JOURNAL OF CLINICAL MICROBIOLOGY, Feb. 1988, p. 388-391 Vol. 26, No. 20095-1137/88/020388-04$02.00/0Copyright © 1988, American Society for Microbiology

Proctitis and Fatal Septicemia Caused by Plesiomonas shigelloidesin a Bisexual Man

FREDERICK S. NOLTE,1'2* ROBERT M. POOLE,3 GERALD W. MURPHY,3 CORNELL CLARK,2AND BERNARD J. PANNER2

Departments of Microbiology and Immunology,' Medicine,3 and Pathology and Laboratory Medicine?University ofRochester Medical Center, Rochester, New York 14642

Received 13 August 1987/Accepted 28 October 1987

A case of proctitis and fatal septicemia caused by Plesiomonas shigelloides in a 42-year-old bisexual male isreported. The medical history of the patient was significant for an aortic valve replacement 3 years before butwas otherwise unremarkable. A serum specimen obtained at autopsy was negative for antibody to humanimmunodeficiency virus by Western blot (immunoblot) analysis. P. shigelloides isolated from blood wassusceptible to all antibiotics tested, agglutinated in Shigella group D antiserum, possessed a >100-megadaltonplasmid, and was noninvasive in a HeLa cell invasion assay. The previous reports of Plesiomonas bacteremicinfections are reviewed, and possible pathogenic mechanisms are discussed.

Plesiomonas shigelloides is a motile, gram-negative, fac-ultatively anaerobic bacillus of the family Vibrionaceae (31).It was first isolated in 1947 by Ferguson and Henderson (10),who named it C27. Since then, it has been variously knownas Pseudomonas shigelloides (3), Pseudomonas michigani(26), Aeromonas shigelloides (9), Fergusonia shigelloides(29), and Vibrio shigelloides (13). P. shigelloides normallyinhabits surface waters and soil in temperate and tropicalareas of the world and is not considered part of the indige-nous microbiota of the human gastrointestinal tract (2).Worldwide, P. shigelloides has been implicated in several

large outbreaks of gastroenteritis (25, 30) and in sporadiccases of diarrheal illness (24). Plesiomonas enteric infectionsoccurring in the United States have recently been reviewed(15), and reports of extraintestinal infection with P. shigel-loides are rare. Here, we report a case of invasive Plesio-monas infection that resulted in bacteremia and death of anadult patient.Case report. A 42-year-old bisexual man came to the

emergency department of Strong Memorial Hospital, Roch-ester, N.Y., on 1 August 1986 with nausea, diarrhea, backpain, mental confusion, and diffuse arthralgias. His medicalhistory was significant for a congenital bicuspid aortic valvewith stenosis. He had undergone aortic valve replacementwith a Lillihei-Kaster tilting-disk prosthesis 3 years beforeand was maintained on the anticoagulant warfarin. He alsotook furosemide and digoxin for mild congestive heart failurebut was sufficiently compensated to ride a bicycle severalmiles per day. A routine physical examination performed 2weeks before admission revealed normal prosthetic valvesounds; the leukocyte count and hematocrit were normal,and the prothrombin time was 1.5 x the control value. Hissexual history was notable for multiple homosexual experi-ences.Three days before admission, he noted the onset of

crampy lower-abdominal pain associated with watery diar-rhea and intermittent fever. On the day of admission, hecomplained of severe back pain and diffuse arthralgias.

Physical examination revealed a delirious man with atemperature of 37.5°C, blood pressure of 130/70 mm Hg, anda pulse rate of 112 beats per min. The skin was warm and

* Corresponding author.

dry, and conjunctivae were injected. The lungs were clear toauscultation. Examination of the heart revealed a normal S1and a crisp prosthetic S2 with a 2/6 systolic murmur at theaortic area, as well as a short diastolic murmur heard best atthe base. There was no Quincke's pulse or Corrigan's pulse.The remainder of the examination was normal.

