Neisseria gonorrhoeae: un patógeno díscolo: conceptos microbiológicos, resistencia a antimicrobianos y su vigilancia epidemiológica en Chile / Neisseria gonorrhoeae: a wayward pathogen: microbiological concepts, antimicrobial resistance and its epidemiological surveillance in Chile

Resumen Neisseria gonorrhoeae es un diplococo gramnegativo, no móvil, esporulado, aerobio o anaerobio facultativo, catalasa y oxidasa positivas. Las infecciones de transmisión sexual causadas por este microorganismo son un problema de salud pública definido como tal desde el siglo XIX, representando una gran amenaza para la salud humana debido a la su alta prevalencia y multirresistencia a antimicrobianos. En las últimas décadas han aumentado los reportes de cepas resistentes a penicilina, fluoroquinolonas, sulfonamidas, tetraciclina, macrólidos, y más recientemente a cefalosporinas y azitromicina. Tal panorama ha generado preocupación a nivel mundial, debido al aumento de casos de gonorrea asociados a cepas multirresistentes. En Chile se desarrolló desde el 2010 hasta el 2018 el Programa de Vigilancia de N. gonorrhoeae a nivel nacional con el objeto de caracterizar esta infección en las regiones y registrar la resistencia a los antimicrobianos. Esta revisión presenta un análisis sistemático bibliográfico, actualizado, de los principales aspectos de este microorganismo, su respuesta a antimicrobianos, y entrega pautas de diagnóstico y tratamiento, a la espera de avanzar en la comprensión del mecanismo molecular y las interacciones metabólicas e inmunológicas que determinan la infección, con miras a diseñar una vacuna efectiva.

Abstract Neisseria gonorrhoeae is a nonmotile, sporulated, aerobic or facultative anaerobic gram-negative diplococcus, catalase and oxidase positive. Sexually transmitted infections caused by this microorganism were established as public health problem since the 19th century, representing a great threat to human health due to its high prevalence and multi-resistance to antimicrobials. In recent decades, reports of strains resistant to penicillin, fluoroquinolones, sulfonamides, tetracycline, macrolides, and more recently to cephalosporins and azithromycin have increased. Such a panorama has generated concern worldwide, due to the increase in cases of gonorrhea associated with multi-resistant strains. In Chile, from 2010 to 2018, the National Surveillance Program for N. gonorrhoeae was developed in order to characterize this infection in the regions and record antimicrobial resistance. This review presents an updated, systematic bibliographic analysis of the main aspects of this microorganism, its response to antimicrobials, and provides diagnostic and treatment guidelines, while waiting to advance in the understanding of the molecular mechanism and the metabolic and immunological interactions that determine infection, with a view to designing an effective vaccine.

Temporal evolution of antimicrobial resistance among Neisseria gonorrhoeae clinical isolates in the most populated South American Metropolitan Region

A total of 124 Neisseria gonorrhoeae isolates recovered during a 12-year period (2003-2015) from outpatients assisted at Centro de Referência e Treinamento DST/AIDS-CRT of São Paulo city, Brazil, were analysed. The following resistance rates were observed: penicillin-59.6%, ciprofloxacin-15.3%, and azithromycin-6.7%. Although reduced susceptibility to these drugs was observed since 2003, no ceftriaxone-resistant isolates were detected. Ciprofloxacin- and azithromycin non-susceptible isolates were grouped in 11 clusters. Mutations were detected in GyrA and ParC of isolates 124 and 260, and a C2611T substitution on 23S rRNA alleles was also observed in isolate 260. Both isolates belonged to ST1901/ST6210 (MSLT/NG-MAST schemes).

Resistência de Neisseria gonorrhoeae a antimicrobianos na prática clínica: como está o Brasil? / Antimicrobials resistance of Neisseria gonorrhoeae in clinical practice: where Brazil stands?

Estima-se que um milhão de infecções sexualmente transmissíveis (IST) sejam adquiridas por dia no mundo, segundo a Organização Mundial da Saúde. Elas podem ser causadas por diversos micro-organismos pelo contato sexual. Embora tratáveis, as infecções, como a clamidiana, sífilis, tricomoníase e gonorreia, são responsáveis por 350 milhões de novos casos de IST anualmente no mundo. A gonorreia é a segunda IST bacteriana mais prevalente no planeta e tem chamado atenção nos últimos anos em decorrência da baixa eficácia em seu tratamento. O agente etiológico é a Neisseria gonorrhoeae. Na maioria das mulheres, a infecção por esse micro-organismo é assintomática, dificultando ainda mais seu diagnóstico e tratamento e, portanto, aumentando o risco de desenvolvimento de suas complicações associadas. Mesmo quando diagnosticada, essa infecção está sujeita a um alto índice de insucesso terapêutico que se deve, principalmente, à grande plasticidade genética da N. gonorrhoeae para aquisição de genes cromossômicos ou plasmidiais de resistência. O aumento da resistência desse micro-organismo a antimicrobianos comumente utilizados no tratamento, como penicilina, tetraciclina e ciprofloxacina, tem sido relatado em diversos países. No Brasil, poucos estudos estão disponíveis, mas em alguns estados já foram relatadas linhagens resistentes à ciprofloxacina. Dessa forma, deve-se ressaltar a importância de novos estudos que visem descrever o perfil da resistência da N. gonorrhoeae a antimicrobianos. Tais achados certamente nortearão a implementação de sistemas de vigilância epidemiológica no país visto que, até o momento, as infecções por N. gonorrhoeae sequer estão incluídas na lista nacional de doenças e agravos de notificação compulsória.(AU)

