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ANTIBIOTICS FOR APPENDICECTOMY IN CHILDREN AND ADOLESCENTS DURING THE PERIOPERATIVE PERIOD: AN INTEGRATIVE REVIEW

ABSTRACT

Objective:

To analyze the preoperative use of antibiotics in children and adolescents requiring appendectomy.

Data source:

Integrative review was performed in the MEDLINE, Latin American and Caribbean Health Sciences (LILACS) and Cochrane databases and the PubMed portal, with no time limit. The keywords used were: appendicitis, child, adolescent and antibacterial with Boolean AND. The articles included were published in Portuguese, English or Spanish and whose participants were under 18 years of age. Review articles and guidelines were excluded. The studies were classified according to their level of evidence and 24 papers were selected.

Data collection and analysis:

Seven randomized clinical trial studies (level of evidence II), eight cohorts (level III), seven retrospective observational studies (level V) and two historical documentary analysis (level IV) were selected. The studies addressed antibiotics used in acute appendicitis in both uncomplicated and complicated cases. Antibiotics initiated in the preoperative period showed a decrease in the rates of surgical wound infections. First-line (empiric) regimens were tested for sensitivity to microorganisms in peritoneal material cultures, however the results were controversial. Broad-spectrum antibiotics have been suggested in some studies because they have good coverage, but in others they have not been recommended because of the risk of developing bacterial resistance. Shorter administration time and earlier change to the oral route reduced hospitalization time.

Conclusions:

There are several clinical protocols with different antibiotics. However, there is no standardization concerning the type of antibiotic drug, time of use, or route.

Keywords:
Appendicitis; Appendectomy; Antibacterials; Kid; Teenager

RESUMO

Objetivo:

Analisar o uso de antibióticos em crianças e adolescentes no perioperatório de apendicectomia.

Fonte de dados:

Realizou-se uma revisão integrativa, nas bases de dados MEDLINE, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Cochrane e no portal PubMed, sem limite de tempo. As palavras-chave utilizadas foram: apendicite, criança, adolescente e antibacterianos com booleano AND. Os artigos incluídos foram publicados nos idiomas português, inglês ou espanhol e cujos participantes tivessem idade inferior a 18 anos. Os artigos de revisão e diretrizes foram excluídos. A qualidade da evidência foi analisada, e foram selecionados 24 artigos.

Síntese dos dados:

Sobre os estudos selecionados, sete foram ensaios clínicos randomizados (nível de evidência II), oito coortes (nível III), sete observacionais retrospectivos (nível V) e duas análises documentais históricas (nível IV). Os estudos abordaram antibióticos usados na apendicite aguda em suas formas não complicada e complicada. Os antibióticos iniciados no pré-operatório evidenciaram diminuição nas taxas de infecção da ferida cirúrgica. Os esquemas de primeira linha (empíricos) foram testados em relação à sensibilidade dos microrganismos nas culturas de material peritoneal, no entanto os resultados foram controversos. Sugeriram-se antibióticos de amplo espectro em alguns estudos por apresentar boa cobertura, no entanto em outros eles não foram recomendados, pelo risco de desenvolver resistência bacteriana. O menor tempo de administração e a mudança mais precoce para a via oral reduziram o tempo de internação.

Conclusões:

Existe um grande número de protocolos clínicos com antibióticos diversos, no entanto não existe padronização em relação ao tipo de antibiótico, tempo de uso nem via.

Palavras-chave:
Apendicite; Apendicectomia; Antibacterianos; Criança; Adolescente

INTRODUCTION

Acute appendicitis is the predominant abdominal surgical emergency among children and adolescents between 10 and 20 years of age,11. Sulu B, Günerhan Y, Palanci Y, Isler B, Caglayan K. Epidemiological and demographic features of appendicitis and influences of several environment factors. Ulus Travma Acil Cerrahi Derg. 2010;16:38-42. however, its diagnosis remains a challenge for pediatricians, since the disease often manifests itself atypically, appearing as an another condition, which can delay diagnosis, which complicates the evolution of the disease, culminating in infection, perforation and sepsis, contributing to an increase in the associated morbidity rate.22. Graff LG, Robinson D. Abdominal pain and emergency department evaluation. Emerg Med Clin North Am. 2001;19:123-36.,33. Rothrock SG, Pagane J. Acute appendicitis in children: emergency department diagnosis and a management. Ann Emerg Med. 2000;36:39-51.

