Efficacy of benzathine penicillin G in group A streptococcal pharyngitis: Reevaluation

To the Editor.— The suggestion of Nordin1 that there may be a need to re-evaluate the current recommended prophylaxis for children with rheumatic fever is valid, particularly if carefully planned and controlled studies could be carried out. However, the author's contention that "It has been assumed that the levels of penicillin [following monthly intramuscular injection of 1.2 million units of benzathine penicillin G] are adequate to prevent reinfection with group A streptococcus, and hence to prevent recurrences of rheumatic fever" has always been qualified by others.

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A Review of the Rationale and Advantages of Various Mixtures of Benzathine Penicillin G

PEDIATRICS ◽

10.1542/peds.97.6.960 ◽

1996 ◽

Vol 97 (6) ◽

pp. 960-963

Author(s):

James W. Bass

Keyword(s):

Clinical Response ◽

Gold Standard ◽

Streptococcal Pharyngitis ◽

Penicillin G ◽

Benzathine Penicillin ◽

Cure Rate ◽

Parenteral Treatment ◽

Benzathine Penicillin G ◽

Local Reactions

Intramuscular benzathine (BZ) penicillin G has been accepted as the gold standard for treatment of patients with streptococcal pharyngitis since it was first introduced in 1952. Unfortunately, it has been associated with pain and tenderness at the site of injection. Efforts to lessen this by combining it with varied quantities of procaine (PC) penicillin G have been successful, decreasing the incidence of significant local reactions to 5% to 10%, little more than that seen with PC penicillin alone. A preparation containing 600 000 U BZ penicillin G and 600 000 U PC penicillin in 2 mL has been marketed since the mid-1950s as CR Bicillin 600/600 but the content of BZ penicillin G has been considered adequate only for children who weigh <60 pounds. This prompted the evaluation of a preparation containing 900 000 U BZ penicillin G plus 300 000 U PC penicillin G in a 2-mL injection. Of 400 children with streptococcal pharyngitis 100 each received this preparation, 600 000 U BZ penicillin G alone in 1 mL, 1.2 million U BZ penicillin G alone in 2 mL or 600 000 U BZ penicillin G plus 600 000 U PC penicillin G in 2 mL Clinical response was equal in all four groups; all patients were well in 36 to 48 hours. The two preparations containing PC penicillin G had significantly less severe local reactions and throat cultures were negative in all by 48 hours; it remained positive in some patients who received BZ penicillin G alone after 72 hours. The cure rate in patients receiving the 900 000/300 000 combination of BZ and PC penicillin G was equal to that in patients who received 1.2 million U BZ penicillin G with these added advantages. This combination offers optimal parenteral treatment for streptococcal pharyngitis in all children who weigh <140 pounds and it has been marketed for this purpose since 1976.

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Rheumatic Fever Prophylaxis Using Benzathine Penicillin G (BPG): Two-week Versus Four-week Regimens: Comparison of Two Brands of BPG

PEDIATRICS ◽

10.1542/peds.97.6.992 ◽

1996 ◽

Vol 97 (6) ◽

pp. 992-995

Author(s):

Ahmed Samir Kassem ◽

Salah R. Zaher ◽

Hamida Abou Shleib ◽

Abdel Ghany El-Kholy ◽

Ahmed A. Madkour ◽

...

Keyword(s):

Rheumatic Fever ◽

Recurrence Rate ◽

Penicillin G ◽

Diffusion Method ◽

High Recurrence Rate ◽

Benzathine Penicillin ◽

Benzathine Penicillin G ◽

Group A ◽

Upper Respiratory ◽

The Difference

Objective. 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? Methodology. 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. 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 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. 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 brands might contribute to the high recurrence rate of RF reported in Egypt.

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Aseptic myonecrosis following intramuscular benzathine penicllin G injection: a novel syndrome

Diagnosis ◽

10.1515/dx-2016-0040 ◽

2017 ◽

Vol 4 (1) ◽

pp. 51-54 ◽

Cited By ~ 3

Author(s):

Nicholas Ryan ◽

Andrew Olson

Keyword(s):

Side Effects ◽

Injection Site ◽

Pediatric Patient ◽

Similar Case ◽

Streptococcal Pharyngitis ◽

Penicillin G ◽

Injection Site Pain ◽

Benzathine Penicillin ◽

Benzathine Penicillin G ◽

Site Pain

AbstractWe report a novel syndrome of aseptic myonecrosis in a child occurring after intramuscular (IM) benzathine penicillin G injection for the treatment of streptococcal pharyngitis. Common side effects of IM injection, including transient injection site pain and inflammation, are common and well described. However, isolated myonecrosis following IM injection in the pediatric patient has not been previously reported. Only one similar case, following IM diclofenac injection, has been discussed in the adult literature.

