RESUMEN
BACKGROUND: Diabetes complicates tuberculosis (TB) treatment including a prolonged time of sputum culture conversion to negative growth. Since 2013 in Virginia, interventions early in the treatment course have used therapeutic drug monitoring and dose correction for isoniazid and rifampin after 2 weeks of TB treatment in patients with diabetes along with nurse manager initiated diabetes education and linkage to care. METHODS: A retrospective cohort study of the state TB registry was performed for patients initiating drug-susceptible pulmonary TB treatment that were matched for age, gender, chest imaging and sputum smear status to compare time to sputum culture conversion and other clinical outcomes in the pre-and post-intervention groups. RESULTS: Three hundred sixty-three patients had documented time to sputum culture conversion in the pre-and post-intervention periods, including 56 (15%) with diabetes. Seventy-four (57%) of all patients with diabetes were ≥60 years of age at treatment initiation. Twenty-six patients with diabetes were matched in each group. Mean time to sputum culture conversion in the post-intervention group was 42 ± 22 days compared to the pre-intervention group of 62 ± 31 days (p = 0.01). In the post-intervention group 21 (80%) of patients with diabetes had culture conversion by 2 months compared to 13 (50%) in the pre-intervention group (p = 0.04). CONCLUSIONS: Early interventions for diabetes related TB in the programmatic setting may hasten sputum culture conversion.
Asunto(s)
Antituberculosos/uso terapéutico , Complicaciones de la Diabetes , Esputo/microbiología , Tuberculosis/tratamiento farmacológico , Adulto , Anciano , Antituberculosos/farmacología , Monitoreo de Drogas , Intervención Educativa Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Estudios Retrospectivos , Tuberculosis/complicaciones , VirginiaRESUMEN
Therapeutic drug monitoring may be useful in tuberculosis management, but programmatic implementation is understudied. We performed a retrospective cohort study to determine prevalence of lower than expected levels of isoniazid, rifampin, ethambutol, and pyrazinamide measured at time of estimated peak serum concentration. Patients were tested for serum concentration at 2 hours after medication administration. When patients were tested, 22 had concentrations lower than expected range for rifampin, 23 of 39 patients had low levels of isoniazid, and 8 of 26 patients had low levels of ethambutol; all 20 patients tested for pyrazinamide were within expected range. Over 26 months, 42 patients met criteria for slow response. Diabetes was associated with slow response (p<0.001), and persons with diabetes were more likely than persons without diabetes to have low rifampin levels (p = 0.03). Dosage adjustment of rifampin was more likely to elevate serum concentration to the target range than adjustment of isoniazid given in daily doses (p = 0.01).
Asunto(s)
Antituberculosos/administración & dosificación , Antituberculosos/sangre , Monitoreo de Drogas , Programas de Gobierno , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antituberculosos/uso terapéutico , Estudios de Cohortes , Etambutol/administración & dosificación , Etambutol/sangre , Etambutol/uso terapéutico , Femenino , Humanos , Isoniazida/administración & dosificación , Isoniazida/sangre , Isoniazida/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rifampin/administración & dosificación , Rifampin/sangre , Rifampin/uso terapéutico , Resultado del Tratamiento , Virginia/epidemiología , Adulto JovenRESUMEN
Hybridization of digested DNA to probes derived from repeated sequences has proven to be an extremely powerful epidemiologic tool for studying the relatedness of fungi. The dispersed nature of these sequences throughout the genome provides the discriminatory power for distinguishing two independent isolates from each other based on banding pattern. The genome of Cryptococcus neoformans contains a number of classes of transposable elements, which are often present in multiple copies. We characterized a probe related to the Ty3/gypsy class of transposable elements called TCN1 and used it to screen multiple isolates from all four serotypes of C. neoformans. DNA with TCN1 homology could be amplified from each isolate of serotypes A and D and all isolates hybridized to a probe derived from TCN1. Isolates from serotype B and C were also tested for the presence of a TCN1 homolog, however, only some of these isolates yielded both a TCN1-specific PCR product or hybridization signal. Comparison of the TCN1 hybridization patterns of serotypes A and D to multiple RAPD patterns of the same isolates suggested that TCN1 was more discriminating and therefore, a useful epidemiological tool.
