Bloodstream Infections In Adults Research Articles

An Emergent Change in Epidemiologic and Microbiological Characteristics of Bloodstream Infections in Adults With Febrile Neutropenia Resulting From Chemotherapy for Acute Leukemia and Lymphoma at Reference Centers in Chile, Ecuador, and Peru.

Febrile neutropenia is a life-threatening condition commonly observed in patients with hematologic malignancies. The aim of this article is to provide updated knowledge about bloodstream infections in febrile neutropenia episodes within the Andean region of Latin America. This retrospective study was based in 6 hospitals in Chile, Ecuador, and Peru and included adult patients with acute leukemia or lymphoma and febrile neutropenia between January 2019 and December 2020. Of the 416 febrile neutropenia episodes, 38.7% had a bloodstream infection, 86% of which were caused by gram-negative rods, with Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa being the most frequently identified bacteria. K pneumoniae isolates were more frequently resistant than E coli to cefotaxime (65% vs 39.6%), piperacillin-tazobactam (56.7% vs 27.1%), and imipenem (35% vs 2.1%) and were more frequently multidrug resistant (61.7% vs 12.5%). Among P aeruginosa, 26.7% were resistant to ceftazidime, piperacillin-tazobactam, and imipenem, and 23.3% were multidrug resistant. Overall 30-day mortality was 19.8%, being higher with vs without a bloodstream infection (26.7% vs 15.3%, P = .005). Fever duration was also significantly longer, as well as periods of neutropenia and length of hospital stay for patients with bloodstream infection. Additionally, the 30-day mortality rate was higher for episodes with inappropriate vs appropriate empirical antibiotic therapy (41.2% vs 26.6%, P = .139). Considering the high rates of bacteria-resistant infection and 30-day mortality, it is imperative to establish strategies that reduce the frequency of bloodstream infections, increasing early identification of patients at higher risks of multidrug bacteria resistance, and updating existing empirical antibiotic recommendations.

Risk factors associated with inappropriate empirical antimicrobial treatment in bloodstream infections. A cohort study.

Introduction: Bloodstream infections (BSI) are a major cause of mortality all over the world. Inappropriate empirical antimicrobial treatment (i-EAT) impact on mortality has been largely reported. However, information on related factors for the election of i-EAT in the treatment of BSI in adults is lacking. The aim of the study was the identification of risk-factors associated with the use of i-EAT in BSI. Methods: A retrospective, observational cohort study, from a prospective database was conducted in a 400-bed acute-care teaching hospital including all BSI episodes in adult patients between January and December 2018. The main outcome variable was EAT appropriation. Multivariate analysis using logistic regression was performed. Results: 599 BSI episodes were included, 146 (24%) received i-EAT. Male gender, nosocomial and healthcare-associated acquisition of infection, a high Charlson Comorbidity Index (CCI) score and the isolation of multidrug resistant (MDR) microorganisms were more frequent in the i-EAT group. Adequation to local guidelines' recommendations on EAT resulted in 91% of appropriate empirical antimicrobial treatment (a-EAT). Patients receiving i-EAT presented higher mortality rates at day 14 and 30 when compared to patients with a-EAT (14% vs. 6%, p = 0.002 and 22% vs. 9%, p < 0.001 respectively). In the multivariate analysis, a CCI score ≥3 (OR 1.90 (95% CI 1.16-3.12) p = 0.01) and the isolation of a multidrug resistant (MDR) microorganism (OR 3.79 (95% CI 2.28-6.30), p < 0.001) were found as independent risk factors for i-EAT. In contrast, female gender (OR 0.59 (95% CI 0.35-0.98), p = 0.04), a correct identification of clinical syndrome prior to antibiotics administration (OR 0.26 (95% CI 0.16-0.44), p < 0.001) and adherence to local guidelines (OR 0.22 (95% CI 0.13-0.38), p < 0.001) were identified as protective factors against i-EAT. Conclusion: One quarter of BSI episodes received i-EAT. Some of the i-EAT related factors were unmodifiable (male gender, CCI score ≥3 and isolation of a MDR microorganism) but others (incorrect identification of clinical syndrome before starting EAT or the use of local guidelines for EAT) could be addressed to optimize the use of antimicrobials.

