This study aimed to determine the predictors of persistent candidemia and examine the impact of biofilm formation by Candida isolates in adult patients with candidemia. Of the adult patients with candidemia in Kaohsiung Chang Gung Memorial Hospital between January 2007 and December 2012, 68 case patients with persistent candidemia (repeated candidemia after a 3-day systemic antifungal therapy) and 68 control patients with non-persistent candidemia (Candida clearance from the bloodstream after a 3-day systemic antifungal therapy) were included based on propensity score matching and matching for the Candida species isolated. Biofilm formation by the Candida species was assessed in vitro using standard biomass assays. Presence of central venous catheters (CVCs) at diagnosis (adjusted odd ratio [AOR], 3.77; 95% confidence interval [CI], 1.09–13.00, p = 0.04), infection with higher biofilm forming strains of Candida species (AOR, 8.03; 95% CI, 2.50–25.81; p < 0.01), and receipt of suboptimal fluconazole doses as initial therapy (AOR, 5.54; 95% CI, 1.53–20.10; p < 0.01) were independently associated with persistent candidemia. Biofilm formation by Candida albicans, C. tropicalis, and C. glabrata strains was significantly higher in the case patients than in the controls. There were no significant differences in the overall mortality and duration of hospitalization between the two groups. Our data suggest that, other than presence of retained CVCs and use of suboptimal doses of fluconazole, biofilm formation was highly associated with development of persistent candidemia.
Summary Poor clinical outcomes for invasive aspergillosis are associated with antifungal resistance. Performing antifungal susceptibility tests on clinically relevant Aspergillus isolates from patients and environmental regions with known azole resistance is recommended. The aim of the study was to assess the presence of azole resistance in clinical Aspergillus spp. isolates and those from hospital environments and farmlands within a 40 km radius of the hospital. Clinical Aspergillus spp. isolates were cultured, as well as environmental Aspergillus spp. isolates obtained from air samples. Samples were subcultured in azole‐containing agar plates. Isolates with a positive screening test were subjected to YeastOne methods to determine their minimum inhibitory concentrations of antifungals. Resistance mechanisms were investigated in the azole‐resistant Aspergillus spp. isolates. No azole‐resistant clinical or environmental A flavus, A oryaze, A niger or A terreus isolates were found in the present study. All A fumigatus clinical isolates were azole‐susceptible. Seven A fumigatus environmental isolates were associated with cyp51A mutations, including two that harboured TR34/L98H mutations with S297T/F495I substitutions, two with TR34/L98H mutations and three with TR46/Y121F/T289A mutations. One of these isolates was collected from farmland, one was from A ward and five were from B ward. The proportion of azole‐resistant A fumigatus was 10.2% (6/59) and 3.2% (1/31) in the hospital environments and the farmlands near the hospital, respectively. The results showed that azole‐resistant A fumigatus existed within hospital environments. This emphasises the importance of periodic surveillance in hospital environments and monitoring for the emergence of azole‐resistant A fumigatus clinical isolates.
Cryptococcal meningoencephalitis (CM) is a treatable condition, but it leads to excessive morbidity and mortality. We collected 115 non-duplicated Cryptococcus clinical isolates during 2013–2020 in southern Taiwan to perform antifungal susceptibility testing. Multi-locus sequence typing was performed on 96 strains from patients with CM (n = 47) or cryptococcemia (n = 49). In addition, the epidemiological and clinical characteristics of patients with CM during 2013–2020 (n = 47) were compared with those during 2000–2010 (n = 46). During 2013–2020, only one C. neoformans isolate (0.9%) had a fluconazole minimum inhibitory concentration of >8 μg/mL. Amphotericin B (AMB), flucytosine (5FC), and voriconazole were highly active against all C. neoformans/C. gattii isolates. The most common sequence type was ST5. Among these 47 patients with CM, cerebrospinal fluid cryptococcal antigen (CSF CrAg) titer >1024 was a significant predictor of death (odds ratio, 48.33; 95% CI, 5.17–452.06). A standard induction therapy regimen with AMB and 5FC was used for all patients during 2013–2020, but only for 2.2% of patients in 2000–2010. The in-hospital CM mortality rate declined from 39.1% during 2000–2010 to 25.5% during 2013–2020, despite there being significantly younger patients with less CSF CrAg >1024 during 2000–2010. The study provides insight into the genetic epidemiology and antifungal susceptibility of Cryptococcus strains in southern Taiwan. The recommended antifungal drugs, AMB, 5FC, and FCZ, remained active against most of the Cryptococcus strains. Early diagnosis of patients with CM and adherence to the clinical practice guidelines cannot be overemphasized to improve the outcomes of patients with CM.
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