Mortality Of Bloodstream Infections Research Articles

The Impact of Bacterial Biofilms on End-Organ Disease and Mortality in Patients with Hematologic Malignancies Developing a Bloodstream Infection.

ABSTRACTBacterial bloodstream infection (BSI) represents a significant complication in hematologic patients. However, factors leading to BSI and progression to end-organ disease and death are understood only partially. The study analyzes host and microbial risk factors and assesses their impact on BSI development and mortality. A total of 96 patients with hematological malignancies and BSI were included in the study. Host-associated risk factors and all causes of mortality were analyzed by multivariable logistic regression at 30 days after BSI onset of the first neutropenic episode. The multidrug-resistant profile and biofilm production of bacterial isolates from primary BSI were included in the analysis. Median age was 60 years. The underlying diagnoses were acute leukemia (55%), lymphoma (31%), and myeloma (14%). A total of 96 bacterial isolates were isolated from BSIs. Escherichia coli was the most common isolate (29.2%). Multidrug-resistant bacteria caused 10.4% of bacteremia episodes. Weak biofilm producers (WBPs) were significantly (P < 0.0001) more abundant (72.2%) than strong biofilm producers (SBPs) (27.8%). Specifically, SBPs were 7.1% for E. coli, 93.7% for P. aeruginosa, 50% for K. pneumoniae, and 3.8% for coagulase-negative staphylococci. Mortality at day 30 was 8.3%, and all deaths were attributable to Gram-negative bacteria. About 22% of all BSIs were catheter-related BSIs (CRBSIs) and mostly caused by Gram-positive bacteria (79.0%). However, CRBSIs were not correlated with biofilm production levels (P = 0.75) and did not significantly impact the mortality rate (P = 0.62). Conversely, SBP bacteria were an independent risk factor (P = 0.018) for developing an end-organ disease. In addition, multivariate analysis indicated that SBPs (P = 0.013) and multidrug-resistant bacteria (P = 0.006) were independent risk factors associated with 30-day mortality. SBP and multidrug-resistant (MDR) bacteria caused a limited fraction of BSI in these patients. However, when present, SBPs raise the risk of end-organ disease and, together with an MDR phenotype, can independently and significantly concur at increasing the risk of death.IMPORTANCE Bacterial bloodstream infection (BSI) is a significant complication in hematologic patients and is associated with high mortality rates. Despite improvements in BSI management, factors leading to sepsis are understood only partially. This study analyzes the contribution of bacterial biofilm on BSI development and mortality in patients with hematological malignancies (HMs). In this work, weak biofilm producers (WBPs) were significantly more abundant than strong biofilm producers (SBPs). However, when present, SBP bacteria raised the risk of end-organ disease in HM patients developing a BSI. Besides, SBPs, together with a multidrug-resistant (MDR) phenotype, independently and significantly concur at increasing the risk of death in HM patients. The characterization of microbial biofilms may provide key information for the diagnosis and therapeutic management of BSI and may help develop novel strategies to either eradicate or control harmful microbial biofilms.

Epidemiology and outcomes of bloodstream infections in severe burn patients: a six-year retrospective study

BackgroundInfection is the leading cause of morbidity and mortality among burn patients, and bloodstream infection (BSI) is the most serious. This study aimed to evaluate the epidemiology and clinical outcomes of BSI in severe burn patients.MethodsClinical variables of all patients admitted with severe burns (≥ 20% total body surface area, %TBSA) were analyzed retrospectively from January 2013 to December 2018 at a teaching hospital. The Kaplan–Meier method was utilized for plotting survival curves. Multivariate logistic regression and Cox regression model were also performed.ResultsA total of 495 patients were evaluated, of whom 136 (27.5%) had a BSI. The median time from the patients being burned to BSI was 8 days. For BSI onset in these patients, 47.8% (65/136) occurred in the first week. The most frequently isolated causative organism was A. baumannii (22.7%), followed by methicillin-resistant Staphylococcus aureus (18.7%) and K. pneumoniae (18.2%), in patients with BSI. Multivariate logistic regression analysis showed that %TBSA (p = 0.023), mechanical ventilation (p = 0.019), central venous catheter (CVC) (p < 0.001) and hospital length of stay (27d vs 50d, p < 0.001) were independent risk factors associated with BSI. Cox regression model showed that acute kidney injury (HR, 12.26; 95% CI 2.31–64.98; p = 0.003) and septic shock (HR, 4.36; 95% CI 1.16–16.34; p = 0.031) were identified as independent predictors of 30-day mortality of BSI in burn patients.ConclusionsMultidrug resistant gram-negative bacteria were the main pathogens of BSI in severe burn patients. Accurate evaluation of risk factors for BSI and the mortality of BSI in severe burn patients may improve early appropriate management.

