ß-(1→3)-D-glucan- and mannan-guided early termination of antifungal therapy in ICU patients: a randomized controlled study.

Candida spp. are frequently encountered in specimens from ICUs. However, most of these detections represent colonization. Nevertheless, clinical practice shows that a considerable proportion of these patients will receive antifungal therapy (AT). ß-(1→3)-D-glucan (BDG) and mannan are fungal biomarkers with high negative predictive values. We aimed to examine whether biomarker-guided discontinuation of AT can reduce the antifungal consumption. Therefore, we conducted a prospective, randomized intervention study between 1 April 2019 and 31 March 2020. All adult ICU patients with a newly started systemic AT but without fungal infection were eligible for inclusion. Enrolled patients were randomized into an intervention and a control group. In both groups, serum BDG and mannan were determined on days 1 and 2 of AT. If all measurements were negative, AT was discontinued in the intervention group. The primary endpoint was antifungal use. The study was terminated after 12 months. Until this time-point, 41 patients had been included. In the intervention group (n = 19), AT was stopped in only two patients because all others showed either positive BDG and/or mannan levels. One of these two patients developed candidemia and AT had to be restarted. There was no significant difference in the primary and secondary endpoints. In summary, the strategy of using two negative BDG and mannan levels to stop AT failed to reduce antifungal consumption in our cohort. Indeed, there will inevitably be patients with invasive candidiasis in whom necessary AT is discontinued. The optimal patient population, biomarker set, and termination criteria are critical to the success of biomarker-based termination strategies.

Evaluation of targeted versus universal prophylaxis for the prevention of invasive fungal infections following lung transplantation.

BACKGROUND: Antifungal prophylaxis to prevent invasive fungal infections (IFI) is widely used following lung transplantation, but the optimal strategy remains unclear. We compared universal with targeted antifungal prophylaxis for effectiveness in preventing IFI. METHODS: Adult patients who underwent lung transplantation at the University of Michigan from /1 July 2014-31 December 2017 were studied for 18 months post-transplant. Universal prophylaxis consisted of itraconazole with or without inhaled liposomal amphotericin B. Using specific criteria, targeted prophylaxis was given with voriconazole for patients at risk for invasive pulmonary aspergillosis (IPA) and with fluconazole or micafungin for patients at risk for invasive candidiasis. Risk factors, occurrence of proven/probable IFI, and mortality were analyzed for the two prophylaxis cohorts. RESULTS: Of 105 lung transplant recipients, 84 (80%) received a double lung transplant, and 38 (36%) of patients underwent transplant for pulmonary fibrosis. Fifty-nine (56%) patients received universal antifungal prophylaxis, and 46 (44%), targeted antifungal prophylaxis. Among 20 proven/probable IFI, there were 14 IPA, 4 invasive candidiasis, 1 cryptococcosis, and 1 deep sternal mold infection. Six (10%) IFI occurred in the universal prophylaxis cohort and 14 (30%) in the targeted prophylaxis cohort. Five of 6 (83%) IFI in the universal prophylaxis cohort, compared with 9/14 (64%) in the targeted prophylaxis cohort, were IPA Candida infections occurred only in the targeted prophylaxis cohort. The development of IFI was more likely in the targeted prophylaxis cohort than the universal prophylaxis cohort, HR = 4.32 (1.51-12.38), P = .0064. CONCLUSIONS: Universal antifungal prophylaxis appears to be more effective than targeted antifungal prophylaxis for prevention of IFI after lung transplant.

