Intramuscular Injection Of Benzathine Penicillin Research Articles

Therapy for Lyme arthritis: Strategies for the treatment of antibiotic‐refractory arthritis

Lyme arthritis, caused by the tick-borne spirochete Borrelia burgdorferi (1), typically causes intermittent or persistent arthritis in a few large joints, especially the knee, for several years (2). Treatment recommendations have changed over time. In the early 1980s, 3 intramuscular injections of benzathine penicillin or a 10-day course of high-dose intravenous (IV) penicillin cured only 35–55% of patients (3). In the late 1980s, treatment with IV ceftriaxone for 2 weeks was effective in 90% of patients (4,5); slightly better results were achieved with 4 weeks of therapy (6), but adverse events occurred more frequently. During the same period of time, a 4-week course of oral doxycycline or amoxicillin was also effective in 90% of patients with Lyme arthritis (7). However, joint swelling in some patients remained unresponsive to oral therapy and re-treatment with a 2-week course of IV ceftriaxone (7). To date, little information is available about therapy for such patients. One non–antibiotic-treated patient had resolution of joint swelling following hydroxychloroquine therapy (8). Sixteen of 20 patients with persistent arthritis despite antibiotic therapy experienced resolution after arthroscopic synovectomy (9). In 2000, an expert panel from the Infectious Diseases Society of America (IDSA) presented guidelines for the treatment of Lyme disease (10). The panel recommended initial treatment with oral doxycycline or amoxicillin for 4 weeks for patients with Lyme arthritis and no concomitant neurologic abnormalities. Results of a cost–benefit analysis suggested that such therapy is as effective as IV therapy, is safer than IV therapy, and is considerably less expensive (11). For patients in whom arthritis is persistent despite receiving 4 weeks of oral antibiotic therapy, the panel recommended re-treatment with another 4-week course of oral antibiotics or with a 2–4-week course of IV ceftriaxone. However, in a small percentage of patients, proliferative synovitis (12,13) persists for months to several years, even after 2 months of treatment with oral antibiotics, 1 month of treatment with IV antibiotics, or both, which we have termed antibiotic-refractory (or slowly resolving) Lyme arthritis.

NICOLAU SYNDROME AFTER INTRAMUSCULAR BENZATHINE PENICILLIN TREATMENT

Nicolau syndrome (livedoid dermatitis) is a very rare complication of intramuscular injections and manifests as excruciating pain immediately after injection. We describe a 3-year-old boy with diagnosis of Nicolau syndrome after intramuscular benzathine penicillin injection to the midanterior part of the left thigh. He was treated with hyberbaric oxygen and pentoxyphilline in addition to supportive treatment and recovered with no sequelae.

Rheumatic fever

There have been numerous reports stating that treatment of acute rheumatic fever with either aspirin or corticosteroids does not alter the long-term outcome of rheumatic heart disease. Yet, it should be emphasized that most of these studies were carried out with the first generic corticosteroids before the advent of the more active and more potent corticosteroid agents. In spite of this caveat, there is no question that all the clinical and laboratory parameters of inflammation (erythrocyte sedimentation rate, C-reactive protein) return to normal much more rapidly with corticosteroids than with aspirin alone. It is therefore our belief that steroids should be used when clinical and laboratory evidence of carditis exists, and aspirin should be reserved for cases of acute rheumatic arthritis with no evidence of carditis. The incidence of long-term valvular disease in active carditis may be decreased with steroid therapy. For example, the number of valve replacements differs markedly in centers that do use steroids and in those that do not. In Capetown, South Africa, where steroids are routinely used for carditis, valve replacement is quite rare. In contrast, in Johannesburg, where steroids are rarely used, the rate of valve replacement is quite high. The racial backgrounds of both groups of patients are similar, thus eliminating the question of racial differences. Concerning secondary prophylaxis, there is also controversy concerning the best second-line therapy. It is now well known that monthly intramuscular injections of benzathine penicillin are really effective for only 20 days. Thus, there is a window in which penicillin coverage is not adequate. To circumvent this problem, some investigators give benzathine penicillin every 3 weeks. These injections are quite painful, however, and it has been our "rule" that compliance with this treatment is inversely proportional to the ratio of the size of the child to the mother. In our own experience over 30 years with the follow-up of more than 300 patients with acute rheumatic fever, careful discussion of the consequences of missing oral doses has been adequate to insure proper compliance. An analysis of our patients on oral penicillin prophylaxis compared with other groups using benzathine penicillin revealed that there was very little difference in recurrence rate.

