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1.
Clin Infect Dis ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32766725

RESUMO

BACKGROUND: Novel treatment strategies to slow the continued emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae are urgently needed. A molecular assay that predicts in vitro ciprofloxacin susceptibility is now available but has not been systematically studied in human infections. METHODS: Using a genotypic polymerase chain reaction assay to determine the status of the N. gonorrhoeae gyrase subunit A serine 91 codon, we conducted a multisite prospective clinical study of the efficacy of a single oral dose of ciprofloxacin 500 mg in patients with culture-positive gonorrhea. Follow-up specimens for culture were collected to determine microbiological cure 5-10 days post-treatment. RESULTS: Of the 106 subjects possessing culture-positive infections with wild-type gyrA serine N. gonorrhoeae genotype, the efficacy of single-dose oral ciprofloxacin treatment in the per-protocol population was 100% (95% 1-sided confidence interval, 97.5-100%). CONCLUSIONS: Resistance-guided treatment of N. gonorrhoeae infections with single-dose oral ciprofloxacin was highly efficacious. The widespread introduction and scale-up of gyrA serine 91 genotyping in N. gonorrhoeae infections could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible. CLINICAL TRIALS REGISTRATION: NCT02961751.

2.
Clin Infect Dis ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32766821

RESUMO

BACKGROUND: Neisseria gonorrhoeae culture is necessary to determine antimicrobial resistance, but typically requires specimen collection by clinicians. We sought to determine the sensitivity of patient-collected specimens for N. gonorrhoeae culture. METHODS: We performed N. gonorrhoeae cultures on paired, clinician- and patient-collected specimens from the pharynx (n=93), rectum (n=88), endocervix/vagina (n=89), and urethra/urine (46). We calculated the percent concordance and the kappa statistic for paired-specimen results, and determined the test sensitivity for each specimen type using positivity of either specimen in a pair as a gold standard defining the presence of true infection. RESULTS: At least one specimen was positive in 26%, 31%, 61% and 3% in the pharynx, rectum, urethra/urine, and endocervix/vagina paired specimens, respectively. Patient- and clinician-collected results were highly concordant at the pharynx (95%, kappa 0.85), rectum (99%, kappa 0.97), urethra/urine (83%, kappa=0.87) and endocervix/vagina (100%, kappa 1.0) (p<0.005 for all comparisons). Patient-collected pharyngeal and rectal swabs and urine were 92%, 96%, 96% sensitive, while clinician-collected specimens at these anatomic sites were 87.5%, 100%, 94% sensitive (p>0.05 for all comparisons). Among 24 urine specimens held for 4 - 22 hours post collection, 100% yielded concordant N. gonorrhoeae culture results compared to immediate processing. CONCLUSIONS: Patient- and clinician-collected specimens are comparably sensitive for N. gonorrhoeae culture. These findings suggest that patient-collected specimens could be used to expand the availability of gonococcal antimicrobial resistance testing for both clinical and surveillance purposes.

3.
Clin Infect Dis ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32750107

RESUMO

BACKGROUND: Nongonococcal urethritis (NGU) is a common syndrome with no known etiology in up to 50% of cases. We estimated associations between urethral bacteria and NGU in men who have sex with men (MSM) and men who have sex with women (MSW). METHODS: Urine was collected from NGU cases (129 MSM; 121 MSW) and controls (70 MSM; 114 MSW) attending a Seattle STD clinic. Cases had ≥5 polymorphonuclear leukocytes on Gram stain plus symptoms or discharge; controls had <5 PMNs, no symptoms, no discharge. NGU was considered idiopathic when Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenovirus, and herpes simplex virus were absent. The urethral microbiota was characterized using 16S rRNA gene sequencing. Compositional lasso analysis was conducted to identify associations between bacterial taxa and NGU, and to select bacteria for targeted quantitative PCR (qPCR). RESULTS: Among NGU cases, 45.2% were idiopathic. Based on compositional lasso analysis, we selected Haemophilus influenzae (HI) and Mycoplasma penetrans (MP) for targeted qPCR. Compared to 182 men without NGU, the 249 men with NGU were more likely to have HI (14% vs. 2%) and MP (21% vs. 1%) (both p≤0.001). In stratified analyses, detection of HI was associated with NGU among MSM (12% vs. 3%, p=0.036) and MSW (17% vs. 1%, p<0.001), but MP was associated with NGU only among MSM (13% vs. 1%, p=0.004). Associations were stronger in men with idiopathic NGU. CONCLUSIONS: HI and MP are potential causes of male urethritis. MP was more often detected among MSM than MSW with urethritis.

