Dynamic cytokine profiles of bloodstream infection caused by Klebsiella pneumoniae in China.

OBJECTIVES: The aim of this work was to assess dynamic cytokine profiles associated with bloodstream infection (BSI) caused by Klebsiella pneumoniae (Kpn) and investigate the clinical features associated with mortality. METHODS: A total of 114 patients with positive BSI-Kpn and 12 sepsis individuals without blood positive bacteria culture were followed up. Cytokine profiles were analyzed by multiplex immunoassay on the first, third, seventh and fourteenth day after diagnosis. The test cytokines included arginase, interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-4, IL-6, IL-10, IL-12 (p70), and IL-23. The minimum inhibitory concentration (MIC) of 24 antibiotics were tested for BSI-Kpn. Risk factors associated with the 30-day mortality and 120-day mortality were evaluated using logistic analyses and nomogram. RESULTS: There were 55 out of 114 patients with BSI-Kpn were included. All isolates showed high susceptibility rate to novel avibactam combinations. The level of arginase was the highest in carbapenem-resistant Kpn (CRKP) patients. The AUCs of arginase, TNF-α and IL-4 reached 0.726, 0.495, and 0.549, respectively, whereas the AUC for the combination of these three cytokines was 0.805. Notably, 120-day mortality in patients with CRKP was higher than carbapenem-sensitive K. pneumoniae (CSKP). Furthermore, the long-term and high levels of IL-6 and IL-10 were associated with death. CONCLUSIONS: High expression of arginase is correlated with CRKP. In addition, BSI-CRKP could result in indolent clinic course but poor long-term prognosis. Continuous increase of IL-6 and IL-10 were associated with mortality.

Retrospective analysis of molecular characteristics, risk factors, and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections.

BACKGROUND: Klebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis. RESULTS: Our study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357-61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312-16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119-11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226-2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922-23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with blaKPC-2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU. CONCLUSIONS: The analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians' understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes.

Neonatal bacteraemia in Ireland: A ten-year single-institution retrospective review.

Neonatal sepsis is a catastrophic condition of global concern, with reported mortality rates exceeding 10%. Bloodstream infections are an important cause of sepsis, and epidemiological studies of these infections are crucial for predicting the most common aetiological agents and antimicrobial susceptibility patterns and for developing antimicrobial guidelines. For the ten-year study period from July 2013 to June 2023, all neonatal bacteraemia cases were reviewed prospectively using an enhanced surveillance protocol. The patients were stratified according to their age at the time of blood culture collection: early onset if diagnosed in the first 72 hours of life, and late onset if diagnosed after that time. During the study period, 170 blood cultures were positive from 144 patients, of which 89 specimens from 64 patients represented the growth of significant pathogens. Coagulase-negative staphylococci (CoNS) were the most common pathogens identified (52%, 33/64), followed by Escherichia coli (14%, 9/64), Group B Streptococcus (GBS: 11%, 7/64) and Staphylococcus aureus (11%, 7/64). GBS was more commonly identified in early onset patients, while CoNS were predominantly associated with late onset. The presence of an intravascular catheter, maternal urinary tract infections and the receipt of total parenteral nutrition or transfused blood were identified as significant risk factors. The fatality rate was 8% (5/64). in summary, this study provides a detailed overview of the epidemiology of neonatal bacteraemia in a large teaching hospital in the Midwest of Ireland over a decade.

Clinical features and risk factors for mortality in patients with Klebsiella pneumoniae bloodstream infections.

