Research

Original Investigation

Antibiotic Duration After Laparoscopic Appendectomy for Acute Complicated Appendicitis Charles C. van Rossem, MD; Marc H. F. Schreinemacher, MD, PhD; Anna A. W. van Geloven, MD, PhD; Willem A. Bemelman, MD, PhD; for the Snapshot Appendicitis Collaborative Study Group

IMPORTANCE Optimal duration of antibiotic treatment to reduce infectious complications

after an appendectomy for acute complicated appendicitis remains unclear. OBJECTIVE To investigate the effect of antibiotic duration on infectious complications after laparoscopic appendectomy for acute complicated appendicitis. DESIGN, SETTING, AND PARTICIPANTS National multicenter prospective, observational, surgical resident–led cohort study conducted in June and July 2014. This study involved academic teaching hospitals (n = 8), community teaching hospitals (n = 38), and community nonteaching hospitals (n = 16), and all consecutive patients (n = 1975) who underwent surgery for suspected acute appendicitis. EXPOSURES Patients treated laparoscopically for whom the antibiotic regimens were prolonged postoperatively because of complicated appendicitis. MAIN OUTCOMES AND MEASURES Receiving either 3 or 5 days of antibiotic treatment as planned and additional variables were explored as risk factors for infectious complications using regression analyses. RESULTS A total of 1975 patients were included in 62 participating Dutch hospitals; 1901 (96.3%) of these underwent an appendectomy for acute appendicitis and laparoscopy was used in 74.4% of these patients (n = 1415). In 415 laparoscopically treated patients, antibiotic treatment was continued for more than 24 hours because of acute complicated appendicitis (29.3%). The prescribed antibiotic duration varied between 2 and 6 days in all of these patients. In 123 patients (29.6%), the length of treatment was adjusted. A shorter duration of antibiotic treatment (3 days instead of 5) had no significant effect on any infectious complication (odds ratio [OR], 0.93; 95% CI, 0.38-2.32; P = .88) or on intra-abdominal abscess development (OR, 0.89; 95% CI, 0.34-2.35; P = .81). Perforation of the appendix was the only independent risk factor for the development of an infectious complication (OR, 4.90; 95% CI, 1.41-17.06; P = .01) and intra-abdominal abscess (OR, 7.46; 95% CI, 1.65-33.66; P = .009) in multivariable regression analysis. CONCLUSIONS AND RELEVANCE Lengthening of postoperative antibiotic treatment to 5 days was not associated with a reduction in infectious complications. Further restriction of antibiotic treatment can be considered in nonperforated complicated appendicitis.

Author Affiliations: Department of Surgery, Tergooi Hospital, Hilversum, the Netherlands (van Rossem, van Geloven); Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands (Schreinemacher, Bemelman). Group Information: Snapshot Appendicitis Collaborative Study Group members are listed at the end of the article.

JAMA Surg. doi:10.1001/jamasurg.2015.4236 Published online November 18, 2015.

Corresponding Author: Charles C. van Rossem, MD, Tergooi Hospital, Department of Surgery, PO Box 10016, 1201 DA Hilversum, the Netherlands ([email protected]).

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Research Original Investigation

Antibiotic Duration After Laparoscopic Appendectomy

U

ncomplicated and complicated appendicitis are currently distinguished as 2 different disease entities that require different treatments.1 The role of antibiotic treatment as an alternative for surgery in simple or uncomplicated appendicitis has been studied in adults2-4 and, more recently, in children.5,6 Acute complicated appendicitis with necrosis or perforation of the appendix is treated by appendectomy and usually followed by additional antibiotic treatment aimed at reducing postoperative infectious complications. Restriction and proper use of antibiotics are important for reducing and preventing harmful adverse effects to the patients and preventing antibiotic resistance.7 In American guidelines, an antibiotic length of 4 to 7 days is advised after complicated appendicitis.8 To our knowledge, few studies have investigated the reduction of antibiotic administration after appendectomy and these were mostly performed in children.9-11 Restricting antibiotic duration to fewer than 5 days after surgery in complicated appendicitis is seldom done, fearing infectious complications. However, 3 days of antibiotic treatment has been observed to be feasible and safe in a retrospective cohort of adults with complicated appendicitis.12 The objectives of this prospective study were to investigate the relation of antibiotic duration and infectious complications and to identify possible risk factors for a postoperative infectious complication after laparoscopic appendectomy for acute complicated appendicitis.

