, Gonzalez

, et al. Wound classification in pediatric surgical procedures: Measured and found wanting. J Pediatr Surg, 2016; 51:1014–1016.

16.

Anderson

, Kaye

, Classen

, et al. Strategies to prevent surgical site infections in acute care hospitals. Infect Control Hosp Epidemiol, 2008; 29(Suppl 1):S51–61.

17.

Allegranzi

, Aiken

, Zeynep Kubilay

, et al. A multimodal infection control and patient safety intervention to reduce surgical site infections in Africa: A multicentre, before-after, cohort study. Lancet Infect Dis, 2018; 18:507–515.

18.

Keenan

, Speicher

, Thacker

, et al. The preventive surgical site infection bundle in colorectal surgery: An effective approach to surgical site infection reduction and health care cost savings. JAMA Surg, 2014; 149:1045–1052.

19.

Nordin

, Sales

, Besner

, et al. Effective methods to decrease surgical site infections in pediatric gastrointestinal surgery. J Pediatr Surg, 2017; 53:52–59.

20.

Toltzis

, O'Riordan

, Cunningham

, et al. A statewide collaborative to reduce pediatric surgical site infections. Pediatrics, 2014; 134:e1174–1180.

21.

Bert

, Giacomelli

, Amprino

, et al. The “bundle” approach to reduce the surgical site infection rate. J Eval Clin Pract, 2017; 23:642–647.

22.

Leaper

, Tanner

, Kiernan

, et al. Surgical site infection: Poor compliance with guidelines and care bundles. Int Wound J, 2015; 12:357–362.

23.

Allegranzi

, Bischoff

, de Jonge

, et al. New WHO recommendations on preoperative measures for surgical site infection prevention: An evidence-based global perspective. Lancet Infect Dis, 2016; 16:e276–e287.

24.

Berríos-Torres

, Umscheid

, Bratzler

, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg, 2017; 152:784.

25.

Bratzler

, Houck

. Antimicrobial prophylaxis for surgery: An advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis, 2004; 38:1706–1715.

26.

, Aleem

, Tsang

, et al. Increasing compliance with an antibiotic prophylaxis guideline to prevent pediatric surgical site infection: Before and after study. Ann Surg, 2015; 262:403–408.

27.

Ciofi Degli Atti

, Alegiani

, Raschetti

, et al. A collaborative intervention to improve surgical antibiotic prophylaxis in children: Results from a prospective multicenter study. Eur J Clin Pharmacol, 2017; 73:1141–1147.

28.

World Health Organization. Global Guidelines for the Prevention of Surgical Site Infection. Geneva: World Health Organization; 2018.

29.

Rangel

, Islam

, St. Peter SD, et al. Prevention of infectious complications after elective colorectal surgery in children: An American Pediatric Surgical Association Outcomes and Clinical Trials Committee comprehensive review. J Pediatr Surg, 2015; 50:192–200.

30.

Jaworski

, Kansy

, Dzierzanowska-Fangrat

, Maruszewski

. Antibiotic prophylaxis in pediatric cardiac surgery: Where are we and where do we go? A systematic review. Surg Infect, 2019; 20:253–260.

31.

Balkhy

, Zingg

. Update on infection control challenges in special pediatric populations. Curr Opin Infect Dis, 2014; 27:370–378.

32.

Kagen

, Bilker

, Lautenbach

, et al. Risk adjustment for surgical site infection after median sternotomy in children. Infect Control Hosp Epidemiol, 2007; 28:398–405.

33.

Duque-Estrada

, Duarte

, Rodrigues

, Raphael

. Wound infections in pediatric surgery: A study of 575 patients in a university hospital. Pediatr Surg Int, 2003; 19:436–438.

34.

Gras-Le Guen

, Dumont

, Pichenot

, et al. Neonatal surgical antibioprophylaxis: Which target? Which propositions?. Arch Pediatr, 2013; 20(Suppl 3):S83–85.

35.

Laituri

, Arnold

. A standardized guideline for antibiotic prophylaxis in surgical neonates. Semin Pediatr Surg, 2019; 28:53–56.

36.

Subramanyam

, Schaffzin

, Cudilo

, et al. Systematic review of risk factors for surgical site infection in pediatric scoliosis surgery. Spine J, 2015; 15:1422–1431.

37.

PROSPERO. 2019. www.crd.york.ac.uk/PROSPERO/#myprospero (Last accessed June 18, 2022).

