Double-blind comparison of oral gentamicin and nalidixic acid in the treatment of acute shigellosis in children. Comparative efficacies of single intravenous doses of ceftriaxone and ampicillin for shigellosis in a placebo-controlled trial. Single dose of azithromycin or three-day course of ciprofloxacin as therapy for epidemic dysentery in Kenya. Acute Dysentery Study Group. Therapy for shigellosis. I. Randomized, double-blind trial of nalidixic acid in childhood shigellosis. Randomised comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis. Comparative efficacy of pivmecillinam and cotrimoxazole in acute shigellosis in children. Comparison of single-dose treatment with norfloxacin and standard 5-day treatment with trimethoprim-sulfamethoxazole for acute shigellosis in adults. Comparative efficacy of furazolidone and nalidixic acid in the empirical treatment of acute invasive diarrhea: randomized clinical trial. Treatment of shigellosis: V. Comparison of azithromycin and ciprofloxacin. A double-blind, randomized, controlled trial. Comparison of pivmecillinam and nalidixic acid in the treatment of acute shigellosis in children. Comparative efficacy of nalidixic acid and ampicillin for severe shigellosis. A randomized, controlled, single-blind study comparing furazolidone with trimethoprim-sulfamethoxazole in the empirical treatment of acute invasive diarrhea. Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children. Therapy for shigellosis. II. Randomized, double-blind comparison of ciprofloxacin and ampicillin.
To compare the efficacy of oral gentamicin with nalidixic acid in the treatment of acute shigellosis, we studied, in a double blind-trial, 79 comparable children with bloody diarrhoea of less than 72 h duration. Of them Shigella spp. were isolated in 71 patients. Patients were randomly assigned to receive either gentamicin 30 mg/kg/day or nalidixic acid 60 mg/kg/day, both given orally in four equal doses for 5 days. Stool frequency differed significantly between the groups from day two until completion of the study. Treatment failure was observed in 14 (42 per cent) patients receiving oral gentamicin compared to none of those with nalidixic acid-sensitive strains of Shigella spp. (P = 0.0002). Although all the shigella isolates were sensitive to gentamicin in vitro, 19 (58 per cent) patients on gentamicin therapy failed to eliminate shigella organisms from stool, compared to none in the nalidixic acid treated group infected with nalidixic acid-sensitive Shigella spp. (P < 0.001). One patient in each group had a bacteriological relapse. We conclude that gentamicin given orally was therapeutically ineffective in the treatment of acute shigellosis. To evaluate ceftriaxone for the treatment of shigellosis, 94 adult males with acute dysentery were randomly assigned to receive ceftriaxone (1 g), ampicillin (4 g), or saline placebo intravenously in single doses in a double-blind design. Stool cultures were positive for Shigella dysenteriae in 52 patients, S. flexneri in 38 patients, and other species in 4 patients. Both ceftriaxone and ampicillin caused reductions in the mean duration of fever and the means of daily stool frequency 2 to 4 days after therapy versus placebo (P less than 0.05). The ability of ceftriaxone to reduce stool frequency during 6 days after treatment was significant in patients with S. flexneri infections (P less than 0.05), whereas S. dysenteriae infections were relatively refractory to improvement by both antibiotics. Neither drug had a significant effect on overall duration of diarrhea, blood in stool, or tenesmus. Ampicillin reduced the mean duration of positive stool cultures after treatment from 2.6 days in the placebo group to 1.1 days (P less than 0.05), whereas ceftriaxone did not affect the duration of Shigella sp. excretion. These results indicate that single intravenous doses of ceftriaxone and ampicillin caused some clinical improvement in acute shigellosis but only ampicillin exerted a bacteriological effect on Shigella sp. excretion. nan We compared nalidixic acid, 55 mg/kg/day, with ampicillin, 100 mg/kg/day, both given orally for 5 days, in the treatment of children with dysentery caused by shigellosis. All patients entered into the study had illness of less than 72 hours' duration and no prior allopathic drug therapy. Treatment was randomized and administered in double-blind fashion. Patients initially treated with ampicillin who were infected with a Shigella strain resistant to ampicillin were considered as a separate group (ampicillin-R). All isolates were susceptible to nalidixic acid. Similar percentages of patients treated with nalidixic acid (26/32, 81%) and with ampicillin (17/22, 77%) were clinically cured by the end of therapy; the rate in ampicillin-R (3/14, 21%) patients was significantly lower (p less than 0.001). Stool frequency in patients treated with nalidixic acid was significantly less than for ampicillin-treated or ampicillin-R patients during the final 3 study days. All patients treated with nalidixic acid and ampicillin had Shigella eradicated from their stool by day 3, compared with 77% (10/13) of ampicillin-R patients (p less than 0.05, ampicillin-R vs nalidixic acid or ampicillin). We conclude that nalidixic acid is an effective alternative to ampicillin in the treatment of shigellosis caused by nalidixic acid-susceptible strains. Infections caused by multiply resistant Shigella species are a major cause of childhood morbidity and mortality in Third World countries. The fluoroquinolone agent ciprofloxacin is active in vitro against these strains of bacteria, but has not been routinely used to treat acute childhood infections because of concern that quinolones may cause arthropathy in children. We undertook a randomised double-blind study to test the effects of ciprofloxacin treatment in children with shigella dysentery.
