Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Trimethoprim-sulfamethoxazole reduced bacterial peritonitis occurrence in cirrhosis

ACP J Club. 1995 Sept-Oct;123:42. doi:10.7326/ACPJC-1995-123-2-042


Source Citation

Singh N, Gayowski T, Yu VL, Wagener MM. Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial. Ann Intern Med. 1995 Apr 15;122:595-8.


Abstract

Objective

To evaluate the efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis and ascites.

Design

Randomized controlled trial with median 90-day follow-up.

Setting

University-affiliated U.S. Veterans Affairs medical center.

Patients

60 patients (median age 45 y) with documented cirrhosis and ascites. Exclusion criteria were allergy to sulfonamides, renal failure, or active spontaneous bacterial peritonitis or extraperitoneal infection.

Intervention

30 patients were assigned to trimethoprim-sulfamethoxazole, 1 double-strength tablet, 5 times/wk, Monday through Friday. 30 patients were assigned to receive no prophylaxis. Randomization was stratified by serum bilirubin, ascitic fluid protein, and serum creatinine levels.

Main outcome measures

Development of spontaneous bacteremia or spontaneous bacterial peritonitis.

Main results

Overall, infectious complications developed in 1 patient (3.3%) receiving trimethoprim-sulfamethoxazole compared with 9 patients (30%) not receiving prophylaxis (P = 0.006) (Table). Spontaneous bacterial peritonitis or spontaneous bacteremia developed in 1 patient (3.3%) receiving trimethoprim-sulfamethoxazole compared with 8 patients (26.7%) receiving no prophylaxis (P = 0.011) (Table). None of the patients developed adverse effects. 2 patients (7%) receiving trimethoprim-sulfamethoxazole compared with 6 patients (20%) receiving no prophylaxis died (P = 0.15). No death was attributed directly to infection in either group.

Conclusion

Compared with no prophylaxis, trimethoprim-sulfamethoxazole reduced the incidence of spontaneous bacterial peritonitis and spontaneous bacteremia in patients with cirrhosis and ascites.

Source of funding: Not stated.

For article reprint: Dr. V.L. Yu, Infectious Diseases Section, Veterans Affairs Medical Center, University Drive, Pittsburgh, PA 15240, USA. FAX 412-688-6950.


Table. Trimethoprim-sulfamethoxazole vs no prophylaxis for the prevention of spontaneous bacterial peritonitis*

Outcomes at median 90 d Trimethoprim-sulfamethoxazole No prophylaxis RRR (95% CI) NNT (CI)
Infectious complications 3.3% 30% 89% (39 to 98) 4 (2 to 11)
Spontaneous bacterial peritonitis 3.3% 26.7% 88% (30 to 98) 4 (2 to 16)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

Spontaneous bacterial peritonitis occurs in one quarter of patients with ascites, particularly if hepatic function is poor or ascites protein is low (1). Probability of recurrence and mortality are high (51% and 79%, respectively), and about half of the deaths are attributed to infection (2). Several studies have shown that recurrence of spontaneous bacterial peritonitis can be prevented by antibiotics. The first of these studies was by Gines and colleagues (3), who used norfloxacin. Although successful in preventing recurrence, these studies were not ideal because they used expensive drugs and decreased neither the mortality rate nor the cost as measured by the number of hospital admissions. The study by Singh and colleagues also addressed the question of cost, which was reduced from $590 to $31 for a 1-year course of norfloxacin compared with trimethoprim-sulfamethoxazole. Mortality, however, still was not decreased. This is not unexpected, because a larger sample of patients would have been required to achieve the necessary power to detect a difference in mortality between the treatment groups.

Singh and colleagues argue that the regimen studied is superior to previous forms of prophylaxis because it is less likely to select resistant organisms and because it also covers gram-positive bacteria. Prophylaxis of spontaneous bacterial peritonitis with trimethoprim-sulfamethoxazole appears reasonable. Larger studies are needed, however, to show that prophylaxis prolongs life and lowers the cost of hospitalization. In view of the dismal prognosis that exists when spontaneous bacterial peritonitis has occurred, these patients should be evaluated for liver transplantation.

Jürg Reichen, MD
University of BerneBerne, Switzerland


References

1. Audreu M, Sola R, Sitges-Serra A, et al. Risk factors for spontaneous bacterial peritonitis in cirrhotic patients with ascites. Gastroenterology. 1993;104:1133-8.

2. Tito L, Rimola A, Gines P, et al. Recurrence of spontaneous bacterial peritonitis in cirrhosis: frequency and predictive factors. Hepatology. 1988;8:27-31.

3. Gines P, Rimola A, Planas R, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind-placebo-controlled trial. Hepatology. 1990;12:716-24.