INTRODUCTION: Concern about Klebsiella pneumoniae (K. pneumoniae) bloodstream infections (KP-BSIs) is widespread because of their high incidence and lethality. The aim of this study was to investigate the clinical features of, and risk factors for mortality caused by KP-BSIs. METHODOLOGY: This was a single-center retrospective observational study performed between 1 January 2019 and 31 December 2021, at a tertiary hospital. All patients with KP-BSIs were enrolled and their clinical data were retrieved from electronic medical records. RESULTS: A total of 145 patients were included (121 in the survival group and 24 in the non-survival group). There was a higher proportion of lower respiratory tract infections in the non-survival group than in the survival group (33.3% vs. 12.4%) (p < 0.05). There was a higher proportion of multi drug resistant (MDR) strains of K. pneumoniae in the non-survival group than in the survival group (41.7% vs. 16.5%) (p < 0.05). Multivariate analysis revealed that sequential organ failure assessment (SOFA) score > 6.5 (OR, 13.71; 95% CI, 1.05-179.84), admission to the intensive care unit (ICU) (OR, 2.27; 95% CI, 0.26-19.61) and gastrointestinal bleeding (OR, 19.97; 95% CI, 1.11-361.02) were independent risk factors for death in patients with KP-BSIs. CONCLUSIONS: Among all KP-BSIs, a high proportion of K. pneumoniae originated from lower respiratory tract infections, and a high proportion of K. pneumoniae were MDR; however, mortality was not influenced. SOFA score > 6.5, admission to the ICU, and gastrointestinal bleeding were independent risk factors for death in patients with KP-BSI.

Clinical and microbiological characteristics of persistent Staphylococcus aureus bacteremia, risk factors for mortality, and the role of CD4+ T cells.

This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4+ T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4+ T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4+ T cells might play a pivotal role in SAB PB.

Impact of multidrug resistance on outcomes in hematologic cancer patients with bacterial bloodstream infections.

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003-2007) to 39.7% (2018-2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum ß-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

Diagnostic and therapeutic yield of imaging studies in Polymicrobial and Monomicrobial Gram-negative bloodstream infections - a retrospective cohort study.

PURPOSE: Appropriate antimicrobial therapy and surgical drainage, improve survival in patients with Gram negative bloodstream infections (BSI). Data about the yield of imaging studies in polymicrobial BSI is sparse. The aim of the study was to assess the need for imaging studies and surgical drainage among patients with polymicrobial compared to monomicrobial BSI. RESULTS: In a retrospective cohort study of adult patients with Gram negative BSI, 135 patients with monomicrobial BSI were compared to 82 with polymicrobial BSI. Imaging studies were performed in 56.3 % of patients with monomicrobial BSI and in 50 % of polymicrobial BSI (p=0.4), surgical drainage was performed in 20.1 % of patients with monomicrobial BSI and 27.2 % of polymicrobial BSI (p=0.25). Surgical drainage was performed in 26.2 % of patients who survived vs. 11.8 % of patients who died (p=0.035). CONCLUSIONS: There is no difference in the diagnostic approach to monomicrobial and polymicrobial Gram-negative BSI. Surgical drainage is associated with decreased mortality.

Modelling the implementation of narrow versus broader spectrum antibiotics in the empiric treatment of E. coli bacteraemia.

The implementation of new antimicrobial resistance stewardship programs is crucial in optimizing antibiotic use. However, prescription choices can be difficult during empiric therapy; clinicians must balance the survival benefits of broader spectrum antibiotics with associated increases in resistance. The aim of this study was to evaluate the overall feasibility of switching to narrow spectrum antibiotics during the empiric treatment of E. coli bacteraemia by quantifying changes in resistance rates, antibiotic usage, and mortality using a deterministic state-transition model. Three unique model scenarios (A, B, and C), each representing a progressively broader spectrum empiric treatment regimen, were used to compare outcomes at 5 years. We show that the empiric use of the narrowest spectrum (first-line) antibiotics can lead to reductions in resistance to second-line antibiotics and the use of third-line antibiotics, but they also lead to increases in resistance to first-line therapy and higher mortality. Crucially, we find that shortening the duration of empiric and overall treatment, as well as reducing the baseline mortality rate, are important for increasing the feasibility of switching to narrow spectrum antibiotics in the empiric treatment of E. coli bacteraemia. We provide a flexible model design to investigate optimal treatment approaches for other bacterial infections.

Hospital mortality and length of stay associated with Enterobacterales positive blood cultures: a multicenter analysis.

