To what degree could clinical trials in evidence based medicine reflect reality in the treatment of candidemia?

IntroductionEvidenced based medicine (EBM) is necessary to standardize or treatment for infection since EBM is established based on the results of clinical trials. Entry criteria for clinical trials are very strict, and many patients have difficulties in being enrolled in any clinical trials regarding candidemia. It is questionable if the results of clinical trials reflect the real world of general medicine in this case.Patients and methodsFor the purpose of examining how many patients could join any randomized clinical trials for the treatment of candidemia, we reviewed all the candidemia patients in our institute during 2014–2018. The patients were divided into two groups: patients who were eligible for clinical trials (participation possible group), and those who were not (participation impossible group). Exclusion criteria for clinical trials were set based on previous clinical trials.ResultsA total of 70 patients was enrolled in this study. The median age was 73 years (range 36–93 years). Of these, 41 patients (59%) were male. As for site of infections, catheter related blood stream infection was most frequently seen in 37 (53%). Seventeen patients (24%) were classified as participation possible group and 53 patients (76%) were participation impossible group. Comparing the two groups, participation possible group patients have much better performance status, have less comorbidities and have longer overall survival times than participation impossible group patients.ConclusionOnly 24% of candidemia patients were eligible for the clinical trials. Thus, we can see that clinical trials might not correctly reflect the real world among candidemia patients.     

Azoles versus conventional amphotericin B for the treatment of candidemia: A meta-analysis of randomized controlled trials

Because exclusive use of echinocandins can induce the drug-resistant strains, appropriate use of azoles and polyenes is still necessary in the treatment of candidemia. In this study, we conducted a meta-analysis of randomized controlled trials regarding the efficacy and safety of azole and polyene antifungals in the treatment of candidemia. MEDLINE and the Cochrane Register of Controlled Trials were used as reference databases, and papers published up to June 10, 2019 were searched. The search results were carefully scrutinized, duplicate references were removed, and the study was ultimately carried out using three reports. Among azole antifungals, fluconazole and voriconazole were extracted, however; only conventional amphotericin B (AMPH-B) was extracted among polyene antifungals. Treatment successes with the use of azoles and AMPH-B were compared, and findings showed that AMPH-B was significantly superior (RR = 0.90, 95% CI 0.82–1.00, p = 0.04). However, there was no significant difference in mortality (RR = 0.87, 95% CI 0.72–1.07, p = 0.19). Analysis of adverse events showed that renal disorders were significantly less common with azoles than with AMPH-B (RR = 0.26, 95% CI 0.10–0.68, p = 0.006). In conclusion, AMPH-B were superior to azoles in terms of efficacy, but had a risk of causing renal disorders.     

Individual risk factors and critical care unit effects on Invasive Candida Infection occurring in critical care units in the UK: A multilevel model

Geographical variation is observed in invasive candida infection (ICI) and differences between critical care units (CCUs) may contribute. To examine rates, risk factors and individual and unit‐level variation of ICI in UK CCUs. Data from the Fungal Infection Risk Evaluation Study was used to examine individuals admitted to 96 CCUs in the UK; July 2009‐March 2011. Cases were non‐neutropenic individuals aged 18 years and over with ICI identified after admission. Mixed‐effects Poisson regression models adjusted for the CCU. There were 225 cases of ICI, a rate of 6.84/10 000 bed days and a threefold variation between the lowest and highest UK regions. Independent risk factors included abdominal surgery (adjusted incidence rate ratio (AIRR) 2.03 95% CI 1.49, 2.76), parenteral nutrition (AIRR 1.89 95% CI 1.33, 2.70), fungal colonisation at two or more sites (AIRR 2.30 95% CI 1.34, 3.95) and indwelling devices. Approximately 4% of the variation in ICI rates could be attributed to the CCU. We identified independent risk factors for ICI and showed, for the first time, that the critical care unit effect was small. Despite this, future studies should consider the hierarchical structure of the data to ensure robust estimates.     

Clinical and epidemiological characteristics and risk factors for mortality in patients with candidemia in hospitals from Bogotá, Colombia

BackgroundBloodstream infection by Candida species has a high mortality in Latin American countries. The aim of this study was to describe the characteristics of patients with documented bloodstream infections caused by Candida species in third level hospitals and determine the risk factors for in-hospital-mortality.MethodsPatients from seven tertiary-care hospitals in Bogotá, Colombia, with isolation of a Candida species from a blood culture were followed prospectively from March 2008 to March 2009. Epidemiologic information, risk factors, and mortality were prospectively collected. Isolates were sent to a reference center, and fluconazole susceptibility was tested by agar-based E-test. The results of susceptibility were compared by using 2008 and 2012 breakpoints. A multivariate analysis was used to determinate risk factors for mortality.ResultsWe identified 131 patients, with a median age of 41.2 years. Isolates were most frequently found in the intensive care unit (ICU). Candida albicans was the most prevalent species (66.4% of the isolates), followed by C. parapsilosis (14%). Fluconazole resistance was found in 3.2% and 17.6% of the isolates according to the 2008 and 2012 breakpoints, respectively. Fluconazole was used as empirical antifungal therapy in 68.8% of the cases, and amphotericin B in 22%. Hospital crude mortality rate was 35.9%. Mortality was associated with age and the presence of shock at the time of Candida detection. Fluconazole therapy was a protective factor for mortality.ConclusionsCandidemia is associated with a high mortality rate. Age and shock increase mortality, while the use of fluconazole was shown to be a protective factor. A higher resistance rate with new breakpoints was noted.     