The effect of migration on the incidence and mortality of bloodstream infection: a Danish register-based cohort study

ObjectivesTo investigate bloodstream infection (BSI) related to migrant status by comparing the incidence and mortality in migrants with that in non-migrants. MethodsIn this register-based cohort study we linked a cohort of migrants and non-migrants with a bacteraemia database covering two regions in Denmark. We included first-time BSI between January 2000 and December 2015 in individuals ≥18 years. Migrants were categorized according to status: refugees or family-reunified migrants. Incidence rate ratio and mortality rate ratio were analysed using Poisson regression. ResultsWe identified 493 080 non-migrants, of which 3405 had BSI, and 80 740 migrants with 576 cases; of the latter, 40 222 were family-reunified migrants with 226 cases and 40 518 were refugees with 350 cases. Refugees had a higher risk of BSI than non-migrants (adjusted IRR 1.19, 95%CI 1.01–1.40). Family-reunified migrants and refugees had a higher risk of Gram-negative BSIs (adjusted IRR 1.23, 95%CI 1.00–1.51 and 1.57, 95%CI 1.32–1.86), respectively, and a lower risk of Gram-positive BSIs (adjusted IRR 0.65, 95%CI 0.51–0.83 and 0.77, 95%CI 0.63–0.95), respectively, compared to non-migrants. Originating from Southeast Asia and the Pacific was associated with an increased risk of BSI compared to non-migrants (adjusted IRR 1.26, 95%CI 1.07–1.49). We found no differences in the adjusted 30-day or 90-day mortality according to migrant status. ConclusionsVulnerability towards BSI differs according to migrant status. Refugees had a higher risk of BSI overall. Both refugees and family-reunified migrants had a higher incidence of Gram-negative BSI than non-migrants. Similarly, migrants from Southeast Asia and the Pacific had a higher risk of BSI than non-migrants.

Long-Term Impact of an Educational Antimicrobial Stewardship Program on Management of Patients with Hematological Diseases.

Antimicrobial stewardship programs (ASPs) in hematological patients are especially relevant. However, information about ASPs in this population is scarce. For 11 years, we quarterly assessed antimicrobial consumption and incidence and death rates of multidrug-resistant (MDR) bloodstream infections (BSI) in the hematology Department. Healthcare activity indicators were also monitored yearly. We performed an interrupted time-series analysis. Antimicrobials showed a sustained reduction with a relative effect of −62.3% (95% CI −84.5 to −40.1) nine years after the inception of the ASP, being especially relevant for antifungals (relative effect −80.4%, −90.9 to −69.9), quinolones (relative effect −85.0%, −102.0 to −68.1), and carbapenems (relative effect −68.8%, −126.0 to −10.6). Incidence density of MDR BSI remained low and stable (mean 1.10 vs. 0.82 episodes per 1000 occupied bed days for the pre-intervention and the ASP period, respectively) with a quarterly percentage of change of −0.3% (95% CI −2.0 to 1.4). Early and late mortality of MDR BSI presented a steady trend (quarterly percentage of change −0.7%, 95% CI −1.7 to 0.3 and −0.6%, 95% CI −1.5 to 0.3, respectively). Volume and complexity of healthcare activity increased over the years. The ASP effectively achieved long-term reductions in antimicrobial consumption and improvements in the prescription profile, without increasing the mortality of MDR BSI.

Prevalence, predictors, and mortality of bloodstream infections due to methicillin-resistant Staphylococcus aureus in patients with malignancy: systemic review and meta-analysis

BackgroundCancer patients are more likely to develop and die of bloodstream infection (BSI) than noncancer patients. Methicillin-resistant Staphylococcus aureus (MRSA), which is associated with immense mortality and economic burden worldwide, is not covered by the recommended initial antibiotic therapy for cancer patients with BSI. This systemic review was performed to estimate the global methicillin-resistant Staphylococcus aureus (MRSA) prevalence among bacteremia in patients with malignancy, and further study the predictors and mortality of cancer patients with MRSA bacteremia.MethodsThe PubMed and EMBASE databases were searched for studies published from Jan. 2000 to Mar. 2020 that provided primary data on the prevalence, predictors, or mortality of MRSA bacteremia in cancer patients. A random-effects model meta-analysis was performed to estimate the pooled prevalence of MRSA with 95% confidence intervals (95% CIs).ResultsThe pooled prevalence of MRSA was 3% (95% CI 2–5%) among all bloodstream infections (BSIs) and 44% (95% CI 32–57%) among S. aureus bacteremia in cancer patients. Based on geographical stratification, the pooled prevalence was 5% in Africa (95% CI 1–14%), 1% in Americas (95% CI 1–2%), 2% in Europe (95% CI 1–4%), 4% in Western Pacific (95% CI 2–7%), 8% in South-east Asia (95% CI 4–14%) and 0% in Eastern Mediterranean (95% CI 0–3%). No significant temporal change in MRSA rates was detected in this analysis (R2 = 0.06; P = 0.24). Predictors for MRSA BSIs among cancer patients were identified by comparison with their methicillin-susceptible counterparts, and they were mainly related to healthcare-associated infections and immunosuppression. Finally, the 60-day mortality in adult cancer patients with MRSA BSIs was reported to be 12%, and the 6-month overall mortality was 43.2%, with community-onset infection, secondary BSI, and vancomycin MIC≥2 g/mL being the risk factors for mortality.ConclusionsAlthough the prevalence of MRSA BSIs among cancer patients is relatively low, it did not decline over time as MRSA BSIs in the general hospital population and the high mortality rate was related to MRSA BSIs in patients with malignancy.