According to the World Health Organization, approximately one million sexually transmitted infections (STI) are acquired daily in the world. These infections can be caused by several microorganisms via contact. The treatable STI, such as chlamydia, syphilis, trichomoniasis and gonorrhea, account for 350 million new cases of STI each year worldwide. Gonorrhoea is caused by Neisseria gonorrhoeae and is the second most common bacterial STI in the world. It has drawn more attention in the last years due to the low efficacy in its treatment. Most women with this infection are asymptomatic, which makes its diagnosis and treatment troublesome increasing the risk for its associated complications. Even when diagnosed, this infection is subject to a high rate of therapeutic failure mainly due to the great genetic plasticity of N. gonorrhoeae for the acquisition of chromosomal or resistance plasmid enes. Increased resistance of this microorganism to antimicrobials commonly used in treatment such as penicillin, tetracycline and ciprofloxacin has been reported in several countries. In Brazil, few studies are available, but in some states strains resistant to ciprofloxacin were alreadyreported. The refore, it is important to highlight the importance of new studies aimed at describing the resistance profile of N. gonorrhoeae to antimicrobials in Brazil context. These findings will certainly guide the implementation of epidemiological surveillance systems in the country, since until now N. gonorrhoeae infections do not figure into the national list of compulsorily notifiable diseases.(AU)

Antimicrobial resistance in Neisseria gonorrhoeae: history, molecular mechanisms and epidemiological aspects of an emerging global threat

ABSTRACT Neisseria gonorrhoeae is the agent of gonorrhea, a sexually transmitted infection with an estimate from The World Health Organization of 78 million new cases in people aged 15-49 worldwide during 2012. If left untreated, complications may include pelvic inflammatory disease and infertility. Antimicrobial treatment is usually effective; however, resistance has emerged successively through various molecular mechanisms for all the regularly used therapeutic agents throughout decades. Detection of antimicrobial susceptibility is currently the most critical aspect for N. gonorrhoeae surveillance, however poorly structured health systems pose difficulties. In this review, we compiled data from worldwide reports regarding epidemiology and antimicrobial resistance in N. gonorrhoeae, and highlight the relevance of the implementation of surveillance networks to establish policies for gonorrhea treatment.

Increasing Incidence of High-Level Tetracycline-Resistant Neisseria gonorrhoeae due to Clonal Spread and Foreign Import

PURPOSE: The detection of high-level tetracycline-resistant strains of Neisseria gonorrhoeae (TRNG) can make important epidemiological contributions that are relevant to controlling infections from this pathogen. In this study, we aimed to determine the incidence of TRNG isolates over time and also to investigate the characteristics and genetic epidemiology of these TRNG isolates in Korea. MATERIALS AND METHODS: The antimicrobial susceptibilities of 601 isolates of N. gonorrhoeae from 2004 to 2011 were tested by standard Clinical and Laboratory Standards Institute methods. To determine the molecular epidemiological relatedness, N. gonorrhoeae multi-antigen sequence typing was performed. RESULTS: The incidence of TRNG increased from 2% in 2004 to 21% in 2011. The minimum inhibitory concentration distributions of ceftriaxone and susceptibility of ciprofloxacin in TRNG were different from non-TRNG and varied according to the year of isolation. Most of the TRNG isolates collected from 2004 to 2007 exhibited genetic relatedness, with sequence type (ST) 1798 being the most common. From 2008 to 2011, the STs of the isolates became more variable and introduction of genetically unrelated TRNG were noted. CONCLUSION: The increased incidence of TRNG strains until 2007 appears to be due, at least in part, to clonal spread. However, we propose that the emergence of various STs since 2008 could be associated with foreign import.

