Spontaneous Bacterial Peritonitis: Clues to its Pathogenesis

By Andres T. Blei MD

Infections are an important factor in the morbidity and mortality of patients with acute and chronic liver failure. Infection of the ascitic fluid can occur without a primary intra-abdominal source and the term spontaneous bacterial peritonitis (SBP) reflects the extemporaneous nature of the infection as well as the predominant etiologic role of aerobic bacteria.

Pathogenesis

The predominance of gram-negative organisms in SBP suggests a role for intra-abdominal events. Passage of bacteria into the ascitic fluid could occur across intestinal tissue, whose permeability characteristics are affected by portal hypertension. A reduced intestinal transit time may also play a role, as experimental studies have shown a favorable prophylactic effect of cisapride, a prokinetic agent.

A more recent study has demonstrated the presence of positive cultures of mesenteric lymph nodes in patients with cirrhosis at the time of transplantation (1). These findings support a pathogenic role for bacterial translocation into lymph nodes. As S. pneumoniae is the second most common organism isolated in SBP, bacteremia from other sources with localization in the ascitic fluid will also be a route of infection.

Diagnosis

A low threshold for diagnostic paracentesis is required. Patients with SBP may present without classic signs of infection; sometimes a deterioration of mental state or worsening renal function are clues to its presence. SBP is a complication of tense ascites and seldom occurs in patients with minimal fluid accumulation. A PMN count of ?250 mm3 has the best sensitivity and specificity for diagnosis.

In spite of placing samples in blood culture bottles to increase the ability to detect micro-organisms, there is still a sizable proportion of negative cultures, therefore, blood and urine cultures should also be obtained. Culture-negative neutrocytic ascites is managed in similar fashion to culture-positive SBP. A low ascitic fluid glucose (<50 mg/dl), a higher ascitic protein count (>1 g/dl) and more than one bacterial species in cultures are clues for secondary peritonitis.

Management

Antibiotics are started prior to microbiological confirmation. Many studies have been performed using cefotaxime, a third generation cephalosporin, which is given at a minimum of 2g every 12 hours for five days. Recent studies show similar good results with ampicillin-sulbactam.

Changes in antibiotic regimens can occur after bacterial identification and sensitivity as well as after a repeat paracentesis at 48 hours, where a reduction of the PMN count below 75 percent of the original level is sought. Aminoglycosides should not be administered, as renal toxicity is high even in the presence of normal trough levels.

SBP complicated with renal failure carries a high mortality rate. The deterioration in renal function can continue even after bacterial eradication, with features of oliguria, avid sodium retention and renal vasoconstriction, leading to progressive renal failure, i.e. the hepatorenal syndrome. In a recent controlled trial, albumin infusion at the onset of the clinical picture significantly decreased the incidence and mortality of such patients (2). It was administered intravenously at a dose of 1.5 g/kg in the first three days and at 1 g/kg in the subsequent four days.

Prevention

Patients who survive the first episode of SBP are at risk of a second episode and should receive antibiotic prophylaxis. Most controlled studies have been performed with norfloxacin, an effective agent but one that can induce resistance in the bacterial flora. Alternatives, such as ampicillin-sulbactam and trimethoprim-sulphomethoxasole, have been explored, but large scale results are not yet available. More controversial is primary prophylaxis, as patients with ascites, poor liver function and a low protein (<1g/dl) level in the ascitic fluid carry an approximate 20 percent risk of developing SBP at one year. A recent consensus conference (3) indicated a lack of sufficient data to recommend this approach.

The consensus conference did widen the indications of antibiotic prophylaxis to include gastrointestinal hemorrhage in cirrhosis, as several studies have shown a benefit of antibiotic prophylaxis on rates of rebleeding and survival using norfloxacin 400 mg/d for seven days. (Ciprofloxacin and ampicillin-sulbactam are possible alternatives.) Patients with ascites and gastrointestinal hemorrhage should receive a diagnostic tap prior to the initiation of antibiotics.

The progression of SBP signals the need to consider liver transplantation in the appropriate candidate. Survival one year after SBP is reduced to 30-40 percent, which reflects the other complications that can develop in chronic liver failure.

References

1.Cirera et al. J Hepatol. 2000 (in press).
2.Sort et al. New Engl J Med. 1999; 341:403-9.
3.Rimola et al. J Hepatol. 2000; 32:142-159.

Dr. Blei is professor of medicine and surgery at Northwestern University Medical School. He can be reached at XXX-XXX-XXXX and at xxxxxx@xxx.xxx.

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