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An intramuscular (IM) suspension of benzathine penicillin G (BPG) has been used as first-line therapy for the treatment of syphilis worldwide since its approval in the 1950s. However, there are limited reports about the pharmacokinetics of BPG. A Phase 1 study was conducted on eight Japanese healthy participants to investigate the pharmacokinetics (samples collected predose to 648 h post-dose) and safety of 2.4 million units of BPG after a single IM injection. Following administration, penicillin G, the active moiety of BPG, was absorbed slowly from the injection site with a median time to C max (t max ) of 48 h post-dose. After the achievement of C max , concentrations of penicillin G declined slowly in a monophasic fashion with a mean apparent terminal half-life of 189 h. Geometric mean AUC inf and C max were 50770 ng•h/mL and 259 ng/mL, respectively. Median time (range) above the well-accepted therapeutic concentration (18 ng/mL) for syphilis treatment was 561 h (439-608 h [18-25 days]), which reached and exceeded the necessary duration of 7-10 days for syphilis treatment. Two participants were underdosed with residual drug left in the syringe due to the high viscosity of the drug product. Only one (12.5%) participant reported a mild adverse event of nasopharyngitis, which was considered not related to the study treatment. The study results supported BPG approval in Japan as an option for syphilis treatment., (© 2024 Pfizer Inc. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

BACKGROUND Myositis is an inflammatory myopathy that can be caused by a variety of drugs, diseases, and toxins. The U.S. military uses chemoprophylaxis with intramuscular penicillin G to prevent group A streptococcal infection. We present a case of penicillin G-induced myositis, a rare cause of drug-induced myositis with limited discussion in the medical literature. CASE REPORT A 25-year-old man with no pertinent medical history presented to the Emergency Department with right hip and leg pain after receiving a single dose of intramuscular penicillin G as part of standard prophylaxis for group A streptococcal infection during basic military training. He reported pain and leg weakness that was exacerbated by physical exertion and weight bearing but had no systemic symptoms, such as fevers or chills. Initial radiographs of the hip were normal; however, subsequent magnetic resonance imaging of the hip revealed intramuscular edema and features consistent with myositis of the right proximal thigh and hip musculature. He was admitted for isolated right gluteal myositis, attributed to his preceding local penicillin injection. He recovered with symptomatic care over the following 2 weeks, with return to baseline function. CONCLUSIONS This case highlights a rare complication of intramuscular penicillin G as a cause of acute isolated myositis. It serves to inform physicians of this rare complication and to recommend the consideration of intramuscular penicillin G as a causative etiology in individuals presenting with myositis and recent penicillin G exposure.

Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal. It has previously been demonstrated that BPG delivered subcutaneously at a standard dose is safe and tolerable and has favorable pharmacokinetics, setting the scene for improved regimens with less frequent administration. The safety, tolerability, and pharmacokinetics of subcutaneous infusions of high-dose BPG were assessed in 24 healthy adult volunteers assigned to receive either 3.6, 7.2, or 10.8 MU (three, six, and nine times the standard dose, respectively) as a single subcutaneous infusion. The delivery of the BPG to the subcutaneous tissue was confirmed with ultrasonography. Safety assessments, pain scores, and penicillin concentrations were measured for 16 weeks post-dose. Subcutaneous infusion of penicillin (SCIP) was generally well tolerated with all participants experiencing transient, mild infusion-site reactions. Prolonged elevated penicillin concentrations were described using a combined zero-order (44 days) and first-order ( t 1/2 = 12 days) absorption pharmacokinetic model. In simulations, time above the conventionally accepted target concentration of 20 ng/mL (0.02 µg/mL) was 57 days for 10.8 MU delivered by subcutaneous infusion every 13 weeks compared with 9 days of every 4-weekly dosing interval for the standard 1.2 MU intramuscular dose (i.e., 63% and 32% of the dosing interval, respectively). High-dose SCIP (BPG) is safe, has acceptable tolerability, and may be suitable for up to 3 monthly dosing intervals for secondary prophylaxis of RHD., Competing Interests: The authors declare no conflict of interest.

Introduction: Spinal cord injury is a devastating complication, though rare but possible following the intramuscular injection of the Penicillin. The spinal cord injury can be permanent, leaving the patient with paralysis, bowel and bladder incontinence, and with other associated morbidities., Case Presentation: We report a 25-year-old gentleman who developed anterior spinal cord syndrome following the benzathine benzylpenicillin injection. In this case report, we discuss the clinical details, possible hypothesis behind spinal cord ischaemia and literature review., Discussion: Spinal cord ischaemia or infarction occurs due to embolism of the Penicillin products. The products following injection are carried as emboli retrogradely through the superior gluteal artery and can cause infarction to the cord's anterior part., (© 2022. Crown.)