Ceftriaxona 500mg para tratamento da Neisseria gonorrhoeae resistente à ciprofloxacina / Ceftriaxone 500mg for treatment of Neisseria gonorrhoeae resistant to ciprofloxacin

CONTEXTO: A gonorreia é uma das infecções bacterianas mais frequentes e é causada pela Neisseria gonorrhoeae. Encontra-se atualmente entre as cinco principais infecções sexualmente transmissíveis mais notificadas na população masculina. Dentre as mudanças propostas pelo PCDT para Infecções Sexualmente Transmissíveis - IST em discussão, recebe destaque a alteração do esquema terapêutico atualmente em uso para o controle da Neisseria gonorrhoeae no Brasil, que prevê a substituição da ciprofloxacina 500mg, dose única via oral, pela ceftriaxona 500mg, dose única via intramuscular. Essa alteração tem como principal objetivo conter o desenvolvimento de maior resistência bacteriana aos antibióticos disponíveis na rede pública para o tratamento desse agravo. TRATAMENTO: Para a escolha do tratamento da infecção gonocócica a OMS estabelece critérios de eficácia, segurança, custo, adesão e disponibilidade, nos seguintes termos: -Eficácia: os medicamentos utilizados devem ter uma taxa de cura de pelo menos 95%. Esquemas terapêuticos com eficácia entre 85% e 95% devem ser utilizados com cautela e abaixo de 85% são considerados inaceitáveis. -Segurança: a presença de efeitos colaterais é a segunda maior preocupação na escolha dos tratamentos e desempenha papel de extrema relevância em mulheres grávidas ou em aleitamento, portanto, o nível de toxicidade deve permanecer dentro de padrões aceitáveis para a saúde do paciente, do feto e do bebê. -Custo: o custo do medicamento deve ser analisado e comparado aos custos de retratamento, eventuais complicações, e risco de transmissão e resistência. -Observância e aceitabilidade: os tratamentos devem ser de preferência em dose única e administrados por via oral. -Disponibilidade: os tratamentos selecionados devem levar em conta a aprovação sanitária no país. Além desses critérios, devem ser consideradas as co-infecções existentes e o risco de redução da eficácia para outras indicações terapêuticas. A TECNOLOGIA: A ceftriaxona é um antibiótico de terceira geração da família da cefalosporina registrado na ANVISA, por meio da Resolução 252 de 5 de março de 2001. O medicamento está disponível no mercado em diferentes apresentações, todas injetáveis, sendo indicado para o tratamento de eventos de sepsemia; meningite; infecções intra-abdominais (peritonites, infecções do trato gastrintestinal e biliar); infecções ósseas, articulares, tecidos moles, pele e feridas; infecções em pacientes imunocomprometidos; infecções renais e do trato urinário; infecções do trato respiratório, particularmente pneumonia e infecções otorrinolaringológicas; infecções genitais, inclusive gonorreia; profilaxia de infecções pré-operatórias; Borreliose de Lyme (Doença de Lyme). RECOMENDAÇÃO DA CONITEC: Na 34ª Reunião da CONITEC, realizada no dia 2 de abril de 2015, os membros do plenário deliberaram por unanimidade recomendar a incorporação da ceftriaxona 500mg injetável para o tratamento de gonorreia resistente à ciprofloxacina, conforme normas técnicas definidas pelo Ministério da Saúde. Foi assinado o Registro de Deliberação nº 110/2015. DECISÃO: PORTARIA Nº 58, de 1 de outubro de 2015 - Torna pública a decisão de incorporar a ceftriaxona 500mg injetável para o tratamento de gonorreia resistente à ciprofloxacina, conforme normas técnicas definidas pelo Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS.

Adaptation and validation of the Inventory of Family Protective Factors for the Portuguese culture / Adaptação e Validação do Instrumento Inventory of Family Protective Factors para a cultura portuguesa / Adaptación y Validación del Instrumento Inventory of Family Protective Factors para la cultura portuguesa

OBJECTIVES: to adapt and validate the Inventory of Family Protective Factors (IFPF) for the Portuguese culture. This instrument assesses protective factors that contribute to family resilience. Studies addressing resilience are embedded within the salutogenic paradigm, i.e. it addresses protective factors of individuals or groups without underestimating risk factors or vulnerability. METHOD: in order to assess the IFPF's linguistic and conceptual equivalence, the instrument was translated, retro-translated and the think-aloud protocol was used. We then verified the instrument's sensitiveness, reliability and validity of results to assess its psychometric characteristics. A factor analysis was performed of the principal components with varimax rotation of the scale's items and Cronbach's alpha coefficient was calculated for each dimension. A total of 85 families with disabled children, selected through simple random sampling, self-administered the instrument. RESULTS: the IFPF presents psychometric characteristics that are appropriate for the Portuguese population (Cronbach's alpha = .90). CONCLUSION: the IFPF was adapted and validated for the Portuguese culture and is an instrument to be used in studies intended to assess protective factors of family resilience. .

