Evaluation of the efficacy, safety and toleration of azithromycin vs. penicillin V in the treatment of acute streptococcal pharyngitis in children: results of a multicenter, open comparative study. The Swiss Tonsillopharyngitis Study Group. Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates. Comparative efficacy and safety of 3-day azithromycin and 10-day penicillin V treatment of group A beta-hemolytic streptococcal pharyngitis in children. Standardized symptomatic treatment versus penicillin as initial therapy for streptococcal pharyngitis. Adverse and beneficial effects of immediate treatment of Group A beta-hemolytic streptococcal pharyngitis with penicillin. Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis. Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two- week versus four-week regimens: comparison of two brands of BPG. Streptococcal-A tonsillopharyngitis: a 5-day course of cefuroxime axetil versus a 10-day course of penicillin V. results depending on the children's age. A double-blind randomized trial comparing the efficacy and safety of a 5-day course of cefotiam hexetil with that of a 10-day course of penicillin V in adult patients with pharyngitis caused by group A beta-haemolytic streptococci.
For many years alternatives to penicillin have been studied for the management of pediatric group A beta-hemolytic Streptococcus (GABHS) pharyngitis. As a result of its pharmacokinetic profile azithromycin is unique among these alternative antimicrobials in allowing once daily dosing and shorter duration of treatment. However, the optimum dose (e.g. 10 or 12 mg/kg/day) and duration (e.g. 3 or 5 days) of azithromycin therapy have not been defined yet.
                An open, comparative multicenter study was conducted in 343 children with clinical symptoms of GABHS pharyngitis and a positive culture to evaluate the efficacy and safety of azithromycin (10 mg/kg) once daily for 3 days compared with penicillin V three times daily for 10 days.
                Among the evaluable patients bacteriologic eradication documented at follow-up visits was inferior with azithromycin when compared with penicillin V therapy: at Days 9 to 20 (mean, 12 days), negative cultures in 65% (99 of 152 patients) vs. 82% (128 of 126 patients) (P < 0.001); and at Days 17 to 57 (mean, 25 days), in 55% vs. 80% (P < 0.001). Overall clinical success (cure or improvement) was achieved in 93% (149 of 160 patients) of azithromycin-treated and in 89% (143 of 160 patients) of penicillin-treated patients (P > 0.50). There was no correlation between bacteriologic response and clinical outcome, as assessed shortly after completion of therapy or during 6-month follow-up. Both treatments were well-tolerated.
                In the present study on GABHS pharyngitis in children, a once daily (10-mg/kg), 3-day oral regimen of azithromycin was as clinically effective and as safe as traditional penicillin but appeared inferior in eliminating GABHS from the throat. To determine whether recurrence rates for group A beta-hemolytic streptococcal (GABHS) pharyngitis are related to the time of initiation of antibiotic therapy, we randomly assigned 113 patients with GABHS pharyngitis either to a group that began a 10-day course of penicillin V at the time of diagnosis or to a group that began the same antibiotic regimen after a dealy of 48 hours. Follow-up throat culture specimens were obtained 4 days, 2 months, and 4 months after the completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. Serotyping of all GABHS isolates was performed to distinguish between recurrences with homologous serotypes and new acquisitions with heterologous serotypes. There was no significant difference between the two treatment groups in age, gender, duration of illness before enrollment in the study, initial clinical presentation, or compliance. Of the 50 patients in the immediate-treatment group, 6 (12%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. Of the 63 patients in the delayed-treatment group, 9 (14%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. These data indicate that a 48-hour delay in the initiation of penicillin therapy for GABHS pharyngitis does not reduce the recurrence rate. The efficacy and safety of a 3-day course of azithromycin oral suspension (10 mg/kg of body weight once daily) were compared with those of penicillin V (50,000 U/kg/day in two divided doses) in children aged 3 to 12 years for the treatment of symptomatic pharyngitis caused by the group A beta-hemolytic streptococcus (GABHS). For the 154 evaluable patients, the original infecting strain of GABHS was eliminated at the end of follow-up (34 to 36 