The incidence and risk factors of proximal lower extremity deep vein thrombosis without pharmacologic prophylaxis in critically ill surgical Taiwanese patients: A prospective study.

Background: Venous thromboembolism (VTE) in critically ill patients has been well-studied in Western countries. Many studies have developed risk assessments and established pharmacological protocols to prevent deep venous thrombosis (DVT). However, the DVT rate and need for pharmacologic VTE prophylaxis in critically ill Taiwanese patients are limited. This study aimed to prospectively determine the DVT incidence, risk factors, and outcomes in critically ill Taiwanese patients who do not receive pharmacologic VTE prophylaxis. Methods: We conducted a prospective study in a surgical intensive care unit (SICU) of a tertiary academic medical center in Taiwan. Adult patients admitted to SICU from March 2021 to June 2022 received proximal lower extremities DVT surveillance with venous duplex ultrasound. No patient received pharmacologic VTE prophylaxis. The outcomes were the incidence and risk factors of DVT. Results: Among 501 enrolled SICU patients, 21 patients (4.2%) were diagnosed with proximal lower extremities DVT. In a multivariate regression analysis, hypoalbuminemia (odd ratio (OR) = 6.061, 95% confidence interval (CI): 1.067-34.421), femoral central venous catheter (OR = 4.515, 95% CI: 1.547-13.174), ICU stays more than 10 days (OR = 4.017, 95% CI: 1.270-12.707), and swollen leg (OR = 3.427, 95% CI: 1.075-10.930) were independent risk factors for DVT. In addition, patients with proximal lower extremities DVT have more extended ventilator days (p = 0.045) and ICU stays (p = 0.044). Conclusion: Our findings indicate critically ill Taiwanese patients have a higher incidence of DVT than results from prior retrospective studies in the Asian population. Physicians who care for this population should consider the specific risk factors for DVT and prescribe pharmacologic prophylaxis in high-risk groups.

An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies.

Bispecific antibodies have gained increasing popularity as therapeutics as they enable novel activities that cannot be achieved with monospecific antibodies. Some of the most popular bispecific formats are molecules in which two Fab arms with different antigen specificities are combined into one IgG-like molecule. One way to produce these bispecific molecules requires the discovery of antibodies against the two antigens of interest that share a common light chain. Here, we present the generation and characterization of a common light chain mouse model, in which the endogenous IGKJ cluster is replaced with a prearranged, modified murine IGKV10-96/IGKJ1 segment. We demonstrate that genetic modification does not impact B-cell development. Upon immunization with ovalbumin, the animals generate an antibody repertoire with VH gene segment usage of a similar diversity to wildtype mice, while the light chain diversity is restricted to antibodies derived from the prearranged IGKV10-96/IGKJ1 germline. We further show that the clonotype diversity of the common light chain immune repertoire matches the diversity of immune repertoire isolated from wildtype mice. Finally, the common light chain anti-ovalbumin antibodies have only slightly lower affinities than antibodies isolated from wildtype mice, demonstrating the suitability of these animals for antibody discovery for bispecific antibody generation.

Feasibility of High-Cellular-Resolution Full-Field, Artificial-Intelligence-Assisted, Real-Time Optical Coherence Tomography in the Evaluation of Vitiligo: A Prospective Longitudinal Follow-Up Study.

Vitiligo, a psychologically distressing pigmentary disorder characterized by white depigmented patches due to melanocyte loss, necessitates non-invasive tools for early detection and treatment response monitoring. High-cellular-resolution full-field optical coherence tomography (CRFF-OCT) is emerging in pigmentary disorder assessment, but its applicability in vitiligo repigmentation after tissue grafting remains unexplored. To investigate the feasibility of CRFF-OCT for evaluating vitiligo lesions following tissue grafting, our investigation involved ten vitiligo patients who underwent suction blister epidermal grafting and laser ablation at a tertiary center between 2021 and 2022. Over a six-month period, clinical features, dermoscopy, and photography data were recorded. Utilizing CRFF-OCT along with artificial intelligence (AI) applications, repigmentation features were captured and analyzed. The CRFF-OCT analysis revealed a distinct dark band in vitiligo lesion skin, indicating melanin loss. Grafted areas exhibited melanocytes with dendrites around the epidermal-dermal junction and hair follicles. CRFF-OCT demonstrated its efficacy in the early detection of melanocyte recovery and accurate melanin quantification. This study introduces CRFF-OCT as a real-time, non-invasive, and in vivo evaluation tool for assessing vitiligo repigmentation, offering valuable insights into pigmentary disorders and treatment responses.

