RESUMO
Mycoplasma genitalium is a sexually transmitted infection ordinarily treated with azithromycin. Emerging resistance to macrolide is linked to mutations in the 23S rRNA gene. We analysed the frequency of such mutations of M. genitalium isolates from patients that were symptomatic, and from sexual partners of symptomatic individuals, from October to December of 2015, in the Skåne Region of Sweden. Mutations were analysed by the use of DNA sequencing. Overall, 11.9% (145/1,311) and 17.0% (116/704) of females and males were positive for M. genitalium, respectively. Macrolide resistant mutations were detected in 13% (31/239) of M. genitalium isolates from first-test patient samples. Twenty-one (8.8%) and 10 (4.2%) of the isolates had point mutations of the 23S-gene at position 2072 and 2071, respectively. Two different M. genitalium isolates were detected simultaneously in two cases. In summary, we found a relatively low rate of macrolide-resistant M. genitalium in the region of Southern Sweden.
Assuntos
Antibacterianos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Macrolídeos/uso terapêutico , Mutação , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/efeitos dos fármacos , Mycoplasma genitalium/genética , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/transmissão , Estudos Retrospectivos , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , Doenças Bacterianas Sexualmente Transmissíveis/transmissão , Suécia/epidemiologia , Adulto JovemRESUMO
The antibiotic spectinomycin is a potent inhibitor of bacterial protein synthesis with a unique mechanism of action and an excellent safety index, but it lacks antibacterial activity against most clinically important pathogens. A series of N-benzyl-substituted 3'-(R)-3'-aminomethyl-3'-hydroxy spectinomycins was developed on the basis of a computational analysis of the aminomethyl spectinomycin binding site and structure-guided synthesis. These compounds had ribosomal inhibition values comparable to spectinomycin but showed increased potency against the common respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Moraxella catarrhalis, as well as the sexually transmitted bacteria Neisseria gonorrhoeae and Chlamydia trachomatis. Non-ribosome-binding 3'-(S) isomers of the lead compounds demonstrated weak inhibitory activity in in vitro protein translation assays and poor antibacterial activity, indicating that the antibacterial activity of the series remains on target against the ribosome. Compounds also demonstrated no mammalian cytotoxicity, improved microsomal stability, and favorable pharmacokinetic properties in rats. The lead compound from the series exhibited excellent chemical stability superior to spectinomycin; no interaction with a panel of human receptors and drug metabolism enzymes, suggesting low potential for adverse reactions or drug-drug interactions in vivo; activity in vitro against a panel of penicillin-, macrolide-, and cephalosporin-resistant S. pneumoniae clinical isolates; and the ability to cure mice of fatal pneumococcal pneumonia and sepsis at a dose of 5 mg/kg. Together, these studies indicate that N-benzyl aminomethyl spectinomycins are suitable for further development to treat drug-resistant respiratory tract and sexually transmitted bacterial infections.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Descoberta de Drogas , Farmacorresistência Bacteriana , Infecções Respiratórias/tratamento farmacológico , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , Espectinomicina/farmacologia , Animais , Antibacterianos/efeitos adversos , Antibacterianos/síntese química , Antibacterianos/farmacocinética , Bactérias/metabolismo , Bactérias/patogenicidade , Proteínas de Bactérias/biossíntese , Chlorocebus aethiops , Simulação por Computador , Desenho Assistido por Computador , Modelos Animais de Doenças , Interações Medicamentosas , Estabilidade de Medicamentos , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/microbiologia , Ribossomos/efeitos dos fármacos , Ribossomos/metabolismo , Doenças Bacterianas Sexualmente Transmissíveis/diagnóstico , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , Espectinomicina/efeitos adversos , Espectinomicina/análogos & derivados , Espectinomicina/síntese química , Espectinomicina/farmacocinética , Relação Estrutura-Atividade , Células VeroRESUMO
A novel, one-step electrochemical biosensing technique has been developed by utilizing a strategy in which a biomolecule controls transport of CdS-signaling nanoparticles to the surface of an electrode. The viability of this approach was explored using DNA as a model target biomolecule. The capture and signaling probes both contain nucleic acid sequences that are complementary to the target DNA. The detection chamber consists of a gold matrix modified with the capture probe on the bottom, a glassy carbon (GC) working electrode on the top, and a buffered electrolyte containing the signaling probe conjugated with the CdS nanoparticle. When target DNA is not present in the chamber, the CdS-signaling probe is freely transported to the GC electrode where CdS accumulates during the preconcentration step and undergoes electrochemical anodic stripping voltammetry (ASV) that subsequently generates a current signal during the following oxidative stripping step. On the other hand, target DNA present in the sample undergoes simultaneous hybridization to both the capture and signaling probes in a sandwich-like manner. This phenomenon leads to fixation of the CdS nanoparticles on the bottom of the chamber, thus preventing their electrochemical reduction on the GC electrode. As a result, the electrochemical signal is reduced in the presence of target DNA. Based on the reduction of the current signal, target DNA from C. trachomatis was successfully detected without the need for any complicated secondary procedures. This electrochemical one-step detection method could serve as a conceptually new technology enabling highly convenient biosensing that is applicable to point-of-care testing (POCT).