Initial laboratory tests showed a leukocyte count of 1,200with 69% polymorphonuclear cells and 13% band forms, aplatelet count of 145,000/mm3, and a hematocrit of 45%. Theprothrombin time was 42 s. A chest X ray revealed clear lungfields with massive cardiomegaly. The electrocardiogramshowed left ventricular hypertrophy.Vancomycin (500 mg every 6 h), gentamicin (100 mg every

8 h), and nafcillin (2 g every 4 h) were administered afterblood and urine cultures were obtained. Approximately 3 hafter admission, the blood pressure of the patient decreasedto 80/40 mm Hg, the temperature rose to 39.5°C, and thepulse and respiration rates increased to 124 and 56/min,respectively. Laboratory tests at this time showed a plateletcount of 60,000/mm3, a hematocrit of 38%, prolonged pro-thrombin and partial thromboplastin times, and a fibrinogenlevel of 289 mg/dl. The patient was transferred to theintensive care unit where, despite maximal supportive mea-sures, he suffered irreversible hypotension and died approx-imately 9 h after admission.Postmortem examination revealed focal hemorrhagic le-

sions in the rectal mucosa, transmural hemorrhage, andacute inflammation (Fig. 1). A Brown-Brenn stain revealedgram-negative rods within the inflammatory cells (Fig. 2).There was no bacterial endocarditis or prosthetic valvulardisruption. A serum specimen obtained at autopsy wasnegative for human immunodeficiency virus antibody, asdetermined by the Western blot (immunoblot) technique atthe New York State Health Department Laboratory, Al-bany. (An enzyme-linked immunosorbent assay could not bedone because of sample hemolysis.)

Bacteriology. Three of three cultures (BACTEC system;Johnston Laboratories, Inc., Towson, Md.) of blood drawnfrom the patient at admission grew P. shigelloides that wassusceptible to ampicillin, cefazolin, chloramphenicol, genta-micin, and trimethoprim-sulfamethoxazole, as determinedby disk diffusion testing (21). Quantitative cultures of heartblood at autopsy grew >1,000 CFU ofP. shigelloides per ml.

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FIG. 1. Tissue section of rectum obtained at autopsy. The section shows diffuse inflammatory response with polymorphonuclearleukocytes, extending through the mucosa, submucosa, and muscularis. Hematoxylin and eosin stain; bar, 100 ,um.

The organism was identified by the API 20E system(Analytab Products, Plainview, N.Y.) (profile no. 7144204),and the identification was confirmed by conventional tubebiochemical tests (31). The organism reacted with Shigellagroup D antiserum (Fisher Scientific Co., Orangeburg, N.Y.)in a slide agglutination test. P. shigelloides was screened forplasmids by the method of Kado and Liu (19). The ability ofthis strain to penetrate and replicate within epithelial cellswas assessed with a HeLa cell invasion assay (12). A recentclinical isolate of Shigella flexneri and Escherichia coliATCC 25922 served as positive and negative controls, re-spectively, in the HeLa cell assay.

Discussion. P. shigelloides-associated gastroenteritis maybe present as a mild self-limited illness or as a mucoid,bloody diarrhea with polymorphonuclear leukocytes foundon fecal smears (15, 24). In a recent prospective, nationwidecase-control study of Plesiomonas enteric infections, Holm-berg et al. (15) reported that the symptoms observed in 31study patients suggested a disease caused by enteroinvasivebacteria. In one of these patients, sigmoidoscopy showedmultiple punctate lesions in the distal bowel. In our patient,the gross and microscopic examinations of the rectum re-vealed focal hemorrhagic lesions of mucosa and transmuralacute inflammatory response. Although no ante- or postmor-tem cultures of the bowel contents or wall were obtained, thepresence of many gram-negative bacilli within the inflamma-tory cells suggests that P. shigelloides was responsible forthe acute proctitis and that the rectum provided the portal ofentry to the bloodstream.The acquisition ofP. shigelloides by persons in the United

States is significantly associated with consumption of rawshellfish or recent foreign travel (15). The history of ourpatient did not include either activity. However, consideringthat the organism may be ubiquitous in aquatic environmentsduring the summer, other means of acquisition must exist.

There are 10 previous reports of Plesiomonas bacteremicinfection in the literature. Applebaum et al. (1), Dahm andWeinberg (6), Dudley et al. (7), and Pathak et al. (22) eachreported one case of neonatal sepsis and meningitis. Ellnerand McCarthy (8) and McNeeley et al. (20) each reportedone case in a patient with sickle-cell disease. Gordon et al.(11) reported a case of Plesiomonas bacteremia and septicarthritis in an elderly patient with rheumatoid arthritis,Felty's syndrome, and alcoholic cirrhosis. Humphreys et al.

w

FIG. 2. Tissue section of rectum obtained at autopsy. Manyacute inflammatory cells, predominantly polymorphonuclear leuko-cytes and gram-negative bacteria, were found in the submucosa.Arrow points to an intracellular gram-negative bacillis. Brown-Brenn stain; bar, 10 p.m.

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390 NOTES

(16) reported a case of P. shigelloides septicemia and pleuraleffusion in a patient with alcoholic liver disease. Fulminantsepticemia, disseminated intravascular coagulation, and Wa-terhouse-Friderichsen syndrome caused by this organism ina splenectomized patient free of Hodgkin's disease for 5years were reported by Curti et al. (5). All of the above-mentioned infections occurred in patients whose defenseswere compromised either by extreme youth or by significantunderlying disease, and eight ofthe nine cases were fatal. Inall but one of the cases in adults, the portal of Plesiomonasentry to the bloodstream was presumed to be the gastroin-testinal tract. Recently, Ingram et al. (18) reported a nonfatalcase of gastroenteritis, sepsis, and osteomyelitis caused byP. shigelloides in an apparently immunocompetent patient.The medical history of our patient was remarkable only for

an aortic valve replacement 3 years ago. But despite hisapparent good health, he developed proctitis and fatal sep-ticemia. His homosexual encounters placed him at increasedrisk for human immunodeficiency virus infection, which canresult in profound compromise of the immune system.However, in a serum specimen obtained at autopsy, nohuman immunodeficiency virus antibody was detected byWestern blot analysis, and a routine physical examinationperformed 2 weeks before admission to the hospital wasunremarkable. Fatal Plesiomonas septicemia would be anunusual initial presentation of acquired immunodeficiencysyndrome or its related complex.

Several attempts to evaluate the enteropathogenicity of P.shigelloides have been made. Sanyal et al. (28) and Huq andIslam (17) demonstrated that the majority of human clinicalisolates they tested could cause fluid accumulation in ligatedrabbit ileal loops. However, Pitarangsi et al. (23) found thatnone of 27 isolates was cytotoxic to Y-1 adrenal cells, waspositive in the suckling mouse assay, distended rabbit ilealloops, or was positive in the Sereny test. Likewise, Holm-berg et al. (15) showed that none of 31 isolates obtained frompatients in the United States produced Shiga-like toxin or E.coli heat-labile toxin or was positive in the Sereny test forinvasiveness. Herrington et al. (14) conducted various invitro, animal, and volunteer studies on five P. shigelloidesisolates from patients with diarrhea. The only result sugges-tive of a role for P. shigelloides in diarrheal illness was theability ofone strain to invade the distal ileum of a gnotobioticpiglet.Although no direct evidence of enteroinvasiveness exists

for P. shigelloides, many strains share at least two propertiesassociated with virulence in Shigella species. The invasivephenotype of shigellae involves multiple factors, includingthe O antigen of the lipopolysaccharide and the presence ofa large plasmid (27). Many Plesiomonas strains demonstrateserological cross-reactivity with group D shigellae and pos-sess plasmids with molecular masses of >150 megadaltons(15). The isolate from our patient agglutinated with group Dantiserum and possessed a plasmid with a molecular mass of>100 megadaltons. We did not examine this large plasmidfor the presence of gene sequences common to the inva-siveness plasmids in Shigella spp. Although the diseaseproduced in our patient was consistent with that caused byan enteroinvasive pathogen, attempts to demonstrate inva-siveness in vitro with the HeLa cell invasion assay wereunsuccessful. Although the strain described here and fivestrains tested in a HeLa cell assay by Herrington et al. (14)were noninvasive, Binnis et al. (4) reported that 5 of 16 (31%)P. shigelloides strains isolated from children with acutediarrhea exhibited invasiveness for HeLa cells comparableto that of Shigella sonnei. However, no correlation between

invasiveness and the production of Shigella O antigens wasdemonstrated. It is possible that in our patient mechanicaldamage to the mucosa resulting from rectal intercourseprovided P. shigelloides, which lacks the ability to penetratean intact epithelium, direct access to the submucosa.