Prognostic factors for critically ill surgical patients with unplanned intensive care unit readmission: Developing a novel predictive scoring model for predicting readmission.

BACKGROUND: Unplanned readmission to the surgical intensive care unit has been demonstrated to worsen patient outcomes. Our objective was to identify risk factors and outcomes associated with unplanned surgical intensive care unit readmission and to develop a predictive scoring model to identify patients at high risk of readmission. METHODS: We retrospectively analyzed patients admitted to the surgical intensive care unit (2020-2021) and categorized them as either with or without unplanned readmission. RESULTS: Of 1,112 patients in the derivation cohort, 76 (6.8%) experienced unplanned surgical intensive care unit readmission, with sepsis being the leading cause of readmission (35.5%). Patients who were readmitted had significantly higher in-hospital mortality rates than those who were not. Multivariate analysis identified congestive heart failure, high Sequential Organ Failure Assessment-Hepatic score, use of carbapenem during surgical intensive care unit stay, as well as factors before surgical intensive care unit discharge such as inadequate glycemic control, positive fluid balance, low partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, and receipt of total parenteral nutrition as independent predictors for unplanned readmission. The scoring model developed using these predictors exhibited good discrimination between readmitted and non-readmitted patients, with an area under the curve of 0.74. The observed rates of unplanned readmission for scores of <4 points and ≥4 points were 4% and 20.2% (P < .001), respectively. The model also demonstrated good performance in the validation cohort, with an area under the curve of 0.74 and 19% observed unplanned readmission rate for scores ≥4 points. CONCLUSION: Besides congestive heart failure, clinicians should meticulously re-evaluate critical variables such as the Sequential Organ Failure Assessment-Hepatic score, partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, glycemic control, and fluid status before releasing the patient from the surgical intensive care unit. It is crucial to determine the reasons for using carbapenems during surgical intensive care unit stay and the causes for the inability to discontinue total parenteral nutrition before discharging the patient from the surgical intensive care unit.

VHH CDR-H3 conformation is determined by VH germline usage.

VHHs or nanobodies are single antigen binding domains originating from camelid heavy-chain antibodies. They are used as diagnostic and research tools and in a variety of therapeutic molecules. Analyzing variable domain structures from llama and alpaca we found that VHHs can be classified into two large structural clusters based on their CDR-H3 conformation. Extended CDR-H3 loops protrude into the solvent, whereas kinked CDR-H3 loops fold back onto framework regions. Both major families have distinct properties in terms of their CDR-H3 secondary structure, how their CDR-H3 interacts with the framework region and how they bind to antigens. We show that the CDR-H3 conformation of VHHs correlates with the germline from which the antibodies are derived: IGHV3-3 derived antibodies almost exclusively adopt a kinked CDR-H3 conformation while the CDR-H3 adopts an extended structure in most IGHV3S53 derived antibodies. We do not observe any bias stemming from V(D)J recombination in llama immune repertoires, suggesting that the correlation is the result of selection processes during B-cell development. Our findings demonstrate a previously undescribed impact of germline usage on antigen interaction and contribute to a better understanding on how properties of the antibody framework shape the immune repertoire.

Clinical impact of carbapenems in critically ill patients with valproic acid therapy: A propensity-matched analysis.

