Prosthetic valve endocarditis caused by pasteurella dagmatis.

ABSTRACT: This case of prosthetic valve endocarditis due to Pasteurella dagmatis is the first to be reported in the English language medical literature. The two reported cases of native valve endocarditis due to P dagmatis are reviewed, and the treatment of Pasteurella-induced endocarditis is discussed.

PASTEURELLA is a genus of gram-negative bipolar staining coccobacilli of worldwide distribution. Pasteurella species are primarily animal pathogens frequently inhabiting the upper respiratory and gastrointestinal tracts of mammals and birds, and rarely of healthy humans. (1,2) Over the past several years, reports of human infections by Pasteurella sp have been increasing and range from localized infections and abscesses to septicemia, meningitis, and endocarditis. Although chronic diseases such as cirrhosis, emphysema, and immunocompromised states (including those due to steroid therapy) predispose to serious Pasteurella infections, otherwise healthy individuals can be infected as well. (2) Infections with Pasteurella sp are most often associated with animal exposure, though absence of an exposure history is not uncommon. Two cases of native valve endocarditis caused by P dagmatis have been published. We present the first reported case of prosthetic valve endocarditis due to P dagmatis, with associated lumbar osteomyelitis and glomerulonephritis.

CASE REPORT

A 78-year-old man who had had a porcine aortic valve replacement was admitted with a 3-month history of fever and chills, generalized malaise, weight loss, cough, and back pain. The back pain had recently become so severe that he was unable to walk, but he had no associated bowel or bladder dysfunction. The patient had no history of known animal contact, steroid use, or lung or liver disease. On physical examination, the temperature was 100[degrees]F, blood pressure 130/80 mm Hg, pulse rate 82/min, and respiratory rate 20/min. The oropharynx and lungs were clear, the neck was supple, and abdominal examination was unremarkable. A grade 2/6 systolic murmur was heard loudest at the base, but there were no stigmas of endocarditis (ie, petechial rashes, splinter hemorrhages, Osler or Janeway lesions). There was no vertebral tenderness, and findings on neurologic examination were normal. Chest x-ray film showed no abnormalities. Electrocardiogram showed first-degree AV block with left ventricular hypertrophy and oc casional premature ventricular contractions.

Laboratory studies showed a normal white blood cell count (7,500/[mm.sup.3], normocytic anemia, mildly abnormal liver function values (aspartate aminotransferase 61 U/L, alanine aminotransferase 48 U/L, [gamma]-glutamyltransferase 129 U/L), low albumin level (2.8 g/dL), elevated creatinine level (2.7 mg/dL), and mildly elevated erythrocyte sedimentation rate (39 mm/hr). Urinalysis was negative for protein but showed 20 to 25 (3+) red blood cells, and the culture was negative. Magnetic resonance imaging of the spine was consistent with diskitis and osteomyelitis at L3-L4, without evidence of compression or abscess. A transthoracic echocardiogram revealed an aortic cusp vegetation without aortic insufficiency or perivalvular extension. Initial blood cultures were reported negative, and treatment was empirically started with vancomycin, ceftriaxone, and gentamicin for culture-negative endocarditis. On clay 2, a bone biopsy of the vertebral lesion was done. On clay 6, 1 of 3 blood cultures yielded a gram-negative bacillus that was identified on day 10 as P dagmatis. The biopsy of the L3-L4 lesion revealed neither growth in culture, evidence of acid-fast bacillus infection, nor evidence of inflammation on histopathology. In the absence of valvular dysfunction, surgery was not done. The patient completed 6 weeks of ceftriaxone therapy, with good clinical response. Repeated cultures of blood, obtained 2 weeks after the course of antibiotics were negative.

DISCUSSION

Approximately 20 species of Pasteurella have been identified. (3,1) The principal reservoir is the upper respiratory tract of animals, with high carriage rates in cats and dogs: P canis has been isolated from dogs, P stomatis and P dagmatis from cats and dogs, P multocida from many birds and animals, particularly cats and dogs. The other species rarely cause disease in humans: P pneumotropica has been isolated in mice and rats, P aerogenes from swine, P caballi from horses, P volantium from birds, and P haemolytica from cattle. The animal species are associated with upper and lower respiratory tract disease, as well as septicemia, in their respective hosts. Pasteurella aerogenes is also associated with abortion in swine, and P haemolytica is also associated with mastitis in cattle. Two species are not associated with animal hosts: P bettyae has been isolated from human urogenital infections, and P ureae has been isolated from patients with pneumonia.

