What Is Causing This Persistent Diarrhea?

A 52-year-old woman presented with a 12-day history of diarrhea and mild stool incontinence that began 2 to 3 hours after a routine screening colonoscopy. Six or 7 bowel movements of liquid, orange-yellow feces occurred each day for 12 days. The patient reported that associated nausea, flatulence, and severe abdominal cramping were relieved by the bowel movements. She also reported that a small amount of mucus was occasionally observed in the stool and that bright red blood streaks appeared on used toilet paper, although the stool itself was not bloody. She was able to tolerate a full diet, although food exacerbated the urgency. She was afebrile during this illness.

The patient had eaten shrimp 3 days before the onset of her symptoms. She denied any significant travel, contact with an aquatic environment, or sick contacts. She otherwise had been in good health.

The physical examination was significant only for hyperactive bowel sounds. Initial laboratory tests revealed the following values: sodium, 142 mmol/L; potassium, 4.2 mmol/L; chloride, 103 mmol/L; bicarbonate, 30 mmol/L; blood urea nitrogen, 14 mg/dL; and creatinine, 0.8 mg/dL. Total bilirubin level was 0.5 mg/dL (normal, 0.1 to 1.2 mg/ dL); aspartate aminotransferase, 36 U/L; alanine aminotransferase, 68 U/L(normal, 0 to 35 U/L); and alkaline phosphatase, 54 U/L (normal, 30 to 120 U/L). The white blood cell count was 7300/?L, with 68% neutrophils, 18% lymphocytes, 12% monocytes, and 1% eosinophils. The thyroid-stimulating hormone level was within normal limits.

A stool specimen revealed numerous bacteria, but no white blood cells were seen. Stool specimens were sent for culture, and the patient was discharged from the clinic. The importance of adequate hydration was stressed, and the patient was instructed to go to the emergency department if signs or symptoms increased in severity.

DIFFERENTIAL DIAGNOSIS

Dr Steele:

This patient has acute gastroenteritis. Unfortunately, there are no clear clinical clues as to the cause. During the colonoscopy, biopsy specimens were obtained, which would explain blood in the stools, but the procedure itself would not cause persistent diarrhea.

The absence of fever suggests infection with a viral pathogen such as rotavirus, norovirus, enteric adenovirus, coronavirus, astrovirus, or calicivirus. On the other hand, the presence of blood almost rules out rotavirus and is most frequently observed in Shigella infection, which characteristically causes a very high fever.

The patient experienced nausea but not vomiting. Vomiting is common with Salmonella infection and most viral causes of gastroenteritis, but it is unusual in infections caused by other bacterial pathogens, such as Shigella, Yersinia, and Campylobacter. The dysenteric form of amebiasis is another possible cause. The patient's clinical symptoms are quite compatible with this diagnosis and include pain, tenesmus, and flatulence. Fever and abdominal distention are often experienced, but this presentation is variable. Fresh stool should be examined for trophozoites.

Apathogen of increasing concern is Escherichia coli 0157:H7. This strain causes hemorrhagic colitis, and it is capable of producing hemolytic uremic syndrome (HUS). Infection with E coli 0157:H7 is much more common in children younger than 5 years but can develop in adults. Many laboratories now routinely screen for the causative pathogen. If E coli infection is suspected, it is important to withhold antibiotics until a definitive diagnosis is made and infection with E coli 0157:H7 is ruled out. Use of antibiotics in the presence of E coli 0157:H7 increases the risk of HUS development.

With any episode of bloody diarrhea, we must consider Clostridium difficile infection, but there is no mention of the patient receiving antibiotics, and the mild nature of the diarrhea does not warrant oral metronidazole or vancomycin therapy. Therefore, I would wait before sending a stool specimen to be tested for C difficile toxin.

