RESUMO
INTRODUCTION: Increasing use of nucleic acid amplification tests (NAATs) as the primary means of diagnosing gonococcal infection has resulted in diminished availability of Neisseria gonorrhoeae antimicrobial susceptibility data. We conducted a prospective diagnostic assessment of a real-time PCR assay (NGSNP) enabling direct detection of gonococcal ciprofloxacin susceptibility from a range of clinical sample types. METHODS: NGSNP, designed to discriminate an SNP associated with ciprofloxacin resistance within the N. gonorrhoeae genome, was validated using a characterized panel of geographically diverse isolates (nâ=â90) and evaluated to predict ciprofloxacin susceptibility directly on N. gonorrhoeae-positive NAAT lysates derived from genital (nâ=â174) and non-genital (nâ=â116) samples (nâ=â290), from 222 culture-confirmed clinical episodes of gonococcal infection. RESULTS: NGSNP correctly genotyped all phenotypically susceptible (nâ=â49) and resistant (nâ=â41) panel isolates. Ciprofloxacin-resistant N. gonorrhoeae was responsible for infection in 29.7% (nâ=â66) of clinical episodes evaluated. Compared with phenotypic susceptibility testing, NGSNP demonstrated sensitivity and specificity of 95.8% (95% CI 91.5%-98.3%) and 100% (95% CI 94.7%-100%), respectively, for detecting ciprofloxacin-susceptible N. gonorrhoeae, with a positive predictive value of 100% (95% CI 97.7%-100%). Applied to urogenital (nâ=â164), rectal (nâ=â40) and pharyngeal samples alone (nâ=â30), positive predictive values were 100% (95% CI 96.8%-100%), 100% (95% CI 87.2%-100%) and 100% (95% CI 82.4%-100%), respectively. CONCLUSIONS: Genotypic prediction of N. gonorrhoeae ciprofloxacin susceptibility directly from clinical samples was highly accurate and, in the absence of culture, will facilitate use of tailored therapy for gonococcal infection, sparing use of current empirical treatment regimens and enhancing acquisition of susceptibility data for surveillance.
Assuntos
Antibacterianos/uso terapêutico , Ciprofloxacina/farmacologia , Genitália/microbiologia , Gonorreia/tratamento farmacológico , Gonorreia/microbiologia , Testes de Sensibilidade Microbiana/métodos , Neisseria gonorrhoeae/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Masculino , Medicina de Precisão , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: To investigate a potential outbreak of high-level azithromycin resistant (HL-AziR) gonococcal infections diagnosed in eight patients attending a sexual health clinic in Leeds, North England, between November 2014 and March 2015. METHODS: Eight cases of infection with gonococci exhibiting azithromycin minimum inhibitory concentrations (MICs) ≥256â mg/L were identified from patients in Leeds as part of the routine service provided by the Sexually Transmitted Bacteria Reference Unit. All patient records were reviewed to collate epidemiological and clinical information including evaluation of patient management. Whole-genome sequencing (WGS) was performed on seven gonococcal isolates to determine Neisseria gonorrhoeae multiantigen sequence type (NG-MAST), WGS comparison and mutations in the 23S rRNA genes. RESULTS: All patients were heterosexual (five male, three female) from a range of ethnic backgrounds and from the Leeds area. Three patients were linked by partner notification. All patients were infected at genital sites and two women had pharyngeal infection also. Six patients received the recommended first-line therapy for uncomplicated gonorrhoea, one was treated for pelvic inflammatory disease and one received spectinomycin followed later by ciprofloxacin. Test of cure was achieved in seven patients and confirmed successful eradication. All seven isolates sequenced were identical by NG-MAST and WGS comparison, and contained an A2143G mutation in all four 23S rRNA alleles. CONCLUSIONS: Epidemiological and microbiological investigations confirm that an outbreak of a gonococcal strain showing HL-AziR is ongoing in the North of England. Every effort should be made to identify and curtail dissemination of this strain as it presents a significant threat to the current recommended front-line dual therapy.