                We compared the efficacy and toxic effects of ciprofloxacin suspension (10 mg/kg every 12 h for 5 days, maximum individual dose 500 mg) with those of pivmecillinam tablets (15-20 mg/kg every 8 h for 5 days, maximum individual dose 300 mg). We enrolled 143 children aged 2-15 years with dysentery of 72 h or less duration. Patients stayed in hospital for 6 days, and were followed up 7, 30, and 180 days after hospital discharge. Joint symptoms and function were assessed daily for 6 days. Clinical success was defined as the absence of frank dysentery on day 3, and on day 5 no bloody-mucoid stools, one or no watery stool, six or fewer total stools, and no fever. If no shigella were isolated from faecal samples on day 3 or thereafter, treatment was judged bacteriologically successful.
                13 patients were excluded since they did not meet eligibility criteria; 10 withdrew before day 5. Thus 120 patients (60 in each group) completed the study. Treatment was clinically successful in 48 (80%) of 60 patients who received ciprofloxacin and in 39 (65%) of 60 patients who received pivmecillinam (p=0.10). Treatment was bacteriologically successful in all of the patients receiving ciprofloxacin, and in 54 (90%) of the patients receiving pivmecillinam (p=0.03). Joint pain after treatment began in 13 (18%) of 71 patients who received ciprofloxacin and 16 (22%) of 72 patients who received pivmecillinam (p>0.2), and no patient had signs of arthritis.
                In our trial, ciprofloxacin suspension and pivmecillinam had the same clinical efficacy. Ciprofloxacin had greater bacteriological efficacy and was not associated with the development of arthropathy. We conclude that ciprofloxacin is an effective and safe drug for use in multiply resistant childhood shigellosis. In a prospective randomized double-blind trial, pivmecillinam was compared with cotrimoxazole (TMP-SMX), both given orally for a period of 5 days, for the treatment of 59 children with shigellosis. 29 patients were treated with pivmecillinam and 30 with cotrimoxazole. 14% of shigella organisms isolated were resistant to pivmecillinam and 21% to TMP-SMX. The diarrhea persisted for a mean (+/- SD) period of 74 +/- 24.8 h in the pivmecillinam-treated patients versus 73.8 +/- 34 h in the TMP-SMX-treated patients. Duration of fever, positive stool culture, visible blood, occult blood, and pus cells in the stools were similar for both treatment groups. Five patients (17%) in the pivmecillinam group and 4 patients (13%) in the cotrimoxazole group fulfilled the clinical criteria that defined treatment failure. One patient (3.4%) in the pivmecillinam group and 2 (6.6%) in the TMP-SMX group evidenced recurrence of the diarrheal symptoms at the follow-up visit. No major drug-related side effects were observed in either group. We concluded that pivmecillinam is equivalent to cotrimoxazole in the treatment of shigellosis in children. Shigellae have been shown to be highly susceptible to new quinolone agents, with average MICs for 90% of isolates of less than 0.1 microgram/ml. Because these agents also reach high concentrations in the stool after a single dose, the effectiveness of a single 800-mg dose of norfloxacin and of 5-day treatment with trimethoprim-sulfamethoxazole (TMP-SMX) were compared in a randomized trial. Patients with clinical dysentery received one of these treatment regimens, and clinical data and follow-up culture results were analyzed for patients whose stool culture on presentation grew shigellae. When 55 patients with shigellosis (26 treated with TMP-SMX, 29 treated with norfloxacin) whose bacterial isolates were susceptible to the antibiotic given were compared by treatment group, no significant differences were seen in days of illness (mean, 2.5 +/- 0.65 days with TMP-SMX and 2.0 +/- 0.47 days with norfloxacin; P = 0.200) or number of unformed stools after starting treatment (mean, 9.7 +/- 2.37 stools with TMP-SMX and 7.6 +/- 3.19 stools with norfloxacin; P = 0.312). Resistance in vitro to TMP-SMX was seen in 15% of Shigella isolates, whereas none was resistant to norfloxacin. Bacteriologic failure was found in 1 patient among 24 receiving TMP-SMX and in none of 25 patients receiving norfloxacin. One single dose of norfloxacin was as effective as 5 days of treatment with TMP-SMX in these adults with shigellosis. Efficacy of furazolidone and nalidixic acid was compared in a randomized trial involving 72 children with acute invasive diarrhea. Thirty six children received furazolidone (7.5 mg/kg/day) and 36 children received nalidixic acid (55 mg/kg/day). Clinical characteristics of the two treatment groups were comparable on admission. Of these, 34 children in furazolidone treated group and 29 children in nalidixic acid treated group completed the full course of treatment and were analyzed finally for clinical efficacy. Clinical cure was observed in 29(85.3%) children treated with furazolidone and 29(100.0%) children treated with nalidixic acid. Nalidixic acid treated group had statistically significantly higher cure rate (p = 0.039) as compared to furazolidone treated group. However, 85% cure rate in furazolidone treated group may be potentially useful for the treatment of acute invasive diarrhea because of decreasing efficacy of nalidixic acid against shigellosis in many countries. Treatment of shigellosis is currently limited by the high prevalence of multidrug-resistant strains of Shigella.
