Nosocomial Bloodstream Infections Research Articles

Attributable mortality of candidemia after introduction of echinocandins.

Candidemia is among the most frequent nosocomial bloodstream infections. Landmark case-control studies on amphotericin B and fluconazole estimated attributable mortality rates of 38% and 49%, respectively. After introduction of echinocandins, these may have decreased. In a case-control design, 100 consecutive, hospitalised patients with candidemia were enrolled at the University Hospital of Cologne, Germany between 2014 and 2017. Controls were patients without candidemia matched for age, sex, year and duration of hospitalisation, main admission diagnosis and Patient Clinical Complexity Level (PCCL). Main data captured were risk factors for candidemia, attributable mortality rates and diagnostic and therapeutic adherence according to the EQUAL Candida score. Overall mortality rates for cases and controls were 43% and 17% (P<.001), respectively; day 30 mortality rates were 38% and 11% (P=.03), accounting for an attributable mortality of 26% and 27%. Guideline adherence was higher in surviving vs non-surviving patients: while survivors reached a median of 17 (IQR: 16-19) points, non-surviving cases reached a median 16 (IQR: 14-18) points out of 22 maximum achievable points (P=.028). Risk factors for candidemia were more frequent in cases compared to control patients, especially chronic pulmonary disease (25% vs 16%; P=n.s.), chronic liver disease (21% vs 6%; P=.002), stay on intensive care unit (70% vs 64%; P=n.s.), respiratory failure (56% vs 50%; P=n.s.) and central venous catheter (97% vs 35%; P<.001). Attributable mortality of nosocomial candidemia is still substantial but has decreased compared to previous studies with similar design.

Functional Characterization of a Novel Oxidative Stress Protection Protein in the Pathogenic Yeast Candida glabrata.

Candida species are important pathogens of humans and the fourth most commonly isolated pathogen from nosocomial blood stream infections. Although Candida albicans is the principle causative agent of invasive candidosis, the incidence of Candida glabrata infections has rapidly grown. The reason for this increase is not fully understood, but it is clear that the species has a higher innate tolerance to commonly administered azole antifungals, in addition to being highly tolerant to stresses especially oxidative stress. Taking the approach that using the model organism, Saccharomyces cerevisiae, with its intrinsic sensitivity to oxidative stress, we hypothesized that by expressing mediators of stress resistance from C. glabrata in S. cerevisiae, it would result in induced resistance. To test this we transformed, en-masse, the C. glabrata ORFeome library into S. cerevisiae. This resulted in 1,500 stress resistant colonies and the recovered plasmids of 118 ORFs. Sequencing of these plasmids revealed a total of 16 different C. glabrata ORFs. The recovery of genes encoding known stress protectant proteins such as GPD1, GPD2 and TRX3 was predicted and validated the integrity of the screen. Through this screen we identified a C. glabrata unique ORF that confers oxidative stress resistance. We set to characterise this gene herein, examining expression in oxidative stress sensitive strains, comet assays to measure DNA damage and synthetic genetic array analysis to identify genetic interaction maps in the presence and absence of oxidative stress.

Ba813 harboring Bacillus cereus, genetically closely related to Bacillus anthracis, causing nosocomial bloodstream infection: Bacterial virulence factors and clinical outcome.