A practical update on the epidemiology and risk factors for the emergence and mortality of bloodstream infections from real-world data of 3014 hematological malignancy patients receiving chemotherapy.

Background: Bloodstream infection (BSI) is a common and serious complication after patients with hematologic malignancies (HM) receiving chemotherapy. This study examined real-world data seeking to characterize HM BSI and identify risk factors for BSI emergence and mortality.Methods: We retrospectively analyzed the pathogenic epidemiology, antibiotic resistance, and BSI risk factors in a single-center cohort including 3014 consecutive patients with HM receiving chemotherapy between 2013 and 2016. Results of the pathogenic epidemiology were validated via comparison to available reported data.Results: We found that 725 patients (24.1%) had BSIs. Gram-negative (G-) bacteria represented 64.7% of the 744 isolated pathogenic strains, while Gram-positive (G+) bacteria and fungi accounted for 27.7% and 7.7% of the BSIs, respectively. The most common isolates were Klebsiella pneumoniae (19.2%), and 95.1% of the multidrug-resistant strains (MDR) were extended-spectrum beta-lactamase producing strains. G- bacteria were the main microflora responsible for BSI in our cohort of Chinese HM patients compared to studies in developed countries or in neutropenic children with HM or solid tumors. Multivariate analysis revealed that male sex, age ≥ 45 and < 65 yr, hospital length of stay ≥ 9d, neutropenia ≥ 7d before cultures, ≥ 2 antibiotics, and infections (gastrointestinal, perirectal, or urinary tract) independently predicted BSI emergence. Furthermore, age ≥ 65 yr, neutropenia ≥ 7d before blood cultures, no HM remission, lower white blood cell count, ≥ 3 antibiotics, respiratory infections, and Acinetobacter baumannii and Stenotrophomonas maltophilia BSI were independent predictors of 30-day mortality.Conclusions: G- bacteria were the predominant microflora during the study period and antibiotic resistance levels of the pathogens detected were high, especially for MDR strains. The mortality of BSI patients was high in this large cohort. Close attention should be paid to the risk factors identified here to facilitate timely and effective clinical management of such patients.

Enterococcal bloodstream infections in critically ill patients with COVID-19: a case series

Background An unexpected high prevalence of enterococcal bloodstream infection (BSI) has been observed in critically ill patients with COVID-19 in the intensive care unit (ICU). Materials and methods The primary objective was to describe the characteristics of ICU-acquired enterococcal BSI in critically ill patients with COVID-19. A secondary objective was to exploratorily assess the predictors of 30-day mortality in critically ill COVID-19 patients with ICU-acquired enterococcal BSI. Results During the study period, 223 patients with COVID-19 were admitted to COVID-19-dedicated ICUs in our centre. Overall, 51 episodes of enterococcal BSI, occurring in 43 patients, were registered. 29 (56.9%) and 22 (43.1%) BSI were caused by Enterococcus faecalis and Enterococcus faecium, respectively. The cumulative incidence of ICU-acquired enterococcal BSI was of 229 episodes per 1000 ICU admissions (95% mid-p confidence interval [CI] 172–298). Most patients received an empirical therapy with at least one agent showing in vitro activity against the blood isolate (38/43, 88%). The crude 30-day mortality was 42% (18/43) and 57% (4/7) in the entire series and in patients with vancomycin-resistant E. faecium BSI, respectively. The sequential organ failure assessment (SOFA) score showed an independent association with increased mortality (odds ratio 1.32 per one-point increase, with 95% confidence interval 1.04–1.66, p = .021). Conclusions The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19. Our results suggest a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome. KEY MESSAGES The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19. The crude 30-day mortality of enterococcal BSI in critically ill patients with COVID-19 may be higher than 40%. There could be a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.

Attributable mortality of ICU acquired bloodstream infections: a propensity-score matched analysis.