Most human Pasteurella infections are caused by P multocida and less frequently by P canis, P stomatis, and P dagmatis. Proposed mechanisms of spread include animal bites, scratches, and possibly airborne or vector transmission with known animal exposure, without a history of bites or scratches. (2,5) However, Hubbert and Rosen(1) showed that up to 31% of patients had no history of animal contact or exposure. Pasteurella infections in humans are usually manifested as either focal skin and soft tissue infection after direct animal contact, chronic respiratory tract infections, bacteremia with or without metastatic lesions, or meningitis. (2,6) Cellulitis is the most common Pasteurella infection, developing after an animal bite or scratch. It is characterized by inflammation at the site within 24 hours of the bite, followed by a rapidly spreading erythema. Regional lymphadenopathy, fever, or discharge may occur. Infections may develop local abscesses and tenosynovitis. Septic arthritis, osteomyelitis, bacteremi a, endocarditis, and central nervous system infections are rare. (3)

Virulent strains of P multocida possess fimbriae to adhere to the mucosal epithelium of the upper respiratory tract of animals. Some strains of P multocida and P haemolytica produce a cytotoxin and leukotoxin, respectively, to impair the host immune response. Several Pasteurella species have a polysaccharide capsule that provides antiphagocytic properties and impairs intracellular killing in neutrophils. (3,4) Virulence seems to be related to capsular characteristics, larger capsules being associated with increased virulence. (3)

Chronic lung disease and liver disease have been associated with Pasteurella infections unrelated to animal bites. (2,7) As in our patient, this association has not been found with Pasteurella infective endocarditis. As reported by a recent review, only 1 of 16 patients with endocarditis had cirrhosis, and none had chronic obstructive lung disease. (8)

The first case of P dagmatis endocarditis, initially designated Pasteurella new species, occurred in a healthy man after a cat bite. (9) He had renal insufficiency, likely due to glomerulonephritis but eventually recovered after penicillin therapy. The second case, complicated by vertebral osteomyelitis, involved the native mitral valve of a 55-year-old cirrhotic women, with a known history of animal contact. (10) The patient responded to 6 weeks of antibiotic therapy with ceftriaxone. Our patient presented with definite prosthetic valve endocarditis according to the Duke classification, the major criterion being positive' echocardiographic findings. Minor criteria were preexisting heart valve disease, fever, immunologic phenomenon, and blood culture positive for an organism not typical in infective endocarditis. (11)

The pathogen, a slow growing pleomorphic gram-negative rod that could not be cultured by either the VITEK or API systems, was inoculated into broths and slants. The isolate grew equally well on sheep blood agar, with and without factors V and X, as on chocolate blood agar, thus eliminating Haemophilus as the possible pathogen. (12) The growth characteristics--oxidase-negative, MacConkey-negative, glucose-positive, motility-negative, urea-positive, and indole-positive--identified the pathogen as P dagmatis. Approximately 4% of P dagmatis are catalse-negative, as was the isolated organism. The indole-positive, ornithine decarboxylase-negative, urea-positive pattern distinguish P dagmatis from other Pasteurella species and the related Actinobacillus genus. (13)

The number of case reports of Pasteurella-induced endocarditis involving native valves has increased. Also, a case of prosthetic aortic valve endocarditis caused by P multocida has been reported in a 72-year-old woman with metastatic abscess formation in the left psoas muscle. (8) There was a known cat exposure but no bite or scratch, and the patient responded well to medical therapy alone. It appears that endocarditis due to Pasteurella commonly leads to metastatic complications.

Although resistance has been reported among animal isolates, [beta]-lactam antibiotics are the preferred treatment for Pasteurella infections in humans. Parenteral agents with good activity against Pasteurella sp include penicillin, ampicillin, mezlocillin, piperacillin, cefuroxime, ceftriaxone, and cefotaxime. (7,14,15) Prolonged antibiotic therapy is required for patients with either osteomyelitis or endocarditis.