                To determine the efficacy of azithromycin in the treatment of shigellosis.
                Randomized, double-blind clinical trial.
                Diarrhea treatment center in Dhaka, Bangladesh.
                70 men with shigellosis that had lasted 72 hours or less.
                Patients stayed in the hospital for 6 days. Thirty-four patients were randomly assigned to receive 500 mg of azithromycin on study day 1, followed by 250 mg once daily for 4 days; 36 patients were assigned to receive 500 mg of ciprofloxacin every 12 hours for 5 days.
                Clinical treatment failure was considered to have occurred if frank dysentery persisted for 72 hours after therapy began or if on study day 5 a patient had more than six stools, had any bloody-mucoid stools, had more than one watery stool, or had an oral body temperature exceeding 37.8 degrees C. Bacteriologic treatment failure was considered to have occurred if Shigella strains could be isolated from a stool sample after study day 2. Therapy was considered either clinically or bacteriologically successful in patients who completed therapy and did not meet criteria for failure.
                Therapy was clinically successful in 28 (82%) patients who received azithromycin and 32 (89%) patients who received ciprofloxacin (difference, -7% [95% Cl, -23% to 10%]). Therapy was bacteriologically successful in 32 (94%) patients receiving azithromycin and 36 (100%) patients receiving ciprofloxacin (difference, -6% [Cl, -14% to 2%]). Peak serum concentrations of azithromycin were equal to the minimum inhibitory concentration (MIC) of the infecting Shigella strains, whereas serum concentrations of ciprofloxacin were 28 times the MIC. Stool concentrations of both drugs were more than 200 times the MIC.
                Azithromycin is effective in the treatment of moderate to severe shigellosis caused by multidrug-resistant Shigella strains. The efficacy of oral pivmecillinam was compared with nalidixic acid in the treatment of acute shigellosis in children 1-8 years of age. In a double-blind trial we studied 80 comparable children with bloody diarrhoea of less than 3 days' duration. Shigella spp. was isolated in 71 children. Patients were randomly assigned to receive either pivmecillinam, 50 mg/kg.day, or nalidixic acid, 60 mg/kg.day, both given orally for 5 days. The stool frequency decreased progressively in both treatment groups. Nalidixic acid failed to eradicate Shigella species in 10 patients, compared with three in the pivmecillinam group (p = 0.04). Similarly, clinical failure was observed in 11 of 37 patients receiving nalidixic acid and in 2 of 26 patients infected with nalidixic acid-susceptible strains as against none in the group receiving pivmecillinam. The results suggest that pivmecillinam given orally was, in fact, more effective than nalidixic acid in the treatment of acute shigellosis in children, particularly when the resistant strains are taken into account. nan An outpatient study of 125 children with acute invasive diarrhea was conducted at the Hospital Infantil de Mexico Federico Gomez. Through a single-blind randomization, we compared the efficacy of furazolidone, 7.5 mg/kg/day (49 patients), with trimethoprim-sulfamethoxazole (TMP-SMX), 8 mg/40 mg/kg/day (52 patients), each given for 5 days. A control group of 24 patients received no antimicrobials. Stool samples were collected from all patients at the time of admission, and active drugs were administered before the stool culture results were available. At baseline, 48 of 125 patients (38.5%) had negative stool cultures. In the other patients, the most frequently isolated pathogens were Shigella sp and enteropathogenic Escherichia coli. Of the total population who completed the study 43 of 49 (87.8%) of the patients in the furazolidone group and 43 of 52 (82.7%) of the patients in the TMP-SMX group achieved clinical cure by day 3, compared with 10 of 22 (45.5%) of the patients in the control group. Day 3 cure rates were similar between groups, independent of baseline stool culture results. Of those patients who had positive stool cultures on day 1, 20 of 34 (58.8%) in the furazolidone group and 19 of 29 (65.5%) in the TMP-SMX group had negative culture results on day 6, compared with 4 of 12 (33.3%) in the control group. Overall, clinical and bacteriologic success was achieved in 31 of 49 (63%) patients treated with furazolidone and in 36 of 52 (69%) patients treated with TMP-SMX, compared with 5 of 22 (23%) patients in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) Acute invasive diarrhea is a potentially serious condition in children. Because of the increasing resistance of enteric pathogens to commonly used oral antibiotics, intramuscular ceftriaxone has become the routine drug in the treatment of acute invasive diarrhea requiring an emergency visit in southern Israel. The inconvenience of this parenteral regimen created an increased need for oral pediatric formulations for the treatment of invasive diarrhea.