Ingram et al. (18) recently reviewed the experiences intreating extraintestinal P. shigelloides infections. Of 10patients, 9, including our own, died despite the administra-tion of appropriate antibiotics. The one successful outcomeoccurred with an immunocompetent patient without severeunderlying disease. Although our patient was in previousgood health, the poor response to antibiotic therapy may beattributable to the advanced state of his infection when hecame to the hospital.

This case report demonstrates that P. shigelloides cancause a life-threatening infection in the appropriate clinicalsetting and that much remains to be learned about itspathogenicity. The major unresolved issue in this case iswhether this strain possesses some as yet undefined viru-lence properties or whether unidentified host factors predis-posed the patient to fatal Plesiomonas septicemia.

We thank Luisa Beltran for technical assistance and Frederick A.Klipstein for review of the manuscript.

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Browne, and H. J. Koornhof. 1978. Neonatal septicemia andmeningitis due to Aeromonas shigelloides. J. Pediatr. 92:676-677.

2. Arai, T., N. Ikejima, T. Itoh, S. Sakai, T. Shimada, and R.Sakazaki. 1980. A survey of Plesiomonas shigelloides fromaquatic environments, domestic animals, pets and humans. J.Hyg. 84:203-211.

3. Bader, R. E. 1954. Uber die Herstellung eines agglutinierendenSerums gegen due Rundform von Shigella sonnei mit einemStamm der Gattung Pseudomonas. Z. Hyg. Infektionskr. 140:450-456.

4. Binnis, M. M., S. Vaughn, S. C. Sanyal, and K. M. Timmis.1984. Invasive ability of Plesiomonas shigelloides. Zentralbl.Bakteriol. Mikrobiol. Hyg. Ser. A 257:343-347.

5. Curti, A. J., J. H. Lin, and K. Szabo. 1985. Overwhelmingpost-splenectomy infection with Plesiomonas shigelloides in apatient cured of Hodgkin's disease. Am. J. Clin. Pathol. 83:522-524.

6. Dahm, L. J., and A. G. Weinberg. 1980. Plesiomonas (Aero-monas) shigelloides septicemia and meningitis. South. Med. J.73:393-394.

7. Dudley, A. G., W. Mays, and L. Sale. 1982. Plesiomonas(Aeromonas) shigelloides meningitis in a neonate-a case re-port. J. Med. Assoc. Ga. 71:775-776.

8. Eliner, P. D., and L. R. McCarthy. 1973. Aeromonas shigel-loides: a case report. Am. J. Clin. Pathol. 59:216-218.

9. Ewing, W., R. Hugh, and J. Johnson. 1961. Studies on theAeromonas group. U.S. Department of Health, Education, andWelfare, Communicable Disease Center, Atlanta.

10. Ferguson, W., and N. Henderson. 1947. Description of strainC27: a motile organism with the major antigen of Shigella sonneiphase I. J. Bacteriol. 54:179-181.

11. Gordon, D. L., C. R. Philpot, and C. McGuire. 1983. Plesio-monas shigelloides septic arthritis complicating rheumatoidarthritis. Aust. N.Z. J. Med. 13:275-276.

12. Hale, T. L., and S. B. Formal. 1981. Protein synthesis in HéLaor Henle 407 cells infected with Shigella dysenteriae 1, Shigellaflexneri 2a, or Salmonella typhimurium W118. Infect. Immun.32:137-144.

13. Hendrie, M. S., J. M. Shewan, and M. Véron. 1971. Aeromonasshigelloides (Bader) Ewing et al.: a proposal that it be trans-ferred to the genus Vibrio. Int. J. Syst. Bacteriol. 21:25-27.

