The Development and Validation of a Machine Learning Model to Predict Bacteremia and Fungemia in Hospitalized Patients Using Electronic Health Record Data.

OBJECTIVES: Bacteremia and fungemia can cause life-threatening illness with high mortality rates, which increase with delays in antimicrobial therapy. The objective of this study is to develop machine learning models to predict blood culture results at the time of the blood culture order using routine data in the electronic health record. DESIGN: Retrospective analysis of a large, multicenter inpatient data. SETTING: Two academic tertiary medical centers between the years 2007 and 2018. SUBJECTS: All hospitalized patients who received a blood culture during hospitalization. INTERVENTIONS: The dataset was partitioned temporally into development and validation cohorts: the logistic regression and gradient boosting machine models were trained on the earliest 80% of hospital admissions and validated on the most recent 20%. MEASUREMENTS AND MAIN RESULTS: There were 252,569 blood culture days-defined as nonoverlapping 24-hour periods in which one or more blood cultures were ordered. In the validation cohort, there were 50,514 blood culture days, with 3,762 cases of bacteremia (7.5%) and 370 cases of fungemia (0.7%). The gradient boosting machine model for bacteremia had significantly higher area under the receiver operating characteristic curve (0.78 [95% CI 0.77-0.78]) than the logistic regression model (0.73 [0.72-0.74]) (p < 0.001). The model identified a high-risk group with over 30 times the occurrence rate of bacteremia in the low-risk group (27.4% vs 0.9%; p < 0.001). Using the low-risk cut-off, the model identifies bacteremia with 98.7% sensitivity. The gradient boosting machine model for fungemia had high discrimination (area under the receiver operating characteristic curve 0.88 [95% CI 0.86-0.90]). The high-risk fungemia group had 252 fungemic cultures compared with one fungemic culture in the low-risk group (5.0% vs 0.02%; p < 0.001). Further, the high-risk group had a mortality rate 60 times higher than the low-risk group (28.2% vs 0.4%; p < 0.001). CONCLUSIONS: Our novel models identified patients at low and high-risk for bacteremia and fungemia using routinely collected electronic health record data. Further research is needed to evaluate the cost-effectiveness and impact of model implementation in clinical practice.

The Diagnostic Value of Procalcitonin Versus Other Biomarkers in Prediction of Bloodstream Infection.

BACKGROUND: We compared the diagnostic utility of procalcitonin (PCT), C-reactive protein (CRP), and hematological markers, including white blood cell count (WBC), neutrophils (NEU), percentage of neutrophils (NEU%), lymphocytes (LYM), neutrophil-lymphocyte count ratio (NLCR), and platelet count (PLT) for predicting bloodstream infection (BSI), which was confirmed by blood culture (BC). METHODS: A retrospective analysis was conducted for 1807 inpatients. The level of PCT, CRP, blood cells, and blood culture results were compared between the positive blood culture group and negative blood culture group; each indicator was analyzed in the performance of bacterial BSI diagnosis by drawing ROC curves. RESULTS: Blood cultures were positive in 230 patients; hence, the prevalence of bacteremia was 12.7%. There were significant differences in the median value for each marker between positive group BCs and negative group BCs (p < 0.05). The areas under the receiver operating characteristic curves (ROC-AUCs) of PCT, CRP, WBC, NEU, NUE%, LYM, NLCR, and PLT for discriminating positive BCs from negative BCs were 0.811, 0.654, 0.612, 0.634, 0.684, 0.595, 0.682, and 0.633 respectively. PCT concentrations of gram-negative (14.94 ng/mL, IQR 2.93  48.76) were significantly higher than gram-positive (4.74 ng/mL, IQR 1.22  17.5) and fungal (1.47 ng/mL, IQR 0.66  35.34). CONCLUSIONS: PCT proved to be the most reliable predictor of BSI, second were NEU% and NLCR. A higher PCT level was found in patients with a gram-negative BSI compared to gram-positive BSI and fungal BSI.

