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Timing of antimicrobial prophylaxis and infectious complications in pediatric patients undergoing appendectomy
Journal of Pediatric Surgery 53 (2018) 449–451
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Timing of antimicrobial prophylaxis and infectious complications in pediatric patients undergoing appendectomy Cristen N. Litz ⁎, Jessica B. Asuncion, Paul D. Danielson, Nicole M. Chandler Division of Pediatric Surgery, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, United States
a r t i c l e
i n f o
Article history: Received 10 February 2017 Received in revised form 26 April 2017 Accepted 4 May 2017 Key words: Pediatric surgery Appendectomy Antimicrobial prophylaxis Infection prevention Surgical site infection Quality improvement
a b s t r a c t Purpose: Antibiotic administration within one hour prior to incision is a common quality metric; however, antibiotics are typically started at the time of diagnosis in pediatric patients with acute appendicitis. The purpose was to determine if antibiotic administration within one hour prior to incision reduces the incidence of surgical site infections (SSI) in pediatric patients with acute appendicitis started on parenteral antibiotics upon diagnosis. Methods: A retrospective review was performed of 478 patients aged 0–18 years who underwent appendectomy for acute appendicitis from 7/2013 to 4/2015. Patients were categorized based on timing of antibiotic administration; there were 198 patients in Group A (b 60 min before) and 280 in Group B (N60 min before). Results: Demographics and operative time (A: 30.5 ± 9.9 vs B: 30.8 ± 12.2 min, p = 0.51) were similar. Procedures were performed laparoscopically and the groups had similar proportions of single-incision operations (A: 53% vs B: 55%, p = 0.64). There was no difference in the incidence of superficial SSI (A: 2.0% vs B: 2.1%, p = 1.0) or intraabdominal abscess (A: 4.0% vs B: 3.6%, p = 0.81) and this remained true when stratified by intraoperative classification. Conclusion: Antibiotic administration within one hour of appendectomy in pediatric patients with acute appendicitis who receive antibiotics at diagnosis did not change the incidence of postoperative infectious complications. Type of study: Treatment study. Level of evidence: III. © 2017 Elsevier Inc. All rights reserved.
Appendicitis is the most common surgical emergency in children and wound infections are the most frequent postoperative complication [1]. Surgical site infections (SSIs) are a great burden on the healthcare system, accounting for approximately two billion dollars in excess healthcare expenditures annually because of longer hospital stays, higher rates of hospital readmission, and increased requirements for home health care and medical supplies [2]. Because of the frequency of appendicitis, there is a rich opportunity to evaluate and improve clinical practice, as postoperative wound infections are one of the most commonly tracked outcome measures [3]. There remains significant variance in the management of pediatric appendicitis and a dearth of pediatric-specific guidelines regarding infection prevention measures [2,4]. According to the American Pediatric Surgical Association (APSA) Outcomes and Clinical Trials Committee, there is Grade A evidence that pediatric patients with appendicitis should receive preoperative broad-spectrum antibiotics and it is standard practice to begin antibiotics at the time of diagnosis [2]. However,
pediatric-specific evidence supporting the commonly used quality metric of antibiotic administration within one hour of operation is lacking [5,6]. The practice of antimicrobial prophylaxis administration one hour prior to incision originated as a Surgical Care Improvement Project (SCIP) measure that was developed for adults without evidence of preoperative infection with the goal of achieving serum and tissue drug levels for the duration of surgery that exceed the minimum inhibitory concentration of the organisms likely to be encountered [7]. This measure was based on evidence from adult literature and similar evidence does not exist for children. An APSA review of pediatric antibiotic prophylaxis in 2015 stated that high quality data to guide clinical practice in children are needed [5]. The purpose of this study was to determine the impact of administering antibiotics within one hour prior to incision on infectious complications in pediatric patients with acute appendicitis who are started on parenteral antibiotics upon diagnosis. 1. Methods
⁎ Corresponding author at: Johns Hopkins All Children's Hospital, Outpatient Care Center, 601 5th Street South, Dept. 70-6600, 3rd Floor, Saint Petersburg, FL 33701, United States. Tel.: +1 727 767 4170; fax: +1 727 767 4346. E-mail addresses: [email protected] (C.N. Litz), [email protected] (J.B. Asuncion), [email protected] (P.D. Danielson), [email protected] (N.M. Chandler). http://dx.doi.org/10.1016/j.jpedsurg.2017.05.005 0022-3468/© 2017 Elsevier Inc. All rights reserved.