Background: Valproic acid (VPA) is one of the most widely used broad-spectrum antiepileptic drugs, and carbapenems (CBPs) remain the drug of choice for severe infection caused by multidrug-resistant bacteria in critically ill patients. The interaction between VPA and CBPs can lead to a rapid depletion of serum VPA level. This may then cause status epilepticus (SE), which is associated with significant mortality. However, the prognostic impact of drug interactions in critically ill patients remains an under-investigated issue. Objective: The aim of this study was to compare the prognosis of critically ill patients treated with VPA and concomitant CBPs or other broad-spectrum antibiotics. Methods: Adult patients admitted to a medical center intensive care unit between January 2007 and December 2017 who concomitantly received VPA and antibiotics were enrolled. The risk of reduced VPA serum concentration, seizures and SE, mortality rate, length of hospital stay (LOS), and healthcare expenditure after concomitant administration were analyzed after propensity score matching. Results: A total of 1,277 patients were included in the study, of whom 264 (20.7%) concomitantly received VPA and CBPs. After matching, the patients who received CBPs were associated with lower VPA serum concentration (15.8 vs. 60.8 mg/L; p < 0.0001), a higher risk of seizures (51.2 vs. 32.4%; adjusted odds ratio [aOR], 2.19; 95% CI, 1.48-3.24; p < 0.0001), higher risk of SE (13.6 vs. 4.7%; aOR, 3.20; 95% CI, 1.51-6.74; p = 0.0014), higher in-hospital mortality rate (33.8 vs. 24.9%; aOR, 1.57; 95% CI, 1.03-2.20; p = 0.036), longer LOS after concomitant therapy (41 vs. 30 days; p < 0.001), and increased healthcare expenditure (US$20,970 vs. US$12,848; p < 0.0001) than those who received other broad-spectrum antibiotics. Conclusion: The administration of CBPs in epileptic patients under VPA therapy was associated with lower VAP serum concentration, a higher risk of seizures and SE, mortality, longer LOS, and significant utilization of healthcare resources. Healthcare professionals should pay attention to the concomitant use of VPA and CBPs when treating patients with epilepsy. Further studies are warranted to investigate the reason for the poor outcomes and whether avoiding the co-administration of VPA and CBP can improve the outcomes of epileptic patients.

Magnolol regulates miR-200c-3p to inhibit epithelial-mesenchymal transition and retinoblastoma progression by modulating the ZEB1/E-cadherin axis in vitro and in vivo.

BACKGROUND: Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3-4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear. PURPOSE: The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, ß-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo. RESULTS: Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/ß-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma. CONCLUSION: Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time.

Size Reduction of the Right Amygdala in Chronic Pain Patients with Emotional Stress: A Systematic Review and Meta-Analysis.

The structural impact of chronic pain on amygdala in chronic pain (CP) patients remains unclear, although major depression and anxiety are known to be associated with its increase and decrease in size, respectively. This study aimed at examining the relationship between emotional stress and amygdala size in CP patients. The effects of mediating and moderating variables were also examined. The PubMed, Embase, and Web of Science databases were searched for English clinical trials from inception to February 2022 using the appropriate keyword strings. We compared the differences in amygdala size assessed with magnetic resonance imaging between CP patients with emotional stress and healthy counterparts. Of the 49 full-text articles identified, 13 studies enrolling 1,551 participants including 738 CP patients with emotional stress and 813 controls were analyzed. Emotional stress evaluated with questionnaires based on Beck depression inventory, Hamilton depression/anxiety scale, state-trait anxiety inventory, and hospital anxiety and depression scale revealed significant differences between CP patients with emotional stress and controls, indicating a subclinical but significant level of emotional stress in CP patients. The results demonstrated an amygdala shrinkage among CP patients with emotional stress compared to the controls, especially the right side (P = .02). Besides, pain from a single body region was more likely to impact the amygdala size compared to diffuse pain (P = .02). Regression analysis revealed no significant association between continuous variables (age, gender, pain duration/intensity) and amygdala size. Our findings demonstrated that emotional stress was associated with a reduced right amygdala size in CP patients.

Association between Wakeup Frequency at Night and Atherogenic Dyslipidemia: Evidence for Sex Differences.

