Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study.

BACKGROUND: Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both in vitro and in vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis. METHODS: We used an in vitro culturing system of T. pallidum to perform drug susceptibility testing and applied quantitative PCR targeting the tp0574 gene to measure bacterial growth. To confirm in vivo efficacy, fifteen rabbits were infected intradermally with T. pallidum at eight sites each and randomly allocated to an experimental treatment (linezolid, moxifloxacin, clofazimine) or a control arm (benzathine penicillin G [BPG], untreated). The primary outcome was treatment efficacy defined as the time to lesion healing measured from the date of treatment start. Secondary outcomes were absence of treponemes or treponemal mRNA in injection sites, absence of seroconversion, and cerebrospinal fluid (CSF) abnormalities and negative rabbit infectivity tests (RIT). FINDINGS: Linezolid showed in vitro bactericidal activity at concentrations of 0.5 µg/mL or higher. When administered orally to experimentally infected rabbits, it induced healing of early lesions at a time similar to BPG (hazard ratio 3.84; 95% CI 2.05-7.17; p < 0.0001 compared to untreated controls). In linezolid-treated animals, dark-field microscopy and qPCR assessment showed no presence of treponemes after day 3 post-treatment start, serologic test did not convert to positive, CSF had no abnormalities, and RIT was negative. Moxifloxacin and clofazimine failed to inhibit bacterial growth in vitro and could not cure the infection in the rabbit model. INTERPRETATION: Linezolid, a low-cost oxazolidinone, has in vitro and in vivo activity against T. pallidum, with efficacy similar to BPG in treating treponemal lesions in the animal model. Our findings warrant further research to assess the efficacy of linezolid as an alternative to penicillin G to treat syphilis in human clinical trials. FUNDING: European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement No. 850450).

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

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.

Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy.

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.

Gangrena de Fournier. Perspectivas actuales / Fournier´s gangrene. Current perspectives

La Gangrena de Fournier (GF) es una fascitis necrotizante sinérgica, multimicrobiana, de origen infeccioso, que produce gangrena de piel de región genital, perineal, o perianal. Su mayor frecuencia se observa en pacientes de 20 a 50 años, los varones se afectan más que las hembras en proporción 10:1 y la tasa de mortalidad aún es alta. El manejo clínico debe ser rápido y oportuno, con aplicación intravenosa de líquidos, electrolitos y antibióticos de amplio espectro; a fin de lograr la estabilización hemodinámica del paciente antes de la intervención quirúrgica. La cirugía precoz con debridamiento extenso de tejidos desvitalizados, constituye la base principal del mismo

The Fournier Gangrene (FG) is a synergistic, polymicrobial, necrotizing fasciitis with infectious origin that produces gangrene of the perineal, genital or perianal skin. The number bigger than cases happens between 20 at 50 years, the males are affected more than the females in proportion 10:1 and the mortality rate is high yet. The clinical manage of the GF must be fast and opportune with intravenous application of fluids, electrolytes and systemic broad-spectrum antibiotic therapy; and avoid the hemodynamic stabilization of the patient before the surgery. The precocious surgery with debridament of the necrotizing tissues constitutes the main objective of the treatment

[Quality assessment of antibiotic prescriptions dispensed at public health units in Belo Horizonte, Minas Gerais, Brazil, 2002]. / Avaliação da qualidade das prescrições de antimicrobianos dispensadas em unidades públicas de saúde de Belo Horizonte, Minas Gerais, Brasil, 2002.

Overuse of antibiotics is a public health problem and has raised discussions concerning their rational use. This cross-sectional study focuses on the use of systemic antibiotics under the Belo Horizonte Municipal Health Department, Minas Gerais, Brazil, evaluating prescriptions dispensed in March 2002, based on WHO indicators for antibiotic use. On average, 20% of prescriptions dispensed involved at least one systemic antibiotic, among which approximately 46% originated from health care facilities not belonging to the municipal system itself. Amoxicillin was the most frequently prescribed antibiotic, followed by benzathine penicillin. Recording of technical data (dose, intervals between doses, administration, and treatment period) varied from 23.6 to 99.6%. Some 10% of prescriptions failed to specify the treatment period. The study showed the need for rules to allow quality improvement of antibiotic prescriptions, assuring the rational use of such medication by municipal health services.