Oral lichen planus induced by long-term use of antimicrobials for recurrent aphthous ulcer: A case report and literature review. / é•¿æœŸä½¿ç”¨æŠ—èŒè¯ç‰©æ²»ç–—å¤å‘æ€§å£è ”æºƒç–¡å¼•èµ·å£è ”æ‰å¹³è‹”è—“1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

The precise etiology of oral lichen planus (OLP) is still unclear, but the existing evidence suggests that drug intake, virus infection, fungal infection, psychological disorders, and immunodeficiency are closely associated with the pathogenesis of OLP. We report a case of OLP accompanied with candidiasis induced by long-term use of antimicrobials for recurrent aphthous ulcer (RAU) and update the literature, to discuss the possible association between OLP and misuse of antimicrobials, and to inform general dentists and pharmacists the importance for practice with optimal antimicrobial stewardship. In this case, a 42-year-old man presented to Xiangya Stomatological Hospital with white reticular patterns spreading in the oral cavity for almost 1 year. He was diagnosed with OLP via histopathological examination. He had a 5-year history of RAU which occurred every 1-2 months, and he was given antimicrobials ingested or injected whenever the ulcers came up. Satisfactory treatment results were obtained by stopping the abuse of antimicrobials and local antifungal therapy. Meanwhile, the exacerbation and alleviation of OLP was closely related to the administration of antimicrobials. Combined with literature review, antimicrobial might contribute to the development of OLP by inducing candidiasis, a common side-effect of misuse of antimicrobials. Considering the seriousness of antimicrobial resistance and opportunistic infection, dentists should prescribe antimicrobials judiciously according to guidelines and evidence-based indications. Appropriate prescribing of antimicrobials is a professional responsibility to all dentists.

(1,3)-ß-D-Glucan-based empirical antifungal interruption in suspected invasive candidiasis: a randomized trial.

BACKGROUND: (1,3)-ß-D-Glucan has been widely used in clinical practice for the diagnosis of invasive Candida infections. However, such serum biomarker showed potential to guide antimicrobial therapy in order to reduce the duration of empirical antifungal treatment in critically ill septic patients with suspected invasive candidiasis. METHODS: This was a single-centre, randomized, open-label clinical trial in which critically ill patients were enrolled during the admission to the intensive care unit (ICU). All septic patients who presented invasive Candida infection risk factors and for whom an empirical antifungal therapy was commenced were randomly assigned (1:1) in those stopping antifungal therapy if (1,3)-ß-D-glucan was negative ((1,3)-ß-D-glucan group) or those continuing the antifungal therapy based on clinical rules (control group). Serum 1,3-ß-D-glucan was measured at the enrolment and every 48/72 h over 14 days afterwards. The primary endpoint was the duration of antifungal treatment in the first 30 days after enrolment. RESULTS: We randomized 108 patients into the (1,3)-ß-D-glucan (n = 53) and control (n = 55) groups. Median [IQR] duration of antifungal treatment was 2 days [1-3] in the (1,3)-ß-D-glucan group vs. 10 days [6-13] in the control group (between-group absolute difference in means, 6.29 days [95% CI 3.94-8.65], p < 0.001). Thirty-day mortality was similar (28.3% [(1,3)-ß-D-glucan group] vs. 27.3% [control group], p = 0.92) as well as the overall rate of documented candidiasis (11.3% [(1,3)-ß-D-glucan group] vs. 12.7% [control group], p = 0.94), the length of mechanical ventilation (p = 0.97) and ICU stay (p = 0.23). CONCLUSIONS: In critically ill septic patients admitted to the ICU at risk of invasive candidiasis, a (1,3)-ß-D-glucan-guided strategy could reduce the duration of empirical antifungal therapy. However, the safety of this algorithm needs to be confirmed in future, multicentre clinical trial with a larger population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03117439 , retrospectively registered on 18 April 2017.

Implementation of a Nurse-Driven Protocol for Catheter Removal to Decrease Catheter-Associated Urinary Tract Infection Rate in a Surgical Trauma ICU.

INTRODUCTION: Early removal of urinary catheters is an effective strategy for catheter-associated urinary tract infection (CAUTI) prevention. We hypothesized that a nurse-directed catheter removal protocol would result in decreased catheter utilization and CAUTI rates in a surgical trauma intensive care unit (STICU). METHODS: We performed a retrospective, cohort study following implementation of a multimodal CAUTI prevention bundle in the STICU of a large tertiary care center. Data from a 19-month historical control were compared to data from a 15-month intervention period. Pre- and postintervention indwelling catheter utilization and CAUTI rates were compared. RESULTS: Catheter utilization decreased significantly with implementation of the nurse-driven protocol from 0.78 in the preintervention period to 0.70 in the postintervention period (P < .05). As a result of the bundle, the CAUTI rate declined significantly, from 5.1 to 2.0 infections per 1000 catheter-days in the pre- vs postimplementation period (Incident Rate Ratio [IRR]: 0.38, 95% confidence interval: 0.21-0.65). CONCLUSIONS: Implementation of a nurse-driven protocol for early urinary catheter removal as part of a multimodal CAUTI intervention strategy can result in measurable decreases in both catheter utilization and CAUTI rates.

