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BACKGROUND: The decision to use a particular test to diagnose patients presenting with symptoms of vaginitis and/or STI is based primarily on the prevailing standards of care in the clinic at which the patient evaluation takes place. As a result, laboratory testing of vaginal samples for these patients often involves either an STI or a vaginitis test, but rarely both options simultaneously, which complicates the diagnosis and management of concurrent infections. METHODS: Using de-identified remnant vaginal specimens from symptomatic patients previously tested for STI (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC) and Trichomonas vaginalis (TV)) with the Becton Dickinson (BD) CTGCTV2 assay for BD MAX System, positivity for bacterial vaginosis (BV) and Candida spp (associated with vulvovaginal candidiasis (VVC)) were evaluated using the molecular-based BD MAX Vaginal Panel. FINDINGS: The rate of STI/BV co-infection was 79.4% (227/286) in this symptomatic population, while that of STI/VVC was 27.0% (77/285). Women diagnosed with any one of the three STIs tested had an OR 2.86 (95% CI, 1.99, 4.11; p<0.0001) for a concurrent BV infection and OR 0.96 (95% CI, 0.67, 1.37; p=0.8085) for infection with Candida species. CONCLUSION: Our results suggest that women being tested for STI have a high prevalence of co-infection with BV and a lower, although appreciable, prevalence of co-infection with VVC. The detection of co-occurring vaginal infections can be facilitated by molecular testing using a single sample.
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Gepotidacin is a triazaacenaphthylene antibiotic with activity against Neisseria gonorrhoeae including strains resistant to current agents. We tested 145 N. gonorrhoeae isolates by agar dilution according to Gonococcal Isolate Surveillance Program and Clinical and Laboratory Standards Institute methodologies. Gepotidacin demonstrated a minimum inhibitory concentration (MIC)50 of 0.25 µg/mL and a MIC90 of 0.5 µg/mL (highest gepotidacin MIC was 1 µg/mL) against the 145 N. gonorrhoeae isolates tested. We also assessed the impact of test variables on antimicrobial susceptibility test results for gepotidacin, ciprofloxacin, and ceftriaxone against 10 N. gonorrhoeae isolates. Media type had the biggest effect but wasn't specific to gepotidacin. Gepotidacin MICs were also affected by inoculum, pH, and 10% CO2. These in vitro data indicate that further study of gepotidacin is warranted for potential use in treating gonorrhea infections and highlight the importance of controlling for media type, inoculum, CO2, and pH when performing MIC testing with gepotidacin.
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Acenaftenos/farmacología , Antibacterianos/farmacología , Compuestos Heterocíclicos con 3 Anillos/farmacología , Pruebas de Sensibilidad Microbiana/métodos , Neisseria gonorrhoeae/efectos de los fármacos , Dióxido de Carbono/análisis , Medios de Cultivo , Farmacorresistencia Bacteriana/efectos de los fármacos , Gonorrea/microbiología , Humanos , Concentración de Iones de Hidrógeno , Masculino , Pruebas de Sensibilidad Microbiana/instrumentación , Neisseria gonorrhoeae/aislamiento & purificaciónRESUMEN
Growth in open-source hardware designs combined with the decreasing cost of high-quality 3D printers have supported a resurgence of in-house custom lab equipment development. Herein, we describe a low-cost (< $400), open-source CO2 incubator. The system is comprised of a Raspberry Pi computer connected to a 3D printer controller board that has controls for a CO2 sensor, solenoid valve, heater, and thermistors. CO2 is supplied through the sublimation of dry ice stored inside a thermos to create a sustained 5% CO2 supply. The unit is controlled via G-Code commands sent by the Raspberry Pi to the controller board. In addition, we built a custom software application for remote control and used the open-source Grafana dashboard for remote monitoring. Our data show that we can maintain consistent CO2 and temperature levels for over three days without manual interruption. The results from our culture plates and real-time PCR indicate that our incubator performed equally well when compared to a much more expensive commercial CO2 incubator. We have also demonstrated that the antibiotic susceptibility assay can be performed in this low-cost CO2 incubator. Our work also indicates that the system can be connected to incubator chambers of various chamber volumes.
