Units Of Benzathine Penicillin Research Articles

A Case of Endemic Syphilis, Iran

A Case of Endemic Syphilis, Iran

Factors Associated With Loss of Penicillin G Concentrations in Serum After Intramuscular Benzathine Penicillin G Injection

An interval of 3-4 weeks between intramuscular injections of 1.2 million units of benzathine penicillin G as prophylaxis against group A streptococcal infection is recommended by health organizations for patients with pediatric rheumatic fever and heart disease. We reviewed the literature for evidence of the persistence of serum penicillin G during the first 4 weeks after the recommended dose of benzathine penicillin G. The weighted-mean concentration was <0.02 µg/mL by 3 weeks after the initial dose. Weighted means were lower in studies done after 1990 than before (P<0.01), in studies dealing with secondary versus primary prophylaxis (P<0.01) and in studies in children versus those in adults (P<0.02). Recommendations for benzathine penicillin G prophylaxis may need reevaluation.

Management of Adult Syphilis

There are several important unanswered key questions in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these important questions. A single dose of 2.4 million units of benzathine penicillin G remains the drug of choice for managing early syphilis. Enhanced antibiotic therapy has not been shown to improve treatment outcomes, regardless of human immunodeficiency virus (HIV) status. Although additional data on the efficacy of azithromycin in treating early syphilis have emerged, reported increases in the prevalence of a mutation associated with azithromycin resistance precludes a recommendation for its routine use. Cerebrospinal fluid (CSF) examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms. In those persons with early syphilis who do not achieve a ≥ 4-fold serologic decline in their rapid plasma reagin (RPR) titers 6-12 months after adequate therapy and those with late latent infection who do not achieve a similar decline within 12-24 months, CSF examination should be considered. Among HIV-infected persons, CSF examination among all those with asymptomatic late latent syphilis is not recommended owing to lack of evidence that demonstrates clinical benefit. HIV-infected persons with syphilis of any stages whose RPR titers are ≥ 1:32 and/or whose CD4 cell counts are <350 cells/mm(3) may be at increased risk for asymptomatic neurosyphilis. If CSF pleocytosis is evident at initial CSF examination, these examinations should be repeated every 6 months until the cell count is normal. Several important questions regarding the management of syphilis remain unanswered and should be a priority for future research.

Syphilitic Balanitis of Follmann: Three Case Reports

A 20-year-old heterosexual man presented at our sexually transmitted diseases clinic with an erosive balanitis of 3 weeks’ duration. He had had unprotected sexual intercourse with a prostitute 5 weeks previously. Examination revealed a diffuse induration of the glans penis with an eroded area (Fig. 1). No chancre was observed. Voluminous tender inguinal lymphadenopathy was present. Dark-field examination (DFE) was negative. Serological testing for syphilis was positive: a fluorescent treponemal antibody-absorbed (FTA-abs) test gave a result of 1:25,600 and a Venereal Disease Research Laboratory (VDRL) test a result of 1:64. A T. pallidum haemagglutination (TPHA) test was also positive (3+). Bacterial cultures were positive for Staphylococcus aureus. Mycological and herpes simplex virus (HSV) cultures and HIV serology were negative. The patient was treated with 2.4 million units of benzathine-penicillin, administered intramuscularly.