Do Wound Cultures Give Information About the Microbiology of Blood Cultures in Severe Burn Patients?

BACKGROUND: Blood stream infection (BSI) and the subsequent development of sepsis are among the most common infection complications occurring in severe burn patients. This study was designed to evaluate the relationship between the burn wound flora and BSI pathogens. METHODS: Documentation of all bacterial and fungal wound and blood isolates from severe burn patients hospitalized in the burn unit and intensive care unit was obtained from medical records retrieved retrospectively from a computerized, hospital-wide database over a 13-year period. All data were recorded in relation to the Ryan score. RESULTS: Of 195 severe burn patients, 88 had at least 1 BSI episode. Transmission of the same pathogen from wound to blood was documented in 30% of the patients, with a rising BSI frequency as the Ryan score increased. There were a total of 263 bacteremic episodes in 88 study patients, 44% of blood isolates were documented previously in wound cultures, and transmission of the same pathogen from wound to blood was noted in 65% of bacteremic patients. CONCLUSIONS: When there is clinical suspicion of sepsis, appropriate empirical systemic antibiotic therapy should be broad spectrum and should rely on the susceptibility of the organisms from recent cultures of the burn wound surface, until the blood cultures results are completed.

Saccharomyces cerevisiae fungemia, a possible consequence of the treatment of Clostridium difficile colitis with a probioticum.

The yeast Saccharomyces boulardii is a biotherapeutic agent used for the prevention and treatment of several gastrointestinal diseases, such as diarrhoea caused by Clostridium difficile, in addition to the antibiotic therapy. In this study we report a case of Saccharomyces cerevisiae fungemia in a patient with Clostridium difficile-associated diarrhoea (CDAD) treated orally with S. boulardii in association with vancomycin. The identification of the S. cerevisiae was confirmed by molecular technique. Fungemia is a rare, but a serious complication to treatment with probiotics. We believe it is important to remind the clinicians of this risk when prescribing probiotics, especially to immunocompromised patients.

False-positive Aspergillus antigenemia due to blood product conditioning fluids.

The presence of Aspergillus antigens in blood transfusion components from different manufacturers was analyzed. Galacomannans were found in transfused patients, pooled platelet concentrates, fresh frozen plasma, and packed red cells collected using Fresenius Kabi bags. Galacomannans were also found in blood collection anticoagulant and platelet additive solution from this manufacturer.

Early ultrasonographic finding of septic thrombophlebitis is the main indicator of central venous catheter removal to reduce infection-related mortality in neutropenic patients with bloodstream infection.

BACKGROUND: Septic thrombophlebitis increases patient morbidity and mortality following metastatic infections, pulmonary emboli, and/or septic shock. Central venous catheter (CVC) removal for occult septic thrombophlebitis challenges current strategy in neutropenic patients. PATIENTS AND METHODS: We prospectively evaluated infection-related mortality in 100 acute leukemia patients, with CVC-related bloodstream infection (CRBSI) after chemotherapy, who systematically underwent ultrasonography to identify the need for catheter removal. Their infection-related mortality was compared with that of a historical cohort of 100 acute leukemia patients, with CRBSI after chemotherapy, managed with a clinically driven strategy. Appropriate antimicrobial therapy was administered in all patients analyzed. RESULTS: In the prospective series, 30/100 patients required catheter removal for ultrasonography-detected septic thrombophlebitis after 1 median day from BSI onset; 70/100 patients without septic thrombophlebitis retained their CVC. In the historical cohort, 60/100 patients removed the catheter (persistent fever, 40 patients; persistent BSI, 10 patients; or clinically manifest septic thrombophlebitis, 10 patients) after 8 median days from BSI onset; 40/100 patients retained the CVC because they had not clinical findings of complicated infection. At 30 days median follow-up, one patient died for infection in the ultrasonography-assisted group versus 17 patients in the historical cohort (P<0.01). With the ultrasonography-driven strategy, early septic thrombophlebitis detection and prompt CVC removal decrease infection-related mortality, whereas clinically driven strategy leads to inappropriate number, reasons, and timeliness of CVC removal. CONCLUSION: Ultrasonography is an easy imaging diagnostic tool enabling effective and safe management of patients with acute leukemia and CRBSI.