OBJETIVOS: adaptar e validar o Inventory of Family Protective Factors para a cultura portuguesa. Esse instrumento avalia os fatores protetores que contribuem para a resiliência familiar. Os estudos sobre resiliência inserem-se no paradigma salutogênico, abordando os fatores protetores dos indivíduos, ou grupos, sem subestimar os fatores de risco ou vulnerabilidade. MÉTODO: para avaliar a equivalência linguística e conceitual do Inventory of Family Protective Factors realizou-se a tradução, retroversão e reflexão falada; para aferir as características psicométricas do instrumento, verificou-se a sensibilidade, confiabilidade e a validade dos resultados. Foi realizada uma análise fatorial de componentes principais com rotação Varimax dos itens da escala e calculou-se o coeficiente alfa de Cronbach para cada dimensão. Através de uma amostragem aleatória simples, aplicou-se esse instrumento a 85 famílias de crianças com necessidades especiais que o autopreencheram. RESULTADOS: o Inventory of Family Protective Factors apresenta características psicométricas adequadas para a população portuguesa (alfa de Cronbach de .90). CONCLUSÃO: o Inventory of Family Protective Factors foi adaptado e validado para a cultura portuguesa. Considera-se que se trata de um instrumento útil para estudos nos quais há a proposta de avaliar os fatores protetores da resiliência familiar. .

OBJETIVOS: adaptar y validar el Inventory of Family Protective Factors (IFPF) para la cultura portuguesa. Este instrumento evalúa los factores protectores que contribuyen para la resiliencia familiar. Los estudios sobre resiliencia se insieren en el paradigma salutogénico, abordando los factores protectores de los individuos o grupos, sin subestimar los factores de riesgo o vulnerabilidad. MÉTODO: para evaluar la equivalencia lingüística y conceptual del IFPF realizamos la traducción, retrotraducción y reflexión hablada; para evaluar las características psicométricas del instrumento verificamos la sensibilidad, confiabilidad y la validez de los resultados. Realizamos un análisis factorial de los componentes principales con rotación varimax de los ítems de la escala y calculamos el coeficiente Alpha de Cronbach para cada dimensión. A través de un muestreo aleatorio simple, aplicamos este instrumento a 85 familias de niños con necesidades especiales que lo autollenaron. RESULTADOS: el IFPF presenta características psicométricas adecuadas para la población portuguesa (alfa de Cronbach de 0,90). CONCLUSIÓN: el IFPF fue adaptado y validado para la cultura portuguesa. Consideramos que se trata de un instrumento útil para estudios que se propongan evaluar los factores protectores de la resiliencia familiar. .

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from patients attending a public referral center for sexually transmitted diseases in Belo Horizonte, State of Minas Gerais, Brazil

Introduction The aim of this study was to determine the antimicrobial susceptibility of Neisseria gonorrhoeae isolates obtained from patients attending a public referral center for sexually transmitted diseases and specialized care services (STD/SCS) in Belo Horizonte, Brazil. Methods Between March 2011 and February 2012, 201 specimens of Neisseria gonorrhoeae were consecutively obtained from men with symptoms of urethritis and women with symptons of cervicitis or were obtained during their initial consultation. The strains were tested using the disk diffusion method, and the minimum inhibitory concentrations of azithromycin, cefixime, ceftriaxone, ciprofloxacin, chloramphenicol, penicillin, tetracycline and spectinomycin were determined using the E-test. Results The specimens were 100% sensitive to cefixime, ceftriaxone and spectinomycin and exhibited resistances of 4.5% (9/201), 21.4% (43/201), 11.9% (24/201), 22.4% (45/201) and 32.3% (65/201) to azithromycin, ciprofloxacin, chloramphenicol, penicillin and tetracycline, respectively. Intermediate sensitivities of 17.9% (36/201), 4% (8/201), 16.9% (34/201), 71.1% (143/201) and 22.9% (46/201) were observed for azithromycin, ciprofloxacin, chloramphenicol, penicillin and tetracycline, respectively. The specimens had plasmid-mediated resistance to penicillin PPNG 14.5% (29/201) and tetracycline TRNG 11.5% (23/201). Conclusions The high percentage of detected resistance to penicillin, tetracycline, chloramphenicol and ciprofloxacin indicates that these antibiotics are not appropriate for gonorrhea treatment at the Health Clinic and possibly in Belo Horizonte. The resistance and intermediate sensitivity of these isolates indicates that caution is recommended in the use of azithromycin and emphasizes the need to establish mechanisms for the surveillance of antimicrobial resistance for the effective control of gonorrhea. .

Emergence of decreased susceptibility to extended-spectrum cephalosporins in Neisseria gonorrhoeae in India.