Congenital Syphilis: An Economic Evaluation of a Prevention Program in China

Until now there has been no data to show the effectiveness or benefits of screening for syphilis in gravidas in China. This study was to assess the effectiveness of a program preventing mother-to-child-transmission of syphilis and to reveal factors impacting the benefit. A cohort of 159,017 gravidas were screened for syphilis by serologic methods and infected individuals were treated with 3 injections of 2.4 million units of benzathine penicillin in Shenzhen in 2005. The pregnancy outcomes were compared for this cost-effectiveness analysis in 2 scenarios, intervention with screening and treatment versus no intervention. Eight hundred twenty-seven pregnant women (0.52%) were diagnosed with syphilis and treated subsequently. Of these, 200 gestations ended in miscarriage. Four babies were diagnosed with congenital syphilis; 25 neonates with low birth weight; 1 died after birth. The total cost was $636,748. On average, every $770 identified 1 infected mother. Every $4391 prevented 1 congenital syphilis; every $5135 prevented 1 low birth weight; and every $7075 prevented 1 death. One disability adjusted life year could be saved by $215. In total the program reached a benefit to cost ratio of 21.76. Sensitivity analyses revealed that this ratio was mainly impacted by the prevalence of syphilis in pregnant women and the rate of miscarriage. Screening for antenatal syphilis combined with intervening during gestation is highly effective in China. Reducing the percentage of spontaneous/induced abortion would be one of the most effective methods of further increasing the benefits of this screening.

Alopecia syphilitica-report of a patient with secondary syphilis presenting as moth-eaten alopecia and a review of its common mimickers

Alopecia syphilitica is an uncommon manifestation of secondary syphilis, occurring in only 4 percent of these individuals. It is non-inflammatory and non-cicatricial hair loss that can present in a diffuse pattern, a moth-eaten pattern, or a combination of both. A 38-year-old, otherwise asymptomatic, homosexual man is described whose initial presentation of syphilis was patchy, moth-eaten, alopecia. In addition, differentiating features of alopecia syphilitica and other similar appearing non-cicatricial alopecias are reviewed. Conditions that mimic moth-eaten alopecia include other localized and non-cicatricial alopecias, such as alopecia areata, alopecia neoplastica, tinea capitis, and trichotillomania. The distinguishing clinical and laboratory features of alopecia syphilitica include other mucocutaneous changes associated with secondary syphilis, when present, and a positive serology for syphilis. The treatment of choice is a single intramuscular injection 2.4 million units of benzathine penicillin G for patients without immunocompromise; however, our patient was treated with three weekly doses because of concern about possible HIV positivity. The hair loss usually resolves within 3 months of treatment.