Apparent failure of one injection of benzathine penicillin G for syphilis during pregnancy in human immunodeficiency virus-seronegative African women.

Syphilis remains a major cause of premature birth, fetal and perinatal death, and congenital syphilis in South Africa, despite systematic antenatal screening by rapid plasma reagin and treatment with 2.4 million U of benzathine penicillin G. To determine whether one injection of 2.4 million of U of benzathine penicillin G, as recommended by the 1993 Centers for Disease Control and Prevention guidelines, is sufficient treatment for early syphilis during pregnancy. Outcome of pregnancy was prospectively analyzed after zero to three weekly intramuscular injections of benzathine penicillin G in 180 of 212 human immunodeficiency virus-seronegative black urban women with syphilis in Pretoria, South Africa. One hundred eight women receiving two or three weekly intra-gluteal injections of benzathine penicillin G had a favorable pregnancy outcome. However, after only one injection, lower birth weight, increased immaturity, prematurity, and total preterm birth rate resulted. Total pregnancy loss and perinatal mortality were also increased. After exclusion of patients treated with oral penicillin derivatives and adjustment for the estimated duration of treponemicidal levels at 3 weeks after injection, the perinatal outcome was reanalyzed. Treponemicidal coverage of 3 weeks or less resulted in decreased birth weight (2,748 vs. 3,130 g, P = 0.004) compared with treponemicidal coverage lasting longer than 3 weeks. In addition, the relative risks for prematurity (relative risk [RR], 8.5; 95% confidence interval [CI95], 2.5-28), perinatal mortality (RR, 20.5; CI95, 2.3-184), and congenital syphilis (RR 2.0; CI95-0.6-6.8) were increased when coverage was less then 3 weeks. These results were comparable to those obtained when no treatment was given. Most of the incompletely treated women delivered at less than 4 weeks after they received their injection. These also had the worst neonatal outcome. Impaired outcome due to short treatment clustered in early attenders of prenatal care (before the 28th week of gestation) and when the initial rapid plasma reagin titer was higher than 16. Although numbers were small for a firm conclusion, incompletely treated and untreated women who had taken intercurrent oral ampicillin had an improved birth weight, lower prematurity rate, and lower fetal rate. One intramuscular injection of 2.4 million U benzathine penicillin G or treponemicidal concentrations lasting 3 weeks or less is not sufficient therapy for pregnant women with syphilis. Although fetal outcome is clearly improved at birth with more than one injection, without follow-up of the neonates, complete cure cannot be predicted from these data. To obtain treponemicidal activity for longer than 3 weeks, the authors recommend administration of two injections of 2.4 million U benzathine penicillin at least 1 week apart, if possible at 4 weeks or more before delivery. This therapy is especially important for patients who attend prenatal care before 28 weeks of pregnancy or when the rapid plasma reagin titer is higher than 16.

Pharmacokinetics of benzathine penicillin G: Serum levels during the 28 days after intramuscular injection of 1,200,000 units

Because of published data suggesting the inadequacy of once-every-4-weeks intramuscular injections of benzathine penicillin G for secondary rheumatic fever prevention, serum penicillin levels were determined at 1, 3, 10, 21, and 28 days after administration of 1,200,000 units of this repository penicillin. A total of 193 samples were studied. Mean serum penicillin levels remained greater than or equal to 0.02 micrograms/ml for 21 days, but by 28 days only 44% of the serum samples had detectable levels of penicillin and only 36% had levels greater than or equal to 0.02 micrograms/ml. Patients weighing more than 45 kg had significantly lower serum penicillin levels than did those who weighed less. There were similar correlations with body surface area and with age. These data indicate that a significant percentage of patients receiving benzathine penicillin G prophylaxis for prevention of recurrent attacks of rheumatic fever are not protected during the fourth week. More frequent administration of benzathine penicillin G should be considered in instances of high risk of recurrence of rheumatic fever.

