Eur J Pediatr Surg 2014; 24(05): 410-418
DOI: 10.1055/s-0033-1352524
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Ertapenem versus Standard Triple Antibiotic Therapy for the Treatment of Perforated Appendicitis in Pediatric Patients: A Prospective Randomized Trial

Nazan Dalgic
1   Division of Pediatric Infectious Diseases, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
,
Cetin Ali Karadag
2   Division of Pediatric Surgery, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
,
Banu Bayraktar
3   Division of Microbiology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
,
Mesut Sancar
4   Department of Clinical Pharmacy, Faculty of Pharmacy, Marmara University, Istanbul, Turkey
,
Ozlem Kara
2   Division of Pediatric Surgery, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
,
Suleyman Pelit
3   Division of Microbiology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
,
Suleyman Celebi
2   Division of Pediatric Surgery, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
,
Ihsan Kafadar
1   Division of Pediatric Infectious Diseases, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
,
Ali Ihsan Dokucu
2   Division of Pediatric Surgery, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
› Author Affiliations
Further Information

Publication History

30 January 2013

02 July 2013

Publication Date:
27 August 2013 (online)

Abstract

Background The primary objective of this study was to compare triple therapy with ertapenem treatments in pediatric patients with perforated appendicitis, especially in terms of postoperative infectious complications. The secondary objective of this study was to assess the relative impact of therapy with ertapenem and triple antibiotic regimen on the emergence of resistant bacteria in bowel flora in the patients.

Materials and Methods Children aged 3 months to 17 years with perforated appendicitis were randomized 1:1 to receive ertapenem or triple therapy. Serial rectal cultures were obtained from participants enrolled in the study, allowing assessment of the relative impact of therapy with ertapenem and triple therapy on bowel colonization by resistant bacteria.

Results In this study, 107 patients were included. No difference existed in time to full oral intake and regular diet, the length of antibiotic therapy, the length of the postoperative hospitalization, or the length of hospital stay between the two groups. Patients in the triple-therapy group were more likely to suffer from a postoperative infectious complication than those in the ertapenem group (6/54 vs. 2/53, p > 0.05). Bowel colonization with resistant organisms at the end of therapy in the triple-therapy group was significantly different than in the ertapenem group (35.2 vs. 11.3%, p < 0.05).

Conclusions Bowel colonization with resistant bacteria was less likely to occur after ertapenem treatment than triple therapy. The results of this trial suggest that ertapenem may be a useful option that could eliminate the need for combination and/or multidosed antibiotic regimens for the empiric treatment of perforated appendicitis in children.