Retrospective evaluation of the area over the neutrophil curve index to predict early infection in hematopoietic stem cell transplantation recipients.

We investigated the impact of neutropenia on the development of early bloodstream and pulmonary infections in hematopoietic stem cell transplantation (HSCT) recipients, and evaluated the utility of an index (D-index) that reflects both the intensity and duration of neutropenia. Fifty-eight patients (23 autologous, 35 allogeneic HSCT recipients) were enrolled in this retrospective study. The D-index was defined as the area over the neutrophil curve during neutropenia. We also evaluated the utility of the cumulative D-index from the start of neutropenia until the development of infection (c-D-index), which may enable real-time assessment of the risk for infection. The patients showed 12 and 7 episodes of bloodstream and pulmonary infection, respectively. The D-index, days of neutropenia (<500/microL) and days of profound neutropenia (<100/microL) had at least a nearly significant impact on the development of both bloodstream and pulmonary infections. On the other hand, the c-D-index, cumulative days of neutropenia, and cumulative days of profound neutropenia significantly affected pulmonary infection, but not bloodstream infection. The c-D-index had a high negative predictive value of 97.4% for pulmonary infection with a cutoff of 5500, but the area under the receiver operating characteristic curve was similar to that of the cumulative days of neutropenia and profound neutropenia. Our results showed that although the c-D-index may be useful for identifying patients who are at low risk for early pulmonary infection after HSCT, its performance was similar to that of the simple duration of neutropenia.

Applicability of an in-house saponin-based extraction method in Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry system for identifying bacterial and fungal species in positively flagged pediatric VersaTREK blood cultures.

BACKGROUND/PURPOSE: Early identification of pathogens causing bloodstream infection (BSI) is critical for prompt administration of appropriate antimicrobial therapy. METHODS: We used an in-house saponin-based extraction method to evaluate the performance of Bruker Biotyper MALDI-TOF MS system (MALDI Biotyper) for bacterial and fungal identification in 2013 positively-flagged VersaTREK blood culture bottles. RESULTS: A total of 180 monomicrobial and 23 polymicrobial positive blood cultures were investigated. Among monomicrobial positive blood cultures, the MALDI Biotyper recognized 90.6% and 81.7% of organisms directly from the flagged blood culture bottles to the genus and species levels, respectively. The MALDI Biotyper also correctly characterized one of the polymicrobial organisms to the species level in 20 (87%) bottles and to the genus level in 21 (91.3%) bottles. The overall identification rate using our protocol was 90.6% (184/203) and 82.3% (167/203) for genus and species levels, respectively. Identification accuracy was higher for Gram-positive than Gram-negative organisms and was the lowest for yeasts. Score values of identification were ≥1.500 for 200 (98.5%) bottles, ≥1.700 for 195 (96.1%) bottles and ≥2.000 for 182 (89.7%) bottles. Moreover, 83.5% and 92% of the isolates were identified precisely to species and genus level with the lower cutoff score of 1.500. Using our protocol also helped identifying BSI pathogens 18-24 h earlier compared to the sub-cultured colonies. CONCLUSION: Using Bruker MALDI Biotyper for identification of isolates directly from positive VersaTREK blood culture bottles, our in-house saponin-based protocol provided a more rapid turn-around time for correct identification of BSI pathogens than the conventional methods.

Septicemia after chemotherapy for childhood acute lymphoblastic leukemia in China: A multicenter study CCCG-ALL-2015.

