Listeria monocytogenes--induced monomicrobial non-neutrocytic bacterascites.

ABSTRACT

Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis of the liver. The organisms most commonly involved in this infection are gram negative bacteria like Escherichia coli and Klebsiella pneumoniae, and grain-positive bacteria like Streptococcus pneumoniae and Staphylococcus aureus. Listeria monocytogenes is an uncommon gram-positive bacillus implicated in infections in neonates, pregnant females, the elderly, and immunocompromised patients. Listeria monocytogenes--induced SBP is rare, with less than 40 cases reported in the medical literature. Monobacterial non-neutrocytic bacterascites (MNB) is a variant of SBP, where the ascitic fluid culture is positive but the ascitic neutrophil count is less than 250/[mm.sup.3]. Forty percent of these patients will subsequently have SBP. Only 2 cases of MNB from L monocytogenes have previously been reported. We report a case of MNB in a patient with cirrhosis whose ascitic neutrophil count was 164/mm3, but Gram stain and m icrobiologic culture showed the growth of L monocytogenes.

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SPONTANEOUS BACTERIAL PERITONITIS (SBP) is a common complication of cirrhosis, with an incidence as high as 30%. The most common pathogens are enteric gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, and Enterococcus organisms, followed by gram-positive bacteria like Streptococcus pneumoniae and Staphylococcus aureus. Listeria monocytogenes is increasingly implicated as the etiologic agent of SBP in recent literature. We report a patient with L monocytogenes-induced monomicrobial non-neutrocytic bacterascites and review the literature regarding incidence, diagnostic pitfalls, and disease management.

CASE REPORT

A 56-year-old white man presented with a 1-week history of increasing abdominal girth, swelling of the lower extremities, and fever. He denied having any abdominal pain. His medical history included transitional cell carcinoma of the urinary bladder treated with surgical resection, and cirrhosis of the liver due to alcohol abuse. His vital signs were blood pressure 138/84 mm Fig, heart rate 108/mm, respiratory rate 20/mm, and oral temperature of 38.3[degrees]C. Physical examination revealed the presence of spider nevi on the chest, gynecomastia, and decreased axillary hair. He had massive ascites without any abdominal tenderness, and bowel sounds were normal. The patient had a right-sided inguinal hernia and bilateral testicular atrophy. There was 2+ pitting edema of the lower extremities. Findings from the neurologic examination were normal, and there was no evidence of asterixis.

Laboratory investigations revealed a white blood cell count of 6,400/[mm.sup.3] with a normal differential count. Hemoglobin level was 12 g/dL. Liver function tests were significant for normal transaminase levels and an alkaline phosphatase level of 186 U/L; total bilirubin level was 1.3 mg/dL; serum albumin level 2.2 g/dL. Pancreatic enzyme and serum electrolyte values were unremarkable. A diagnostic paracentesis was done, and analysis of the ascitic fluid identified a white blood cell count of 1,109/[mm.sup.3], with a differential count of 15% neutrophils, 75% lymphocytes, and 8% macrophages. The albumin level in the ascitic fluid was 0.85 g/dL, with glucose level of 149 mg/dL. Gram stain of the ascitic fluid showed gram-positive bacilli, and culture of ascitic fluid identified L monocytogenes. Blood cultures remained negative for growth of any microorganism.

The patient was initially started on empiric therapy with cefotaxime, but this was switched to ampicillin after the microbiologic culture results were known. There was symptomatic improvement and resolution of the fever after 3 days of treatment with ampicillin. Paracentesis was repeated on the fifth day after admission and showed a decrease of the ascitic white blood cell count to 495/[mm.sup.3], with a differential count of 1% neutrophils, 77% lymphocytes, and 18% macrophages. The Gram stain and culture results of the second sample of ascitic fluid were negative for growth of microorganisms. The patient subsequently improved and was discharged from the hospital.