Analysis of Blood Culture Collection and Laboratory Processing Practices in Israel

Blood culturing is a critical diagnostic procedure affecting patient outcomes and antibiotic stewardship. Although there are standards for blood culturing, the process is not often measured. To evaluate processes related to the diagnosis of bloodstream infection and compare them with best practices. A quality improvement study using laboratory data from January 1 to June 30, 2019, was conducted in 28 (96.6%) Israeli acute care hospitals. All blood cultures (BCs) performed on samples from adults and children in a period of 147 hospital-months were analyzed. Data analysis was performed from April 12, 2021, to September 9, 2022. True pathogen detection rate, contamination rate, proportion of adults with blood cultures performed, proportion of adult culturing episodes with only 1 set or bottle used, and median time of steps from sample collection to pathogen identification. The data set consisted of 348 987 BC bottles. Bloodstream infection was detected in a median of 6.7% (IQR, 5.8%-8.2%) of adult culturing episodes and 1.1% (IQR, 0.7%-1.9%) of pediatric episodes. Eleven of 27 hospitals (40.7%) with adult patients met the standard of a contamination rate of less than 3% and only 2 hospitals (7.4%) met the more stringent standard of less than or equal to 1% contamination rate. The percentage of adults with blood cultures ranged from 2.7% to 29.0% (mean [SD], 15.7% [6.0%]). There was an association between sampling rate and pathogen detection until BCs were performed in 17% of adult admissions. The percentage of solitary BCs ranged from 47.8% to 94.4%. An estimated 1745 of 7436 (23.5%) adult bloodstream infections went undetected because solitary BCs were performed, anaerobic bottles were not used, or BCs were not performed. Median processing time was 51.2 (IQR, 33.9-78.0) hours, 3 times the optimal time: 4.4 (IQR, 1.7-12.5) hours for the preanalytical stage, 15.9 (IQR, 10.2-23.6) hours from incubation to growth detection, 4.5 (IQR, 1.5-10.7) hours from detection to Gram stain, and 30.9 (IQR, 22.0-41.9) hours from detection to isolate identification. An 8.6-hour delay was related to off-hours operating of laboratories. The findings of this study suggest that the multistep process of blood culturing is not managed comprehensively in Israel, leading to poor clinical practices and delayed results.

Incidence, microbiological aspects and associated risk factors of catheter-related bloodstream infections in adults on chronic haemodialysis at a tertiary hospital in Uganda

The high burden of infectious complications among patients receiving haemodialysis (HD) via central venous catheters increases morbidity and mortality. This study determined the incidence of catheter-related bloodstream infections (CRBSIs), microbiological profile of causative organisms, and associated predictors in patients on chronic HD. A prospective single-centre cohort study of 121 adult patients with end-stage kidney disease was conducted from October 2019 to March 2020. Antibiotic susceptibility was determined by the Kirby-Bauer disk diffusion method. Cox proportional hazards model was used to determine predictors of CRBSI. The mean age was 50 (standard deviation 14.9) years and the median duration of follow-up was 69 (interquartile range 23-124) days. At least one CRBSI was recorded for 41% of patients, at a rate of 5.2 infections per 1000 patient-days. Causative organisms were predominantly Gram-negative bacteria (60.3%), and 36.5% of all isolates were multi-drug resistant. Anaemia [hazard ratio (HR) 5.44, P=0.019, 95% confidence interval (CI) 1.32-22.48] and previous bloodstream infection [HR 2.47, P=0.028, 95% CI 1.10-5.54] were predictors of CRBSI. The high incidence of CRBSI in patients on chronic HD with predominance of Gram-negative bacteria means that catheter care bundles should include Gram-negative coverage.