Secondary antibiotic prophylaxis with regular intramuscular benzathine penicillin G (BPG) is the cornerstone of rheumatic heart disease management. However, there is a growing body of evidence that patients with rheumatic heart disease who have severe valvular heart disease with or without reduced ventricular function may be dying from cardiovascular compromise following BPG injections. This advisory responds to these concerns and is intended to: (1) raise awareness, (2) provide risk stratification, and (3) provide strategies for risk reduction. Based on available evidence and expert opinion, we have divided patients into low- and elevated-risk groups, based on symptoms and the severity of underlying heart disease. Patients with elevated risk include those with severe mitral stenosis, aortic stenosis, and aortic insuffiency; those with decreased left ventricular systolic dysfunction; and those with no symptoms. For these patients, we believe the risk of adverse reaction to BPG, specifically cardiovascular compromise, may outweigh its theoretical benefit. For patients with elevated risk, we newly advise that oral prophylaxis should be strongly considered. In addition, we advocate for a multifaceted strategy for vasovagal risk reduction in all patients with rheumatic heart disease receiving BPG. As current guidelines recommend, all low-risk patients without a history of penicillin allergy or anaphylaxis should continue to be prescribed BPG for secondary antibiotic prophylaxis. We publish this advisory in the hopes of saving lives and avoiding events that can have devastating effects on patient and clinician confidence in BPG.

We here report the case of a 9-year-old child suffering from Nicolau syndrome involving the left pelvic limb with severe acute limb ischemia following intramuscular benzathine penicillin injection into the buttock. Given the rarity of acute limb ischemia in children, this case of complicated Nicolau syndrome combining acute arterial thrombosis and severe rhabdomyolysis leading to rescue hip dislocation is very interesting., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Somnoma Jean-Baptiste Tougouma et al.)

Nicolau syndrome (NS) is a rare injection site reaction, following intramuscular injection of drugs characterized by severe pain, skin discoloration and varying level of tissue necrosis. The case outcomes vary from severe pain, atrophic ulcers to sepsis and limb amputation. We describe a case of the five-year-old girl with diagnosis of NS after intramuscular benzathine penicillin injection. The case was complicated with above the knee amputation of lower limb. This case report intends to remind clinicians that such rare cases should always be thought of in all patients receiving whatsoever drug via intramuscular injections., Competing Interests: The authors declare no competing interests., (Copyright: Walaza Phiri et al.)

Background: Penicillin G Benzathine (PGB) is the cornerstone of syphilis treatment. However, its intramuscular (IM) administration is associated with pain at the site of injection. The dilution of PGB with local anesthetics is recommended in some guidelines, but the evidence that supports it, particularly in adults and in HIV infection, is scarce. Preliminary clinical experience also suggests that the IM administration of PGB through increased needle gauges might improve its tolerability. The aim of the study to identify less painful ways of administering IM PGB in the treatment of syphilis in adults., Methods: Multicenter, randomized, double-blinded clinical trial in patients diagnosed with primary syphilis that required a single IM injection of PGB 2400,00 IU. Patients were randomized to receive PGB diluted with 0.5 mL mepivacaine 1% (MV) or PGB alone, and both groups either with a long 19G or short 21G IM needle. The primary objective was the effect on local pain immediately after the administration through a visual scale questionnaire on pain (0 to 10)., Results: One hundred eight patients were included, 27 in each group. Ninety-four (94.4%) were male, and 41.7% were also HIV-infected. Mean age 36.6 years (SD 11). Significant differences in immediate pain intensity were observed when comparing the long 19G group with anesthesia (mean pain intensity, [MPI] 2.92 [CI 95% 1.08-4.07]) vs long 19G without anesthesia (MPI 5.56 [CI 95% 4.39-6.73), p < 0.001; and also between short 21G group with anesthesia (MPI 3.36 [CI 95% 2.22-4.50]) vs short 21G without anesthesia (MPI 5.06 [CI 95% 3.93-6.19]), p = 0.015). No significant differences in immediate pain were observed between 19G and 21G in the presence or absence of anesthesia (p = 1.0 in both cases). No differences were found between study arms after 6 and 24 h., Conclusions: The IM administration of 1% mepivacaine-diluted PGB induces significantly less immediate local pain as compared to PGB alone. The needle gauge did not have any effect on the pain. Based on these results, we suggest anesthetic-diluted IM PGB as the standard treatment for primary syphilis., Trial Registration: EudraCT 2014-003969-24 (Date of registration 18/09/2014).

