Anti-fungal therapy in the treatment of perforated peptic ulcers: what’s the evidence?

Huston JM, et al. Role of Empiric Anti-Fungal Therapy in the Treatment of Perforated Peptic Ulcer Disease: Review of the Evidence and Future Directions. Surg Infect (Larchmt). 2019 Dec;20(8):593-600.

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Results: There are no randomized clinical trials comparing outcomes specifically for patients with PPU treated with or without empiric anti-fungal therapy. We identified one randomized multi-center trial evaluating outcomes for patients with intra-abdominal perforations, including PPU, that were treated with or without empiric anti-fungal therapy. We identified one single-center prospective series and three additional retrospective studies comparing outcomes for patients with PPU treated with or without empiric anti-fungal therapy. 

Conclusion: The current evidence reviewed here does not demonstrate efficacy of anti-fungal agents in improving outcomes in patients with PPU. As such, we caution against the routine use of empiric anti-fungal agents in these patients. Further studies should help identify specific subpopulations of patients who might derive benefit from anti-fungal therapy and help define appropriate treatment regimens and durations that minimize the risk of resistance, adverse events, and cost.

Horn CB, et al. Pre-Operative Anti-Fungal Therapy Does Not Improve Outcomes in Perforated Peptic Ulcers. Surg Infect (Larchmt). 2018 Aug/Sep;19(6):587-592.

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Results: There were 107 patients with PPUs who received operative management; 27 (25.2%) received pre-operative anti-fungal therapy; 33 (30.8%) received peritoneal fluid culture, and 17 cultures (51.5%) were positive for fungus. The presence of fungus in the cultures did not affect the outcomes. There were no differences in length of stay (LOS), intensive care unit (ICU) LOS, ventilator days, 30-day re-admission rates, or rates of intra-abdominal abscess formation or fungemia in patients who received pre-operative anti-fungal drugs regardless of the presence of fungi in the peritoneal fluid.

Conclusion: Candida has been recovered in 29%-57% of peritoneal fluid cultures in patients with PPUs. However, no studies have evaluated pre-operative anti-fungal therapy in PPUs. Our data suggest that pre-operative anti-fungal drugs are unnecessary in patients undergoing operative management for PPU.

Kwan JR, Lim M, Ng F, Shelat V. Fungal Isolates in Peritoneal Fluid Culture Do Not Impact Peri-Operative Outcomes of Peptic Ulcer Perforation. Surg Infect (Larchmt). 2019 Dec;20(8) :619-624.

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Results: The median age was 58 (interquartile range [IQR] 44-70) years with 110 (20.3%) females. In addition to hypertension and hyperlipidemia, diabetes mellitus (13.5%), ischemic heart disease (2.6%), and heart failure (2.4%) were common. Fungus was cultured from peritoneal fluid in 209 (38.6%) patients. Median American Society of Anesthesiology (ASA) score was 2 (IQR 2-3) and median Mannheim peritonitis index (MPI) score was 15 (IQR 10-20). Free air was detected in 323 (59.6%) patients and 52 (9.6%) patients had gastrectomy. Median length of stay was 7 (IQR 6-11) days. All-cause complications were seen in 53 (9.8%) patients, of whom 37 patients (6.8%) developed intra-abdominal collection, 20 patients (3.7%) had anastomotic leakage, and 12 patients (2.2%) required repeat operation. Thirty-day mortality was seen in 47 (8.7%) patients. Multivariable analysis showed age (median age, 64; IQR 53-74) as a predictor of fungal growth (p < 0.001) but fungal growth not a predictor of adverse peri-operative outcomes.

Conclusion: Fungal isolates in peritoneal fluid cultures are more likely to occur in older patients who have PPU. Presence of fungal isolates does not impact peri-operative outcomes.

Li WS, Lee CH, Liu JW. Antifungal therapy did not improve outcomes including 30-day all-cause mortality in patients suffering community-acquired perforated peptic ulcer-associated peritonitis with Candida species isolated from their peritoneal fluid. J Microbiol Immunol Infect. 2017 Jun;50(3):370-376.

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Results: Among the 133 included patients, 76 did not receive (Group 1) and 57 did receive (Group 2) antifungal therapy. Sixteen (12%) of the overall included patients died within 30 days. Shock [odds ratio (OR), 5.6; 95% confidence interval (CI), 1.9-16.5; p = 0.002] and higher Acute Physiology and Chronic Health Evaluation II score (>20; OR, 9.5; 95% CI, 1.1-80.7; p = 0.04) were independently associated with 30-day mortality. Among the 80 matched patients from Groups 1 and 2 (1:1 matched) with the closest propensity score, no significant difference was found in 30-day all-cause mortality, time to mortality, the need for reoperation/abscess formation/anastomotic leakage, prolonged intensive care unit stay, and prolonged mechanical ventilator dependence between patients with and without antifungal therapy.

Conclusion: Our study provides solid evidence supporting the notions that antifungal therapies do not benefit patients suffering PPU peritonitis with Candida species isolated from their ascites in general, and antifungal therapy could be reserved for patients who are critically ill and/or severely immunocompromised.

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