Tertiary syphilis

Case 1 A 42‐year‐old married man reported heterosexual behavior with multiple partners, chronic alcoholism, and a previous history of urethritis. He presented with a 1‐year history of two asymptomatic, erythematous to violaceous, annular or polycyclic plaques, involving the anterior aspect of the left thigh. The lesions had raised, well‐defined, infiltrated borders, with irregular crusted ulcers at the periphery, and there was central healing with atrophy (Fig. 1). Histologic examination of a skin biopsy specimen showed lymphocytes and plasma cells infiltrating the superficial and deep dermis, and epithelioid granulomas. Warthin–Starry stain for spirochetes was negative. Venereal Disease Research Laboratory (VDRL) test was reactive (1 : 64) and Treponema pallidum hemagglutination assay (TPHA) was positive. Tests for hepatitis B, hepatitis C, human immunodeficiency virus‐1 (HIV‐1), and HIV‐2 were negative. Neurologic examination revealed changes attributable to chronic alcoholism. VDRL test and TPHA of cerebrospinal fluid were negative. Echocardiogram showed moderate dilatation of the ascending aorta, thickening of the aortic valves, and moderate aortic insufficiency. The patient received 2.4 million units of benzathine penicillin G, intramuscularly, once per week for three consecutive weeks, with rapid resolution of the lesions. His wife had a nonreactive VDRL test and positive TPHA, and was treated with the same regimen.Erythematous to violaceous plaque, with crusted and ulcerated border, on the left thighimageCase 2 A 32‐year‐old married woman of rural background and residence presented with a 1‐year history of occasionally pruritic, papulonodular lesions, involving the presternal (Fig. 2) and left eyebrow (Fig. 3) regions, papules in a polycyclic configuration, and clusters of erythematous, infiltrated nodules, some of which showed ulceration with a surface crust. There was central atrophy and noncontractile scarring. Her husband had been treated for primary syphilis approximately 5 years earlier with benzathine penicillin G; however, the wife was not notified and therefore was not treated. Histologic examination of a presternal lesion revealed erosion and acanthosis with irregular papillomatosis of the epidermis, a dense superficial dermal infiltrate of lymphocytes, plasma cells, and epithelioid cells, and granulomas with multinucleated giant cells. Warthin–Starry stain was negative. VDRL test was reactive (1 : 128) and TPHA was positive. Serology for hepatitis B and C and for HIV‐1 and HIV‐2 was negative. VDRL and TPHA analyses of the cerebrospinal fluid were negative. The patient was treated with 2.4 million units of benzathine penicillin G, intramuscularly, once per week for 3 weeks, with rapid resolution of the lesions. One year after treatment, there was slight central, noncontractile atrophy and peripheral hyperpigmentation (Fig. 4).Clustered, infiltrated nodules, with crusted surfaces and central atrophic scarring, in the presternal regionimageInfiltrated nodules with crusted surfaces on the left eyebrowimagePresternal lesions, 1 year after treatmentimageCase 3 Accompanied by a social worker, this single, mentally retarded, indigent 42‐year‐old man presented with a greater than 1‐year history of two fetid, erythematous to violaceous, exudative plaques with ulcerated bases and circinate, ulcerated borders, involving the inner aspects of both thighs (Fig. 5). Histologic examination showed marked pseudoepitheliomatous hyperplasia of the epidermis and marked inflammation of the papillary and reticular dermis, mainly with plasma cells (Fig. 6). Warthin–Starry stain was negative. VDRL test was reactive (1 : 8) and TPHA was positive. Serologic tests for hepatitis B and C and for HIV‐1 and HIV‐2 were negative. Neurologic examination revealed profound memory impairment and abnormal balance. Computed tomography scan of the head and evaluation of the cerebrospinal fluid were unremarkable. The patient was treated with three intramuscular injections of benzathine penicillin G, 2.4 million units, over three consecutive weeks. The lesions responded rapidly to treatment, with evolution to peripheral hyperpigmentation and central, noncontractile atrophy.Ulcerated plaques involving the inner aspect of both thighsimageInflammatory infiltrate with predominance of plasma cells (hematoxylin and eosin, ×1000)image

An unusual cause of paraplegia

A 40-year-old man was admitted to hospital with an acute onset of paraplegia of 5 days' duration, preceded by vague back pain in the interscapular region for 2 months. The pain was intermittent and was relieved by rest and analgesics. He had no significant past medical history. Physical examination revealed a gibbus at the level of the thoracic (T4–T6) vertebrae and signs of extramedullary cord compression at T7 level. Cardiovascular, respiratory, abdominal and ophthalmological examination was unremarkable and there were no Marfanoid features. Full blood count, biochemical and lipid profile, and electrocardiogram were within the normal range. Sputum examination was negative for acid-fast bacilli. Chest X-ray (Figure 1) showed mediastinal widening and X-ray of dorsolumbar spine showed scoliosis at T5–T8 with convexity to the right. Magnetic resonance imaging revealed gross dilatation of the arch of aorta and two large saccular aneurysms with size of 11.3 cm × 10.8 cm and 9.4 cm × 10.2 cm, causing destruction of T6–T9 vertebrae and spinal cord compression (Figure 2). A positive serum VDRL (venereal disease research laboratory test) and TPHA (Treponema pallidum haemaglutination assay) confirmed that the patient had syphilis. Enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) was negative. CSF analysis was normal and the CSF VDRL and TPHA were non-reactive. A diagnosis of cardiovascular syphilis was made and oral prednisolone was started followed by 2.4 million units of benzathine penicillin G. While awaiting surgery the patient's condition deteriorated rapidly as a result of a rupture of the aneurysm and he died despite aggressive resuscitation efforts. Autopsy confirmed syphilitic aortic aneurysm with destruction of vertebrae and direct spinal cord compression.