In view of the relevance of this condition, the following must be considered: early diagnosis, so as not to delay surgical intervention; and antibiotic therapy in the perioperative period, which greatly reduces the incidence of persistent or recurrent infection and can be performed with therapy according to the type of appendicitis.44. Nadler EP, Gaines BA, Therapeutic Agents Committee of the Surgical Infection Society. The Surgical Infection Society guidelines on antimicrobial therapy for children with appendicitis. Surg Infect (Larchmt). 2008;9:75-83. There are many controversies regarding prophylaxis and the treatment of acute appendicitis, in particularly to the antibiotic regimens used in Pediatric services.

It should be remembered that patients with complicated or perforated appendicitis (defined by intraoperative and / or histopathological diagnosis of perforated appendix) are more prone to the formation of intra-abdominal abscesses than those with uncomplicated appendicitis (without evidence of appendiceal perforation), and require antibiotic coverage against gram-negative and anaerobic agents. This circumstance is also valid for the prophylaxis of surgical site infections.44. Nadler EP, Gaines BA, Therapeutic Agents Committee of the Surgical Infection Society. The Surgical Infection Society guidelines on antimicrobial therapy for children with appendicitis. Surg Infect (Larchmt). 2008;9:75-83. In view of this context, it is questioned: which antibiotics have been used in the perioperative period in children and adolescents submitted to appendectomy?

This study aimed to analyze the available evidence in the literature on the use of antibiotics in children and adolescents in the perioperative appendectomy.

METHOD

An integrative literature review was performed with six phases:

  • Forming the guiding question.

  • Literature search or sampling.

  • Selection of the component searches of the review sample.

  • Critical analysis of included studies.

  • Discussion of results.

  • Presentation of the review, with consequent critical examination of results.55. Souza MT, Silva MD, Carvalho R. Integrative review: what is it? How to do it? Einstein (Sao Paulo). 2010;8:102-6.

The guiding question was: what are the antibiotics used in children and adolescents in the perioperative appendectomy? We used the PICO strategy, an acronym in the English and Portuguese languages which corresponds to the following elements:

  • P - population: children and adolescents undergoing appendectomy due to acute appendicitis.

  • I - intervention: normalization of the use of antibiotics in the perioperative period.

  • C - comparison: with patients, prior to standardization.

  • O - outcomes: reduction of length of hospital stay.66. Bernardo WM, Nobre MR, Jatene FB. Evidence-based clinical practice. Part II - searching evidence databases. Rev Bras Reumatol. 2004;44:403-9.

A matched search was conducted in the MEDLINE, Latin American and Caribbean Health Sciences (LILACS) and Cochrane databases and in the PubMed portal, without temporal delimitation of the publications, by two individual researchers, in September 2017. We used the Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH) apendicite/appendicitis/criança/child/adolescente/adolescent/apendicectomia/appendectomy/antibacterianos/anti-bacterial agents. For the systematization of searches, the descriptors had to be cross-linked, using the Boolean operator AND in the following search equation: appendicitis and child and adolescent and anti-bacterial agents; appendectomy and child and adolescent and anti-bacterial agents.

The included inclusion criteria were: studies on the theme available in full, published in the Portuguese, English or Spanish languages, and whose participants were under the age of 18. The review studies and guidelines were excluded. The articles were selected in September 2017, by two researchers, in different searches. 515 articles were identified in PubMed; 339 in MEDLINE; 17 in LILACS; and 36 in Cochrane. However, according to the researchers’ agreement, only 389 articles were selected as they met the inclusion criteria. Among these 389 articles, only 106 were applicable for eligibility evaluation, because the others did not respond to the guiding question. Only 24 articles were included in the systematic review, considering that the others did not meet the age criterion or were duplicates.

In this study, we used the Preferred Reporting Items for Systematic Review and Meta-Analyzes (PRISMA)77. Fuchs SC, Paim BS. Meta-analysis and systematic review of observational studies. Rev HCPA. 2010;30:294-301. was used to explain the search and selection of studies, according to the flowchart detailed in Figure 1. The articles were classified in relation to the level of evidence (LoE) according to the adaptation of the classification proposed by Torres-Gomes.88. Torres-Gómez A. Niveles de evidencia en ortopedia. Rev Mex Ortop Ped. 2009;11:4. Systematic reviews of randomized clinical trials were defined as LoE I; randomized controlled trials, LoE II; cohort studies and case control, LoE III; case series, LoE IV; and narrative review, as well as other drawings, LoE V.