                To evaluate the efficacy and safety of a suspension formulation of ciprofloxacin in the treatment of acute invasive diarrhea in infants and children.
                From July 1996 through December 1997, 201 evaluable children ages 6 months to 10 years (35% <1 year; 70% <3 years) presenting with acute invasive diarrhea at the Pediatric Emergency Room were randomized to receive either ciprofloxacin suspension (10 mg/kg twice a day + im placebo; n = 95) or im ceftriaxone (50 mg/kg/day + placebo suspension; n = 106) for 3 days in a double blind manner. Stool cultures for Shigella, Salmonella, Campylobacter spp. and diarrheagenic Escherichia coli were obtained on Days 1, 3, 4 to 5 and 21 +/- 5. Clinical response and safety were assessed on Days 1, 2, 3, 4 to 5 and 21 +/- 5.
                We isolated 127 pathogens from 121 (60%) patients: 73 (57%) Shigella; 23 (18%) Salmonella; 18 (14%) E. coli; and 13 (10%) Campylobacter. Overall bacteriologic eradication on Day 4 to 5 was 99% for Shigella, 77% for Salmonella and 77% for Campylobacter, with no difference between the 2 groups. Clinical cure or improvement was observed in 100 and 99% of the ciprofloxacin and ceftriaxone groups, respectively. Serum ciprofloxacin values determined on Day 3 of the treatment were higher in the majority of patients than were the MIC50 and MIC90 values for the Shigella and Salmonella spp. isolated. Possible drug-related adverse events occurred in 13 patients [ciprofloxacin, 8 (8%); ceftriaxone, 5 (4.7%)] and were mild and transient. Joint examination was normal during and after completion of therapy in all patients.
                Oral ciprofloxacin was as safe and effective as intramuscular ceftriaxone for the empiric treatment of acute invasive diarrhea in ambulatory pediatric patients requiring an emergency room visit. Ciprofloxacin, 500 mg every 12 h, was compared with ampicillin, 500 mg every 6 h, both given for 5 days, in the treatment of 121 adult males hospitalized with severe shigellosis. Treatment was randomized and double-blinded. At the completion of treatment, there was resolution or marked improvement in symptoms in 57 (95%) of 60 ciprofloxacin-treated patients, 23 (88%) of 26 ampicillin-treated patients infected with an ampicillin-susceptible strain of Shigella, and 15 (43%) of 35 ampicillin-treated patients infected with an ampicillin-resistant strain of Shigella (ampicillin-R group) (P less than .01, ciprofloxacin or ampicillin groups vs. ampicillin-R group). Bacteriologic failure was less common (P less than .025) in the ciprofloxacin group (0/60) than in the ampicillin (3/26, 12%) or ampicillin-R groups (5/35, 14%). Ciprofloxacin-treated patients had a mean of 29 stools during the study, compared with 46 for ampicillin-treated patients (P = .004). Thus ciprofloxacin seems to be an effective, and perhaps superior, alternative to ampicillin in treating patients with shigellosis.
Antibiotics reduce the duration of Shigella dysentery.
Regularly updated local or regional antibiotic sensitivity patterns to different species and strains of Shigella are required to guide empiric therapy. More trials adhering to standard guidelines are required to evaluate the role of antibiotics in the treatment of severe forms of Shigella dysentery and in groups who are at high risk of complications.