Sustained viremia during highly active antiretroviral therapy with accelerated proviral DNA decay in the setting of infection with syphilis

Highly active antiretroviral therapy (HAART) suppresses viral replication to undetectable levels in most adherent HIV-1-infected individuals. Although intermittent isolated episodes of detectable viremia are common and not necessarily associated with treatment failure [1], persistently detectable viremia is generally regarded as such and often results in a change in regimen [2]. Although sustained viremia during therapy is probably a result of the emergence of a drug-resistant variant [3], non-adherence [4,5] or superinfection with a drug-resistant virus [6] could also lead to viremia during therapy. Measurable HIV-1-RNA levels in the plasma may also reflect the release of particles from recently activated, previously infected cells harboring provirus, including resting lymphocytes and macrophages. We detail the course of a 28-year-old Caucasian gay man, who was found to be viremic on three consecutive monthly visits after 18 months of effective HAART. The viremia resolved without a change in treatment and no viremia has been detectable for the past 17 months. The patient was self-referred to the Aaron Diamond AIDS Research Center on 4 February 2000. The subject had participated in a recombinant envelope vaccine trial, was negative serologically on 13 December 1999 and was newly HIV-1 positive on 26 January 2000. On 8 February 2000 a regimen of abacavir 600 mg, lamivudine 300 mg, indinavir 2400 mg and amprenavir 900 mg a day was initiated. After 16 weeks, indinavir was discontinued and substituted with amprenavir 1200 mg/ritonavir 200 mg a day. On 30 October 2001 the patient presented with complaints of lymphadenopathy in the inguinal region. He described two brief episodes of low-grade fevers in August and September of 2001, and concomitantly reported multiple anal-receptive sexual encounters without the use of condoms. Examination revealed bilateral non-tender lymphadenopathy. A serological test for syphilis was newly positive at a 1 : 64 dilution. The patient was treated with three injections of 2.4 million units of benzathine penicillin. Low-level viremia was detected at 4-week intervals beginning at week 68 (3 July 2001), and continued until week 84 (14 September 2001) of HAART (Fig. 1a). To investigate whether the viremia resulted from superinfection, we compared the V3 region of the envelope gene from plasma virus at baseline and week 84. The V3 region was amplified using a modified nested reverse transcriptase–polymerase chain reaction as previously described [7]. The consensus sequences of the two timepoints were 100% homologous, providing conclusive evidence that the virus that initially infected this patient was the same as that being detected in the patient's plasma during rebound.Fig. 1.: (a) Longitudinal determination of plasma viremia (HIV-1-RNA copies/ml in log 10 ) and CD4 T-cell count (cells/mm 3 ) while on antiretroviral therapy. Viral load (□) is plotted on a semi-log scale, whereas CD4 cell count (●) is on a linear scale. The viral load values at the times of ‘blip’ are denoted as VL. The dotted line indicates the lower limit of detection of HIV-1 RNA (< 50 copies/ml). (b) Proviral DNA (▴) and HIV-1 RNA (□) (copies/ml) of patient from weeks 55 to 110 of highly active antiretroviral therapy. A fivefold drop in proviral DNA is noted immediately before increased viremia. The dotted line indicates the lower limit of detection of HIV-1 RNA (< 50 copies/ml). HAART, Highly active antiretroviral therapy.Having ruled out superinfection, we then asked whether resistance to the antiviral agent was emerging. Clonal sequencing of the HIV-1 protease and reverse transcriptase regions was performed. Six clones at baseline and 10 clones at week 84 were studied. Reverse transcriptase–polymerase chain reaction, cloning and sequencing of pol were performed as described elsewhere [8,9]. No resistance-conferring mutations in protease or reverse transcriptase were detected. We then asked whether the detectable viremia was a result of low-level replication from a sequestered site. We performed longitudinal assessments of the levels of proviral DNA in patient peripheral blood mononuclear cells. We hypothesized that the proviral DNA levels would remain stable or increase slightly if there was ongoing viral replication during HAART. Conversely, if viremia resulted from the expression of HIV-1 proviral DNA without replication, the proviral DNA levels would decrease. Proviral DNA was measured using the Amplicor HIV-DNA Monitor Test (Roche, Alameda, CA, USA) with modifications as published [10]. Proviral DNA levels decreased sharply between weeks 68 and 76 (Fig. 1b). These data suggest that the measurable HIV-1-RNA levels may have originated from activated reservoirs. We hypothesize that this activation is a result of immune stimulation caused by infection with syphilis. This observation suggests that efforts should be made to study apparent virological failure carefully before a particular regimen is abandoned.