4.
Sex Transm Dis ; 47(5): 321-325, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32304528

RESUMO

BACKGROUND: Rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are increasingly recognized as common infections among women. Little is known about the prevalence of rectal Mycoplasma genitalium (MG), rectal MG/CT/GC coinfection, or MG antimicrobial resistance patterns among women. METHODS: In 2017 to 2018, we recruited women at high risk for CT from Seattle's municipal sexually transmitted disease clinic. Participants self-collected vaginal and rectal specimens for CT/GC nucleic acid amplification testing. We retrospectively tested samples for vaginal and rectal MG using nucleic acid amplification testing and tested MG-positive specimens for macrolide resistance-mediating mutations (MRM) and ParC quinolone resistance-associated mutations (QRAMs). RESULTS: Of 50 enrolled women, 13 (26%) tested positive for MG, including 10 (20%) with vaginal MG and 11 (22%) with rectal MG; 8 (62%) had concurrent vaginal/rectal MG. Five (38%) were coinfected with CT, none with GC. Only 2 of 11 women with rectal MG reported anal sex in the prior year. Of MG-positive specimens, 100% of rectal and 89% of vaginal specimens had an MRM. There were no vaginal or rectal MG-positive specimens with ParC QRAMs previously associated with quinolone failure. Five MG-infected women received azithromycin for vaginal CT, 4 of whom had a MG MRM detected in their vaginal and/or rectal specimens. CONCLUSIONS: We observed a high prevalence of macrolide-resistant vaginal and rectal MG among a population of women at high risk for CT. This study highlights how the use of antimicrobials designed to treat an identified infection-in this case, CT-could influence treatment outcomes and antimicrobial susceptibility in other unidentified infections.

5.
PLoS Biol ; 18(3): e3000651, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32191696

RESUMO

Rapid antibiotic susceptibility testing (AST) for Neisseria gonorrhoeae (Ng) is critically needed to counter widespread antibiotic resistance. Detection of nucleic acids in genotypic AST can be rapid, but it has not been successful for ß-lactams (the largest antibiotic class used to treat Ng). Rapid phenotypic AST for Ng is challenged by the pathogen's slow doubling time and the lack of methods to quickly quantify the pathogen's response to ß-lactams. Here, we asked two questions: (1) Is it possible to use nucleic acid quantification to measure the ß-lactam susceptibility phenotype of Ng very rapidly, using antibiotic-exposure times much shorter than the 1- to 2-h doubling time of Ng? (2) Would such short-term antibiotic exposures predict the antibiotic resistance profile of Ng measured by plate growth assays over multiple days? To answer these questions, we devised an innovative approach for performing a rapid phenotypic AST that measures DNA accessibility to exogenous nucleases after exposure to ß-lactams (termed nuclease-accessibility AST [nuc-aAST]). We showed that DNA in antibiotic-susceptible cells has increased accessibility upon exposure to ß-lactams and that a judiciously chosen surfactant permeabilized the outer membrane and enhanced this effect. We tested penicillin, cefixime, and ceftriaxone and found good agreement between the results of the nuc-aAST after 15-30 min of antibiotic exposure and the results of the gold-standard culture-based AST measured over days. These results provide a new pathway toward developing a critically needed phenotypic AST for Ng and additional global-health threats.


Assuntos
Antibacterianos/farmacologia , DNA Bacteriano/metabolismo , Desoxirribonuclease I/metabolismo , Neisseria gonorrhoeae/efeitos dos fármacos , Tensoativos/farmacologia , beta-Lactamas/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Gonorreia/microbiologia , Gonorreia/urina , Humanos , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/crescimento & desenvolvimento , Neisseria gonorrhoeae/isolamento & purificação , Fenótipo , Reprodutibilidade dos Testes , Fatores de Tempo , Fluxo de Trabalho
6.
Protein Sci ; 29(3): 768-778, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31930578

RESUMO

Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) are the most commonly reported sexually transmitted bacteria worldwide and usually present as co-infections. Increasing resistance of Ng to currently recommended dual therapy of azithromycin and ceftriaxone presents therapeutic challenges for syndromic management of Ng-Ct co-infections. Development of a safe, effective, and inexpensive dual therapy for Ng-Ct co-infections is an effective strategy for the global control and prevention of these two most prevalent bacterial sexually transmitted infections. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a validated drug target with two approved drugs for indications other than antibacterials. Nonetheless, any new drugs targeting GAPDH in Ng and Ct must be specific inhibitors of bacterial GAPDH that do not inhibit human GAPDH, and structural information of Ng and Ct GAPDH will aid in finding such selective inhibitors. Here, we report the X-ray crystal structures of Ng and Ct GAPDH. Analysis of the structures demonstrates significant differences in amino acid residues in the active sites of human GAPDH from those of the two bacterial enzymes suggesting design of compounds to selectively inhibit Ng and Ct is possible. We also describe an efficient in vitro assay of recombinant GAPDH enzyme activity amenable to high-throughput drug screening to aid in identifying inhibitory compounds and begin to address selectivity.