Other organisms that once were not thought to be significant stool pathogens but may be the cause of this patient's symptoms include Cryptosporidium, Dientamoeba fragilis, Balantidium coli, Aeromonas, and Plesiomonas shigelloides. For completeness, infection with the parasite Giardia intestinalis, another common cause of diarrhea in children but unusual in adults, should be considered in the differential diagnosis.

With the exception of providing symptomatic therapy, I would wait to receive results from the routine examination of stool specimens before instituting treatment, and I would not look for unusual pathogens unless the diarrhea worsens or persists for longer than 3 weeks.

HOSPITAL COURSE

 Stool cultures contained a heavy growth of Aeromonas hydrophila. There was no evidence of C difficile, Salmonella, Shigella, Campylobacter jejuni,Vibrio cholerae, Yersinia, or E coli 0157:H7. A hydrophila is susceptible to ciprofloxacin; therefore, the patient was given a 5-day course, 500 mg bid. Symptoms improved; the frequency of diarrhea decreased and no associated nausea, flatulence, or abdominal cramping was experienced. A repeated stool culture was negative for A hydrophila as well as other potential stool pathogens. The incidence of passing loose stools continued to lessen until a solid bowel movement occurred 32 days after the onset of symptoms.

FINAL DIAGNOSIS

 Acute gastroenteritis caused by Aeromonas hydrophila

DISCUSSION

Although Aeromonas species have been implicated as a cause of diarrhea in both healthy children and adults, the clinical significance of these organisms as stool pathogens remains controversial. A hydrophila was isolated from the stool of our patient, who presented with acute gastroenteritis that slowly responded to currently recommended antibiotic therapy

A hydrophila is a gram-negative, flagellated bacterium that is widely distributed in freshwater, estuarine, and marine environments worldwide. ^1,2 Some strains are capable of causing illness in fish and amphibians as well as in humans who may acquire infections through open wounds or by ingestion of a sufficient number of the organisms in food or water. Avariety of manifestations ranging from wound infections to bacteremia have been associated with Aeromonas species, but these organisms are most commonly isolated from the human GI tract.³

The virulence of Aeromonas species is, most likely, multifactorial. Possible virulence factors include toxins (cytotoxic and cytotonic); proteases; hemolysins; lipases; adhesions; agglutinins; pili; enterotoxins; various enzymes; and outer membrane arrays, such as an S-layer and capsule.^4-7 In addition to the presence of virulence factors, the host immune response to the infection influences the severity of the infection.⁸

The role of this organism in causing GI disease in healthy persons has been debated; Aeromonas strains have been recovered in up to 3.2% of stool specimens from persons without obvious GI disease. Studies exist, however, that support the contention that Aeromonas can be an intestinal pathogen in healthy persons. In a 1- year prospective study of children with diarrhea, A hydrophila was isolated from 10.2% of symptomatic persons and from only 0.6% of controls. ⁹ In a retrospective review, Aeromonas was isolated from 2.8% of adults with diarrhea.¹⁰ In fact, it was more commonly isolated than Salmonella, Shigella, and Campylobacter.¹⁰ Other supportive evidence comes from a large study that identified Aeromonas as a cause of traveler's diarrhea in 2% of patients,¹¹ and a study that found that 4.7% of 3501 diarrheal stool samples from patients hospitalized during 2000-2001 were positive for Aeromonas.¹²

Aeromonas infection is associated with a variety of symptoms. The most widely reported is a mild, selflimited, watery, non-bloody, nonmucoid diarrhea, which is commonly seen in children during the late spring, summer, and early fall. Adults, in particular, may present with a protracted, non-bloody diarrheal illness that is without signs of colitis and lasts several weeks.¹³ Acute and chronic bloody diarrhea with mucus and abdominal pain occur in both children and adults infected with Aeromonas.¹³

Most cases of suspected Aeromonas- associated diarrhea are apparently self-limited. Although therapy may be helpful, no controlled clinical trials have been performed that clearly show benefits of antibiotic therapy. Nevertheless, it has been suggested that initial empirical therapy for suspected A hydrophila infection should include a fluoroquinolone or trimethoprim/sulfamethoxazole, pending species identification and susceptibility testing. Therapy with ampicillin or a first-generation cephalosporin is not appropriate.