CONCLUSION

Ours is the third case of infective endocarditis caused by P dagmatis reported in the literature. Moreover, it is the first case of P dagmatis endocarditis involving a prosthetic valve. It appears that Pasteurella sp are becoming a more commonly recognized cause of infective endocarditis. Patients may have a history of animal contact or predisposing factors such as pulmonary or liver disease, but many patients do not have the defined risk factors. It is essential to consider the possibility of Pasteurella sp when confronted with a patient with endocarditis. These organisms, thus far, remain susceptible to antimicrobials commonly used for treatment of endocarditis, and properly instituted medical therapy is completely effective.

References

(1.) Hubbert WT, Rosen MN II: Pasteurella multocida infections in man unrelated to animal bite. Am J Public Health 1970; 60:1109-1117

(2.) Furie RA, Cohen RP, Hartman BJ, et al: Pasteurella multocida infection: report in urban setting and review of spectrum of human disease. N Y State J Med 1980; 80:1597-1602

(3.) Zurlo JJ: Pasteurella species. Principles and Practice of Infections Diseases. Mandell CL, Bennett JE, Dolin R (eds). New York, Churchill Livingstone, 5th Ed, 2000, pp 2402-2405

(4.) Holmes B, Pickett MJ, Hollis DG: Pasteurella. Manual of Clinical Microbiology. Murray PR, Baron EJ, Pfaller MA, et al (eds). Washington, DC, American Society of Microbiology, 6th Ed, 1999, pp 632-633

(5.) Singh CP, Sprurrel JR: Pasleurella multocida endocarditis. BMJ 1983; 286:1862-1863

(6.) Jones FL Jr, Smull CE: Infections in man due to Pasteurella multocida. importance of human carrier. Pa Med J 1973; 76:41-45

(7.) Dibb WL, Digranes A: Characteristics of 20 human Pasteurella isolates from animal bite wounds. Acta Pathol Microbial Scand (Sect B) 1981; 89:137-141

(8.) Nettles RE, Sexton DJ: Pasteurella multocida prosthesic valve endocarditis: case report and review. Clin Infect Dis 1997; 25:920-921

(9.) Gump DW, Holden RA: Endocarditis caused by a new species of Pasteurella. Ann Intern Med 1972; 76:275-278

(10.) Sorbello AF, O'Donnell J, Kaiser-Smith J, et al: Infective endocarditis due to Pasteurella dagmatis: case report and review. Clin Infect Dis 1994; 18:336-338

(11.) Durack DT, Lukes AS, Bright DK: New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med 1994; 96:200-209

(12.) Elsaghier AAF, Kibbler CC, Hamilton-Miller JMT: Pasteurella multocida as an infectious cause of endocarditis. Clin Infect Dis 1998; 27:410-411

(13.) Pickett MJ, Hollis DG, Bottone EJ: Miscellaneous gram negative bacteria. Manual of Clinical Microbiology. Balows A, Hausler WJ, Hellmann KL, et al (eds). Washington, DC, American Society of Microbiology, 5th Ed, 1991, pp 410-428

(14.) Goldstein EJC, Citron DM: Comparative activities of cefuroxime, amoxicillin-clavulanic acid, ciproflaxin, enoxacin and ofloxacin against aerobic and anaerobic bacteria isolated from bite wounds. Antimicrob Agents Chemother 1988; 32:1143-1148

(15.) Weber DJ, Wolfson JS, Swartz MN, et al: Pasteurella multocida infections: report of 34 cases and review of literature. Medicine 1984; 63:133-154

KEY POINTS

* Reports of Pasteurella infections in humans are increasing and range from local soft tissue infections to septicemia, meningitis, and endocarditis.

* Pasteurella infections are often associated with exposure to animals.

* Pasteurella dagmatis, a pathogen found in cats and dogs, has been associated with two cases of native valve endocarditis, and now with the first case of prosthetic valve endocarditis.

* Pasteurella dagmatis, like most Pasteurella species isolated from infections in humans, remains susceptible to [beta]lactam antibiotics.