Comparative efficacies of single intravenous doses of ceftriaxone and ampicillin for shigellosis in a placebo-controlled trial. Treatment of shigellosis: V. Comparison of azithromycin and ciprofloxacin. A double-blind, randomized, controlled trial. Randomised comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis. Antimicrobial therapy for travelers' diarrhea. Therapy for shigellosis. I. Randomized, double-blind trial of nalidixic acid in childhood shigellosis. Double-blind comparison of oral gentamicin and nalidixic acid in the treatment of acute shigellosis in children. Comparison of single-dose treatment with norfloxacin and standard 5-day treatment with trimethoprim-sulfamethoxazole for acute shigellosis in adults. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Empiric antimicrobial therapy of domestically acquired acute diarrhea in urban adults. Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children. Effective duration of antimicrobial therapy for the treatment of acute lobar nephronia. Quality control in chronic wound management: the role of local povidone-iodine (Betadine) therapy. Comparison of pivmecillinam and nalidixic acid in the treatment of acute shigellosis in children. Short-term treatment of acute urinary tract infection in girls. Copenhagen Study Group of Urinary Tract Infections in Children.
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. 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. 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. Three clinical trials were carried out to examine the efficacy of various antimicrobial agents in the treatment of travelers' diarrhea among students from the United States in Mexico. Thirty-seven subjects received twice daily for five days 160 mg of trimethoprim (TMP) and 800 mg of sulfamethoxazole (SMZ), 38 received 200 mg of TMP, and 35 received a placebo. Another group of students were given 100 mg of furazolidone (47 students) or ampicillin (47 students) four times a day for five days. In the third study, 500 mg of bicozamycin (72 students) or a placebo (68 students) was given four times a day for three days. Most students who received TMP-SMZ (78%), TMP (84%), or bicozamycin (85%) had recovered by 48 hr after initiation of treatment, as compared with 14% and 47% in the corresponding placebo groups and 55% in the furazolidone group. The agents had a positive effect for all etiologic categories, including diarrhea due to enterotoxigenic Escherichia coli and Shigella strains and illness without any established etiologic agents. Treatment failures were unusual with TMP-SMZ, TMP, and bicozamycin therapy (5% vs. 39% for the placebo-treated students). The drugs were well tolerated. The use of TMP-SMZ or TMP alone in the empiric treatment of moderate to severe travelers' diarrhea is advocated. 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. 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. 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. Inappropriate antibiotic use for pulmonary infiltrates is common in the intensive care unit (ICU). We sought to devise an approach that would minimize unnecessary antibiotic use, recognizing that a gold standard for the diagnosis of nosocomial pneumonia does not exist. In a randomized trial, clinical pulmonary infection score (CPIS) (Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D. Lew, and P. M. Suter. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129) was used as operational criteria for decision-making regarding antibiotic therapy. Patients with CPIS </= 6 (implying low likelihood of pneumonia) were randomized to receive either standard therapy (choice and duration of antibiotics at the discretion of physicians) or ciprofloxacin monotherapy with reevaluation at 3 d; ciprofloxacin was discontinued if CPIS remained </= 6 at 3 d. Antibiotics were continued beyond 3 d in 90% (38 of 42) of the patients in the standard as therapy compared with 28% (11 of 39) in the experimental therapy group (p = 0.0001). In patients in whom CPIS remained </= 6 at the 3 d evaluation point, antibiotics were still continued in 96% (24 of 25) in the standard therapy group but in 0% (0 of 25) of the patients in the experimental therapy group (p = 0.0001). Mortality and length of ICU stay did not differ despite a shorter duration (p = 0.0001) and lower cost (p = 0.003) of antimicrobial therapy in the experimental as compared with the standard therapy arm. Antimicrobial resistance, or superinfections, or both, developed in 15% (5 of 37) of the patients in the experimental versus 35% (14 of 37) of the patients in the standard therapy group (p = 0.017). Thus, overtreatment with antibiotics is widely prevalent, but unnecessary in most patients with pulmonary infiltrates in the ICU. The operational criteria used, regardless of the precise definition of pneumonia, accurately identified patients with pulmonary infiltrates for whom monotherapy with a short course of antibiotics was appropriate. Such an approach led to significantly lower antimicrobial therapy costs, antimicrobial resistance, and superinfections without adversely affecting the length of stay or mortality. From June 1985 to September 1987, 202 adults were enrolled in a randomized, double-blinded study comparing ciprofloxacin (500 mg) with sulfamethoxazole and trimethoprim (160 mg/800 mg) or placebo for adults with acute diarrhea. All patients were treated on the day of presentation and received medication on a twice-daily schedule (every 12 hours) for 5 days. Bacterial isolates from these patients included 35 Campylobacter, 18 Shigella, and 15 Salmonella. Treatment at the time of presentation with ciprofloxacin compared with placebo shortened the duration of diarrhea (2.4 vs 3.4 days), and increased the percentage of patients cured or improved by treatment days 1, 3, 4, and 5. Similar significant differences for sulfamethoxazole and trimethoprim compared with placebo were not seen. 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. Effective treatment of acute lobar nephronia (ALN) can prevent its progression to renal abscess. The goal of this prospective study was to compare the treatment efficacy for pediatric patients who had ALN with a 3- vs 2-week intravenous plus oral antimicrobial-therapy regimen.