38.

Liberati

, Altman

, Tetzlaff

, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med, 2009; 6:e1000100.

39.

Moher

, Liberati

, Tetzlaff

, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med, 2009; 6:e1000097.

40.

Wells

, Shea

, O'Connell

, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2013. www.ohri.ca/programs/clinical_epidemiology/oxford.asp (Last accessed January 28, 2021.

41.

Data collection form for intervention review: RCTs and non-RCTs of The Cochrane Collaboration. https://dplp.cochrane.org/data-extraction-forms (Last accessed November 28, 2018).

42.

Higgins JPT Savovic

, Page

, et al. Revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0). TEMPLATE FOR COMPLETION. 2018. https://drive.google.com/file/d/1Qnqk8q5t0M5Sb9yjrCN5Unbz6aDyTrIC/viewLast accessed February 10, 2019).

43.

Penson

, Krishnaswami

, Jules

, et al. Evaluation and treatment of cryptorchidism. Rockville MD: Agency for Healthcare Research and Quality. Comparative Effectiveness Review; 88. 2012. http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=1352&pageaction=displayproduct (Last accessed June 18, 2022).

44.

Usang

, Sowande

, Adejuyigbe

, et al. The role of preoperative antibiotics in the prevention of wound infection after day case surgery for inguinal hernia in children in Ile Ife, Nigeria. Pediatr Surg Int, 2008; 24:1181–1185.

45.

Vaze

, Samujh

, Narasimha Rao

. Risk of surgical site infection in paediatric herniotomies without any prophylactic antibiotics: A preliminary experience. Afr J Paediatr Surg, 2014; 11:158–161.

46.

Osuigwe

, Ekwunife

, Ihekowba

. Use of prophylactic antibiotics in a paediatric day-case surgery at NAUTH, Nnewi, Nigeria: A randomized double-blinded study. Trop Doct, 2006; 36:42–44.

47.

Khanal

P GR

, Bhusal

. Comparison of postoperative infection and graft uptake rate using single dose of intravenous co-amoxiclav versus no antibiotic in children undergoing myringoplasty: A randomized controlled trial. Int J Pediatr Otorhinolaryngol, 2020; 131:109893.

48.

Söderquist-Elinder

, Hirsch

, Bergdahl

, et al. Prophylactic antibiotics in uncomplicated appendicitis during childhood: A prospective randomised study. Eur J Pediatr Surg, 1995; 5:282–285.

49.

Monaco

, Tavernese

, Agostini

, Marchetti

. Evaluation of antibiotic prophylaxis in reducing postoperative infection after mandibular third molar extraction in young patients. J Oral Maxillofac Surg, 2009; 67:1467–1472.

50.

Bansal

, Altermatt

, Nadal

, Berger

. Lack of benefit of preoperative antimicrobial prophylaxis in children with acute appendicitis: A prospective cohort study. Infection, 2012; 40:635–641.

51.

Battin

, Jamalpuri

, Bough

, Voss

. Antibiotic prophylaxis and neonatal surgical site infection. J Paediatr Child Health, 2016; 52:913–914.

52.

Bucher

, Warner

, Dillon

. Antibiotic prophylaxis and the prevention of surgical site infection. Curr Opin Pediatr, 2011; 23:334–338.

53.

Chan

, Whittam

, Moser

EAS

, et al. Adverse events associated with surgical antibiotic prophylaxis for outpatient circumcisions at US children's hospitals. J Pediatr Urol 2017;13:205.e201–205.

54.

Ellett

, Prasad

, Purves

, Stec

. Post-surgical infections and perioperative antibiotics usage in pediatric genitourinary procedures. J Pediatr Urol, 2015; 11:358:e351–356.

55.

Engelmann

, Wenning

, Fertig

, et al. Antibiotic prophylaxis in the management of percutaneous endoscopic gastrostomy in infants and children. Pediatr Int, 2015; 57:295–298.

56.

Formaini

, Jacob

, Willis

, Kean

. Evaluating the use of preoperative antibiotics in pediatric orthopaedic surgery. J Pediatr Orthop, 2012; 32:737–740.

57.

Horwitz

, Chwals

, Doski

, et al. Pediatric wound infections: a prospective multicenter study. Ann Surg, 1998; 227:553–558.

58.

Katz

, Schwartz

, Moront

, et al. Prophylactic antibiotics do not decrease the incidence of wound infections after laparoscopic pyloromyotomy. J Pediatr Surg, 2011; 46:1086–1088.