Successful management of fungal pericarditis and endocarditis in a neonate: A case report

Neonatal fungal endocarditis is a rare but serious infection, which does not have a well-accepted management method. This is the second report of this condition in Saudi Arabia. A preterm, very low birth weight, female neonate presented with fever and shortness of breath. An echocardiogram showed moderate pericardial effusion and two masses in the heart, one in the right ventricle and the other in the inferior portion of the posterior mitral valve of the left ventricle. Blood and pericardial fluid cultures revealed an infection with Candida albicans. The patient received a 60 days course of intravenous fluconazole and amphotericin B lipid complex. At the conclusion of treatment, she was discharged in good condition with no echocardiographic evidence of pericardial effusion or fungal vegetations. Thus, a successful outcome to a serious case of fungal endocarditis was achieved through aggressive antifungal therapy with intravenous fluconazole and amphotericin B lipid complex.     

Mortality and risk factor analysis for Candida blood stream infection: A three-year retrospective study

BackgroundThe aim of this study was to evaluate the possible risk factors for mortality in adult patients with candidemia by investigating the causative agents, underlying conditions and predisposing factors.Material and methodsThe data including causative Candida species, predisposing factors, and underlying conditions of candidemia patients between the years 2015–2017 were collected and the impact of these factors on mortality was evaluated. Patients were divided into two groups as died (died patients within 30 days of the onset of candidemia) and survived and risk factors were evaluated for each group.ResultsWe found 163 adult candidemia cases during the study period. Overall 30-day mortality was 40.5%. Candida parapsilosis was the most frequent causative agent (49.1%). C. parapsilosis candidemia was more common in the survived group compared with the died group (n: 49 (61.3%) vs. n: 31 (38.8%), P = 0.888). Mortality rates were significantly higher in patients with dialysis (n: 27 (69.2%) vs. n: 12 (30.8%), P < 0.00) and concurrent bacteremia (n: 20 (57.1%) vs. n: 15 (42.9%), P = 0.024). Survival rates were significantly higher in patients with follow-up blood cultures (n: 75 (65.8%) vs. n: 39 (34.2%), P = 0.013). The most important source of candidemia was catheter (49.7%), and C. parapsilosis was the most common causative agent (58%). The catheter was removed in 96.3% of these patients and the mortality rate was 38.5%. All of the patients received antifungal therapy and there was no significant difference between the effects of antifungals on mortality (n: 65 (39.9%) vs. 98 (60.1%), P = 0.607).ConclusionsDialysis and concurrent bacteremia are strong predictors of mortality in 30 days within patients with candidemia, whereas follow-up blood cultures have a protective role with lower mortality rates. In our study, the most important source of candidemia was catheter, and C. parapsilosis was the most common causative agent. The catheter was removed in almost all patients and the mortality rate was almost one third among these patients.     

Comparison of knowledge to antimicrobial stewardship institution policies targeting Staphylococcus aureus bacteremia and candidemia between medical doctors and pharmacists in an academic teaching hospital in Japan

Staphylococcus aureus bacteremia (SAB) and candidemia have significant impacts on mortality. Both have important implications for antimicrobial stewardship programs (ASPs). However, there are limited data regarding who should be educated and what components should be considered for the ASPs. Hence, we investigated the possibility of the key elements for implications of SAB and candidemia managements for ASPs.We conducted a cross-sectional study on the knowledge of antimicrobial stewardship institution policies targeting SAB and candidemia for all medical doctors (MDs) and pharmacists to using an E-learning system. To compare the differences in proportions of appropriate knowledge between junior residents and other MDs, and all MDs and pharmacists, we performed bivariate analyses using Fisher's exact test and χ² test with odds ratios (ORs) with 95% confidence intervals (CIs).In total, all 395 MDs (71 junior residents, 137 senior residents and fellows, and 187 attending doctors) and all 63 pharmacists including 4 antimicrobial stewardship teams pharmacists responded to survey. MDs other than junior residents responded significantly inappropriately to the questions on the candidemia than junior residents (OR = 0.6, 95% CI: 0.4–1.0). Pharmacists had a significantly lower proportion of appropriate knowledge to the candidemia than MDs (OR = 0.4, 95% CI: 0.2–0.8). The major pitfall was failure to consult an ophthalmologist (82.5%).Next step, we will conduct educational intervention about institution policies, and evaluate whether to improve the knowledges and practices by pre-post test and chart review.