Challenging perceptions of non-compliance with rheumatic fever prophylaxis in a remote Aboriginal community.

AIM: To identify factors that affect rheumatic fever prophylaxis for remote-living Aboriginal patients, and to determine the proportion who received adequate prophylaxis. DESIGN AND SETTING: Interview (with analysis based on principles of grounded theory) of patients with a history of rheumatic fever or rheumatic heart disease and their relatives, and health service providers in a remote Aboriginal community; audit of benzathine penicillin coverage of patients with rheumatic heart disease. PARTICIPANTS: 15 patients with rheumatic heart disease or a history of rheumatic fever, 18 relatives and 18 health care workers. RESULTS: Patients felt that the role of the clinic was not only to care for them physically, but that staff should also show nurturing holistic care to generate trust and treatment compliance. Differing expectations between patients and health care providers relating to the responsibility for care of patients absent from the community was a significant factor in patients missing injections. Neither a biomedical understanding of the disease nor a sense of taking responsibility for one's own health were clearly related to treatment uptake. Patients did not generally refuse injections, and 59% received adequate prophylaxis (> 75% of prescribed injections). CONCLUSION: In this Aboriginal community, concepts of being cared for and nurtured, and belonging to a health service were important determinants of compliance.

Profilaxis de la enfermedad reumática / Prophylaxis of rheumatic fever

La enfermedad reumática (ER) es una enfermedad febril multisistématica, afecta el tejido conectivo de articulaciones, corazón, cerebro y piel. Capaz de producir cardiopatía reumática crónica (CRC), tiende a recidivar y afecta de preferencia a la población joven. Para que un individuo enferme de una susceptibilidad propia y de una infección faringoamigdalina por S. pyogenes. se ha estimado que en el mundo existen 12 millones de personas afectadas por ER/CRC y que mueren 400.000 al año. En chile la incidencia ha disminuido lenta y sostenidamente hasta 0,6/100.000 habitantes en 1990. Estudios publicados en 1950 demostraron que se podían prevenir los episodios de ER activa erradicando el S. pyogenes de la faringe(profilaxis primaria) y que con terapia antiestreptocóccica mantenida se evitaban las recaídas de episodios agudos de ER (profilaxis secundaria). Durante más de 40 años el antimicrobiano de elección, tanto para profilaxis primaria como secundaria, ha sido la penicilina, que requiere un tiempo de acción de al menos 10 días para erradicar el S. pyogenes de faringe. Para el tratamiento de la faringoamigdalitis estreptocóccica se recomienda su uso en forma de penicilina benzatina o bien oral, por 10 días. En los últimos años han surgido terapias alternativas, especialmente con cefalosporinas; quienes las recomiendan alegan un mayor porcentaje de erradicación faríngea de S. pyogenes. Sin embargo ningún tratamiento lo erradica en el 100 por ciento de los casos, la mayoría de las alternativas requiere también 10 días de tratamiento y son de alto costo, lo que atenta contra la adhesividad al tratamiento y riesgo de no cumplir su objetivo final, la cual es prevenir la ER activa. Lo anterior ha hecho que la AAP, la AAC y la OMS sigan recomendando la penicilina para el, tratamiento de la faringoamigdalitis causada por S. pyogenes. La profilaxis secundarias con penicilina benzatina cada 4 semanas ha demostrado en el tiempo ser eficaz en prevenir las recidivasde ER activa y en disminuir la letalidad por CRC. La duración en el tiempo de la profilaxis secundaria depende del tipo y gravedad del episodio de ER activa y de la edad del enfermo

A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda.