Institutional Review Board approval was obtained (No. 00098589). A retrospective cohort study was performed of patients who underwent appendectomy from July 2013 through April 2015. Patients were included if they were 0–18 years of age and underwent appendectomy for acute appendicitis. Exclusion criteria included patients who underwent interval appendectomy, had concurrent procedures performed at the time
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C.N. Litz et al. / Journal of Pediatric Surgery 53 (2018) 449–451
of appendectomy, did not receive preoperative antibiotics, or received antibiotics more than six hours prior to incision. All operations were performed by one of four pediatric surgeons via a multiport or singleincision laparoscopic technique. Patients were categorized into two groups based on the timing of the administration of the last dose of antibiotic prior to incision: Group A (0–60 min before incision) and Group B (61–360 min before incision). Medical records were reviewed and the following data were collected: age, body mass index (BMI) percentile, presenting white blood cell count (WBC), time of antibiotic administration, operative start time, operative duration, and the intraoperative classification of appendicitis. Per protocol at our institution, once the diagnosis of appendicitis is made parenteral antibiotics are initiated and patients receive scheduled redosing until the operation. There is no standard protocol for antibiotic readministration within one hour prior to incision and, instead, this is based on surgeon discretion. The standard antibiotic used for prophylaxis is cefoxitin unless patients have penicillin or cephalosporin allergies, in which case they receive ciprofloxacin and metronidazole. In our community, it is common for transferred patients to receive piperacillin/tazobactam at outside hospitals prior to transfer. The six hour cutoff was chosen since the vast majority of patients in the study received preoperative antibiotics that are dosed every six hours (92% received cefoxitin or zosyn). This protocol utilizes a standardized classification system for the degree of appendicitis based on intraoperative findings which guides postoperative antibiotic management [8–10]. Patients with acute appendicitis do not receive postoperative antibiotics and those with gangrenous or perforated appendicitis are admitted for parenteral antibiotics. Our institution recently completed a randomized controlled study that found that patients with suppurative appendicitis can be discharged home immediately following appendectomy on a 7-day course of oral antibiotics with no difference in infectious complications compared to traditional management (hospital admission for parenteral antibiotics), and this is now our standard practice [article in press]. Patients typically present for postoperative follow-up between 2 and 4 weeks after surgery. The clinic notes and any emergency department (ED) visits or hospital readmissions within 30 days of surgery were reviewed for superficial surgical site infections, intraabdominal abscesses (IAA), or other complications. The primary outcome was the incidence of superficial surgical site infections. Secondary outcomes included the incidence of intraabdominal abscesses, other complications including Clostridium difficile colitis, and hospital readmissions within 30 days. Continuous variables were analyzed by Student's t test or the Mann–Whitney U test as indicated. Categorical data were analyzed with Fisher's exact test. Statistical significance was set at p b 0.05.
Table 1 Demographic and clinical information.
Age, yr BMI percentile WBC, n × 103/μL Case time, min Technique, n (%) - Multiport - SIL OR findingsa, n (%) - Acute - Suppurative - Gangrenous - Perforated - Normal
Group A (n = 198)
Group B (n = 280)
p-Value
11.0 65.1 15.3 30.5
11.1 59.9 14.8 30.8
0.77 0.22 0.27 0.51
± ± ± ±
3.7 (0.4–17.6) 32.6 (2.0–99.7) 5.0 (4.7–27.5) 9.9 (12–70)
± ± ± ±
3.7 (0.9–18.0) 31.9 (0.0–99.6) 5.3 (3.7–36.9) 12.2 (13–80)
94 (47) 104 (53)
126 (45) 154 (55)
0.64
114 (58) 50 (25) 5 (3) 27 (14) 2 (1)
169 (60) 56 (20) 12 (4) 38 (14) 5 (2)
0.57 0.18 0.45 1.0 0.70
BMI = body mass index percentile; WBC = white blood cell count; SIL = single-incision laparoscopy. Continuous data presented as mean ± standard deviation (range). a Acute—inflammation, dilation, or hyperemia limited to the appendix; Suppurative—nonperforated appendix with fibrinous exudate or turbid peritoneal fluid; Gangrenous—gray/black discoloration of the wall without a hole in the appendix or fecalith outside the appendix; Perforated—hole in the appendix or fecalith in the abdomen.