Assuntos
Azitromicina/farmacologia , Surtos de Doenças/estatística & dados numéricos , Farmacorresistência Bacteriana/efeitos dos fármacos , Gonorreia/epidemiologia , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Adulto , Azitromicina/administração & dosagem , Técnicas de Tipagem Bacteriana , Ceftriaxona/administração & dosagem , Ciprofloxacina/administração & dosagem , DNA Bacteriano , Surtos de Doenças/prevenção & controle , Doxiciclina/administração & dosagem , Inglaterra/epidemiologia , Feminino , Gonorreia/tratamento farmacológico , Gonorreia/prevenção & controle , Heterossexualidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/isolamento & purificação , Resultado do TratamentoRESUMO
OBJECTIVES: Reference laboratories are increasingly using more sensitive rapid molecular techniques, such as nucleic acid amplification tests (NAATs), to diagnose infections with Neisseria gonorrhoeae. We determined the proportion of patients at sentinel genitourinary medicine clinics in England whose NAAT-positive diagnoses were also culture-positive for N. gonorrhoeae, and investigated whether they differed from those that were not. METHODS: Behavioural and clinical data from all NAAT-positive patients reported from 23 clinics included in the Gonoccocal Resistance to Antimicrobials Surveillance Programme from July to September 2012 were included in this analysis. Unadjusted and adjusted associations between patient characteristics and culture-positive infection with N. gonorrhoeae were determined. RESULTS: Of 3076 NAAT-positive patients, 46.4% had culture-positive infections. Most NAAT-positive patients were <35 years old (73.0%), white (67.9%), and men who had sex with men (60.1%). Women and men who had sex with men were less likely than heterosexual men to have culture-positive infections (adjusted OR (95% CI) 0.53 (0.41 to 0.68), p<0.001; and 0.74 (0.59 to 0.93), p=0.010, respectively), while those who were symptomatic (4.61 (3.92 to 5.42), p<0.001), and those presenting with infection at multiple sites (2.15 (1.76 to 2.62), p<0.001) were more likely to have culture-positive infections. CONCLUSIONS: Although gonococcal isolates were available from almost half of the NAAT-positive patients, culture was not attempted or may have failed in the remainder. Patients with culture-positive isolates were not representative of all NAAT-positive patients. Routine culture is necessary for monitoring emerging antimicrobial resistance and to inform gonorrhoea treatment guidelines.
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Doenças Urogenitais Femininas/microbiologia , Gonorreia/diagnóstico , Doenças Urogenitais Masculinas/microbiologia , Neisseria gonorrhoeae/isolamento & purificação , Comportamento Sexual/estatística & dados numéricos , Antibacterianos/administração & dosagem , DNA Bacteriano/isolamento & purificação , Farmacorresistência Bacteriana , Inglaterra/epidemiologia , Feminino , Doenças Urogenitais Femininas/epidemiologia , Gonorreia/epidemiologia , Gonorreia/prevenção & controle , Humanos , Masculino , Doenças Urogenitais Masculinas/epidemiologia , Neisseria gonorrhoeae/genética , Técnicas de Amplificação de Ácido Nucleico , Guias de Prática Clínica como Assunto , Sensibilidade e Especificidade , Vigilância de Evento SentinelaRESUMO
BACKGROUND: Gonorrhea treatment is challenging because of the emergence of resistance, treatment failure with existing drugs, and the lack of alternative agents. This study investigates the feasibility of targeting previously recommended antimicrobials to specific population subgroups where the prevalence of infection susceptible to these antimicrobials is above the World Health Organization cautionary treatment threshold of 95%. METHODS: Descriptive data from the Gonococcal Resistance to Antimicrobials Surveillance Programme for England and Wales were analyzed to investigate patient characteristics associated with infection with susceptible isolates using univariate and multivariable analyses. RESULTS: Of 6173 isolates from 2007 to 2011, 4684 (82%) were susceptible to penicillin, 3899 (68%) to ciprofloxacin, and 5240 (91%) to cefixime. All subgroups of the MSM population had fewer than 95% of isolates susceptible to penicillin, ciprofloxacin, or cefixime. Higher proportions of isolates from heterosexual patient subgroups were susceptible to these antimicrobials. Multivariable models identified the following associations between patient characteristics and infection with susceptible isolates: patients aged 13 to 24 years (penicillin: 92.3% susceptible adjusted odds ratio and associated 95% confidence interval [aOR CI] 1.84-2.97; ciprofloxacin: 88.3%, aOR CI 2.22-3.39; cefixime: 98.7%, aOR CI 1.29-3.52) patients of black ethnicity (penicillin: 93.9%, aOR CI 2.72-4.91; ciprofloxacin: 92.0%, aOR CI 3.94-6.7; cefixime: 99.1%, aOR CI 1.78-6.4), and patients with concurrent chlamydia (penicillin: 93.9%, aOR CI 1.8-3.22; ciprofloxacin: 91.7%, aOR CI 2.71-4.58; cefixime: 99.0%, aOR CI 1.27-4.54). CONCLUSIONS: This study demonstrated that of the previous first-line therapies, cefixime would be the only antimicrobial suitable for use for infection in heterosexual patients alone.