Fetal Syphilis

In Brief Objective To examine the pathophysiology of fetal syphilis and correlate hematologic, immunologic, and sonographic findings. Methods Twenty-four women with untreated syphilis during pregnancy were prospectively identified. Sonography with amniocentesis and percutaneous umbilical blood sampling were performed. Darkfield examination, rabbit infectivity testing, and polymerase chain reaction for detection of Treponema pallidum were performed on amniotic fluid. Hematologic and chemical testing of fetal blood was performed using standard techniques. Fetal antitreponemal IgM was detected by Western blot assay. Maternal syphilis was treated with 2.4 to 4.8 million units of benzathine penicillin G intramuscularly. Neonatal outcomes and signs of congenital syphilis were recorded. Results Six women had primary, 12 had secondary, and six had early latent syphilis. Sixty-six percent of fetuses (95% confidence interval [CI] 47%, 82%) had either congenital syphilis or detection of Treponema pallidum in amniotic fluid. Sixty-six percent had hepatomegaly, including three fetuses (12.5%, 95% CI 4%, 31%) with ascites. Fetal antitreponemal IgM was detected in three cases. Abnormal liver transaminases were found in 88% (CI 69%, 96%), anemia in 26% (CI 13%, 47%), and thrombocytopenia in 35% (CI 19%, 55%). Maternal treatment was successful in 83% (CI 64%, 93%). Risk of treatment failure was significantly increased when hepatomegaly and ascites were present (P = .01). Conclusion Findings with fetal syphilis are similar to those of neonatal syphilis. We hypothesize that fetal transaminase elevation occurs early in the course of infection; hematologic abnormalities and hydrops occur later. Severity of disease may be associated with risk of treatment failure. The fetus infected with syphilis may manifest hepatomegaly, abnormal liver function tests, anemia, and thrombocytopenia similar to the infected neonate.

Fetal syphilis: clinical and laboratory characteristics

Objective: To examine the pathophysiology of fetal syphilis and correlate hematologic, immunologic, and sonographic findings. Methods: Twenty-four women with untreated syphilis during pregnancy were prospectively identified. Sonography with amniocentesis and percutaneous umbilical blood sampling were performed. Darkfield examination, rabbit infectivity testing, and polymerase chain reaction for detection of Treponema pallidum were performed on amniotic fluid. Hematologic and chemical testing of fetal blood was performed using standard techniques. Fetal antitreponemal IgM was detected by Western blot assay. Maternal syphilis was treated with 2.4 to 4.8 million units of benzathine penicillin G intramuscularly. Neonatal outcomes and signs of congenital syphilis were recorded. Results: Six women had primary, 12 had secondary, and six had early latent syphilis. Sixty-six percent of fetuses (95% confidence interval [CI] 47%, 82%) had either congenital syphilis or detection of Treponema pallidum in amniotic fluid. Sixty-six percent had hepatomegaly, including three fetuses (12.5%, 95% CI 4%, 31%) with ascites. Fetal antitreponemal IgM was detected in three cases. Abnormal liver transaminases were found in 88% (CI 69%, 96%), anemia in 26% (CI 13%, 47%), and thrombocytopenia in 35% (CI 19%, 55%). Maternal treatment was successful in 83% (CI 64%, 93%). Risk of treatment failure was significantly increased when hepatomegaly and ascites were present ( P = .01). Conclusion: Findings with fetal syphilis are similar to those of neonatal syphilis. We hypothesize that fetal transaminase elevation occurs early in the course of infection; hematologic abnormalities and hydrops occur later. Severity of disease may be associated with risk of treatment failure.