Table 2 compares postoperative outcomes between the two groups. There was no significant difference in the 30-day hospital readmission rate (A: 4.5% vs B: 5%, p = 1.0). The overall incidence of superficial SSI was similar between groups (A: 2% vs B: 2.1%, p = 1.0). In Group A, all 4 SSIs occurred in patients with acute appendicitis, whereas in Group B, 4 SSIs occurred in patients with acute appendicitis and 2 occurred in patients with suppurative appendicitis. The overall incidence of IAAs was also similar between groups (A: 4% vs B: 3.6%, p = 0.81). The majority of IAAs occurred in patients with perforated appendicitis and the incidence was similar between patients with perforated appendicitis in both groups (A: 18.5% vs B: 23.7%, p = 0.76). Two other complications in Group A included one patient with C. difficile colitis and one patient who was readmitted for management of an ileus. Other complications in Group B included one patient with C. difficile colitis, one patient readmitted for management of an ileus, and one patient who developed a small bowel obstruction requiring exploratory laparotomy and lysis of adhesions.
2. Results Six hundred ten patients underwent appendectomy during the study period. Patients were excluded for the following reasons: 45 did not have the timing of antibiotic administration documented (43 of whom were transferred from outside hospitals), 33 underwent an interval appendectomy, 28 received antibiotics after incision in the operating room, and 26 received antibiotics more than 6 hours prior to incision. There were 478 patients included in the analysis: 198 patients in Group A and 280 patients in Group B. Table 1 shows demographic and clinical information. The groups were similar in age (A: 11.0 ± 3.7 vs B: 11.1 ± 3.7 years, p = 0.77) and BMI percentile (A: 65.1 ± 32.6 vs B: 59.9 ± 31.9, p = 0.22). The groups had similar presenting white blood cell counts (A: 15.3 ± 5.0 × 10 3/μL vs B: 14.8 ± 5.3 × 10 3/μL, p = 0.27). Operative time was similar between groups (A: 30.5 ± 9.9 vs B: 30.8 ± 12.2 min, p = 0.51). Both groups had a similar proportion of patients who underwent appendectomy via a single-incision laparoscopic technique (A: 53% vs B: 55%, p = 0.64). There was no significant difference in the intraoperative findings between the two groups.
Table 2 Postoperative outcomes.
Superficial SSI - Acute - Suppurative - Gangrenous - Perforated - Normal - Overall IAA - Acute - Suppurative - Gangrenous - Perforated - Normal - Overall 30-day readmission, n (%) 30-day other complication, n (%)
Group A
Group B
p-value
4/114 (3.5) 0/50 0/5 0/27 0/2 4/198 (2)
4/169 (2.4) 2/56 (3.6) 0/12 0/38 0/5 6/280 (2.1)
0.72 NA NA NA NA 1.0
0/114 3/50 (6) 0/5 5/27 (18.5) 0/2 8/114 (4) 9 (4.5) 2 (1)
0/169 0/56 1/12 (8.3) 9/38 (23.7) 0/5 10/169 (3.6) 14 (5) 3 (1)
NA NA NA 0.76 NA 0.81 1.0 1.0
SSI = surgical site infection; IAA = intraabdominal abscess. Data presented as # occurrences/# patients (%).