One of the most common endocrinological disorder affecting women in adolescence is Polycystic Ovarian Syndrome (PCOS). Women suffering from PCOS diagnosed with follicles in ovaries show enlarged reproductive organs with small filled follicles. Unusual bleeding, prolonged menstruation, unwanted hair growth, accumulation of fat and acne are the most common problems experienced by adolescents with PCOS. Nowadays, PCOS is treated successfully with the oral antidiabetic drug, metformin and hormone replacement therapy. Its off-label use is still controversial with unknown mechanisms due to patient risk versus benefit hypothesis by practitioners as they successfully treat PCOS in adolescents with metformin. But in few reported cases metformin has potential to induce back pain and swollen joints less frequently with rare cases of behavior alteration. Penicillin belongs to the beta-lactam antibiotics and is most commonly used to treat rheumatic fever although it has potential to cause allergic reactions affecting 10% of patients who exhibit IgE-mediated immunological reactions. Here, we present a case of a female diagnosed with PCOS who after treatment with metformin for more than two years, reported with hyperuricemia, migraine, neurological pain, severe joint and knee pains on shoulders and legs, and rheumatic fever. After treatment with benzathine benzyl penicillin for rheumatic fever, the patient also exhibited Type IV delayed hypersensitivity reaction.

Anetoderma is a rare benign condition of diverse etiology whose characteristic is the diminution or absence of the dermal elastic fibers. Classified as primary and secondary, the latter associated with tumors, inflammatory, and infectious diseases. Although the etiology of the lesions is well described in literature, the pathogenesis is still poorly determined. Anetoderma in syphilis is rare, and occurs even in the most uncommon cutaneous manifestations of the disease, such as the nodular form. In order to better understand the changes that lead to elastolysis, we propose a better correlation with the histopathological findings of the lesions that precede it. We present two cases of anetoderma secondary to syphilis, whose clinical aspects resembled the pattern of their initial secondary syphilis rash.

Background: Erysipelas and cellulitis (hereafter referred to as 'cellulitis') are common bacterial skin infections usually affecting the lower extremities. Despite their burden of morbidity, the evidence for different prevention strategies is unclear., Objectives: To assess the beneficial and adverse effects of antibiotic prophylaxis or other prophylactic interventions for the prevention of recurrent episodes of cellulitis in adults aged over 16., Search Methods: We searched the following databases up to June 2016: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched five trials registry databases, and checked reference lists of included studies and reviews for further references to relevant randomised controlled trials (RCTs). We searched two sets of dermatology conference proceedings, and BIOSIS Previews., Selection Criteria: Randomised controlled trials evaluating any therapy for the prevention of recurrent cellulitis., Data Collection and Analysis: Two authors independently carried out study selection, data extraction, assessment of risks of bias, and analyses. Our primary prespecified outcome was recurrence of cellulitis when on treatment and after treatment. Our secondary outcomes included incidence rate, time to next episode, hospitalisation, quality of life, development of resistance to antibiotics, adverse reactions and mortality., Main Results: We included six trials, with a total of 573 evaluable participants, who were aged on average between 50 and 70. There were few previous episodes of cellulitis in those recruited to the trials, ranging between one and four episodes per study.Five of the six included trials assessed prevention with antibiotics in participants with cellulitis of the legs, and one assessed selenium in participants with cellulitis of the arms. Among the studies assessing antibiotics, one study evaluated oral erythromycin (n = 32) and four studies assessed penicillin (n = 481). Treatment duration varied from six to 18 months, and two studies continued to follow up participants after discontinuation of prophylaxis, with a follow-up period of up to one and a half to two years. Four studies were single-centre, and two were multicentre; they were conducted in five countries: the UK, Sweden, Tunisia, Israel, and Austria.Based on five trials, antibiotic prophylaxis (at the end of the treatment phase ('on prophylaxis')) decreased the risk of cellulitis recurrence by 69%, compared to no treatment or placebo (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.13 to 0.72; n = 513; P = 0.007), number needed to treat for an additional beneficial outcome (NNTB) six, (95% CI 5 to 15), and we rated the certainty of evidence for this outcome as moderate.Under prophylactic treatment and compared to no treatment or placebo, antibiotic prophylaxis reduced the incidence rate of cellulitis by 56% (RR 0.44, 95% CI 0.22 to 0.89; four studies; n = 473; P value = 0.02; moderate-certainty evidence) and significantly decreased the rate until the next episode of cellulitis (hazard ratio (HR) 0.51, 95% CI 0.34 to 0.78; three studies; n = 437; P = 0.002; moderate-certainty evidence).The protective effects of antibiotic did not last after prophylaxis had been stopped ('post-prophylaxis') for risk of cellulitis recurrence (RR 0.88, 95% CI 0.59 to 1.31; two studies; n = 287; P = 0.52), incidence rate of cellulitis (RR 0.94, 95% CI 0.65 to 1.36; two studies; n = 287; P = 0.74), and rate until next episode of cellulitis (HR 0.78, 95% CI 0.39 to 1.56; two studies; n = 287). Evidence was of low certainty.Effects are relevant mainly for people after at least two episodes of leg cellulitis occurring within a period up to three years.We found no significant differences in adverse effects or hospitalisation between antibiotic and no treatment or placebo; for adverse effects: RR 0.87, 95% CI 0.58 to 1.30; four studies; n = 469; P = 0.48; for hospitalisation: RR 0.77, 95% CI 0.37 to 1.57; three studies; n = 429; P = 0.47, with certainty of evidence rated low for these outcomes. The existing data did not allow us to fully explore its impact on length of hospital stay.The common adverse reactions were gastrointestinal symptoms, mainly nausea and diarrhoea; rash (severe cutaneous adverse reactions were not reported); and thrush. Three studies reported adverse effects that led to discontinuation of the assigned therapy. In one study (erythromycin), three participants reported abdominal pain and nausea, so their treatment was changed to penicillin. In another study, two participants treated with penicillin withdrew from treatment due to diarrhoea or nausea. In one study, around 10% of participants stopped treatment due to pain at the injection site (the active treatment group was given intramuscular injections of benzathine penicillin).None of the included studies assessed the development of antimicrobial resistance or quality-of-life measures.With regard to the risks of bias, two included studies were at low risk of bias and we judged three others as being at high risk of bias, mainly due to lack of blinding., Authors' Conclusions: In terms of recurrence, incidence, and time to next episode, antibiotic is probably an effective preventive treatment for recurrent cellulitis of the lower limbs in those under prophylactic treatment, compared with placebo or no treatment (moderate-certainty evidence). However, these preventive effects of antibiotics appear to diminish after they are discontinued (low-certainty evidence). Treatment with antibiotic does not trigger any serious adverse events, and those associated are minor, such as nausea and rash (low-certainty evidence). The evidence is limited to people with at least two past episodes of leg cellulitis within a time frame of up to three years, and none of the studies investigated other common interventions such as lymphoedema reduction methods or proper skin care. Larger, high-quality studies are warranted, including long-term follow-up and other prophylactic measures.