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Antibacterianos/farmacología , Dióxido de Carbono/análisis , Gonorrea/diagnóstico , Incubadoras/estadística & datos numéricos , Neisseria gonorrhoeae/crecimiento & desarrollo , Impresión Tridimensional/instrumentación , Dióxido de Carbono/química , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Humanos , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/aislamiento & purificación , Programas InformáticosRESUMEN
We evaluated microbiological correlates for the successful treatment of Neisseria gonorrhoeae isolates from a phase 2 study of gepotidacin, a novel triazaacenaphthylene antibacterial, for therapy of uncomplicated urogenital gonorrhea. Culture, susceptibility testing, genotypic characterization, and frequency of resistance (FoR) were performed for selected isolates. Microbiological success was defined as culture-confirmed eradication of N. gonorrhoeae Against 69 baseline urogenital isolates, gepotidacin MICs ranged from ≤0.06 to 1 µg/ml (MIC90 = 0.5 µg/ml). For gepotidacin, the ratio of the area under the free-drug concentration-time curve to the MIC (fAUC/MIC) was associated with therapeutic success. Success was 100% (61/61) at fAUC/MICs of ≥48 and decreased to 63% (5/8) for fAUC/MICs of ≤25. All 3 isolates from microbiological failures were ciprofloxacin resistant, had a baseline gepotidacin MIC of 1 µg/ml, and carried a preexisting ParC D86N mutation, a critical residue for gepotidacin binding. In a test-of-cure analysis, the resistance to gepotidacin emerged in 2 isolates (MICs increased ≥32-fold) with additional GyrA A92T mutations, also implicated in gepotidacin binding. Test-of-cure isolates had the same sequence type as the corresponding baseline isolates. For 5 selected baseline isolates, all carrying a ParC D86N mutation, the in vitro FoR to gepotidacin was low (10-9 to 10-10); the resistant mutants had the same A92T mutation as the 2 isolates in which resistance emerged. Five participants with isolates harboring the ParC D86N mutation were treatment successes. In summary, fAUC/MICs of ≥48 predicted 100% microbiological success, including 3 isolates with the ParC D86N mutation (fAUC/MICs ≥ 97). Pharmacokinetic/pharmacodynamic determinations may help to evaluate new therapies for gonorrhea; further study of gepotidacin is warranted. (This study has been registered at ClinicalTrials.gov under identifier NCT02294682.).
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Acenaftenos/farmacocinética , Antibacterianos/farmacocinética , Topoisomerasa de ADN IV/genética , Farmacorresistencia Bacteriana/genética , Gonorrea/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Neisseria gonorrhoeae/efectos de los fármacos , Acenaftenos/sangre , Acenaftenos/farmacología , Administración Oral , Adulto , Antibacterianos/sangre , Antibacterianos/farmacología , Área Bajo la Curva , Técnicas de Tipificación Bacteriana , Cultivo de Sangre , Ciprofloxacina/uso terapéutico , Topoisomerasa de ADN IV/metabolismo , Esquema de Medicación , Femenino , Expresión Génica , Gonorrea/sangre , Gonorrea/microbiología , Gonorrea/patología , Compuestos Heterocíclicos con 3 Anillos/sangre , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Mutación , Neisseria gonorrhoeae/enzimología , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/aislamiento & purificación , Resultado del TratamientoRESUMEN
[This corrects the article DOI: 10.1038/s41522-017-0020-7.].
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Fecal microbiota transplantation has been shown to be an effective treatment for patients with recurrent C. difficile colitis. Although fecal microbiota transplantation helps to re-establish a normal gut function in patients, the extent of the repopulation of the recipient microbial community varies. To further understand this variation, it is important to determine the fate of donor microbes in the patients following fecal microbiota transplantation. We have developed a new method that utilizes the unique single nucleotide variants of gut microbes to accurately identify microbes in paired fecal samples from the same individual taken at different times. Using this method, we identified transplant donor microbes in seven recipients 3-6 months after fecal microbiota transplantation; in two of these fecal microbiota transplantation, we were able to identify donor microbes that persist in recipients up to 2 years post-fecal microbiota transplantation. Our study provides new insights into the dynamics of the reconstitution of the gastrointestinal microbe community structure following fecal microbiota transplantation.