Background. In the past, Neisseria gonorrhoeae has developed resistance to antimicrobial agents used for its treatment. Consequently, extended-spectrum cephalosporins form the mainstay of treatment for gonorrhoea. Methods. Samples from 88 patients attending the sexually transmitted diseases clinics from December 2009 to January 2011 in two referral hospitals in New Delhi were studied. Antimicrobial susceptibility testing was done using the disc diffusion method as per the calibrated dichotomous sensitivity technique against the following antibiotics: penicillin (0.5 i.u.), tetracycline (10 μg), nalidixic acid (30 μg), ciprofloxacin (1 μg), spectinomycin (100 μg), ceftriaxone (0.5 μg) and cefpodoxime (10 μg) (Oxoid UK). Azithromycin (15 μg) (Oxoid, UK) was tested as per the guidelines of the Clinical and Laboratory Standards Institute. Minimum inhibitory concentrations were determined using the Etest for penicillin, tetracycline, ciprofloxacin, ceftriaxone, spectinomycin and azithromycin as per the manufacturer’s instruction (Biomerieux, France). Results. Eighteen isolates of Neisseria gonorrhoeae were obtained. Three of these had decreased susceptibility to ceftriaxone and cefpodoxime by the disc diffusion method. The minimum inhibitory concentrations of ceftriaxone for two isolates were 0.064 μg/ml and for one isolate it was 0.125 μg/ml. Conclusion. Higher minimum inhibitory concentrations to extended-spectrum cephalosporins is of concern as it has been shown to precede treatment failure. This may warrant its use in increased/multiple dosages alone or possibly in combination (dual therapy), thereby complicating effective disease control. Our report is in accordance with earlier reports from different parts of the world. Therefore, a continuous surveillance of antimicrobial resistance is crucial to tailor treatment schedules for Neisseria gonorrhoeae in a particular geographical region.

An insight into the drug resistance profile & mechanism of drug resistance in Neisseria gonorrhoeae.

Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neissseria gonorrhoeae is considered to be most important because of emerging antibiotic resistant strains that compromise the effectiveness of treatment of the disease - gonorrhoea. In most of the developing countries, treatment of gonorrhoea relies mainly on syndromic management rather than the aetiological based therapy. Gonococcal infections are usually treated with single-dose therapy with an agent found to cure > 95 per cent of cases. Unfortunately during the last few decades, N. gonorrhoeae has developed resistance not only to less expensive antimicrobials such as sulphonamides, penicillin and tetracyclines but also to fluoroquinolones. The resistance trend of N. gonorrhoeae towards these antimicrobials can be categorised into pre-quinolone, quinolone and post-quinolone era. Among the antimicrobials available so far, only the third-generation cephalosporins could be safely recommended as first-line therapy for gonorrhoea globally. However, resistance to oral third-generation cephalosporins has also started emerging in some countries. Therefore, it has become imperative to initiate sustained national and international efforts to reduce infection and misuse of antibiotics so as to prevent further emergence and spread of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimise treatment regimens, but also to gain insight into how gonococcus develops drug resistance. Knowledge of mechanism of resistance would help us to devise methods to prevent the occurrence of drug resistance against existing and new drugs. Such studies could also help in finding out new drug targets in N. gonorrhoeae and also a possibility of identification of new drugs for treating gonorrhoea.

Fluoroquinolone resistance among Neisseria gonorrhoeae isolates from Shanghai, China: Detection of quinolone resistancedetermining region mutations.

Background & objectives: Fluoroquinolone has a broad spectrum of antimicrobial activity, and is widely used for gonorrhoea treatment. However, its effi cacy can be compromised by the drug-resistance property of Neisseria gonorrhoeae isolates. Most resistant cases of N. gonorrhoeae are associated with mutations in the quinolone-resistance-determining-region (QRDR) within genes of gyrA and parC. This study was undertaken to describe resistance profi le of N. gonorrhoeae to fl uoroquinolones in Shanghai, P.R. of China, and also associated resistance mutations in gyrA and parC. Methods: Eighty N. gonorrhoeae isolates were collected from Shanghai Skin Disease & Sexually Transmitted Disease Hospital or DongFang Hospital during April 2005 to April 2006 in Shanghai, P.R. of China. The minimum inhibitory concentrations (MIC) of fl uoroquinolones for these isolates were determined by an agar dilution method. Mutation patterns within gyrA and parC were determined by direct sequencing or by using established restriction fragment length polymorphisms (RFLP) methods. Results: Ninety fi ve per cent (76 of 80) of isolates were resistant, 3.75 per cent (3 of 80) intermediate resistant, and 1.25 per cent (1 of 80) were sensitive to fl uoroquinolone drug ciprofl oxacin. Sequencing and RFLP analysis of gyrA and parC revealed that all resistant isolates had dual mutations of S91F and D95A/G/N in gyrA. Some isolates had an extra mutation within parC either of D86N, S87N or E91A/G. Mutation patterns for gyrA and parC were signififififi cantly (P<0.05) associated with MICs level. Interpretation & conclusions: Mutations of S91F and D95A/G/N in gyrA combined with S87N in parC was the most prevalent mutation pattern of fl uoroquinolone resistant N. gonorrhoeae isolates. This mutation pattern was associated with a high level of quinolone resistance (MIC >16.0 μg/ml) which can serve as a maker for quinolone-resistance prediction in Shanghai, P.R. of China.