Background: Nicolau syndrome is a rare condition consisting in tissue ischemia and necrosis following intramuscular, intra-articular or subcutaneous injection., Patients and Methods: Immediately after gluteal intramuscular injection of benzathine-penicillin, a 10-year-old male child presented an extensive painful violaceous lesion on the left buttock associated with urinary incontinence and left lower-limb paresis. Additional underlying muscular damage was supported by high serum levels of creatine kinase and lactate dehydrogenase. Treatment was based on fluid expansion, intravenous steroids and anticoagulants, resulting in improvement of cutaneous and muscular lesions. Improvement in terms of neurological dysfunction was obtained after regular neuromuscular rehabilitation., Discussion: This case underlines the need to prevent Nicolau syndrome by means of compliance with the technical recommendations for intramuscular injections., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

We 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.

Background: Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting., Methodology: We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1-15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%., Findings: The mean age of participants was 9.5 years (S.D.3.1, range: 1-15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2-100) in the azithromycin group and 96.9% (95% CI: 94.1-99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9-64.9) in the azithromycin group and 49.1% (95% CI: 41.2-56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority., Conclusions: A single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular benzathine penicillin for the treatment of early yaws among Ghanaian patients, and provides additional support for the WHO policy for use of oral azithromycin for the eradication of yaws in resource-poor settings., Trial Registration: Pan African Clinical Trials Registry PACTR2013030005181 http://www.pactr.org/., Competing Interests: The authors have declared that no competing interests exist.

Rare complications have been documented due to inadvertent intravascular administration of penicillin such as Nicolau syndrome (lipoatrophy), transverse myelitis, injury to sciatic nerve as well as Hoigne syndrome (transient central nervous system dysfunction).1 We present a case report where a young male developed Nicolau syndrome and transverse myelitis after receiving benzathine penicillin injection., (© Journal of the Association of Physicians of India 2011.)

Introduction: The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated., Methods: In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance., Results: The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p<0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04-1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19-0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08-0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted., Conclusions: Treatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.

