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


Therapeutics

Norfloxacin reduced spontaneous bacterial peritonitis in hospitalized patients with cirrhosis

ACP J Club. 1991 May-June;114:79. doi:10.7326/ACPJC-1991-114-3-079


Source Citation

Soriano G, Guarner C, Teixidó M, et al. Selective intestinal decontamination prevents spontaneous bacterial peritonitis. Gastroenterology. 1991;100:477-81. [PubMed ID: 1985045]


Abstract

Objective

To determine whether norfloxacin reduces the incidence of spontaneous bacterial peritonitis in hospitalized patients with cirrhosis and low levels of ascitic fluid protein.

Design

Randomized, unblinded, controlled trial.

Setting

Not stated.

Patients

63 patients with cirrhosis (confirmed by histologic results in 22), consecutively admitted to the hospital with ascites, who had < 1.5 g/dL of total protein concentration in ascitic fluid on an admission diagnostic paracentesis, were included in the trial. All patients had a negative ascitic fluid culture with < 500 neutrophils/µL in the ascitic fluid at admission.

Intervention

Patients assigned to intervention received norfloxacin (n = 32), 400 mg/d orally, while hospitalized, starting within 8 hours of admission. The average duration of treatment was for 20 days. Patients assigned to the control group (n = 31) did not receive norfloxacin.

Main outcome measures

Patients were closely monitored for bacterial infections and norfloxacin side effects, including spontaneous bacterial peritonitis.

Main results

The rate of infection was lower in the nonfloxacin than control group (P < 0.005) (Table). No cases (0%) of spontaneous bacterial peritonitis occurred in the intervention group compared with 7 cases (23%) in the control group (P < 0.05). The incidence of infections in the control group was similar for patients admitted exclusively for ascites and for patients admitted for other problems, such as encephalopathy, jaundice, wasting, or anemia. No differences existed between the intervention and control groups in the length of hospitalization, diuretic treatment, or incidence of gastrointestinal bleeding or encephalopathy. 2 deaths occurred in the norfloxacin group and 5 in the control group (not significant). None of the intervention group died from infection; 4 of 5 deaths in the control group were caused by infection. 2 patients had adverse effects (skin rash, fever) that resolved when norfloxacin treatment was discontinued.

Conclusion

Norfloxacin decreased the incidence of hospital-acquired infections in hospitalized patients with cirrhosis and low ascitic fluid levels of protein.

Source of funding: Not stated.

Address for article reprint: Dr. C. Guarner, Servicio de Patología Digestiva, Hospital de la Santa Creu i Sant Pau. Avinguda Sant Antoni Maria Claret, 167, 08025 Barcelona, Spain.


Table. Norfloxacin vs control (no norfloxacin) in hospitalized patients with cirrhosis*

Outcome Norfloxacin Control RRR (95% CI) NNT (CI)
Infection 3% 42% 93% (60 to 99) 3 (2 to 5)

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


Commentary

The results of this study suggest that prophylactic norfloxacin administered to hospitalized patients with low ascitic fluid protein concentrations may prevent spontaneous bacterial peritonitis and other hospital-acquired infections. Several features of this study must be considered before such prophylaxis is adopted in practice. The study was not blinded, and untreated patients received more diagnostic paracenteses (to look for spontaneous bacterial peritonitis) than did the treated group. Because spontaneous bacterial peritonitis may sometimes occur without dramatic clinical signs, it is possible that an increased frequency of surveillance contributed to the increased detection of spontaneous bacterial peritonitis in untreated patients. Also, it is possible in a nonblinded study that administration of co-maneuvers (such as special care to prevent respiratory or urinary infections) may have contributed to a decreased rate in the norfloxacin group.

Nonetheless these findings are important and provocative. The effect of antibiotic prophylaxis in reducing spontaneous bacterial peritonitis is in keeping with the findings of a more recent study where trimethoprim-sulphamethoxazole was used (1).

David F. Ransohoff, MD
Yale UniversityNew Haven, Connecticut, USA.


Reference

1. 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;122:595-8.


Author's Response

Terri Betts, BSc (Pharm), University Hospital, Shaughnessy Site, Vancouver, British Columbia, wrote to inform us that we were in error in describing norfloxacin as “an oral nonabsorbable antibiotic” in this abstract. She writes, “The original article does not identify it as such, and norfloxacin is known to be moderately well absorbed after oral administration, with estimated bioavailability of 30% to 75%. Peak levels of 1.5 to 2 mg/L are attained at 1 to 2 hours after the dose. Therapeutic urinary levels are maintained for 12 to 24 hours and exceed 100 mg/L for at least 8 hours after a 400-mg oral dose. However, norfloxacin and other quinolones also reach very high fecal concentrations, ranging from 200 to 2000 mg/kg (1). Given its antimicrobial spectrum and high levels achieved in the intestinal lumen, norfloxacin would likely be efficacious for intestinal decontamination in a manner similar to oral nonabsorbable antibiotics (2). Systemic absorption and high urinary levels may have made an additional contribution to the lower rates of spontaneous peritonitis in the treatment group through prophylaxis of urinary tract infection. In his commentary, Dr. Ransohoff mentions the possible effect that prevention of urinary infection may have had on the outcome of the study.”

1. Stein GE. Review of the bioavailability and pharmacokinetics or oral norfloxacin. Am J Med. 1987;82(Suppl 6B):18-21.

2. Nord CE. Effect of new quinolones on human gastrointestinal microflora. Rev Infect Dis. 1988;10(Suppl 1):S193-6.