Prevalence and species distribution of Candida bloodstream infection in children and adults in two teaching university hospitals in Egypt: first report of Candida kefyr

BackgroundCandidemia is a pervasive problem associated with significant morbidity and mortality in health care settings. This study aimed to determine the changing distribution of Candida species and the emergence of uncommon species.MethodsThis was a cross-sectional study performed in two Cairo University hospitals between 2019 and 2020. All Candida species isolates recovered from blood cultures of adults and pediatrics patients admitted to the hospitals were included. Candida isolates were identified by chromogenic Candida agar and Vitek2 YST identification card. Candida kefyr was confirmed by chip array.ResultsCandida species were responsible for 1.6% of bloodstream infections in adults and 10.8% in pediatric patients. C. albicans was the most prevalent species representing 27.8% in adults and 48.3% in pediatrics. Non-albicans species (NAC) represented the most isolated Candida species among adults and pediatrics (72.2% and 51.6%, respectively) with the predominance of C. tropicalis (27.8% and 22.5%, respectively) followed by C. parapsilosis (16.7% and 10.8%, respectively). The uncommon Candida, which is Candida species other than C. albicans, C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei, represents 16.6% and 14% of all candidemia in adults and pediatrics, respectively. Only one of each of C. lusitaniae, C. utilis, and C. kefyr were detected in adults. C. lusitaniae was the most frequently recovered uncommon Candida among pediatrics resulting in 6.4% of candidemia followed by C. famata (4.3%), C. utilis (2.2%), and C. kefyr (1.1%).ConclusionsC. albicans is still the primary species isolated from pediatrics and adults with candidemia despite the considerable shift to the non-albicans species. C. tropicalis and C. parapsilosis are the most prevalent NAC. The increased prevalence of uncommon Candida species is alarming and necessitates a prompt stewardship program.

Epidemiology, microbiological and clinical characteristics of Enterococcus species bloodstream infections: A 10-year retrospective cohort study from Qatar

Background and objectiveEnterococcus species is one of the leading causes of community and healthcare-associated infections resulting in significant morbidity and mortality. In this study, we aim to evaluate the epidemiology, microbiological and clinical characteristics of Enterococcus Blood Stream Infections (BSIs) over 10 years period in a national secondary care setting. MethodsA retrospective cohort study was conducted on verified cases of enterococcal BSIs in adults from January 2009–December 2018 from specialized care hospitals at Hamad Medical Corporation, Qatar. Epidemiological, microbiological and clinical data were reported and analyzed. ResultsA total of 263 enterococcus BSIs cases were identified, predominant were males (65%) with a median age of 63 (IQR 48–74). E. faecalis and E. faecium were predominate at 93.5% (73.38% and 20.15% respectively). Diabetes was the commonest premorbid condition (54.3%) followed by chronic kidney disease (36.5%). Central lines and genitourinary were the most common sources (18.25%, 14.83% respectively) while no identified source was reported in 45.25% of cases. Ampicillin susceptibility was 82.51% while vancomycin resistance was reported in 10.6% of isolates. Successful bacteremia clearance was achieved in 81.37% of cases at a mean of 4 days (Range 2–5 days) while metastatic complications occurred in 5.3% of cases. Univariate mortality risk analysis was associated with ICU admission, low level of consciousness, high bacteremia scores, and presence of catheters. The 30 days mortality was high at 66.54% with CKD and cancer patients at the highest mortality risks (OR 16.334 (CI 4.2–62.4) and 16 (CI 3–84) respectively. ConclusionSignificant mortality was associated with enterococcus BSI despite low rates for ampicillin and vancomycin resistance necessitating early identification of susceptible patients to instigate suitable preventive measures.

The Monte Carlo Simulation of Three Antimicrobials for Empiric Treatment of Adult Bloodstream Infections With Carbapenem-Resistant Enterobacterales in China.