Sister-chromatid exchange analysis on long-term benzathine penicillin for secondary prophylaxis of rheumatic fever.

A single intra-muscular injection of 1.2 millions units of benzathine penicillin every 4 weeks is the most widely used method for the antibiotic prophylaxis of rheumatic fever. The aim of this study is to evaluate the effect of long-term benzathine penicillin on DNA in patients with rheumatic fever. Thirty children with confirmed rheumatic fever who were on the benzathine penicillin prophylaxis were enrolled in the study, and 30 similar normal children served as a control group. To detect any DNA damage, SCE analysis were performed in circulating lymphocytes of the subjects. A statistically significant increased frequency of SCE was observed in children on the benzathine penicillin prophylaxis (no = 30, mean SCEs/cell +/- SD 7.54 +/- 1.81) as compared to a control group (no = 30, mean SCEs/cell +/- SD 5.82 +/- 1.40). It has been suggested that the difference in the SCE frequencies was induced by the administration of the benzathine penicillin for a long time, and further investigations are needed to confirm this toxic effect.

Efficacy of treatment for syphilis in pregnancy

Objective: To evaluate prospectively the Centers for Disease Control and Prevention (CDC) recommended regimens for the treatment of antepartum syphilis and prevention of congenital syphilis. Methods: This was a prospective evaluation of recommended syphilis treatment regimens from September 1, 1987, to August 31, 1989, at Parkland Memorial Hospital, Dallas, Texas. Women with syphilis were staged and treated according to CDC recommendations. Treatment included 2.4 million units of intramuscular (IM) benzathine penicillin G for primary, secondary, or early latent (less than 1 year) syphilis. Women with late latent (uncertain or longer than 1 year) syphilis were treated with 7.2 million units of benzathine penicillin G IM over 3 weeks. Results: During the study period, 448 of 28,552 women (1.6%) delivered were diagnosed with syphilis. One hundred eight were diagnosed at delivery and treated postpartum. The remaining 340 (75.9%) gravidas with untreated syphilis attending prenatal clinic comprised the study group. The success of therapy in preventing congenital syphilis was as follows: primary syphilis, 27 of 27; secondary syphilis, 71 of 75; early latent syphilis, 100 of 102; and late latent syphilis, 136 of 136. The success rate for all stages of syphilis was 334 of 340 (98.2%). The success rate of therapy in secondary syphilis was significantly different from that of the other groups ( P = .03). Two of the six fetal treatment failures produced preterm stillborns. Only one maternal treatment failure occurred, in a human immunodeficiency virus-infected woman. Conclusion: The CDC-recommended regimens for the prevention of congenital syphilis and treatment of maternal infection are effective, but the highest risk of fetal treatment failure exists with maternal secondary syphilis.