Bacillus cereus commonly causes catheter-related bloodstream infections (BSIs) in hospital settings, and occasionally occurs fatal central nervous system (CNS) complications. B. cereus harboring Ba813, a specific chromosomal marker of Bacillus anthracis, has been found in patients with severe infection and nosocomial BSI. However, the bacteriological profile and clinical feature of Ba813 (+) B. cereus are unclear. Fifty-three patients with B. cereus BSI were examined. Isolates were evaluated for Ba813, B. anthracis-related and food poisoning-related virulence, multilocus sequencing typing, and biofilm formation. Patients’ clinical records were reviewed retrospectively. The 53 isolates were comprised of 29 different sequence types in two distinct clades. Seventeen of the 53 (32%) B. cereus isolates including five sequence types possessed Ba813 and were classified into Clade-1/Cereus-III lineage which is most closely related to Anthracis lineage. No B. cereus possessed B. anthracis-related virulence genes. Ba813 (+) strains showed a lower prevalence of enterotoxin genes than Clade-2 strains (n = 4), but no difference from Clade-1. Ba813 (+) strains showed significantly lower biofilm formation than Clade-1/non-Cereus-III (n = 22) and Clade-2 strains, respectively. Compared to Clade-1/non-Cereus-III and Clade-2 B. cereus, Ba813 (+) strains were isolated more frequently from elderly patients, patients with indwelling central venous catheter rather than peripheral venous catheter, and patients who remained in the hospital for longer before BSI onset. No significant differences in disease severity or mortality were observed. Though two of the ten Ba813 (-) strains in Clade-1/Cereus III were isolated from the patients with CNS complication, no significant difference was observed in the bacterial profile and clinical characteristics among Clade-1/Cereus III strains. In conclusion, our report suggested that Ba813-harboring B. cereus strains, genetically closely related to B. anthracis, were abundant among B. cereus strains in the hospital setting, and might cause catheter-related nosocomial BSI. However, it did not affect the clinical outcomes.

Summer, sun and sepsis-The influence of outside temperature on nosocomial bloodstream infections: A cohort study and review of the literature.

BackgroundThe incidence of many infections is seasonal e.g. surgical site infections, urinary tract infection and bloodstream infections. We questioned whether there is seasonal variation even in climate-controlled hospitalized patients, and analyzed the influence of climate parameters on nosocomial bloodstream infections.Methods and findingsThe retrospective cohort study is based on two databases: The German national surveillance system for nosocomial infections in intensive care units (ICU-KISS) from 2001 to 2015 and aggregated monthly climate data. Primary bloodstream infection (PBSI) is defined as a positive blood culture with one (or more) pathogen(s) which are not related to an infection on another site and which were not present at admission. Monthly infection data were matched with postal code, calendar month and corresponding monthly climate and weather data. All analyses were exploratory in nature. 1,196 ICUs reported data on PBSI to KISS. The ICUs were located in 779 hospitals and in 728 different postal codes in Germany. The majority of the 19,194 PBSI were caused by gram-positive bacteria. In total, the incidence density of BSI was 17% (IRR 1.168, 95%CI 1.076–1.268) higher in months with high temperatures (≥20°C) compared to months with low temperatures (<5°C). The effect was most prominent for gram-negatives; more than one third (38%) higher followed by gram-positives with 13%. Fungi reached their highest IRR at moderately warm temperatures between 15–20°C. At such temperatures fungi showed an increase of 33% compared to temperatures below 5°C. PBSI spiked in summer with a peak in July and August. PBSI differed by pathogen: The majority of bacteria increased with rising temperatures. Enterococci showed no seasonality. S. pneumoniae reached a peak in winter time. The association of the occurrence of PBSI and temperatures ≥20°C was stronger when the mean monthly temperature in the month prior to the occurrence of BSI was considered instead of the temperature in the month of the occurrence of BSI. High average temperatures ≥20°C increased the risk of the development of a PBSI by 16% compared with low temperatures <5°C.ConclusionsMost nosocomial infections are endogenous in nature; the microbiome plays a crucial role in host health. If gut and skin microbiome varies with season, environmental parameters will contribute to the observed incidence patterns. Similarly, the impact of global warming on both local weather patterns and extreme weather events may influence the acquisition of pathogens. A better understanding of the etiology of these infections is needed to provide guidance for future infection control strategies.

