***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: OBJECTIVE This prospect i ve study was aim ed 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 ? METHODOLOGY Three hundred sixty rheumatic patients aged 4 to 20 years were r and omly 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 r and omly assigned to receive a 4-week injection of 1.2 million U of either a locally manufactured BPG br and ( 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 . RESULTS 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 br and s 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 br and . CONCLUSION 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 br and s might contribute to the high recurrence rate of RF reported in Egypt To compare the merits of 3-week versus 4-week injections of benzathine penicillin G in preventing recurrence of rheumatic fever  , 179 patients aged 4 to 19 years were assigned to one of the two programs . Age , weight , cardiac status , and streptococcal infections among the patients and their family members studied in each program were comparable . Eight-two patients and their family members were monitored for streptococcal infections . Compliance in the two programs was comparable . Of the 63 patients who stayed in the 4-week program , RF recurred in six , as a result of prophylaxis failure in five and associated with partial compliance in one . Of the 90 patients in the 3-week program , RF recurred in one , associated with partial compliance ; no failures occurred ( P = 0.01 ) . We recommended that for RF chemoprophylaxis in individuals at great risk , regardless of age , benzathine penicillin injections should be administered every 3 rather than every 4 weeks OBJECTIVE To compare the efficacy of injections of 1.2 million units of benzathine penicillin G given every 3 weeks versus every 4 weeks for secondary prevention of rheumatic fever , based on the long-term outcome of patients receiving such prophylaxis . METHODS A total of 249 consecutive patients with rheumatic fever , r and omly assigned to either a 3-week or a 4-week regimen , were examined every 3 to 6 months , and followed for 794 and 775 patient-years , respectively . RESULTS Compliance with each regimen was comparable : 83 ( 66.9 % ) of 124 patients in the 3-week group versus 92 ( 73.6 % ) of 125 patients in the 4-week group stayed in the program ( p > 0.05 ) . Streptococcal infections occurred less frequently in those receiving the 3-week regimen : 7.5 versus 12.6 per 100 patient-years ( p < 0.01 ) . Prophylaxis failed in 2 patients receiving the 3-week regimen and in 10 receiving the 4-week regimen ( 0.25 and 1.29 per 100 patient-years respectively ; p = 0.015 ) . Serum penicillin levels were adequate ( > or = 0.02 micrograms/ml ) in 100 ( 56 % ) of 179 sample s obtained 21 days after penicillin injection in the 3-week regimen , and in 51 ( 33 % ) of 155 sample s obtained 28 days after injection in the 4-week regimen ( p < 0.01 ) . Of 71 patients with mitral regurgitation in the 3-week regimen , 47 ( 66 % ) no longer had the murmur ; of 87 patients in the 4-week regimen , 40 ( 46 % ) no longer had the murmur ( p < 0.05 ) . CONCLUSIONS This 12-year controlled study indicates that the outcome of patients with rheumatic fever is better with a 3-week than with a 4-week penicillin prophylaxis regimen . Greater emphasis and more widespread use of the 3-week regimen should be recommended OBJECTIVE 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 ) .  STUDY DESIGN We started , in 1979 , r and omly 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 . SUBJECTS 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 . RESULTS 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 % . CONCLUSIONS This 12-year prospect i ve 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 An appraisal is made of toxic , microbiogenic , and allergic side effects occurring in man as a result of large amounts of penicillin increasingly used in medical and veterinary practice . The allergic reactions constitute the most common and significant side effects of penicillin . The major antigenic determinant in penicillin allergy , the penicilloyl group derived from the penicillanic acid nucleus , is common to all penicillins and explains , at least in part , the cross-reactivity of man to any penicillin derivative or preparation . Available data do not permit conclusions as to the true frequency of allergic reactions to penicillin which are reported to vary from 0.7 - 10 % in different studies in different countries . Among the side effects , the anaphylactic type may occur in about 0.015 - 0.004 % with a fatality rate from shock of 0.0015 - 0.002 % among treated patients . There is no convincing evidence that the frequency of allergic side effects to penicillin has increased in the last 10 years in relation to the increasing , worldwide use of penicillin . Persons in contact with penicillin may respond by producing antibodies , the presence of which can be determined by immunological procedures , and these are believed to be partly responsible for sudden penicillin side reactions . Routine prospect i ve skin testing prior to penicillin administration can not , however , be generally advocated at present but , in special instances , it can be undertaken in cooperation with specialists and competent laboratories . The present investigation includes a study of 151 anaphylactic fatalities reported to have followed penicillin administration . Of these persons , 14 % had evidence of previous allergies of some kind , 70 % had received penicillin previously , and 1/3 of these had already experienced prior sudden allergic reactions . In most of these fatal cases , the symptoms leading to death occurred within 15 minutes . An Expert Committee of the World Health Organization has emphasized that most anaphylactic fatalities can be prevented by measures to reduce penicillin sensitization environmentally in the population on the 1 h and , and by the preparedness of doctors on the other . ( author 's modified For preventing recurrences of rheumatic fever , a repetitive oral penicillin regimen was planned to mimic the action of monthly injections of long-acting penicillin G benzathine . The oral regimen ( TCP ) contained a therapeutic high level dose for the first ten days of each month , and a continuous low level dose for the remainder of the month . In 343 young rheumatic patients , observed during four calendar years , the group receiving injections had a streptococcal infection attack rate of 6.6 per 100 patient-years , and a rheumatic recurrence rate of 0.6 % . For patients receiving TCP , the corresponding rates were 22.7 % and 4.8 % ; these rates were higher than the injection rates even when assessed in a subgroup of patients who maintained TCP with excellent fidelity . The TCP results were not significantly different from those of previously tested oral regimens , in which lower doses of penicillin were used Sixty four children who presented with the initial attack of acute rheumatic fever and maintained continuous regular secondary prophylaxis  , were followed up prospect ively for 12.3 years ( an observation period of 775 patient-years ) . The prevalence rate of rheumatic heart disease in the 29 children who had carditis in the initial attack and in the 35 children who had no carditis initially was 49 vs 0 % , respectively . The overall prevalence rate of rheumatic heart disease was 20 % . Mitral incompetence developed in 11 patients ( 17 % ) , aortic incompetence in 2 ( 3 % ) and mitral stenosis in 2 ( 3 % ) . None of the patients developed aortic stenosis . Two recurrences developed with a recurrence rate of 0.003 per patient per year . One patient needed cardiac surgery and there was no mortality . These data strongly suggest that continuous regular secondary prophylaxis can prevent or significantly reduce the development of mitral and aortic valve stenosis , the prevalence rate of rheumatic heart disease and mortality 
    Output:
    
CONCLUSIONS Intramuscular penicillin seemed to be more effective than oral penicillin in preventing RF recurrence and streptococcal throat infections .
Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections .