Background Bloodstream Infections Research Articles

Retrospective evaluation of rapid genotypic ID and phenotypic AST systems on positive blood culture turnaround time and simulated potential impacts on bloodstream infection management

Abstract Background Bloodstream infections are linked to heightened morbidity and mortality rates. The consequences of delayed antibiotic treatment can be detrimental. Effective management of bacteraemia hinges on rapid antimicrobial susceptibility testing. Objectives This retrospective study examined the influence of the VITEK® REVEAL™ Rapid AST system on positive blood culture (PBC) management in a French tertiary hospital. Materials and methods Between November 2021 and March 2022, 79 Gram-negative monomicrobial PBC cases underwent testing with both VITEK®REVEAL™ and VITEK®2 systems. Results The study found that VITEK®REVEAL™ yielded better results than the standard of care, significantly shortening the time to result (7.0 h compared to 9.6 h) as well as the turnaround time (15 h compared to 31.1 h) when applied for all isolates. Conclusions This study implies that the use of VITEK®REVEAL™ enables swift adaptations of antibiotic treatment strategies. By considerably minimizing the turnaround time, healthcare professionals can promptly make necessary adjustments to therapeutic regimens. Notably, these findings underscore the potential of VITEK®REVEAL™ in expediting appropriate antibiotic interventions, even in less ideal conditions. Further studies in varied laboratory contexts are required to validate these encouraging outcomes.

Rapid diagnosis of bloodstream infections using a culture-free phenotypic platform

BackgroundBloodstream infections (BSIs) are a life-threatening acute medical condition and current diagnostics for BSIs suffer from long turnaround time (TAT). Here we show the validation of a rapid detection-analysis platform (RDAP) for the diagnosis of BSIs performed on clinical blood samplesMethodsThe validation was performed on a cohort of 59 clinical blood samples, including positive culture samples, which indicated confirmed bloodstream infections, and negative culture samples. The bacteria in the positive culture samples included Gram-positive and Gram-negative pathogenic species. RDAP is based on an electrochemical sandwich immunoassay with voltage-controlled signal amplification, which provides an ultra-low limit of detection (4 CFU/mL), allowing the platform to detect and identify bacteria without requiring culture and perform phenotypic antibiotic susceptibility testing (AST) with only 1–2 h of antibiotic exposure. The preliminary diagnostic performance of RDAP was compared with that of standard commercial diagnostic technologies.ResultsUsing a typical clinical microbiology laboratory diagnostic workflow that involved sample culture, agar plating, bacteria identification using matrix-assisted laser desorption ionization time-of-flight (MALDI TOF) mass spectrometry, and AST using MicroScan as a clinical diagnostic reference, RDAP showed diagnostic accuracy of 93.3% and 95.4% for detection-identification and AST, respectively. However, RDAP provided results at least 15 h faster.ConclusionsThis study shows the preliminary feasibility of using RDAP to rapidly diagnose BSIs, including AST. Limitations and potential mitigation strategies for clinical translation of the present RDAP prototype are discussed. The results of this clinical feasibility study indicate an approach to provide near real-time diagnostic information for clinicians to significantly enhance the treatment outcome of BSIs.

Bacterial etiology and antimicrobial resistance pattern of pediatric bloodstream infections: a 5-year experience in an Iranian referral hospital

BackgroundBloodstream infections (BSI) are the major cause of morbidity and mortality in children in developing countries. The purpose of the current study was to establish the antimicrobial susceptibility pattern of bacterial isolates from bloodstream infections at Children’s Medical Center Hospital (CMC), Tehran, Iran.MethodsWe retrospectively recorded all positive blood cultures and antimicrobial susceptibility of all bloodstream isolates among children admitted to CMC, during 5 years. Specimen culture, bacterial identification, and antimicrobial susceptibility testing were performed according to standard laboratory methods.ResultsFrom 3,179 pathogens isolated from the blood cultures 2,824 bacteria were cultured, with 1,312 cases being identified as Gram-positive bacteria (46%) and 1,512 cases as Gram-negative bacteria (54%). The most common Gram-negative bacteria isolated were as follows: Pseudomonas spp. (n = 266, 17.6%), Klebsiella pneumoniae (n = 242, 16%), Stenotrophomonas maltophilia (n = 204, 13.5%), Enterobacter spp. (n = 164, 10.8%), Escherichia coli (n = 159, 10.5%), Pseudomonas aeruginosa (n = 126, 8.3%), Serratia marcescens (n = 121, 8%), and Acinetobacter baumannii (n = 73, 4.8%). The most common Gram-positive bacteria isolated were coagulase-negative staphylococci (CONS) (n = 697, 53%), Streptococcus spp. (n = 237, 18%), Staphylococcus aureus (n = 202, 15%) and Enterococcus spp. (n = 167, 12.7%). 34% of bacterial strains were isolated from ICUs. The rates of methicillin resistance in S. aureus and CONS were 34% and 91%, respectively. E. coli isolates showed high resistance to cefotaxime (84%). All isolates of K. pneumoniae were susceptible to colistin and 56% were susceptible to imipenem. P. aeruginosa isolates showed high susceptibility to all antibiotics.ConclusionsOur findings emphasize the need of clinicians having access to up-to-date bacterial susceptibility data for routinely prescribed drugs. Continuous monitoring of changes in bacterial resistance will aid in the establishment of national priorities for local intervention initiatives in Iran. The increased risk of BSI caused by antibiotic-resistant organisms, emphasizes the significance of implementing appropriate antibiotic prescribing regulations and developing innovative vaccination techniques in Iran.

Impact of a multidisciplinary management team on clinical outcome in ICU patients affected by Gram-negative bloodstream infections: a pre-post quasi-experimental study

BackgroundBloodstream infections (BSIs) by Gram-negative pathogens play a major role in intensive care patients, both in terms of prevalence and severity, especially if multi-drug resistant pathogens are involved. Early appropriate antibiotic therapy is therefore a cornerstone in the management of these patients, and growing evidence shows that implementation of a multidisciplinary team may improve patients’ outcomes. Our aim was to evaluate the clinical and microbiological impact of the application of a multidisciplinary team on critically ill patients.MethodsPre-post study enrolling critically ill patients with Gram negative bloodstream infection in intensive care unit. In the pre-intervention phase (from January until December 2018) patients were managed with infectious disease consultation on demand, in the post-intervention phase (from January until December 2022) patients were managed with a daily evaluation by a multidisciplinary team composed of intensivist, infectious disease physician, clinical pharmacologist and microbiologist.ResultsOverall, 135 patients were enrolled during the study period, of them 67 (49.6%) in the pre-intervention phase and 68 (50.4%) in the post-intervention phase. Median age was 67 (58–75) years, sex male was 31.9%. Septic shock, the need for continuous renal replacement therapy and mechanical ventilation at BSI onset were similar in both groups, no difference of multidrug-resistant organisms (MDRO) prevalence was observed. In the post-phase, empirical administration of carbapenems decreased significantly (40.3% vs. 62.7%, p = 0.02) with an increase of appropriate empirical therapy (86.9% vs. 55.2%, p < 0.001) and a decrease of overall antibiotic treatment (12 vs. 16 days, p < 0.001). Despite no differences in delta SOFA and all-cause 30-day mortality, a significant decrease in microbiological failure (10.3% vs. 29.9%, p = 0.005) and a new-onset 30-day MDRO colonization (8.3% vs. 36.6%, p < 0.001) in the post-phase was reported. At multivariable analysis adjusted for main covariates, the institution of a multidisciplinary management team (MMT) was found to be protective both for new MDRO colonization [OR 0.17, 95%CI(0.05–0.67)] and microbiological failure [OR 0.37, 95%CI (0.14–0.98)].ConclusionsThe institution of a MMT allowed for an optimization of antimicrobial treatments, reflecting to a significant decrease in new MDRO colonization and microbiological failure among critically ill patients.

Use of ClearGuard HD caps in pediatric hemodialysis patients

BackgroundBloodstream infections (BSIs) are a leading cause of hospitalizations and mortality among patients receiving hemodialysis (HD) therapy, especially those with a central venous catheter (CVC) for dialysis access. The use of chlorhexidine impregnated catheter caps (ClearGuard) has been associated with a decrease in the rate of HD catheter-related BSIs (CA-BSIs) in adults; similar data have not been published for children.MethodsWe compared CA-BSI data from participating centers within the Standardizing Care to Improve Outcomes in Pediatric Endstage Kidney Disease (SCOPE) collaborative based on the center’s use of ClearGuard caps for patients with HD catheter access. Centers were characterized as ClearGuard (CG) or non-ClearGuard (NCG) centers, with CA-BSI data pre- and post-CG implementation reviewed. All positive blood cultures in participating centers were reported to the SCOPE collaborative and adjudicated by an infectious disease physician.ResultsData were available from 1786 SCOPE enrollment forms completed January 2016–January 2022. January 2020 served as the implementation date for analyzing CG versus NCG center data, with this being the time when the last CG center underwent implementation. Post January 2020, there was a greater decrease in the rate of HD CA-BSI in CG centers versus NCG centers, with a decrease from 1.18 to 0.23 and 0.41 episodes per 100 patient months for the CG and NCG centers, respectively (p = 0.002).ConclusionsRoutine use of ClearGuard caps in pediatric dialysis centers was associated with a reduction of HD CA-BSI rates in pediatric HD patients.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Aerobic Bacterial Profile of Sepsis and Its Antibiotic Susceptibility Pattern Among Patients in a Rural Tertiary Care Center.

Background Bloodstream infections (BSI) are one of the most life-threatening infections associated with high morbidity and mortality. Early diagnosis with appropriate and timely treatment improves the patient outcome. The recent surge in multidrug-resistant (MDR) strains is a matter of concern. This study aims to determine the bacterial etiology and antibiotic sensitivity pattern in BSI among different age groups. Materials and methods The microbiological data of blood culture and sensitivity between April 2019 and April 2021 were extracted from the laboratory recordsand analyzed for the bacterial profile and antibiotic sensitivity pattern. Results Out of the total 3893 blood cultures received during the study period from April 2019 to April 2021, 194 pathogens were isolated, accounting for a prevalence of 4.98%. Among 194 patients with culture-proven BSI, 54.12% (105/194) were adults, and 45.87% (89/194) were children. Of these 194 bacterial isolates, 58.76% (114/194) were gram-negative bacteria, and 41.24% (80/194) were gram-positive bacteria. With regard to the bacteria isolated,Enterococcusspecies with 23.71% (46/194) andAcinetobacterspecies with 22.16% (43/194) were the most common bacteria. The prevalence of MDR was 59.27% (115/194). Notable MDR types were methicillin-resistantStaphylococcus aureus(MRSA) in 15/22 (68.2%) and extended-spectrum beta-lactamase (ESBL) producers in 15/48 (31.25%) cases. Conclusion There is a significant geographical diversity of bacteria causing sepsis and their antibiotic susceptibility pattern. Recent trends showthat multidrug-resistant gram-negative bacilli are the predominant isolates causing BSI. Increased antibiotic resistance is leading to treatment failure and poor clinical outcomes. Hence, there is a need to monitor antibiotic resistance among patients with BSI.

Clinical value of droplet digital PCR in the diagnosis and dynamic monitoring of suspected bacterial bloodstream infections

BackgroundBloodstream infections (BSIs) represent a significant public health challenge due to their high morbidity and mortality. The clinical prognosis of BSIs is closely related to the timely and accurate diagnosis and the rational use of initial antimicrobials. We aimed to evaluate the clinical value of droplet digital PCR (ddPCR) in rapid diagnosis and dynamic monitoring of BSIs. MethodsIn this prospective study, using a ddPCR-based approach which detects 18 common pathogens, we compared the detection results and clinical concordance rates of ddPCR with blood culture (BC) in 211 patients with suspected BSIs. Further, the inflammatory profile of BSIs with Gram-negative bacteria was analyzed by Olink proteomics platform. ResultsOur data showed that the positive detection rate of ddPCR was 48.82%, which was higher than that of BC (9.48%). For BC-validated BSIs, ddPCR had a sensitivity of 90.00% and a specificity of 55.50%. When considering clinically-validated BSIs, the diagnostic value of ddPCR improved with a sensitivity of 92.59% and a specificity of 78.46%.The bacterial load detected by ddPCR was correlated with traditional clinical inflammatory indicators such as interleukin-6 (IL-6) and C-reactive protein (CRP). In addition, using Olink proteomics platform, we revealed that serological osteoprotegerin (OPG), interleukin-8 (IL-8), interleukin-18 receptor 1 (IL-18R1), C–C motif chemokine 20 (CCL20) and IL-6 were substantially elevated in Gram-negative bacteria-associated BSIs, which could serve as novel auxiliary diagnostic indicators for Gram-negative bacteria BSIs. ConclusionddPCR has the potential to provide early pathogen diagnosis, dynamic monitoring, and treatment regimen optimization for patients with BSIs.

Machine learning pipeline for blood culture outcome prediction using Sysmex XN-2000 blood sample results in Western Australia

BackgroundBloodstream infections (BSIs) are a significant burden on the global population and represent a key area of focus in the hospital environment. Blood culture (BC) testing is the standard diagnostic test utilised to confirm the presence of a BSI. However, current BC testing practices result in low positive yields and overuse of the diagnostic test. Diagnostic stewardship research regarding BC testing is increasing, and becoming more important to reduce unnecessary resource expenditure and antimicrobial use, especially as antimicrobial resistance continues to rise. This study aims to establish a machine learning (ML) pipeline for BC outcome prediction using data obtained from routinely analysed blood samples, including complete blood count (CBC), white blood cell differential (DIFF), and cell population data (CPD) produced by Sysmex XN-2000 analysers.MethodsML models were trained using retrospective data produced between 2018 and 2019, from patients at Sir Charles Gairdner hospital, Nedlands, Western Australia, and processed at Pathwest Laboratory Medicine, Nedlands. Trained ML models were evaluated using stratified 10-fold cross validation.ResultsTwo ML models, an XGBoost model using CBC/DIFF/CPD features with boruta feature selection (BFS) , and a random forest model trained using CBC/DIFF features with BFS were selected for further validation after obtaining AUC scores of 0.76 pm 0.04 and 0.75 pm 0.04 respectively using stratified 10-fold cross validation. The XGBoost model obtained an AUC score of 0.76 on a internal validation set. The random forest model obtained AUC scores of 0.82 and 0.76 on internal and external validation datasets respectively.ConclusionsWe have demonstrated the utility of using an ML pipeline combined with CBC/DIFF, and CBC/DIFF/CPD feature spaces for BC outcome prediction. This builds on the growing body of research in the area of BC outcome prediction, and provides opportunity for further research.

Performance evaluation of InfectID-BSI: A rapid quantitative PCR assay for detecting sepsis-associated organisms directly from whole blood

BackgroundBloodstream infections (BSIs) (presence of pathogenic organism in blood) that progress to sepsis (life-threatening organ dysfunction caused by the body's dysregulated response to an infection) is a major healthcare issue globally with close to 50 million cases annually and 11 million sepsis-related deaths, representing about 20% of all global deaths. A rapid diagnostic assay with accurate pathogen identification has the potential to improve antibiotic stewardship and clinical outcomes. MethodsThe InfectID-Bloodstream Infection (InfectID-BSI) test is a real-time quantitative PCR assay, which detects 26 of the most prevalent BSI-causing pathogens (bacteria and yeast) directly from blood (without need for pre-culture). InfectID-BSI identifies pathogens using highly discriminatory single nucleotide polymorphisms located in conserved regions of bacterial and fungal genomes. This report details the findings of a patient study which compared InfectID-BSI with conventional blood culture at two public hospitals in Queensland, Australia, using 375 whole blood samples (from multiple anatomical sites, eg. left arm, right arm, etc.) from 203 patients that have been clinically assessed to have signs and symptoms of suspected BSI, sepsis and septic shock. FindingsInfectID-BSI was a more sensitive method for microorganism detection compared with blood culture (BacT/ALERT, bioMerieux) for positivity rate (102 vs 54 detections), detection of fastidious organisms (Streptococcus pneumoniae and Aerococcus viridans) (25 vs 0), detection of low bioburden infections (measured as genome copies/0.35 mL of blood), time to result (<3 h including DNA extraction for InfectID-BSI vs 16 h–48 h for blood culture), and volume of blood required for testing (0.5 mL vs 40–60 mL). InfectID-BSI is an excellent ‘rule out’ test for BSI, with a negative predictive value of 99.7%. InfectID-BSI's ability to detect ‘difficult to culture’ microorganisms re-defines the four most prevalent BSI-associated pathogens as E. coli (28.4%), S. pneumoniae (17.6%), S. aureus (13.7%), and S. epidermidis (13.7%). InterpretationInfectID-BSI has the potential to alter the clinical treatment pathway for patients with BSIs that are at risk of progressing to sepsis.

Blood culture contamination in a tertiary care hospital: a retrospective three-year study

BackgroundBloodstream infections (BSI) are a leading cause of morbidity and mortality in hospitalized patients worldwide. A blood culture is the primary tool for determining whether a patient has BSI and requires antimicrobial therapy, but it can result in an inappropriate outcome if the isolated microorganisms are deemed contaminants from the skin. Despite the development of medical equipment and technology, there is still a percentage of blood culture contamination. The aims of this study were to detect the blood culture contamination (BCC) rate in a tertiary care hospital in Palestine and to identify the departments with the highest rates along with the microorganisms isolated from the contaminated blood samples.MethodBlood cultures that were taken at An-Najah National University Hospital between January 2019 and December 2021 were evaluated retrospectively. Positive blood cultures were classified as either true positives or false positives based on laboratory results and clinical pictures. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 21. A p-value of less than 0.05 was considered statistically significant for all analyses.ResultsOut of 10,930 blood cultures performed in the microbiology laboratory from 2019 to 2021, 1479 (13.6%) were identified as positive blood cultures that showed microbial growth. Of these, 453 were blood culture contaminations, representing 4.17% of total blood cultures and 30.63% of the positive blood culture samples. The highest rate of contamination was in the hemodialysis unit (26.49%), followed by the emergency department (15.89%). Staphylococcus epidermidis was the most prevalent (49.2%), followed by Staphylococcus hominis (20.8%) and Staphylococcus haemolyticus (13.2%). The highest annual contamination rate was observed in 2019 (4.78%) followed by 2020 (3.95%) and the lowest was in 2021 (3.79%). The rate of BCC was decreasing, although it did not reach statistically significant levels (P value = 0.085).ConclusionThe rate of BCC is higher than recommended. The rates of BCC are different in different wards and over time. Continuous monitoring and performance improvement projects are needed to minimize blood culture contamination and unnecessary antibiotic use.

Bloodstream Infection and Colorectal Cancer Risk in Queensland Australia, 2000-2019

BackgroundBloodstream infections may occur as a complication of colorectal cancer or be a marker for its occult presence. The objectives of this study were to quantify the overall and etiology-specific risks for incident colorectal cancer-associated bloodstream infection. MethodsPopulation-based surveillance for community-onset bloodstream infection was conducted among adults aged 20 years and older in Queensland, Australia between 2000 and 2019. Statewide databases were used to identify patients with incident colorectal cancer and collect clinical and outcome information. ResultsAfter exclusion of 1794 patients with prior colorectal cancer, a cohort of 84,754 patients was assembled, of which 1030 had colorectal cancer-associated bloodstream infection and 83,724 had no colorectal cancer. Bloodstream infection was associated with a 16-fold annualized increased risk for diagnosis of colorectal cancer (incidence rate ratio 16.1; 95% confidence interval [CI], 15.1-17.1) in the adult population. Patients who had colorectal cancer-associated bloodstream infection were more likely to be older and male, have hospital-onset and polymicrobial infections, and have fewer non-cancer-related comorbidities. The organisms associated with highest risk for colorectal cancer included Clostridium species (relative risk [RR] 6.1; 95% CI, 4.7-7.9); especially C. septicum (RR 25.0; 95% CI, 16.9-35.7), Bacteroides species (RR 4.7; 95% CI, 3.8-5.8); especially B. ovatus (RR 11.8; 95% CI, 2.4-34.5), Gemella species (RR 6.5; 95% CI, 3.0-12.5), Streptococcus bovis group (RR 4.4; 95% CI, 2.7-6.8); especially S. infantarius subsp. coli (RR 10.6; 95% CI, 2.9-27.3), Streptococcus anginosus group (RR 1.9; 95% CI, 1.3-2.7), and Enterococcus species (RR 1.4; 95% CI, 1.1-1.8). ConclusionAlthough much attention has been afforded to S. bovis group over the past decades, there are many other isolates associated with higher risk for colorectal cancer-associated bloodstream infections.

Early detection of plasma d-lactate: Toward a new highly-specific biomarker of bacteraemia?

BackgroundBloodstream infections are a leading cause of mortality. Their detection relies on blood cultures (BCs) but time to positivity is often between tens of hours and days. d-lactate is a metabolite widely produced by bacteria but very few in human. We aimed to evaluate d-lactate, d-lactate/l-lactate ratio and d-lactate/total lactate ratio in plasma as potential early biomarkers of bacteraemia on a strictly biological standpoint. MethodsA total of 228 plasma specimens were collected from patients who had confirmed bacteraemia (n = 131) and healthy outpatients (n = 97). Specific l-lactate and d-lactate analyses were performed using enzymatic assays and analytical performances of d-lactate, d-lactate/total lactate and d-lactate/l-lactate ratios for the diagnosis of bacteraemia were assessed. ResultsA preliminary in vitro study confirmed that all strains of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were able to produce d-lactate at significant levels. In patients, plasma d-lactate level was the most specific biomarker predicting a bacteraemia profile with a specificity and predictive positive value of 100% using a cut-off of 131 μmol.L−1. However, sensitivity and negative predictive value were rather low, estimated at 31% and 52%, respectively. d-lactate displayed an Area Under Receiver Operating Characteristic (AUROC) curve of 0.696 with a P value < 0.0001. There was no difference of d-lactate levels between BCs bottles positive for Gram-positive or Gram-negative bacteria (p = 0.55). Conclusiond-lactate shows promise as a specific early biomarker of bacterial metabolism. The development of rapid automated assays could raise clinical applications for infectious diseases diagnosis including early bacteraemia prediction.