Figure 1
Research flowchart: identification, screening, eligibility and inclusion of scientific articles in the integrative review, according to Preferred Reporting Items for Systematic Review and Meta-Analyzes (PRISMA, 2009).77. Fuchs SC, Paim BS. Meta-analysis and systematic review of observational studies. Rev HCPA. 2010;30:294-301.

Subsequently, a critical and detailed analysis was carried out, with analogy to the theoretical knowledge and identification of the conclusions and implications of the standardization of the use of antibiotics in children and adolescents in the perioperative period of appendectomies. From the 24 articles selected for the literature review, two matrices were generated for the presentation of the results and discussion, seeking to integrate these for the construction of a general conception, as recommended in the literature.55. Souza MT, Silva MD, Carvalho R. Integrative review: what is it? How to do it? Einstein (Sao Paulo). 2010;8:102-6. The first matrix shows the characterization of the studies. The second one describes the standardization used in the perioperative appendectomy and its main results.

RESULTS

The 24 studies were coded from E1 to E24. In relation to their characterization, they present diversity in the countries where they were performed, the participants and the methodological design. These characteristics are shown in Table 1. It can be seen in Table 1 that the articles were developed in several countries, such as the United States of America (USA, E5, E7, E14, E15, E17, E19, E23, E24) , France (E2, E3, E12), England (E1, E10), Turkey (E8, E20), China (E6), New Zealand (E4), The Netherlands (E11), Ireland (E18) and Finland (E21). Such approaches were all carried out in hospitals.

Table 1
Characterization of the scientific production on the repercussions of the standardization of antibiotic use during the perioperative period in children and adolescents submitted to appendectomy.

Regarding the methodological design, seven studies were randomized clinical trials (LoE II), eight cohorts (LoE III), seven retrospective observational studies (LoEV) and two could be classified as documentary studies (LoE IV). Two of the studies were multicenter and performed in the United States. Regarding the sample size, samples ranging from 26 to 24,984 participants are found in the studies.

Table 2 shows the results of the randomized clinical trials, Table 3 shows the results of the cohort studies and Table 4 shows the results of the retrospective studies, with the standardization of the antibiotics used in the perioperative period in patients submitted to appendectomy. In these tables, it is possible to observe the diverse antimicrobial regimens used in the perioperative period of children and adolescents submitted to appendectomy, regarding the choice of antibiotics, associations, dose, duration of treatment and route of administration, however, the common objective was to cover aerobic (mainly gram-negative) and anaerobic microorganisms, with the knowledge that both surgical wound infection and intra-abdominal abscess formation are associated with advanced disease. First-line protocols were initiated empirically, and in cases of perforated appendicitis treatment failure, according to some studies, the result of cultures of peritoneal material collected at the time of surgery should be used in order to improve practice.

Table 2
Review of the main results from the randomized clinical trials.

Table 3
Review of the main results of the cohort studies.

Table 4
Review of the main results of the retrospective studies.

DISCUSSION

The studies included in the review dealt with antibiotic protocols both in acute appendicitis in general and specifically in its uncomplicated and complicated forms, however the greatest number of investigations involved perforated appendicitis as it is associated with increased morbidity.33. Rothrock SG, Pagane J. Acute appendicitis in children: emergency department diagnosis and a management. Ann Emerg Med. 2000;36:39-51.

There were three studies reporting appendicitis in general, as well as reduction of surgical wound infection in the pediatric population, with the prophylactic use of antibiotics in the preoperative period in patients submitted to appendectomy. One of these studies was a cohort study performed in England (1982) with 118 patients who underwent appendectomy and who had confirmed histopathological appendicitis.99. Wright JE. Appendicitis in childhood: Reduction in wound infection with preoperative antibiotics. Aust N Z J Surg. 1982;52:127-9. Thus, different antibiotics were used preoperatively, according to progression of the disease:

  • Less than 24 hours and no peritonitis (group I): intravenous ampicillin.

  • 24 to 48 hours without peritonitis (group II): ampicillin+kanamycin intravenously.

  • Above 48 hours or with peritonitis clinic (group III): kanamycin+lincomycin, intravenously.

The continuation of the antibiotics in the postoperative period was not relevant to the study. Among all the patients, only three had wound infection (2.5%) and only one of them was a wound abscess (0.8%). There were no occurrences of intra-abdominal abscesses.1010. Kronmam MP, Oron AP, Ross RK, Hersh AL, Newland JG, Golding A, et al. Extended-versus narrower-spectrum antibiotics for appendicitis. Pediatrics. 2016;138:1-9.