AIM: This study aimed to determine whether sleep disturbance, defined as the wakeup frequency at night, is associated with atherogenic dyslipidemia and to explore possible sex differences. METHODS: A total of 1,368 adults aged 19-70 years were included in the study of lifestyles and atherogenic dyslipidemia at the National Taiwan University Hospital in the period of 2008-2012. They completed a questionnaire regarding lifestyle information and sleep quality, including sleep hour duration, use of sleeping pills, and wakeup frequency during nighttime sleep. The measured lipid profiles included total cholesterol, triglycerides, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), non-HDL-C, and small dense LDL-C (sdLDL-C). Multivariate logistic regression was performed to determine habitual interrupted sleep and the odds ratio of atherogenic dyslipidemia following adjustment for conventional risk factors and for sex-based subgroup analysis. RESULTS: A wakeup frequency ≥ 3 times per night was independently associated with an increased risk [odds ratio (95% confidence interval)] of dyslipidemia was 1.96 (1.17-3.28), and non-HDL-C ≥ 160 mg/dL was 1.78 (1.09-2.89). A higher wakeup frequency was associated with increased atherogenic dyslipidemia in women than in men. The multivariate adjusted relative risks for non-HDL ≥ 160 mg/dL and cholesterol ≥ 200 mg/dL were 3.05 (1.27-7.34) and 4.01(1.29-12.45) for female individuals with insomnia and those with a wakeup frequency ≥ 2 times per night, respectively. CONCLUSION: A higher wakeup frequency was associated with atherogenic dyslipidemia in Taiwanese adults, particularly in women. This study also provided another evidence of increasing cardiovascular diseases in subjects with habitual interrupted sleep.

Impact of Illness Severity and Interventions on Successful Weaning from Nasal CPAP in Very Preterm Neonates: An Observational Study.

This study aims to identify clinical variables that could affect successful weaning from nasal continuous positive airway pressure (NCPAP) in very preterm infants. Infants born at a gestational age (GA) of <32 weeks were retrospectively enrolled. Weaning from NCPAP was initiated when the infants were clinically stable. In the univariate analysis, GA, birth weight, body weight (BW) z-score at the time of successful NCPAP weaning, intubation, total duration of intubation, respiratory distress syndrome grade, APGAR score at the 1 and 5 min, initial shock, anemia, bronchopulmonary dysplasia, number of blood transfusions, total duration of dopamine use, administration of more than two doses of surfactant, use of aminophylline, use of a diuretic, and total duration of total parenteral nutrition were significantly associated with postmenstrual age (PMA) at the time of successful NCPAP weaning. Multivariate analysis showed that the total duration of intubation, bronchopulmonary dysplasia, and administration of more than two doses of surfactant were positively associated with PMA at the time of successful NCPAP weaning. A reverse association was noted between BW z-score and PMA at the time of successful NCPAP weaning. Sufficient nutrition and avoidance of further ventilator-induced lung injury could decrease NCPAP duration in very preterm infants.

New developments in neonatal respiratory management.

Respiratory distress syndrome (RDS) is the major cause of respiratory failure in preterm infants due to immature lung development and surfactant deficiency. Although the concepts and methods of managing respiratory problems in neonates have changed continuously, determining appropriate respiratory treatment with minimal ventilation-induced lung injury and complications is crucially important. This review summarizes neonatal respiratory therapy's advances and available strategies (i.e., exogenous surfactant therapy, noninvasive ventilation, and different ventilation modes), focusing on RDS management.

The Risk of Bleeding and Adverse Events with Clopidogrel in Elective Hip and Knee Arthroplasty Patients.

Orthopedic surgeons often face a clinical dilemma on how to manage antiplatelet therapies during the time of surgery. This retrospective study is aimed to investigate the bleeding risk and adverse events in patients who hold or keep clopidogrel during elective major joints arthroplasty. Two hundred and ninety-six patients that were treated with clopidogrel while undergoing total hip or knee joint replacement between January 2009 and December 2018 were studied. Group 1 included 56 patients (18.9%) who kept using clopidogrel preoperatively. Group 2 included 240 patients who hold clopidogrel use ≥5 days preoperatively. Blood transfusion rates, estimated blood loss, complication rates, and adverse cardiocerebral events were collected and analyzed. The mean total blood loss was more in the group 1 patients as compared with that in the group 2 patients (1212.3 mL (685.8 to 2811.8) vs. 1068.9 mL (495.6 to 3294.3), p = 0.03). However, there was no significant difference between the two groups of patients regarding transfusion rates, bleeding-related complications, and infection rates. There was a trend toward a higher incidence of adverse cardiocerebral events in patients withholding clopidogrel for more than 5 days before surgery. The results of this study suggest that clopidogrel continuation could be safe and advisable for patients at thrombotic risk undergoing primary major joint replacement. Acute antiplatelet withdrawal for an extended period of time might be associated with an increased risk of postoperative thromboembolic events. More studies are required in the future to further prove this suggestion.