Delayed time to antimicrobial susceptibility results can impact patients' outcomes. Our study evaluated the impact of susceptibility turnaround time (TAT) and inadequate empiric antibacterial therapy (IET) in patients with bloodstream infections (BSI) caused by Enterobacterales (ENT) species on in-hospital mortality and length of stay (LOS). This retrospective, multicenter investigation which included 29,570 blood ENT-positive admissions across 161 US healthcare facilities evaluated the association between antimicrobial susceptibility testing (AST) TAT, carbapenem susceptibility, and empiric therapy on post-BSI in-hospital mortality and LOS following an ENT BSI event in adult patients. After adjusting for outcomes covariates, post-BSI in-hospital mortality was significantly higher for patients in the IET vs adequate empiric therapy (AET) group [odds ratio (OR): 1.61 (95% CI: 1.32, 1.98); P < 0.0001], and when AST TAT was >63 h [OR:1.48 (95% CI: 1.16, 1.90); P = 0.0017]. Patients with carbapenem non-susceptible (carb-NS) ENT BSI had significantly higher LOS (16.6 days, 95% CI: 15.6, 17.8) compared to carbapenem susceptible (carb-S, 12.2 days, 95% CI: 11.8, 12.6), (P < 0.0001). Extended AST TAT was significantly associated with longer LOS for TAT of 57-65 h and >65 h (P = 0.005 and P< 0.0001, respectively) compared to TAT ≤42 h (reference). Inadequate empiric therapy (IET), carb-NS, and delayed AST TAT are significantly associated with adverse hospital outcomes in ENT BSI. Workflows that accelerate AST TAT for ENT BSIs and facilitate timely and adequate therapy may reduce post-BSI in-hospital mortality rate and LOS.IMPORTANCEFor patients diagnosed with bloodstream infections (BSI) caused by Enterobacterales (ENT), delayed time to antimicrobial susceptibility (AST) results can significantly impact in-hospital mortality and hospital length of stay. However, this relationship between time elapsed from blood culture collection to AST results has only been assessed, to date, in a limited number of publications. Our study focuses on this important gap using retrospective data from 29,570 blood ENT-positive admissions across 161 healthcare facilities in the US as we believe that a thorough understanding of the dynamic between AST turnaround time, adequacy of empiric therapy, post-BSI event mortality, and hospital length of stay will help guide effective clinical management and optimize outcomes of patients with ENT infections.

Epidemiology and clinical relevance of persistent bacteraemia in patients with Gram-negative bloodstream infection: a retrospective cohort study.

OBJECTIVES: The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. METHODS: We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. RESULTS: In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. CONCLUSIONS: Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia.

Carbapenem combination therapy versus standard of care for persistent methicillin-susceptible Staphylococcus aureus bacteraemia.

BACKGROUND: Successful use of carbapenems in combination with cefazolin or oxacillin for treatment of MSSA bacteraemia has been described; however, comparative data to standard treatment approaches are lacking. METHODS: This was a multicentre, retrospective study of adult patients with MSSA bacteraemia for >48 h. Standard treatment was considered monotherapy with cefazolin, oxacillin or nafcillin. Combination therapy was defined as the addition of ertapenem or meropenem to standard treatment for at least 24 h. The primary outcome was duration of bacteraemia defined as time from administration of an antibiotic with in vitro activity to first negative blood culture. Time to blood culture sterilization was compared through risk-set matching with aid of a propensity score. RESULTS: Overall, 238 patients were included; 66% (157/238) received standard treatment and 34% (81/238) received combination therapy. The median (IQR) time to carbapenem initiation was 4.7 (3.63-6.5) days. Patients who received combination therapy were younger (P = 0.012), more likely to have endocarditis (P = 0.034) and had longer median duration of bacteraemia (P < 0.001). After applying risk-set matching, patients who received combination therapy experienced faster time to blood culture sterilization compared with control patients [HR = 1.618 (95% CI; 1.119-2.339) P = 0.011]. Using a paired hazard model, 90 day mortality rates were not statistically different among patients who received combination therapy versus matched controls [HR = 1.267 (95% CI; 0.610-2.678), P = 0.608]. DISCUSSION: Carbapenem combination therapy resulted in faster time to blood culture sterilization, but no differences in overall mortality rates. Randomized trials are critical to determine the utility of carbapenem combination therapy.

Assessment of Posttransplant Bacteremia Caused by Extended-Spectrum Beta-Lactamase-Producing Gram-Negative Bacteria Among Kidney Transplant Recipients.