Candidemia: characteristics in elderly patients

Candidemia is a nosocomial bloodstream infection and an important cause of comorbidity and mortality. Elderly patients present the highest rates of candidemia but data about this population is scarce. To describe characteristics of candidemia in elderly patients, to identify risk factors associated with mortality and to evaluate the usefulness of a predictive score. A retrospective observational study of candidemia in elderly patients from a tertiary care hospital was carried out. We analyzed all Candida bloodstream infections during an eight-year period in patients older than 60 years. Fifty-nine episodes were included. Diabetes was the most frequent comorbidity. Most candidemia were catheter related infections (45%). Only 17% of patients had a Candida score > 2.5. Overall mortality at 48 hours was 20%, and at 15 days was 49%. Mortality-related factors were shock, assisted mechanical ventilation, thrombocytopenia, renal failure and leukocytosis (p range < 0.0001-0.006). On multivariate analysis septic shock was independently associated with mortality (HR 4.02 [CI 95% 1.18-13.72] p = 0.026). Nearly half of patients with candidemia died during the first fifteen days. Shock, assisted mechanical ventilation, thrombocytopenia, renal failure, and leukocytosis were factors associated with mortality. The predictive score was not useful in this population.

Prevalence and Clonal Distribution of Azole-Resistant Candida parapsilosis Isolates Causing Bloodstream Infections in a Large Italian Hospital.

The most prevalent cause of nosocomial bloodstream infection (BSI) among non-C. albicans Candida species, Candida parapsilosis, may not only be resistant to azole antifungal agents but also disseminate to vulnerable patients. In this survey of BSIs occurring at a large Italian hospital between May 2014 and May 2019, C. parapsilosis accounted for 28.5% (241/844) of all Candida isolates causing BSI episodes. The majority of episodes (151/844) occurred in medical wards. Across the 5 yearly periods, the rates of azole non-susceptibility were 11.8% (4/34), 17.8% (8/45), 28.6% (12/42), 32.8% (19/58), and 17.7% (11/62), respectively, using the Sensititre YeastOne® method. Among azole non-susceptible isolates (54/241; 22.4%), 49 were available for further investigation. Using the CLSI reference method, all 49 isolates were resistant to fluconazole and, except one (susceptible dose-dependent), to voriconazole. Forty (81.6%) isolates harbored the Erg11p Y132F substitution and nine (18.4%) isolates the Y132F in combination with the Erg11p R398I substitution. According to their genotypes, as defined using a microsatellite analysis based on six short tandem repeat markers, 87.7% of isolates (43/49) grouped in two major clusters (II and III), whereas 4.1% of isolates (2/49) belonged to a separate cluster (I). Interestingly, all the isolates from cluster II harbored the Y132F substitution, and those from cluster III harbored both Y132F and R398I substitutions. Of 56 non-Italian isolates included as controls, two Indian isolates with the Y132F substitution had a genotype clearly differing from that of the isolates from clusters II and I. In conclusion, these findings show the dominance of clonal Y132F isolates in our hospital and suggest detection of the Y132F substitution as helpful tool to prevent transmission among hospitalized patients at risk of BSI.

Antimicrobial Resistance Pattern of Nosocomial Infections at a Referral Teaching Hospital

Background: The choice of appropriate antibiotics to treat nosocomial infections requires knowledge of antibiotic resistance pattern in the hospitals. The aim of this study was to determine antimicrobial resistance patterns of common pathogens of nosocomial infections (pneumonia, UTI, bloodstream infection, wound infection) in a referral teaching hospital. Methods: This cross-sectional study was conducted over a 6-month period. The pathogens isolated from biological samples of hospitalized patients with nosocomial pneumonia, UTI, bloodstream infection, or wound infection underwent antibiotic susceptibility testing by Kirby-Bauer method (disk diffusion test). Results: Over the study period, 442 cases of infection were recorded. Pneumonia (n = 204, 46.2%) and UTI (n = 118, 26.7%) showed the most frequency followed by BSI (n = 71, 16.1%) and wound infection (n = 49, 11%). Acinetobacter baumannii was the most common pathogen of nosocomial pneumonia infection that showed the most susceptibility to colistin (100%). Escherichia coli, the most common pathogen of urinary tract infections, showed the highest sensitivity to colistin (100%). Staphylococcus epidermidis was the most common bloodstream infection pathogen that showed the most sensitivity to vancomycin (100%). Enterococcus spp., the most common pathogens of wound infection, had the most susceptibility to linezolid (100%). Conclusion: Nosocomial infections in our hospital have high rate of resistance to antibiotics representing the importance of improvement in antibiotic use and infection control. J Pharm Care 2020; 8(1): 26-34.

