Subcutaneous infusion of high-dose benzathine penicillin G is safe, tolerable, and suitable for less-frequent dosing for rheumatic heart disease secondary prophylaxis: a phase 1 open-label population pharmacokinetic study.

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 (t1/2 = 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.

Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial.

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).

Report: Metformin potential in predisposing arthralgia, type II cross reactivity secondary to group A streptococcus infection & other comorbidities in treating PCOS.

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.

Interventions for the prevention of recurrent erysipelas and cellulitis.

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.

[Nicolau livedoid dermatitis with severe neurological involvement in a child]. / Dermite livédoïde de Nicolau avec atteinte neurologique sévère chez un enfant.

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.

Acute Transverse Myelitis and Nicolau Syndrome after Benzathine Penicillin Injection.

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.

Reducing the pain of intramuscular benzathine penicillin injections in the rheumatic fever population of Counties Manukau District Health Board.

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.

Confirmed penicillin allergy among patients receiving benzathine penicillin prophylaxis for acute rheumatic fever.

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.

A 25-Year-Old Military Recruit with Isolated Myositis Following Routine Chemoprophylaxis with Intramuscular Benzathine Penicillin G.

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.

Pharmacokinetics and Safety of Intramuscular Injectable Benzathine Penicillin G in Japanese Healthy Participants.

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 Cmax (tmax) of 48 h post-dose. After the achievement of Cmax, concentrations of penicillin G declined slowly in a monophasic fashion with a mean apparent terminal half-life of 189 h. Geometric mean AUCinf and Cmax 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.

Azithromycin versus penicillin G benzathine for early syphilis.

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.

Penicillin Reactions in Patients With Severe Rheumatic Heart Disease: A Presidential Advisory From the American Heart Association.

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.

Spinal cord ischaemia following the gluteal injection of Benzathine benzylpenicillin.

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.

Adverse effects associated with inadvertent intravenous penicillin G procaine-penicillin G benzathine administration in two dogs and a cat.

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.

Screening for syphilis infection in pregnancy: U.S. Preventive Services Task Force reaffirmation recommendation statement.

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.).

Screening for syphilis infection in pregnant women: evidence for the U.S. Preventive Services Task Force reaffirmation recommendation statement.

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.

Nicolau livedoid dermatitis following intramuscular benzathine penicillin injection.

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.

Nicolau syndrome following intramuscular benzathine penicillin injection: a case report.

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.

[Severe acute limb ischemia resulting in rescue disarticulation in a patient with Nicolau syndrome following intramuscular penicillin injection: a case report]. / Ischémie aiguë de membre sévère sanctionnée par désarticulation de sauvetage dans un contexte de syndrome de Nicolau suite à une injection intramusculaire de pénicilline: à propos d'un cas.

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.