Introduction: The aim of this study was to predict and evaluate three antimicrobials for treatment of adult bloodstream infections (BSI) with carbapenem-resistant Enterobacterales (CRE) in China, so as to optimize the clinical dosing regimen further.Methods: Antimicrobial susceptibility data of blood isolates were obtained from the Blood Bacterial Resistance Investigation Collaborative Systems in China. Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) of tigecycline, polymyxin B, and ceftazidime/avibactam against CRE.Results: For the results of PTAs, tigecycline following administration of 50 mg every 12 h, 75 mg every 12 h, and 100 mg every 12 h achieved > 90% PTAs when minimum inhibitory concentration (MIC) was 0.25, 0.5, and 0.5 μg/mL, respectively; polymyxin B following administration of all tested regimens achieved > 90% PTAs when MIC was 1 μg/mL with CRE; ceftazidime/avibactam following administration of 1.25 g every 8 h, 2.5 g every 8 h achieved > 90% PTAs when MIC was 4 μg/mL, 8 μg/mL with CRE, respectively. As for CFR values of three antimicrobials, ceftazidime/avibactam achieved the lowest CFR values. The highest CFR value of ceftazidime/avibactam was 77.42%. For tigecycline and ceftazidime/avibactam, with simulated regimens daily dosing increase, the CFR values were both increased; the highest CFR of tigecycline values was 91.88%. For polymyxin B, the most aggressive dosage of 1.5 mg/kg every 12 h could provide the highest CFR values (82.69%) against CRE.Conclusion: This study suggested that measurement of MICs and individualized therapy should be considered together to achieve the optimal drug exposure. In particular, pharmacokinetic and pharmacodynamic modeling based on local antimicrobial resistance data can provide valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.

Prognostic factors of Candida spp. bloodstream infection in adults: A nine-year retrospective cohort study across tertiary hospitals in Brazil and Spain

Mortality rates among adults with candidemia vary widely in different geographical settings. Studies directly comparing epidemiology and clinical practices between countries are scarce and could bring insights into improving clinical outcomes. Retrospective cohort including adults with candidemia diagnosed in five tertiary hospitals from Brazil and Spain between 2010-2018. Adequate therapeutic management included appropriate antifungal therapy and central-venous-catheter (CVC) removal within 48h of fungemia. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors associated with 30-day mortality. Overall, 720 patients were included, being 323 from Spain. Spanish patients received echinocandins more often (52·5% vs. 39·3%, p=0.001), initiated antifungals earlier [2 (0-7) vs. 2 days (0-16), p<0.001], and had faster CVC-removal [1 (0-42) vs. 2 days (0-38), p=0.012]. Mortality was higher among Brazilians at 14 days (35·8% vs. 20·1%, p<0.001), and at 30 days (51·9% vs. 31·6%, p<0.001). Factors associated with mortality included: age [OR 1·02, 95%CI (1·008-1·032), p=0·001], neutropenia [OR 3·24, 95%CI (1·594-6·585), p=0·001], chronic pulmonary disease [OR 2·26, 95%CI (1·495-3·436), p<0·001], corticosteroids [OR 1·45, 95%CI (1·018-2·079), p=0·039], Pitt-Score>1 [OR 2·56, 95%CI (1·776-3·690), p<0·001], and inadequate therapeutic management [OR 2·84, 95%CI (1·685-4·800), p<0·001]. Being from Spain [OR 0·51, 95%CI (0·359-0·726), p<0·001] and C. parapsilosis [OR 0·36, 95%CI (0·233-0·568), p<0·001] were protective. Higher mortality rates were observed in Brazil. Factors associated with 30-day mortality included mainly epidemiological characteristics and inadequate therapeutic management. Thus, effective and prompt antifungals combined with CVC-removal still need to be emphasized in order to improve the prognosis of adults with candidemia. Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2017/02203-7); CAPES Foundation (PDSE 88881.187981/2018-01).

Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study)

The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60-81 years) and 3656 (58.3%; 95% confidence interval 57.1-59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients' profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.