Do antimicrobial-impregnated central venous catheters prevent nosocomial bloodstream infection in neonates?

Do antimicrobial-impregnated central venous catheters prevent nosocomial bloodstream infection in neonates?

Characteristics and outcome of nosocomial bloodstream infection in patients with acute-on-chronic liver failure.

Patients with acute-on-chronic liver failure (ACLF) have a high risk of developing infections while hospitalized. Nosocomial bloodstream infection (BSI) is not uncommon, particular in patients who receive invasive operation, which may have negative impact on prognosis. In this study, we aim to investigate the characteristics and short-term outcome of nosocomial BSI in patients with ACLF. Sixty-three patients with ACLF and nosocomial BSI from January 2014 to December 2015 were retrospectively studied. Clinical characteristics and distribution of bacteria at the time of BSI onset and short-term mortality were collected. The most common etiology of ACLF was hepatitis B virus infection. Eighty-one percent of ACLF patients had other types of infections at BSI onset. Gram-negative bacteria (77.8%) were the main pathogens, among which Escherichia coli was responsible for 46.9%. Staphylococcus epidermidis was the main Gram-positive bacteria. The most prevalent multidrug resistance (MDR) bacteria was extended-spectrum β-lactamase (ESBL)-producing E. coli. The overall 28-day mortality rate was 42.9%. Multivariate analysis found that model for end-stage liver disease (MELD) score and number of organ failures were predictors of 28-day mortality. The area under the receiver operating characteristic of the numbers of organ failures to predict 28-day mortality was higher than MELD score (0.833 vs. 0.784, 0.4099), but without significant difference. Gram-negative bacteria were the most prevalent pathogens and ESBL-producing bacteria were responsible for most of the MDR bacteria in patients with ACLF and nosocomial BSI. Higher MELD score and multiorgan failure were associated with worse outcomes.

Multi-drug resistance of blood stream, urinary tract and surgical site nosocomial infections of Acinetobacter baumannii and Pseudomonas aeruginosa among patients hospitalized at Felegehiwot referral hospital, Northwest Ethiopia: a cross-sectional study

BackgroundMulti-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa are major causes of nosocomial infections globally. They are the current World Health Organization critical priority pathogens for resistance, Antimicrobial resistance (AMR) surveillance and discovery of new antibiotics. However, there is paucity of data on nosocomial infections (NIs) caused by such superbugs in Ethiopia. Therefore, this study determined the magnitude and profile of nosocomial MDR A. baumannii and P. aeruginosa infections among patients hospitalized at Felegehiwot referral hospital, Northwest Ethiopia.MethodsA cross-sectional study was conducted at Felegehiwot referral hospital from April 1 to July 31, 2018. A total of 238 patients with blood stream, urinary tract and surgical site NIs were enrolled conveniently. Either blood, urine and wound swab specimens were collected and processed using standard bacteriological procedures. A. baumannii and P. aeruginosa isolates were identified using standard bacteriological techniques and confirmed by automated Vitek2 Compact. Antimicrobial susceptibility testing on isolates was performed using the disk diffusion technique. The results were interpreted as per the standard zone sizes of Clinical and Laboratory Standards Institute.Chi-square test was done to determine associations among variables. P value < 0.05 was considered statistical significant.ResultsThe median age of participants was 29 years. Overall,20(8.4%) of patients had nosocomial MDR A. baumannii and P. aeruginosa infections. The proportion of nosocomial MDR blood stream, urinary tract and surgical site infections were 13(8.9%), 5(8.3%) and 2 (6.3%), respectively. Patients with NI had lower mean age (24.9 years) (P = 0.035). All isolates of NIs were from patients with intravenous catheterization. The frequency of NI was 9(3.8%) for MDR A. baumannii and 11(4.6%) for MDR P.aeruginosa. A. baumannii and P. aeruginosa isolates were 100% MDR. All isolates of A. baumannii and P. aeruginosa were 100% resistant to ampicillin and piperacillin.A. baumannii isolates were 33.3 and 44.5% resistance against meropenem and ciprofloxacin, respectively while P.aeruginosa isolates revealed 36.4 and 45.5% resistance against ciprofloxacin and meropenem, respectively.ConclusionsHealth care associated infections of MDR A.baumannii and P. aeruginosa are critical problems in the study area. Therefore, urgent focused interventions required to contain the spreading of MDR NIs. Treatment of NIs for patients on health care should be guided by antimicrobial susceptibility testing.

