Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two- week versus four-week regimens: comparison of two brands of BPG. Three- versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever. Do patients with sore throat benefit from penicillin? A randomized double-blind placebo-controlled clinical trial with penicillin V in general practice. Adverse and beneficial effects of immediate treatment of Group A beta-hemolytic streptococcal pharyngitis with penicillin. Failure to eradicate Group A beta-haemolytic streptococci (GABHS) from the upper respiratory tract after antibiotic treatment. Standardized symptomatic treatment versus penicillin as initial therapy for streptococcal pharyngitis. Penicillin for acute sore throat in children: randomised, double blind trial. Multicentre evaluation of azithromycin and penicillin V in the treatment of acute streptococcal pharyngitis and tonsillitis in children. Azithromycin versus penicillin V in the treatment of paediatric patients with acute streptococcal pharyngitis/tonsillitis. Paediatric Azithromycin Study Group.
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. To investigate the effects of 3-week versus 4-week administration of benzathine penicillin G (BPG) on the incidence of Group A streptococcal infections and the recurrences of rheumatic fever (RF).
                We started, in 1979, randomly allocating all patients with RF to a 3-week or 4-week BPG prophylaxis program. They were examined at the RF clinic, every 3 to 6 months, and at any time they did not feel well. During 1979 to 1989, throat cultures and sera for antistreptolysin O and streptozyme titers were obtained at each clinic visit. Chest radiographs, electrocardiogram, color Doppler echocardiograms, and acute phase reactants were obtained.
                Two hundred forty-nine patients fulfilled the revised Jones criteria and were followed until December 1991: 124 in the 3-week and 125 in the 4-week program. Their age, sex, weight, percentage with history of RF, severity of cardiac involvement, follow-up duration, and compliance to program were comparable. Eight hundred eighty throat cultures were collected in the 3-week program and 770 were collected in the 4-week program. Six hundred sixteen and 627 sera were determined in each program for antistreptolysin O, and 582 and 592 sera for streptozyme titers.
                True streptococcal infections occurred in both programs: 39 infections in the 3-week program, and 59 infections in the 4-week program (7.5 vs 12.7 per 100 patient-years). Four infections with no antibody response occurred in the 3-week program, and three such infections in the 4-week program. Nine RF recurrences occurred in 8 patients in the 3-week program, and 16 recurrences in 16 patients in the 4-week program. Prophylaxis failure occurred in 2 of 124 patients in the 3-week program, and in 10 of 125 patients in the 4-week program (0.25 vs 1.29 per 100 patient-years). The overall recurrences/infections rate in each program was comparable, 13.6% vs 15.5%, but the recurrences/ infections rate due to prophylaxis failure was higher in the 4-week program than in the 3-week program, 3.0% versus 9.7%.
                This 12-year prospective and controlled study documented that streptococcal infections and RF recurrences occurred more often in the 4-week program than in the 3-week program. The risk of prophylaxis failure was fivefold greater in the 4-week program than in the 3-week program. The effect of antibiotic therapy in sore throat is questionable and this dilemma has been complicated by the emergence of multiple resistant strains of micro-organisms.
                A randomized double-blind placebo-controlled clinical trial was undertaken in patients aged 4-60 years to assess the efficacy of penicillin V on the clinical course and bacteriological response in patients with sore throat in general practice.
                Two hundred and thirty-nine patients presenting with an acute sore throat to 37 general practices in the Netherlands who were clinically suspected of group A beta-haemolytic streptococci (GABHS) were randomized for treatment with penicillin V (n = 121) or placebo (n = 118). Resolution of sore throat, fever and return to daily activities were evaluated by the general practitioner 2 days after the start of treatment and by the patients keeping a diary for 7 days. The result of throat culture after 2 days was evaluated.
                A difference in resolution of sore throat was present after 2 days in all patients, but was a result of GABHS-positive patients (n = 111; 46%) in favour of those randomized for penicillin V (adjusted odds ratio 5.3; 95% CI 1.9-15.1). An effect in the course of fever was also seen in GABHS-positive patients (adjusted odds ratio 5.3; 95% CI 1.02-27.7). A difference of 1-2 days was seen in clinical recovery. No difference was found in daily activities between the treatment groups. After 2 days, 4% of the penicillin-treated patients harboured GABHS compared with 75% of the placebo group.
                Only GABHS-positive patients benefit from penicillin V in their clinical cure in the first few days. Therefore, rapid testing is necessary. Treatment may be beneficial with regard to the clinical course, but it is not necessary. 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. The clinical efficacy, safety and bacteriological eradication of Group A beta-haemolytic streptococci (GABHS) from the throat was studied after treatment of streptococcal tonsillopharyngitis with three commonly used oral antibiotics in a prospective, open labelled, comparative, randomised trial of 265 evaluable patients seen in one centre. All three antibiotics were administered in the recommended doses; penicillin V q8 hourly and clarithromycin q12 hourly were given for 10 days and cefprozil q12 hourly for 5 days. Clinical results and adverse events were similar for all three antibiotics used, with a prompt clinical outcome of >95%. Cefprozil had the best bacteriological eradication rate (failed to eradicate: 13.2, 15.1, 2.3; relapses: 13.2, 11.4, 5.7%, for penicillin, clarithromycin and cefprozil, respectively). Oral penicillin remains a clinically effective and safe antibiotic for the treatment of streptococcal pharyngitis. However, compliance and convenience for parents and children when they are asked to follow a 10 days course, especially when the patient has improved from the second or third day, together with the high incidence of bacteriological eradication failures, is an issue. 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. To assess the effectiveness of penicillin for three days and treatment for seven days compared with placebo in resolving symptoms in children with sore throat.