OBJECTIVE: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. STUDY DESIGN: Randomized, controlled, community-based trial in Rakai District, Uganda. METHODS: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. RESULTS: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. CONCLUSIONS: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

PIP: An ongoing (1994-98) randomized, community-based trial in Uganda's Rakai District is assessing the assumption that intensive sexually transmitted disease (STD) control efforts result in marked declines in HIV/AIDS prevalence. Described, in this article, are the project design and findings of the first-round baseline survey. 56 communities were grouped into 10 clusters designed to encompass social/sexual networks and clusters within blocks were randomly assigned to the intervention or control arm. All consenting permanent residents of the district are visited in their homes at 10-month intervals where they are administered extensive questionnaires, provide urine and vaginal swab samples, and are offered mass treatment regardless of symptoms or laboratory testing (single oral dose STD treatment in the intervention arm and anthelmintics and iron folate in the control arm). Both groups receive identical health education, condom promotion, and serologic counseling services. In the first round of home visits, 5834 intervention and 5784 control arm subjects were enrolled, representing about 90% of eligible adults. The groups were comparable in terms of sociodemographic and behavioral characteristics and baseline rates of HIV and STDs. 16.9% of subjects were HIV-positive, 10.0% had syphilis, 23.8% of women had trichomonas, and 50.9% had bacterial vaginosis. Detailed STD assessment is expected not only to document the relationship between STD control and HIV, but also to identify which STDs confer the greatest population attributable risk for HIV transmission, facilitating targeted control efforts in the future.

Processo cicatricial utilizando Staphisagria e Penicilina apos rumenotomia experimental em caprinos / Healing process employ of penicilin and Staphisagria in goat after experimental rumenotomy. (AU)

Com o objetivo de avaliar a evolucao do processo cicatricial em caprinos submetidos a rumenotomia experimental e, tratados nos pos operatorio com penicilina benzatina e Staphisagria, 30 cabras foram divididas em 3 grupos com 10 animais cada, e submetidas a intervencao cirurgica recebendo em seguida a terapeutica determinada para seu grupo. Avaliacoes clinicas foram feitas pelo periodo de 15 dias, sendo em seguida realizado biopsia da cicatriz da pele ao rumem. Os resultados obtidos demonstraram nao haver diferenca significativa no processo cicatricial dos animais que receberam diferentes tratamentos.(AU)

Acquired ocular syphilis: diagnosis and treatment.

We present our findings in 14 patients with a serologically verified diagnosis of ocular syphilis. Although most patients had iridocyclitis, other ocular findings included episcleritis, scleritis, vitritis, retinitis, papillitis, panuveitis, cystoid macular edema, and retinal detachment. Most patients had only ocular manifestations of syphilis with no other definitive symptoms. Without the use of specific treponemal serologic tests, the diagnosis of ocular syphilis would have been missed in at least 20% of patients. Furthermore, 80% of patients were negative for antibody to syphilis in the cerebrospinal fluid, and therefore, this test should not be used to determine treatment for ocular syphilis. Currently, the most effective therapy for ocular syphilis is the same as that for neurosyphilis (i.e., high-dose intravenous penicillin G 12 to 24 million units/day for ten to 14 days). Human immunodeficiency virus-positive patients should receive a full 14 days of high-dose intravenous penicillin G plus intramuscular benzathine penicillin 2.4 million units weekly for three weeks because their immune defenses are likely to be impaired.

Clindamycin treatment of chronic pharyngeal carriage of group A streptococci.

We previously demonstrated that chronic pharyngeal carriage of group A beta-hemolytic streptococci (GABHS) can be terminated by intramuscular administration of benzathine penicillin plus 4 days of orally administered rifampin. Because an effective oral regimen would be desirable, we compared clindamycin with P + R for treating GABHS carriage. Healthy, symptom-free GABHS carriers were randomly assigned to receive orally administered clindamycin (20 mg/kg per day) three times a day for 10 days or intramuscularly administered benzathine penicillin with oral doses of rifampin (20 mg/kg per day) twice a day for 4 days. Compliance was documented by antibiotic activity in urine. Throat cultures for GABHS were obtained every 3 weeks for up to 9 weeks after treatment. Patients who had positive throat cultures for their original GABHS T type 3 weeks after randomization were crossed over to the other treatment. Treatment success was defined as eradication of the original GABHS T type, with all follow-up cultures negative. Clindamycin eradicated carriage in 24 (92%) of 26 patients; penicillin plus rifampin was effective in 12 (55%) of 22 patients (p less than 0.025). Including patients crossed over 3 weeks after enrollment, clindamycin was effective in 28 (85%) of 33 treatment courses compared with 12 of 22 courses of penicillin plus rifampin (p less than 0.05). We conclude that 10 days of oral clindamycin therapy was significantly more effective than benzathine penicillin plus 4 days of orally administered rifampin for treatment of symptom-free GABHS carriers.

