RESUMO
BACKGROUND: The HONEYPOT trial failed to establish the superiority of exit-site application of Medihoney compared with nasal mupirocin prophylaxis for the prevention of peritonitis in peritoneal dialysis (PD) patients. This study aimed to assess the representativeness of the patients in the HONEYPOT trial to the Australian and New Zealand PD population. METHODS: This study compared baseline characteristics of the 371 PD patients in the HONEYPOT trial with those of 6,085 PD patients recorded on the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. RESULTS: Compared with the PD population, the HONEYPOT sample was older (standardized difference [d] = 0.19, p = 0.003), more likely to be treated with automated PD (d = 0.58, p < 0.001), had higher residual renal function (d = 0.26, p < 0.001) and a higher proportion of participants with end-stage kidney disease due to polycystic kidney disease (d = 0.17) and lower proportion due to diabetes (d = -0.17) and glomerulonephritis (d = -0.18) (p < 0.001), and lower proportions of indigenous people (d = -0.17, p < 0.001), current smokers (d = -0.10, p < 0.001), and people with prior histories of hemodialysis (d = -0.16, p < 0.001), diabetes mellitus (d = -0.18, p < 0.001), and coronary artery disease (d = -0.15, p < 0.001). CONCLUSIONS: HONEYPOT trial participants tended to be healthier than the Australian and New Zealand PD patient population. Although the differences between the groups were generally modest, it is possible that their cumulative effect may have had some impact on external generalizability, which is not an uncommon occurrence in clinical trials.
Assuntos
Mel/efeitos adversos , Mupirocina/administração & dosagem , Diálise Peritoneal/efeitos adversos , Peritonite/prevenção & controle , Idoso , Austrália , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Defesa do Paciente , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Projetos de Pesquisa , Sujeitos da Pesquisa/estatística & dados numéricos , Estudos RetrospectivosRESUMO
Candida glabrata can rapidly acquire mutations that result in drug resistance, especially to azoles and echinocandins. Identification of genetic mutations is essential, as resistance detected in vitro can often be correlated with clinical failure. We examined the feasibility of using whole genome sequencing (WGS) for genome-wide analysis of antifungal drug resistance in C. glabrata. The aim was torecognize enablers and barriers in the implementation WGS and measure its effectiveness. This paper outlines the key quality control checkpoints and essential components of WGS methodology to investigate genetic markers associated with reduced susceptibility to antifungal agents. It also estimates the accuracy of data analysis and turn-around-time of testing. Phenotypic susceptibility of 12 clinical, and one ATCC strain of C. glabrata was determined through antifungal susceptibility testing. These included three isolate pairs, from three patients, that developed rise in drug minimum inhibitory concentrations. In two pairs, the second isolate of each pair developed resistance to echinocandins. The second isolate of the third pair developed resistance to 5-flucytosine. The remaining comprised of susceptible and azole resistant isolates. Single nucleotide polymorphisms (SNPs) in genes linked to echinocandin, azole and 5-flucytosine resistance were confirmed in resistant isolates through WGS using the next generation sequencing. Non-synonymous SNPs in antifungal resistance genes such as FKS1, FKS2, CgPDR1, CgCDR1 and FCY2 were identified. Overall, an average of 98% of the WGS reads of C. glabrata isolates mapped to the reference genome with about 75-fold read depth coverage. The turnaround time and cost were comparable to Sanger sequencing. In conclusion, WGS of C. glabrata was feasible in revealing clinically significant gene mutations involved in resistance to different antifungal drug classes without the need for multiple PCR/DNA sequencing reactions. This represents a positive step towards establishing WGS capability in the clinical laboratory for simultaneous detection of antifungal resistance conferring substitutions.
Assuntos
Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Candida glabrata/genética , Sequenciamento Completo do Genoma/métodos , Farmacorresistência Fúngica , MutaçãoRESUMO
During 2014, henipavirus infection caused severe illness among humans and horses in southern Philippines; fatality rates among humans were high. Horse-to-human and human-to-human transmission occurred. The most likely source of horse infection was fruit bats. Ongoing surveillance is needed for rapid diagnosis, risk factor investigation, control measure implementation, and further virus characterization.
Assuntos
Surtos de Doenças , Infecções por Henipavirus/epidemiologia , Henipavirus/classificação , Adolescente , Adulto , Doenças dos Animais/epidemiologia , Doenças dos Animais/virologia , Animais , Sequência de Bases , Criança , Pré-Escolar , Feminino , Henipavirus/genética , Infecções por Henipavirus/diagnóstico , Infecções por Henipavirus/história , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Tipagem Molecular , Filipinas/epidemiologia , Filogenia , Vigilância da População , Alinhamento de Sequência , Sorotipagem , Proteínas Virais/química , Proteínas Virais/genética , Adulto JovemRESUMO
BACKGROUND: Invasive candidiasis (IC) is an important healthcare-related infection, with increasing incidence and a crude mortality exceeding 50%. Numerous treatment options are available yet comparative studies have not identified optimal therapy. METHODS: We conducted an individual patient-level quantitative review of randomized trials for treatment of IC and to assess the impact of host-, organism-, and treatment-related factors on mortality and clinical cure. Studies were identified by searching computerized databases and queries of experts in the field for randomized trials comparing the effect of ≥2 antifungals for treatment of IC. Univariate and multivariable analyses were performed to determine factors associated with patient outcomes. RESULTS: Data from 1915 patients were obtained from 7 trials. Overall mortality among patients in the entire data set was 31.4%, and the rate of treatment success was 67.4%. Logistic regression analysis for the aggregate data set identified increasing age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02; P = .02), the Acute Physiology and Chronic Health Evaluation II score (OR, 1.11; 95% CI, 1.08-1.14; P = .0001), use of immunosuppressive therapy (OR, 1.69; 95% CI, 1.18-2.44; P = .001), and infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11-2.39; P = .01) as predictors of mortality. Conversely, removal of a central venous catheter (CVC) (OR, 0.50; 95% CI, .35-.72; P = .0001) and treatment with an echinocandin antifungal (OR, 0.65; 95% CI, .45-.94; P = .02) were associated with decreased mortality. Similar findings were observed for the clinical success end point. CONCLUSIONS: Two treatment-related factors were associated with improved survival and greater clinical success: use of an echinocandin and removal of the CVC.