Background: Beta-lactam antibiotics are the most frequent drugs prescribed in children worldwide. Acute rheumatic fever (ARF) is the major cause of acquired heart disease among children and adolescents. Recurrences due to inadequate penicillin prophylaxis are responsible for chronic valvular lesions requiring surgery. The fear of a severe allergic reaction is the leading cause of discontinuing prophylaxis., Objective: In this study, we aimed to reveal the frequency of adverse events and real allergic reactions to benzathine penicillin among children who are followed in our paediatric cardiology clinic with a diagnosis of ARF., Materials Methods: The children who were followed with a diagnosis of ARF between January 2005 and December 2011 were searched for a history of penicillin allergy. Patients with a positive history were evaluated in our paediatric allergy clinic. Skin tests and provocation tests were performed with parental consent., Results: In total 535 children with a diagnosis of ARF were analysed for the study. Median follow up period was 24 months (12-36) [median (%25-75)]. Eleven of our 535 (11/17.641 injection) ARF patients were suspected to have allergic reactions after 17.641 penicillin injections but only one (0.18%) was diagnosed to have penicillin allergy after detailed evaluation., Conclusion: Our data suggest that the frequency of penicillin allergy is much lower than suspected among children on penicillin prophylaxis for ARF. Consequently, penicillin prophylaxis should not be given up without proper evaluation of drug allergy., (Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.)

Nicolau syndrome is a rare, potentially severe complication that may occur after any drug injection, particularly after intramuscular injection. It is characterized by the acute onset of cutaneous and soft-tissue aseptic necrosis. Here, we report the case of a 14-year-old boy diagnosed with Nicolau syndrome on the right lower limb, after a benzathine-penicillin intramuscular injection for suspected rheumatic fever. The short-term progression was marked by uncomplicated rhabdomyolysis and the constitution of homolateral testicular torsion. The cutaneous-muscular disorders evolved favorably under symptomatic treatment. We discuss this insufficiently known complication of intramuscular injection, which may motivate reduced use of this route of drug administration in children and strict adherence to the procedure. Furthermore, it is important to note that Nicolau syndrome may evolve to homolateral testicular torsion, as, to the best of our knowledge, is reported for the first time in this case., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Aim: To evaluate the effectiveness of lignocaine and a vibrating device with cold pack (Buzzy) for pain management of intramuscular (IM) benzathine penicillin injections in the rheumatic fever (RF) population of Counties Manukau District Health Board (CMDHB)., Methods: Four hundred and five RF patients receiving four weekly injections in the CMDHB region were offered 0.25 mL of lignocaine 2% and Buzzy for pain management of their injections. The lignocaine was mixed in with the benzathine penicillin prior to administration. A pre and post survey assessed pain scores during, 2-min and 1-h post administration and the following day. Questions assessing fear were also included., Results: In total 49% of patients responded to the survey. There were 118 surveys paired pre and post intervention. Pain at injection delivery and fear scores were higher for participants ≤13 years of age. Overall pain scores were significantly reduced over all four time points. There was also a significant reduction in fear of the injections. Lignocaine and Buzzy resulted in a greater reduction in pain than lignocaine alone, only when the injection was being administered to those ≤13 years. After five months, a file audit showed that 66% of all RF patients of CMDHB were choosing to use lignocaine and 43% were choosing to use Buzzy. In total, 71% of all RF patients were choosing one or both of these analgesic interventions., Conclusion: This study demonstrates a clinically important reduction in the subjective experience of pain when two analgesic interventions were offered with IM delivery of benzathine penicillin. These pain reduction strategies have been popular in the RF population of CMDHB with a 71% uptake and a corresponding reduction in pain and fear., (© 2013 Counties Manukau Health. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Objective: To estimate the risk of serious adverse reactions to benzathine penicillin in pregnant women for preventing congenital syphilis., Methods: We searched for clinical trials or cohorts that assessed the incidence of serious adverse reactions to benzathine penicillin in pregnant women and the general population (indirect evidence). MEDLINE, EMBASE, Scopus and other databases were searched up to December 2012. The GRADE approach was used to assess quality of evidence. Absolute risks of each study were calculated along with their 95% confidence intervals (95% CI). We employed the DerSimonian and Laird random effects model in the meta-analyses., Results: From 2,765 retrieved studies we included 13, representing 3,466,780 patients. The studies that included pregnant women were conducted to demonstrate the effectiveness of benzathine penicillin: no serious adverse reactions were reported among the 1,244 pregnant women included. In the general population, among 2,028,982 patients treated, 4 died from an adverse reaction. The pooled risk of death was virtually zero. Fifty-four cases of anaphylaxis were reported (pooled absolute risk = 0.002%; 95% CI: 0%-0.003% I(2) = 12%). From that estimate, penicillin treatment would be expected to result in an incidence of 0 to 3 cases of anaphylaxis per 100,000 treated. Any adverse reactions were reported in 6,377 patients among 3,465,322 treated with penicillin (pooled absolute risk = 0.169%; 95% CI: 0.073%-0.265% I(2) = 97%). The quality of evidence was very low., Conclusion: Studies that assessed the risk of serious adverse events due to benzathine penicillin treatment in pregnant women were scarce, but no reports of adverse reactions were found. The incidence of severe adverse outcomes was very low in the general population. The risk of treating pregnant women with benzathine penicillin to prevent congenital syphilis appears very low and does not outweigh its benefits. Further research is needed to improve the quality of evidence.

