Spontaneous bacterial peritonitis with Pasteurella multocida in cirrhosis: case report and review of literature.

Abstract: Most Pasteurella multocida human infections involve skin and soft tissues and invariably develop after a bite or a scratch from a dog or a cat. However, other infections with this organism occur infrequently. Enteric microorganisms are the common cause of spontaneous bacterial peritonitis (SBP). We report a case of SBP in a cirrhotic patient from P multocida. English literature (Pubmed) review revealed 12 adult cases of SBP in cirrhotic patients with P multocida. Nine patients were exposed to animals, though a break in the skin or a bite was not reported in each case. The SBP was fatal in four of these patients.

Key Words: cirrhosis, Pasteurella multocida, spontaneous bacterial peritonitis

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A 48-year-old man with a history of hepatic cirrhosis, ascites, esophageal varices, hepatitis C, and anemia was admitted for lower abdominal pain, increasing abdominal girth, and diarrhea for 2 days. The patient had two healthy pet dogs but he denied any dog bites, scratching, or licking of open wounds. (1-11)

Case Report

Examination revealed an afebrile, tachycardic man with blood pressure of 164/84 mm Hg. There was no evidence of bite or scratch marks. The abdomen was distended and tender with evidence of massive ascites. A paracentesis showed ascitic fluid white blood cell count of 21,300/[mm.sup.3] with 89% neutrophils and a negative Gram stain. Fluid was cultured in the following media: blood, McConckey, calcium nutrient agar plate, kanamycin-vancomycin, phenylethyl alcohol, chocolate agar, and thioglycolate. None grew any organism. The patient was empirically treated with cefotaxime. Blood cultures grew Pasteurella multocida in all of the four bottles sent simultaneously with the ascitic fluid. The antibiotic was changed to amoxicillin. The patient improved significantly and was discharged on the eighth day.

Discussion

Culture-negative neutrocytic ascites (CNNA) is diagnosed when the ascitic fluid culture grows no bacteria, the ascitic fluid polymorphonuclear neutrophil (PMN) count is [greater than or equal to]250 cells/[mm.sup.3], no antibiotics have been given, and there is no other explanation for an elevated ascitic PMN. It may be difficult to recover organisms from peritoneal fluid cultures, presumably because the burden of organisms is low. Also, most episodes of CNNA are diagnosed by insensitive culture methods for which there are insufficient numbers of bacteria to reach the threshold of detectability. Inoculation into blood culture bottles can lead to detection of a single organism in the cultured aliquot of fluid. (12)

The route of infection for spontaneous bacterial peritonitis (SBP) is presumed to be hematogenous, lymphatogenous, or transmural migration. It is postulated that the hematogenous route is most likely in cirrhotic patients. The hepatic reticuloendothelial system is known to be a major site for removal of bacteria from blood, and animal studies have suggested that destruction of blood-borne bacteria by this system is impaired in experimental cirrhosis and alcoholic liver disease. The decrease in phagocytic activity seen with alcohol abuse and cirrhosis is due to inadequate intracellular killing of monocytes and neutrophils and impaired opsonisation. (1)

The most frequently recovered pathogen in SBP is Escherichia coli (37%), followed by Klebsiella pneumoniae (17%) and other streptococci including enterococci.

P multocida is an aerobic, facultatively anaerobic, Gramnegative coccobacillus that inhabits the oral cavity and the gastrointestinal tract of 70 to 90% of cats and 50 to 66% of dogs. (13)

It is most commonly a pathogen in acute skin, soft tissue, bone, and joint infections after an animal bite or a scratch or from licking of open wounds by these animals. The infections are also known to develop in patients exposed to animals but without a history of bites or scratches. (1) Respiratory tract and intra-abdominal infections have been associated with possible inhalation of the organism. (14) P multocida wound infection, septic arthritis, pneumonia, or meningitis can cause bacteremia, with or without metastatic lesions. (6) Nasopharyngeal colonization with P multocida with transient bacteremia and seeding of the peritoneum in immunocompromised cat owners could play an important role in the development of SBP. (6)

Several in vitro studies indicate that penicillin is the best treatment of virtually all forms of P multocida infections. Many cephalosporins demonstrate in vitro activity against P multocida, and activity increases with the later generation cephalosporins.

The Table summarizes the characteristics of 13 patients with P multocida SBP. Nine of these had positive blood cultures and two had a proven CNNA. Eleven patients received antibiotics. Four patients died, of which all but one received antibiotics. All of the treated patients received a cephalosporin or penicillin, except the two patients who finally died of the SBP.

Conclusion

Two of the four deaths occurred in the patients who were not treated with the appropriate antibiotics. It might have been secondary to a delay in diagnosis or a failure to suspect P multocida as a causative organism for the SBP in the respective patients. With early recognition of the disease and prompt and appropriate antimicrobial treatment, the in-hospital mortality rate of SBP has been reduced to approximately 20%. The lowest mortality rate, which was achieved with a combination treatment of cefotaxime and albumin, was 10%, (15) as opposed to 33.33% in our case series.