BACKGROUND: Septicemia is an important cause of treatment-related mortality and treatment failure in pediatric acute lymphoblastic leukemia (ALL) in developing countries. A multicenter CCCG-ALL-2015 study was conducted in China and factors associated with septicemia and mortality were studied. METHODS: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included. Patients with documented septicemia were identified from the Data Center and additional data were collected. RESULTS: A total of 4080 patients were recruited in the study and 527 patients with septicemia were identified (12.9%, 95% CI 11.9%-13.9%). The intermediate risk (IR)/high risk (HR) group had significantly higher incidence of septicemia as compared with low risk (LR) group, 17.1% vs 9.1% (OR 2.07, 95% CI 1.71-2.49, P < .001). Induction phase was the period with majority of septicemia episodes happened, 66.8% in LR and 56.1% in IR/HR groups. Gram-positive bacteria accounted for 54.1%, gram-negative bacteria 44.5%, and fungus 1.4% of positive cultures. Multidrug-resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.4% (95% CI 1.9%-4.9%). Multiple logistic regression identified female gender, comorbid complications, and fungal infection as risk factors associated with mortality. Gram-negative septicemia was associated with higher mortality, 4.9% vs 1.4% (OR 0.28, 95% CI 0.09-0.88, P = .02). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%. CONCLUSION: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to the reports of western countries. The septicemia-related mortality rate was low. There was marked variation in the incidence of septicemia among the centers.

Rapid identification of bloodstream bacterial and fungal pathogens and their antibiotic resistance determinants from positively flagged blood cultures using the BioFire FilmArray blood culture identification panel.

BACKGROUND/PURPOSE: Rapid and accurate identification of pathogens and their antibiotic resistance directly from flagged blood cultures can aid clinicians in optimizing early antibiotic treatment and improve the clinical outcomes, especially in settings associated with high rates of bloodstream infection caused by vancomycin-resistant Enterococci (VRE) and carbapenem-resistant Enterobacteriaceae (CRE). We compared the results of the BioFire FilmArray Blood Culture Identification (BCID) panel with those of conventional methods for identifying the pathogens and their antibiotic susceptibility status. METHODS: In total, 100 randomly selected positive blood cultures (BACTEC Plus Aerobic/F bottles or BACTEC Anaerobic Lytic/10 bottles) were analyzed. The pathogen detection efficiency of FilmArray BCID panel was compared with that of conventional method using MALDI-TOF MS system (Bruker MALDI Biotyper) and susceptibility testing by the Vitek 2 system. The sequencing analysis of antibiotic resistance genes was performed for discrepant results obtained from MALDI Biotyper and Vitek 2. RESULTS: Among the 100 positively flagged blood cultures, 94% of FilmArray BCID panel results were consistent with the MALDI Biotyper results. All five VRE isolates positive for vanA/vanB genes, 10 of 12 Staphylococcus species positive for mecA gene, and only one Klebsiella pneumoniae isolate positive for K. pneumoniae carbapenemase gene (blaKPC) detected in the FilmArray BCID panel were also concordant with results by the results by conventional susceptibility testing/molecular confirmation. CONCLUSIONS: The FilmArray BCID panel results not only demonstrated good correlation with conventional blood culture identification and susceptibility results but also provided results rapidly, especially for the early detection of MRSA, VRE and blaKPC-mediated CRE.

Burden of early-onset candidemia: analysis of culture-positive bloodstream infections from a large U.S. database.