Background: Syphilis is a complex systemic disease caused by a spirochete, Treponema pallidum. The World Health Organization estimates that at least 12 million people worldwide are currently infected with syphilis. In this review we compared two current standards of treatment for early syphilis, benzathine benzylpenicillin (penicillin G) and azithromycin., Objectives: To evaluate the efficacy and safety of azithromycin versus benzathine penicillin (penicillin G) for early syphilis., Search Methods: We searched the following databases using the search terms detailed in Appendix 1: the Cochrane Sexually Transmitted Diseases Group Specialized Register (July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library (Issue 7 2011), MEDLINE (1948 to July 2011), EMBASE (1980 to July 2011), PsycINFO (1806 to July 2011) and the Chinese Biological Medicine Literature Database (CBM) (1978 to 2011). The search was not limited by language., Selection Criteria: Randomized controlled trials comparing azithromycin with benzathine penicillin G at any dose for the treatment of early syphilis., Data Collection and Analysis: Two review authors independently applied the inclusion criteria to potential studies, with any disagreements resolved by discussion. The risk of bias of each study was assessed by the same two review authors. We pooled data using an odds ratio (OR)., Main Results: Three studies (generating four eligible study comparisons) were included. One study is ongoing. There was no statistically significant difference between azithromycin and benzathine penicillin treatment in the odds of cure (OR 1.04, 95% CI 0.69 to 1.56); nor any difference at three months (OR 0.97, 95% CI 0.62 to 1.50), six months (OR 1.09, 95% CI 0.76 to 1.54) or nine months (OR 1.45, 95% CI 0.46 to 6.42). Subgroup analysis by primary and latent syphilis and by dose of azithromycin (2 g and 4 g) did not explain the variation between the study results. The reporting of computed mild to tolerated adverse events, from two included trials, indicated no statistically significant difference between azithromycin and benzathine penicillin (OR 1.43, 95% CI 0.42 to 4.95), although with a high level of heterogeneity (P = 0.05, I(2) = 74%)., Authors' Conclusions: Differences in the odds of cure did not reach statistical significance when azithromycin was compared with benzathine penicillin for the treatment of early syphilis. No definitive conclusion can be made regarding the relative safety of benzathine penicillin G and azithromycin for early syphilis. Further studies on the utility of benzathine penicillin G for early syphilis are warranted.

Case Description: 2 dogs and a cat were inadvertently given penicillin G procaine-penicillin G benzathine IV instead of propofol during induction of anesthesia for routine dental prophylaxis. One dog and the cat required hospitalization because of severe neurologic impairment and cardiopulmonary arrest (cat); the remaining dog did not develop any clinical signs., Clinical Findings: In the 2 animals that developed signs consistent with an immediate adverse reaction, clinical signs included muscle tremors, seizures, blindness, vocalization, agitation, and transient loss of vision. Hypothermia, pruritus, hypotension, and cardiac arrest were also documented., Treatment and Outcome: The 2 affected patients responded to treatment with anticonvulsant medications, centrally acting muscle relaxants, sedation, and intensive supportive care including IV fluid administration and oxygen supplementation as needed. Cardiopulmonary cerebral resuscitation was performed successfully in the cat. The dog that did not develop any clinical signs was not treated. The 2 affected patients recovered fully and were discharged from the hospital after 3 to 4 days with no apparent sequelae., Clinical Relevance: Penicillin G procaine-penicillin G benzathine and propofol are common drugs in veterinary practice and may both be administered to patients undergoing elective procedures. Because of their similar milky white appearance, veterinarians should label syringes and take care to avoid this medication error. There is no specific antidote for penicillin orprocaine toxicosis. Aggressive and immediate treatment is required in patients that develop an adverse reaction to ensure a successful outcome.