C.N. Litz et al. / Journal of Pediatric Surgery 53 (2018) 449–451
3. Discussion This is the first pediatric-specific study that aimed to determine the impact of administering antibiotics within one hour prior to incision on infectious complications in patients with acute appendicitis who are started on parenteral antibiotics upon diagnosis. The overall rate of superficial surgical site infections in this study was 2.1% which is similar to the previously published rates of 2.0% for multiport laparoscopic appendectomy and 4.3% for single-incision laparoscopic appendectomy [11]. Sixty percent of patients with acute appendicitis in this study did not receive antibiotics within one hour prior to incision, and had no significant difference in infectious complications compared to those patients who received antibiotics within one hour prior to incision. The variation in antibiotic prophylaxis administration seen in this study is similar to the variance described by other authors. Recent retrospective cohort studies using the Pediatric Health Information System (PHIS) database have shown that there is substantial hospital and procedural-level variability in the practice of antimicrobial prophylaxis nationwide [6,12]. Perhaps the most significant factor accounting for the observed variation in practice patterns is the lack of pediatricspecific guidelines. It is possible that because the evidence used in the development of current guidelines was largely derived from adult data from 1979 to 1989, pediatric surgeons may not believe that it is applicable to their patients [6,12,13]. Though the evidence regarding timing of antibiotic prophylaxis in pediatric patients with appendicitis is lacking, recent studies evaluating timing of antibiotic prophylaxis for children undergoing a variety of operations have shown results similar to ours. One study of 9465 children who underwent a variety of elective or nonelective operations found no significant difference in the relative risk of developing an SSI between patients who received antibiotic prophylaxis within 60 min prior to incision and those who received it more than 60 min prior to incision [14]. Another large, retrospective case–control study of children who developed an SSI after clean or clean-contaminated operations compared patients who received antibiotic prophylaxis less than 30 min prior to incision and 30–60 min prior to incision, and those who did not receive prophylaxis and found that the timing of antibiotic administration was not associated with development of an SSI [15]. Risk factors for development of an SSI differed from adult risk factors and included age (neonates) and race (African-American), whereas wound classification was not associated with development of an SSI. Our study provides further support that infection control measures should reflect the differences between these populations. Antibiotics are the most common class of medications associated with adverse drug reactions in the pediatric population [16]. Sandora et al. [6] found that children who receive antimicrobial prophylaxis had higher odds of developing C. difficile colitis and requiring perioperative epinephrine and diphenhydramine. In addition to preventable adverse drug effects, overutilization of antibiotics results in increased hospital resource utilization and potential for increased resistance of organisms [13]. One patient in each group in our study developed C. difficile colitis; however, it is possible that more patients are needed to detect adverse drug reactions. A small number of patients who received perioperative antibiotics outside the time frame specified in our inclusion criteria were excluded from analysis. Of the 28 patients who received antibiotics after incision while still in the operating room, none developed an infectious complication. There was one IAA and there were no superficial SSIs in the 26
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patients who received their last dose of preoperative antibiotics more than six hours prior to incision. There are several limitations to this study. First, this was a retrospective, single-institution study performed at a free-standing children's hospital, thus its results may not be generalizable to other institutions with different practices. Second, there is a possibility of underestimating postoperative complications as they were identified by reviewing the medical record and complications are not captured if patients do not return to our institution. Third, 43 patients who were transferred from outside hospitals had to be excluded because of missing data which could impact the results. Fourth, the six-hour cutoff used in the study may not be generalizable at institutions that use preoperative antibiotics with different dosing intervals. Lastly, the relatively small sample size may not have adequate power to detect a difference in infectious complications, and a larger, prospective study may be warranted.
4. Conclusion Administering antibiotics within one hour of appendectomy in pediatric patients with acute appendicitis who receive antibiotics at diagnosis did not change the incidence of postoperative infectious complications. Future research efforts should focus on creating quality measures based on pediatric-specific evidence.