Aetiology of genital ulceration in the Gambia.

The aetiology of genital ulceration was studied in 104 unselected patients (94 men, 10 women) attending a sexually transmitted disease (STD) clinic in the Gambia. Chancroid was diagnosed in 54 (52%), syphilis in 23 (22%), lymphogranuloma venereum (LGV) in seven (7%), and herpes in six (6%). In 28 (27%) patients no diagnosis was reached. Ten (10%) patients were found to have both chancroid and syphilis, three (3%) had both LGV and syphilis, and one (1%) had both herpes and syphilis. Trimethoprim 160 mg and sulphamethoxazole 800 mg twice daily for one week was found to be effective in the treatment of chancroid. This regimen with a single intramuscular injection of benzathine penicillin 2.4 MIU is recommended for the treatment of genital ulcers in Gambian health centres without laboratory facilities.

The 1970 Epidemic of Diphtheria in San Antonio

Diphtheria affected 201 persons in San Antonio, Texas, from 1 December 1969 to 31 December 1970. Three unimmunized children died. The predominant signs and symptoms were sore throat, fever, dysphagia, nausea, and headache. A distinctive edema of the neck was commoner in adults than in children. Infection with beta hemolytic streptococci did not affect the course of diphtheria or the response to treatment. Corynebacterium diphtheriae was sensitive to ampicillin, clindamycin, erythromycin, penicillin, tetracycline, and rifampin. Partial or complete resistance to cephalexin, Colistin, lincomycin, and oxacillin was found. Both penicillin by intramuscular injection and erythromycin by intravenous injection eradicated C. diphtheriae from the pharynx of hospitalized patients. Oral erythromycin treatment compared with a single intramuscular injection of benzathine penicillin showed that benzathine penicillin can be used as an alternate to erythromycin for termination of the carrier state.

1.2 Million, Not 12 Million, Units

A dosage error occurred in the ORIGINAL CONTRIBUTION, "Rheumatic Fever in Mississippi: 104 Cases Seen Over a Decade," published in the March 8 issue (<b>215</b>:1626-1630, 1971). In column one, page 1629, under the side headPROPHYLACTIC Therapy, the correct monthly intramuscular injection of benzathine penicillin G was<b>1.2</b>million units (not 12 million units, as published).

Treatment of streptococcal pharyngitis: Influence of penicillinase-producing staphylococci

A study was undertaken to determine the influence, if any, of penicillinase-producing staphylococci in the upper respiratory tract on penicillin treatment of streptococcal pharyngitis. Cultures were obtained, during a 5 month period, from the nose and throat of patients with evidence of an upper respiratory infection who were seen in a private pediatric group practice. In those patients exhibiting Group A streptococci, follow-up cultures were obtained from 10 days to 30 days later. Streptococcal isolates were grouped and typed and staphylococcal isolates were tested for coagulase and penicillinase activity. Cultures were obtained from a total of 1,231 children. Group A streptococci were isolated from 315 children and adequate follow-up studies were obtained from 163. Ninety per cent of these children were treated with a single intramuscular injection of benzathine penicillin G, 1.2 million units; the remainder received oral penicillin or some other antibiotic for 10 days. Penicillinase-producing staphylococci were isolated concomitantly with streptococci on initial culture in 54 of the 163 children (33 per cent). Streptococci were isolated on a subsequent culture from 5 of these 54 children (9 per cent) and from 14 of the 109 children (13 per cent) without penicillinase-producing staphylococci on initial culture. After therapy, penicillinase-producing staphylococci were isolated from 69 of the 163 children (42 per cent). Streptococci were isolated on subsequent culture from 8 of these 69 children (11.5 per cent) and from 11 of the 94 children without penicilIin-producing staphylococci after therapy (11.6 per cent). As an indirect quantitative measurement of penicillinase, the growth of staphylococcal strains in various concentrations of penicillin was determined. Eleven per cent of strains isolated from the initial cultures of children who continued to exhibit Group A streptococci on follow-up cultures grew in a concentration of 400 units of penicillin. Fifteen per cent of staphylococcal strains isolated from children in whom streptococci were eradicated grew in this concentration of penicillin. These data indicate that peniciIlinase-producing staphylococci in the upper respiratory tract probably do not influence the effectiveness of benzathine penicillin treatment for streptococcal pharyngitis.