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BACKGROUND: Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient's gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice. RESULTS: A total of nine samples from three human donors, recipient's pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01%). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8%, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55%, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2-4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7% of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10%. CONCLUSION: We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early after transplant. The commensal microbes present at early times post FMT out competed non-commensal microbes (e.g. such as unclassified Clostridiales) for niche space. The selective advantage of these commensal microbes to occupy niches in the gastrointestinal tract helps to explain the success of FMT to reconstitute the gut microbe community of patients with recurrent C. difficile infections.
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Bacterias/crecimiento & desarrollo , Clostridioides difficile/fisiología , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Anciano , Anciano de 80 o más Años , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Infecciones por Clostridium/microbiología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
We report the use of fecal microbiota transplantation in a single heart-kidney transplant recipient with recurrent Clostridium difficile, vancomycin-resistant Enterococcus (VRE) fecal dominance, and recurrent VRE infections. Fecal microbiota transplantation resulted in the reconstruction of a diverse microbiota with (1) reduced relative abundance of C difficile and VRE and (2) positive clinical outcome.
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BACKGROUND: Progressive resistance to antimicrobial agents has reduced options for gonorrhea therapy worldwide. Solithromycin (CEM-101) is a novel oral fluoroketolide antimicrobial with substantial in vitro activity against Neisseria gonorrhoeae. METHODS: We conducted a phase 2 trial of 2 oral doses of solithromycin (1200 and 1000 mg) for treatment of uncomplicated gonorrhea. RESULTS: A total of 59 participants were enrolled and treated in this trial; 28 participants received 1200 mg of solithromycin and 31 received 1000 mg. Forty-six (78%) participants had positive cultures for N. gonorrhoeae at the time of enrollment: 24 of the 28 persons (86%) who received 1200 mg of oral solithromycin, and 22 of 31 (71%) who received 1000 mg. In addition, 8 participants had positive pharyngeal gonococcal cultures, and 4 had positive rectal cultures. All patients with positive cultures for N. gonorrhoeae were cured at all sites of infection. Chlamydia trachomatis and Mycoplasma genitalium coinfections were evaluated using nucleic acid amplification tests and were negative at 1 week of follow-up in 9 of 11 (82%) participants positive for C. trachomatis and 7 of 10 (70%) participants positive for M. genitalium. Mild dose-related gastrointestinal side effects (nausea, loose stools, vomiting) were common but did not limit therapy. CONCLUSIONS: Oral single-dose solithromycin, in doses of 1000 mg and 1200 mg, was 100% effective for treatment of culture-proven gonorrhea at genital, oral, and rectal sites of infection and is a promising new agent for gonorrhea treatment. CLINICAL TRIALS REGISTRATION: NCT01591447.
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Antibacterianos , Gonorrea/tratamiento farmacológico , Macrólidos , Triazoles , Administración Oral , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Femenino , Gonorrea/microbiología , Humanos , Macrólidos/administración & dosificación , Macrólidos/efectos adversos , Macrólidos/uso terapéutico , Masculino , Persona de Mediana Edad , Neisseria gonorrhoeae/efectos de los fármacos , Triazoles/administración & dosificación , Triazoles/efectos adversos , Triazoles/uso terapéutico , Adulto JovenRESUMEN
Tests for Chlamydia trachomatis and Neisseria gonorrhoeae, which can provide results rapidly to guide therapeutic decision-making, offer patient care advantages over laboratory-based tests that require several days to provide results. We compared results from the Cepheid GeneXpert CT/NG (Xpert) assay to results from two currently approved nucleic acid amplification assays in 1,722 female and 1,387 male volunteers. Results for chlamydia in females demonstrated sensitivities for endocervical, vaginal, and urine samples of 97.4%, 98.7%, and 97.6%, respectively, and for urine samples from males, a sensitivity of 97.5%, with all specificity estimates being ≥ 99.4%. Results for gonorrhea in females demonstrated sensitivities for endocervical, vaginal, and urine samples of 100.0%, 100.0%, and 95.6%, respectively, and for urine samples from males, a sensitivity of 98.0%, with all estimates of specificity being ≥ 99.8%. These results indicate that this short-turnaround-time test can be used to accurately test patients and to possibly do so at the site of care, thus potentially improving chlamydia and gonorrhea control efforts.