Two cases of bloodstream infections associated with opportunistic bacterial species (Enterococcus hirae and Enterobacter xiangfangensis) in companion animals

BackgroundBloodstream infections are a matter of concern in small animal veterinary practice. Few reports are avaiable, especially regarding the role of opportunistic bacteria in becoming infectious. This report aims to add to the current veterinary literature on two opportunistic bacterial species (Enterococcus hirae and Enterobacter xiangfangensis) associated with bloodstream infections in small animals admitted to the Bologna University Veterinary Hospital.Case presentationIn the first case, a 15-year-old, immunocompromised, cardiopathic dog was admitted to the hospital for anorexia and diarrhea. The patient had a history of previous surgery and hospitalization. After three days, hyperthermia, leukopenia and hyperlactatemia were recorded, and blood culture revealed positivity for Enterococcus hirae, identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The patient’s general conditions progressively worsened, and the patient was euthanized. In the second case, a 2-year-old cat with chronic ocular herpesvirus infection and hypertrophic cardiomyopathy was admitted to the hospital for anorexia and hyperthermia. The cat was hospitalized one week before and received antimicrobial treatment for urinary tract infection by Staphylococcus felis. Hypokalemia and lymphopenia were also diagnosed. The patient progressively improved and was discharged after three days. On the same day, blood culture taken at admission revealed positivity for Enterobacter xiangfangensis, identified using MALDI-TOF MS. After five days, the patient returned with neurological symptoms, hypothermia and bradycardia, and was euthanized.ConclusionsIn small animal veterinary practice, the impact of opportunistic bacterial agents (such as E.hirae and E.xiangfangensis) on bloodstream infections remains unclear. As in human medicine, they can be contracted in every healthcare setting and considered hospital-acquired infections. In this report, we highlighted the threat they pose especially in patients with multiple risk factors. Rapid and accurate diagnostic tools (such as MALDI-TOF MS) could be particularly important for reducing the severity of the infections.

Incidence, aetiology and temporal trend of bloodstream infections in southern Sweden from 2006 to 2019: a population-based study.

BackgroundBloodstream infections (BSI) are a public health concern, and infections caused by resistant bacteria further increase the overall BSI burden on healthcare.AimTo provide a population-based estimate of BSI incidence and relate this to the forthcoming demographic ageing western population change.MethodsWe retrieved positive blood cultures taken from patients in the Skåne region, southern Sweden, 2006-2019 from the Clinical Microbiology Department database and estimated incidence rates (IR), stratified by age (0-49, 50-64, 65-79, ≥ 80 years), sex, year, and species and described antimicrobial susceptibility for Enterobacterales.ResultsWe identified 944,375 blood culture sets, and 129,274 (13.7%) were positive. After deduplication and removal of contaminants, 54,498 separate BSI episodes remained. In total, 30,003 BSI episodes (55%) occurred in men. The overall IR of BSI was 307/100,000 person-years, with an average annual increase of 3.0%. Persons ≥ 80 years had the highest IR, 1781/100,000 person-years, as well as the largest increase. Escherichia coli (27%) and Staphylococcus aureus (13%) were the most frequent findings. The proportion of Enterobacterales isolates resistant to fluoroquinolones and third generation cephalosporins increased from 8.4% to 13.6%, and 4.9% to 7.3%, (p for trend < 0.001), with the largest increase in the oldest age group.ConclusionWe report among the highest BSI IRs to date worldwide, with a higher proportion among elderly persons and males, including resistant isolates. Given expected demographic changes, these results indicate a possible substantial future BSI burden, for which preventive measures are needed.

Epidemiology and mortality outcome of carbapenem- and colistin-resistant Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa bloodstream infections

BackgroundBloodstream infections caused by carbapenem-resistant Gram-negative bacteria represent a major therapeutic challenge to clinicians worldwide. This study examined the epidemiology of carbapenem and colistin resistance in Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii blood isolates in an academic institution in Oman. MethodsAdult patients with bloodstream infections caused by Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii, between January 1, 2017, and December 31, 2020, were identified. Rates of carbapenem resistance, carbapenem-colistin dual resistance, and 30-day all-cause mortality were examined. Results585 non-repeat bloodstream infections due to Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii were identified during the study period. OXA-48 was the most prevalent carbapenemase gene in carbapenem-resistant K. pneumoniae blood isolates. Carbapenem resistance was observed in 160 (27.7%) of blood isolates, with 131 (81.9%) of these being healthcare-onset cases. Carbapenem resistance was highest in Acinetobacter baumannii (80.4%), followed by Klebsiella pneumoniae (46.4%), and Pseudomonas aeruginosa (29.9%). Sixteen (13.4%) of the carbapenem-resistant blood isolates were found to be colistin resistant. Thirty-day all-cause mortality was 68.1% in patients with bloodstream infections caused by carbapenem-resistant isolates, versus 21.3% in patients with bloodstream infections caused by carbapenem-susceptible isolates. ConclusionThe prevalence of carbapenem resistance and carbapenem-colistin dual resistance in Gram-negative blood culture isolates from patients with bloodstream infections is unacceptably high. Patients with bloodstream infections due to carbapenem-resistant isolates had substantially higher mortality.