Sensitivity reactions to intramuscular injection of benzathine penicillin.

SINCE Wannamaker and his colleagues1 and Bernstein et al.2 demonstrated that daily oral administration of penicillin for ten days will successfully control epidemics of disease due to Group A streptococci among military personnel, the problem of employing penicillin as a prophylactic agent in such epidemics has become largely a practical one. For mass prophylaxis it is necessary to administer tablets daily. The attendant problems of ensuring that each man takes the drug at the proper times and the constant supervision by medical personnel of the overall operation make this form of prophylaxis difficult when large numbers of people are involved. . . .

Untoward reactions to benzathine penicillin G in a study of rheumatic-fever prophylaxis in adults.

MONTHLY intramuscular injections of benzathine penicillin G§ were given over a period of several years to a group of adults with rheumatic heart disease for rheumatic-fever prophylaxis. This report deals with the side reactions that were encountered. There were 32 patients in the group, ranging in age from twenty to fifty-four years; 5 were over thirty, 2 in their forties, and 2 over the age of fifty. The total patient months of prophylaxis was four hundred and sixty-eight; the average number of months per patient was fourteen and six tenths. Seven patients were in the program for two years or . . .

Mass prophylaxis of epidemic streptococcal infections with benzathine penicillin G. II. Experience at a naval training center during the winter of 1956-57.

THE most recent of the Navy Medical Department's continuing studies on practical and effective methods of controlling epidemic streptococcal infections in recruit populations is herein reported. The method of prophylactic intramuscular injection of benzathine penicillin G for this purpose was a direct outgrowth of the studies done at the same station in the previous winter by Schreier et al.1 Starting in December, when the prevalence of streptococcal infections began to increase, Schreier and his co-workers administered 600,000 units of benzathine penicillin G to all new recruits within a few days after their arrival at the station. Experience had shown that . . .

Effect of intramuscular injections of benzathine penicillin G on some acute-phase reactants.

BENZATHINE penicillin (N,N′-dibenzylethylenediamine dipenicillin G) is a long-acting repository penicillin that provides low serum penicillin levels for three or four weeks after a single intramuscular injection of 1,200,000 units.1 It has been shown to be highly effective and safe in preventing recurrences of rheumatic fever in children2 and is being widely used for this purpose as well as for the treatment of streptococcal pharyngitis. It was observed that after the intramuscular injection of this compound, in addition to local inflammatory reaction and fever,1 , 2 elevation of the erythrocyte sedimentation rate and appearance of C-reactive protein were apt to occur. Since both . . .

Studies in the home treatment of streptococcal disease. II. A comparison of the efficacy of oral administration of penicillin and intramuscular injection of benzathine penicillin in the treatment of streptococcal pharyngitis.

PATIENTS with streptococcal pharyngitis were formerly treated by the Home Medical Service of the Massachusetts Memorial Hospitals with a seven-day course of penicillin by mouth. However, when it became apparent that more than a third of these patients were failing to take the full prescribed course of penicillin, it was decided to change to intramuscular injections of benzathine penicillin.1 There have been many favorable reports in the recent literature concerning the effectiveness of a single injection of benzathine penicillin G for the treatment of infections with the beta-hemolytic streptococcus.2 3 4 A single injection of 600,000 units of this repository penicillin has . . .

Studies in the home treatment of streptococcal disease. I. Failure of patients to take penicillin by mouth as prescribed.

PATIENTS with streptococcal pharyngitis were formerly treated by the Home Medical Service of the Massachusetts Memorial Hospitals with a seven-day course of penicillin by mouth. However, when it became apparent that more than a third of these patients were failing to take the full prescribed course of penicillin, it was decided to change to intramuscular injections of benzathine penicillin.1 There have been many favorable reports in the recent literature concerning the effectiveness of a single injection of benzathine penicillin G for the treatment of infections with the beta-hemolytic streptococcus.2 3 4 A single injection of 600,000 units of this repository penicillin has . . .