We propose that a high level of suspicion should be maintained, particularly for patients with a history of cirrhosis and animal contact. Cirrhotic patients with a risk of SBP should completely avoid animal contact. These patients may benefit from empirical antibiotic coverage for P multocida, which may reduce the high mortality rate associated with this kind of infection.

Table. Patient characteristics

                                                         Animal, type
Reference              Yr/sex     Clinical data          of exposure

Tseng HK et al         43 male    Hepatitis B          Sick-appearing
  (February 2001)                 Liver cirrhosis        stray dogs, no
                                  Esophageal varices     bite or scratch
                       54 male    Hepatitis C-related
                                    cirrhosis
                                  Diabetes mellitus
Beales et al           43 male    Inactive alcoholic   None, no bite or
  (April 1999)                      cirrhosis            scratch
                                  Encephalopathy
                                    grade 2
Koch CA et al          66 female  Biopsy-proven        Cat, no bite or
  (March 96)                        alcoholic            scratch
                                    cirrhosis            mentioned
                                  Squamous cell
                                    carcinoma of the
                                    neck
Fernandez-Esparrach    69 female  Liver cirrhosis,     Cat, no bite or
  et al (March 1994)                pleural effusion     scratch
Honberg PZ et al       12 male    Cirrhosis            None, scratch-
  (June 1986)                     Acute active           scar
                                    hepatitis of         found
                                    unknown cause
Vakil N et al          43 male    Alcoholic liver      Pet dog, licking
  (July 1985)                       disease              and scratching
                                  Portal hypertension
Patton F et al         48 male    Alcoholic liver      Game cocks and
  (November 1980)                   disease              pet pig, no
                                  Portal hypertension    bite or scratch
                                  Esophageal varices
Szpak CA et al (June   55 male    Micronodular         None, no bite or
  1980)                             cirrhosis            scratch
                                  Acute hemorrhagic
                                    gastritis
Jacobson JA et al      61 male    Biopsy-proven        Dog, no bite or
  (November 1977)                   cirrhosis            scratch
                                  Esophageal varices
                                  Gastric ulcer
Gerding DN et al       51 male    50% gastric          Cat, scratch
  (March 1976)                      resection
                                  Billroth 2
                                    anastomosis for
                                    peptic ulcer
                                    disease
                                  Chronic subhepatic
                                    abscess with a
                                    sinus tract
                                    suprahepatic
                                    abscess
                       62 male    Bleeding             None, no bite or
                                    hemorrhoids          scratch
                                  Asterexis
Our case (occurred in  48 male    Hepatic cirrhosis    2 dogs, no bite
  July 2002)                        with ascites         or scratch
                                  Esophageal varices
                                  Hepatitis C
                                    infection

                       Ascitic fluid       Blood    Ascitic fluid
Reference                cultures         cultures      WBCs

Tseng HK et al         Not mentioned      Positive  Not mentioned
  (February 2001)
                       Not mentioned      Positive  Not mentioned
Beales et al           Positive           Negative  5,300 with
  (April 1999)                                        95% PMNs
Koch CA et al          Positive           Not done   9,650 with
  (March 96)                                          82% PMNs
Fernandez-Esparrach    Positive (pleural  Positive  105,000
  et al (March 1994)     fluid was also               (pleural
                         positive for                 fluid with
                         Pasteurella                  98% PMNs)
                         multocida)
Honberg PZ et al       Positive           Negative  Not mentioned
  (June 1986)
Vakil N et al          Positive           Positive  4,040 with
  (July 1985)                                         90% PMNs
Patton F et al         Positive           Positive  Not mentioned
  (November 1980)
Szpak CA et al (June   Positive           Positive  760 with 76%
  1980)                                               PMNs
Jacobson JA et al      Negative           Positive  1st set: 19,700
  (November 1977)                                     with 100%
                                                      PMNs
                                                    2nd set: 2,800
                                                      with 90%
                                                      PMNs
Gerding DN et al       Positive           Negative  2,900 with
  (March 1976)                                        100%
                                                      PMNs
                       Positive           Positive  2,200 with
                                                      85% PMNs
Our case (occurred in  Negative           Positive  21,300 with
  July 2002)                                          89% PMNs

