The Question of Antibiotic Therapy in Pediatric Enteroinvasive Diarrhea
Abstract & Commentary
Source: Leibovitz E, et al. Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children. Pediatr Infect Dis J 2000;19:1060-1067.
In an effort to optimize the outpatient management of dysentery in children, Leibovitz and colleagues studied 201 cases of invasive diarrhea seen in the pediatric emergency department (ED) in Beer Sheva, Israel. Children already on antibiotics for another reason; those with previous cardiac, renal, or hepatic disease; and those requiring hospitalization were excluded. Seventy-one (35%) were younger than 1 year of age, and 85% were younger than 5 years of age. Average temperature was 39.1° C. Eighty-three (42%) had more than seven bloody-mucoid stools in 24 hours. Mean symptom score was 6.0 (out of 10 maximum). All cases were documented to have greater than 15 white blood cells (WBCs) per high power field on microscopic examination of stool. Mean C-reactive protein was 6.8 (normal: < 1.0). Patients had clinical evaluation, stool cultures, and laboratory tests at enrollment, and on days 1, 2, 3, 5, and 21 during follow-up. In double-blind, prospective fashion, cases were randomized to either three days of oral ciprofloxacin (CIP) solution plus placebo intramuscular (IM) injection, or IM ceftriaxone (CTX) plus placebo oral solution. A pediatric rheumatologist examined each child on follow-up visits.
Overall, clinical "success" was achieved in 200 (99.5%) patients. The only failure involved a 5-year-old with Shigella, who was still febrile at day 4 of CIP. Of all isolates (n = 127), Shigella species were most frequent (57%), followed by Salmonella (18%), E. coli (15%), and Campylobacter (10%). Eradication rates were not statistically different between CIP and CTX for infections with Shigella (100% vs 97%), Salmonella (73% vs 80%), and Campylobacter (71% vs 83%), respectively. There was no significant difference in symptom scores, temperature resolution, and C-reactive protein between treatment groups. Children in each group had normal pediatric rheumatologist joint examinations at each follow-up visit. Vomiting and dehydration occurred more often with CIP than CTX (8 vs 3 cases, respectively). The authors conclude that oral CIP is as effective and safe as IM CTX in pediatric dysentery cases.
Comment by Michael Felz, MD
This study intrigues me for several reasons. First, detection of WBCs in stool wet mounts, as demonstrated by the authors, is simple, rapid, and helpful in distinguishing bacterial from viral diarrhea. Yet this test often is underutilized in acute care settings. I learned to personally inspect stool for WBCs during missionary work in rural Papua New Guinea, but find clinicians in the United States ill-prepared to take this five-minute step in the laboratory. Just this winter, I have seen two children with bloody diarrhea in which sheets of WBCs were visualized on microscopy by me; each grew Salmonella. Second, oral CIP achieved clinical success remarkably quickly and reliably in 99% of cases, echoing the data on dysentery in adults. This study advances CIP as an attractive oral option for ED management, pending cultures. Finally, no arthropathy was found in 21 days of follow-up, adding to the accumulated evidence that quinolones may well be safe in children, as documented in hundreds of cystic fibrosis, osteomyelitis, neutropenic, and chronic otitis media patients requiring prolonged therapy with CIP.
Several questions arise from this study, however. Can the results from Israel be generalized to the United States? How does one decide whether to use antibiotics at all, as opposed to watchful waiting, in children sick enough to appear in the ED? What is the risk of hemo-lytic uremic syndrome associated with empiric antibiotic therapy in cases where E. coli 0157:H7 eventually grows in culture (0 cases in this series)? (See also "Hemolytic uremic syndrome in children receiving antibiotics for E. coli infection," in Emerg Med Alert 2000;7:18-19.) Is 21 days long enough to observe for arthropathy from CIP?
Yet, on balance, I think this study strengthens the armamentarium for treating the wide range of pathogens responsible for invasive diarrhea in the pediatric ED, once clinicians decide that children are ill enough to require therapy, and wish to avoid painful IM injections. Treatment could be as easy as "a sip of CIP."
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