days after treatment started) from 67 (85.8%) of 78 penicillin-treated patients and 41 (53.9%) of 76 azithromycin-treated patients (P < 0.0001). Overall clinical success was achieved in 71 (91.0%) of 78 penicillin V-treated patients and 57 (75.0%) of 76 azithromycin-treated patients (P < 0.05). Potential drug-related adverse events were reported for 5.5 and 8.6% of the penicillin V- and azithromycin-treated patients, respectively (P = 0.6). In the present study, a once-daily (10 mg/kg), 3-day oral regimen of azithromycin was as safe as a 10-day course of penicillin but did not represent an effective alternative to penicillin for the treatment of GABHS pharyngitis, even for those children with azithromycin-susceptible strains. A multicenter, double-blind, randomized, placebo-controlled trial was conducted to determine whether the addition of penicillin was superior to patient education and anti-inflammatory drug therapy for relief of the acute discomforts of pharyngitis caused by group A beta-hemolytic streptococcus (GABHS). One hundred seventy-eight patients, aged 4 to 29 years, received appropriate symptomatic therapy, including specific doses of aspirin or acetaminophen, plus penicillin (91 patients) or placebo (87) for the initial 48 hours of illness. All had 24-hour office and 48-hour telephone reevaluations. In 123 patients (57 with clinically severe pharyngitis), throat cultures yielded GABHS. Penicillin provided a margin of 20% improvement over anti-inflammatory therapy for the complaint of sore throat only after 48 hours of treatment (for the 123 patients with GABHS, p = 0.01; for the 57 with both severe pharyngitis and GABHS, p = 0.05). No significant improvement was noted for fever, malaise, odynophagia, exudate, adenitis, or pharyngitis. The failure of penicillin to provide much additional benefit makes its routine early prescription specifically for symptomatic relief questionable. One hundred forty-two children with presumed Group A beta-hemolytic streptococcal (GABHS) pharyngitis were enrolled in a randomized double blind prospective study comparing the consequences of immediate penicillin treatment with treatment delayed for 48 to 56 hours. One hundred fourteen of the enrolled patients were culture-positive. An adverse impact of early antibiotic therapy was noted; the incidence of subsequent infections with GABHS was significantly greater in those treated at the initial office visit with penicillin. In the month following documented evaluation of GABHS, a recurrence occurred 2 times more frequently in those treated with penicillin immediately compared with those for whom treatment was delayed 48 to 56 hours. Late recurrences (beyond 1 month but in the same streptococcal season) occurred 8 times more frequently (P less than 0.035). Delay in penicillin treatment did not increase GABHS intrafamilial spread. Symptoms of both groups were assessed for 2 days following the initiation of treatment. Both placebo-treated and penicillin-treated groups used aspirin or acetaminophen ad libitum. Penicillin was shown to reduce fever and relieve sore throat, dysphagia, headache, abdominal pain, lethargy and anorexia significantly beyond that achieved with aspirin or acetaminophen alone. Penicillin had no effect on culture-negative cases. We examined the effect of antibiotic therapy on the clinical course of group A beta-hemolytic streptococcal (GABHS) pharyngitis in 260 children. After a throat culture had been obtained, each child was evaluated for the presence of predetermined signs and symptoms, and was then randomized in a double-blind manner to receive penicillin V, cefadroxil, or placebo. Of the 194 children with throat cultures positive for GABHS, 68 received penicillin V, 70 received cefadroxil, and 56 received placebo. Approximately 18 to 24 hours later, each patient returned for reevaluation. Significantly fewer children who had received either penicillin or cefadroxil had persistence of each of the three objective signs and each of the three subjective symptoms than did children who had received placebo. In addition, the evaluating physician, parents, and patients all believed that significantly fewer of the patients given antibiotic failed to demonstrate overall clinical improvement. This prospective study was aimed at answering two important questions: 1) Is a biweekly schedule of 1.2 million U intramuscular benzathine penicillin G (BPG) superior to a 4-week one in the prevention of upper respiratory Group A beta-hemolytic streptococcal (GABHS) infections and rheumatic fever (RF) recurrences? 2) Is there a difference in the bioavailability of BPG obtained from different manufacturers?