Assuntos
Antifúngicos/administração & dosagem , Candidíase Invasiva/tratamento farmacológico , Adulto , Idoso , Cateterismo Venoso Central/efeitos adversos , Equinocandinas/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Suspensão de TratamentoRESUMO
OBJECTIVES: The primary objective of this study is to determine whether daily exit-site application of standardized antibacterial honey (Medihoney Antibacterial Wound Gel; Comvita, Te Puke, New Zealand) results in a reduced risk of catheter-associated infections in peritoneal dialysis (PD) patients compared with standard topical mupirocin prophylaxis of nasal staphylococcal carriers. DESIGN: Multicenter, prospective, open label, randomized controlled trial. SETTING: PD units throughout Australia and New Zealand. PARTICIPANTS: The study will include both incident and prevalent PD patients (adults and children) for whom informed consent can be provided. Patients will be excluded if they have had (1) a history of psychological illness or condition that interferes with their ability to understand or comply with the requirements of the study; (2) recent (within 1 month) exit-site infection, peritonitis, or tunnel infection; (3) known hypersensitivity to, or intolerance of, honey or mupirocin; (4) current or recent (within 4 weeks) treatment with an antibiotic administered by any route; or (5) nasal carriage of mupirocin-resistant Staphylococcus aureus. METHODS: 370 subjects will be randomized 1:1 to receive either daily topical exit-site application of Medihoney Antibacterial Wound Gel (all patients) or nasal application of mupirocin if staphylococcal nasal carriage is demonstrated. All patients in the control and intervention groups will perform their usual exit-site care according to local practice. The study will continue until 12 months after the last patient is recruited (anticipated recruitment time is 24 months). MAIN OUTCOME MEASURES: The primary outcome measure will be time to first episode of exit-site infection, tunnel infection, or peritonitis, whichever comes first. Secondary outcome measures will include time to first exit-site infection, time to first tunnel infection, time to first peritonitis, time to infection-associated catheter removal, catheter-associated infection rates, causative organisms, incidence of mupirocin-resistant microbial isolates, and other adverse reactions. CONCLUSIONS: This multicenter Australian and New Zealand study has been designed to provide evidence to help nephrologists and their PD patients determine the optimal strategy for preventing PD catheter-associated infections. Demonstration of a significant improvement in PD catheter-associated infections with topical Medihoney will provide clinicians with an important new prophylactic strategy with a low propensity for promoting antimicrobial resistance.
Assuntos
Infecções Relacionadas a Cateter/etiologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres de Demora/efeitos adversos , Mel , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/instrumentação , Administração Tópica , Adulto , Austrália , Criança , Estudos de Coortes , Humanos , Nova Zelândia , Projetos de PesquisaRESUMO
We evaluated a combined panfungal PCR-reverse line blot (RLB) hybridization assay based on internal transcribed spacer 1 (ITS1) and ITS2 region polymorphisms to identify 159 Candida, Cryptococcus neoformans, and Aspergillus isolates (22 species). Its utility to identify fungal pathogens directly from 27 clinical specimens was also determined. ITS sequence analysis was performed to resolve discrepant identifications or where no RLB result was obtained. Species-specific ITS2- and ITS1-based probes correctly identified 155 of 159 isolates (98%) and 149 (93.7%) isolates, respectively. All strains were unambiguously differentiated with the exception of cross-reactivity between the Candida norvegensis probe and Candida haemulonii DNA product. Species identification of the pathogen was made for all 21 specimens (sensitivity of 100%) where species-specific probes were included in the RLB; however, there was no ITS2 probe-based hybridization signal for two specimens. Results were concordant with the culture results for 18 (85.7%) specimens. The assay was able to provide species identification in the absence of a culture result (two specimens) and to detect mixed infection (one specimen). The results indicate that the RLB assay is capable of reliably detecting yeasts and Aspergillus spp. in clinical specimens and that the incorporation of both ITS1- and ITS2-targeted probes is required for optimal sensitivity. The test has potential utility in the early diagnosis of invasive fungal infection, since "fungal" DNA was detected in all 27 specimens. Prior to incorporation of probes to detect other fungal species, ITS sequencing may be performed to achieve species identification.