Importance of daptomycin dosage on the clinical outcome in liver transplant recipients with vancomycin-resistant enterococci infection.

We retrospectively studied 16 (3 colonization and 13 infections) early post-liver transplant (≤60-day after transplantation) patients with vancomycin-resistant enterococci (VRE) colonization/infection from 2016 to 2019. All VRE isolates were Enterococcus faecium. Of 13 patients with VRE infection, 12 (92.3%) underwent living-donor liver transplantation and 1 underwent deceased donor liver transplantation. Among these 13 patients, the median time from transplant to emergence of VRE infection was 12 days. The median interval from VRE infection to death was 27 days. Of these 13 patients, eleven patients (8 survived; 3 died) received daptomycin therapy for VRE. Among them, 4 (36.3%) received daptomycin doses <8 mg/kg. Non-survivors (n = 3) received significantly lower daptomycin dose than survivors (n = 8; p = .040). Daptomycin doses <8mg/kg were more frequently associated with non-survivors (n = 3) than with survivors (n = 8; p = .024). In summary, the suboptimal dosage of daptomycin may have contributed to a higher rate of in-hospital mortality. Doses ≥8 mg/kg may be needed to adequately treat VRE infection in liver transplant recipients.

Computer-Aided Detection (CADe) System with Optical Coherent Tomography for Melanin Morphology Quantification in Melasma Patients.

Dark skin-type individuals have a greater tendency to have pigmentary disorders, among which melasma is especially refractory to treat and often recurs. Objective measurement of melanin amount helps evaluate the treatment response of pigmentary disorders. However, naked-eye evaluation is subjective to weariness and bias. We used a cellular resolution full-field optical coherence tomography (FF-OCT) to assess melanin features of melasma lesions and perilesional skin on the cheeks of eight Asian patients. A computer-aided detection (CADe) system is proposed to mark and quantify melanin. This system combines spatial compounding-based denoising convolutional neural networks (SC-DnCNN), and through image processing techniques, various types of melanin features, including area, distribution, intensity, and shape, can be extracted. Through evaluations of the image differences between the lesion and perilesional skin, a distribution-based feature of confetti melanin without layering, two distribution-based features of confetti melanin in stratum spinosum, and a distribution-based feature of grain melanin at the dermal-epidermal junction, statistically significant findings were achieved (p-values = 0.0402, 0.0032, 0.0312, and 0.0426, respectively). FF-OCT enables the real-time observation of melanin features, and the CADe system with SC-DnCNN was a precise and objective tool with which to interpret the area, distribution, intensity, and shape of melanin on FF-OCT images.

Teicoplanin versus ß-lactam for febrile patients with Staphylococcus-like bacteremia: focus on methicillin-susceptible Staphylococcus aureus bacteremia.

