Does treatment of bloody diarrhea due to Shigella dysenteriae type 1 with ampicillin precipitate hemolytic uremic syndrome?

Diarrhea-associated hemolytic uremic syndrome (HUS), the most common cause of acute renal failure in infancy and childhood, is often associated with infection by organisms producing Shiga toxin (ST) or Shiga-like toxin (SLT), mainly verocytotoxin-producing Escherichia coli (VTEC O157:H7) and Shigella dysenteriae type 1 (1,2). Although antibiotics are believed to be essential in treating shigellosis, treatment of S. dysenteriae type 1 patients with antibiotics to which the organism is resistant has been considered a risk factor for HUS (3,4). Until 1993, HUS was rarely reported from Saudi Arabia. Four cases of diarrhea-associated HUS due to S. dysenteriae type 1 were identified in 1989 (J. Hibbs and A. Mishkas, unpublished report), and one case of HUS attributed to plasma transfusion was documented in 1988 (5). In May 1993, four dysentery-associated HUS cases in two families were reported from northwestern Saudi Arabia (Tabuk). S. dysenteriae type 1 was isolated from the stool of each HUS patient. The organism was also isolated from 6 of the other 10 members of the two families who had dysentery. All isolates were resistant to trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, and ampicillin but sensitive to nalidixic acid. The two families had just returned from a 1-week visit to relatives in two neighboring villages in Gizan. This densely populated region in southwestern Saudi Arabia has about 1.2 million people living in more than 4,000 villages; the population is relatively poor and uneducated, and environmental sanitation is generally inadequate. We defined a case of HUS as any case of bloody diarrhea (BD) that had all of the following: acute renal failure (serum urea nitrogen, 18 mg/dL (or 6.3 mmol/L); or creatinine, 1.3 mg/dL (or 115 mmol/L)); thrombocytopenia (platelet count 130,000/mm3); and hemolytic anemia (hemoglobin level less than 10 g/dL; or hematocrit less than 30%; or appearance of fragmented red cells on direct microscopy). We standardized the treatment of BD in the Gizan region as follows: No antibiotics were given for treatment of BD at the primary health care centers (PHCCs) before a stool specimen was taken for culture and sensitivity testing. After reviewing the preliminary results, we either recommended use of nalidixic acid for treatment of BD or were guided by the results of the stool culture. This protocol was followed for management of BD in the entire region. Parasitologic, bacteriologic, and biochemical tests and drug treatment regimens were obtained for all patients admitted with BD or HUS to the regional referral hospital or five district hospitals in the outbreak area. BD cases were identified through hospital admission records, visits to PHCCs in the affected villages, interviews with family members of the identified patients, and school visits. We visited the houses of all HUS and BD patients and interviewed family members to ascertain which antibiotic was used to treat the BD patients; mothers were shown bottles and boxes of antibiotics and were asked to identify the antibiotic used for treating the children with BD. We identified 233 cases of BD occurring from February through July 1993 among 79 families scattered over 19 contiguous villages. Affected villages were predominantly in southern Gizan region near the Yemeni border. One hundred ninety patients (81.5%) consulted PHCCs; of those, 97 (51%) were referred to hospitals, and 81 (43%) were admitted. Thirty-four other BD patients were admitted directly to hospitals (a total of 115 admissions). In nine BD cases patients did not seek medical care including seven (3%) who used traditional treatment (the Wicka plant). In 23 (10%) patients, 13 male and 10 female, BD developed into HUS. Four isolates of S. dysenteriae type 1 that showed the same antibiotic susceptibility described earlier were obtained from four patients with BD in different villages in the middle of the outbreak. We used Cary-Blair transport medium for transporting stool specimens collected before antibiotic treatment from newly recognized patients with BD. However, communityand hospital-based interviews showed that the sequence of symptoms was almost identical in all of the 233 BD cases: the condition started with colicky abdominal pain and tenesmus (69%), followed by watery diarrhea (60%), which rapidly became only Dispatches