OBJECTIVES: : To characterize the epidemiology and burden of early-onset, nonnosocomial candidemia. DESIGN: : Retrospective review of Cardinal Health Outcomes Research Database, which comprises all acute care admissions at participating hospitals. SETTING: : A total of 176 acute care hospitals. PATIENTS: : All patients admitted from 2000 through 2005 who had early-onset bloodstream infection, defined as presence of both a positive blood culture drawn within 1 day before or within 48 hrs after hospital admission and an appropriate diagnostic code for infection. INTERVENTION: : None. MEASUREMENTS AND MAIN RESULTS: : To evaluate the impact of different pathogens on clinical and economic outcomes, we performed mixed-effect logistic and linear regression analyses and controlled for potential confounding factors. Of 64,307 early-onset bloodstream infections, 738 (1.2%) were positive for Candida. The rate of early-onset candidemia nearly doubled between 2000 and 2003 (p < .001) and then stabilized. Crude in-hospital mortality was higher for candidemia than for bacterial bloodstream infection (28.3% vs. 15.0%; p < .0001). Compared with patients with bacterial bloodstream infections, patients with candidemia were more likely to have been admitted within 30 days and to have been transferred from another healthcare facility. Compared with Gram-negative bacterial bloodstream infection and after controlling for other risk factors, candidemia was associated with increased mortality risk (odds ratio, 2.38; 95% confidence interval, 1.94-2.91; p < .0001), longer attributable hospital stay (4.8 days; 95% confidence interval, 4.1-5.5; p < .0001), and higher attributable hospital costs ($12,617; 95% confidence Interval, $10,755-$14,479; p < .0001). CONCLUSIONS: : Early-onset candidemia seems to be a distinct entity, which is increasing in frequency and is associated with increased mortality risk, longer hospital stay, and higher hospital costs relative to bacterial bloodstream infection.

Rapid diagnosis of candidaemia by real-time PCR detection of Candida DNA in blood samples.

This study prospectively evaluated an 18S rRNA gene-targeted real-time PCR approach in comparison with standard blood culture (BC) diagnostics for rapid diagnosis of candidaemia in a large study population of 384 patients, including 902 whole blood samples from 468 infectious episodes (IEs) of 329 adults and 55 children with haematological malignancies and various forms of immunodeficiency, and intensive care unit patients. Seven out of eight BC-proven cases (87.5 %) of candidaemia and seven out of twelve BC-positive samples (58.3 %) were positive by the Candida-specific PCR. A positive PCR result was also obtained for 28/460 BC-negative samples from IEs, including 8 patients with culture-confirmed Candida infection at primary sterile body sites. Of the PCR-positive, culture-negative patients, more than 50 % received systemic antifungal therapy. In 432/460 BC-negative IEs, the Candida specific-PCR was negative, resulting in a negative predictive value of 99.8 %. In conclusion, the Candida specific-PCR approach facilitates rapid detection of Candida DNA in blood samples of patients at risk of candidaemia within a few hours. Although standard BC diagnostics appear to remain indispensable for the detection of all cases of candidaemia, this PCR assay allowed the detection of candidaemia at a mean of 3 days earlier than BC diagnostics. Thus, it enables earlier antifungal therapy for patients with suspected candidaemia and may prevent further complications.

Empirical treatment of candidemia in intensive care units: fluconazole or broad-spectrum antifungal agents?

The fear of candidemia caused by a fluconazole-resistant species of Candida is causing many intensive care units (ICUs) to switch empiric therapy from this drug to broad-spectrum antifungal agents. We studied the epidemiology and antifungal susceptibility of Candida isolates involved in cases of candidemia among adult and pediatric patients in ICUs from 1984 to 2006. We documented 307 episodes of candidemia in 307 patients, of which only eight episodes (2.6%) were caused by a fluconazole-resistant isolate. At least three of the eight patients from whom fluconazole-resistant strains were recovered had recently received fluconazole. Overall, only 1.6% of the episodes of candidemia caused by fluconazole-resistant strains (five patients) occurred in individuals with no evidence of previous fluconazole administration. In conclusion, the use of broad-spectrum antifungal agents is not justified in ICUs with a low proportion of candidemia episodes caused by fluconazole-resistant strains of Candida.

Bacteraemia and candidaemia: a considerable and underestimated complication of severe rotavirus gastroenteritis.