Diagnostic value of Candida mannan antigen and anti-mannan IgG and IgM antibodies for Candida infection.

OBJECTIVE: To assess the diagnostic value of serum Candida mannan antigen (MN) and anti-mannan IgG and IgM antibodies for candidiasis. METHODS: This study was a prospective cohort study. Clinical data and venous blood samples from 23 medical centres in Beijing, China were collected between 1 January 2017 and 31 December 2018. All collected specimens were tested within one week for serum Candida MN and IgG and IgM antibodies using an ELISA kit. RESULTS: A total of 452 patients were enrolled, including 188 patients in the Candida exposure groups (56 patients with Candida bloodstream infection, 69 patients with Candida-positive tracheal aspirate cultures and 63 patients with Candida-positive urine cultures) and 264 patients in the control groups (212 healthy controls and 52 patients with bacteraemia). The receiver operating characteristic (ROC) curve of the 56 patients with Candida bloodstream infection and 212 healthy controls showed that serum MN and IgG had good diagnostic value. The area under the ROC curve (AUC) values were 0.812 (95% CI, 0.750-0.873) and 0.866 (95% CI, 0.808-0.924), respectively, wherein the MN specificity and sensitivity were 86.79% and 60.71%, and the IgG were 84.43% and 80.36%, respectively. The AUC of the combination of serum MN and IgG was 0.871(95% CI, 0.813-0.929), and the specificity and sensitivity were 93.87% and 57.14%. CONCLUSIONS: The serum levels of Candida MN and its IgG antibody have diagnostic value for Candida bloodstream infection, and combination of MN and IgG can improve diagnostic specificity and may provide a new approach for diagnosis of candidaemia.

Pooled analysis of T2 Candida for rapid diagnosis of candidiasis.

BACKGROUND: The present meta-analysis examined the diagnostic accuracy of T2 Candida for candidiasis. METHODS: The literature databases, such as PubMed, Embase, DVIO, Cochrane library, Web of Science, and CNKI, were searched on T2 Candida detection. RESULTS: A total of 8 articles, comprising of 2717 research subjects, were included in the study. The pooled sensitivity and specificity were 0.91 (95% confidence interval (CI): 0.88-0.94) and 0.94 95% CI: 0.93-0.95), respectively. The pooled positive likelihood ratio and negative likelihood ratio was 10.16 (95% CI: 2.75-37.50) and 0.08 (95% CI: 0.02-0.35), respectively. The combined diagnostic odds ratio is 133.65 95% CI: 17.21-1037.73), and the AUC of SROC is 0.9702 [(SE = 0.0235), Q* = 0.9201(SE = 0.0381)]. CONCLUSIONS: The current evidence supported that T2 Candida has high accuracy and sensitivity and is of major clinical significance in the diagnosis of Candida infection.

Vitamin D-supplemented yogurt drink reduces Candida infections in a paediatric intensive care unit: a randomised, placebo-controlled clinical trial.