DISCUSSION

Listeria organisms are aerobic or facultative anaerobic, intracellular, gram-positive bacilli found in sewage, poultry, dairy products, decaying vegetables, dust, and water. Of the 7 strains of Listeria reported thus far, only L monocytogenes is pathogenic to humans. (1) Listeria monocytogenes is known to cause disease in neonates, pregnant females, the elderly population, and immunocompromised hosts. Unlike most foodborne pathogens that cause gastrointestinal disease, the most common presentations of L monocytogenes infection are bacteremia and meningitis. The rise in the reported incidence of this organism is attributed to increased awareness, increased number of immunocompromised hosts, and better microbiologic identification. Other manifestations of L monocytogenes infection include cerebritis, (2) septic arthritis, (3) endophthalmitis, (4) endocarditis, (5) and peritonitis. (6-12) Spontaneous bacterial peritonitis is a rare presentation of Listeria infection, with less than 40 cases cited in Medline sinc e 1966.

Most cases of L monocytogenes-induced SBP occur in patients with chronic liver disease. It has also been reported after bowel wall injury resulting from paracentesis, (6) esophagoduodenoscopy, (9) malignancy, (10) hepatic transplantation, (13) and continuous ambulatory peritoneal dialysis. (14) Patients with cirrhosis of the liver have depressed reticuloendothelial activity, decreased ascitic-fluid opsonic activity bowel wall edema, and bacterial colonization of the small bowel (15) moreover, there is decreased clearance of bacteria from the blood stream in these patients. (16) Patients with cirrhosis are also in a state of iron overload, and iron is known to enhance the in vitro growth of Listeria. (17) These factors may predispose patients with cirrhosis to Listeria infection. Listeria monocytogenes colonizes the human gastrointestinal tract; a 5% fecal prevalence of L monocytogenes has been found in healthy, asymptomatic individuals. (18) The proposed mechanism of transmission of infection in SBP is transl uminal migration of Listeria via the gastrointestinal tract after colonization. Despite the worldwide prevalence of listeriosis, two thirds of the cases of SBP caused by L monocytogenes have been reported from Spain. The exact reason for this regional predilection is not known, though dietary habits have been implicated in its pathogenesis.

Monomicrobial non-neutrocytic bacterascites (MNB) is a variant of SBP; it is diagnosed when the culture of ascitic fluid yields bacteria, but the neutrophil count is less than 250/[mm.sup.3]. Our patient had an ascitic fluid neutrophil count of 164/[mm.sup.3]. Before our report of this case, there have been only 2 case reports of L monocytogenes-induced MNB in the medical literature. (11,19) Most cases of SBP due to Listeria have been reported to have an ascitic fluid neutrophil count more than 250/[mm.sup.3]. (8) High ascitic monocyte counts have also been reported in L monocytogenes infection. (19) Monocytes exposed to Mycobacterium tuberculosis release monocyte chemoattractant protein-1, which attracts monocytes and lymphocytes. It is possible that a similar mechanism works in Listeria infection as well; however, our patient did not have ascitic fluid monocytosis.

Patients with ascitic total-protein levels of less than 1 g/dL are at high risk of SBP due to decreased ascitic-fluid opsonic activity. Our patient had an ascitic-fluid protein level of 1.34 g/dL. Ascitic-fluid opsonic activity, however, does not protect against L monocytogenes--induced SBP, since it is an intracellular pathogen whose clearance is mediated by cellular immunity. (19)

Microbiologic diagnosis of L monocytogenes can be difficult. Its morphology can easily be confused with other gram-positive bacilli, diphtheroids and Enterococcus organisms; moreover, biochemical tests like the bile esculin test and the salt tolerance test give positive results in both L monocytogenes and Enterococcus species infections. Catalase activity and a characteristic tumbling motility pattern may help differentiate Listeria organisms in such circumstances. (20) Ascitic-fluid Gram stain has rarely been reported to be positive in the diagnosis of L monocytogenes-induced SBP, and most of the time the diagnosis is made from culture results. (8,9) Our patient, however, had a positive Gram stain along with positive microbiologic cultures.