Asunto(s)
Criptococosis/microbiología , Cryptococcus neoformans/clasificación , Sondas de ADN/genética , Retroelementos/genética , Cryptococcus neoformans/genética , Dermatoglifia del ADN/métodos , ADN de Hongos/química , ADN de Hongos/genética , Humanos , Reacción en Cadena de la Polimerasa/métodos , Técnica del ADN Polimorfo Amplificado Aleatorio , SerotipificaciónRESUMEN
Bordetella holmesii is a Gram-negative bacterium first identified in 1995. It can cause pertussis-like symptoms in humans. B. holmesii contains insertion sequences IS481 and IS1001, two frequently used targets in the PCR diagnosis of Bordetella pertussis and Bordetella parapertussis infections. To investigate the prevalence of B. holmesii in Finnish and Dutch patients with pertussis-like symptoms and whether B. holmesii has caused any false-positive results in diagnostic PCRs, B. holmesii-specific real-time PCRs were developed. The Finnish methods were conventional IS481 PCR and B. holmesii-specific real-time PCR (LightCycler, Roche) targeting the B. holmesii recA gene. The Dutch methods were IS481 and IS1001 PCRs with conventional or real-time formats and B. holmesii-specific real-time PCR targeting the homologue of IS1001. Of 11,319 nasopharyngeal swabs, 2804 were collected from Finnish patients from 2000 to 2003, and 8515 from Dutch patients from 1992 to 2003. B. holmesii DNA was not found in the samples analysed. The results suggest that B. holmesii is not among the causative agents of pertussis-like symptoms in Finnish and Dutch patients and thus does not in practice confound IS481 and IS1001 PCRs.
Asunto(s)
Bordetella/aislamiento & purificación , ADN Bacteriano/genética , Nasofaringe/microbiología , Tos Ferina/epidemiología , Proteínas Bacterianas/genética , Secuencia de Bases , Bordetella/genética , Elementos Transponibles de ADN/genética , Finlandia/epidemiología , Humanos , Datos de Secuencia Molecular , Países Bajos/epidemiología , Reacción en Cadena de la Polimerasa/métodos , Rec A Recombinasas/genética , Sensibilidad y Especificidad , Alineación de Secuencia , Tos Ferina/diagnósticoRESUMEN
Candida dubliniensis is a newly identified species of Candida that is phenotypically similar to but genetically distinct from C. albicans. This organism has been recovered with increasing frequency from the oral cavities of human immunodeficiency virus (HIV)-infected and AIDS patients and has been implicated as a causative agent of oral candidiasis and systemic disease. In the present study we characterized the molecular mechanisms of resistance to fluconazole (FLC) in C. dubliniensis clinical isolates from two different HIV-infected patients with oropharyngeal candidiasis. Isolates were identified to the species level by phenotypic and genotypic tests. DNA-typing techniques were used to assess strain identity. Antifungal susceptibility testing was performed by NCCLS techniques. Northern blotting analysis was used to monitor the expression of genes encoding lanosterol demethylase (ERG11) and efflux transporters (CDR and MDR1) in matched sets of C. dubliniensis-susceptible and -resistant isolates by using probes generated from their homologous C. albicans sequences. In addition, ERG11 genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. Decreasing susceptibilities to FLC were detected in C. dubliniensis isolates recovered from both patients during the course of treatment. FLC-resistant C. dubliniensis isolates from one patient demonstrated combined upregulation of the MDR1, CDR1, and ERG11 genes. Among the isolates from the second patient, all isolates showing decreased susceptibility to FLC demonstrated upregulation of MDR1, whereas the levels of mRNA for the ERG11 genes remained constant and the expression of CDR genes was negligible. Fourteen point mutations were found in the ERG11 genes of the isolates with decreased susceptibility to FLC. These data demonstrate that the development of azole resistance in C. dublinensis clinical isolates from HIV-infected patients treated with FLC is mediated by multiple molecular mechanisms of resistance, similar to the observations found in the case of C. albicans.