Assuntos
Técnicas Biossensoriais/métodos , Chlamydia trachomatis/isolamento & purificação , DNA/isolamento & purificação , Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Compostos de Cádmio/química , Chlamydia trachomatis/química , Chlamydia trachomatis/patogenicidade , DNA/química , Ouro/química , Humanos , Hibridização de Ácido Nucleico , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , Transdução de Sinais , Sulfatos/químicaRESUMO
Antibiotic resistance is an emerging public health problem especially due to the continuous use of antibiotics that selects more aggressive and resistant species. In the present study the authors determined the antibiotic sensitivity of 128 Mycoplasma hominis strains obtained from urethral swabs of male patients (mean age 36 years). The Mycoplasma IST 2 strip was used to test antibiotic susceptibility: 88% of analysed strains were found to be resistant to erythromycin and azithromycin, 75% to clarithromycin, 50% to ofloxacin and ciprofloxacin, and 12% to tetracycline. All strains were susceptible to josamycin, doxycycline and pristinamycin. Results were comparable to those of a recent study by Savarino-Mattei which also showed high resistance of M hominis to macrolide antibiotics and to ciprofloxacin and susceptibility to tetracyclines. Doxycycline is currently the antibiotic of first choice for treating M hominis infections.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma hominis/efeitos dos fármacos , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , Adulto , Antibacterianos/farmacologia , Doxiciclina/uso terapêutico , Humanos , Josamicina/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/microbiologia , Mycoplasma hominis/isolamento & purificação , Pristinamicina/uso terapêutico , Saúde Pública , Doenças Bacterianas Sexualmente Transmissíveis/diagnóstico , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , Manejo de Espécimes , Resultado do Tratamento , Uretra/microbiologiaRESUMO
Among 254 Neisseria gonorrhoeae isolates from a sexually transmitted infection (STI) clinic in northern Taiwan, 69 isolates were found to contain the mosaic penA (MA) gene and were associated with elevated cefixime and ceftriaxone MICs. Most of these MA gene-harboring isolates were also resistant to penicillin (71.4%) and ciprofloxacin (100%) and were from men who have sex with men (MSM) or from bisexual men (81.2%). Three major sequence types (ST835, ST2180, and ST2253) constituted 55.7% of these isolates. The major sequence types harboring the mosaic penA gene may represent major sexual networks responsible for the emergence/introduction and the spread of the multidrug-resistant clones in Taiwan.
Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Neisseria gonorrhoeae/efeitos dos fármacos , Proteínas de Ligação às Penicilinas/genética , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/patogenicidade , Penicilinas/farmacologia , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , TaiwanRESUMO
The efficacy of indigal plus containing indol-3-carbinol, epigallocatexin-3-gallat and Serenoa repens extract in combination with sparfloxacin was studied in a trial with participation of 30 patients with chronic infectious prostatitis associated with intracellular agents. Group 1 (n=15) received indigal plus (2 capsules twice a day for 3 months) and sparfloxacin (200 mg twice a day for 1 month). Group 2 including 15 matched controls received sparfloxacin alone according to the same schedule. The examination included questionnaire survey (IPSS, QoL, NIH-CPSI), blood count, urinalysis, PSA test, microscopy, bacteriological study of prostatic secretion, uroflowmetry, transrectal ultrasound investigation of the prostate with residual urine assay, laser doppleroflowmetry. The examinations were performed on the treatment day 30, 60 and 90. After the antibacterial treatment chlamidia, ureaplasma and E.coli were detected in 13.3, 6.7 and 26.7% patients of the control group, in 6.7, 6.7 and 6.7% patients of the study group, respectively. Thus, the addition of a pathogenetic drug indigal plus to sparfloxacin treatment promoted normalization of apoptosis of the infected cells, led to more effective bacterial eradication, enhanced regression of the symptoms. It is recommended to include indigal plus in a basic scheme of treatment of patients with chronic infectious prostatitis.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Próstata/efeitos dos fármacos , Prostatite/tratamento farmacológico , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Apoptose/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Catequina/análogos & derivados , Catequina/uso terapêutico , Doença Crônica , Combinação de Medicamentos , Quimioterapia Combinada , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/uso terapêutico , Humanos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/uso terapêutico , Próstata/diagnóstico por imagem , Próstata/microbiologia , Próstata/patologia , Prostatite/microbiologia , Prostatite/patologia , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , Doenças Bacterianas Sexualmente Transmissíveis/patologia , Inquéritos e Questionários , Resultado do Tratamento , Ultrassonografia , Urodinâmica/efeitos dos fármacosRESUMO
We studied 94 patients with chronic prostatitis (CP) in combination with urogenital chlamydiasis. The patients were divided into three groups. Group 1 consisted of 32 patients with bacterial prostatitis and sexually transmitted infection (STI). They were treated with fromilid in a dose 500 mg twice a day. Group 2 (n = 27) received also low-intensity laser radiation (LILR) on the prostatic gland. Group 3 patients (n = 35) with abacterial prostatitis were given fromilid (500 mg twice a day). We studied prostatic hemodynamics with color doppler mapping. A specific feature of prostatic vascularisation in CP and STI versus healthy subjects is heterogeneous decline of vessels density in ischemic zones with parallel decrease in these vessels diameter. A peripheral prostatic zone in CP patients with STI was characterized by lower vascularisation than central one. This deteriorates the course of the disease. The results of the study show that adjuvant LILR in CP patients with STI raises efficacy of therapy by 11%. Investigation of prostate vascularisation and hemodynamics of its vessels in CP patients with STI using transrectal ultrasonography and dopplerography provide detailed information about prostatic structure allowing for lesion zones. This facilitates choice of an optimal complex treatment with application of LELR in peripheral inflammation of the prostate.