BACKGROUND: Extended-spectrum beta-lactamase-producing gram-negative rods (ESBL-GNR) are a rising cause of bacteremia in kidney transplant recipients (KT). The study purpose was to examine patient mortality, allograft survival, estimated glomerular filtration rate (eGFR) at the end of 1 year, and readmission rates while looking at treatment strategies among KTs with ESBL-GNR and non-ESBL-GNR bacteremia at our institution. METHODS: This study was a retrospective, cohort analysis of KTs with gram-negative bacteremia from January 1, 2020, to December 31, 2021. The primary outcome of the study was mortality. Patient outcomes were assessed for 365 days after positive blood cultures. RESULTS: The study included 63 patients. Of these, 18 (29%) patients had bacteremia caused by an ESBL-GNR and 45 (71%) patients had bacteremia caused by a non-ESBL-GNR. Patient survival at 90 days was 94% in the ESBL-GNR group and 96% in the non-ESBL-GNR group. Ciprofloxacin was the most common antimicrobial therapy at discharge (68.9%) in the non-ESBL-GNR group whereas ertapenem was the most common in the ESBL-GNR group (44.5%). Median eGFR at discharge was 41 mL/min/1.73 m2 in the ESBL-GNR group and 48 mL/min/1.73 m2 in the non-ESBL-GNR group. Ninety-day readmission occurred in 9 (50%) ESBL-GNR patients and 14 (32%) non-ESBL-GNR patients. None of the above comparisons are statistically significant (p > 0.05). Eleven (61%) ESBL-GNR and 2 (4%) non-ESBL-GNR patients used outpatient parenteral antimicrobial therapy (p < 0.001). CONCLUSIONS: Among KTs with ESBL-GNR bacteremia, no significant difference was detected in mortality or allograft function compared to non-ESBL-GNR bacteremia.

Extended-Infusion ß-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Current evidence is conflicting for associations of extended-infusion ß-lactam (EI-BL) therapy with clinical outcomes. Objective: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI). Design, Setting, and Participants: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion ß-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023. Exposures: EI-BL (ie, ≥3-hour infusion). Main Outcomes and Measures: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the ß-lactam used to treat the index GN-BSI). Results: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35). Conclusions and Relevance: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

Multicenter study on clinical outcomes and poor prognostic factors in patients with Klebsiella pneumoniae bacteremia receiving cefoperazone/sulbactam treatment.

BACKGROUND: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied. OBJECTIVES: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates. METHODS: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed. RESULTS: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes. CONCLUSION: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes.

Analysis of bacteraemia caused by group C and G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis) in Western Sydney over a 6-year period (2015-2020).

PURPOSE: Streptococcus dysgalactiae subsp. equisimilis (SDSE) has increasingly been recognised as a significant pathogen that causes a myriad of infections, ranging from cellulitis to invasive infections, including bacteraemia and even toxic shock syndrome. The aim of this study was to examine the epidemiology and disease manifestations of bacteraemia caused by SDSE. METHODS: We retrospectively reviewed cases of SDSE bacteraemia in adults aged ≥ 18 years admitted to four public hospitals in Western Sydney, Australia, between January 2015 and December 2020. We reviewed demographics, comorbidities, disease manifestations, management, and outcomes. RESULTS: There were 108 patients with SDSE bacteraemia over a six-year period. The median age of individuals with SDSE bacteraemia was 70 years (interquartile range, IQR, 58-85 years). Cardiovascular disease (46%), chronic skin conditions (44%) and diabetes (37%) were the most common comorbidities. Ten patients (9%) with SDSE bacteraemia had healthcare-acquired infections. Skin and skin structure infections (SSTIs) were the most common presentations (59%), while bone and joint infections (BJIs) represented 13% of the cases. Twenty patients (19%) had septic shock on presentation. Fifteen patients (14%) were prescribed clindamycin, while one patient received intravenous immunoglobulin (IVIg). Infective endocarditis (IE) was present in 3% of patients; however, only 44% of the total patients had an echocardiogram. The 30-day mortality rate was 13%, but it was greater in those aged > 75 years (21%). The average length of hospital stay for patients who survived was 15 days, and the average duration of intravenous therapy was 12 days. CONCLUSION: SDSE bacteraemia is typically a community-onset infection with a fifth of patients in our cohort presenting with septic shock. Though complications such as BJI (13%) and IE (3%) are infrequent, 30-day mortality is high at 21% in those aged > 75 years.