59.

Khoshbin

, So

, Aleem

, et al. Antibiotic prophylaxis to prevent surgical site infections in children: A prospective cohort study. Ann Surg, 2015; 262:397–402.

60.

Nuzzi

, Greene

, Meara

, et al. Surgical site infection after skin excisions in children: Is field sterility sufficient?. Pediatr Dermatol, 2016; 33:136–141.

61.

Perotti

, Abousamra

, Rogers

, et al. Prophylactic antibiotics in soft-tissue procedures in children with cerebral palsy. J Child Orthop, 2018; 12:279–281.

62.

Porras-Hernandez

, Vilar-Compte

, Cashat-Cruz

, et al. A prospective study of surgical site infections in a pediatric hospital in Mexico City. Am J Infect Control, 2003; 31:302–308.

63.

Rensing

, Whittam

, Chan

, et al. Is surgical antibiotic prophylaxis necessary for pediatric orchiopexy?. J Pediatr Urol, 2018; 14:261:e261–261.

64.

Segal

, Kang

, Albersheim

, et al. Surgical site infections in infants admitted to the neonatal intensive care unit. J Pediatr Surg, 2014; 49:381–384.

65.

Shah

, Christensen

, Wagner

, et al. Retrospective evaluation of antimicrobial prophylaxis in prevention of surgical site infection in the pediatric population. Paediatr Anaesth, 2014; 24:994–998.

66.

Varik

, Kirsimägi Ü, Värimäe

, et al. Incidence and risk factors of surgical wound infection in children: A prospective study. Scand J Surg, 2010; 99:162–166.

67.

Williams

, Lautz

, Hendrickson

, Oyetunji

. Antibiotic prophylaxis for pyloromyotomy in children: An opportunity for better stewardship. World J Surg, 2018; 42:4107–4111.

68.

Wood

, Nthumba

, Stepita-Poenaru

, Poenaru

. Pediatric surgical site infection in the developing world: A Kenyan experience. Pediatr Surg Int. 2012; 28:523–527.

69.

Smith

, Patel

, Zamilpa

, et al. Analysis of preoperative antibiotic prophylaxis in stented, distal hypospadias repair. Can J Urol, 2017; 24:8765–8769.

70.

Krom

, van den Hoek

CMW

, Benninga

, et al. Do antibiotics reduce the incidence of infections after percutaneous endoscopic gastrostomy placement in children?. J Pediatr Gastroenterol Nutr, 2020; 71:23–28.

71.

Ladd

, Nemeth

, Kirincich

, et al. Supraumbilical pyloromyotomy: A unique indication for antimicrobial prophylaxis. J Pediatr Surg, 2005; 40:974–977.

72.

Van Els

, Van Driel

, Kneepkens

, De Meij

TGJ

. Antibiotic prophylaxis does not reduce the infection rate following percutaneous endoscopic gastrostomy in infants and children. Acta Paediatr, 2017; 106:801–805.

73.

Jones

, Shepherd

, Robinson

, Khandekar

. Surgical site infection following elective nonspinal paediatric orthopaedic surgery: A prospective review. J Pediatr Orthop B, 2019; 28:89–93.

74.

Kaabachi

, Letaief

, Nessib

, et al. Prevalence and risk factors for postoperative infection in pediatric orthopedic surgery: A study of 458 children. Rev Chir Orthop Reparatrice Appar Mot, 2005; 91:103–108.

75.

Hasan

, Saleh

, Hossain

, et al. Antibiotic prophylaxis is unnecessary in clean surgery. Mymensingh Medical J, 2013; 22:342–344.

76.

Egger

, Smith

, Schneider

, Minder

. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997; 315:629–634.

77.

Penson

, Krishnaswami

, Jules

, et al. AHRQ Comparative Effectiveness Reviews: Evaluation and treatment of Cryptorchidism. Rockville, MD: Agency for Healthcare Research and Quality; 2012.

78.

Hart

, Postlethwait

, Brown

Jr , et al. Postoperative wound infections: A further report on ultraviolet irradiation with comments on the recent (1964) national research council cooperative study report. Ann Surg, 1968; 167:728–743.

79.

Culver

, Horan

, Gaynes

, et al. Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infections Surveillance System. Am J Med, 1991; 91:152s–157s.

80.