References [1] Dunn JC. Appendicitis. In: Coran AG, editor. Pediatric surgery. 7th ed. Philadelphia: Mosby; 2012. p. 1255–63. [2] Lee SL, Islam S, Cassidy LD, et al. Antibiotics and appendicitis in the pediatric population: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee Systematic Review. J Pediatr Surg 2010;45:2181–5. [3] Rogers AP, Zens TJ, Leys CM, et al. A call for a standardized definition of perforated appendicitis. J Pediatr Surg 2017;52(1):89–92. [4] Foster CB, Sabella C. Health-care associated infections in children. JAMA 2011;305: 1480–1. [5] Rangel SJ, Islam S, 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. [6] Sandora TJ, Fung M, Melvin P, et al. National variability and appropriateness of surgical antibiotic prophylaxis in US children's hospitals. JAMA Pediatr 2016;170(6):570–6. [7] Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Am J Surg 2005;189: 395–404. [8] Farach SM, Danielson PD, Walford NE, et al. Operative findings are a better predictor of resource utilization in pediatric appendicitis. J Pediatr Surg 2015;50(9):1574–8. [9] Emil S, Gaied F, Lo A, et al. Gangrenous appendicitis in children: a prospective evaluation of definition, bacteriology, histopathology, and outcomes. J Surg Res 2012; 177(1):123–6. [10] St. Peter SD, Sharp SW, Holcomb WG, et al. An evidence-based definition for perforated appendicitis derived from a prospective randomized trial. J Pediatr Surg 2008; 43(12):2242–5. [11] Zhang Z, Wang Y, Li R, et al. Systematic review and metaanalysis of single-incision versus conventional laparoscopic appendectomy in children. J Pediatr Surg 2015; 50:1600–9. [12] Rangel SJ, Fung M, Graham DA, et al. Recent trends in the use of antibiotic prophylaxis in pediatric surgery. J Pediatr Surg 2011;46:366–71. [13] Voit SB, Todd JK, Nelson B, et al. Electronic surveillance system for monitoring surgical antimicrobial prophylaxis. Pediatrics 2005;116(6):1317–22. [14] Khoshbin A, So JP, Aleem IS, et al. Antibiotic prophylaxis to prevent surgical site infections in children: a prospective cohort study. Ann Surg 2015;262:397–402. [15] Butcher BT, Guth RM, Elward AM, et al. Risk factors and outcomes of surgical site infection in children. J Am Coll Surg 2011;212:1033–8. [16] Smyth R, Gargon E, Kirkham J, et al. Adverse drug reactions in children—a systematic review. PLoS One 2012;7:e24061.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Timing of antimicrobial prophylaxis and infectious complications in pediatric patients undergoing appendectomy Cristen N. Litz ⁎, Jessica B. Asuncion, Paul D. Danielson, Nicole M. Chandler Division of Pediatric Surgery, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, United States
a r t i c l e
i n f o
Article history: Received 10 February 2017 Received in revised form 26 April 2017 Accepted 4 May 2017 Key words: Pediatric surgery Appendectomy Antimicrobial prophylaxis Infection prevention Surgical site infection Quality improvement
a b s t r a c t Purpose: Antibiotic administration within one hour prior to incision is a common quality metric; however, antibiotics are typically started at the time of diagnosis in pediatric patients with acute appendicitis. The purpose was to determine if antibiotic administration within one hour prior to incision reduces the incidence of surgical site infections (SSI) in pediatric patients with acute appendicitis started on parenteral antibiotics upon diagnosis. Methods: A retrospective review was performed of 478 patients aged 0–18 years who underwent appendectomy for acute appendicitis from 7/2013 to 4/2015. Patients were categorized based on timing of antibiotic administration; there were 198 patients in Group A (b 60 min before) and 280 in Group B (N60 min before). Results: Demographics and operative time (A: 30.5 ± 9.9 vs B: 30.8 ± 12.2 min, p = 0.51) were similar. Procedures were performed laparoscopically and the groups had similar proportions of single-incision operations (A: 53% vs B: 55%, p = 0.64). There was no difference in the incidence of superficial SSI (A: 2.0% vs B: 2.1%, p = 1.0) or intraabdominal abscess (A: 4.0% vs B: 3.6%, p = 0.81) and this remained true when stratified by intraoperative classification. Conclusion: Antibiotic administration within one hour of appendectomy in pediatric patients with acute appendicitis who receive antibiotics at diagnosis did not change the incidence of postoperative infectious complications. Type of study: Treatment study. Level of evidence: III. © 2017 Elsevier Inc. All rights reserved.