The infection in the patient described in this report fits the pattern of A hydrophila gastroenteritis. The most likely cause was the ingestion of seafood. (Iatrogenic inoculation by the colonoscope is unlikely given the time between the procedure and the onset of symptoms, but it remains a possibility.) The organism has been associated with shrimp.One study, conducted in India, that examined the bacterial flora associated with freshwater shrimp found that Aeromonas constituted 38% of surface and GI flora.¹⁴

Treatment of this patient with a fluoroquinolone resulted in a fairly rapid clearing of the organism and cessation of flatulence, cramping, and nausea, but there was slow resolution of diarrhea. This observation also has been reported by Palfreeman and colleagues.¹⁵

This report supports the view that Aeromonas may act as a GI pathogen in healthy persons and should be included in the differential diagnosis in relation to examination of stool cultures from patients presenting with acute diarrhea.

References:

• Holmes P, Niccolls LM, Sartory DP. The ecology of mesophilic Aeromonas in the aquatic environment. In: Austin B, ed. The Genus: Aeromonas. New York: John Wiley & Sons Ltd; 1996: 127.

• Martin-Carnahan A, Joseph SW. Aeromonas. In: Boone DR, Castenholz RW, Garrity GM, et al. Bergey’s Manual of Systemic Bacteriology. 2nd ed. New York: Springer; 2001.

• Freij BJ. Aeromonas: biology of the organism and diseases in children. Pediatr Infect Dis. 1984;3: 164-175.

• Cahill MM. Virulence factors in motile Aeromonas species. J Appl Bacteriol. 1990;69:1-16.

• Janda JM. Recent advances in the study of the taxonomy, pathogenicity, and infectious syndromes associated with the genus Aeromonas. Clin Microbiol Rev. 1991;4:397-410.

• Kirov SM. Bacteria that express lateral flagella enable dissection of the multifunctional roles of flagellas in pathogenesis. FEMS Microbiol Lett. 2003;224:151-159.

• Sha J, Kozlova EV, Fadl AA, et al. Molecular characterization of a glucose-inhibited division gene, gidA, that regulates cytotoxic enterotoxin of Aeromonas hydrophila. Infect Immun. 2004; 72:1084-1095.

• Galindo CL, Sha J, Fadl AA, et al. Host immune responses to Aeromonas virulence factors. Curr Immunol Rev. 2006;2:13-26.

• Gracey M, Burke V, Robinson J. Aeromonasassociated gastroenteritis. Lancet. 1982;11:1304- 1306.

• George WL, Nakata MM, Thompson J, White ML. Aeromonas-related diarrhea in adults. Arch Intern Med. 1985;145:2207-2211.

• Sinha S, Shimada T, Ramamurthy T, et al. Prevalence, serotype distribution, antibiotic susceptibility and genetic profiles of mesophilic Aeromonas species isolated from hospitalized diarrhoeal cases in Kolkata, India. J Med Microbiol. 2004;53:527-534.

• Vila J, Ruiz J, Gallardo F, et al. Aeromonas spp. and traveler’s diarrhea: clinical features and antimicrobial resistance. Emerg Infect Dis. 2003; :552-555. 

• Farraye FA, Peppercorn MA, Ciano PS, Kavesh WN. Segmental colitis associated with Aeromonas hydrophila. Am J Gastroenterol. 1989; 84:436- 438.

• Jeyasekaran G, Ganesan P, Anandaraj R, et al. Quantitative and qualitative studies on the bacteriological quality of Indian white shrimp (Penaeus indicus) stored in dry ice. Food Microbiol. 2006;23:526-533.

• Palfreeman SJ, Waters LK, Norris M. Aeromonas hydrophila gastroenteritis. Aust N Z J Med. 1983; 13:524-525.