BACKGROUND: The prevalence of Candida infections in paediatric intensive care units (PICUs) has dramatically increased as a result of resistance to conventional anti-fungal treatments. Because vitamin D has been shown to exhibit fungicidal activity against Candida infection in an in vitro antimicrobial screening, we aimed to investigate the effect of vitamin D on Candida infections in the PICU. METHODS: Four hundred sixteen eligible children aged between 12 months to 5 years old admitted to the PICU, who were on broad-spectrum antibiotic therapy, participated in the study. Patients were randomly assigned to two study groups, receiving a plain yogurt drink (placebo group) or supplemented with 300 IU day-1 vitamin D (VD group). Primary outcome was defined as the incidences of Candida colonisation (Candida isolated from rectal swab) 14 days after enrollment. Secondary outcome measures were Candida growth in blood (candidaemia) and urine (candiduria). RESULTS: The prevalence of candiduria as well as candidaemia was significantly lower in the VD-treated group (26 cases) than in the placebo group (62 cases). The mean (SD) length of PICU stay was obviously lowered in the VD group [11.8 (1.2) days] compared to the placebo group [15.2 (2.3 days)], whereas cases of patient death were similar between the two groups. CONCLUSIONS: Supplementation of vitamin D effectively reduces infections of Candida in children who were critically ill and on broad-spectrum antibiotic treatment.

Zinc supplementation reduces Candida infections in pediatric intensive care unit: a randomized placebo-controlled clinical trial.

Resistance to anti-fungal drugs has become the main cause for increasing incidence rate of Candida infections in pediatric intensive care units (PICU). Zinc supplementation has been shown to exhibit beneficial effects on many pediatric illnesses. This study aimed to investigate the efficacy of zinc supplementation on prevalence of candidemia and candiduria infections in PICU. 724 eligible children between 1 to 5 years old admitted in PICU were randomly assigned into either zinc supplementation group or placebo group. Primary endpoints were the number of Candida infections, length of PICU stay and cases of patient death 14 days after enrollment. Secondary endpoints were the incidence rates of candidemia and candiduria. The incidences of candiduria and candidemia were significantly lower in the zinc group than the placebo group. The length of PICU stay and cases of patient death were obviously lowered in the zinc group compared to the placebo group. In conclusion, zinc supplementation shows beneficial clinical efficacy in reducing Candida infections among PICU patients on broad-spectrum antibiotics with critical illnesses.

Analyzing candidemia guideline adherence identifies opportunities for antifungal stewardship.

Candidemia epidemiology varies significantly by region; thus, local data are essential for evidence-based decision-making in prophylaxis and treatment. Current management strategies are derived from large randomized controlled trials mostly executed in large high-volume tertiary care centers. Results may not be entirely transferable to smaller hospitals. This study investigates epidemiology, diagnosis, and treatment standards in six hospitals in the Cologne metropolitan area (number of inhabitants approx. one million). We assessed adherence to the current guideline of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the Infectious Diseases Society of America (IDSA) using the EQUAL Candida Score of the European Confederation of Medical Mycology (ECMM). Data were documented by trained medical students as part of an integrated research and teaching concept at the University of Cologne. Between January 2014 and June 2017, 77 patients had candidemia, corresponding to an incidence of 0.2 cases/1000 admissions. While 55 patients were enrolled, 22 patients were excluded due to incompletely retrievable health records. Fluconazole monotherapy was the preferred first-line treatment in cases with Candida albicans infection (21/29). A central vascular catheter was present in 40 patients and was removed in 17 (43%) during treatment. Overall mortality at 30 days was 44%. Patients reached a mean EQUAL Candida Score of 9.9 (range 8-14), which was well below the maximum score of 22 for perfect guideline adherence. In summary, management of candidemia differed from current European recommendations. It remains unclear to what extent enhanced adherence would improve patient outcome. Larger prospective studies need to answer that question.

Periprosthetic Joint Infection With Fungal Pathogens.