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Técnicas Bacteriológicas/métodos , Chlamydia trachomatis/aislamiento & purificación , Gonorrea/diagnóstico , Linfogranuloma Venéreo/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Neisseria gonorrhoeae/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Chlamydia trachomatis/genética , Femenino , Humanos , Masculino , Neisseria gonorrhoeae/genética , Sistemas de Atención de Punto , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
We evaluated Neisseria gonorrhoeae Etest minimum inhibitory concentrations (MICs) relative to agar dilution MICs for 664 urethral isolates for ceftriaxone (CRO) and azithromycin (AZM), 351 isolates for cefpodoxime (CPD) and 315 isolates for cefixime (CFM). Etest accurately determined CPD, CFM and AZM MICs, but resulted in higher CRO MICs.
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Antibacterianos/farmacología , Azitromicina/farmacología , Cefalosporinas/farmacología , Neisseria gonorrhoeae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodos , Neisseria gonorrhoeae/aislamiento & purificación , Uretra/microbiologíaRESUMEN
Screening for subclinical herpes simplex virus type 2 (HSV-2) may be a useful adjunct in human immunodeficiency virus (HIV) care. However, HSV-2 serological tests have been suggested to perform less well in HIV-infected populations. In this study, HerpeSelect HSV-2 ELISA was compared with the Sure-Vue Rapid HSV-2 Test for HSV-2 screening of sera from 310 HIV-infected persons receiving care at an HIV-dedicated clinic in the Southeastern United States. In the study, assay agreement and whether the performance of both tests, rather than 1 test alone, would improve screening accuracy were determined. Overall percent test agreement was 96%. Negative percent agreement was best at a HerpeSelect index value <0.90 and positive percent agreement was best at a HerpeSelect index value ≥3.0 (97% and 100%, respectively). Using the manufacturer's established cutoffs for a HerpeSelect positive test result versus negative test result, discordant results between assays occurred in 4% of the cases, and the majority of these cases occurred when the HerpeSelect index value was between 0.9 and 2.9. These data suggest a good correlation between the HerpeSelect and the Sure-Vue HSV-2 Rapid Test in a U.S. HIV-infected population and suggest that confirmatory testing may not help in HSV-2 diagnosis except in cases where HerpeSelect index values are between 0.9 and 3.0.
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Infecciones por VIH/complicaciones , Herpes Genital/complicaciones , Herpesvirus Humano 2/aislamiento & purificación , Pruebas Serológicas/normas , Adolescente , Adulto , Anciano , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Herpes Genital/sangre , Herpes Genital/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Adulto JovenRESUMEN
PURPOSE: To examine resident workflow as part of an institutional approach to redesigning the processes of health care delivery. METHOD: In 2003 the authors observed the workflows for 24 hours of seven residents who were at various levels of training (two each from the internal medicine, pediatrics, and obstetrics and gynecology programs, and one from general surgery) at Denver Health Medical Center, an urban, public teaching hospital. RESULTS: Although the residents spent varying proportions of their time in various activities, all had extremely fragmented workflows as they engaged in from 5.0 to 11.3 different activities per hour of nonsleeping time, many of which required only minutes to complete. All residents experienced frequent interruptions and changes in focus. The internal medicine and surgery residents spent large amounts of time traveling, covering three and six miles, respectively, during their 24-hour shifts. Three of the residents slept between one-quarter and one-third of their time on duty (one without any interruption). CONCLUSIONS: The authors suggest that fragmented workflow exists in all residency programs and that applying the same work limitations to all residents in all training programs (to reduce fatigue-related errors) may be overly restrictive. Improving these processes of care will be difficult and will likely require analytic skills and knowledge of systems engineering that most physicians do not have.