Shorter Total Length of Stay After Intraperitoneal Fosfomycin, Metronidazole, and Molgramostim for Complicated Appendicitis: A Pivotal Quasi-Randomized Controlled Trial

Abstract

Background: We aimed to investigate the difference in the total length of hospital stay (LOS) after intraperitoneal vs. intravenous antibiotic treatment in patients with complicated appendicitis. Methods: We conducted a quasi-randomized prospective clinical trial. The intervention group received 4 g fosfomycin, 1 g metronidazole, and 50 µg recombinant human granulocyte-macrophage colony-stimulating factor intraperitoneally, which was left in the abdominal cavity, immediately after laparoscopic appendectomy. Postoperatively, this group received antibiotics orally. The control group received intravenous antibiotics both during surgery and postoperatively. We primarily evaluated total LOS within 30 days. Furthermore, we evaluated harms and adverse events, Gastrointestinal Quality of Life Index, postoperative complications, and convalescence. Participants were followed for 30 days postoperatively. Results: A total of 12 participants concluded the trial. The total LOS was significantly shorter in the intervention group (six participants, median 13 h; range 2-21 h) than in the control group (six participants, median 84 h; range 67-169 h), p = 0.017. Comparable harms and Gastrointestinal Quality of Life Index scores were found in the two groups. The time to return to normal activities was median 6 and 10 days for the intervention and the control group, respectively. There were no serious adverse events related to the trial nor any complications in the intervention group. In the control group, two patients developed intraabdominal abscesses. Conclusions: The intervention group had a significantly shorter total LOS. The study was not powered to assess differences in complications, but the results indicate that Fonnes et al. Short LOS for Complicated Appendicitis the intervention seems to be a safe regimen, which can be investigated further to treat patients with complicated appendicitis.

Parenteral Fosfomycin in Gastrointestinal Surgery: A Systematic Review

“…1. Finally, 15 unique studies [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] were included in this systematic review as five reports had overlapping populations with the included studies [31][32][33][34][35].…”

“…The characteristic of the included studies is depicted in ▶table 1. The majority of the included studies were RCTs [16,[20][21][22][23][24][26][27][28], three studies were retrospective cohort studies [19,29,30],…”

“…The rate of intraabdominal abscess was reported by eight studies [16,18,19,[21][22][23][24]26] (▶ Fig. 2b).…”

“…Sepsis was defined as e. g. "clinical, with malaise and fever" [21] or "temperature > 38.5 ̊C, together with rigors and poor general condition" [22]. No patients were reported to suffer from sepsis in the two emergency studies with small populations [16,18]. For elective procedures, the rate of sepsis for patients receiving fosfomycin vs. comparison ranged from 1-2 % vs. 1-3 %.…”

“…Most of the patients treated with fosfomycin (51 %) had undergone an elective procedure [17,[19][20][21][22][24][25][26], the most common being colorectal procedures or cholecystectomy (Supplementary File table 1). Almost one-fourth of patients treated with fosfomycin (23 %) underwent an emergency procedure [16,18,23,30] including laparoscopic cholecystectomy or appendectomy. The remaining three studies reported on a mixed population of patients undergoing either an elective or emergency procedure [27][28][29].…”