 
  • References

  • 1 Dougherty SH, Sirinek KR, Schauer PR , et al. Ticarcillin/clavulanate compared with clindamycin/gentamicin (with or without ampicillin) for the treatment of intra-abdominal infections in pediatric and adult patients. Am Surg 1995; 61 (4) 297-303
  • 2 Yellin AE, Johnson J, Higareda I , et al. Ertapenem or ticarcillin/clavulanate for the treatment of intra-abdominal infections or acute pelvic infections in pediatric patients. Am J Surg 2007; 194 (3) 367-374
  • 3 Curran TJ, Muenchow SK. The treatment of complicated appendicitis in children using peritoneal drainage: results from a public hospital. J Pediatr Surg 1993; 28 (2) 204-208
  • 4 Gollin G, Abarbanell A, Moores D. Oral antibiotics in the management of perforated appendicitis in children. Am Surg 2002; 68 (12) 1072-1074
  • 5 Lund DP, Murphy EU. Management of perforated appendicitis in children: a decade of aggressive treatment. J Pediatr Surg 1994; 29 (8) 1130-1133 , discussion 1133–1134
  • 6 Fishman SJ, Pelosi L, Klavon SL, O'Rourke EJ. Perforated appendicitis: prospective outcome analysis for 150 children. J Pediatr Surg 2000; 35 (6) 923-926
  • 7 Newman K, Ponsky T, Kittle K , et al. Appendicitis 2000: variability in practice, outcomes, and resource utilization at thirty pediatric hospitals. J Pediatr Surg 2003; 38 (3) 372-379 , discussion 372–379
  • 8 Vane DW, Fernandez N. Role of interval appendectomy in the management of complicated appendicitis in children. World J Surg 2006; 30 (1) 51-54
  • 9 St Peter SD, Little DC, Calkins CM , et al. A simple and more cost-effective antibiotic regimen for perforated appendicitis. J Pediatr Surg 2006; 41 (5) 1020-1024
  • 10 Kohler J, Dorso KL, Young K , et al. In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother 1999; 43 (5) 1170-1176
  • 11 Gill CJ, Jackson JJ, Gerckens LS , et al. In vivo activity and pharmacokinetic evaluation of a novel long-acting carbapenem antibiotic, MK-826 (L-749,345). Antimicrob Agents Chemother 1998; 42 (8) 1996-2001
  • 12 Goldstein EJ, Citron DM, Vreni Merriam C, Warren Y, Tyrrell KL. Comparative in vitro activities of ertapenem (MK-0826) against 1,001 anaerobes isolated from human intra-abdominal infections. Antimicrob Agents Chemother 2000; 44 (9) 2389-2394
  • 13 Pelak BA, Woods GL, Teppler H, Friedland I, Bartizal K, Motyl M. Comparative in-vitro activities of ertapenem against aerobic bacterial pathogens isolated from patients with complicated intra-abdominal infections. J Chemother 2002; 14 (3) 227-233
  • 14 Arguedas A, Cespedes J, Botet FA , et al; Protocol 036 Study Group. Safety and tolerability of ertapenem versus ceftriaxone in a double-blind study performed in children with complicated urinary tract infection, community-acquired pneumonia or skin and soft-tissue infection. Int J Antimicrob Agents 2009; 33 (2) 163-167
  • 15 Solomkin JS, Mazuski JE, Bradley JS , et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010; 50 (2) 133-164
  • 16 Mazuski JE, Sawyer RG, Nathens AB , et al; Therapeutic Agents Committee of the Surgical Infections Society. The Surgical Infection Society guidelines on antimicrobial therapy for intra-abdominal infections: evidence for the recommendations. Surg Infect (Larchmt) 2002; 3 (3) 175-233
  • 17 Sanabria A. Decision-making analysis for selection of antibiotic treatment in intra-abdominal infection using preference measurements. Surg Infect (Larchmt) 2006; 7 (5) 453-462
  • 18 Safdar N, Maki DG. The commonality of risk factors for nosocomial colonization and infection with antimicrobial-resistant Staphylococcus aureus, enterococcus, gram-negative bacilli, Clostridium difficile, and Candida. Ann Intern Med 2002; 136 (11) 834-844
  • 19 Bodey GP, Fainstein V, Garcia I, Rosenbaum B, Wong Y. Effect of broad-spectrum cephalosporins on the microbial flora of recipients. J Infect Dis 1983; 148 (5) 892-897
  • 20 Paterson DL. “Collateral damage” from cephalosporin or quinolone antibiotic therapy. Clin Infect Dis 2004; 38 (Suppl. 04) S341-S345
  • 21 Donskey CJ, Chowdhry TK, Hecker MT , et al. Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients. N Engl J Med 2000; 343 (26) 1925-1932
  • 22 Hoyen CK, Pultz NJ, Paterson DL, Aron DC, Donskey CJ. Effect of parenteral antibiotic administration on establishment of intestinal colonization in mice by Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases. Antimicrob Agents Chemother 2003; 47 (11) 3610-3612
  • 23 Donskey CJ. The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clin Infect Dis 2004; 39 (2) 219-226
  • 24 Flynn DM, Weinstein RA, Nathan C, Gaston MA, Kabins SA. Patients' endogenous flora as the source of “nosocomial” Enterobacter in cardiac surgery. J Infect Dis 1987; 156 (2) 363-368
  • 25 St Peter SD, Tsao K, Spilde TL , 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 (6) 981-985
