Candidemia in patients with cardiovascular implantable electronic devices.

PURPOSE: Current guidelines recommend complete extraction of cardiovascular implantable electronic devices (CIEDs) in the case of persistent or recurrent fungemia without other identifiable sources, though supporting evidence is lacking. We sought to evaluate the prognosis of patients with candidemia and CIEDs. METHODS: Twelve consecutive patients (54 ± 12 years, 8 male) with CIED and concurrent candidemia were reviewed. RESULTS: At the time of diagnosis with candidemia, seven patients were immunocompromised, six were on long-term antibacterial therapy, two were intravenous drug users, four were on chronic hemodialysis, and six had a central venous catheter. Four patients were confirmed as definite CIED infection as vegetation was visible on lead by echocardiogram. The other 8 patients were considered possible CIED infection with candidemia of unknown focus. All patients with visible vegetation underwent CIED removal without complications, and other patients were initially managed non-operatively. After 1 year of follow-up, 7 patients had died and at extended follow-up, all patients without lead removal died while 3 of 4 patients with lead extraction survived. Of note, 50% of deaths in the patients without lead removal were associated with fungal sepsis. CONCLUSIONS: Candida fungemia is associated with a high mortality. CIED removal should be an early consideration in these patients even if lead vegetations are not seen.

Native valve endocarditis due to Candida albicans in two children: Two new case reports.

Candida endocarditis (CE) is a rare and serious complication of candidemia. Using current diagnostic tools a confirmed diagnosis is often delayed and outcomes remain poor. The majority of new cases occur following cardiac valvular surgery, and/or in patients with the following risk factors: intravenous drug use, cancer chemotherapy, prolonged presence of central venous catheters, and prior history of bacterial endocarditis. It is not a common complication in non-neutropenic patients particularly with the absence of a prosthetic valve, and very few reports in the literature are available. Attempting to add to the limited data, 211 candidemia episodes from 172 nonneutropenic pediatric cases between January 2008 and December 2017 were evaluated. All patients were considered asymptomatic for underlying heart disease. However, 2 (0.9%) patients with a central venous catheter were determined as having endocarditis following echocardiography.

The incidence of endophthalmitis or macular involvement and the necessity of a routine ophthalmic examination in patients with candidemia.

BACKGROUND: The incidence of ocular candidiasis (OC) in patients with candidemia varies across different reports, and the issue of whether routine ophthalmoscopy improves outcomes has been raised. This study investigated the incidence of OC and evaluate whether the extent of OC impacts the clinical outcomes. METHODS: This retrospective study included non-neutropenic patients with candidemia who underwent treatment at one of 15 medical centers between 2010 and 2016. Chorioretinitis without other possible causes for the ocular lesions and endophthalmitis was classified as a probable OC. If signs of chorioretinitis were observed in patients with a systemic disease that causes similar ocular lesions, they were classified as a possible OC. RESULTS: In total, 781 of 1089 patients with candidemia underwent an ophthalmic examination. The prevalence of OC was 19.5%. The time from the collection of a positive blood culture to the initial ophthalmic examination was 5.0 ± 3.9 days in patients with OC. The leading isolate was Candida albicans (77.9%). Possible OC was associated with unsuccessful treatments (resolution of ocular findings) (odds ratio: 0.354, 95% confidence interval: 0.141-0.887), indicating an overdiagnosis in patients with a possible OC. If these patients were excluded, the incidence fell to 12.8%. Endophthalmitis and/or macular involvement, both of which require aggressive therapy, were detected in 43.1% of patients; a significantly higher incidence of visual symptoms was observed in these patients. CONCLUSION: Even when early routine ophthalmic examinations were performed, a high incidence of advanced ocular lesions was observed. These results suggest that routine ophthalmic examinations are still warranted in patients with candidemia.

Use of T2MR in invasive candidiasis with and without candidemia.

The mortality associated with invasive candidiasis remains unacceptably high. The T2 magnetic resonance (T2MR) assay is a novel US FDA-approved molecular diagnostic assay for the diagnosis of candidemia that can rapidly detect the five most commonly isolated Candida spp. In clinical trials, T2MR has exhibited good clinical sensitivity and specificity. Potential benefits from the adoption of T2MR technology in the diagnostic and therapeutic algorithms for invasive candidiasis can arise from timely diagnosis of disease, increased case detection, tailored therapy and decrease in empiric antifungal treatment. As everyday clinical experience with the assay is evolving, we discuss the utility of T2MR in invasive candidiasis with and without candidemia based on the currently available evidence regarding its performance.