Methods

Infectious Complications Superficial surgical site infection was recorded when administration of antibiotics (restart or lengthening for this reason), whether in combination with drainage of a wound abscess, was necessary. An intra-abdominal abscess was defined as a postoperative intra-abdominal fluid collection diagnosed by crosssectional imaging for which administration of antibiotics (restart or lengthening) or a radiological or surgical intervention was needed. Any infectious complication was defined as a superficial surgical site infection, an intra-abdominal abscess, or both. Postoperative ileus was reported as an adverse event when resumption of oral diet was not achieved within 5 days after surgery.14

Study Design

Statistical Analysis

A surgical resident–led prospective, observational, cohort study was conducted in 62 Dutch hospitals including all consecutive patients who underwent surgery for suspected acute appendicitis between June 1, 2014, and July 31, 2014, preceded by a pilot phase in 8 hospitals in May 2014. All patients were treated according to the local hospital protocol that was based on the Dutch guideline for appendicitis.13 One local investigator was responsible for identifying patients and collecting the data that were entered anonymized into an electronic database. The medical ethics committee in the Academic Medical Center in Amsterdam approved the study design and judged that no informed consent from the patients was necessary because of the observational study design without additional burden for the patient. For this analysis, only patients who underwent a laparoscopic appendectomy for acute complicated appendicitis were included. Both pediatric and adult patients were included in this analysis. The primary outcome was the effect of antibiotic treatment length on the infectious complication rate. To identify in-hospital and out-hospital complications during the 30-day follow-up, the electronic patient database system was checked to monitor visits at the emergency department, postoperative imaging or intervention, unscheduled outpatient visits, and hospital readmission.

Dichotomous outcomes were compared using the χ2 test or Fisher exact test where appropriate and comparison of nonparametric outcome (medians) was calculated with the MannWhitney U test. A 2-sided P < .05 was considered significant. Univariable odds ratios (ORs) and 95% CIs were calculated using logistic regression analysis for identifying risk factors for infectious complications and intra-abdominal abscesses. A multivariable logistic regression model was built for variables with P < .20 in univariable analysis and 3 or 5 days of postoperative antibiotic treatment as planned. Statistical analyses were performed using SPSS version 21 (IBM). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement was used in the study design and for preparing the article.15

Complicated Appendicitis and Antibiotic Treatment Complicated appendicitis was defined as necrosis or perforation of the appendix or if an extensive purulent peritonitis was E2

found during laparoscopy for which the surgeon prolonged antibiotic treatment for more than 24 hours. Two lengths of antibiotic treatment were registered; the duration as prescribed by the local surgeon directly after surgery and the duration that the patient eventually received. The actual received duration of antibiotics was retrieved from the medical prescription system. Intravenous antibiotics or a combination with an oral regimen was also registered. In case of the latter, the total duration of antibiotic treatment was calculated and used for analysis. A new course of antibiotics that was started for a complication after the initial course was finished was not included in the registered treatment duration. Patients were treated according to the local hospital protocol based on local resistance pattern (in the Netherlands, usually a combination of cephalosporin and metronidazole).

Results Included Patients A total of 1975 patients underwent surgery for suspected acute appendicitis in 62 Dutch hospitals in the 2-month period (3 months in pilot centers). Among the participating hospitals were all academic teaching hospitals (n = 8), 84% of the community teaching hospitals (n = 38) and 41% of the community nonteaching hospitals (n = 16). The laparoscopic approach was used in 1415 patients (74.4%) who underwent an

JAMA Surgery Published online November 18, 2015 (Reprinted)

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jamasurgery.com

Antibiotic Duration After Laparoscopic Appendectomy

Original Investigation Research

Table 1. Demographics and Outcome After Variable Durations of Antibiotic Treatments No. (%) Characteristic Median age, y

Total (n = 415) 44.0

2-3 d Received (n = 89) 46.0

4-5 d Received (n = 225) 43.0

>5 d Received (n = 101) 43.0

P Valuea .62b

Sex Male

197 (47.5) 43 (48.3)

108 (48.0)

46 (45.5)

Female

218 (52.5) 46 (51.7)

117 (52.0)

55 (54.5)

401 (96.6) 86 (96.6)

216 (96.0)

99 (98.0)

9 (4.0)

2 (2.0)

354 (85.3) 68 (76.4)

193 (85.8)

93 (92.1)

61 (14.7) 21 (23.6)

32 (14.2)

8 (7.9)

51.0

52.0

52.0

.90

ASA classification 1 or 2 3 or 4

14 (3.4)

3 (3.4)

.65

Surgeon Consultant or supervised resident Resident without supervising consultant

.009

Operating time Median

50.0

Daytime, 8 AM-6 PM

186 (45.0) 40 (46.0)

96 (42.7)

50 (49.5)

On call, 6 PM-8 AM

227 (55.0) 47 (54.0)

129 (57.3)

51 (50.5)

NA

NA

Missing

2

NA

.63b

.51

Antibiotic administration Only intravenous

185 (58.7) 78 (87.6)

106 (47.1)

60 (59.4)

Combination of intravenous and oral

130 (41.3) 11 (12.4)

119 (52.9)

41 (40.6)