7.
Clin Infect Dis ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31712813

RESUMO

BACKGROUND: CDC guidelines recommend 240 mg gentamicin plus 2g azithromycin for the treatment of gonorrhea in cephalosporin-allergic patients. The efficacy of gentamicin alone in the treatment of pharyngeal gonorrhea is uncertain. METHODS: Between September 2018 - March 2019, we enrolled men who have sex with men (MSM) with NAAT-diagnosed pharyngeal gonorrhea in a single-arm, unblinded clinical trial. Men received a single 360mg intramuscular (IM) dose of gentamicin and underwent test-of-cure (TOC) by culture 4-7 days later. The study measured creatinine at enrollment and TOC, serum gentamicin concentration post-dose to establish peak concentration (Cmax), and standard antimicrobial minimal inhibitory concentrations (MIC) by agar dilution. The trial was designed to establish a point estimate for gentamicin's efficacy for pharyngeal gonorrhea. We planned to enroll 50 evaluable subjects; assuming gentamicin was 80% efficacious, the trial would establish a 95% confidence interval of 66%-90%. We planned interim analyses at n=10 and n=25. RESULTS: The study was stopped early due to poor efficacy. Of 13 enrolled men, 10 were evaluable, and only two (20%, 95%CI: 2.5% - 55.6%) were cured. Efficacy was not associated with gentamicin Cmax or MIC. No participants experienced renal insufficiency. The mean creatinine percent change was +5.2% (range: -6.7%, +21.3%). Six (46%) subjects experienced headache; all deemed unrelated to treatment. CONCLUSIONS: Gentamicin alone failed to eradicate N. gonorrhoeae from the pharynx. Clinicians should use caution when treating gonorrhea with CDC's current alternative regimen (gentamicin 240mg plus azithromycin 2g) given increases in azithromycin resistance and gentamicin's poor efficacy at the pharynx.

9.
Sex Transm Dis ; 46(12): 805-809, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31259853

RESUMO

From February 2015 to October 2017, among 20 men who have sex with men with Mycoplasma genitalium-associated nongonococcal urethritis, 15% had macrolide resistance and S83I ParC mutations. Azithromycin followed by moxifloxacin cleared Mycoplasma genitalium in 2 of 2 with and 11 of 13 without S83I mutations. Dual failures were cleared after doxycycline. S83I mutations were not associated with moxifloxacin failure.

10.
BMC Microbiol ; 19(1): 76, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961546

RESUMO

BACKGROUND: Phenotypic fluoroquinolone resistance was first reported in Western Kenya in 2009 and later in Coastal Kenya and Nairobi. Until recently gonococcal fluoroquinolone resistance mechanisms in Kenya had not been elucidated. The aim of this paper is to analyze mutations in both gyrA and parC responsible for elevated fluoroquinolone Minimum Inhibitory Concentrations (MICs) in Neisseria gonorrhoeae (GC) isolated from heterosexual individuals from different locations in Kenya between 2013 and 2017. METHODS: Antimicrobial Susceptibility Tests were done on 84 GC in an ongoing Sexually Transmitted Infections (STI) surveillance program. Of the 84 isolates, 22 resistant to two or more classes of antimicrobials were chosen for analysis. Antimicrobial susceptibility tests were done using E-test (BioMerieux) and the results were interpreted with reference to European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. The isolates were sub-cultured, and whole genomes were sequenced using Illumina platform. Reads were assembled de novo using Velvet, and mutations in the GC Quinolone Resistant Determining Regions identified using Bioedit sequence alignment editor. Single Nucleotide Polymorphism based phylogeny was inferred using RaxML. RESULTS: Double GyrA amino acid substitutions; S91F and D95G/D95A were identified in 20 isolates. Of these 20 isolates, 14 had an additional E91G ParC substitution and significantly higher ciprofloxacin MICs (p = 0.0044*). On the contrary, norfloxacin MICs of isolates expressing both GyrA and ParC QRDR amino acid changes were not significantly high (p = 0.82) compared to MICs of isolates expressing GyrA substitutions alone. No single GyrA substitution was found in the analyzed isolates, and no isolate contained a ParC substitution without the simultaneous presence of double GyrA substitutions. Maximum likelihood tree clustered the 22 isolates into 6 distinct clades. CONCLUSION: Simultaneous presence of amino acid substitutions in ParC and GyrA has been reported to increase gonococcal fluoroquinolone resistance from different regions in the world. Our findings indicate that GyrA S91F, D95G/D95A and ParC E91G amino acid substitutions mediate high fluoroquinolone resistance in the analyzed Kenyan GC.