Epidemiologic features, clinical characteristics, and predictors of mortality in patients with candidemia in Alameda County, California; a 2017–2020 retrospective analysis

BackgroundBloodstream infections caused by Candida species are responsible for significant morbidity and mortality worldwide, with an ever-changing epidemiology. We conducted this study to assess trends in the epidemiologic features, risk factors and Candida species distribution in candidemia patients in Alameda County, California.MethodsWe analyzed data collected from patients in Alameda County, California between 2017 and 2020 as part of the California Emerging Infections Program (CEIP). This is a laboratory-based, active surveillance program for candidemia. In our study, we included incident cases only.ResultsDuring the 4-year period from January 1st, 2017, to December 31st, 2020, 392 incident cases of candidemia were identified. The mean crude annual cumulative incidence was 5.9 cases per 100,000 inhabitants (range 5.0–6.5 cases per 100,000 population). Candida glabrata was the most common Candida species and was present as the only Candida species in 149 cases (38.0%), followed by Candida albicans, 130 (33.2%). Mixed Candida species were present in 13 patients (3.3%). Most of the cases of candidemia occurred in individuals with one or more underlying conditions. Multivariate regression models showed that age ≥ 65 years (RR 1.66, CI 1.28–2.14), prior administration of systemic antibiotic therapy, (RR 1.84, CI 1.06–3.17), cirrhosis of the liver, (RR 2.01, CI 1.51–2.68), and prior admission to the ICU (RR1.82, CI 1.36–2.43) were significant predictors of mortality.ConclusionsNon-albicans Candida species currently account for the majority of candidemia cases in Alameda County.

Epidemiology and outcomes of culture-positive bloodstream pathogens prior to and during the SARS-CoV-2 pandemic: a multicenter evaluation

BackgroundBloodstream infections (BSIs) are an important cause of morbidity and mortality in hospitalized patients. We evaluate incidence of community- and hospital-onset BSI rates and outcomes before and during the SARS-CoV-2 pandemic.MethodsWe conducted a retrospective cohort study evaluating patients who were hospitalized for ≥ 1 day with discharge or death between June 1, 2019, and September 4, 2021, across 271 US health care facilities. Community- and hospital-onset BSI and related outcomes before and during the SARS-CoV-2 pandemic, including intensive care admission rates, and overall and ICU-specific length of stay (LOS) was evaluated. Bivariate correlations were calculated between the pre-pandemic and pandemic periods overall and by SARS-CoV-2 testing status.ResultsOf 5,239,692 patient admissions, there were 20,113 community-onset BSIs before the pandemic (11.2/1000 admissions) and 39,740 (11.5/1000 admissions) during the pandemic (P ≤ 0.0062). Corresponding rates of hospital-onset BSI were 2,771 (1.6/1000 admissions) and 6,864 (2.0/1000 admissions; P < 0.0062). Compared to the pre-pandemic period, rates of community-onset BSI were higher in patients who tested negative for SARS-CoV-2 (15.8/1000 admissions), compared with 9.6/1000 BSI admissions among SARS-CoV-2-positive patients. Compared with patients in the pre-pandemic period, SARS-CoV-2-positive patients with community-onset BSI experienced greater ICU admission rates (36.6% vs 32.8%; P < 0.01), greater ventilator use (10.7% vs 4.7%; P < 0.001), and longer LOS (12.2 d vs 9.1 d; P < 0.001). Rates of hospital-onset BSI were higher in the pandemic vs the pre-pandemic period (2.0 vs 1.5/1000; P < 0.001), with rates as high a 7.3/1000 admissions among SARS-CoV-2-positive patients. Compared to the pre-pandemic period, SARS-CoV-2-positive patients with hospital-onset BSI had higher rates of ICU admission (72.9% vs 55.4%; P < 0.001), LOS (34.8 d vs 25.5 d; P < 0.001), and ventilator use (52.9% vs 21.5%; P < 0.001). Enterococcus species, Staphylococcus aureus, Klebsiella pneumoniae, and Candida albicans were more frequently detected in the pandemic period.Conclusions and relevanceThis nationally representative study found an increased risk of both community-onset and hospital-onset BSI during the SARS-CoV-2 pandemic period, with the largest increased risk in hospital-onset BSI among SARS-CoV-2-positive patients. SARS-CoV-2 positivity was associated with worse outcomes.

