Comparative efficacies of pivmecillinam and ampicillin in acute shigellosis

Abstract

The clinical efficacies of pivmecillinam and ampicillin were compared in a randomized double-blind trial in the treatment of acute shigellosis. Of In developing countries, shigellosis is a disease that causes severe morbidity, even mortality, in young children. Clinical studies have shown that appropriate antibiotic therapy decreases the duration of fever, diarrhea, abdominal pain, and excretion of Shigella organisms in the stool (4, 5, 7). Although mecillinam is highly active against Shigella strains in vitro (6, 9), its usefulness in the treatment of shigellosis is limited because of the need for parenteral delivery. Pivmecillinam, the pivaloyloxymethyl ester of mecillinam, is well absorbed from the gastrointestinal tract and during or after absorption is rapidly hydrolyzed to mecillinam. The hydrolysis is catalyzed by enzymes present in blood and in many tissues, including intestinal mucosa (8,11,13 tions and cultures were repeated daily for 7 consecutive days after the onset of therapy. All specimens were plated on MacConkey and shigella-salmonella agar. Typical lactosenegative colonies were transferred to Kligler iron agar and were differentiated with polyvalent typing sera and with selective biochemical tests. In vitro antibiotic disk sensitivities were performed on all Shigella isolates, using the Bauer-Kirby method (1).Mecillinam disks containing 33 jig of drug were obtained from Leo Pharmaceuticals; a clear zone of more than 16 mm in diameter was used to indicate sensitivity. The leukocyte count and urinalysis were done for each patient on the day of admission and on day 7 of hospitalization. Patients were asked to return 2 weeks after discharge, at which time microscopic examination, a stool culture, and complete blood count were performed. Careful attention was given to adverse effects during therapy, such as urticaria, penicillin hypersensitivity, nausea, and vomiting.Treatment groups were compared with respect to the number of stools per 24 h; duration of bloody diarrhea, abdominal pain, fever, and tenesmus; and positive stool cultures. Diarrhea was defined as three or more stools per day. Statistical significance was done by Student's t test. RESULTSStool cultures were positive for shigella in 44 patients. Of these, 22 patients received pivmecillinam and 22 patients received ampicillin. The mean durations of prehospitalization illness were 3.8 days in patients treated with pivmecillinam and 3.5 days in patients treated with ampicillin. The most common presenting symptoms were passage of bloody mucoid stool (100%), abdominal pain or cramps (93%), tenesmus (93%), and fever (70%). On physical examination, 41% of the patients had an elevated body temperature and 55% of the patients had tenderness over the lower abdomen (Table 1).Shigella flexneri (57%) and Shigella dysenteriae 1 (30%)were the most frequently isolated bacterial species in stool cultures. In vitro antibiotic resistance was greatest to tetra-643 on May 12, 2018 by guest http://aac.asm.org/ Downloaded from

Comparative efficacies of single intravenous doses of ceftriaxone and ampicillin for shigellosis in a placebo-controlled trial

“…However, more rapid clinical improvement, as shown by reductions of fever and stool frequencies on certain days, was observed in patients treated with both ceftriaxone and ampicillin when compared with placebo. This clinical response is consistent with results with other beta-lactam antibiotics including ampicillin and pivmecillinam (8). Furthermore, the observed responses when drugs were given by the intravenous route suggest that the antibiotics exerted their therapeutic activities in tissues rather than in the intestinal lumen.…”

“…Although shigellosis is usually a self-limited disease and does not always require antibiotic therapy, patients with severe colitis are benefited by appropriate antibiotic therapy. Clinical studies have shown that appropriate antibiotic therapy decreases the duration of diarrhea, fever, abdominal pain, and excretion of Shigella organisms in the stool (7,8,15). A practical approach to treatment of shigellosis is single-dose therapy.…”

Magnitude of Drug Resistant Shigellosis: A Report From Bangalore

“…Data from the literature suggest that Azithromycin and Mecillinam have shown promise in treatment of Shigellosis. [12,13] The study shows the occurrence of drug resistant Shigellosis. Antibiotics may not be necessary for mild cases and if required should be guided by local data.…”

Part II. Analysis of data gaps pertaining toShigellainfections in low and medium human development index countries, 1984–2005

“…Most recently, strains of S. dysenteriae type 1 circulating in South Asia have demonstrated resistance to multiple fluoroquinolones, with susceptibility only to azithromycin, pivmecillinam and third-generation cephalosporins [35][36][37][38][39][40][41][42]105]. Studies of the efficacy of these agents against S. dysenteriae type 1 are rare and have only been conducted in adults [107,108]. It is vital to better characterize effective antimicrobial agents and regimens for the treatment of multiplyresistant S. dysenteriae type 1 infection in children and adults ahead of the next epidemic.…”