Reference              Antibiotics              Outcome

Tseng HK et al         Cephalothin and          No death
  (February 2001)        gentamicin followed
                         by ceftriaxone and
                         amikacin then
                         cefoxitin and
                         gentamicin
                       Cephalothin and
                         gentamicin followed
                         by oral cephalexin
Beales et al           2 g cefotaxime IV BID    No death
  (April 1999)
Koch CA et al          Ceftriaxone              Continued abdominal
  (March 96)                                      pain but no death;
                                                  follow-up of
                                                  abdominal pain
                                                  revealed hepatic
                                                  cancer with portal,
                                                  celiac, and
                                                  paracaval
                                                  adenopathy
Fernandez-Esparrach    Ceftriaxone              Progressive hepatic
  et al (March 1994)                              failure and death in
                                                  the 3rd week
Honberg PZ et al       Netilmicin,              No death
  (June 1986)            metronidazole
                         followed by
                         penicillin
Vakil N et al          12 g ampicillin QD       Oliguria, drowsiness,
  (July 1985)                                     development of
                                                  asterixis and death
                                                  on the 14th day
Patton F et al         1 g ampicillin IV q 6 h  Patient remained
  (November 1980)        and 100 mg               afebrile
                         gentamicin IV q 8 h
Szpak CA et al (June   2 million penicillin     Recovery
  1980)                  units
                         IV q 4 h for 14 d
Jacobson JA et al      100 mg gentamicin IV     Recovery
  (November 1977)        q 8 h and 2 g
                         ampicillin IV q 6 h
Gerding DN et al       Clindamycin and          Increased hepatic
  (March 1976)           gentamicin               failure and death on
                                                  the 20th day
                       Oxygen, albumin,         Death 7 h after
                         plasma, no               admission
                         antibiotics
Our case (occurred in  2 g cefotaxime IV BID    Recovery
  July 2002)             followed by
                         amoxicillin

WBCs, white blood cells: PMNs, polymorphonuclear neutrophils. References
2 through 11.

Accepted July 16, 2004.

References

1. Zurlo J. Pasteurella species; Levison ME, Bush LM. Peritonitis and other intra-abdominal infections, in Mandell, Douglas and Bennetts's Principle and Practice of Infectious Diseases. 5th edition, 2000, pp 2402-2405; pp 821-855.

2. Vakil N, Adiyody J, Treser G, et al. Pasteurella multocida septicemia and peritonitis in a patient with cirrhosis: case report and review of the literature. Am J Gastroenterol 1985;565:80-87.

3. Patton F, Dumas M, Cannon NJ. Pasteurella multocida septicemia and peritonitis in a cirrhotic cock trainer with a pet pig. N Engl J Med 1980;303:1126-1127.

4. Szpak CA, Woodard BH, White JO, et al. Bacterial peritonitis and bacteremia associated with Pasteurella multocida. South Med J 1980;73:801-803.

5. Gerding DN, Khan MY, Ewing JW, et al. Pasteurella multocida peritonitis in hepatic cirrhosis with ascites. Gastroenterology 1976;70:413.

6. Koch CA, Mabee CL, Robyn JA, et al. Exposure to domestic cats: risk factor for Pasteurella multocida peritonitis in liver cirrhosis? Am J Gastroenterol 1996;91:1447.

7. Beales IL. Comment. Am J Gastroenterol 1999;94:1110-1111.

8. Honberg PZ, Frederiksen W. Isolation of Pasteurella multocida in a patient with spontaneous peritonitis and liver cirrhosis. J Clin Microbiology 1986;5:340.

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10. Fernandez-Esparrach G, Mascaro J, Rota R, et al. Septicemia, peritonitis and empyema due Pasteurella multocida in a cirrhotic patient. Clinical Infect Dis 1994;18:486.

11. Jacobsen JA, Miner P, Duffy O. Pasteurella multocida bacteremia associated with peritonitis and cirrhosis. Am J Gastroenterol 1977;5:489-491.

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13. Griego RD, Rosen T, Orengo IF, et al. Dog, cat, and human bites: a review. J Am Acad Dermatol 1995;33:1019.

14. Holst E, Rollof J, Larsson L et al. Characterization and distribution of Pasteurella species recovered from infected humans. J Clin Microbiol 1992;30:2984-2987.

15. Suzuki K, Takikawa Y. Marked improvement in the resolution of, and survival rates in, spontaneous bacterial peritonitis. J Gastroenterol 2002;37:149-150.

RELATED ARTICLE: Key Points

* Spontaneous bacterial peritonitis (SBP) caused by Pasteurella multocida is rare.

* P multocida SBP has a very high mortality rate when it occurs.

* Avoidance of animal contact and empiric antibiotic coverage for P multocida is advocated.

Ila Tamaskar, MD, and Keyvan Ravakhah, MD, MBA, FACP 

From the Department of Medicine, Huron Hospital, Cleveland Clinic Health System, Cleveland, OH.

Financial support of the study was provided by Huron Hospital, Department of Medicine, Cleveland, OH.

Reprint requests to Dr. Ila Tamaskar, Huron Hospital, 13951 Terrace Road, Cleveland, OH 44112.