Incidence, risk factors and healthcare costs of central line-associated nosocomial bloodstream infections in hematologic and oncologic patients

Non-implanted central vascular catheters (CVC) are frequently required for therapy in hospitalized patients with hematological malignancies or solid tumors. However, CVCs may represent a source for bloodstream infections (central line-associated bloodstream infections, CLABSI) and, thus, may increase morbidity and mortality of these patients. A retrospective cohort study over 3 years was performed. Risk factors were determined and evaluated by a multivariable logistic regression analysis. Healthcare costs of CLABSI were analyzed in a matched case-control study. In total 610 patients got included with a CLABSI incidence of 10.6 cases per 1,000 CVC days. The use of more than one CVC per case, CVC insertion for conditioning for stem cell transplantation, acute myeloid leukemia, leukocytopenia (≤ 1000/μL), carbapenem therapy and pulmonary diseases were independent risk factors for CLABSI. Hospital costs directly attributed to the onset of CLABSI were 8,810 € per case. CLABSI had a significant impact on the overall healthcare costs. Knowledge about risk factors and infection control measures for CLABSI prevention is crucial for best clinical practice.

In vitro characterization, ADME analysis, and histological and toxicological evaluation of BM1, a macrocyclic amidinourea active against azole-resistant Candida strains

Candida species are one of the most common causes of nosocomial bloodstream infections among the opportunistic fungi. Extensive use of antifungal agents, most of which were launched on the market more than 20 years ago, led to the selection of drug-resistant or even multidrug-resistant fungi. We recently described a novel class of antifungal macrocyclic compounds with an amidinourea moiety that is highly active against azole-resistant Candida strains. A compound from this family, BM1, was investigated in terms of in vitro activity against various Candida species, including C. auris isolates, interaction with the ABC transporter, CDR6, and in vivo distribution and safety. In vitro assays (CYP inhibition, microsomal stability, permeability, spot assays) were used to collect chemical and biological data; animal models (rat) paired with LC-MS analysis were utilised to evaluate in vivo toxicology, pharmacokinetics, and distribution. The current research shows BM1 has a low in vivo toxicity profile, affinity for the renal system in rats, and good absorption, distribution, metabolism, and excretion (ADME). BM1 also has potent activity against azole-resistant fungal strains, including C. auris isolates and CDR6-overexpressing strains. The results confirmed low minimum inhibitory concentrations (MICs) against several Candida species, including preliminary data vs. C. auris. BM1 has good ADME and biochemical characteristics, is suitable and safe for daily administration and is particularly indicated for renal infections. These data indicate BM1 and its derivatives form a novel, promising antifungal class.

Persistent Systemic Microbial Translocation, Inflammation, and Intestinal Damage During Clostridioides difficile Infection.

Background Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI.MethodsPatients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively.ResultsOverall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P < .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values.ConclusionsCDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated.

Etiology, drug sensitivity profiles and clinical outcome of bloodstream infections: A retrospective study of 784 pediatric patients with hematological and neoplastic diseases