Appendicitis is the most common surgical emergency in children and wound infections are the most frequent postoperative complication [1]. Surgical site infections (SSIs) are a great burden on the healthcare system, accounting for approximately two billion dollars in excess healthcare expenditures annually because of longer hospital stays, higher rates of hospital readmission, and increased requirements for home health care and medical supplies [2]. Because of the frequency of appendicitis, there is a rich opportunity to evaluate and improve clinical practice, as postoperative wound infections are one of the most commonly tracked outcome measures [3]. There remains significant variance in the management of pediatric appendicitis and a dearth of pediatric-specific guidelines regarding infection prevention measures [2,4]. According to the American Pediatric Surgical Association (APSA) Outcomes and Clinical Trials Committee, there is Grade A evidence that pediatric patients with appendicitis should receive preoperative broad-spectrum antibiotics and it is standard practice to begin antibiotics at the time of diagnosis [2]. However,
pediatric-specific evidence supporting the commonly used quality metric of antibiotic administration within one hour of operation is lacking [5,6]. The practice of antimicrobial prophylaxis administration one hour prior to incision originated as a Surgical Care Improvement Project (SCIP) measure that was developed for adults without evidence of preoperative infection with the goal of achieving serum and tissue drug levels for the duration of surgery that exceed the minimum inhibitory concentration of the organisms likely to be encountered [7]. This measure was based on evidence from adult literature and similar evidence does not exist for children. An APSA review of pediatric antibiotic prophylaxis in 2015 stated that high quality data to guide clinical practice in children are needed [5]. The purpose of this study was to determine the impact of administering antibiotics within one hour prior to incision on infectious complications in pediatric patients with acute appendicitis who are started on parenteral antibiotics upon diagnosis. 1. Methods
⁎ Corresponding author at: Johns Hopkins All Children's Hospital, Outpatient Care Center, 601 5th Street South, Dept. 70-6600, 3rd Floor, Saint Petersburg, FL 33701, United States. Tel.: +1 727 767 4170; fax: +1 727 767 4346. E-mail addresses: [email protected] (C.N. Litz), [email protected] (J.B. Asuncion), [email protected] (P.D. Danielson), [email protected] (N.M. Chandler). http://dx.doi.org/10.1016/j.jpedsurg.2017.05.005 0022-3468/© 2017 Elsevier Inc. All rights reserved.
Institutional Review Board approval was obtained (No. 00098589). A retrospective cohort study was performed of patients who underwent appendectomy from July 2013 through April 2015. Patients were included if they were 0–18 years of age and underwent appendectomy for acute appendicitis. Exclusion criteria included patients who underwent interval appendectomy, had concurrent procedures performed at the time
450
C.N. Litz et al. / Journal of Pediatric Surgery 53 (2018) 449–451
of appendectomy, did not receive preoperative antibiotics, or received antibiotics more than six hours prior to incision. All operations were performed by one of four pediatric surgeons via a multiport or singleincision laparoscopic technique. Patients were categorized into two groups based on the timing of the administration of the last dose of antibiotic prior to incision: Group A (0–60 min before incision) and Group B (61–360 min before incision). Medical records were reviewed and the following data were collected: age, body mass index (BMI) percentile, presenting white blood cell count (WBC), time of antibiotic administration, operative start time, operative duration, and the intraoperative classification of appendicitis. Per protocol at our institution, once the diagnosis of appendicitis is made parenteral antibiotics are initiated and patients receive scheduled redosing until the operation. There is no standard protocol for antibiotic readministration within one hour prior to incision and, instead, this is based on surgeon discretion. The standard antibiotic used for prophylaxis is cefoxitin unless patients have penicillin or cephalosporin allergies, in which case they receive ciprofloxacin and metronidazole. In our community, it is common for transferred patients to receive piperacillin/tazobactam at outside hospitals prior to transfer. The six hour cutoff was chosen since the vast majority of patients in the study received preoperative antibiotics that are dosed every six hours (92% received cefoxitin or zosyn). This protocol utilizes a standardized classification system for the degree of appendicitis based on intraoperative findings which guides postoperative antibiotic management [8–10]. Patients with acute appendicitis do not receive postoperative antibiotics and those with gangrenous or perforated appendicitis are admitted for parenteral antibiotics. Our institution recently completed a randomized controlled study that found that patients with suppurative appendicitis can be discharged home immediately following appendectomy on a 7-day course of oral antibiotics with no difference in infectious complications compared to traditional management (hospital admission for parenteral antibiotics), and this is now our standard practice [article in press]. Patients typically present for postoperative follow-up between 2 and 4 weeks after surgery. The clinic notes and any emergency department (ED) visits or hospital readmissions within 30 days of surgery were reviewed for superficial surgical site infections, intraabdominal abscesses (IAA), or other complications. The primary outcome was the incidence of superficial surgical site infections. Secondary outcomes included the incidence of intraabdominal abscesses, other complications including Clostridium difficile colitis, and hospital readmissions within 30 days. Continuous variables were analyzed by Student's t test or the Mann–Whitney U test as indicated. Categorical data were analyzed with Fisher's exact test. Statistical significance was set at p b 0.05.
Table 1 Demographic and clinical information.