Changes in Antimicrobial Resistance and Etiology of Blood Culture Isolates: Results of a Decade (2010-2019) of Surveillance in a Northern Region of Colombia.

BackgroundBloodstream infections (BSI) are important causes of morbidity and mortality worldwide. Antimicrobial surveillance is essential for identifying emerging resistance and generating empirical treatment guides, the purpose of this study is to analyze trends in antimicrobial susceptibility of BSI from 2010 to 2019 in healthcare institutions from Medellin and nearby towns in Colombia.MethodsA Whonet database was analyzed from the GERMEN antimicrobial surveillance network; frequency and antibiotic susceptibility trends were calculated on more frequent microorganisms using Mann Kendall and Sen’s Slope Estimator Test.Results61,299 isolates were included; the three microorganisms more frequent showed a significant increasing trend through time E. coli (Sen’s Slope estimator = 0.7 p = <0.01) S. aureus (Sen’s Slope estimator = 0.60 p = <0.01) and K. pneumonia (Sen’s Slope estimator = 0.30 p = <0.01). E. coli showed a significant increase trend in cefepime and ceftazidime resistance, while K. pneumoniae showed a significant increase in resistance to cefepime, ciprofloxacin, and gentamicin. P. aeruginosa increases its susceptibility to all analyzed antibiotics and S. aureus to oxacillin. No increasing trend was observed for carbapenem resistance.ConclusionAn upward trends was observed in more frequent microorganisms and resistance to third and fourth-generation cephalosporins for E. coli and K pneumoniae; in contrast, not increasing trends in antibiotic resistance was observed for P. aeruginosa and S. aureus. The essential role of AMR-surveillance programs is to point out and identify these trends, which should improve antibiotic resistance control.

Early deaths associated with community-acquired and healthcare-associated bloodstream infections: a population-based study, Finland, 2004 to 2018.

BackgroundBloodstream infections (BSI) cause substantial morbidity and mortality.AimWe explored the role of causative pathogens and patient characteristics on the outcome of community-acquired (CA) and healthcare-associated (HA) BSI, with particular interest in early death.MethodsWe used national register data to identify all BSI in Finland during 2004–18. We determined the origin of BSI, patients´ underlying comorbidities and deaths within 2 or 30 days from specimen collection. A time-dependent Cox model was applied to evaluate the impact of patient characteristics and causative pathogens on the hazard for death at different time points.ResultsA total of 173,715 BSI were identified; 22,474 (12.9%) were fatal within 30 days and, of these, 6,392 (28.4%) occurred within 2 days (7.9 deaths/100,000 population). The 2-day case fatality rate of HA-BSI was higher than that of CA-BSI (5.4% vs 3.0%). Patients who died within 2 days were older than those alive on day 3 (76 vs 70 years) and had more severe comorbidities. Compared with other BSI, infections leading to death within 2 days were more often polymicrobial (11.8% vs 6.3%) and caused by Pseudomonas aeruginosa (6.2% vs 2.0%), fungi (2.9% vs 1.4%) and multidrug-resistant (MDR) pathogens (2.2% vs 1.8%), which were also predictors of death within 2 days in the model.ConclusionsOverrepresentation of polymicrobial, fungal, P. aeruginosa and MDR aetiology among BSI leading to early death is challenging concerning the initial antimicrobial treatment. Our findings highlight the need for active prevention and prompt recognition of BSI and appropriate antimicrobial treatment.

A phase I/II study of adoptive immunotherapy using donor liver graft-derived natural killer cells to prevent bloodstream infection after liver transplantation: a study protocol

BackgroundBloodstream infections (BSIs) are among the most lethal complications of liver transplantation (LT). Natural killer (NK) cells are an important component of innate immunity and play an essential role in infection and cancer. Adoptive transfer of activated NK cells has the potential to decrease post-LT infections, including BSIs.MethodsIn this prospective, single-center, interventional, single-arm, historical control, phase I/II study, 37 LT recipients will enroll. The patient will receive a single infusion of donor liver-derived NK cells 3−5 days after LT.DiscussionThe primary endpoint is the incidence of BSIs during the first month after LT. Secondary endpoints include overall survival, adverse events, immunological responses, hepatocellular or de novo malignancy, and incidence of infectious disease.Trial registrationThis study was prospectively registered with UMIN000019183 (https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000022074) on November 1, 2015 and jRCTa060190036 on February 27, 2020.