Bloodstream infections (BSI) represent one of the most serious complications in patients in the hematology-oncology unit. In this study, the prevalence, distribution, drug sensitivity profiles, and clinical outcome of BSI were analyzed in pediatric patients with hematological malignancies. Patients admitted to the pediatric hematology-oncology unit at Shenzhen Children's Hospital (Shenzen, China) between January 2016 and December 2017 were enrolled. Their medical records, including gender, age, primary diseases, and microbiology results of all clinical specimens, were reviewed. The incidence of BSI, microbiology characteristics,and effectiveness of antimicrobial therapy were analyzed. A total of 125 BSI cases in 108 patients (mean age, 5.5 years) were recorded, of which 69 (55.2%) were nosocomial BSI cases. The overall rate of BSI was 18.8% in the hematology-oncology unit, of which 75 (75.2%) episodes were neutropenic patients. Patients with nosocomial BSIs and the neutropenic group were older (p#.02, p#.03). HSCTs and AML were more often observed in nosocomial BSIs, while solid tumors were more found in nonnosocomial and non-neutropenic BSIs. BSIs were dominated by Gram-negative pathogens (49.6%) in the hematology-oncology unit compared with Gram-positive pathogens (39.2%). The most common pathogens were coagulase-negative Staphylococcus (24.2%) followed by Klebsiella pneumonia (15.2%), Escherichia coli (12.5%), viridans streptococci (8.2%), and Candida species (7.8%). The antibiotic therapy success rate in patients was 93.5%. Based on our center's experience, Gram-negative pathogens were commonly observed among pediatric hematology-oncology patients with BSI. Coagulase-negative Staphylococcus and K. pneumoniae predominated and antibiotic therapy was effective in these patients.

Pathogen-focused Clinical Development to Address Unmet Medical Need: Cefiderocol Targeting Carbapenem Resistance.

Historically, the regulatory requirements of the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for developing new antibiotics have not addressed pathogen-focused indications for drug approval. The design of the necessary randomized controlled trials traditionally involves the enrollment of patients with site-specific infections caused by susceptible as well as resistant pathogens. Cefiderocol has undergone a streamlined clinical development program to address serious carbapenem-resistant infections. The regulatory approach, and the pivotal clinical trials, differed between the FDA and EMA. In the United States, the APEKS-cUTI (Acinetobacter, Pseudomonas, Escherichia coli, Klebsiella, Stenotrophomonas–complicated urinary tract infection) study was conducted to provide the basis for FDA approval of a site-specific cUTI indication. The EMA, however, preferred the CREDIBLE-CR (A MultiCenter, RandomizED, Open-label ClInical Study of S-649266 or Best AvailabLE Therapy for the Treatment of Severe Infections Caused by Carbapenem-Resistant Gram-negative Pathogens) study, in which patients with nosocomial pneumonia, bloodstream infections, or cUTIs were enrolled if they had a carbapenem-resistant pathogen. The resulting European label will be pathogen focused rather than infection site specific (ie, treatment of gram-negative infection in patients with limited treatment options). The implications and limitations of these different regulatory processes are discussed.

Functional characterisation of novel oxidative stress protection proteins in the pathogenic yeast Candida glabrata

Candida species are important pathogens of humans and are the fourth most commonly isolated pathogen from nosocomial blood stream infections. Although Candida albicans is the principle causative agent of invasive candidiasis, the incidence of C. glabrata infection has grown rapidly. The reason for this increase is not fully understood but it is clear that the species has a higher innate tolerance to commonly administered azole antifungals, in addition to being highly tolerance to combinatorial stresses. Using S. cerevisiae, as a model due to its intrinsic sensitivity to combinatorial stress and hypothesizing that the expression of mediators of Candida glabrata combinatorial stress resistance (CSR) in S. cerevisiae would lead to induced resistance. To test this we transformed, en-masse, the Candida glabrata ORFeome into S. cerevisiae. This resulted in 1,500 CSR colonies and recovered plasmids of 118 ORFS. Sanger sequencing of these plasmids revealed a total of 29 different C. glabrata ORFS. The recovery of genes encoding known stress protectant proteins e.g. GPD1, GPD2 and TRX3 was predicted and validated the integrity of the screen. Through this screen we identified four C. glabrata unique ORFs that confer CSR and we are in the process of characterising.