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Adolescente , Adulto , Cefixima/farmacologia , Ciprofloxacina/farmacologia , Inglaterra/epidemiologia , Monitoramento Epidemiológico , Estudos de Viabilidade , Feminino , Gonorreia/epidemiologia , Heterossexualidade , Humanos , Masculino , Penicilinas/farmacologia , Prevalência , Comportamento Sexual , País de Gales/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The European Gonococcal Antimicrobial Surveillance Programme performs antimicrobial resistance surveillance and is coordinated by the European Centre for Disease Prevention and Control. This study used epidemiological and behavioral data combined with the gonococcal susceptibility profiles to determine risk factors associated with harboring resistant gonococci in Europe. METHODS: From 2009 to 2011, gonococcal isolates from 21 countries were submitted to the European Gonococcal Antimicrobial Surveillance Programme for antimicrobial susceptibility testing. Patient variables associated with resistance to azithromycin, cefixime, and ciprofloxacin were identified using univariate and multivariable logistic regression analyses of odds ratios. Geometric means for ceftriaxone and cefixime minimum inhibitory concentrations (MICs) were compared for patients of different sexual orientation and sex. RESULTS: A total of 5034 gonococcal isolates were tested from 2009 to 2011. Isolates exhibiting resistance to cefixime (MIC > 0.125 mg/L) and ciprofloxacin (MIC > 0.5 mg/L) were significantly associated with infection in heterosexuals (males only for ciprofloxacin), older patients (>25 years of age), or those without a concurrent chlamydial infection in the multivariable analysis. The geometric mean of cefixime and ceftriaxone MICs decreased from 2009 to 2011, most significantly for men who have sex with men, and isolates from male heterosexuals exhibited the highest MICs in 2011. CONCLUSIONS: The linking of epidemiological and behavioral data to the susceptibility profiles of the gonococcal isolates has allowed those at higher risk for acquiring antimicrobial resistant Neisseria gonorrhoeae to be identified. Improved data numbers and representativeness are required before evidence-based risk groups can be identified, and subsequent focused treatments or public health intervention strategies can be initiated with confidence.
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Anti-Infecciosos/administração & dosagem , Resistência Microbiana a Medicamentos , Gonorreia/prevenção & controle , Neisseria gonorrhoeae/efeitos dos fármacos , Adulto , Anti-Infecciosos/farmacologia , Azitromicina/farmacologia , Cefixima/farmacologia , Ceftriaxona/farmacologia , Europa (Continente)/epidemiologia , Feminino , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Fatores de Risco , Vigilância de Evento SentinelaRESUMO
OBJECTIVES: Identification of genetic targets specific to Neisseria gonorrhoeae for use in molecular detection methods has been a challenge. The porA pseudogene in N gonorrhoeae has been commonly used but recently gonococcal isolates giving a negative result in these PCRs have been reported. Here we describe the characterisation of two such gonococcal isolates received by the reference service at the Health Protection Agency, London, England. METHODS: Phenotypic characterisation was achieved using conventional biochemical and immunological tests, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS), antimicrobial susceptibility testing, serovar determination and detection of meningococcal PorA using monoclonal antibody 4BG4-E7. Genetic species confirmation was determined using commercial and in house PCRs and 16S rRNA gene sequencing. Molecular typing using the N gonorrhoeae multi-antigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) was performed. The DNA sequence of the full-length gonococcal porA pseudogene was determined and compared with published sequences. RESULTS: Both isolates were confirmed, biochemically and immunologically as N gonorrhoeae, but repeatedly gave negative results with two in house real-time PCR assays for the porA pseudogene. Further characterisation of these isolates identified the presence of a meningococcal porA sequence and showed these isolates belong to serovar Bropyst, and to NG-MAST sequence type (ST) 5967 and MLST ST1901. CONCLUSIONS: Gonococcal isolates that give false negative results with porA pseudogene PCR assays have now been identified in four countries, three of which are in Europe, and do not appear clonal. This report highlights the genetic diversity of N gonorrhoeae, which remains a challenge for the molecular detection methods.