Age, yr BMI percentile WBC, n × 103/μL Case time, min Technique, n (%) - Multiport - SIL OR findingsa, n (%) - Acute - Suppurative - Gangrenous - Perforated - Normal
Group A (n = 198)
Group B (n = 280)
p-Value
11.0 65.1 15.3 30.5
11.1 59.9 14.8 30.8
0.77 0.22 0.27 0.51
± ± ± ±
3.7 (0.4–17.6) 32.6 (2.0–99.7) 5.0 (4.7–27.5) 9.9 (12–70)
± ± ± ±
3.7 (0.9–18.0) 31.9 (0.0–99.6) 5.3 (3.7–36.9) 12.2 (13–80)
94 (47) 104 (53)
126 (45) 154 (55)
0.64
114 (58) 50 (25) 5 (3) 27 (14) 2 (1)
169 (60) 56 (20) 12 (4) 38 (14) 5 (2)
0.57 0.18 0.45 1.0 0.70
BMI = body mass index percentile; WBC = white blood cell count; SIL = single-incision laparoscopy. Continuous data presented as mean ± standard deviation (range). a Acute—inflammation, dilation, or hyperemia limited to the appendix; Suppurative—nonperforated appendix with fibrinous exudate or turbid peritoneal fluid; Gangrenous—gray/black discoloration of the wall without a hole in the appendix or fecalith outside the appendix; Perforated—hole in the appendix or fecalith in the abdomen.
Table 2 compares postoperative outcomes between the two groups. There was no significant difference in the 30-day hospital readmission rate (A: 4.5% vs B: 5%, p = 1.0). The overall incidence of superficial SSI was similar between groups (A: 2% vs B: 2.1%, p = 1.0). In Group A, all 4 SSIs occurred in patients with acute appendicitis, whereas in Group B, 4 SSIs occurred in patients with acute appendicitis and 2 occurred in patients with suppurative appendicitis. The overall incidence of IAAs was also similar between groups (A: 4% vs B: 3.6%, p = 0.81). The majority of IAAs occurred in patients with perforated appendicitis and the incidence was similar between patients with perforated appendicitis in both groups (A: 18.5% vs B: 23.7%, p = 0.76). Two other complications in Group A included one patient with C. difficile colitis and one patient who was readmitted for management of an ileus. Other complications in Group B included one patient with C. difficile colitis, one patient readmitted for management of an ileus, and one patient who developed a small bowel obstruction requiring exploratory laparotomy and lysis of adhesions.
2. Results Six hundred ten patients underwent appendectomy during the study period. Patients were excluded for the following reasons: 45 did not have the timing of antibiotic administration documented (43 of whom were transferred from outside hospitals), 33 underwent an interval appendectomy, 28 received antibiotics after incision in the operating room, and 26 received antibiotics more than 6 hours prior to incision. There were 478 patients included in the analysis: 198 patients in Group A and 280 patients in Group B. Table 1 shows demographic and clinical information. The groups were similar in age (A: 11.0 ± 3.7 vs B: 11.1 ± 3.7 years, p = 0.77) and BMI percentile (A: 65.1 ± 32.6 vs B: 59.9 ± 31.9, p = 0.22). The groups had similar presenting white blood cell counts (A: 15.3 ± 5.0 × 10 3/μL vs B: 14.8 ± 5.3 × 10 3/μL, p = 0.27). Operative time was similar between groups (A: 30.5 ± 9.9 vs B: 30.8 ± 12.2 min, p = 0.51). Both groups had a similar proportion of patients who underwent appendectomy via a single-incision laparoscopic technique (A: 53% vs B: 55%, p = 0.64). There was no significant difference in the intraoperative findings between the two groups.
Table 2 Postoperative outcomes.
Superficial SSI - Acute - Suppurative - Gangrenous - Perforated - Normal - Overall IAA - Acute - Suppurative - Gangrenous - Perforated - Normal - Overall 30-day readmission, n (%) 30-day other complication, n (%)
Group A
Group B
p-value
4/114 (3.5) 0/50 0/5 0/27 0/2 4/198 (2)
4/169 (2.4) 2/56 (3.6) 0/12 0/38 0/5 6/280 (2.1)
0.72 NA NA NA NA 1.0
0/114 3/50 (6) 0/5 5/27 (18.5) 0/2 8/114 (4) 9 (4.5) 2 (1)
0/169 0/56 1/12 (8.3) 9/38 (23.7) 0/5 10/169 (3.6) 14 (5) 3 (1)
NA NA NA 0.76 NA 0.81 1.0 1.0
SSI = surgical site infection; IAA = intraabdominal abscess. Data presented as # occurrences/# patients (%).