The mortality attributable to ICU-acquired bloodstream infection (BSI) differs between studies due to statistical methods used for cohort matching. Propensity-score matching has never been used to avoid eventual bias when studying BSI attributable mortality in the ICU. We conducted an observational prospective study over a 4-year period, on patients admitted for at least 48 h in 2 intensive care units. Based on risk factors for death in the ICU and for BSI, each patient with BSI was matched with 3 patients without BSI using propensity-score matching. We performed a competitive risk analysis to study BSI mortality attributable fraction. Of 2464 included patients, 71 (2.9%) had a BSI. Propensity-score matching was highly effective and group characteristics were fully balanced. Crude mortality was 36.6% in patients with BSI and 21.6% in propensity-score matched patients (p=0.018). Attributable mortality of BSI was 2.3% [1.2–4.0] and number needed to harm was 6.7. With Fine and Gray model, a higher risk for death was observed in patients with BSI than in propensity-score matched patients (sub distribution Hazard Ratio (sdHR) = 2.11; 95% CI [1.32–3.37] p = 0.002). Patients with BSI had a higher risk for death and BSI attributable mortality fraction was 2.3%.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10096-021-04215-4.

Epidemiology and Clinical Characteristics of Bloodstream Infection in Patients Under Extracorporeal Membranous Oxygenation.

Bloodstream infection (BSI) is an important complication of extracorporeal membranous oxygenation (ECMO) and a major cause of mortality. This study evaluated the epidemiological and clinical characteristics of BSI that occur during ECMO application according to microbial etiology. Adult patients who underwent ECMO from January 2009 to December 2016 were retrospectively analyzed for BSI episodes at a 2,700-bed, tertiary center. Epidemiological and clinical characteristics and outcomes of BSI were evaluated and were compared for etiologic groups (gram-positive cocci, gram-negative rods, and fungi groups). Risk factors for 14-day mortality were analyzed. A total of 1,100 patients underwent ECMO during the study period, and 65 BSI episodes occurred in 61 patients. The BSI incidence was 8.3 episodes/1,000 ECMO days, which significantly decreased over time (P = 0.03), primarily in gram-positive cocci BSI. Gram-positive cocci, gram-negative rods, and fungi accounted for 38%, 40%, and 22% of the 73 blood isolates, respectively. Baseline characteristics were comparable between groups. Catheter-related infection (CRI) and pneumonia were the most common sources of BSI; 52% of gram-positive cocci BSIs and 79% of fungi BSIs were caused by CRI, and 75% of gram-negative BSIs by pneumonia. Patients with gram-negative rods BSI died more frequently and earlier than those with other BSIs. Independent risk factors for 14-day mortality were older age and gram-negative rods BSI. The decreased BSI incidence during ECMO was mainly because of the decrease of gram-positive cocci BSI. The high early mortality of gram-negative rods BSI makes prevention and adequate treatment necessary.

Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization study.

In observational studies of the general population, higher body mass index (BMI) has been associated with increased incidence of and mortality from bloodstream infection (BSI) and sepsis. On the other hand, higher BMI has been observed to be apparently protective among patients with infection and sepsis. We aimed to evaluate the causal association of BMI with risk of and mortality from BSI. We used a population-based cohort in Norway followed from 1995 to 2017 (the Trøndelag Health Study [HUNT]), and carried out linear and nonlinear Mendelian randomization analyses. Among 55,908 participants, the mean age at enrollment was 48.3 years, 26,324 (47.1%) were men, and mean BMI was 26.3 kg/m2. During a median 21 years of follow-up, 2,547 (4.6%) participants experienced a BSI, and 451 (0.8%) died from BSI. Compared with a genetically predicted BMI of 25 kg/m2, a genetically predicted BMI of 30 kg/m2 was associated with a hazard ratio for BSI incidence of 1.78 (95% CI: 1.40 to 2.27; p < 0.001) and for BSI mortality of 2.56 (95% CI: 1.31 to 4.99; p = 0.006) in the general population, and a hazard ratio for BSI mortality of 2.34 (95% CI: 1.11 to 4.94; p = 0.025) in an inverse-probability-weighted analysis of patients with BSI. Limitations of this study include a risk of pleiotropic effects that may affect causal inference, and that only participants of European ancestry were considered. Supportive of a causal relationship, genetically predicted BMI was positively associated with BSI incidence and mortality in this cohort. Our findings contradict the "obesity paradox," where previous traditional epidemiological studies have found increased BMI to be apparently protective in terms of mortality for patients with BSI or sepsis.

Predictors of mortality and clinical characteristics among carbapenem-resistant or carbapenemase-producing Enterobacteriaceae bloodstream infections in Spanish children.

Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging problem in the paediatric population worldwide with high mortality rates in bloodstream infection (BSI). To evaluate predictors of 30 day mortality in CRE BSI in a paediatric cohort. A retrospective observational single-centre study (December 2005-August 2018) was conducted. Cases of CRE BSI in children 0 to 16 years were included. Microbiological identification (MALDI Biotyper) and antimicrobial susceptibility testing (Vitek2® and MicroScan panel NBC44) according to EUCAST breakpoints were performed. PCR OXVIKP® was used to confirm carbapenemase genes (OXA-48, VIM, KPC, NDM). Demographic characteristics, underlying diseases, source of bacteraemia, antimicrobial therapy and outcomes were collected from medical records. Survival analysis to establish predictors of 30 day mortality was performed. Thirty-eight cases were included; 76.3% were hospital-acquired infections and 23.7% related to healthcare. All patients had at least one underlying comorbidity and 52.6% were recipients of an organ transplant. VIM carbapenemase was the predominant mechanism (92.1%). Previous CRE colonization or infection rate was 52.6%. Intestinal tract (26.3%) and vascular catheter (21.1%) were the most common sources of infection. Crude mortality within 30 days was 18.4% (7/38); directly related 30 day mortality was 10.5%. Conditions associated with an increment in 30 day mortality were intensive care admission and inadequate empirical therapy (P < 0.05). Combination-antibiotic targeted treatment and a low meropenem MIC were not related to improved survival. CRE BSI mortality rate is high. The most important factor related to 30 day survival in our CRE BSI cohort in children was empirical treatment that included at least one active antibiotic.

Risk factors and outcomes of bloodstream infections caused by Acinetobacter baumannii: a case–control study

The risk factors and outcomes of patients with bloodstream infections (BSIs) caused by Acinetobacter baumannii are major concerns in clinical therapy. Multicenter case–control studies were performed to compare the clinical characteristics of 47 A. baumannii BSI patients and 124 matched controls with nonbloodstream A. baumannii infections and the clinical and molecular characteristics of BSI survivors and nonsurvivors. Additionally, the mortality of BSIs was assessed. The clinical characteristics, including neutropenia, ICU admission prior to positive culture, primary infection in the central nervous system, and carbapenem use prior to positive culture, were independently associated with BSI caused by A. baumannii. The mortality of the BSI patients was significantly higher than that of the controls. A high Pitt bacteremia score was found to be an independent predictor of mortality in the BSI patients. The healthcare-associated factors, disease severity level, or antibiotic usage increased the risks of A. baumannii BSI and related mortality.

Risk of New Bloodstream Infections and Mortality Among People Who Inject Drugs With Infective Endocarditis

People who inject drugs (PWID) who are being treated for infective endocarditis remain at risk of new bloodstream infections (BSIs) due to ongoing intravenous drug use (IVDU). To characterize new BSIs in PWID receiving treatment for infective endocarditis, to determine the clinical factors associated with their development, and to determine whether new BSIs and treatment setting are associated with mortality. This retrospective cohort study was performed at 3 tertiary care hospitals in London, Ontario, Canada, from April 1, 2007, to March 31, 2018. Participants included a consecutive sample of all PWID 18 years or older admitted with infective endocarditis. Data were analyzed from April 1, 2007, to June 29, 2018. New BSIs and factors associated with their development, treatment setting of infective endocarditis episodes (ie, inpatient vs outpatient), and 90-day mortality. The analysis identified 420 unique episodes of infective endocarditis in 309 PWID (mean [SD] patient age, 35.7 [9.7] years; 213 episodes [50.7%] involving male patients), with 82 (19.5%) complicated by new BSIs. There were 138 independent new BSIs, of which 68 (49.3%) were polymicrobial and 266 were unique isolates. Aerobic gram-negative bacilli (143 of 266 [53.8%]) and Candida species (75 of 266 [28.2%]) were the most common microorganisms. Ongoing inpatient IVDU was documented by a physician in 194 infective endocarditis episodes (46.2%), and 127 of these (65.5%) were confirmed by urine toxicology results. Multivariable time-dependent Cox regression demonstrated that previous infective endocarditis (hazard ratio [HR], 1.89; 95% CI, 1.20-2.98), inpatient treatment (HR, 4.49; 95% CI, 2.30-8.76), and physician-documented inpatient IVDU (HR, 5.07; 95% CI, 2.68-9.60) were associated with a significantly higher rate of new BSIs, whereas inpatient addiction treatment was associated with a significantly lower rate (HR, 0.53; 95% CI, 0.32-0.88). New BSIs were not significantly associated with 90-day mortality (HR, 1.76; 95% CI, 0.78-4.02); significant factors associated with mortality included inpatient infective endocarditis treatment (HR, 3.39; 95% CI, 1.53-7.53), intensive care unit admission (HR, 9.51; 95% CI, 4.91-18.42), and methicillin-resistant Staphylococcus aureus infective endocarditis (HR, 1.77; 95% CI, 1.03-3.03), whereas right-sided infective endocarditis was associated with a significantly lower mortality rate (HR, 0.41; 95% CI, 0.25-0.67). In this study, new BSIs were common in PWID receiving parenteral treatment for infective endocarditis. Discharging patients to outpatient treatment was not associated with an increase in new BSI incidence or mortality; carefully selected PWID may therefore be considered for such treatment.