Serum susceptibility of Escherichia coli and its association with patient clinical outcomes.

The innate immune system eliminates bloodstream pathogens such as Escherichia coli in part through complement protein deposition and subsequent bacterial death (i.e., "serum killing"). Some E. coli strains have developed mechanisms to resist serum killing, though the extent of variation in serum killing among bloodstream infection (BSI) isolates and the clinical impact of this variation is not well understood. To address this issue, we developed a novel assay that uses flow cytometry to perform high throughput serum bactericidal assays (SBAs) with E. coli BSI isolates (n = 183) to define the proportion of surviving bacteria after exposure to serum. We further determined whether E. coli resistance to serum killing is associated with clinical outcomes (e.g., in-hospital attributable mortality, in-hospital total mortality, septic shock) and bacterial genotype in the corresponding patients with E. coli BSI. Our novel flow cytometry-based SBA performed similarly to a traditional SBA, though with significantly decreased hands-on bench work. Among E. coli BSI isolates, the mean proportion that survived exposure to 25% serum was 0.68 (Standard deviation 0.02, range 0.57-0.93). We did not identify associations between E. coli resistance to serum killing and clinical outcomes in our adjusted models. Together, this study describes a novel flow cytometry-based approach to the bacterial SBA that allowed for high-throughput testing of E. coli BSI isolates and identified high variability in resistance to serum killing among a large set of BSI isolates.

Pathogenic spectrum and drug resistance of bloodstream infection in patients with acute myeloid leukaemia: a single centre retrospective study.

Background: Bloodstream infection (BSI) represent a prevalent complication in haematological malignancies (HMs). Typically, Patients with BSI usually undergo empirical treatment pending pathogen identification. The timely and effective management of BSIs significantly influences patient prognosis. However, pathogen distribution in BSIs exhibits regional variation. In this study, we investigated the clinical characteristics, pathogen spectrum, drug resistance, risk factors of short-term prognosis and long-term prognostic factors of acute myeloid leukemia (AML) patients with BSI at Zhejiang Provincal People's Hospital. Methods: From 2019 to 2021, a total of 56 AML patients with BSI were treated in the Department of Haematology at Zhejiang Province People's Hospital. Data regarding pathogen spectrum and drug resistance were collected for analysis. The patients were stratified into non-survivor cohort and survivor cohort within 30 days after BSI, and the predictors of 30-days mortality were identified through both univariate and multivariate Logistic regression analyses. Furthermore, Kaplan-Meier survival analysis and Cox regression analysis were employed to ascertain the risk factors associated with poor prognosis in AML patients complicated by BSI. Results: A total of 70 strains of pathogenic bacteria were isolated from 56 AML patients with BSI. Gram-negative bacteria constituted the predominant pathogens (71.4%), with Klebsiella pneumoniae being the most prevalent (22.9%). Gram-positive bacteria and fungi accounted for 22.9% and 5.7%, respectively. Univariate and multivariate analyses revealed significant differences in total protein, albumin levels, and the presence of septic shock between the non-survivor cohort and the survior cohort 30 days post-BSI. COX regression analysis showed that agranulocytosis duration exceeding 20 days (HR:3.854; 95% CI: 1.451-10.242) and septic shock (HR:3.788; 95% CI: 1.729-8.299) were independent risk factors for poor prognosis in AML patients complicated by BSI. Notably, the mortality rate within 30 days after Stenotrophomonas maltophilia infection was up to 71.4%. Conclusions: In this study, Gram-negative bacteria, predominantly Klebsiella pneumoniae, constituted the primary pathogens among AML patients with BSIs. Serum albumin levels and the presence of septic shock emerged as independent risk factors for mortality within 30 days among AML patients with BSI. In terms of long-term prognosis, extended agranulocytosis duration exceeding 20 days and septic shock were associated with elevated mortality rates in AML patients with BSI. Additionally, in our centre, Stenotrophomonas maltophilia infection was found to be associated with a poor prognosis. Early intervention for Stenotrophomonas maltophilia infection in our centre could potentially improve patient outcomes.