Efficacy of Treatment for Syphilis in Pregnancy

In Brief Objective To evaluate prospectively the Centers for Disease Control and Prevention (CDC) recommended regimens for the treatment of antepartum syphilis and prevention of congenital syphilis. Methods This was a prospective evaluation of recommended syphilis treatment regimens from September 1, 1987, to August 31, 1989, at Parkland Memorial Hospital, Dallas, Texas. Women with syphilis were staged and treated according to CDC recommendations. Treatment included 2.4 million units of intramuscular (IM) benzathine penicillin G for primary, secondary, or early latent (less than 1 year) syphilis. Women with late latent (uncertain or longer than 1 year) syphilis were treated with 7.2 million units of benzathine penicillin G IM over 3 weeks. Results During the study period, 448 of 28,552 women (1.6%) delivered were diagnosed with syphilis. One hundred eight were diagnosed at delivery and treated postpartum. The remaining 340 (75.9%) gravidas with untreated syphilis attending prenatal clinic comprised the study group. The success of therapy in preventing congenital syphilis was as follows: primary syphilis, 27 of 27; secondary syphilis, 71 of 75; early latent syphilis, 100 of 102; and late latent syphilis, 136 of 136. The success rate for all stages of syphilis was 334 of 340 (98.2%). The success rate of therapy in secondary syphilis was significantly different from that of the other groups (P = .03). Two of the six fetal treatment failures produced preterm stillborns. Only one maternal treatment failure occurred, in a human immunodeficiency virus-infected woman. Conclusion The CDC-recommended regimens for the prevention of congenital syphilis and treatment of maternal infection are effective, but the highest risk of fetal treatment failure exists with maternal secondary syphilis. Benzathine penicillin G given intramuscularly treats maternal syphilis effectively and almost always prevents congenital syphilis.

Long-term outcome of patients with rheumatic fever receiving benzathine penicillin G prophylaxis every three weeks versus every four 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, randomly 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 (≥0.02 μg/ml) in 100 (56%) of 179 samples obtained 21 days after penicillin injection in the 3-week regimen, and in 51 (33%) of 155 samples 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. (J PEDIATR 1994;125:812-6)

Evaluation of secondary prophylactic schemes, based on benzathine penicillin G, for rheumatic fever in children

Serum concentrations of penicillin were measured in children with rheumatic fever. The adequacy of the values after administration of 1.2 million units of benzathine penicillin G every 2 or 3 weeks was confirmed; the adequacy of a 4-week regimen was questionable. The administration of 0.6 million units every 3 weeks was found to be inadequate to maintain serum levels high enough for the secondary prophylaxis of rheumatic fever.

Recurrence of Rheumatic Fever

To the Editor.— In a case report on prophylaxis for rheumatic fever, Nordin1 expressed dismayed surprise that monthly injections of 1.2 million units of benzathine penicillin G (BPG) had failed to prevent the recurrence of rheumatic fever in a 9-year-old girl. Although BPG was clearly the best of the various antistreptococcal prophylactic regimens tested in randomized clinical trials conducted by my colleagues and me at Irvington House during the late 1950s and 1960s, BPG was not perfect.

Rheumatic Fever Article Questioned

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.

Penicillin and Acute Rheumatic Fever

Introduction of secondary prophylaxis for patients with rheumatic fever is felt to be a major reason for improved prognosis of rheumatic heart disease.1,2(p163) The article by Ginsburg et al,3 raising questions concerning the efficacy of this practice, has prompted me to report our experience in the Rainbow Rheumatic Fever Clinic, Rainbow Babies and Childrens Hospital, where more than 80% of the patients receive 1,200,000 units of benzathine penicillin intramuscularly every 28 days. Seventy percent of the patients with rheumatic mitral regurgitation have lost their murmur, and no patient receiving regular intramuscular prophylaxis has developed stenosis.4

Nurse Practitioners and the Treatment of Sore Throats

The facts of the prevention of acute rheumatic fever are disarmingly simple. For a patient with an acute sore throat, we need to know simply, "Is the culture positive for hemolytic streptococci?" If not, the trouble and expense of antibiotics can be spared. If so, several effective options are open to the practitioner. A single injection of 1.2 million units of benzathine penicillin G (or 0.6 million in young children) is optimal treatment. The alternative of ten days of oral penicillin G therapy, or, for penicillin-allergic individuals, of erythromycin therapy, is also effective, but dependent on unpredictable patient fidelity. Unfortunately, the implementation of these principles is more complex than the simple facts of prevention suggest. The best programs for rapid and routine diagnosis of sore throats often have been mounted in communities in which rheumatic fever does not seem to be a problem at all. The streptococcal strains in such