Assuntos
Reações Falso-Negativas , Gonorreia/diagnóstico , Gonorreia/microbiologia , Técnicas de Diagnóstico Molecular/métodos , Neisseria gonorrhoeae/genética , Porinas/genética , Adulto , Técnicas de Tipagem Bacteriana , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Variação Genética , Humanos , Londres , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Neisseria gonorrhoeae/química , Neisseria gonorrhoeae/imunologia , Neisseria gonorrhoeae/fisiologia , Reação em Cadeia da Polimerase/métodos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Sorotipagem , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
OBJECTIVES: After a trend of increasing incidence of gonorrhoea in the 1990s, by 2004 the incidence was declining in England, but continuing to increase in Wales. This prompted an investigation of the epidemiology of gonorrhoea in Wales to inform future prevention and control measures. METHODS: As an extension to Gonococcal Resistance to Antimicrobials Surveillance Programme, between May 2005 and September 2006, 540 consecutive gonococcal isolates were collected from three microbiology laboratories in South Wales. Isolates were typed using Neisseria gonorrhoeae Multi Antigen Sequence Typing tested for susceptibility to therapeutic agents and demographic and behavioural data were collected retrospectively from patient notes. RESULTS: 163 sequence types (STs) were identified in 475 N gonorrhoeae isolates from 502 patient episodes. The most frequently observed STs (>20 isolates) were: 2, 752, 471, 249 and 8, all of which were susceptible to the antimicrobial agents tested. A significant association between ST and sexual orientation was identified, the most frequently observed STs occurring in young (median age <25 years) heterosexuals. STs 147, 4, 1634 and 64 predominated in men who have sex with men. CONCLUSIONS: We confirm the existence of common STs across the UK, as well as identify a number of types that were novel to Wales. Discrete sexual networks were identified, the most localised being in young heterosexuals. Molecular typing provides a method for identifying local clusters of gonorrhoea, and could assist in the implementation and evaluation of targeted interventions.
Assuntos
Gonorreia/epidemiologia , Gonorreia/microbiologia , Tipagem Molecular , Neisseria gonorrhoeae/classificação , Neisseria gonorrhoeae/genética , Adolescente , Adulto , Antibacterianos/farmacologia , Análise por Conglomerados , Demografia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular , Neisseria gonorrhoeae/isolamento & purificação , Comportamento Sexual , País de Gales/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: The third-generation cephalosporins recommended in national guidelines are amongst the last remaining effective agents for treatment of gonorrhoea. This study characterizes gonococcal isolates with decreased cefixime susceptibility from England and Wales. METHODS: A total of 96 isolates of Neisseria gonorrhoeae exhibiting cefixime MICs of ≥0.125 mg/L, either collected as part of the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) between 2005 and 2008 (54 from a total of 4649 isolates) or referred to the national reference laboratory in 2008 and 2009 (42 isolates), were tested for susceptibility to a range of antimicrobial agents and were typed using N. gonorrhoeae multiantigen sequence typing (NG-MAST). RESULTS: All 96 isolates were also resistant to tetracycline (MIC ≥2 mg/L) and ciprofloxacin (MIC ≥16 mg/L) and 56% showed low-level chromosomal resistance to penicillin. Where data were available, the mean patient age was 31 years, and 88% (83/94) of patients were men. Isolates referred through GRASP were predominantly from men who have sex with men (MSM; 29/44, 66%) and from patients of white British ethnicity (25/43, 58%). The majority of isolates belonged either to sequence type (ST) 1407 (71/96, 74%) or to a highly related ST that shares the tpbB allele (allele 110), but with a different por allele (20/96, 21%). ST1407 was found in both MSM (22/29, 76%) and heterosexual patients (12/15, 80%) and among all eight isolates from patients reporting sex abroad. CONCLUSIONS: The emergence of a clonal group of gonococci showing decreased susceptibility to cefixime in England and Wales highlights the need for continued surveillance.
Assuntos
Antibacterianos/farmacologia , Cefixima/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Gonorreia/tratamento farmacológico , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Ciprofloxacina/farmacologia , Inglaterra/epidemiologia , Feminino , Gonorreia/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular , Tipagem Molecular , Neisseria gonorrhoeae/isolamento & purificação , Penicilinas/farmacologia , Comportamento Sexual , Tetraciclina/farmacologia , País de GalesRESUMO
OBJECTIVES: The emergence of decreased susceptibility to third-generation, extended-spectrum cephalosporins in Neisseria gonorrhoeae and associated treatment failures highlights the need to consider alternatives for future therapeutic use, such as gentamicin. METHODS: The three laboratories surveying gonococcal antimicrobial susceptibility as part of the European Network for Sexually Transmitted Infections Surveillance compared agar dilution and Etest to determine gentamicin MICs and performed the first survey of gentamicin susceptibility on 1366 gonococcal isolates from 17 European Union/European Economic Area (EU/EAA) countries in 2009. RESULTS: Sentinel surveillance of gentamicin susceptibility showed that 95% of European isolates were within a narrow MIC range (4-8 mg/L), with 79% showing an MIC of 8 mg/L. Most countries showed little variation, but wider MIC ranges were observed in Greece (1-16 mg/L) and France, Norway and Sweden (2-16 mg/L). While MICs for both methods generally differed by just one doubling dilution, they were lower by Etest. CONCLUSIONS: This is the first reported evidence that the European gonococcal population susceptibility to gentamicin is similar to that reported in other world regions. Clinical trials to evaluate the therapeutic efficacy of gentamicin may be warranted.