C.N. Litz et al. / Journal of Pediatric Surgery 53 (2018) 449–451
3. Discussion This is the first pediatric-specific study that aimed to determine the impact of administering antibiotics within one hour prior to incision on infectious complications in patients with acute appendicitis who are started on parenteral antibiotics upon diagnosis. The overall rate of superficial surgical site infections in this study was 2.1% which is similar to the previously published rates of 2.0% for multiport laparoscopic appendectomy and 4.3% for single-incision laparoscopic appendectomy [11]. Sixty percent of patients with acute appendicitis in this study did not receive antibiotics within one hour prior to incision, and had no significant difference in infectious complications compared to those patients who received antibiotics within one hour prior to incision. The variation in antibiotic prophylaxis administration seen in this study is similar to the variance described by other authors. Recent retrospective cohort studies using the Pediatric Health Information System (PHIS) database have shown that there is substantial hospital and procedural-level variability in the practice of antimicrobial prophylaxis nationwide [6,12]. Perhaps the most significant factor accounting for the observed variation in practice patterns is the lack of pediatricspecific guidelines. It is possible that because the evidence used in the development of current guidelines was largely derived from adult data from 1979 to 1989, pediatric surgeons may not believe that it is applicable to their patients [6,12,13]. Though the evidence regarding timing of antibiotic prophylaxis in pediatric patients with appendicitis is lacking, recent studies evaluating timing of antibiotic prophylaxis for children undergoing a variety of operations have shown results similar to ours. One study of 9465 children who underwent a variety of elective or nonelective operations found no significant difference in the relative risk of developing an SSI between patients who received antibiotic prophylaxis within 60 min prior to incision and those who received it more than 60 min prior to incision [14]. Another large, retrospective case–control study of children who developed an SSI after clean or clean-contaminated operations compared patients who received antibiotic prophylaxis less than 30 min prior to incision and 30–60 min prior to incision, and those who did not receive prophylaxis and found that the timing of antibiotic administration was not associated with development of an SSI [15]. Risk factors for development of an SSI differed from adult risk factors and included age (neonates) and race (African-American), whereas wound classification was not associated with development of an SSI. Our study provides further support that infection control measures should reflect the differences between these populations. Antibiotics are the most common class of medications associated with adverse drug reactions in the pediatric population [16]. Sandora et al. [6] found that children who receive antimicrobial prophylaxis had higher odds of developing C. difficile colitis and requiring perioperative epinephrine and diphenhydramine. In addition to preventable adverse drug effects, overutilization of antibiotics results in increased hospital resource utilization and potential for increased resistance of organisms [13]. One patient in each group in our study developed C. difficile colitis; however, it is possible that more patients are needed to detect adverse drug reactions. A small number of patients who received perioperative antibiotics outside the time frame specified in our inclusion criteria were excluded from analysis. Of the 28 patients who received antibiotics after incision while still in the operating room, none developed an infectious complication. There was one IAA and there were no superficial SSIs in the 26
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patients who received their last dose of preoperative antibiotics more than six hours prior to incision. There are several limitations to this study. First, this was a retrospective, single-institution study performed at a free-standing children's hospital, thus its results may not be generalizable to other institutions with different practices. Second, there is a possibility of underestimating postoperative complications as they were identified by reviewing the medical record and complications are not captured if patients do not return to our institution. Third, 43 patients who were transferred from outside hospitals had to be excluded because of missing data which could impact the results. Fourth, the six-hour cutoff used in the study may not be generalizable at institutions that use preoperative antibiotics with different dosing intervals. Lastly, the relatively small sample size may not have adequate power to detect a difference in infectious complications, and a larger, prospective study may be warranted.
4. Conclusion Administering antibiotics within one hour of appendectomy in pediatric patients with acute appendicitis who receive antibiotics at diagnosis did not change the incidence of postoperative infectious complications. Future research efforts should focus on creating quality measures based on pediatric-specific evidence.
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