The ocular manifestations of syphilis in the human immunodeficiency virus type 1-infected host.

Nine patients with active ocular or optic nerve involvement by syphilis who also had concurrent human immunodeficiency virus type-1 (HIV-1) infection are described. The ocular manifestations of syphilis led to the discovery of HIV-1 seropositivity in four of nine cases. Fifteen eyes were affected. Ocular manifestations were: iridocyclitis in three eyes, vitreitis in one eye, retinitis or neuroretinitis in five eyes, papillitis in two eyes, optic perineuritis in two eyes, and retrobulbar optic neuritis in two eyes. Three patients diagnosed with acquired immune deficiency syndrome (AIDS) had the worst initial visual acuities. Six of nine patients had evidence of concomitant central nervous syndrome (CNS) involvement with syphilis. Benzathine penicillin was administered intramuscularly to three patients. All three had relapses. Seven of nine patients treated intravenously with high-dose penicillin had dramatic responses to therapy with improvement in vision and serologies and no evidence of relapse. Regimens accepted for the treatment of neurosyphilis appear to be adequate for the treatment of ocular syphilis in HIV-1-infected patients though further long-term follow-up will be required.

Randomised observer blind comparative trial of ceftriaxone and penicillin in treating uncomplicated gonorrhoea in men and women.

Ceftriaxone is a third generation cephalosporin with a prolonged half life. It was used in doses of 500 mg intramuscularly in 27 men (group 1) and 23 women (group 2) and 250 mg in 48 men (group 3) and 45 women (group 4) with uncomplicated urogenital gonorrhoea. Similar numbers of patients in each group were treated with 2 MIU intramuscular Bicillin (procaine penicillin 1.5 g plus benzylpenicillin 300 mg (Brocades, Weybridge, Surrey, England). Success of treatment was measured as one or two negative cultures after three or more days. The success rate for ceftriaxone was 100% in 19 evaluable men and 19 women treated with 500 mg and in 38 men and 31 women treated with 250 mg, including one infection due to penicillinase producing Neisseria gonorrhoeae (PPNG). Success rates for Bicillin were 90% (19/21) evaluable patients cured in group 1, 100% (19/19) in group 2, 95% (37/39) in group 3, and 92% (33/36) in group 4. Both drugs were well tolerated. Each isolate of N gonorrhoeae isolated was sensitive to 0.05 mg/l or less of ceftriaxone.

Evaluation of Sch 29482 in experimental syphilis and comparison with penicillin G benzathine in disseminated disease and localized infection.

The present study was designed to assess the in vivo activity of Sch 29482, a new penem antibiotic, against disseminated and localized Treponema pallidum infections in rabbits. Animals were inoculated either intravenously or intradermally. Randomized groups then received 25 or 50 mg of Sch 29482 per kilogram of body weight twice a day for 7 days, two weekly injections of 200,000 U of penicillin G benzathine for comparative purposes, or no antibiotic therapy. In both infection models, striking differences were noted between the untreated control rabbits and rabbits receiving penicillin G benzathine or high-dose Sch 29482. Intravenously infected rabbits did not develop disseminated lesions or orchitis, and chancres produced by intradermal infection regressed and healed rapidly after both treatment regimens. Infectivity studies also suggested that high-dose Sch 29482 and penicillin G benzathine were effective since the testes and lymph nodes of treated animals were free of infectious organisms. Treatment of animals with the lower dose of Sch 29482 represented borderline or suboptimal therapy, with a failure rate of one in four for each infection model.

In vitro and in vivo evaluation of benzamidomethyl-benzylpenicillinate (FI7303). A new 'repository' form.

A new type of hydrolyzable ester of penicillin G, benzamidomethyl benzylpenicillinate (FI 7303), was studied for the antibacterial activity and kinetics of absorption in comparison with DBED-penicillin G. FI 7303 resulted to be a good repository form of penicillin G, slowly eliminated in mouse, dog and man. It exerted a remarkable therapeutic activity in mice infected with Staphylococcus aureus even when administered 26 h before infection. The protective effect in mice was more prolonged than that of DBED-penicillin G, in agreement with the longer persistence of significant blood levels.