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Antibacterianos/farmacologia , Gentamicinas/farmacologia , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Adolescente , União Europeia , Humanos , Testes de Sensibilidade Microbiana/métodos , Neisseria gonorrhoeae/isolamento & purificação , Adulto JovemRESUMO
INTRODUCTION: The arrival of coronavirus disrupted health care systems and forced delays in cancer treatment. We explored the experience of urologists who had to delay their patients' cancer care. METHODS: Urologists who treat prostate, bladder, and renal cancers, selected through purposive sampling, responded to a survey about cancer treatment delay. They were asked about their practice setting, decision making and interactions with patients, and they were asked to reflect on their personal experience. A 0 to 10 point scale, modeled on the National Comprehensive Cancer Network' Distress Thermometer (NCCN-DT), validated for cancer patients with cancer, was used to estimate physician distress. We used descriptive statistics to analyze survey results. RESULTS: Of the 64 participating urologists, 98% delayed surgical treatment; fewer delayed cases of advanced cancers (42% for ≥T3/T4 or Gleason ≥8 prostate cancers, 58% for muscle invasive bladder cancer, 61% for ≥T2 renal cancers). They reported feeling anxious (44%) and helpless (29%), and their median distress score was 5 (range 0-10). They relied on their own risk assessments (67%) and consulted colleagues (56%) and national guidelines (53%) when making treatment deferral decisions. They identified a number of concerns as they resumed surgeries. CONCLUSIONS: Based on a comparison to the NCCN-DT clinical cutoff distress level of 4, urologists experienced moderately high levels of distress as they delayed cancer care during the COVID-19 pandemic and expressed concerns going forward. While the focus on patient care is paramount in a pandemic, it is important to recognize physician distress and develop practical and psychological strategies for distress mitigation.
RESUMO
High-level azithromycin resistance (AZM-HR), defined as a MIC of > or = 256 mg/liter, emerged in Neisseria gonorrhoeae in the United Kingdom in 2004. To determine the mechanism of this novel phenotype, isolates from the United Kingdom that were AZM-HR (n, 19), moderately AZM resistant (MICs, 2 to 8 mg/liter) (n, 26), or sensitive (MICs, 0.12 to 0.25 mg/liter) (n, 4) were screened for methylase (erm) genes and for mutations in the mtrR promoter region, associated with efflux pump upregulation. All AZM-resistant isolates and 12 sensitive isolates were screened for mutations in domain V of each 23S rRNA allele. All AZM-HR isolates contained the A2059G mutation (Escherichia coli numbering) in three (3 isolates) or four (16 isolates) 23S rRNA alleles. Most (22/26) moderately AZM resistant isolates contained the C2611T mutation in at least 3/4 alleles. The remainder contained four wild-type alleles, as did 8/12 sensitive isolates, while one allele was mutated in the remaining four sensitive isolates. Serial passage of AZM-sensitive colonies on an erythromycin-containing medium selected AZM-HR if the parent strain already contained mutation A2059G in one 23S rRNA allele. The resultant AZM-HR strains contained four mutated alleles. Eight isolates (five moderately AZM resistant and three AZM-HR) contained mutations in the mtrR promoter. No methylase genes were detected. This is the first evidence that AZM-HR in gonococci may result from a single point mutation (A2059G) in the peptidyltransferase loop in domain V of the 23S rRNA gene. Mutation of a single allele is insufficient to confer AZM-HR, but AZM-HR can develop under selection pressure. The description of a novel resistance mechanism will aid in screening for the AZM-HR phenotype.
Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Mutação Puntual/genética , RNA Ribossômico 23S/genética , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/genética , Proteínas Repressoras/genéticaRESUMO
BACKGROUND: Gonorrhoea has been among the easiest infections to cure with antibiotics. Nevertheless, emerging resistance has driven repeated treatment shifts. Decreased cephalosporin susceptibility is now being reported. We examined cephalosporin MIC trends for Neisseria gonorrhoeae in the UK and undertook pharmacodynamic analyses to predict efficacy against strains with raised MICs. METHODS: Neisseria gonorrhoeae isolates were collected annually in a structured surveillance from 26 genitourinary medicine clinics in England and Wales. MICs were determined by agar dilution and confirmed by Etests. Pharmacodynamic modelling was performed for cefixime and ceftriaxone with Monte Carlo simulations. RESULTS: There was a progressive emergence of small numbers of gonococci with cephalosporin MICs of 0.125-0.25 mg/L; these were not seen before 2005 but, for ceftriaxone and cefixime, respectively, accounted for 0.4% (95% confidence interval 0.2%-1.1%) and 2.8% (1.6%-4.8%) of the 1253 isolates collected in 2008; such MICs are 16-64 times the modal values for the species. Pharmacodynamic analysis was complicated by evidence that cephalosporins need a longer period with the free drug level above MIC than the 7-10 h required for penicillin G; nevertheless, pharmacodynamic analyses predict that failures with the standard 400 mg cefixime po and 250 mg ceftriaxone im regimens become likely around the present MIC maxima. CONCLUSIONS: Gonococci with ceftriaxone and cefixime MICs of 0.125-0.25 mg/L are accumulating in the UK. These MICs lie on the edge of likely responsiveness to current regimens, which need review. Possible responses include: (i) higher cephalosporin doses; (ii) multidose cephalosporin regimens; (iii) multidrug regimens; (iv) microbiologically directed treatment; or, in the future, (v) drug cycling. The practicalities of these approaches are discussed.
Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Inglaterra , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/isolamento & purificação , Fatores de Tempo , País de GalesRESUMO
OBJECTIVE: To perform a European sentinel surveillance study for antimicrobial resistance (AMR) in Neisseria gonorrhoeae as part of the European Surveillance of Sexually Transmitted Infections Programme. METHODS: From 2006 to 2008 17 countries participated in the AMR surveillance programme. The susceptibility of a total of 3528 consecutive isolates was tested using the agar dilution breakpoint technique or Etests for ciprofloxacin, penicillin, tetracycline, azithromycin, spectinomycin and ceftriaxone. Nitrocefin was used to detect ß-lactamase activity. RESULTS: Rates of resistance to ciprofloxacin, the previously recommended treatment, were high across Europe (42-52%), indicating that usage is no longer appropriate. Although resistance to the currently recommended treatment, ceftriaxone, was not demonstrated, a concerning upward drift in the minimal inhibitory concentration (MIC) distribution was identified since an earlier European study in 2004. No resistance to spectinomycin was seen, whereas azithromycin resistance varied from 2% to 7% and isolates from Scotland (n=4) and Ireland (n=1) showed high-level resistance (MIC >256 mg/l). High-level resistance to tetracycline and penicillin remained relatively constant at 16% and 12%, respectively. CONCLUSIONS: AMR is an ongoing problem in Europe, with high rates of resistance to many previously recommended therapeutic agents observed in many European countries. Continual European and global surveillance of AMR in N gonorrhoeae is essential to monitor for increasing, emerging and high-level resistance to therapeutically relevant agents and to inform treatment guidelines so optimum treatments are administered.
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Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Gonorreia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Europa (Continente)/epidemiologia , Feminino , Gonorreia/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neisseria gonorrhoeae/isolamento & purificação , Garantia da Qualidade dos Cuidados de Saúde , Vigilância de Evento Sentinela , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to investigate the effect of amoxicillin therapy of poultry flocks upon the persistence of commensal Campylobacter spp. and the incidence of antibiotic resistance. METHODS: Four poultry flocks naturally colonized with Campylobacter were treated with amoxicillin and monitored before, during and up to 4 weeks post-treatment. The numbers of Campylobacter were determined and the isolates speciated and typed by flaA short variable region (SVR) sequence analysis and PFGE. The susceptibility of the isolates to antibiotics, presence of the Cj0299 gene encoding a beta-lactamase and beta-lactamase production (nitrocefin hydrolysis) were also determined. RESULTS: Amoxicillin-resistant Campylobacter were isolated from Flock 1 before and during treatment, but Campylobacter were not detected afterwards. Flock 2 was colonized by amoxicillin-susceptible strains throughout sampling. No amoxicillin-resistant isolates arose during or after treatment. Flock 3 contained amoxicillin-susceptible and -resistant types pre-treatment. Resistant isolates were detected during treatment, while antibiotic-susceptible isolates re-emerged at 3 weeks post-treatment. All Campylobacter isolates from Flock 4 were amoxicillin resistant, irrespective of sampling time. All but one of the 82 amoxicillin-resistant (MICs 16 to >128 mg/L) Campylobacter jejuni and Campylobacter coli tested for the presence of Cj0299 carried the gene and all of these produced beta-lactamase. Co-amoxiclav remained active against amoxicillin-resistant isolates. CONCLUSIONS: Amoxicillin therapy had little effect on the numbers of amoxicillin-resistant commensal Campylobacter except for one flock where amoxicillin-resistant Campylobacter temporarily dominated. Amoxicillin therapy did not select amoxicillin-resistant isolates from a previous susceptible strain. Co-amoxiclav remained active against amoxicillin-resistant isolates.