Assuntos
Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Terapia com Luz de Baixa Intensidade , Prostatite , Doenças Bacterianas Sexualmente Transmissíveis , Adolescente , Adulto , Antibacterianos/administração & dosagem , Velocidade do Fluxo Sanguíneo , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/radioterapia , Doença Crônica , Claritromicina/administração & dosagem , Terapia Combinada , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Pentoxifilina/administração & dosagem , Pentoxifilina/uso terapêutico , Próstata/irrigação sanguínea , Próstata/diagnóstico por imagem , Prostatite/tratamento farmacológico , Prostatite/microbiologia , Prostatite/fisiopatologia , Prostatite/radioterapia , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , Doenças Bacterianas Sexualmente Transmissíveis/fisiopatologia , Doenças Bacterianas Sexualmente Transmissíveis/radioterapia , Resultado do Tratamento , Ultrassonografia Doppler em Cores , Vasodilatadores/administração & dosagem , Vasodilatadores/uso terapêuticoRESUMO
A randomized controlled trial was carried out to assess the effectiveness of azithromycin versus a standard regimen with doxycycline/ciprofloxacin in the treatment of sexually transmitted infections in a resource-poor environment. Infection with Chlamydia trachomatis was cured in 23/24 (95.8%) of women in the azithromycin arm versus 19/21 (90.5%) in the doxycycline arm (P = 0.6), resulting in three treatment failures. Gonorrhoea was cured in 55/56 (98.2%) women, with one treatment failure in a patient with concomitant C. trachomatis infection. These results indicate that a single oral dose of azithromycin may prove to be a more effective and convenient treatment for sexually transmitted infections in women in a resource-poor environment
Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Ciprofloxacina/uso terapêutico , Doxiciclina/uso terapêutico , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/economia , Azitromicina/efeitos adversos , Azitromicina/economia , Infecções por Chlamydia/tratamento farmacológico , Ciprofloxacina/economia , Doxiciclina/efeitos adversos , Doxiciclina/economia , Feminino , Seguimentos , Gonorreia/tratamento farmacológico , Recursos em Saúde , Humanos , Doenças Bacterianas Sexualmente Transmissíveis/economia , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , África do Sul , Resultado do TratamentoRESUMO
PROBLEM: Recent reports indicate high incidence of genital infections, most of which are sexually transmitted. Although specific drugs and antibiotics are available for some, a safe spermicidal formulation with wide spectrum antimicrobial action would be a desirable addition to the presently available spermicides. METHODS: Formulations at different dilutions were tested in culture systems on standard strains and clinical isolates including some isolates resistant to drugs. The effect on (HSV)-2 and Chlamydia trachomatis was determined in vivo in progestin sensitized mice. The effect on HIV-1 was investigated in two standardized systems. RESULTS: Polyherbal cream inhibited the growth in culture of clinical isolates of Candida albicans, Candida krusei and Candida tropicalis. Both the polyherbal cream and the Praneem polyherbal pessary inhibited urinary tract Escherichia coli (including multidrug resistant strains), and Neisseria gonorrhoeae (including 2 strains resistant to penicillin). Both formulations manifested virucidal activity against HIV-1 at >2 and 50% dilutions (in two different test systems) on contact for 1-2 min. Intravaginal inoculation of the cream and the pessary suspensions before inoculation of the pathogen prevented lesions and vaginal transmission of HSV-2 and C. trachomatis in progestin sensitized mice. CONCLUSIONS: Polyherbal formulations have wide spectrum antibacterial, antifungal and antiviral effect against the tested sexually transmitted pathogens.