BACKGROUND: Although there is abundant information about bacterial periprosthetic joint infections (PJIs), there is a notable paucity of information about fungal PJIs. The goals of this study are to describe the patient demographics, diagnostic findings, and treatment results of fungal PJIs after total joint arthroplasty. METHODS: We identified 31 fungal PJIs (13 total hip arthroplasties and 18 total knee arthroplasties) in 31 patients treated between 1996 and 2014. This represented 0.9% of the 3525 PJIs treated at our institution during this time period. Candida species accounted for 81% of infections. The mean patient age at diagnosis of fungal PJI was 68 years. Mean follow-up after initiation of treatment was 4 years. RESULTS: In the total hip arthroplasty cohort, survivorship free from all-cause revision or implant removal was 44% at 2 years. Survivorship free from reinfection was 38% at 2 years. Mean Harris hip score was 27 at final follow-up.In the total knee arthroplasty cohort, survivorship free from all-cause revision was 70% at 2 years. Survivorship free from reinfection was 76% at 2 years. Mean Knee Society scores were 36 at final follow-up. CONCLUSION: Fungal PJIs are rare (0.9% of diagnosed PJIs). Survivorship free of all-cause revision or implant removal was very low in the hip group (44% at 2 years), but slightly better in the knee group (70% at 2 years). Moreover, clinical outcomes were poor with high perioperative complication rates. Improved treatment regimens are needed for this unsolved clinical problem.

Initial therapeutic strategy of invasive candidiasis for intensive care unit patients: a retrospective analysis from the China-SCAN study.

BACKGROUND: To investigate the impact of initial antifungal therapeutic strategies on the prognosis of invasive Candida infections (ICIs) in intensive care units (ICUs) in China. METHODS: A total of 306 patients with proven ICIs in the China-SCAN study were analyzed retrospectively. Empiric, pre-emptive, and targeted therapy were adopted based on starting criteria including clinical, microbiological, and other conventional prediction rules. The primary outcome was hospital mortality and the secondary endpoints were duration days in ICU and duration days in hospital. The global responses (clinical and microbiological) at the end of the empirical therapy were also assessed. RESULTS: A total of 268/306 (87.6%) ICI patients received antifungal therapy, including 142/268 (53.0%) initial empirical therapy, 53/268 (19.8%) initial pre-emptive therapy, and 73/268 (27.2%) initial targeted therapy. Compared with the initial empirical antifungal therapy and targeted antifungal therapy, patients with initial pre-emptive antifungal therapy had significantly less clinical remission [11/53 (21.2%) vs. 61/142 (43.3%) vs. 22/73 (30.1%), P = 0.009], higher ICU [26/53 (57.8%) vs. 42/142 (32.2%) vs. 27/73 (43.5%), P = 0.008] and hospital mortality [27/53 (60.0%) vs. 43/142 (32.8%) vs. 29/73 (46.8%), P = 0.004] and more microbiological persistence [9/53 (17.0%) vs. 6/142 (4.2%) vs. 9/73 (12.3%), P = 0.011]. Kaplan-Meier survival analysis revealed that ICI patients with initial pre-emptive antifungal therapy and targeted antifungal therapy were associated with reduced hospital duration compared with patients with initial empirical antifungal therapy after confirmation of fungal infection (log-rank test: P = 0.021). Multivariate regression analysis provided evidence that initial empirical antifungal therapy was an independent predictor for DECREASING the hospital mortality in ICI patients on ICU admission and at ICI diagnosis (odds ratio 0.327, 95% confidence interval 0.160-0.667, P = 0.002; odds ratio 0.351, 95% confidence interval 0.168-0.735, P = 0.006). CONCLUSIONS: The initial therapeutic strategy for invasive candidiasis was independently associated with hospital mortality. Prompt empirical antifungal therapy could be critical to decrease early hospital mortality. TRIAL REGISTRATION: Clinicaltrials.gov NCT01253954 (retrospectively registration date: December 3, 2010).

Is universal antifungal prophylaxis mandatory in adults after lung transplantation? A review and meta-analysis of observational studies.

BACKGROUND: Lung transplant (LTX) recipients are at high risk of invasive Aspergillus infections (IAI). However, no randomized-controlled trials (RCT) or international guidelines on antifungal prophylaxis (AFP) in the LTX population exist. METHODS: A meta-analysis was performed to determine whether AFP reduces the rate of IAI after LTX. A total of six eligible observational studies (five with no prophylaxis, one with targeted prophylaxis, three studies including heart/lung transplantation) with a total of 748 patients were included. RESULTS: The pooled odds ratio (OR) for IAI (62 IFI in the intervention arm and 82 in the control group) was 0.234 (95% confidence interval [CI] 0.097-0.564, P=0.001, z=-3.237). Pooled studies were characterized by substantial heterogeneity (I2 =66.64%); number needed to treat was 6.8. A subgroup analyses with exclusion of heart transplant recipients also showed a statistically significant reduction in IAI with AFP (OR 0.183, 95% CI 0.0449-0.744, P=0.018). CONCLUSION: This study suggests that universal antifungal prophylaxes reduces incidence of IAI after LTX. However, included studies are limited by small sample size, single-center structure without randomization, mixed population (including heart/heart-lung transplant), and heterogeneity due to variations in immunosuppression, type, and duration of AFP. Therefore, there is a clear need for an adequately powered RCT.