Resistencia de Neisseria gonorrhoeae a ciprofloxacina según hábitos sexuales / Ciprofloxacin resistance of Neisseria gonorrhoeae according to sexual habits

En la Argentina los primeros hallazgos de Neisseria gonorrhoeae resistentes a las fluorquinolonas se documentaron en el año 2000. Desde enero de 2005 hasta junio de 2007, se evaluaron 595 hombres que tienen sexo con hombres (HSH) y 571 varones heterosexuales para investigar la presencia de N. gonorrhoeae y la resistencia a los antimicrobianos. La prevalencia de gonorrea en HSH y varones heterosexuales fue 0.091(91/1000) en ambos grupos y el % de N. gonorrhoeae resistente a ciprofloxacina (NGRC) fue 20.0% y 3.8% respectivamente (p: 0.0416). Trece de 106 aislamientos fueron NGRC, correspondieron a 11 HSH y 2 varones heterosexuales. Seis HSH presentaron uretritis, uno de ellos con localización simultánea en recto y cinco pacientes fueron asintomáticos (recto, 2; faringe, 2; uretra, 1). No se pudo demostrar relación epidemiológica entre ellos. Dos varones heterosexuales presentaron uretritis. Los 8 pacientes sintomáticos fueron tratados empíricamente con ciprofloxacina y se documentó fracaso de tratamiento. Estos y los portadores de NGRC recibieron tratamiento con 500 mg de ceftriaxona IM. Los controles postratamiento demostraron la erradicación del microorganismo. Los aislamientos de NGRC presentaron CIM de ciprofloxacina entre 2 y 32 µg/ml, todos fueron beta-lactamasa negativos, 4/13 presentaron resistencia cromosómica a penicilina (CIM= 1 µg/ml), y los rangos de CIM (µg/ml) para los siguientes antibióticos fueron: penicilina: 0.016-1; tetraciclina: 0.125-2; ceftriaxona: 0.004-0.008; eritromicina: 0.032-2; azitromicina: 0.032-0.5; espectinomicina: 8-32. Dado el elevado porcentaje de aislamientos de NGRC en HSH en nuestro hospital, debería utilizarse otro antimicrobiano para el tratamiento empírico en estos pacientes.

The first isolates of Neisseria gonorrhoeae resistant to fluorquinolones in Argentina were reported in 2000. Since January 2005 to June 2007 Neisseria gonorrhoeae was studied in 595 men who have sex with men (MSM) and 571 heterosexual men. The gonorrhea prevalence in MSM and heterosexual men was 0.091(91/1000) and the Neisseria gonorrhoeae ciprofloxacin resistant (CRNG) was 20% in MSM and 3.8% in heterosexual men (p: 0.0416). Thirteen out of 106 isolates from 11 MSM and 2 heterosexual men were CRNG. Six out of eleven MSM had urethritis, one also carried Neisseria gonorrhoeae in rectum and 5 patients were asymptomatic carriers (rectum 2, pharynx 2, urethra 1). No epidemiological relation was found among the patients. Two heterosexual men had urethritis. The 8 symptomatic men were treated with ciprofloxacin but treatment failed in all of them. These patients and the asymptomatic ones were treated with ceftriaxone, 500 mg IM. The post treatment microbiological controls were negative. The CRNG isolates had ciprofloxacin MIC between 2 and 32 (µg/ml), all were negative to penicillinase, 4 out of 13 were chromosomally resistant to penicillin (MIC: 1 µg/ml). The MICs (µg/ml) ranges for several antimicrobial agents were: penicillin: 0.016-1; tetracycline: 0.125-2; ceftriaxone: 0.004-0.008; erythromycin: 0.032-2; azithromycin: 0.032-0.5; spectinomycin: 8-32. Due to the high level of ciprofloxacin-resistant N. gonorrhoeae isolated from MSM in our hospital, another antimicrobial agent for empirical therapy should be used in these patients.

Vigilancia de la resistencia de Neisseria gonorrhoeae en un hospital de la provincia de Santa Fe, Argentina: 1997-2004 / Resistance surveillance of Neisseria gonorrhoeae in a hospital in Santa Fe province, Argentina: 1997-2004

Se determinaron los fenotipos de resistencia caracterizados por la concentración inhibitoria mínima, la difusión con discos y la producción de β-lactamasa de 434 aislamientos de Neisseria gonorrhoeae obtenidos de pacientes atendidos en el Servicio de Enfermedades de Transmisión Sexual del Hospital Dr. José María Cullen, Santa Fe, Argentina. Se realizaron pruebas de sensibilidad a los siguientes antimicrobianos: penicilina, tetraciclina, ciprofloxacina, espectinomicina, azitromicina y ceftriaxona. A tres aislamientos resistentes a ciprofloxacina se les realizó electroforesis de campo pulsado. Se destacaron tres situaciones epidemiológicas de interés: en el año 1997, alta incidencia de aislamientos con resistencia plasmídica a tetraciclina (33,3%); en el período 2002-2004, un aumento significativo de la resistencia plasmídica a penicilina (9,7% a 34,8%); y en el año 2000, la emergencia de dos de los tres primeros aislamientos con resistencia a quinolonas del país. El primer aislamiento resistente a azitromicina en nuestro hospital emerge en el 2004. Este trabajo jerarquiza el rol del Laboratorio de Microbiología Clínica en la orientación del tratamiento empírico de la gonorrea.