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Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Campylobacter/efeitos dos fármacos , Portador Sadio/microbiologia , Farmacorresistência Bacteriana , Aves Domésticas/microbiologia , Seleção Genética , Animais , Técnicas de Tipagem Bacteriana , Campylobacter/classificação , Campylobacter/genética , Campylobacter/isolamento & purificação , Portador Sadio/tratamento farmacológico , Análise por Conglomerados , Contagem de Colônia Microbiana , Impressões Digitais de DNA , Eletroforese em Gel de Campo Pulsado , Flagelina/genética , Genótipo , Testes de Sensibilidade Microbiana , Análise de Sequência de DNA , beta-Lactamases/genéticaRESUMO
The benefits of using a multiplex detection polymerase chain reaction (PCR) assay for Helicobacter pylori speciation and 2 real-time probe hybridization assays determining clarithromycin and tetracycline susceptibilities in gastric biopsies from 171 dyspeptic patients were investigated. Overall, 70 of 71 H. pylori culture-positive biopsies were PCR positive. For the 100 culture-negative biopsies, PCR identified a further 29 H. pylori positives (17% overall) and presence of resistance markers for clarithromycin (20/28) and tetracycline (2/28). The results demonstrated that PCR testing was valuable in providing improved detection rates and antibiotic susceptibility information when H. pylori culture was unsuccessful.
Assuntos
Resistência Microbiana a Medicamentos/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Antibacterianos/farmacologia , Biópsia , Claritromicina/farmacologia , DNA Bacteriano/genética , Dispepsia/microbiologia , Dispepsia/patologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana/métodos , Estômago/patologia , Tetraciclina/farmacologiaRESUMO
AIM: Admitting very elderly, critically ill patients to ICU is controversial. We compared our mortality data in a subgroup of elderly patients to internationally published outcomes. METHODS: Tauranga Hospital ICU retrospectively investigated their mortality outcomes for patients with septic shock. The ANZICS adult database (AORTIC), Tauranga Hospital computer records and medical records were used to identify the study cohort and provide information on demographics, admission times and shock types between January 2009 and December 2014. Patients were divided into groups; not old (<74 years), old (75-84 years) and very old (>85 years) to compare survival statistics at ICU discharge, hospital discharge, 28 days, six months and 12 months. RESULTS: Patients in the >85 year group at Tauranga ICU had a 38.5% survival. CONCLUSION: With careful selection, elderly patients with septic shock may have an acceptable outcome.
Assuntos
Hospitais de Distrito/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Choque Séptico/mortalidade , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Nova Zelândia/epidemiologia , Alta do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Choque Cardiogênico/mortalidade , Taxa de SobrevidaRESUMO
A novel PCR assay (HHLO-16) to screen for presence of 'Helicobacter heilmannii'-like organisms (HHLO) direct from gastric biopsies is described. As 'H. heilmannii' is generally uncultivable, diagnosis of infection is reliant on histology; thus prevalence may be underestimated. Analysis of an HHLO histology-positive human gastric biopsy and 15 gastric biopsies from domestic cats demonstrated that the HHLO-16 assay was more sensitive than an alternative available species-specific PCR assay. Further testing of 131 gastric biopsies from dyspeptic patients demonstrated an HHLO prevalence rate of 2.3% in Southeast England. Subsequent combination of the HHLO-16 assay with a H. pylori-specific PCR assay in a multiplex format (HpHh assay), and repeat analysis of the 131 biopsies showed the HpHh assay was as sensitive as each individual test. This novel PCR assay provides simple concomitant testing of dyspeptic patients for both HHLOs and H. pylori, thereby rapidly identifying individuals requiring eradication therapy.
Assuntos
DNA Bacteriano/análise , Mucosa Gástrica/microbiologia , Helicobacter heilmannii/isolamento & purificação , Helicobacter pylori/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Sequência de Bases , Biópsia por Agulha , Técnicas de Cultura , Mucosa Gástrica/patologia , Infecções por Helicobacter/diagnóstico , Humanos , Dados de Sequência Molecular , Sensibilidade e Especificidade , Reino UnidoRESUMO
Mutations in the NAD(P)H flavin oxidoreductase gene (frxA) are thought to contribute to the development of metronidazole resistance in Helicobacter pylori. To test this further, 44 frxA sequences in 18 patient isolate sets of H. pylori were examined including a unique collection comprising separated Mtz-sensitive (MtzS) and Mtz-resistant (MtzR) subpopulations pre-treatment and matched MtzR strains post-treatment. Sequences of frxA contained frameshift mutations that led to premature protein truncation in at least one strain from most (17/18) patient sets. These mutations were present in all strains, irrespective of Mtz resistotype in 13/18 patients. Frameshift due to a single adenine deletion at nucleotide 53 was the most common mutation and was present in isolates from 11/18 patients. A novel real-time (LightCycler) PCR-based probe hybridization melting-point assay applied to a further 119 isolates confirmed that the frameshift-53 mutation occurred frequently, in 20% of isolates, and could be present in MtzS as well as MtzR strains (42% vs 58%). This study demonstrates that frameshift mutations occur in MtzS strains as well as in MtzR strains, and are thus unlikely to cause Mtz resistance.