Specificity of mannan antigen and anti-mannan antibody screening in patients with haematological malignancies at risk for fungal infection.

Combination of mannan antigen and anti-mannan antibody (Mn/A-Mn) testing has been reported a useful and specific strategy for diagnosis of invasive Candida infections (ICIs). We evaluated Mn/A-Mn as a screening tool in patients with haematological malignancies. This clinical prospective study was performed at the Division of Hematology, Medical University Graz, Austria between July and December 2012. Patients at risk for fungal infection were included into the study and twice weekly screened by Mn/A-Mn testing, yielding 650 samples. Of overall 67 patients 66 had no evidence for ICI. From those, 153/640 serum samples (23.9%) were positive for mannan Ab, and nine (1.4%) for Ag. Most false positive Ab results were observed among 375 samples from patients without haematopoietic stem cell transplantation (34.9% resulted positive). Combined specificity of Mn/A-Mn was 74.8%. Of 10 samples obtained in the single patient with candidemia, five were positive for mannan Ag (from the day of diagnosis up to 40 days after detection of candidemia) and none for Ab. In conclusion, mannan Ab screening yielded a high number of false positive results. While mannan Ag was found to be highly specific and may have potential for diagnostic driven testing, mannan Ab testing cannot be recommended based on our study results.

In vitro evaluation on HeLa cells of protective mechanisms of probiotic lactobacilli against Candida clinical isolates.

AIMS: To characterize in vitro the ability of human Lactobacillus strains to inhibit the adhesion, to displace and to compete with clinically isolated Candida strains. METHODS AND RESULTS: Three types of assays were performed to determine the inhibitory effect of Lactobacillus plantarum 319, Lactobacillus rhamnosus IMC 501, Lactobacillus paracasei IMC 502 and a specific probiotic combination (SYNBIO) on adhesion of Candida pathogens to HeLa cells: blockage by exclusion (lactobacilli and HeLa followed by pathogens), competition (lactobacilli, HeLa and pathogens together) and displacement (pathogens and HeLa followed by the addition of lactobacilli). Bacterial adhesion to HeLa was quantified by microscopy after May-Grünwald/Giemsa stain. The inhibition results highlight a significant (P < 0·05) competition of the considered probiotics against all the Candida strains. The results suggest that the probiotic strains used in this study could prevent colonization of the urogenital tract by relevant pathogens such as Candida strains through barrier and interference mechanisms (mainly displacement and competition), but the degree of inhibition of adhesion was bacterial strain-dependent. CONCLUSIONS: The results support the potential of these Lactobacillus probiotic strains as anti-infective agents in the vagina and encourage further studies about their capacity to prevent and manage urogenital tract infections in females. SIGNIFICANCE AND IMPACT OF THE STUDY: To optimize the defensive properties of the vaginal microbiota, improving the health of many women by probiotic intervention.

Characteristic and clinical relevance of Candida mannan test in the diagnosis of probable invasive candidiasis.