Determinants and outcomes of bloodstream infection in adults associated with one versus two sets of positive index blood cultures

ObjectivesTo investigate whether positivity in one or both index sets of blood cultures influences clinical determinants and mortality when diagnosing bloodstream infections (BSI). MethodsRetrospective population-based surveillance of all mono-microbial BSI was conducted among residents of the western interior of British Columbia. Clinical details were obtained by chart review and all-cause case-fatality was established at 30 days. Index cultures were defined as the first two sets of cultures initially drawn to diagnose incident BSI. ResultsA total of 2500 incident BSI were identified of which 945 (37.8%) and 1555 (62.2%) were based on one and two positive index cultures, respectively. There was an overall difference in the distribution of pathogens, with both Staphylococcus aureus and Streptococcus pneumoniae more likely to have two positive index cultures. Different foci of infection were associated with one versus two positive index cultures. Overall, 409 patients died within 30 days of index BSI for an all-cause case-fatality of 16.4%; with no difference between two positive (250/1555; 16.1%) and one positive (159/945; 16.8%; p 0.3) index blood culture. The number of positive index blood cultures was not associated with 30-day case-fatality after adjustment for confounding variables using logistic regression analysis. ConclusionsAlthough approximately one-third of BSI are diagnosed on the basis of a single positive blood culture and are associated with different clinical determinants, whether one or both index blood cultures are positive is not associated with lethal outcome.

Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT.

Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. The randomised controlled trial was conducted in 18 neonatal intensive care units in England. Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. Current Controlled Trials ISRCTN81931394. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.

Catheter-associated bloodstream infections in adults with cancer: a prospective randomized controlled trial

A common complication of central venous access devices (CVADs) is catheter-associated bloodstream infection (CABSI). We previously demonstrated that insertion of CVADs on the right side was associated with increased risk of CABSI, and hypothesized that this related to the predominance of right-handedness in the patient population, resulting in greater movement and bacterial contamination. To perform a prospective randomized, controlled, non-blinded study to determine whether the side of CVAD insertion influenced the incidence of CABSI. Adult cancer patients were randomly allocated to either dominant or non-dominant side CVAD insertion. The primary endpoint of the study was the number of line-days until CABSI, determined in a blinded fashion by two assessors. In all, 640 CVADs were randomized to dominant (N= 322) or non-dominant (N= 318) side of insertion, 60% had haematological malignancies, and 40% solid tumours. CVADs were a peripherally inserted central catheter line (67%), tunnelled CVAD (23%), and non-tunnelled CVAD (10%). Twenty-two percent of CVADs were complicated by CABSI. The rate of CABSI per 1000 line-days was 3.49 vs 3.66 in the non-dominant vs dominant group (hazard ratio (HR): 0.91; 95% confidence interval (CI): 0.65-1.28). By multivariable analysis, the rate of CABSI was increased by: use of tunnelled CVADs compared to peripherally inserted central venous catheter lines (HR: 2.05; 95% CI: 1.45-2.91); having a haematological malignancy compared to non-gastrointestinal solid tumours (5.55; 2.47-12.5); but not dominant compared to non-dominant side of CVAD (0.97; 0.69-1.36). CABSI in adult patients with cancer was not impacted by whether CVAD insertion was on the dominant or non-dominant side.

Epidemiologic changes in bloodstream infections in Andalucía (Spain) during the last decade

ObjectivesDuring the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain. MethodsData from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006–7 cohort study was performed between October 2006 and March 2007, and the 2016–17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression. ResultsOverall, 1262 episodes of BSI were included, 563 (44.6%) in 2006–7 and 699 (55.3%) in 2016–17. Multivariate models selected the following changes in patients' features in 2016–17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01–1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26–0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71–0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32–0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18–8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03–8.86). ConclusionsWe found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.

Progress towards a coordinated, national paediatric antimicrobial resistance surveillance programme: Staphylococcus aureus, enterococcal and Gram-negative bacteraemia in Australia.