In a cohort study performed over a period of 26 years, a lower rate of surgical wound infections in those who received antibiotic (cefoxitin) via the intravenous route and application of the antibiotic powder in the intraoperative wound was found when compared to the group that received only the intravenous antibiotic (p=0.03).2424. Ein SH, Sandler A. Wound infection prophylaxis in pediatric acute appendicitis: a 26-year prospective study. J Pediatr Surg. 2006;41:538-41.

Finally, regarding the group of prophylactic studies, there is a comparison between two antibiotic regimens used in the preoperative period, which showed no difference in infection rates between those receiving ampicillin / sulbactam and those with cefotaxime+metronidazole, which appeared to be the first adequate prophylaxis regimen for wound infection associated with pediatric appendicitis.2020. Foster MC, Morris DL, Legan C, Kapila L, Slack RC. Perioperative prophylaxis with sulbactam and ampicillin compared with metronidazole and cefotaxime in the prevention of wound infection in children undergoing appendectomy. J Pediatr Surg. 1987;22:869-72.

It is worth noting that studies on the bacterial flora in complicated appendicitis (material collected from the peritoneum during surgery) and its impact on empiric therapies show positive cultures for mixed and anaerobic anaerobes, with Escherichia coli, Milleri group Streptococcus and Pseudomonas aeruginosa appearing more often.1717. Guillet-Caruba C, Cheikhelard A, Guillet M, Bille E, Descamps P, Yin L, et al. Bacteriologic epidemiology and empirical treatment of pediatric complicated appendicitis. Diagn Microbiol Infect Dis. 2011;69:376-81.,1818. Chan KW, Lee KH, Mou JW, Cheung ST, Sihoe JD, Tam YH. Evidence-based adjustment of antibiotic in pediatric complicated appendicitis in the era of antibiotic resistance. Pediatr Surg Int. 2010;26:157-60. One of these studies demonstrated resistance to amoxicillin / clavulanate, but sensitivity to piperacillin / tazobactam in complicated appendicitis, in addition to the evidence that third generation cephalosporin + metronidazole does not include P. aeruginosa in its spectrum and that carbapenems, despite their good action, are not recommended as broad-spectrum antibiotics for empiric therapy, in order to avoid the risk of emergence of bacterial resistance. Aside from that, P. aeruginosa and enterococci are usually resistant to ertapenem, imipenem and meropenem.1717. Guillet-Caruba C, Cheikhelard A, Guillet M, Bille E, Descamps P, Yin L, et al. Bacteriologic epidemiology and empirical treatment of pediatric complicated appendicitis. Diagn Microbiol Infect Dis. 2011;69:376-81.

On the other hand, a retrospective study in France developed over a 20-year period, between 1989-1991, 1999-2000 and 2009-2010, showed that there was no significant increase in the resistance rates of enterobacteria in perforated appendicitis with empiric antibiotic protocols, remaining effective against this microbiota: amoxicillin+clavulanate (100% susceptibility of this compound to anaerobes); imipenem, which has remained effective against all microorganisms; metronidazole, which maintained efficient action against anaerobes (93% susceptibility), as well as aminoglycosides (greater than 90% susceptibility), while ticarcillin / clavulanate was more efficient than expected.1313. Schmitt F, Clermidi P, Dorsi M, Cocquerelle V, Gomes CF, Becmeur F. Bacterial studies of complicated appendicitis over a 20-year period and their impact on empirical antibiotic treatment. J Pediatr Surg. 2012;47:2055-62.

The results show that 25% of the patients with complicated appendicitis did not respond to the triple regimen (ampicillin+cefuroxime+metronidazole), and the result of the peritoneal fluid collection guided the adjustment of the antibiotics,1818. Chan KW, Lee KH, Mou JW, Cheung ST, Sihoe JD, Tam YH. Evidence-based adjustment of antibiotic in pediatric complicated appendicitis in the era of antibiotic resistance. Pediatr Surg Int. 2010;26:157-60. as the one that showed a significant percentage (40%) of patients with complicated appendicitis, presenting microorganisms resistant to first-line antibiotics (cefoxitin) and recommending piperacillin / tazobactam as the most effective empiric therapy for children with perforated appendicitis.2525. Fallon SC, Hassan SF, Larimer EL, Rodriguez JR, Brandt ML, Wesson DE, et al. Modification of an evidence-based protocol for advanced appendicitis in children. J Surg Res. 2013;185:273-7.