Five-year change of prevalence and risk factors for infection and mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection in a tertiary hospital in North China

BackgroundThere are few studies focused on carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI). The aim of this study is to identify the prevalence and risk factors for infection and mortality of CRKP BSI.MethodsSusceptibility of Klebsiella pneumoniae (KP) isolated from blood samples and the proportion of CRKP were recorded annually. One hundred sixty-four patients with CRKP and 328 with carbapenem-susceptible Klebsiella pneumoniae (CSKP) BSI were categorized as the case group and control group to identify risk factors for CRKP infection and mortality by univariable analysis and multivariable logistic-regression analysis.ResultsThe proportion and mortality of CRKP BSI increased significantly, with the percentage of KP in BSI increasing from 7 to 12% from 2014 to 2019 with a concomitant resistance to meropenem increasing from 16.7 to 41.8%. Compared with CSKP group, patients in CRKP group had longer hospitalization time before bacteremia (median 14 vs 4, P < 0.001) and longer total hospitalization time (median 31 vs 19, P < 0.001). The proportion of admission to ICU was higher (70.7% vs 17.7%, P < 0.001), and APACHE II score was higher (median 12 vs 8, P < 0.001). The mortality in CRKP group was 43.9% (72/164), while 14.9% (49/328) in CSKP group (p < 0.001). KP detection in other sites(P = 0.036, OR 1.964), blood purification(P = 0.018, OR 3.326), bronchoscopy(P = 0.011, OR 5.423), surgery (P = 0.001, OR 3.084), carbapenem use(P = 0.001, OR 3.395), tigecycline use(P = 0.006, OR 4.595) were independent risk factors for CRKP BSI. Previous hospitalization (P = 0.048, OR 2.755), long hospitalization (P = 0.003, OR 1.035), bone marrow puncture (P = 0.037, OR3.856), use of β-lactamase inhibitor (P = 0.005, OR 3.890) were independent risk factors for mortality in CRKP BSI.ConclusionThe prevalence and mortality of CRKP BSI are still increasing. Timely treatment of KP infection in other site, strengthening the hospital infection control of blood purification, bronchoscopy and surgery, control the use of carbapenem and tigecycline, may help to prevent CRKP BSI. More preventative hospital resources are needed for severely ill patients with prolonged hospitalizations and intensive care.

Characterisation of antibiotic resistance, virulence, clonality and mortality in MRSA and MSSA bloodstream infections at a tertiary-level hospital in Hungary: a 6-year retrospective study

BackgroundStaphylococcus aureus bloodstream infections (BSI) cause significant morbidity and mortality due to the frequent antibiotic resistance, toxin and adhesin production of the bacterium. These characteristics differ significantly in methicillin resistant (MRSA) and methicillin sensitive S. aureus (MSSA) and also among isolates of different MRSA clones, contributing to the outcome of S. aureus bacteraemia.MethodsIn this study, all MRSA BSI isolates from Semmelweis University, Budapest, Hungary, isolated between 2011–2016 and the same number of matched MSSA (overall 306 isolates) were characterised in terms of antibiotic susceptibility, virulence genes, clonality and their association with all-cause 30-day mortality. Effect of patient related variables, such as age, gender and comorbidities were also investigated.ResultsST22-MRSA-IV and ST5-MRSA-II were the most prevalent clones in our study. SCCmec I isolates showed the highest resistance rates and SCCmec II carried most virulence genes. Infections caused by SCCmec IV isolates were associated with the highest mortality rate (42.2%), despite the similar comorbidity rates of the different patient groups. All-cause 30-day mortality was 39.9% in the MRSA and 30.7% in the MSSA group. Increased teicoplanin MIC was associated with high mortality rate. Resistance to ciprofloxacin, erythromycin and clindamycin was common in MRSA, whereas MSSA isolates were more sensitive to all antibiotics with the exception of doxycycline. All MRSA isolates were sensitive to glycopeptides and linezolid; resistance to rifampicin and sulfamethoxazole-trimethoprim was low. MRSA isolates carried more adhesion genes, superantigens were more frequent in MSSA. Panton-Valentine leukocidin was found in 2.3% of the isolates.ConclusionThis study provides insight into the clonal composition and associated mortality of BSI S. aureus isolates in Hungary. The results suggest that the outcome of the infection is determined by the antibiotic resistance, genotype of the bacterium, and patient-related factors; rather than the virulence factors carried by the bacteria.