254. National Trends in the Japanese Distribution of Major Candida Species Causing Candidemia During 2003–2017: A Report by the Epidemiological Investigation Committee for Human Mycoses in Japan

BackgroundCandida species are a common cause of nosocomial bloodstream infections, and candidemia is associated with high mortality rates among adults and neonates. There is limited epidemiological data regarding candidemia in Japan. Therefore, the Epidemiological Investigation Committee for Human Mycoses in Japan performed a retrospective epidemiological survey of candidemia and causative Candida species.MethodsBlood culture results from 2003 to 2017 were retrospectively evaluated. The data included the center-specific numbers of annual blood cultures, bacterial isolates that included fungi, numbers of fungi, and Candida species. Data were collected from 10 Japanese university hospitals located on all over Japan.ResultsA total of 433,961 blood cultures were included. The prevalence of fungi in all cultures and in positive cultures were 0.53 ± 0.07% and 3.78 ± 0.47%, respectively. Among the results that were positive for Candida species (N = 2,270), C. albicans was the most common species (39.2%) and was followed by C. parapsilosis (22.8%), C. glabrata (15.6%), C. tropicalis (9.7%), C. krusei (2.2%), and others. And the temporal changes in the five major Candida species’ distributions were analyzed. The frequency of C. albicans was 48% in 2003 and 2004, approximately 40% during 2005–2011, approximately 30% in 2012 and 2014, and 40% in 2015–2017. The next most common species were C. parapsilosis and C. glabrata. The frequency of C. parapsilosis was approximately 16% in 2003, approximately 28% during 2005–2009 and 21.7% during 2010–2017. There was a significant difference in the C. parapsilosis rates for the first and second halves of the study period (24.8% vs. 21.7%, P = 0.03). The frequency of C. glabrata was <10% during 2004–2006, and approximately 17% after 2010. C. glabrata was significantly more common in the second half of the study period, compared with in the first half (12.0% vs. 17.3%, P = 0.004). The frequency of C. tropicalis remains stable, and C. krusei was significantly less common in the second half of the study period, compared with in the first half (4.3% vs. 1.6%, P <0.001).ConclusionThe frequency of C. albicans has varied in each year in Japan, while that of C. glabrata has increased. Additional surveys are needed to continuously monitor the trends in the distribution of candidemia in Japan.Disclosures All authors: No reported disclosures.

2885. A Host Transcriptional Signature for Accurate Diagnosis of Candidemia in the Hospital Setting

BackgroundCandidemia is one of the most common nosocomial bloodstream infections in the United States and causes significant morbidity and mortality in hospitalized patients. Improved rapid diagnostics capable of differentiating candidemia from other causes of febrile illness in the hospitalized patient are of paramount importance. Pathogen class-specific biomarker-based diagnostics such as those focusing on host gene expression patterns in circulating leukocytes may offer a promising alternative.MethodsRNA sequencing was performed on peripheral blood samples from 27 hospitalized patients with blood culture positive invasive candidiasis. Samples from healthy controls as well as at-risk subjects with acute febrile illness and similar clinical backgrounds but other infectious or noninfectious etiologies were used as comparator phenotypes (35 subjects with culture-proven bacterial infection, 49 with confirmed viral infection, and 17 with acute noninfectious illness). Bayesian techniques were utilized to develop infection-specific classifiers and leave one out cross-validation was used to estimate the predictive probability of each pathogen class.ResultsCandidemia triggers a unique, robust and conserved transcriptomic response in human hosts with 1,170 genes differentially upregulated compared with healthy controls. Based on this strength of signal, we developed a transcriptomic classifier that was capable of identifying candidemia, viral, or bacterial infection with a high degree of accuracy (auROC for Candida 0.93, Bacterial 0.98, Viral 0.99). The Candida component of this classifier (29-genes) was able to diagnose candidemia with a sensitivity of 88% and specificity of 100%.ConclusionThe host transcriptomic response during candidemia in hospitalized adults is highly conserved and unique from the genomic responses to acute viral and bacterial infection. This approach shows promise for the development of host response-based classifiers capable of differentiating multiple types of clinical illnesses at once in at-risk febrile patients.DisclosuresEphraim L. Tsalik, MD MHS PhD, Immunexpress: Consultant; Predigen, Inc.: Officer or Board Member, Research Grant.