There is increasing knowledge of antimicrobial usage in children yet limited availability of nationally representative paediatric-specific data on antimicrobial resistance. Paediatric data from this national surveillance programme are presented to explore differences between childhood and adult bloodstream infections and antimicrobial resistance surveillance. Using information collected from a prospective coordinated antimicrobial resistance surveillance programme, children ≤18 years and adults >18 years with a positive blood culture for Staphylococcus aureus, Enterococcus spp. or Gram-negative spp. presenting to one of 34 Australian hospitals during 2013-16 were evaluated. Consistent methodologies for key sepsis pathogens were employed and a comparative analysis between children and adults was conducted. There are stark contrasts between children and adults in this national antimicrobial resistance (AMR) data set. Notable differences include lower rates of AMR, different clinical and molecular phenotypes and lower mortality amongst children. The burden of Gram-negative resistance is disproportionately experienced in children, with higher odds of death with an ESBL versus non-ESBL bacteraemia in comparison with adults. These data support that children are not just 'little adults' in the AMR era, and analyses by age group are important to detect differences in antibiotic susceptibility, clinical phenotype and genetic virulence factors. Antimicrobial surveillance incorporated into routine laboratory practice is vital to inform an array of wider applications including antimicrobial guidelines, stewardship and direction for prioritization of novel antimicrobial development.

Pharmacokinetic/Pharmacodynamic Modeling of Seven Antimicrobials for Empiric Treatment of Adult Bloodstream Infections with Gram-Negative Bacteria in China.

Objective: Optimal dosing regimens for achieving a positive clinical outcome were simulated for seven antibiotics commonly used to treat bloodstream infections (BSIs) in adults. Methods and Results: Pharmacokinetic/pharmacodynamic (PK/PD) modeling was used to simulate 17 regimens, including meropenem, imipenem, cefepime, ceftazidime, piperacillin-tazobactam, tigecycline, and polymyxin B based on patients' characteristics and the antimicrobial resistance data for the main pathogens isolated from blood specimens in Shandong province (China). A regimen for which the cumulative fraction of response (CFR) was 90% or more was considered optimal. For Escherichia coli and Klebsiella pneumoniae, all carbapenem regimens, ceftazidime (2gq8h, 0.5 hr, and 3hr infusion), and piperacillin/tazobactam (4.5gq8h, 3 hr infusion) achieved CFRs above 90%. The meropenem regimen (2gq8h, 3 hr) achieved CFRs above 90% for both ceftriaxone or cefotaxime-resistant (CRO/CTX-R) E. coli and K. pneumoniae. For Pseudomonas aeruginosa, ceftazidime and meropenem (2gq8h, 0.5 hr, and 3 hr infusion) achieved optimal CFRs. None of the β-lactam regimens examined achieved a CFR above 80% for Acinetobacter baumannii. For all examined bacteria, polymyxin B (50 mg q12h) led to a CFR above 90%. Conclusion: PK/PD modeling based on local antimicrobial resistance data provides valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.

Ethanol Lock Therapy Markedly Reduces Catheter‐Related Blood Stream Infections in Adults Requiring Home Parenteral Nutrition: A Retrospective Study From a Tertiary Medical Center

The use of central venous catheter (CVC) access for home parenteral nutrition (HPN) is associated with catheter-related bloodstream infections (CRBSIs). There are limited data on the use of ethanol lock therapy (ELT) to prevent CRBSI in adult HPN patients. Our aim was to determine whether the routine institution of ELT decreased the incidence of CRBSI compared with historic controls at Emory University Hospital (EUH) in Atlanta, Georgia, USA. EUH medical records of adult HPN patients discharged with a tunneled, silicone CVC on ELT were retrospectively studied during a pre-hoc determined 14-month observation period (n = 87; 13,386 catheter days) and compared with clinically similar HPN patients from the same institution before institution of the ELT protocol for all appropriate patients. The ELT protocol involved instilling 2mL of 70% ethanol into each catheter lumen daily after the HPN cycle, following initial flushing with normal saline. Only 5 of 87 patients (5.7%) who received ELT were diagnosed with a CRBSI (0.45/1000 catheter days) during observation. We compared these data with our previously published clinically matched patient population from EUH (n = 22) receiving HPN via a silicone CVC without ELT. Of these historical controls, 45.5% were diagnosed with 1 or more CRBSIs (8.7/1000 catheter days) during observation (P <.001 vs the current ELT cohort). In this retrospective study with historical controls from the same academic center, institution of ELT in adults requiring HPN via a silicone CVC was associated with a marked (19-fold) reduction in CRBSI.