Impact of chlorhexidine baths on suspected sepsis and bloodstream infections in hospitalized neonates in Zambia

IntroductionSepsis is the leading cause of infectious morbidity and mortality among hospitalized neonates. In high-resource pediatric and adult intensive care units, use of aqueous chlorhexidine (CHG) solution has been associated with reduced risk of bloodstream infections (BSI). ObjectivesTo assess the impact of bathing of neonates with 2% CHG on BSI, suspected sepsis, and mortality in a low-income country neonatal care unit. MethodsWe conducted a secondary analysis of data from the Sepsis Prevention in Neonates in Zambia (SPINZ) study, a prospective observational cohort study performed at a large public referral hospital in Lusaka, Zambia. The SPINZ study assessed the impact of an infection control bundle (consisting of alcohol hand rub, SMS hygiene reminders, enhanced environmental cleaning, and CHG baths for babies ≥1.5 kg) on sepsis, BSI, and all-cause mortality. Episodic shortages in study staffing resulted in some enrolled babies not receiving a CHG bath. Using Longitudinal Targeted Maximum Likelihood Estimation and Cox proportional hazards regression to adjust for observed confounding, we estimated the causal effect of receiving a CHG bath within the first 3 days of life on suspected sepsis, BSI, and death among inborn babies enrolled during the study implementation and intervention phases. ResultsThe majority of inborn, enrolled babies ≥1.5 kg received a CHG bath within 3 days of NICU admission (864 of 1233, 70%). We found that CHG bathing reduced the hazard rate of BSI among inborn babies ≥1.5 kg by a factor of 0.58 (p = 0.10, 95% CI: 0.31, 1.11), corresponding to an absolute risk reduction of 9.6 percentage points within a week of admission (p = 0.002, 95% CI: 3.4–15.7 percentage points). We did not find a statistically significant effect of CHG bathing on culture-negative sepsis (p = 0.54) or death (p = 0.85). ConclusionIn our single center study, CHG bathing at admission was associated with a reduced risk of BSI due to a pathogenic organism after adjusting for potential confounding. Our results suggest that CHG may be an effective intervention for preventing neonatal sepsis in high-risk, low-income country settings.

Potential Antifungal Targets Based on Glucose Metabolism Pathways of Candida albicans.

In recent years, fungal infections have become a serious health problem. Candida albicans are considered as the fourth most common isolates associated with approximately 40% mortality in bloodstream infections among hospitalized patients. Due to various limitations of classical antifungals used currently, such as limited kinds of drugs, inevitable toxicities, and high price, there is an urgent need to explore new antifungal agents based on novel targets. Generally, nutrient metabolism is involved with fungal virulence, and glucose is one of the important nutrients in C. albicans. C. albicans can obtain and metabolize glucose through a variety of pathways; in theory, many enzymes in these pathways can be potential targets for developing new antifungal agents, and several studies have confirmed that compounds which interfere with alpha-glucosidase, acid trehalase, trehalose-6-phosphate synthase, class II fructose bisphosphate aldolases, and glucosamine-6-phosphate synthase in these pathways do have antifungal activities. In this review, the glucose metabolism pathways in C. albicans, the potential antifungal targets based on these pathways, and some compounds which have antifungal activities by inhibiting several enzymes in these pathways are summarized. We believe that our review will be helpful to the exploration of new antifungal drugs with novel antifungal targets.

Different screening frequencies of carbapenem-resistant Enterobacteriaceae in patients undergoing hematopoietic stem cell transplantation: which one is better?

BackgroundA consensus has been reached that carbapenem-resistant Enterobacteriaceae (CRE) screening in immunosuppressed individuals can reduce the incidence of CRE bloodstream infection (BSI).MethodsWe retrospectively studied the clinical data of 395 consecutive HSCT patients from September 2017 to April 2019. From September 2017 to June 2018 (period 1), 200 patients received single CRE screening before transplantation. From July 2018 to April 2019 (period 2), 195 patients received continuous weekly CRE screening after admission. For patients colonized with CRE, targeted managements were received: (1) contact precautions and (2) preemptive CRE-targeted treatment if necessary.ResultsDuring period 1, 3 patients with CRE colonization were detected (1.5%). The CRE BSI rate was 2.0% (4 patients), and the related 30-day mortality was 50.0% (2 out of 4 patients). During period 2, 21 patients with CRE colonization were detected, and the detection rate was significantly higher than that in period 1 (P < 0.001). Of the 21 colonized patients, 4 (19.0%) patients were identified as positive for CRE at the first screening, 5 (23.8%) were identified at the second screening, and the remaining 12 (57.1%) were identified at the third or later screening. The CRE BSI rate decreased to 0.5% (1/195), and there were no CRE-related death.Fifteen colonized patients developed neutropenic fever. Thirteen colonizers were preemptively treated with tigecycline within 24 h of fever onset, and they achieved rapid temperature control. One colonizer received tigecycline later than 48 h after fever onset and ultimately survived due to the addition of polymyxin. The other received tigecycline later than 72 h after fever onset and died of septic shock.ConclusionThe increase in screening frequency contributed to the detection of patients with CRE colonization. Targeted managements for these colonized patients may contribute to reducing the incidence and mortality of CRE BSI, therefore improving the prognosis of patients.