Regarding the duration of antibiotic therapy in complicated appendicitis, the studies showed that, in contrast to a fixed period of five days, the use of clinical parameters (temperature lower than 38ºC for 24 hours, diet tolerance, independent mobilization and requiring oral analgesia only) for antibiotic suspension reduced hospitalization time without apparent impairment of results.1414. Yu TC, Hamill JK, Evans SM, Price NR, Morreau PN, Upadhyay VA, et al. Duration of postoperative intravenous antibiotics childhood complicated appendicitis: a propensity score-matched comparison study. Eur J Pediatr Surg. 2014;24:341-9.

A prospective cohort study in the United States in 2014 described the early transition from the intravenous antibiotic regimen (piperacillin / tazobactam) to oral (­metronidazole+­sulfamethoxazole / trimethoprim), with options (amoxicillin / clavulanate) for allergic patients who were tolerating the diet. The hospital stay rate was shown to be reduced, as well as readmission rates and complications, indicating a safe and effective transition for the treatment of perforated appendicitis in children.1515. Loux TJ, Falk GA, Burnweit CA, Ramos C, Knight C, Malvezzi L. Early transition to oral antibiotics for treatment of perforated appendicitis in pediatric patients: Confirmation of the safety and efficacy of a growing national trend. J Pediatr Surg. 2016;51:903-7.

In relation to the comparison of the various antibiotic regimens, a multicenter study in the United States (in 23 independent children’s hospitals) deserves to be mentioned, which addressed appendicitis in 24,984 pediatric patients undergoing appendectomy, 17,654 (70.7%) of whom had uncomplicated appendicitis and 7,330 (29.3%) who had complicated appendicitis.

In this retrospective cohort study, broad-spectrum antibiotics (piperacillin / tazobactam, ticarcillin / clavulanate or ceftazidime or cefepime or carbapenem) were compared with narrow- spectrum antibiotics (cefoxitin or ceftriaxone+metronidazole or ceftriaxone or clindamycin+gentamicin or ampicillin / sulbactam or cefoxitin+ceftriaxone+metronidazole), with the objective of evaluating the therapeutic advantage in the empiric use of antimicrobials with broader coverage. Antibiotics were administered on the day of the appendectomy or on the following day.1010. Kronmam MP, Oron AP, Ross RK, Hersh AL, Newland JG, Golding A, et al. Extended-versus narrower-spectrum antibiotics for appendicitis. Pediatrics. 2016;138:1-9.

Regarding the results, treatment failure (postoperative infectious complication) was found in 664 patients (2.7%) in general, with 1.1% in uncomplicated appendicitis and 6.4% in complicated cases (p<0.01). Broad-spectrum antibiotic treatment was not associated with the lowest readmission rate and is probably unnecessary, especially for those with uncomplicated appendicitis.1010. Kronmam MP, Oron AP, Ross RK, Hersh AL, Newland JG, Golding A, et al. Extended-versus narrower-spectrum antibiotics for appendicitis. Pediatrics. 2016;138:1-9.

A randomized trial in the United States in 2006 also showed that the five-day intravenous regimen of two drugs with a a single daily dose (ceftriaxone+metronidazole) was the most efficient and cost-effective in children with perforated aspendicities when compared to the traditional regimen of the three drugs - ampicilina (four daily doses)+gentamicin ­(three daily ­doses)+­clindamycin (four daily doses) -, intravenously for five days.1616. St Peter SD, Tsao K, Spilde TL, Holcamb GW, Sharp SW, Murphy JP, et al. Single daily dosing ceftriaxone and metronidazole vs standard triple antibiotic regimen for perforated appendicitis in children: a prospective randomized trial. J Pediatr Surg. 2008;43:981-5.

There were only two studies which focused on uncomplicated appendicitis, but they had conflicting results. The randomized clinical trial in Turkey involved 100 patients with uncomplicated acute appendicitis, and was divided into four groups:

  • I: did not use antibiotics.

  • II: ornidazole, antimicrobial and antiparasitic derived from 5-nitroimidazolicos, with molecular structure and pharmacological action similar to metronidazole.

  • III: penicillin+tobramycin.

  • IV: piperacillin.