Assuntos
Antibacterianos/farmacologia , DNA Girase/genética , DNA Topoisomerase IV/genética , Fluoroquinolonas/farmacologia , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Substituição de Aminoácidos , Proteínas de Bactérias/genética , Monitoramento Epidemiológico , Feminino , Gonorreia/microbiologia , Humanos , Quênia , Masculino , Testes de Sensibilidade Microbiana , Mutação , Estudos Retrospectivos
11.
Artigo em Inglês | MEDLINE | ID: mdl-30917979

RESUMO

The nimbleness of Neisseria gonorrhoeae to evade the effect of antibiotics has perpetuated the fight against antibiotic-resistant gonorrhea for more than 80 years. The ability to develop resistance to antibiotics is attributable to its indiscriminate nature in accepting and integrating exogenous DNA into its genome. Here, we provide data demonstrating a novel combination of the 23S rRNA A2059G mutation with a mosaic-multiple transferable resistance (mosaic-mtr) locus haplotype in 14 N. gonorrhoeae isolates with high-level azithromycin MICs (≥256 µg/ml), a combination that may confer more fitness than in previously identified isolates with high-level azithromycin resistance. To our knowledge, this is the first description of N. gonorrhoeae strains harboring this novel combination of resistance determinants. These strains were isolated at two independent jurisdictions participating in the Gonococcal Isolate Surveillance Project (GISP) and in the Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) project. The data suggest that the genome of N. gonorrhoeae continues to shuffle its genetic material. These findings further illuminate the genomic plasticity of N. gonorrhoeae, which allows this pathogen to develop mutations to escape the inhibitory effects of antibiotics.


Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Mutação/genética , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Proteínas de Bactérias/genética , Sequência de Bases , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Gonorreia/tratamento farmacológico , Gonorreia/microbiologia , Humanos , Testes de Sensibilidade Microbiana/métodos , RNA Ribossômico 23S/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-30834380

RESUMO

Neisseria gonorrhoeae is the etiological agent of gonorrhea, the second most common notifiable disease in the United States. Here, we used a hybrid approach combining Oxford Nanopore Technologies MinION and Illumina MiSeq sequencing data to obtain closed genome sequences of nine clinical N. gonorrhoeae isolates.

13.
J Infect Dis ; 220(3): 476-483, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-30873541

RESUMO

BACKGROUND: Rectal Chlamydia trachomatis (CT) is common among clinic-attending women, but little is known about clearance and health implications of rectal CT. METHODS: At the municipal sexually transmitted disease clinic in Seattle, Washington, in 2017-2018, we enrolled women at high risk for urogenital CT into an 8-week prospective study. Women received standard CT treatment at enrollment. Women self-collected daily rectal and vaginal specimens for nucleic acid amplification tests (NAATs) and completed weekly sexual exposure diaries. We performed CT culture on the enrollment rectal specimen. RESULTS: We enrolled 50 women; 13 (26%) tested positive for vaginal (n = 11) and/or rectal (n = 11) CT. Sixty percent of women with rectal CT per NAAT were also culture positive. Median time to CT clearance after azithromycin treatment was 8.0 days for vaginal CT and 7.0 days for rectal CT. Eight women with rectal CT at enrollment had at least 1 rectal CT-positive NAAT after clearance of the initial infection; none reported anal sex. CONCLUSIONS: Most NAAT-positive rectal infections were culture positive, suggesting active infection. Time to NAAT clearance of rectal and genital tract CT was similar, and intermittent rectal CT positivity was common in the absence of anal sexual exposure. The cause of recurrent/intermittent rectal CT and the clinical implications of these infections require further study.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Chlamydia/tratamento farmacológico , Reto/microbiologia , Doenças Sexualmente Transmissíveis/tratamento farmacológico , Doenças Sexualmente Transmissíveis/microbiologia , Vagina/microbiologia , Adulto , Azitromicina/uso terapêutico , Chlamydia trachomatis/efeitos dos fármacos , Feminino , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Estudos Prospectivos , Recidiva , Comportamento Sexual/efeitos dos fármacos , Washington , Adulto Jovem
14.
Clin Infect Dis ; 69(1): 113-120, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-30281079