                Three hundred sixty rheumatic patients aged 4 to 20 years were randomly assigned to either a biweekly (190 patients) or 4-week (160 patients) BPG prophylactic schedule and were followed-up monthly for 2 years by clinical examination, throat swab culture for GABHS and measurement of antistreptolysin O titer to detect GABHS infection and/or recurrences of RF (according to revised Jones' Criteria). Thereafter, 34 rheumatic subjects, aged 8 to 16 years were randomly assigned to receive a 4-week injection of 1.2 million U of either a locally manufactured BPG brand (22 patients) or an imported one (12 patients). Sera of all patients were tested for penicillin level by plate diffusion method on days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28 after the intramuscular injection of BPG.
                The GABHS infection rate was found to be 0.2% and 0.3% for patients on the biweekly and 4-week BPG schedules, respectively, with no significant differences between them. However, the RF recurrence rate/patient/year for the 4-week schedule patients (0.12) was double that for the biweekly schedule ones (0.06). Estimation of the bioavailability of the two different brands of BPG demonstrated a difference in their pharmacokinetics and a decrease in the serum penicillin concentration below the minimum inhibitory concentration 3 weeks after the injection of either brand.
                Although a biweekly schedule may not be superior in preventing upper respiratory GABHS infection, it may play a role in preventing the sequelae of such infections. The short duration of penicillinemia explains the superiority of the 2-week schedule in RF prophylais. The difference in the pharmacokinetics of penicillin brands might contribute to the high recurrence rate of RF reported in Egypt. The recommended duration of antibiotic treatment of tonsillopharyngitis caused by group A beta-hemolytic streptococci (GABHS) with penicillin V (PenV) is mostly 10 days. However, compliance with 10-day courses is bad. Shorter therapeutic courses are necessary, especially in young children.
                In a prospective, randomized, multi-center study, children aged 1-17 years with acute tonsillopharyngitis and a positive culture for GABHS were treated with cefuroxime axetil (CAE) 20 mg/kg/day (max. 500 mg) b.i.d. for 5 days or with PenV 50,000 IU/kg (30 mg/kg) t.i.d. for 10 days. Patients were evaluated for clinical efficacy 2-4 and 7-9 days after the end of therapy. Throat swabs were taken 2-4 days after the end of therapy and at the first follow-up visit. Follow-up visits were carried out 7-8 weeks, 6 months and 12 months after study inclusion.
                1,952 patients (CAE for 5 days, 496 patients/PenV for 10 days, 1,456 patients) could be included in the intent-to-treat analysis. Two to 4 days after completion of the treatment course, the bacteriological eradication in group A (1-5 years) and group B (6-17 years) was 90.52 and 89.53% (CAE) vs. 84.13 and 84.20% (PenV), respectively; p = 0.0172; 0.0382; clinical success was 98.30% (CAE) versus 93.25% (PenV), p = 0.0017. Recurrent infections were significantly higher in younger children (group A) under both treatment regimens. Poststreptococcal sequelae (glomerulonephritis) were observed in only 1 case, in the PenV group.
                CAE b.i.d. for 5 days was at least as effective as PenV t.i.d. for 10 days. Incountries with a low incidence of rheumatic fever, CAE for 5 days can be recommended for the therapy of tonsillopharyngitis due to GABHS - also in young children.
                Copyright 2004 S. Karger AG, Basel A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A beta-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course of cefotiam hexetil (CTM) 200 mg bd with that of a 10-day course of penicillin V (PEV) 1 megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group.(ABSTRACT TRUNCATED AT 400 WORDS)
Three to six days of oral antibiotics had comparable efficacy compared to the standard duration 10-day course of oral penicillin in treating children with acute GABHS pharyngitis. . In areas where the prevalence of rheumatic heart disease is still high, our results must be interpreted with caution.