We report the case of a 64-year-old male presenting with a rapidly enlarging painful violaceous plaque in the left buttock and posterior thigh, following a gluteal intramuscular injection of benzathine penicillin. Associated urinary incontinence and lower left limb paresis were consistent with sciatic and lower sacral nerve damage, as confirmed by electromyography. Additional underlying muscular damage was observed in ultrasound and computer tomodensitometry scans and supported by high serum levels of creatine kinase and lactate dehydrogenase. Aggressive treatment was performed with fluid expansion, intravenous steroid bolus, vasodilators and anticoagulation, resulting in slow improvement of cutaneous and muscular lesions. However, no significant effect was observed on neurologic dysfunction after 6 months of regular neuromuscular rehabilitation. Nicolau Livedoid Dermatitis is a rare and potentially fatal condition showing variable levels of tissue impairment and unpredictable course and prognosis. Specific treatment is not consensual and the efficacy of any particular treatment remains to be established.

The Jarisch-Herxheimer reaction (JHR) is a syndrome observed after antimicrobial treatment of some infectious diseases. The syndrome has clinical characteristics of an inflammatory reaction to antibiotic treatment. A prospective study of patients with a clinical and laboratory diagnosis of syphilis was conducted at a sexually transmitted diseases clinic in Rio de Janeiro, Brazil. Patients were treated with benzathine penicillin and observed for the JHR. A total of 115 patients were included in this study. Fifty-one patients (44%) had secondary syphilis; 37 (32%), primary; 26 (23%), latent; and one (1%), tertiary syphilis. Ten patients (9%) developed the JHR. All JHRs occurred in patients with secondary and latent syphilis. No patients experienced an allergic reaction to penicillin. The JHR occurred less frequently than in previous studies. It is important that health-care professionals recognize the clinical characteristics of the JHR so that it is not misinterpreted as an allergic reaction to penicillin.

A 4 year-old boy was admitted to our clinic with symptoms of pain and ecchymosis in his right leg and foot after injection of benzathine penicilline. There was a localized gangrenous area at the femoral injection site. Doppler ultrasonography showed no arterial flow in the femoral artery and clear evidence of acute thrombosis of the superficial femoral and popliteal veins. Femoral arterial and venous thrombectomy and fasciotomy were performed immediately. After surgery the boy was treated by Iloprost infusion and enoxaparine. One week later necrotic changes had regressed, fasciotomies were closed and only the distal phalanx of the third toe needed amputation. Early surgical intervention and standard management combined with Iloprost infusion may help in healing the lesions by increasing extremity perfusion and may prevent extremity loss.

Background: In 2004, the U.S. Preventive Services Task Force strongly recommended that clinicians screen all pregnant women for syphilis infection., Purpose: To update the evidence on screening pregnant women for syphilis infection., Data Sources: MEDLINE searches from 1 January 2003 through 31 July 2008, recent systematic reviews, reference lists of retrieved articles, and expert suggestions., Study Selection: English-language studies were selected to answer the following 2 questions: Does screening for syphilis in pregnancy reduce the prevalence of congenital syphilis in neonates? Are there harms of screening for syphilis or harms of treatment with penicillin in pregnancy to women or neonates? Randomized, controlled trials; meta-analyses; systematic reviews; cohort studies; and ecologic studies were selected for the potential benefits question. Randomized, controlled trials; meta-analyses; systematic reviews; cohort studies; case-control studies; and large case series were selected for the potential harms question., Data Extraction: Information on the study design, selection criteria, demographic characteristics, and clinical outcomes was extracted from each study., Data Synthesis: One study on benefits evaluated the effect before and after the implementation of a universal syphilis screening program for pregnant women and found reductions in rates of congenital syphilis. Two studies on screening accuracy for syphilis reported false-positive rates of less than 1%. One study that used a large insurance claims database reported an incidence of anaphylaxis after oral penicillin of 0.1 per 10,000 dispensings. In a study from Hungary, oral penicillin in pregnancy was not associated with orofacial clefts., Limitations: This was a targeted literature search and could have missed small studies on the benefits and harms of screening for syphilis in pregnancy. We did not review evidence on interventions to improve rates of prenatal screening., Conclusion: New evidence from a study of universal screening supports previous evidence on the effectiveness of screening for syphilis in pregnancy to prevent congenital syphilis. Harms include testing and follow-up for false-positive test results and adverse effects from penicillin treatment.

Description: Update of the 2004 U.S. Preventive Services Task Force statement about screening for syphilis in pregnancy., Methods: The U.S. Preventive Services Task Force did a targeted literature search for evidence on the benefits of screening, the harms of screening, and the harms of treatment of syphilis with penicillin during pregnancy., Recommendation: Screen all pregnant women for syphilis infection. (Grade A recommendation.).