622. The Accessory Genome in Enterococcal Bacteremia: Results from the Vancomycin-Resistant Enterococcal Bacteremia Outcomes Study (VENOUS)

BackgroundVancomycin-resistant enterococci (VRE) are a major cause of nosocomial bloodstream infections. Enterococci exhibit remarkable genomic plasticity and can recombine through the acquisition of genetic material via mobile genetic elements (MGEs), including resistance genes. The accessory genome plays a major role in the evolution of enterococci within the human host. Thus, dissecting the entire genome (pan-genome) is of paramount importance to characterize the population structure of enterococci causing disease.MethodsVENOUS is an ongoing prospective, observational study of adults with enterococcal bacteremia. From September 2016 to March 2018, E. faecalis (Efs) and E. faecium (Efm) were collected in 14 hospitals of a single hospital system and a major cancer center in Houston, TX, and a general hospital in Detroit, MI. Short- and long-read genomic sequencing were performed with Illumina MiSeq and Oxford Nanopore Technologies GridION X5, respectively. A proprietary bioinformatics pipeline was utilized for genome assembly and further analyses.Results156 Efs and 98 Efm isolates from single patients were analyzed. The average proportion of core genes in each genome was 64.6% (53.0–74.1) and 49.1% (45.2–51.0) for Efs and Efm, respectively. The vanA gene cluster was identified in 5.1% (8/157) of Efs and 57.1% (56/98) of Efm. The plasmid-encoded aac(6′)-Ie-aph(2″)-Ia gene conferring high-level resistance to aminoglycosides was found in 37.6% (59/157) Efs, seven of which also possessed vanA. Long-read sequencing of vanA-harboring plasmids from a subset of VRE revealed that the vanA cluster was carried in plasmids ranging from 31.7 to 132.3 kb. Although the vanA operon was fairly conserved, insertions of MGE were identified in the intergenic regions of vanS/vanH and vanX/vanY. Furthermore, a variety of MGE insertions mediated integration of the vanA operon, including IS1216 and IS256 (figure).ConclusionAccessory genes, including AMR genes, comprise a significant proportion of the enterococcal pan-genome, indicating major genetic plasticity within these organisms. Acquired resistance genes seem to have a high degree of recombination and play a substantial role in the expansion of the genomic repertoire in clinical isolates. DisclosuresSamuel L. Aitken, PharmD, Melinta Therapeutics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.

The Epidemiology and Susceptibility of Candidemia in Jerusalem, Israel.

Objectives: Invasive Candida infections pose a major public health problem worldwide and is a major cause of nosocomial bloodstream infection. Our aim was to assess dynamics in incidence, species distribution and antifungal susceptibility of candidemia episodes in Jerusalem, to better understand the epidemiology of invasive isolates and to better direct therapy.Methods: We analyzed the incidence dynamics, species distribution and susceptibility pattern of 899 candidemia episodes during 2005–2016 in Jerusalem.Results: The overall incidence of candidemia was relatively low of 0.62 per 1,000 admissions. Candida albicans was the leading pathogen (39.4%); however, there was a shift toward non-albicans species, with Candida glabrata predominating among them (40%). As expected, more than one-third of candidemias occurred in intensive care units. However, the distribution between species varied and Candida tropicalis was the leading pathogen in hematology-oncology patients. The susceptibility of isolates to antifungals remained stable throughout the years. Only a minority of Candida albicans isolates were non-susceptible to fluconazole (3.3%), however, an unexpectedly high resistance rate (37.8%) was observed in Candida parapsilosis isolates. We found an alarming rate of caspofungin resistance in Candida glabrata (33.6%) and Candida krusei (67%); this may reflect misclassification of resistance by the E-test method.Conclusions: This is the first comprehensive candidemia analysis in the Jerusalem area that should serve as a basis for decision-making regarding appropriate antifungal treatment in the hospital setting. The exceptional high resistance rate amongst Candida parapsilosis emphasizes the importance of antifungal susceptibility monitoring in medical centers serving large urban areas to better direct appropriate treatment.