The empiric treatment of SBP with cefotaxime is not effective against L monocytogenes, since third-generation cephalosporins have reduced affinity for bacterial penicillin-binding protein-3, rendering them ineffective against this organism. (21) The treatment of choice in L monocytogenes--induced SBP is ampicillin, often used in combination with aminoglycosides for synergy. (22) The combination of trimethoprim and sulfamethoxazole has also been used successfully. (23) Erythromycin may be considered as a third-line agent after ampicillin and trimethoprim-sulfamethoxazole. Chloramphenicol, tetracyclines, and quinolones are not effective against L monocytogenes. The duration of treatment for L monocytogenes SBP is not clearly established; clinical improvement of the patient and repetition of paracentesis may help in making this decision. Our patient was given intravenous ampicillin for 5 days, then switched to oral therapy after a repeat ascitic fluid culture was negative. There are no guidelines for prophylacti c treatment after an episode of L monocytogenes--induced SBP.

The mortality in patients with L monocytogenes--induced SBP was found to be as high as 25% in a review of case reports from 1967 through 1989. (8) The prognosis worsens with age, presence of cirrhosis, and underlying defects in cellular immunity.

CONCLUSION

Listeria monocytogenes--induced SBP is being increasingly recognized in patients with cirrhosis. The clinical presentation is no different from other microorganisms; however, the real cue to diagnosis lies in having a high index of suspicion for SBP. Unusual organisms should be suspected in patients with an extra-abdominal site of infection, if SBP does not respond to empiric therapy, or when gram-positive rods or diphtheroids are reported in Gram stain of ascitic fluid. This is particularly important because L monocytogenes does not respond to conventional empiric therapy with third-generation cephalosporins, and there is a high mortality rate associated with the infection.

References

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(4.) Ballon PH, Loffredo FR, Painter B: Listeria endophthalmitis. Arch Qphthalmol 1979; 97:101-102

(5.) Gallagher PG, Watanakunakorn C: Listeria monocytogenes endocarditis. a review of literature, 1950-1986. Scand J Infect Dis 1988; 20:359-368

(6.) Seigfried C, Schubert TT: Secondary bacterial peritonitis due to Listeria monocytogenes after paracentesis. South Med J 1990; 83:213-214

(7.) Kandaswami J, di Bisceglie AM, Gibson 5, et al: SBP caused by infection with Listeria monocytogenes: a case report and review of the literature. Am J Gastroenterol 1993; 9:1556-1558

(8.) Sivalingam JJ, Martin P, Fraimow HS, et al: Listeria monocytogenes peritonitis: case report and literature review. Am J Gastroenterol 1992; 87:1839-1845

(9.) Nguyen HM, Yu LV: Listeria monocytogenes peritonitis in cirrhotic patients. value of ascitic fluid gram stain and a review of literature. Dig Dis Sci 1994; 39:215-218

(10.) Polanco A, Gines C, Canton R, et al: Spontaneous bacterial peritonitis caused by Listeria monocytogenes: two case reports and literature review. Eur J Clin Micro Infect Dis 1992; 11:346-349

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RELATED ARTICLE: KEY POINTS

* Listeria monocytogenes is an uncommon pathogen that causes meningitis and bacteremia in neonates, the elderly, and immunocompromised hosts.

* Spontaneous bacterial peritonitis caused by L monocytogenesis a rare and potentially fatal complication that is being increasingly recognized.

* Patients with cirrhosis may be predisposed to spontaneous bacterial peritonitis caused by L monocytogenes due to decreased ascitic opsonic activity, depressed reticuloendothelial activity, bowel wall edema, and bacterial colonization of the gut.

* Listeria organisms can be morphologically confused with other gram-positive bacteria, enterococci, and diphtheroids.

* Ampicillin is the drug of choice for L monocytogenes--induced spontaneous bacterial peritonitis, with aminoglycosides given for their synergistic effects.

* A high index of suspicion is required for the diagnosis of L monocytogenes infection, and it should be suspected if diphtheroids are reported on the Gram stain or if empiric therapy with cephalosporins is ineffective.

From the Department of Internal Medicine, University of Texas Medical Branch, Galveston.

Reprint requests to Rajiv Gupta, MD, University of Texas Medical Branch, Department of Internal Medicine, 4.112 John Sealy Annex, 301 University Blvd, Galveston, TX 77555-0570.