Background and Objectives: Second degree atrioventricular block Mobitz type I is seen as a transitory change in the presence of inferior wall myocardial infarction or drug intoxication. The objective of this report was to present a case of second degree atrioventricular block Mobitz type I after administration of benzathine penicillin., Case Report: The patient had a syncopal episode and sudoresis after administration of benzathine penicillin. On physical exam, he presented diaphoresis, bradycardia, and irregular heart rate. The electrocardiogram (ECG) showed second degree atrioventricular block Mobitz type I. Intravenous atropine, 0.5 mg, was administered. An ECG done one hour later was normal. The patient remained asymptomatic and, and after six hours he was discharged., Conclusions: The patient developed second degree atrioventricular block Mobitz type I after the administration of benzathine penicillin.

Nicolau syndrome (NS) is a rare complication of an intramuscular injection characterized by severe pain, skin discoloration, and varying levels of tissue necrosis. The case outcomes vary from atrophic ulcers and severe pain to sepsis and limb amputation. We describe a case of a seven-year-old boy with diagnosis of NS after intramuscular benzathine penicillin injection to the ventrolateral aspect of the left thigh. Characteristic violaceous discoloration of skin and immediate injection site pain identified it as a case of NS. The case was complicated by rapid progression of compartment syndrome of the lower limb, proceeding to acute renal failure and death. Associated compartment syndrome can be postulated as a poor prognostic factor for NS.

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.

In this paper a case of good tolerance to benzathine benzylpenicillin, but benzylpenicillin potassium allergy in subject with history of multidrug hypersensitivity was described. The same therapeutic agent is contained in both commercial drugs and dosage formulation can cause the unpredictable adverse drug reactions (ADRs). This thesis was confirmed by positive intradermal test with the same, but negative with other commercial product of benzylpenicillin potassium. Later chromatographic analysis shows drug contaminations. Thus an exclusion of allergy to drug impurities (and additives) is necessary for correct diagnosis benzylpenicillin allergy (and any active constituent). Furthermore, allergy to drug impurities (and additives) closely resemble cross-reactions or multiple chemical sensitivity syndrome (MCSS).

We report a case of sudden hearing loss in a patient with acute exudative tonsillitis, occurring 15 minutes after the intramuscular administration of penicillin. Audiological evaluation documented a profound sensorineural hearing loss of the cochlear type. The mechanism of the hearing loss was probably an immediate hypersensitivity (type I) allergic drug reaction. Penicillin is used frequently for the treatment of several infections. Allergic reactions to penicillin are well known and include urticaria, maculopapular exanthems, angio-oedema, bronchospasm and anaphylaxis, but sudden hearing loss has never been recorded.

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.

Objective: To determine whether injection of patients with Bicillin CR is less painful than injection with Bicillin LA. To discover if Bicillin CR with the addition of procaine, which doubles the volume, causes the injection to be less painful., Design: An experimental, double-blinded crossover design was used for this study., Setting: University children's and women's tertiary care emergency Department (ED) with an annual pediatric census of 22,000., Participants: A convenience sample was enrolled from the student body of a large university and house staff, and employees of a 152 bed children's and women's hospital in southern Alabama. The sample size was limited to 50 participants, all of whom completed the study., Methods: Each participant received two penicillin injections, one Bicillin CR and one Bicillin LA, and rated the pain of the injection immediately after the injection, 1 hour after the injection and 12 hours after the injection. A visual analogue scale was the tool used for measuring the pain. The penicillin injections were randomized using a random number generator., Results: For each of the three periods, comparisons of pain were made between the Bicillin CR versus Bicillin LA injections. Bicillin LA pain score values were consistently higher for all but the 12-hour comparison. These differences were statistically significant (P < 0.008-0.002)., Conclusions: Injection of Bicillin CR with the addition of procaine to the benzathine penicillin G is statistically significantly less painful than the injection of Bicillin LA without the addition of procaine to the benzathine penicillin G, even though the Bicillin LA is one-half the volume of the Bicillin CR due to the addition of procaine to the Bicillin CR.

The authors presents two cases report of allergic retinal vasculitis and allergic optic neuropathy after anaphylactic shock due to the parenteral Moldamin administration. Clinicians should be aware of the possibilities of hypersensitivity ocular reaction in anaphylactic shock, with dramatic consequence on the vision.

Penicillin-induced immune haemolytic anaemia is very rare. A ten year-old-female with rheumatic mitral stenosis on benzathine penicillin prophylaxis presented with features of haemolytic anaemia and investigations supported the diagnosis of immune haemolytic anaemia. Patient responded to discontinuation of the drug and therapy with oral prednisolone. This is first such case reported from India.

A 3-year old girl had localized lipoatrophy after an intragluteal injection of benzathine penicillin G. No associated abnormalities were found.