BACKGROUND: Many studies have shown that vancomycin is inferior to ß-lactam antibiotics in terms of effectiveness in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. However, limited data are available regarding the comparison of clinical outcomes between patients receiving initial teicoplanin and those receiving ß-lactam antibiotics for MSSA bacteremia. METHODS: Eighty-four adults with MSSA bacteremia were included: initial teicoplanin treatment group (n = 28) and ß-lactam treatment group (n = 56). The two groups were further stratified based on propensity score matching according to the outcome analysis using a logistic regression model. We investigated the clinical outcomes between the groups before and after propensity score matching after treatment completion. RESULTS: Pittsburgh bacteremia score ≥ 4 (odds ratio, 60.6; 95%CI, 7.4-496.8) was an independent risk factor for unfavorable outcome. After propensity score matching, the initial teicoplanin treatment group and the ß-lactam treatment group consisted of 28 patients each. No statistically significant differences were observed in the proportions of patients with favorable outcomes and 30-day overall mortality rates between the groups before and after propensity score matching after the completion of teicoplanin or ß-lactam treatment. The Kaplan-Meier 30-day survival curve also showed no significant difference between the patients receiving initial teicoplanin treatment and those receiving ß-lactam treatment before and after matching (hazard ratio, 1.84, 95%CI, 0.60-5.64; and 3.12, 95%CI, 0.98-9.99, respectively). CONCLUSIONS: There were no significant difference in clinical outcomes between initial teicoplanin treatment and ß-lactam treatment among patients with MSSA bacteremia. Pittsburgh bacteremia score ≥ 4 was a significant risk factor for mortality.

Interactions between carbapenems and valproic acid among the patients in the intensive care units.

PURPOSE: To evaluate risk factors for epileptic seizures or status epilepticus (SE) in patients concomitantly receiving valproic acid (VPA) and carbapenems. MATERIALS AND METHODS: Adult patients in the intensive care units (ICUs) who concomitantly received VPA and carbapenems from 2007 to 2017 were included. The impacts of different carbapenems on serum concentration of VPA were compared. RESULTS: Among 162 patients included, 104 (64.2%) and 45 (27.8%) developed epileptic seizures and SE, respectively. The risk factors for epileptic seizures were age (per year increase, adjusted odds ratio [aOR], 1.03), initial antiepileptic regimen (monotherapy and polytherapy, aOR, 0.43 and 0.18, respectively), and VPA serum concentration after concomitant carbapenem administration (per 1 µg/mL increase, aOR, 0.96). VPA serum concentration after concomitant carbapenem administration was an independent risk factor for SE (per µg/mL increase, aOR, 0.98). Concomitant imipenem/cilastatin administration did not significantly decrease VPA serum concentration compared to that by meropenem or ertapenem. The length of stay and number of days on ventilation after concomitant carbapenem administration in the ICUs were significantly more in those with epileptic seizures or SE. CONCLUSIONS: Carbapenems decreased VPA serum concentration and increased the risk of epileptic seizures and SE, which led to increased length of ICU stay.

Impact of biofilm production by Candida species and antifungal therapy on mortality of patients with candidemia.

BACKGROUND AND OBJECTIVES: Few studies have investigated the clinical outcomes of patients with candidemia caused by Candida species with different levels of biofilm formation. We aimed to investigate the impact of antifungal therapy on the outcome of candidemia caused by Candida species that were categorised as low biofilm formers (LBFs), moderate biofilm formers (MBFs), and high biofilm formers (HBFs). METHODS: Adults with candidemia caused by LBF and HBF/MBF Candida species that were susceptible to fluconazole and caspofungin were included to investigate the impact of treatment with fluconazole vs an echinocandin on 30-day crude mortality. RESULTS: In total, 215 patients with candidemia received fluconazole and 116 patients received an echinocandin. In multivariate analysis, Pittsburgh bacteremia score ≥ 4 (adjusted odds ratio [AOR] =2.42; 95% confidence interval [CI], 1.32-4.41), malignancy (AOR = 3.45; 95% CI, 1.83-6.51), not removing the central venous catheter within 48 hours of a positive blood culture (AOR = 4.69; 95% CI, 2.61-8.45), and treatment with fluconazole for candidemia due to HBF/MBF Candida spp. (AOR = 2.23; 95% CI, 1.22-4.06) were independent factors associated with 30-day mortality. Of the 165 patients infected by HBF/MBF Candida isolates, those who received azole therapy had a significantly higher sepsis-related mortality rate than those who received echinocandin therapy (44.9% [49/109] vs 26.8% [15/56], P = .03). CONCLUSIONS: There was a trend of an independent association between fluconazole treatment and poor outcomes in the patients infected by HBF/MBF Candida strains.