Resistance phenotypes characterized by minimum inhibitory concentration, disk diffusion and β-lactamase production were determined in 434 isolates from patients attending the Sexually Transmitted Disease Service at Dr. José María Cullen Hospital in Santa Fe, Argentina. Susceptibility tests to penicillin, tetracycline, ciprofloxacin, espectinomycin, azithromycin and ceftriaxone were performed. Pulsed-field gel electrophoresis was conducted made to on three ciprofloxacin-resistant isolates. Epidemiologically speaking, three interesting events should be highlighted: during 1997, plasmid-mediated high level tetracycline-resistant strains were observed (33.3%); from 2002 to 2004 a significant increase of plasmid-mediated penicillin-resistant strains was registered (9.7% to 34.8%); and in the year 2000 the first two quinolone-resistant strains emerged in the province. In our hospital, the first azithromycin-resistant isolate emerged in 2004. We therefore emphasize the importance of the Clinical Microbiology Laboratory in order to provide information for the empiric treatment of this infection.

Antimicrobial susceptibility profile of Neisseria gonorrhoeae at STI clinic.

A total of 100 consecutive patients who attended a sexually transmitted infections clinic were studied. Thirteen had gonococcal urethritis, of which 10 showed growth of Neisseria gonorrhoeae on culture. All the isolates were tested for antimicrobial susceptibility by Australian Gonococcal Surveillance Programme (AGSP) method and beta lactamase production by chromogenic cephalosporin test. Four patients were co-infected with each of the following: HIV, HBV and Chlamydia trachomatis . Gonococcal urethritis (13%) was found more in male patients. Ten percent gonococcal isolates were penicillinase-producing N. gonorrhoeae , and another 10% were tetracycline-resistant N. gonorrhoeae .

Correlation between In vitro susceptibility and treatment outcome with azithromycin in gonorrhoea: a prospective study.

PURPOSE: This prospective study was carried out to determine the antimicrobial susceptibility of Neisseria gonorrhoeae isolates by disc diffusion method and minimum inhibitory concentration (MIC) by E -test with special reference to azithromycin. Also, the correlation between in vitro susceptibility and treatment outcome with single 2 g oral dose azithromycin was assessed. METHODS: The study included 75 gonococcal isolates from males with urethritis, females with endocervicitis and their sexual contacts. All isolates were subjected to susceptibility testing for penicillin, ciprofloxacin, tetracycline, ceftriaxone, spectinomycin, cefixime and azithromycin. Males with gonococcal urethritis were randomised to receive a single dose of either azithromycin or ceftriaxone. Forty-two men with urethritis received 2 g single oral dose azithromycin, while all other patients were given 250 mg parentral ceftriaxone. All patients were called for follow-up to assess clinical and microbiological cure rates. RESULTS: While all the isolates were susceptible to ceftriaxone, spectinomycin, cefixime and azithromycin; 74 (98.7%), 24 (32%) and 23 (30.7%) strains were resistant to ciprofloxacin, penicillin and tetracycline respectively, by both disc diffusion method and E -test. The MIC range, MIC50 and MIC90 of N. gonorrhoeae strains, to azithromycin were 0.016-0.25, 0.064 and 0.19 microg/mL, respectively. Follow-up attendance of the patients was 52.4 with 100% clinical and microbiological cure rates. CONCLUSIONS: Results of our study indicate that 2 g single oral dose azithromycin is safe and effective in the treatment of uncomplicated gonorrhoea.

Evaluation of the in vitro activity of six antimicrobial agents against Neisseria gonorrhoeae

Use of antimicrobials for the treatment of gonorrhea started in 1930 with the utilization of sulfonamides. With the years other drugs were used for its treatment such as penicillin, tetracycline, spectinomycin, and others. Although highly specific in the beginning, these drugs, with time did not show anymore the expected therapeutic results because of aspects of chromosomal and plasmid-mediated resistance. The purpose of this study was to evaluate the susceptibility of Neisseria gonorrhoeae strains to six drugs used for its treatment (penicillin, tetracycline, cefoxitin, thiamphenicol, spectinomycin and ofloxacin) by the determination of minimal inhibitory concentrations of these drugs. We concluded that drugs, such as cefoxitin, thiamphenicol and spectinomycin still are excellent pharmacological agents for the treatment of gonorrhea. Penicillin, although still efficient, needs more attention regarding its use, as well as ofloxacin, because of the emergence of resistant strains. Tetracycline and its derivatives should be strongly contraindicated for the treatment of gonorrhea.