The gold standard laboratory tests used to diagnose invasive Candida infection (ICI) are based on the in vitro culture of blood or samples from other sterile sites. However, these tests have limited sensitivity (Se) and are generally not diagnostic until late in the infectious process. The Serion Candida mannan kit was evaluated for the diagnosis of ICI at Grenoble University Hospital (France) between 2007 and 2011. The results were then compared with worldwide data published between 1997 and 2011. This retrospective study was based on follow-up from the investigation of 162 patients of whom 91 had proven ICI; 13 had Candida colonization index (CCI) scores ≥0.42, positive mannan tests, with nonconcomitant infections; and 58 had no evidence of Candida infection. Candida albicans, C. glabrata, C. tropicalis, and C. parapsilosis were the etiologic agents in 104 patients. For patients with or without ICI, the 12-week mortality rates were 35/104 (33.7%) and 6/58 (10.3%), respectively. The mannan diagnostic specificity was 51% and Se was 77%. However, in the meta-analysis (n = 1,536), values were 86% and 62%, respectively. Positive mannan test results may appear early (median 6 days) in the development of candidemia and have moderate diagnostic value for ICI, with a negative predictive value of 83%. In patients at risk of ICI with negative candidemia, the combination of Candida mannan test data with a CCI score ≥0.42 may improve the diagnosis of probable ICI.

Candida auris Infection, a Rapidly Emerging Threat in the Neonatal Intensive Care Units: A Systematic Review.

(1) Background: In recent years, a global epidemiological shift in candidemia has been observed, marked by the emergence of resistant non-albicans Candida species. Candida auris, in particular, has become a significant global concern, causing infections in both pediatric and adult populations within healthcare settings. Despite its widespread impact, there is a limited understanding of the clinical course and transmission dynamics of neonatal systemic Candida auris infections, hindering effective prevention and management. This study focused on the epidemiologic data, the clinical presentation, risk factors, and outcome of C. auris infection in neonatal population. (2) Methods: A systematic review of the literature using PubMed and Scopus databases until December 2023 was conducted. (3) Results: A total of 24 relevant studies were identified, encompassing 476 documented cases of Candida auris infection in neonates. Prematurity emerged as a primary risk factor, alongside total parenteral nutrition, central line insertion, mechanical ventilation, and prior broad-spectrum antibiotic use. The mortality rate reached approximately 42%, with therapeutic details sparingly reported in 12% of cases. Treatment strategies varied, with amphotericin B predominantly used as monotherapy, while combination antifungal agents were used in 44% of cases. Notably, 97.4% of cases exhibited fluconazole resistance, and 67.1% showed resistance to amphotericin B. Limited data were available on resistance to other antifungal agents. (4) Conclusions: Despite the rarity of neonatal Candida auris infections, their global occurrence necessitates comprehensive preparedness in patient care. A deeper understanding of Candida auris pathogenesis is crucial for developing effective strategies to control and prevent neonatal infections caused by this pathogen.

Invasive Candida Infection in Patients With Bacterial Infective Endocarditis.

Over 21 months, 12 patients with invasive Candida infections detected during the course of treatment of bacterial endocarditis, including 11 with candidemia, were identified. Invasive Candida infections can occur as a complication of bacterial endocarditis and may occur more frequently in patients with injection drug use and broad-spectrum antibiotic exposure.

Four-Arm δ-Ornithine-Based Polypeptoids Resensitize Voriconazole against Azole-Resistant C. albicans.

Worldwide Candida albicans infections cause a huge burden in healthcare and the efficacy of traditional antifungals is diminished because of the rapid development of antifungal resistance. It is necessary to develop new antifungals or new strategies to make multidrug-resistant (MDR) C. albicans to resensitize to existing antifungal drugs. In this work, a series of 4-arm polypeptoids (FAPs) were synthesized through grafting linear ε-l-lysine or δ-ornithine-based oligopeptides to a trimeric lysine core. The most potent 4R-O7 exhibited excellent activities toward three sensitive and two MDR C. albicans strains with MIC values as low as 24-48 µg/mL (vs 375 µg/mL for ε-polylysine, ε-PL). The mechanism studies revealed that 4R-O7 penetrated the cell membrane and generated ROS to kill cells. 4R-O7 exhibited a synergistic effect (FICI < 0.5) with voriconazole (VOR) and also assisted VOR to restore its efficacy to MDR C. albicans. In addition, the combined use of 4R-O7 and VOR significantly improved the elimination efficacy of mature C. albicans biofilms and enhanced the potency in a mouse subcutaneous C. albicans infection model.