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USE OF BENZATHINE PENICILLIN G IN CARRIERS OF GROUP A BETA-HEMOLYTIC STREPTOCOCCI

Journal of the American Medical Association ◽

10.1001/jama.1956.02960380010004 ◽

1956 ◽

Vol 160 (3) ◽

pp. 162 ◽

Cited By ~ 14

Author(s):

Thomas J. Brooks

Keyword(s):

Penicillin G ◽

Benzathine Penicillin ◽

Benzathine Penicillin G ◽

Group A

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Rheumatic Fever & Rheumatic Heart Disease: Azithromycin Must Replace Penicillin for Treatment and Prophylaxis

Journal of Nepalgunj Medical College ◽

10.3126/jngmc.v12i2.14476 ◽

2016 ◽

Vol 12 (2) ◽

pp. 42-45 ◽

Cited By ~ 1

Author(s):

Arati Lalchandani ◽

Senthi Raj ◽

M. Godara ◽

V. Singh ◽

A. Kumar ◽

...

Keyword(s):

Group A Streptococcus ◽

Low Cost ◽

Secondary Prophylaxis ◽

Sensitivity Test ◽

Penicillin G ◽

Benzathine Penicillin ◽

Benzathine Penicillin G ◽

Daily Dose ◽

Group A ◽

Rheumatic Heart

The standard and age-old treatment of RF/ RHD is a single injection of Benzathine Penicillin G given intramuscular after sensitivity test in a dose of 1.2 million units. For secondary prophylaxis, this is followed by Injection Benzathine Penicillin given intramuscular, each time after sensitivity test, after every 21 days (3weeks), in the same dose of 1.2 million units. The treatment and prophylaxis of RF/ RHD has never seriously been reviewed in the light of newer drugs discovered for GAS (Group A Streptococcus) after Penicillin. All the other drugs mentioned above are oral forms which could never be an alternative to Benzathine Penicillin due to the daily dose required, except for Azithromycin which has a long half-life and several other pharmacological properties which make it an ideal drug for treatment and prophylaxis of RF/ RHD. Benzathine Penicillin G is in use for past 60 years due to convenience of dosing, its undoubted efficacy in eradication of the GABHS, and the low cost. But the scene is changed now.JNGMC Vol. 12 No. 2 December 2014, Page: 42-45

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Inhibiting ability of benzathine penicillin G towards group A Streptococcus β -hemolyticus in 21 and 28 days after a single intramuscular injection

Paediatrica Indonesiana ◽

10.14238/pi43.4.2003.136-9 ◽

2016 ◽

Vol 43 (4) ◽

pp. 136

Author(s):

Bambang Madiyono ◽

Mulyadi M Djer ◽

Sudigdo Sastroasmoro ◽

Amin Subandrio ◽

Erni Erfan

Keyword(s):

Intramuscular Injection ◽

Group A Streptococcus ◽

Penicillin G ◽

Benzathine Penicillin ◽

Mueller Hinton ◽

Single Intramuscular Injection ◽

Benzathine Penicillin G ◽

Group A ◽

Preliminary Study ◽

Mueller Hinton Broth

Background The effectiveness of a single intramuscularbenzathine penicillin G as a secondary prevention of acute rheu-matic fever after 28 days is still controversial. The latest studyshowed that serum penicillin concentration was below protectivelevel in 4 weeks after a single intramuscular injection.Objective This study was a preliminary study to compare the in-hibiting ability of benzathine penicillin G towards group A Strepto-coccus β -hemolyticus in 21 and 28 days after a single IM injectionby using Mueller-Hinton broth method.Methods The inhibiting ability was measured by the serum in-hibitory concentration and serum bactericidal concentration aftera single intramuscular injection of benzathine penicillin G 1.2 mil-lion units.Results The subjects were 28 patients, with mean age of 15.5years (SD 3.4). The numbers of male and female were equal. Meanserum inhibitory concentration in 21 days after a single injectionwas 926.4 (SD 3080.1) and after 28 days was 1540.9 (SD 4275.1),which was not significantly different (p=0.0662). Mean serum bac-tericidal concentration in 21 days after IM injection was 1579.6(SD 4265.7) and in 28 days was 2417 (SD 6849.4) and it was notstatistically different (p=0.2276).Conclusion This study concluded that there was no significantdifference in the inhibiting ability of benzathine penicillin G to-wards group A Streptococcus β -hemolyticus between 21 and 28days after a single intramuscular injection