                Patients who were suspected of having an upper urinary tract infection underwent a systematic scheme of ultrasonographic and computed tomographic (CT) evaluation for ALN diagnosis. Patients with positive CT findings were enrolled and randomly allocated with serial entry for either a total 2-week or a 3-week antibiotic treatment regimen. Antibiotics were changed from an intravenous form to an oral form 2 to 3 days after defervescence of fever. Follow-up clinical evaluations and urine-culture analyses were performed 3 to 7 days after cessation of antibiotic treatment. Patients with persistent infection or relapse were considered as treatment failures.
                A total of 80 patients with ALN were enrolled. Forty-one patients were treated with a 2-week antimicrobial protocol, and the other 39 patients were treated with a 3-week course. Seven treatment failures, 1 persistent infection, and 6 infection relapses were identified, all of which were in the 2-week treatment group. Prolonged fever before admission and positive Escherichia coli growth (>10(5) colony-forming units per mL) in urine culture were noted as risk factors for treatment failure. All treatment failures were managed successfully with an additional 10-day antibiotic course.
                A total of 3 weeks of intravenous and oral antibiotic therapy tailored to the pathogen noted in cultures should be the treatment of choice for pediatric patients with ALN. The treatment of venous leg ulcers is often inadequate, because of incorrect diagnosis, overuse of systemic antibiotics and inadequate use of compression therapy. Stasis dermatitis related to chronic venous insufficiency accompanied by infected superficial ulcers must be differentiated from erysipelas, cellulitis and contact eczema.
                To assess the effectiveness of (1) topical povidone-iodine with and (2) without compression bandages, (3) to compare the efficacy of systemic antibiotics and topical antimicrobial agents to prevent the progression of superficial skin ulcers.
                63 patients presenting ulcerated stasis dermatitis due to deep venous refluxes were included in the study. The clinical stage of all patients was homogeneous determined by clinical, aetiological, anatomical and pathological classification. They were examined by taking a bacteriological swab from their ulcer area. Compression bandages were used in a total of 42 patients. Twenty-one patients with superficial infected (Staphylococcus aureus) ulcers were treated locally with povidone-iodine (Betadine), and 21 patients were treated with systemic antibiotics (amoxicillin). Twenty-one patients were treated locally with Betadine but did not use compression. The end point was the time of ulcus healing. The healing process of the ulcers was related to the impact of bacterial colonization and clinical signs of infection.
                Compression increases the ulcer healing rate compared with no compression. Using the same local povidone-iodine (Betadine) treatment with compression bandages is more effective (82%) for ulcus healing than without compression therapy (62%). The healing rate of ulcers treated with systemic antibiotics was not significantly better (85%) than that of the Betadine group. Using systemic antibiotics, the relapse rate of superficial bacterial infections (impetigo, folliculitis) was significantly higher (32%) than in patients with local disinfection (11%).
                Compression is essential in the mobilization of the interstitial lymphatic fluid from the region of stasis dermatitis. Topical disinfection and appropriate wound dressings are important to prevent wound infection. Systemic antibiotics are necessary only in systemic infections (fever, lymphangitis, lymphadenopathy, erysipelas). 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. The efficiency of treatment of acute urinary tract infections with sulfamethizole for 3 days, sulfamethizole for 10 days, and pivmecillinam for 3 days was compared in a randomized multicentre study comprising 264 girls aged 1-15 years. For ethical reasons children with complicated diseases were not included. In these treatment groups no significant growth after treatment was found in 81%, 77%, and 74%, respectively (NS). New bacteria after treatment were found less frequently after sulfamethizole for 3 days (4%) when compared to sulfamethizole for 10 days (14%) and pivmecillinam for 3 days (13%) (p = 0.048). After pivmecillinam treatment 75% of new bacteria were Streptococcus faecalis versus 25% after sulfamethizole for 3 days and 18% after sulfamethizole for 10 days (p = 0.016). In the subgroup with nephro-urological abnormalities no significant growth after treatment was found in 68% of the sulfamethizole 3-day treated group, 54% of the sulfamethizole 10-day treated group, and 67% of the pivmecillinam 3-day treated group (NS). All treatments resulted in a change in the bacterial sensitivity pattern when bacteria isolated 1-10 days after treatment was compared to those found before treatment. This was more pronounced after the 10-day treatment when compared to the 3-day treatment. The sensitivity patterns of the bacteria isolated from recurrences were similar to those seen before treatment. After treatment there was no difference in the actuarial percentage recurrence-free curves of the 3 treatment groups. Side effects were rare in the sulfamethizole treated groups, and seen more often in the pivmecillinam treated group. 3-day treatment with sulfamethizole or alternatively pivmecillinam is recommended as first choice for treatment of uncomplicated acute urinary tract infections in girls.
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.