Escherichia coli bloodstream infection outcomes and preventability: a six-month prospective observational study

BackgroundEscherichia coli bloodstream infection (BSI) is a common and serious problem, and incidence and antibiotic resistance are increasing. AimTo understand the drivers of outcomes and factors associated with preventable cases at the study institution. MethodsBetween 1st November 2017 and 30th April 2018, cases of E. coli BSI in adults treated as inpatients at the study institution were included in a prospective cohort. Clinical, demographic and laboratory features were recorded, with seven-, 30- and 90-day mortality and length of hospital stay post BSI. Qualitative data on preventability were reviewed independently by two infection specialists. FindingsIn total, 195 cases in 188 patients were included in the analysis. Empirical antibiotics showed in-vitro resistance in 30.9% of cases. Thirty-day mortality was 23.6%, with a median length of hospital stay of seven days. On multi-variable analysis, 30-day mortality was associated with higher Charlson score, residential home residency, higher respiratory rate and higher serum urea, whilst prolonged length of stay was associated with hospital-acquired E. coli BSI. Fifty patients were felt to have avoidable BSI, all of which were health care associated; urinary catheter use, antibiotic-related and procedural complications were the areas of preventability. ConclusionsE. coli BSI has an appreciable mortality, with little in the way of modifiable risk factors for mortality or prolonged hospital stay. Attention to urinary catheter use is likely to be the most useful way to reduce the incidence, but current UK reduction targets may be unachievable.

Performance of the T2Bacteria Panel for Diagnosing Bloodstream Infections: A Diagnostic Accuracy Study.

Blood cultures, the gold standard for diagnosing bloodstream infections (BSIs), are insensitive and limited by prolonged time to results. The T2Bacteria Panel (T2 Biosystems) is a direct-from-blood, nonculture test that identifies the most common ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli). To assess performance of the T2Bacteria Panel in diagnosing suspected BSIs in adults. Prospective patient enrollment (8 December 2015 through 4 August 2017). Eleven U.S. hospitals. 1427 patients for whom blood cultures were ordered as standard of care. Paired blood culture and T2Bacteria testing. Performance of T2Bacteria compared with a single set of blood cultures in diagnosing proven, probable, and possible BSIs caused by T2Bacteria-targeted organisms. Blood culture and T2Bacteria results were positive for targeted bacteria in 3% (39 of 1427) and 13% (181 of 1427) of patients, respectively. Mean times from start of blood culture incubation to positivity and species identification were 38.5 (SD, 32.8) and 71.7 (SD, 39.3) hours, respectively. Mean times to species identification with T2Bacteria were 3.61 (SD, 0.2) to 7.70 (SD, 1.38) hours, depending on the number of samples tested. Per-patient sensitivity and specificity of T2Bacteria for proven BSIs were 90% (95% CI, 76% to 96%) and 90% (CI, 88% to 91%), respectively; the negative predictive value was 99.7% (1242 of 1246). The rate of negative blood cultures with a positive T2Bacteria result was 10% (146 of 1427); 60% (88 of 146) of such results were associated with probable (n= 62) or possible (n= 26) BSIs. If probable BSIs and both probable and possible BSIs were assumed to be true positives missed by blood culture, per-patient specificity of T2Bacteria was 94% and 96%, respectively. Low prevalence of positive blood cultures, collection of a single set of culture specimens, and inability of T2Bacteria to detect nontargeted pathogens. The T2Bacteria Panel rapidly and accurately diagnoses BSIs caused by 5 common bacteria. T2 Biosystems.

Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trial

Bloodstream infection is associated with high mortality and serious morbidity in preterm babies. Evidence from clinical trials shows that antimicrobial-impregnated central venous catheters (CVCs) reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is a paucity of similar evidence for babies receiving neonatal intensive care. This open-label, parallel-group, pragmatic, randomised controlled trial was done in 18 neonatal intensive care units in England. Newborn babies who needed a peripherally inserted CVC (PICC) were allocated randomly (1:1) to receive either a PICC impregnated with miconazole and rifampicin or a standard (non-antimicrobial-impregnated) PICC. Random allocation was done with a web-based program, which was centrally controlled to ensure allocation concealment. Randomisation sequences were computer-generated in random blocks of two and four, and stratified by site. Masking of clinicians to PICC allocation was impractical because rifampicin caused brown staining of the antimicrobial-impregnated PICC. However, participant inclusion in analyses and occurrence of outcome events were determined following an analysis plan that was specified before individuals saw the unblinded data. The primary outcome was the time from random allocation to first microbiologically confirmed bloodstream or cerebrospinal fluid (CSF) infection between 24 h after randomisation and 48 h after PICC removal or death. We analysed outcome data according to the intention-to-treat principle. We excluded babies for whom a PICC was not inserted from safety analyses, as these analyses were done with groups defined by the PICC used. This trial is registered with ISRCTN, number 81931394. Between Aug 12, 2015, and Jan 11, 2017, we randomly assigned 861 babies (754 [88%] born before 32 weeks of gestation) to receive an antimicrobial-impregnated PICC (430 babies) or standard PICC (431 babies). The median time to PICC removal was 8·20 days (IQR 4·77-12·13) in the antimicrobial-impregnated PICC group versus 7·86 days (5·00-12·53) days in the standard PICC group (hazard ratio [HR] 1·03, 95% CI 0·89-1·18, p=0·73), with 46 (11%) of 430 babies versus 44 (10%) of 431 babies having a microbiologically confirmed bloodstream or CSF infection. The time from random allocation to first bloodstream or CSF infection was similar between the two groups (HR 1·11, 95% CI 0·73-1·67, p=0·63). Secondary outcomes relating to infection, rifampicin resistance in positive blood or CSF cultures, mortality, clinical outcomes at neonatal unit discharge, and time to PICC removal were similar between the two groups, although rifampicin resistance in positive cultures of PICC tips was higher in the antimicrobial-impregnated PICC group (relative risk 3·51, 95% CI 1·16-10·57, p=0·018). 60 adverse events were reported from 49 (13%) patients in the antimicrobial-impregnated PICC group and 50 events from 45 (10%) babies in the standard PICC group. We found no evidence of benefit or harm associated with miconazole and rifampicin-impregnated PICCs compared with standard PICCs for newborn babies. Future research should focus on other types of antimicrobial impregnation of PICCs and alternative approaches for preventing infection. UK National Institute for Health Research Health Technology Assessment programme.

Salmonella Typhi From Blood Cultures in the Democratic Republic of the Congo: A 10-Year Surveillance

BackgroundThis study gives an overview of a decade (2007–2017) of hospital-based Salmonella Typhi bloodstream infection (BSI) surveillance in the Democratic Republic of the Congo (DRC), at 4 main sampling sites.MethodsBlood cultures were sampled in hospital-admitted patients with suspected BSI, according to standardized clinical indications. The results of the surveillance period 2015–2017 were compiled with those of previous surveillance periods (2007–2010 and 2011–2014). Whole genome sequencing of isolates with decreased ciprofloxacin susceptibility (DCS) was performed.Results Salmonella Typhi was isolated in 1.4% (531/37 388) and 10.3% (531/5177) of suspected and culture-confirmed BSI episodes, respectively. Salmonella Typhi ranked first among the BSI pathogens in adults (n = 220), but was mostly (n = 301 [56.7%]) isolated from children, of which 72.1% (217/301) and 31.6% (95/301) were <10 years and <5 years old, respectively. Multidrug resistance (MDR), DCS, and combined MDR/DCS were found in 38.3% (n = 180), 24.5% (n = 115), and 11.9% (n = 56) of 470 first isolates, respectively. MDR and DCS rates had increased since 2007, but remained stable during 2015–2017 with no geographical clustering at the province level. Most (91/93 [97.8%]) DCS isolates sequenced belonged to Genotyphi genotype 2.5.1, and gyr S83 was the most frequent DCS mutation (76/93 [81.7%]). Infections occurred perennially, but increased during the rainy season.Conclusions Salmonella Typhi was a frequent cause of BSI in adults and children in DRC, with high rates of antibiotic resistance. Sustainable surveillance and implementation of vaccination are compelling.