Impact of rapid, culture-independent diagnosis of candidaemia and invasive candidiasis in a community health system.

Background: Delay in treatment of candidaemia and invasive candidiasis remains a cause of significant morbidity and mortality in high-risk patients. Widespread empirical utilization of antifungal therapy often occurs in an effort to minimize this risk. Objectives: This study assessed the impact of the T2Candida Panel in a multi-hospital community health system on time to initiation of antifungal therapy in candidaemic patients as well as the utilization of micafungin. Methods: Outcomes were compared between those patients with candidaemia prior to T2Candida implementation and those after implementation. Micafungin utilization for patients with suspected candidaemia/invasive candidiasis was compared with that for patients with a negative T2Candida Panel post-implementation. Results: There was a significant decrease in time to appropriate therapy in the post-T2Candida group (34 versus 6 h, P = 0.0147). Empirical antifungal therapy was avoided in 58.4% of T2Candida-negative patients. Conclusions: These results support the implementation of T2Candida to improve time to appropriate therapy for candidaemic patients while simultaneously expanding antimicrobial stewardship efforts to appropriately utilize antifungals.

T2MR contributes to the very early diagnosis of complicated candidaemia. A prospective study.

Objectives: Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical manifestations may be non-specific and difficult to identify, thus precluding an appropriate treatment. Patients and methods: This was a multicentre prospective study for predicting complicated episodes in patients with bloodstream infection caused by Candida species, while assessing the value of follow-up blood cultures (BCs) and the persistence of positive results for T2Candida MR (T2MR) and blood ß-d-glucan (BDG) tests. Immediately after the first positive BC yielding Candida species, samples were obtained on days 0, +2, +4, +7 and +14, to simultaneously perform follow-up BC, T2MR and BDG. An episode of candidaemia was defined as 'complicated' when (i) it caused septic metastasis; and/or (ii) it was the cause of the patient's death. Results: From January to June 2017, 30 patients were enrolled in the study. Of these, nine (30%) had complicated candidaemia. Values of persistently positive samples for the prediction of complicated episodes for BCs, T2MR and BDG, respectively, were as follows: sensitivity (44.4%, 100%, 100%); specificity (76.1%, 76.1%, 38.9%); positive predictive value (PPV) (44.4%, 64.2%, 40.9%) and negative predictive value (NPV) (76.1%, 100%, 100%). In multivariate analysis, having a positive T2MR within the first 5 days was associated with an almost 37-fold higher risk of developing complicated candidaemia. Conclusions: The T2MR test performed in patients with proven candidaemia may be a better marker of complicated infection than follow-up BCs or BDG. It is possible that this test may change current clinical practice, influencing the length and type of antifungal therapy in this population.

T2 magnetic resonance for the diagnosis of bloodstream infections: charting a path forward.

We discuss four studies in this issue of the Journal of Antimicrobial Chemotherapy that describe experience with T2 magnetic resonance (T2MR) nanodiagnostics for Candida and bacterial bloodstream infections, in the context of the T2MR literature. T2Candida and T2Bacteria panels use a dedicated instrument to detect amplified DNA from microbial cells directly in whole blood. T2Candida gives positive or negative results for C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis. T2Bacteria detects Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli. In recent trials, T2Candida sensitivity and specificity for candidaemia were ∼90% and ∼98%, respectively. Two studies from Spanish hospitals now provide the first data on T2Candida as a prognostic tool. T2Candida was superior to cultures or serum ß-d-glucan in identifying patients with complicated candidaemia, and in predicting the outcomes of empirical antifungal therapy for suspected candidiasis. In a retrospective study from US community hospitals, use of T2Candida was reported to reduce times to appropriate antifungal therapy, shorten courses of empirical therapy, and save an average of US$280 in antifungal costs per patient tested. Finally, a study from a hospital in Rome provides the first clinical data for T2Bacteria: sensitivity and specificity were 89% and 98%, respectively, among patients with positive blood cultures for bacteria detected by the panel, or fulfilling criteria for infection. We conclude that T2MR diagnostics are promising both for detecting bloodstream infections due to Candida and bacteria, and for providing prognostic information. More studies that present real-world performance data are needed.

Is routine ophthalmoscopy really necessary in candidemic patients?