Horan

, Culver

, Gaynes

, et al. Nosocomial infections in surgical patients in the United States, January 1986-June 1992. National Nosocomial Infections Surveillance (NNIS) System. Infect Control Hosp Epidemiol, 1993; 14:73–80.

81.

Bowater

, Stirling

, Lilford

. Is antibiotic prophylaxis in surgery a generally effective intervention? Testing a generic hypothesis over a set of meta-analyses. Ann Surg, 2009; 249:551–556.

82.

Holzheimer

. Antibiotic prophylaxis. In: Holzheimer

, Mannick

(eds): Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt. W. Zuckschwerdt Verlag GmbH, 2001. https://www.ncbi.nlm.nih.gov/books/NBK6917/ (Last accessed March 15, 2021).

83.

National Institute for Health and Care Excellence: Clinical Guidelines: Surgical Site Infections: Prevention and Treatment. London: National Institute for Health and Care Excellence; 2019.

84.

Bratzler

, Dellinger

, Olsen

, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect, 2013; 14:73–156.

85.

Edwards

, Engelman

, Houck

, et al. The Society of Thoracic Surgeons Practice Guideline Series: Antibiotic Prophylaxis in Cardiac Surgery, Part I: Duration. Ann Thorac Surg, 2006; 81:397–404.

86.

catania vd, boscarelli a, lauriti g, et al. risk factors for surgical site infection in neonates: A systematic review of the literature and meta-analysis. Front Pediatr, 2019; 7:101.

87.

Allegranzi

, Nejad

, Combescure

, et al. Burden of endemic health-care-associated infection in developing countries: Systematic review and meta-analysis. Lancet, 2011; 377:228–241.

88.

Ameh

, Mshelbwala

, Nasir

, et al. Surgical site infection in children: Prospective analysis of the burden and risk factors in a sub-Saharan African setting. Surg Infect, 2009; 10:105–109.

89.

Clements

, Fisher

, Quaye

, et al. Surgical site infections in the NICU. J Pediatr Surg, 2016; 51:1405–1408.

90.

Gonzalez

, Dalton

, Kurtz

, et al. Operative wound classification: An inaccurate measure of pediatric surgical morbidity. J Pediatr Surg, 2016; 51:1900–1903.

91.

Snyder

, Johnson

, Tice

, et al. Wound classification in pediatric general surgery: Significant variation exists among providers. J Am Coll Surg, 2013; 217:819–826.

92.

Casanova

, Herruzo

, Diez

. Risk factors for surgical site infection in children. Infect Cont Hosp Epidemiol, 2006; 27:709–715.

93.

Ercole

, Starling

CEF

, Chianca

TCM

, Carneiro

. Applicability of the national nosocomial infections surveillance system risk index for the prediction of surgical site infections: A review. Braz J Infect Dis, 2007; 11:134–141.

94.

Sandora

, Fung

, Melvin

, et al. National variability and appropriateness of surgical antibiotic prophylaxis in US children's hospitals. JAMA Pediatr, 2016; 170:570–576.

95.

Rangel

, Fung

, Graham

, et al. Recent trends in the use of antibiotic prophylaxis in pediatric surgery. J Pediatr Surg, 2011; 46:366–371.

96.

Giordano

, Squillace

, Pavia

. Appropriateness of Surgical antibiotic prophylaxis in pediatric patients in Italy. Infect Control Hosp Epidemiol, 2017; 38:823–831.

97.

Martinez-Sobalvarro

, Júnior

AAP

, Pereira

, et al. Antimicrobial stewardship for surgical antibiotic prophylaxis and surgical site infections: A systematic review. Int J Clin Pharm, 2022; 44:301–319.

98.

Cosgrove

. The relationship between antimicrobial resistance and patient outcomes: Mortality, length of hospital stay, and health care costs. Clin Infect Dis, 2006; 42:S82–S89.

99.

Ferro

. Paediatric prescribing: Why children are not small adults. Br J Clin Pharmacol, 2015; 79:351–353.

100.

Klassen

, Hartling

, Craig

, Offringa

. Children are not just small adults: The urgent need for high-quality trial evidence in children. PLoS Med, 2008; 5:e172.

101.

Gillis

, Loughlan

. Not just small adults: The metaphors of paediatrics. Arch Dis Child, 2007; 92:946–947.

102.

Altman

, Bland

. Statistics notes: Absence of evidence is not evidence of absence. BMJ, 1995; 311:485–485.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.02 MB

0.00 MB