14. Herrington, D. A., S. Tzipori, R. M. Robins-Browne, B. D. Tall,

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15. Holmberg, S. D., K. Wachsmuth, F. W. Hickman-Brenner, P. A.Blake, and J. J. Farmer. 1986. Plesiomonas enteric infections inthe United States. Ann. Intern. Med. 105:690-694.

16. Humphreys, H., B. Keogh, and C. T. Kiane. 1986. Septicemiaand pleural effusion due to Plesiomonas shigelloides. Postgrad.Med. J. 62:663-664.

17. Huq, M. I., and M. R. Islam. 1983. Microbiological and clinicalstudies in diarrhea due to Plesiomonas shigelloides. Indian J.Med. Res. 77:793-797.

18. Ingram, C. W., A. J. Morrison, Jr., and R. E. Levitz. 1987.Gastroenteritis, sepsis, and osteomyelitis caused by Plesio-monas shigelloides in an immunocompetent host: case reportand review of the literature. J. Clin. Microbiol. 25:1791-1793.

19. Kado, C. I., and S.-T. Liu. 1981. Rapid procedure for detectionof large and small plasmids. J. Bacteriol. 145:1365-1373.

20. McNeeley, D., P. Ivy, J. C. Craft, and I. Cohen. 1984. Plesio-monas: biology of the organism and diseases in children.Pediatr. Infect. Dis. 3:176-181.

21. National Committee for Clinical Laboratory Standards. 1984.Performance standards for antimicrobial disk susceptibilitytests. Approved standard M2-A3. National Committee for Clin-ical Laboratory Standards, Villanova, Pa.

22. Pathak, A., J. R. Custer, and J. Levy. 1983. Neonatal septicemiaand meningitis due to Plesiomonas shigelloides. Pediatrics 71:389-391.

23. Pitarangsi, C., P. Echeverria, R. Whitmire, C. Tirapat, S.Formal, G. J. Dammin, and M. Tingtalapong. 1982. Enteropath-ogenicity of Aeromonas hydrophila and Plesiomonas shigel-

loides: prevalence among individuals with and without diarrheain Thailand. Infect. Immun. 35:666-673.

24. Reinhardt, J. F., and L. George. 1985. Plesiomonas shigel-loides-associated diarrhea. J. Am. Med. Assoc. 253:3294-3295.

25. Rutala, W. A., F. A. Sarubi, Jr., C. S. Finch, J. N. McCormack,and G. E. Steinkraus. 1982. Oyster-associated outbreak ofdiarrheal disease possibly caused by Plesiomonas shigelloides.Lancet i:739.

26. Sakazaki, R., R. Namioka, R. Nakaya, and H. Fukumi. 1959.Studies on the so-called paracolon C27 (Ferguson). Jpn. J. Med.Sci. Biol. 12:355-363.

27. Sansonetti, P. J., T. L. Hale, G. J. Dammin, C. Kapfer, H. H.Collins, Jr., and S. B. Formal. 1983. Alterations in the pathoge-nicity of Escherichia coli K-12 after transfer of plasmid andchromosomal genes from Shigella flexneri. Infect. Immun. 39:1392-1402.

28. Sanyal, S. C., B. Saraswathi, and P. Sharma. 1980. Enteropath-ogenicity of Plesiomonas shigelloides. J. Med. Microbiol. 13:401-409.

29. Sebald, M., and M. Véron. 1963. Teneur en bases de l'ADN etclassification des vibrions. Ann. Inst. Pasteur (Paris) 105:897-910.

30. Tsukamoto, T., Y. Kinoshita, T. Shimada, and R. Sakazaki.1978. Two epidemics of diarrhea disease possibly caused byPlesiomonas shigelloides. J. Hyg. 80:275-280.

31. von Graevenitz, A. 1985. Aeromonas and Plesiomonas, p.278-281. In E. H. Lennette, A. Balows, W. J. Hausler, Jr., andH. J. Shadomy (ed.), Manual of clinical microbiology, 4th ed.American Society for Microbiology, Washington, D.C.

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