RESUMO

BACKGROUND: Although Mycoplasma genitalium (MG) is an acknowledged cause of nongonococcal urethritis (NGU), access to diagnostic testing is limited. Syndromic management is common, yet little is known about natural history. METHODS: Between August 2014 and April 2016, 13 heterosexual men aged ≥16 years with MG were identified within a cohort study of men with and without NGU attending an urban sexually transmitted diseases clinic. Men had 6-7 monthly visits. NGU was defined as ≥5 polymorphonuclear leukocytes per high-power field on urethral Gram stain plus either visible urethral discharge or urethral symptoms. Men with NGU received 1 g of azithromycin. Men with persistent NGU received moxifloxacin 400 mg for 14 days. First-void urine was retrospectively tested for MG using transcription-mediated amplification. Resistance-associated mutations were detected by polymerase chain reaction (PCR) and sequencing. Organism load was determined by quantitative PCR. RESULTS: Sixty-two percent of MG-positive men had macrolide resistance-mediating mutations (MRMM) at enrollment; 31% had parC mutations (all outside the quinolone resistance-determining region). MG persisted after azithromycin in 7 men, 6 of whom had MRMM. The median duration of persistence in the absence of curative therapy was 143 days (range, 21-228). Five men experienced symptom resolution after azithromycin, but MG persisted for another 89-186 days before moxifloxacin. Organism load was somewhat lower in MRMM than wild-type infections (P = .16). CONCLUSIONS: The high prevalence of macrolide resistance and long duration of infection after symptom resolution highlights the need for diagnostic MG testing of men with NGU to direct therapy.

16.
Clin Infect Dis ; 66(5): 712-718, 2018 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-29045604

RESUMO

Background: Antimicrobial-resistant Neisseria gonorrhoeae is a major public health threat. The Centers for Disease Control and Prevention (CDC) recommends ceftriaxone 250 mg plus azithromycin (AZM) 1 g for gonorrhea treatment. Resistance to AZM could affect gonorrhea control efforts. Methods: Using gonococcal isolates collected at the Public Health-Seattle & King County (PHSKC) Sexually Transmitted Disease (STD) Clinic from 2012 to 2016, focusing on 2014-2016, we compared cases with the CDC AZM alert value minimum inhibitory concentration (MIC) (≥2 µg/mL) to those with AZM MIC ≤1 µg/mL, antimicrobial susceptibility profiles and clinical outcomes. Results: In 2012 and 2013, none of the 263 patients from whom we isolated N. gonorrhoeae from the urethra were infected with organisms with an AZM MIC ≥2 µg/mL. Between 2014 and 2016, 4.4% of 926 gonorrhea cases demonstrated reduced susceptibility to AZM; 93% of these cases occurred among men who have sex with men (MSM). Among MSM, 5.0% of 2014-2016 cases demonstrated reduced susceptibility to AZM. No AZM alert value isolates had concomitant cephalosporin resistance. There were 2 potential treatment failures: 1 pharyngeal infection treated with AZM 2 g alone, and 1 pharyngeal infection that persisted after study drug. Conclusions: Among MSM with gonorrhea in Seattle, 5% have gonorrhea with reduced susceptibility to AZM. The World Health Organization recommends changing treatment guidelines when >5% of isolates are resistant to a recommended drug. The emergence of resistant AZM gonorrhea should prompt reconsideration of current treatment recommendations, and highlights the need for new therapies for gonorrhea.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Suscetibilidade a Doenças/epidemiologia , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Adulto , Ceftriaxona/uso terapêutico , Resistência às Cefalosporinas , Farmacorresistência Bacteriana , Homossexualidade Masculina , Humanos , Masculino , Testes de Sensibilidade Microbiana , Minorias Sexuais e de Gênero , Washington/epidemiologia
17.
Emerg Infect Dis ; 23(10): 1657-1663, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28930001

RESUMO

We investigated whether outpatient antimicrobial drug prescribing is associated with Neisseria gonorrhoeae antimicrobial drug susceptibility in the United States. Using susceptibility data from the Gonococcal Isolate Surveillance Project during 2005-2013 and QuintilesIMS data on outpatient cephalosporin, macrolide, and fluoroquinolone prescribing, we constructed multivariable linear mixed models for each antimicrobial agent with 1-year lagged annual prescribing per 1,000 persons as the exposure and geometric mean MIC as the outcome of interest. Multivariable models did not demonstrate associations between antimicrobial drug prescribing and N. gonorrhoeae susceptibility for any of the studied antimicrobial drugs during 2005-2013. Elucidation of epidemiologic factors contributing to resistance, including further investigation of the potential role of antimicrobial drug use, is needed.