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ANTIBIOTICS IN THE TREATMENT OF BETA-HEMOLYTIC STREPTOCOCCAL PHARYNGITIS: FACTORS INFLUENCING THE RESULTS

PEDIATRICS ◽

10.1542/peds.25.1.27 ◽

1960 ◽

Vol 25 (1) ◽

pp. 27-34

Author(s):

Maxwell Stillerman ◽

S. H. Bernstein ◽

Martha L. Smith ◽

Stanley B. Gittelson ◽

Samuel Karelitz

Keyword(s):

Clinical Manifestations ◽

Streptococcal Pharyngitis ◽

Penicillin G ◽

Benzathine Penicillin ◽

Cure Rate ◽

Penicillin V ◽

Significant Difference ◽

Penicillin Therapy ◽

Benzathine Penicillin G ◽

Oral Doses

The effectiveness of penicillin V, penicillin V potassium, benzathine penicillin G, erythromycin and tetracycline in eradicating beta-hemolytic streptococci from the pharynx of 410 infected patients or carriers was studied. Penicillin V and penicillin V potassium were administered in daily oral doses of 375 to 750 mg (600,000 and 1,200,000 units), respectively, for 10 days. The benzathine penicillin G was injected once intramuscularly in similar doses. The broad spectrum antibiotics were given in daily oral doses of 30 to 50 mg/kg, up to 1 gm, for 10 days. The bacterial cure rate was 84% for 224 patients treated with penicillin V and penicillin V potassium, and 86% for 129 patients treated with benzathine penicillin G in combined doses. Forty-eight percent of 23 patients treated with erythromycin and 38% of 34 patients treated with tetracycline were cured. The majority of the clinical bacterial relapses developed 14 to 28 days after the onset of treatment with penicillin V orally and 24 to 32 days after benzathine penicillin G, 375 mg intramuscularly. Approximately half of the patients with bacterial relapses had clinical manifestations of pharyngitis. Factors which might be responsible for the development of relapses and failures are discussed. Complications consisted of one case of otitis media and one case of glomerulonephritis, developing 12 and 22 days, respectively, after the onset of treatment. No case of rheumatic fever was observed. The data indicate that penicillin was definitely more effective than erythromycin and tetracycline in eradiating beta-hemolytic streptococci from the host, in the doses used. There was no significant difference in the effectiveness of penicillin V, penicillin V potassium and benzathine penicillin G. Attention is drawn to the relapse-and-failure rate of 15% in these patients despite penicillin therapy.

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A COMPARISON OF ORAL BENZATHINE PENICILLIN G AND SULFONAMIDES FOR THE PREVENTION OF STREPTOCOCCAL INFECTIONS AND RECURRENCES OF RHEUMATIC FEVER

PEDIATRICS ◽

10.1542/peds.15.5.509 ◽

1955 ◽

Vol 15 (5) ◽

pp. 509-515

Author(s):

Milton Markowitz ◽

Woodrow Hemphill

Keyword(s):

Rheumatic Fever ◽

Significant Rise ◽

Penicillin G ◽

Streptococcal Infections ◽

Benzathine Penicillin ◽

Number Of Patients ◽

Benzathine Penicillin G ◽

Daily Dose ◽

Group A ◽

Toxic Reactions

1. The incidence of recurrences of rheumatic fever and streptococcal infections in 82 rheumatic subjects receiving a 200,000 unit tablet of benzathine penicillin G daily was compared with that in 64 rheumatic patients on a standard daily dose of a triple sulfonamide preparation, while both groups were followed for an average period of 13 months. 2. A total of 9 recurrences of rheumatic fever was noted, 4 in the group treated with penicillin and 5 among patients on sulfonamides. 3. The incidence of streptococcal infections as determined by a significant rise in the antistreptolysin O titer was essentially the same in both groups. Group A streptococci were found in the throat in about the same number of patients in each group. 4. Toxic reactions of a mild nature were noted in 7 patients (11 per cent) receiving sulfonamides as compared to 2 patients (2.5 per cent) on oral penicillin. 5. A single daily dose of 200,000 units of benzathine penicillin G is as effective a prophylactic agent as the sulfonamides for the prevention of rheumatic fever. Its chief advantage is the lower incidence of toxic reactions.

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