The purpose of this study was to determine among patients with candidemia the real rate of ophthalmoscopy and the impact of performing ocular assessment on the outcome of the disease. We performed a post hoc analysis of a prospective, multicenter, population-based candidemia surveillance program implemented in Spain during 2010-2011 (CANDIPOP). Ophthalmoscopy was performed in only 168 of the 365 patients with candidemia (46%). Ocular lesions related to candidemia were found in only 13/168 patients (7.7%), of whom 1 reported ocular symptoms (incidence of symptomatic disease in the whole population, 0.27% [1/365]). Ophthalmological findings led to a change in antifungal therapy in only 5.9% of cases (10/168), and performance of the test was not related to a better outcome. Ocular candidiasis was not associated with a worse outcome and progressed favorably in all but 1 evaluable patient, who did not experience vision loss. The low frequency of ophthalmoscopy and ocular involvement and the asymptomatic nature of ocular candidiasis, with a favorable outcome in almost all cases, lead us to reconsider the need for systematic ophthalmoscopy in all candidemic patients.

Therapeutic approach to Candida bezoar in children.

INTRODUCTION: Candida bezoar (CB) is a rare finding in neonates and infants with candiduria, presenting as necrotic debris with proliferating mycelia in the collecting system of the kidney. If initial antifungal medical treatment does not result in clearance of candiduria and disappearance of CB on ultrasound in dilated kidneys, invasive interventions like insertion of nephrostomy tubes (NT) or surgical interventions to drain the kidney are sometimes advocated(.). However, NT placement can be a technical challenge, especially in pre- and dysmature neonates, and NT displacement or obstruction by the CB can lead to suboptimal treatment. Identification of those children who will benefit from invasive renal drainage is important. OBJECTIVE: This study evaluates the management of patients with CB in three tertiary referral hospitals to determine criteria for intervention. MATERIALS AND METHODS: A retrospective multicenter chart analysis was conducted of children with candiduria and ultrasonographic demonstration of CB (diagnosed between March 1995 and August 2012). The indication for invasive renal drainage (if performed) and subsequent clinical outcome, serum creatinine levels and ultrasound findings were assessed. RESULTS: A total of 12 children were included, two of which were premature neonates. Eight children had congenital urogenital anomalies. One older child with acute myeloid leukemia had CB during chemotherapy and one ex-premature developed CB following cerebral candidiasis. All children received systemic antifungal medication; in seven children invasive treatment was added. Indications for invasive treatment were clinical deterioration, progressive renal dilation, pyonephrosis, rising creatinine levels and persistence of CB. Two underwent a Y-cutaneous ureterostomy and nephrostomy tubes were inserted in five children. Percutaneous renal drainage by nephrostomy led to complications in 3 of 6 procedures. In all patients, irrespective of therapeutic modality, follow-up ultrasound demonstrated no de novo changes. No additional parenchymal defects or deterioration of split renal function were seen on DMSA or MAG-3 scan. DISCUSSION: In the literature renal drainage is suggested in case of complete obstruction. However dilatation is a frequent finding in children as part of the congenital renal anomaly and does not necessarily mean that there is obstruction of the urinary tract. Even in children without candida infections the diagnosis of obstruction is not straightforward, while the results of a MAG 3 scan can be obscured by compromised kidney function, parenchymal bacterial infiltration and neonatal immaturity of the kidney. If candiduria and CB persist despite intensive medical treatment, intensive consultation is required before renal drainage, because NT insertion might be a surgical challenge. Complications such as displacement of the NT, urinoma development, or NT obstruction can occur and was seen in three of six procedures. Premature neonates seem to be more prone to complications due to their small anatomical proportions, requiring medical equipment with small diameters prone to displacement and obstruction. Some studies describe successful pharmaceutical management in the majority of patients with CB. Other studies describe unilateral surgical intervention in children with bilateral CB where unilateral drainage did not influence overall renal outcome. This is in line with our results. A limitation of the present study is its retrospective design. In this population, the motivation for invasive renal drainage or conservative management was not well documented in all cases, and was mainly based on clinical and diagnostic parameters like creatinine levels and radiographic findings. CONCLUSION: Renal drainage should be considered in selected cases after failure of systemic antifungal treatment. Inserting and maintaining a nephrostomy tube in young children is associated with a high rate of complications; conservative treatment is likely to be sufficient in the majority of patients with candiduria and CB.

Intermittent aortic insufficiency as an aid to diagnosing obstruction in a HeartMate II continuous-flow left ventricular assist device.

This report details two cases of left ventricular assist device (LVAD)-related fungal infection. In both cases, the infection occurred within the device and formed an obstruction resulting in intermittent variation in the output of the LVAD. This was manifested by a change in the pattern of aortic insufficiency (AI) from continuous to intermittent on transesophageal echocardiography. Recognition of this finding may allow for noninvasive diagnosis of LVAD flow obstruction.