This showed that the use of these antibiotics prophylactically gave no better results than placebos in relation to infectious post-operative complications,1111. Kizilcan F, Tanyel FC, Büyükpamukçu N, Hiçsönmez. The necessity of prophylactic antibiotics in uncomplicated appendicitis during childhood. J Pediatr Surg. 1992;27:586-8. whereas the other study, also a randomized trial, showed that a single dose of metronidazole preoperatively significantly decreased the rate of infectious complications in children with uncomplicated appendicitis compared to the group that received no antibiotics, but no further improvement could be demonstrated when cefuroxime (against aerobic organisms) was added.1212. Söderquist-Elinder C, Hirsch K, Bergdahl S, Rutqvist J, Frenckner B. Prophylactic antibiotics in uncomplicated appendicitis during childhood - a prospective randomized study. Eur J Pediatr Surg. 1995;5:282-5.

In general, it was possible to see how the studies on the subject are thought-provoking and that there is a great variability with regard to the medical protocols used in the treatment of the patients submitted to the surgical procedure.

CONCLUSION

The research found many diverse protocols for the use of antibiotics, which vary according to the severity of appendicitis. Antibiotic monotherapy, as well as narrow-spectrum antibiotics - when compared to multiple and broad-spectrum regimens - did not show any difference in infectious complication rates.

Despite the variation in choice, time of use and administration route of antibiotics, antibiotics should ensure coverage mainly against gram-negative and anaerobic microorganisms. In uncomplicated acute appendicitis, antibiotics are used prophylactically for 24 hours or less and reduce the rates of infectious postoperative complications, whereas in complicated appendicitis these drugs are used therapeutically for a period of 5‒7 days, or, according to more recent research, maintained until the clinical improvement of the patient.

Therefore, despite the evidence in the literature there is no specific conduct that can be followed. The use of complementary antimicrobial treatment in relation to appendectomy is indisputable. Thus, in order to fill this knowledge gap, further studies must be carried out on this subject in the pediatric setting, with the best possible level of evidence.

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    Graff LG, Robinson D. Abdominal pain and emergency department evaluation. Emerg Med Clin North Am. 2001;19:123-36.
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    Rothrock SG, Pagane J. Acute appendicitis in children: emergency department diagnosis and a management. Ann Emerg Med. 2000;36:39-51.
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    Nadler EP, Gaines BA, Therapeutic Agents Committee of the Surgical Infection Society. The Surgical Infection Society guidelines on antimicrobial therapy for children with appendicitis. Surg Infect (Larchmt). 2008;9:75-83.
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    Souza MT, Silva MD, Carvalho R. Integrative review: what is it? How to do it? Einstein (Sao Paulo). 2010;8:102-6.
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    Bernardo WM, Nobre MR, Jatene FB. Evidence-based clinical practice. Part II - searching evidence databases. Rev Bras Reumatol. 2004;44:403-9.
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    Fuchs SC, Paim BS. Meta-analysis and systematic review of observational studies. Rev HCPA. 2010;30:294-301.
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    Torres-Gómez A. Niveles de evidencia en ortopedia. Rev Mex Ortop Ped. 2009;11:4.
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    Wright JE. Appendicitis in childhood: Reduction in wound infection with preoperative antibiotics. Aust N Z J Surg. 1982;52:127-9.
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    Kronmam MP, Oron AP, Ross RK, Hersh AL, Newland JG, Golding A, et al. Extended-versus narrower-spectrum antibiotics for appendicitis. Pediatrics. 2016;138:1-9.
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    Kizilcan F, Tanyel FC, Büyükpamukçu N, Hiçsönmez. The necessity of prophylactic antibiotics in uncomplicated appendicitis during childhood. J Pediatr Surg. 1992;27:586-8.
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    Chan KW, Lee KH, Mou JW, Cheung ST, Sihoe JD, Tam YH. Evidence-based adjustment of antibiotic in pediatric complicated appendicitis in the era of antibiotic resistance. Pediatr Surg Int. 2010;26:157-60.
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    Fallon SC, Hassan SF, Larimer EL, Rodriguez JR, Brandt ML, Wesson DE, et al. Modification of an evidence-based protocol for advanced appendicitis in children. J Surg Res. 2013;185:273-7.
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Funding

  • This study did not receive funding.

Publication Dates

  • Publication in this collection
    04 July 2019
  • Date of issue
    Oct-Dec 2019

History

  • Received
    18 Mar 2018
  • Accepted
    07 July 2018
  • Published
    25 June 2019
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