Assuntos
Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana/genética , Mutação da Fase de Leitura , Helicobacter pylori/efeitos dos fármacos , Metronidazol/farmacologia , Nitrorredutases/genética , Sequência de Aminoácidos , Biomarcadores , Infecções por Helicobacter/microbiologia , Helicobacter pylori/enzimologia , Helicobacter pylori/genética , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Análise de Sequência de DNA , Reino UnidoRESUMO
Stool antigen-testing allows non-invasive detection of Helicobacter pylori that is indicative of active infection. Three commercial kits are currently marketed in the UK for stool antigen-testing. The aim of this study was to conduct a comparative evaluation of the performances of each of these tests, compared with culture and histological examination of gastric biopsies, for pre-treatment diagnosis of infection in an adult dyspeptic population in south-east England. Examination of 112 stool samples by the Premier Platinum HpSA ELISA (Meridian Diagnostics) and by the Amplified IDEIA HpStAR ELISA (DakoCytomation) kits demonstrated that the latter was more sensitive (81.3 versus 93.8%, respectively) and specific (91.7 versus 100.0%, respectively). Additionally, the IDEIA HpStAR was easier to interpret, with OD readings of positive and negative results being far from the recommended cut-off, whereas equivocal results that were generated by the HpSA kit were difficult to interpret. Additional testing of 87 of the 112 stools by the ImmunoCard STAT! HpSA kit (Meridian Diagnostics) demonstrated that this test was easier to perform than ELISA and was more sensitive than the HpSA kit but, compared with the IDEIA HpStAR kit, the ImmunoCard test was less sensitive (87.8 versus 95.9%, respectively) and specific (89.4 versus 100.0%, respectively). Furthermore, the ImmunoCard test generated weakly positive results, correlating with lower OD readings for both ELISA kits, that were difficult to interpret. The Amplified IDEIA HpStAR kit is therefore the most sensitive and specific of the three tests that are available for pre-treatment, non-invasive detection of H. pylori in stool samples in an English adult dyspeptic population.
Assuntos
Antígenos de Bactérias/análise , Dispepsia/etiologia , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Técnicas Imunológicas , Adulto , Idoso , Biópsia , Cromatografia de Afinidade , Inglaterra , Ensaio de Imunoadsorção Enzimática , Reações Falso-Negativas , Reações Falso-Positivas , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/imunologia , Humanos , Pessoa de Meia-Idade , Kit de Reagentes para Diagnóstico , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Effective treatment of gonorrhoea is fundamental to public health control; however, the ability of Neisseria gonorrhoeae to successively develop resistance to different treatments has hampered control efforts. The extended-spectrum cephalosporins--cefixime and ceftriaxone--have been recommended in the UK for treatment of gonorrhoea since 2005. We looked at surveillance data from England and Wales to ascertain the current usefulness of these drugs and to inform changes to national treatment guidelines. METHODS: We obtained data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) for patients attending 26 genitourinary medicine clinics in England and Wales between 2007 and 2011. We did analyses with univariate and multivariable logistic regression methods to identify trends in susceptibility to cephalosporins and risk factors associated with infection with isolates with decreased susceptibility to cefixime, and we assessed changes in prescribing practices. We did molecular typing to investigate genetic relatedness of non-susceptible isolates. FINDINGS: The prevalence of decreased susceptibility to both cefixime and ceftriaxone rose between 2007 and 2010 but was more noticeable for cefixime (an increase from 1·5% in 2007 to 17·1% in 2010), with a bimodal distribution of minimum inhibitory concentration recorded between 2009 and 2010. By multivariable analysis, isolates with decreased susceptibility to cefixime were associated with infection in men who have sex with men (odds ratio 5·47, 95% CI 3·99-7·48; p<0·0001) and year of isolation (in 2010, 13·08, 7·49-22·8; p<0·0001). Such isolates had a largely clonal population, with most belonging to genogroup G1407 and harbouring the penA mosaic gene. Data from 2011 showed a significant decline in prevalence of isolates with decreased cefixime susceptibility, falling from 17·1% in 2010 to 10·8% in 2011 (p<0·0001), concomitant with the change in prescribing practice in 2010 from cefixime to ceftriaxone plus azithromycin. INTERPRETATION: Guidance for treatment of gonorrhoea in England and Wales was changed in 2010 to prolong the use of cephalosporins. The decline in prevalence of isolates with decreased cefixime susceptibility cannot be attributed unequivocally to this change in prescribing practice; however, the association is striking. FUNDING: Department of Health (England), Public Health England.