Despite the high incidence of rotavirus gastroenteritis, secondary bacteraemia later in the course of the disease has rarely been reported. To date, the exact incidence of this complication has not been determined. A prospective study was conducted between January 2007 and December 2008 to determine the incidence of bacteraemia by organisms of the normal intestinal flora during severe rotavirus gastroenteritis. Rotavirus gastroenteritis was diagnosed by antigen detection in stool. A previously described 20-point numerical score system was used to determine the severity of disease. There were 289 cases (30%) of rotavirus gastroenteritis during the study period, 106 (36.7%) of which were accepted to be severe rotavirus gastroenteritis and hospitalized. On admission stool and blood cultures tested negative. In cases of persistent or recurrent fever, additional blood cultures were obtained. Among cases with severe rotavirus gastroenteritis, 4 (3.8%) had positive blood cultures (Klebsiella pneumoniae in 1 patient, Escherichia coli in 1 patient, Pseudomonas aeruginosa and Candida albicans in 1 patient, and Candida albicans in 1 patient). All patients were successfully treated with fluid replacement and antimicrobial therapy. Bacteraemia and candidaemia appear to be a considerable and underestimated complication of severe rotavirus gastroenteritis.

Diagnostic yield of blood cultures from antibiotic-naïve and antibiotically treated patients with haematological malignancies and high-risk neutropenia.

In patients with prolonged episodes of neutropenia, infections are associated with significant mortality. The exact diagnostic yield of blood cultures in this high-risk population is still unclear. To assess the yield of blood cultures, the spectrum of pathogenic organisms and the influence of blood culture results on the therapeutic management, we retrospectively evaluated the results from 2520 blood cultures obtained from 126 consecutive patients with high-risk neutropenia. Bacterial pathogens were detected in 219 blood culture samples (8.7%) of which 172 were Gram-positive and 47 were Gram-negative bacteria. Fungal pathogens were found in 13 blood cultures. A higher rate of Gram-positive pathogens and of fungi was found in patients with central venous catheters. Pathogens were detected in 14.3% of blood cultures obtained before the institution of antibiotic treatment and in 7% of blood cultures obtained under antibiotic treatment. Treatment was modified in 116/232 (50%) of positive blood culture findings. In patients with high-risk neutropenia, blood cultures are a valid diagnostic tool, both in antibiotic-naïve patients and in patients receiving antibiotic treatment, and provide important information for clinical decision making. The epidemiological data obtained are helpful for selecting empirical antibiotic treatment regimens.

[Usefulness of biological markers in the diagnosis of invasive candidiasis]. / Utilidad de los marcadores biológicos en el diagnóstico de la candidiasis invasora.

BACKGROUND: The laboratory diagnosis of invasive candidiasis is based on the demonstration of tissue invasion by Candida, the culture of the fungus in specimens from sterile body sites and the detection of a number of biomarkers including some antibodies, mannan, beta-1,3-D-glucan and Candida DNA. AIMS: Description and evaluation of results obtained in published studies on the usefulness of biomarkers in the diagnosis of invasive candidiasis. METHODS: A search was performed in the PubMed/Medline database from the National Library of Medicine since January 2000 on the usefulness of biomarkers in the diagnosis of invasive candidiasis. Key words used included candidiasis, Candida, diagnosis, biomarkers, antigen, antibodies, DNA, mannan, and beta-1,3-D-glucan. RESULTS: Forty one papers dealing with the use of biomarkers in the diagnosis of invasive candidiasis were selected and evaluated, paying special attention to the sensitivity and specificity obtained with the tests used. CONCLUSIONS: Important advances are being reached in the use of biomarkers for the diagnosis of invasive candidiasis, and some of them are being used to start a preemptive therapy strategy.

Microbiological diagnosis of bacteraemia and fungaemia: Blood cultures and molecular methods. / Diagnóstico microbiológico de la bacteriemia y la fungemia: hemocultivos y métodos moleculares.