  • 26 Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing; Nineteenth informational supplement, M100–S19. Wayne, PA: Clinical and Laboratory Standards Institute; 2009
  • 27 Goldin AB, Sawin RS, Garrison MM, Zerr DM, Christakis DA. Aminoglycoside-based triple-antibiotic therapy versus monotherapy for children with ruptured appendicitis. Pediatrics 2007; 119 (5) 905-911
  • 28 Emil S, Laberge JM, Mikhail P , et al. Appendicitis in children: a ten-year update of therapeutic recommendations. J Pediatr Surg 2003; 38 (2) 236-242
  • 29 Muehlstedt SG, Pham TQ, Schmeling DJ. The management of pediatric appendicitis: a survey of North American Pediatric Surgeons. J Pediatr Surg 2004; 39 (6) 875-879 , discussion 875–879
  • 30 Chen C, Botelho C, Cooper A, Hibberd P, Parsons SK. Current practice patterns in the treatment of perforated appendicitis in children. J Am Coll Surg 2003; 196 (2) 212-221
  • 31 Nadler EP, Reblock KK, Ford HR, Gaines BA. Monotherapy versus multi-drug therapy for the treatment of perforated appendicitis in children. Surg Infect (Larchmt) 2003; 4 (4) 327-333
  • 32 Maltezou HC, Nikolaidis P, Lebesii E, Dimitriou L, Androulakakis E, Kafetzis DA. Piperacillin/Tazobactam versus cefotaxime plus metronidazole for treatment of children with intra-abdominal infections requiring surgery. Eur J Clin Microbiol Infect Dis 2001; 20 (9) 643-646
  • 33 Goldstein EJ, Snydman DR. Intra-abdominal infections: review of the bacteriology, antimicrobial susceptibility and the role of ertapenem in their therapy. J Antimicrob Chemother 2004; 53 (Suppl. 02) ii29-ii36
  • 34 DiNubile MJ, Friedland IR, Chan CY , et al. Bowel colonization with vancomycin-resistant enterococci after antimicrobial therapy for intra-abdominal infections: observations from 2 randomized comparative clinical trials of ertapenem therapy. Diagn Microbiol Infect Dis 2007; 58 (4) 491-494
  • 35 Bhalla A, Pultz NJ, Ray AJ, Hoyen CK, Eckstein EC, Donskey CJ. Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-resistant, gram-negative bacilli and vancomycin-resistant enterococci in the stool of colonized patients. Infect Control Hosp Epidemiol 2003; 24 (9) 644-649
  • 36 Léonard F, Andremont A, Leclerq B, Labia R, Tancrède C. Use of beta-lactamase-producing anaerobes to prevent ceftriaxone from degrading intestinal resistance to colonization. J Infect Dis 1989; 160 (2) 274-280
  • 37 Pletz MW, Rau M, Bulitta J , et al. Ertapenem pharmacokinetics and impact on intestinal microflora, in comparison to those of ceftriaxone, after multiple dosing in male and female volunteers. Antimicrob Agents Chemother 2004; 48 (10) 3765-3772
  • 38 Piroth L, Aubé H, Doise JM, Vincent-Martin M. Spread of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae: are beta-lactamase inhibitors of therapeutic value?. Clin Infect Dis 1998; 27 (1) 76-80
  • 39 Beaber JW, Hochhut B, Waldor MK. SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature 2004; 427 (6969) 72-74
  • 40 Berkowitz FE, Metchock B. Third generation cephalosporin-resistant gram-negative bacilli in the feces of hospitalized children. Pediatr Infect Dis J 1995; 14 (2) 97-100
  • 41 Cavallaro V, Catania V, Bonaccorso R , et al. Effect of a broad-spectrum cephalosporin on the oral and intestinal microflora in patients undergoing colorectal surgery. J Chemother 1992; 4 (2) 82-87
  • 42 Guggenbichler JP, Allerberger FJ, Dierich M. Influence of cephalosporines III generation with varying biliary excretion on fecal flora and emergence of resistant bacteria during and after cessation of therapy. Padiatr Padol 1986; 21 (4) 335-342
  • 43 Cosgrove SE, Kaye KS, Eliopoulous GM, Carmeli Y. Health and economic outcomes of the emergence of third-generation cephalosporin resistance in Enterobacter species. Arch Intern Med 2002; 162 (2) 185-190
  • 44 Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999; 115 (2) 462-474
  • 45 Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare?. Clin Infect Dis 2002; 34 (5) 634-640
  • 46 Ostrowsky BE, Venkataraman L, D'Agata EM, Gold HS, DeGirolami PC, Samore MH. Vancomycin-resistant enterococci in intensive care units: high frequency of stool carriage during a non-outbreak period. Arch Intern Med 1999; 159 (13) 1467-1472
  • 47 Paterson DL, Ko WC, Von Gottberg A , et al. Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol 2001; 39 (6) 2206-2212
  • 48 Paterson DL, Ko WC, Von Gottberg A , et al. International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections. Ann Intern Med 2004; 140 (1) 26-32
  • 49 Trouillet JL, Vuagnat A, Combes A, Kassis N, Chastre J, Gibert C. Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms. Clin Infect Dis 2002; 34 (8) 1047-1054
  • 50 Galli R, Banz V, Fenner H, Metzger J. Laparoscopic approach in perforated appendicitis: increased incidence of surgical site infection?. Surg Endosc 2013; 27 (8) 2928-2933