A utilização de antimicrobianos no tratamento da gonorréia iniciou-se em 1930 com a utilização das sulfonamidas. No decorrer dos anos outras drogas passaram a ser utilizadas em seu tratamento como a penicilina, tetraciclina, espectinomicina e outras. Embora altamente eficazes no início, essas drogas, ao longo do tempo, passaram a não mais apresentar o resultado terapêutico esperado em virtude do aparecimento de quadros de resistência cromossômica e plasmidial. Este trabalho teve por objetivo avaliar a sensibilidade de cepas de Neisseria gonorrhoeae a seis drogas utilizadas no seu tratamento (penicilina, tetraciclina, cefoxitina, tianfenicol, espectinomicina e ofloxacina) através da concentração inibitória mínima. Concluimos que drogas como a cefoxitina, o tianfenicol e a espectinomicina ainda constituem excelentes fármacos para o tratamento da gonorréia. A penicilina, embora ainda eficaz, enseja maiores cuidados na sua utilização, assim como a ofloxacina, frente ao surgimento de cepas resistentes e, a tetraciclina e seus derivados deve ser sobremaneira contra-indicada no tratamento da gonorréia.

Emergence of ciprofloxacin resistant Neisseria gonorrhoeae in north India.

BACKGROUND AND OBJECTIVES: Though quinolones have been recommended as a single dose treatment for uncomplicated gonorrhoea, there have been reports of treatment failure with fluoroquinolones. In this study we determined the antimicrobial susceptibility levels of consecutive isolates of Neisseria gonorrhoeae to examine the emergence of ciprofloxacin resistance N. gonorrhoeae. METHODS: Minimum inhibitory concentration (MIC) of ciprofloxacin and other drugs (penicillin, tetracycline, ciprofloxacin and ceftriaxone) was determined by agar dilution method. MIC was interpreted according to the NCCLS guidelines. beta lactamase production was detected by iodometric method and chromogenic cephalosporin method using nitrocefin disc. RESULTS: A total of 45 consecutive isolates of N. gonorrhoeae were obtained from patients with suspected acute gonococcal uretheritis. Of the 45 isolates, 35 (77.7%) were resistant to ciprofloxacin, 16 (35.5%) showed MIC value greater than 8 microg/ml. All isolates were sensitive to ceftriaxone while 21 isolates (46.6%) were resistant to penicillin and 23 (51%) to tetracycline. Ten isolates (22%) were found to be beta-lactamase producers. INTERPRETATION AND CONCLUSION: Ciprofloxacin resistant N. gonorrhoeae is on the rise in and around Chandigarh (north India). Thus, periodic surveillance of susceptibility levels of N. gonorrhoeae is essential to prevent the dissemination of drug resistant strains in the community.

Comparison of disc diffusion results with minimum inhibitory concentration (MIC) values for antimicrobial susceptibility testing of Neisseria gonorrhoeae.

BACKGROUND & OBJECTIVE: objectives: As antimicrobial susceptibility testing of Neisseria gonorrhoeae provides guidance for appropriate treatment, there is a need for simple, reliable and cost-effective method for susceptibility testing. The present study was aimed to compare the results of two methods of susceptibility testing, minimum inhibitory concentration (MIC) values by E test with disc diffusion results by Australian Gonococcal Surveillance Programme (AGSP) method in N. gonorrhoeae isolates. METHODS: Susceptibility testing for ciprofloxacin, penicillin and ceftriaxone using AGSP method was carried out for 301 confirmed consecutive isolates of N. gonorrhoeae. MIC of ciprofloxacin, penicillin and ceftriaxone was determined by E test in 301, 198 and 128 isolates respectively. The results of the two methods were compared by using Kappa statistics. RESULTS: Moderate levels of agreement for ciprofloxacin (kappa=0.44) and penicillin (kappa=0.54) were observed between the two methods. For ceftriaxone, 96.1 and 0.8 per cent isolates were found to be susceptible and less sensitive respectively by both the methods and per cent agreement between the two methods was 96.9 per cent. INTERPRETATION & CONCLUSION: Both the methods were easy to perform and gave reproducible results. However, disc diffusion method was cost-effective and more feasible in routine diagnostic laboratories in developing countries like India.

Decrease in the incidence of tetracycline resistance in strains of Neisseria gonorrhoeae in the nineties

Antibiotic resistance determined by standard disc-diffusion method on GC agar with supplement B in 583 strains of Neisseria gonorrhoeae encountered between 1991 and 1996 at the University Hospital of the West Indies, Kingston, Jamaica, were analyzed. The level of penicillin resistance varied between 40 and 28 over the years. Tetracycline resistance fell from 44.2 in 1991 to 23.9 in 1996. Twenty-one per cent of the isolates were resistant simultaneously to both penicillin and tetracycline in 1991. The percentage of such strains decreased to 6.5 in 1996. Ceftriaxone was introduced as a first line drug in treatment of gonococcal infections in the late 1980s. The declining trend of tetracycline resistance may be due to a decrease in the usage of tetracycline in recent years