OBJETIVE: In this review we try to update the new procedures applicable in the microbiological diagnosis of bacteriemia and fungemias. METHOD: Review of scientific literature. RESULTS AND CONCLUSIONS: After defining the process and indicating its fundamental principles, the main biomarkers used in clinical practice are reviewed. Subsequently, the particularities of the pre-analytical phase (collection and transport of samples) are highlighted and the steps to follow for the microbiological identification by classical methods are detailed, based on the culture of the blood samples. In the following section, we review the diagnostic methods not culture based, including those that detect the presence of the genome of the microorganism and those based on the study of proteome by mass spectrometry. The last section describes the procedures more frecuently used for the study of antibiotic susceptibility, both by phenotypic and genotypic methods.

Effects of bacteria and yeast on WBC counting in three automated hematology counters.

Bacteria or yeast may be observed on peripheral blood smears and may lead to spuriously elevated platelet counts. They have been reported to disturb the white blood cell (WBC) differential count if they clumped together, and a large number of such microorganisms have been shown to increase WBC counts. The purpose of this study was to evaluate the spurious rise in WBC counts according to species of microorganisms and automated hematology analyzers. The species we selected were Staphylococcus aureus, Escherichia coli, Candida albicans, C. tropicalis, C. krusei, C. dubliniensis, C. glabrata, and C. parapsilosis. We investigated the effects of bacteria and yeast on peripheral blood samples by the ADVIA 120/2120 Hematology System, Sysmex XE-2100 (TOA Medical Electronics, Kobe, Japan) and Coulter LH 750 (Beckman Coulter, Miami, FL, USA). C. albicans, C. tropicalis, C. krusei, and C. dubliniensis had an overt effect on the WBC count at concentrations of up to 1-5 x 10(7) colony-forming units (CFU)/mL in three automated cell counters, and C. glabrata and C. parapsilosis, when present at concentrations of 1-5 x 10(8) CFU/mL, caused a significant increase in the WBC count obtained by the Sysmex XE-2100 but not by the ADVIA 120/2120 system and Coulter LH 750 (p < 0.05). In conclusion, yeast may influence the results of peripheral blood smears only when the yeast concentration is unusually high. The results differed among analyzers and among species of yeast. Hematologists should be aware that samples containing bacteria and yeast may give erroneously high WBC counts and differential leukocyte counts and should review the peripheral blood smear by microscopy.

Early detection of breakthrough trichosporonosis by serum PCR in a cord blood transplant recipient being prophylactically treated with voriconazole.

An 18-year-old man with myelodysplastic syndrome after stem-cell transplantation developed breakthrough trichosporonosis while being administered voriconazole, a broad-spectrum triazole. Importantly, Trichosporon was detected soon after infection by a screening serum polymerase chain reaction test, but not by blood culture. This case illustrates that the serum polymerase chain reaction assay might be effective for early detection of fungemia in immunocompromised patients, including recipients of stem-cell transplants undergoing prophylactic antifungal therapy using voriconazole, which cannot be assumed to always provide complete protection against Trichosporon infection.

[Echinocandins in invasive candidiasis]. / Echinocandine bei invasiven Candida-Infektionen.

Invasive fungal infections on the intensive care unit are predominantly caused by Candida spp., most frequently manifesting as candidemia. In spite of increasing treatment options during the last 2 decades, mortality of invasive candidiasis remains high with 20-50%. With the echinocandins, a new class of antifungal drugs with activity against clinically relevant Aspergillus and Candida spp. has become available since the beginning of the new millennium. The echinocandins have shown convincing efficacy in numerous multicenter, mostly double-blinded phase III clinical trials. These trials compared current standard treatment regimens with the echinocandins anidulafungin, caspofungin, and micafungin. All trials observed noninferiority of the new drugs against the standard treatment; in the case of anidulafungin, superiority against fluconazole was demonstrated. Especially in trials utilizing amphotericin B as comparator, significantly less treatment-related adverse events were observed when using an echinocandin. Echinocandins have a low drug-drug interaction profile and are only marginally affected by liver function. Especially in ICU (intensive care unit) patients frequently showing single- or multiorgan failure and receiving a multitude of drugs with complex interactions, echinocandins have become the treatment of first choice for invasive candidiasis.