                Randomised, double blind, placebo controlled trial.
                43 family practices in the Netherlands.
                156 children aged 4-15 who had a sore throat for less than seven days and at least two of the four Centor criteria (history of fever, absence of cough, swollen tender anterior cervical lymph nodes, and tonsillar exudate). Interventions Patients were randomly assigned to penicillin for seven days, penicillin for three days followed by placebo for four days, or placebo for seven days.
                Duration of symptoms, mean consumption of analgesics, number of days of absence from school, occurrence of streptococcal sequelae, eradication of the initial pathogen, and recurrences of sore throat after six months.
                Penicillin treatment was not more beneficial than placebo in resolving symptoms of sore throat, neither in the total group nor in the 96 children with group A streptococci. In the groups randomised to seven days of penicillin, three days of penicillin, or placebo, one, two, and eight children, respectively, experienced a streptococcal sequela.
                Penicillin treatment had no beneficial effect in children with sore throat on the average duration of symptoms. Penicillin may, however, reduce streptococcal sequelae. Of 96 children (aged 2-12 years) with either acute pharyngitis or acute tonsillitis, 49 received a single daily dose of azithromycin 10 mg/kg (maximum 500 mg) for three days, and 47 received penicillin V at a dose of 125 mg or 250 mg qid (depending on body weight) for ten days. Clinical assessments and laboratory safety tests were performed during and after therapy. Before enrollment, all patients were screened for group A beta-haemolytic streptococci (GABHS) with a rapid test, and a throat swab was taken for confirmatory culture. The presence of GABHS at baseline was confirmed in 41 azithromycin- and 44 penicillin V-treated patients. Cure or improvement was seen in 98% and 100% of azithromycin- and penicillin V-treated patients, respectively. At day 11, bacterial eradication was achieved in 39/41 (95%) azithromycin-treated patients, 38 (93%) of whom were considered clinically cured, while one patient (2%) relapsed. In the penicillin V group, 42/44 (95%) had GABHS eradicated, with 41 (93%) clinically cured and three patients (7%) improved. The remaining two patients in each group were clinically cured despite persistence of Streptococcus pyogenes. At follow-up evaluation (day 30), re-occurrence was observed in 5/37 (14%) and 3/40 (8%) of azithromycin- and penicillin V-treated patients, respectively; all patients were asymptomatic. Both drugs were well-tolerated with only two patients in the azithromycin group complaining of side effects. Treatment related laboratory test abnormalities were observed in 6/47 (13%) and 4/45 (9%) azithromycin- and penicillin V-treated patients, respectively, but none was judged to be clinically significant.(ABSTRACT TRUNCATED AT 250 WORDS) The efficacy and safety of azithromycin and penicillin V in the treatment of acute streptococcal pharyngitis/tonsillitis in paediatric patients were compared in a double-blind, double-dummy prospective study. A total of 489 children (age range, 2-13 years) were randomized to receive treatment with penicillin V (125-250 mg 4 x daily for 10 days) or azithromycin in an oral suspension (10 or 20 mg/kg 1 x daily for 3 days). Only patients with baseline cultures positive for Streptococcus pyogenes and complete clinical and microbiological assessments at the end of the therapy and follow-up one month later were included in the efficacy analysis. A satisfactory clinical response (cure or improvement) was recorded in 99% of the 10 mg/kg azithromycin group, 100% of the 20 mg/kg azithromycin group, and 97% of the penicillin V group at the end of therapy (day 12-14). At the follow-up evaluation (day 28-30), relapse rates in patients cured or improved at the end of therapy were 6%, 5%, and 2%, respectively. Bacteriological eradication rates at the end of therapy were 98% in both azithromycin groups and 92% in patients who received penicillin V (p = 0.011); pathogen recurrence was recorded at follow-up in 4% of the 20 mg/kg azithromycin group and in 6% of both the 10 mg/kg azithromycin and penicillin V groups. Treatment-related adverse events, the majority of mild to moderate severity, occurred in 13% of patients in the 20 mg/kg azithromycin group, 9% in the 10 mg/kg azithromycin group, and 5% in the penicillin V group. Azithromycin in a dosage of 10 or 20 mg/kg/day one daily for three days was as safe and effective as penicillin V administered four times daily in the treatment of paediatric patients with acute pharyngitis/tonsillitis.
Intramuscular penicillin seemed to be more effective than oral penicillin in preventing rheumatic fever recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor quality of trials.