Multi-drug resistant bacteria predict mortality in bloodstream infection in a tertiary setting in Tanzania.

Bloodstream infections (BSI) are serious and life-threatening, associated with high mortality and morbidity. In resource-limited settings, there is a paucity of data on predictors of outcome in patients with BSI. This study aimed at examining the predictors of mortality in patients with BSI as well as bacteria causing BSI. This was a cross-sectional study conducted at Muhimbili National Hospital between April and May 2018. Blood culture results from all inpatients at the clinical microbiology laboratory were recorded and clinical information was retrieved retrospectively from the files. Bacteria from positive blood culture were identified and antimicrobial susceptibility was performed. The overall prevalence of BSI was, 46/402 (11.4% 95% CI 8.6-15), with a case fatality rate of 37%. There was a significantly high rate of BSI in patients who had died (19.5%) compared to those who survived (9.2%) p = 0.008. Gram-negative bacteria (74%) were the common cause of BSI, with a predominance of Enterobacteriaceae (22), followed by Pseudomonas aeruginosa (11). The majority of bacteria (70.5%) isolated from patients with BSI were Multi-drug resistant (MDR). Forty-six percent of Pseudomonas aeruginosa were resistant to meropenem while 68% (15/22) of Enterobacteriaceae were extended-spectrum β lactamase producers. Carbapenemase production was detected in 27% (3/11) of Pseudomonas aeruginosa and one Proteus mirabilis. Forty percent of Staphylococcus aureus were methicillin-resistant Staphylococcus aureus. Positive blood culture (aOR 2.24, 95%CI 1.12-4.47, p 0.02) and admission to the intensive care unit (aOR 3.88, 95%CI 1.60-9.41, p = 0.003) were independent factors for mortality in suspected BSI. Isolation of MDR bacteria was an independent predictor for mortality in confirmed BSI (aOR 15.62, 95%CI 1.24-161.38, p = 0.02). The prevalence of BSI was 11.4%, with the majority of bacteria in BSI were MDR. Positive blood culture, admission to the ICU and MDR were predictors for mortality.

Predictors of Mortality in Bloodstream Infections Caused by Pseudomonas aeruginosa and Impact of Antimicrobial Resistance and Bacterial Virulence.

Whether multidrug resistance (MDR) is associated with mortality in patients with Pseudomonas aeruginosa bloodstream infections (BSI) remains controversial. Here, we explored the prognostic factors of P. aeruginosa BSI with emphasis on antimicrobial resistance and virulence. All P. aeruginosa BSI episodes in a 5-year period were retrospectively analyzed. The impact in early (5-day) and late (30-day) crude mortality of host, antibiotic treatment, and pathogen factors was assessed by multivariate logistic regression analysis. Of 243 episodes, 93 (38.3%) were caused by MDR-PA. Crude 5-day (20%) and 30-day (33%) mortality was more frequent in patients with MDR-PA (34.4% versus 11.3%, P < 0.001 and 52.7% versus 21.3%, P < 0.001, respectively). Early mortality was associated with neutropenia (adjusted odds ratio [aOR], 9.21; 95% confidence interval [CI], 3.40 to 24.9; P < 0.001), increased Pitt score (aOR, 2.42; 95% CI, 1.34 to 4.36; P = 0.003), respiratory source (aOR, 3.23; 95% CI,2.01 to 5.16; P < 0.001), inadequate empirical therapy (aOR, 4.57; 95% CI, 1.59 to 13.1; P = 0.005), shorter time to positivity of blood culture (aOR, 0.88; 95% CI, 0.80 to 0.97; P = 0.010), an exoU-positive genotype (aOR, 3.58; 95% CI, 1.31 to 9.79; P = 0.013), and the O11 serotype (aOR, 3.64; 95% CI, 1.20 to 11.1; P = 0.022). These risk factors were similarly identified for late mortality, along with an MDR phenotype (aOR, 2.18; 95% CI, 1.04 to 4.58; P = 0.040). Moreover, the O11 serotype (15.2%, 37/243) was common among MDR (78.4%, 29/37) and exoU-positive (89.2%, 33/37) strains. Besides relevant clinical variables and inadequate empirical therapy, pathogen-related factors such as an MDR phenotype, an exoU-positive genotype, and the O11 serotype adversely affect the outcome of P. aeruginosa BSI.