Assuntos
Antibacterianos/farmacologia , Prescrições de Medicamentos/estatística & dados numéricos , Farmacorresistência Bacteriana Múltipla , Neisseria gonorrhoeae/efeitos dos fármacos , Cefalosporinas/farmacologia , Cidades , Fluoroquinolonas/farmacologia , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Gonorreia/microbiologia , Humanos , Modelos Lineares , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Análise Multivariada , Neisseria gonorrhoeae/crescimento & desenvolvimento , Estados Unidos/epidemiologia
18.
Clin Infect Dis ; 65(6): 918-923, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28549097

RESUMO

Background: The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We identified a cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. Methods: Eight N. gonorrhoeae isolates collected from 7 patients on Oahu, Hawaii, seen 21 April 2016 through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by the Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 µg/mL and elevated ceftriaxone MICs (≥0.125 µg/mL). Isolates were sent to the University of Washington and CDC for confirmatory agar dilution testing; sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. Results: All isolates had azithromycin MICs >16 µg/mL and 5 had ceftriaxone MICs = 0.125 µg/mL by agar dilution. All isolates were ß-lactamase positive and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use, and no male patients reported male sex partners. All patients were successfully treated. Conclusions: This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer.


Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Ceftriaxona/farmacologia , Busca de Comunicante , Farmacorresistência Bacteriana Múltipla , Gonorreia/microbiologia , Gonorreia/transmissão , Neisseria gonorrhoeae/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Ceftriaxona/uso terapêutico , Ciprofloxacino/farmacologia , Quimioterapia Combinada , Feminino , Gonorreia/tratamento farmacológico , Hawaii , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neisseria gonorrhoeae/enzimologia , Neisseria gonorrhoeae/genética , Penicilinas/farmacologia , Tetraciclina/farmacologia , Adulto Jovem , beta-Lactamases/metabolismo
20.
J Antimicrob Chemother ; 71(10): 2798-803, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27439524

RESUMO

OBJECTIVES: MDR MRSA isolates cultured from primates, their facility and primate personnel from the Washington National Primate Research Center were characterized to determine whether they were epidemiologically related to each other and if they represented common local human-associated MRSA strains. METHODS: Human and primate nasal and composite environmental samples were collected, enriched and selected on medium supplemented with oxacillin and polymyxin B. Isolates were biochemically verified as Staphylococcus aureus and screened for the mecA gene. Selected isolates were characterized using SCCmec typing, MLST and WGS. RESULTS: Nasal cultures were performed on 596 primates and 105 (17.6%) were MRSA positive. Two of 79 (2.5%) personnel and two of 56 (3.6%) composite primate environmental facility samples were MRSA positive. Three MRSA isolates from primates, one MRSA from personnel, two environmental MRSA and one primate MSSA were ST188 and were the same strain type by conventional typing methods. ST188 isolates were related to a 2007 ST188 human isolate from Hong Kong. Both MRSA isolates from out-of-state primates had a novel MLST type, ST3268, and an unrelated group. All isolates carried ≥1 other antibiotic resistance gene(s), including tet(38), the only tet gene identified. CONCLUSIONS: ST188 is very rare in North America and has almost exclusively been identified in people from Pan-Asia, while ST3268 is a newly reported MRSA type. The data suggest that the primate MDR MRSA was unlikely to come from primate centre employees. Captive primates are likely to be an unappreciated source of MRSA.


Assuntos
Portador Sadio/veterinária , Farmacorresistência Bacteriana Múltipla/genética , Staphylococcus aureus Resistente à Meticilina/fisiologia , Doenças dos Primatas/microbiologia , Primatas/microbiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/transmissão , Animais , Proteínas de Bactérias/genética , Microbiologia Ambiental , Genótipo , Humanos , Pessoal de Laboratório , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Nariz/microbiologia , Proteínas de Ligação às Penicilinas/genética , Doenças dos Primatas/epidemiologia , Doenças dos Primatas/transmissão , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/veterinária , Estados Unidos/epidemiologia
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