Intravenous Fosfomycin as Adjunctive Therapy for Gram-Negative Bacteria Bloodstream Infections: A Propensity Score Adjusted Retrospective Cohort Study.

BACKGROUND: The role of intravenous fosfomycin (iv-FOS) as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI) needs to be evaluated in clinical practice, as in vitro data show potential efficacy. METHODS: All consecutive patients with a GNB-BSI from 01 January 2021 to 01 April 2023 were included. Primary outcome was 30-day mortality. A Cox regression analysis was used to identify predictors of mortality; an inverse-probability of treatment-weighting (IPTW) analysis was also performed. RESULTS: Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson comorbidity index of 5 (3-7). At GNB-BSI onset, the median SOFA score was 5 (2-7) and 122 patients (34%) presented with septic shock. Pathogens were principally Klebsiella pneumoniae (42%), Escherichia coli (28%) and Pseudomonas aeruginosa (17%); of them, 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); a combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) g/daily. The use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, P = 0.147). However, on multivariable Cox-regression, combination therapy with iv-FOS resulted in protection for mortality (aHR 0.51, 95% CI 0.28-0.92), but not other combo-therapies (HR 0.69, 95% CI 0.44-1.16). This result was also confirmed with the IPTW-adjusted Cox model (aHR 0.52, 95% CI 0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA > 6, PITT ≥ 4) and when iv-FOS was initiated within 24 hours of GNB-BSI onset. CONCLUSIONS: Fosfomycin in combination therapy for GNB-BSI may have a role in improving survival. These results justify the development of further clinical trials.

Hospital-Onset Bacteremia Among Neonatal Intensive Care Unit Patients.

Importance: The Centers for Disease Control and Prevention plans to introduce hospital-onset bacteremia (HOB) as a health care-associated infection measure. The epidemiology and clinical characteristics of HOB among infants admitted to the neonatal intensive care unit (NICU) are unknown. Objective: To estimate the rate of HOB among infants admitted to the NICU, measure the association of HOB risk with birth weight group and postnatal age, and estimate HOB-attributable mortality. Design, Setting, and Participants: This retrospective multicenter cohort study and emulated trial from 2016 to 2021 included a convenience sample of 322 NICUs in the United States. Participants were infants admitted to participating NICUs for 4 or more days. Exposures: The primary exposures were birth weight and postnatal age. Additional exposures included small for gestational age and central line presence. Main Outcomes and Measures: The primary study outcomes were HOB and HOB-attributable mortality. Results: Of 451 443 included infants, 250 763 (55.6%) were male, 200 680 (44.4%) were female, and 62 091 (13.8%) were born 1500 g or less. Of 9015 HOB events that occurred among 8356 infants (2%) during 8 163 432 days at risk (unadjusted incidence rate, 1.1 per 1000 patient-days; 95% CI, 1.0-1.2), 4888 HOB events (54.2%) occurred in the absence of a central line. Within the first 2 weeks after birth, the HOB rate was 14.2 per 1000 patient-days (95% CI, 12.6-16.1) among infants born 750 g or less, to 0.4 events per 1000 patient-days among infants born more than 2500 g (95% CI, 0.4-0.5). Among infants born 750 g or less, the relative HOB risk decreased by 90% after day 42 compared with days 4 to 14 (incidence rate ratio [IRR], 0.10; 95% CI, 0.1-0.1). Conversely, among infants born more than 2500 g, the relative HOB risk increased by 50% after day 42 compared with days 4 to 14 (IRR, 1.5, 95% CI, 1.2-1.9). Compared with otherwise similar infants without HOB, infants with HOB had an absolute difference in attributable mortality of 5.5% (95% CI, 4.7-6.3). Conclusions and Relevance: This study found that HOB events in the NICU are associated with increased mortality. Birth weight is an important risk factor for HOB; however, the relative rate of HOB decreases over postnatal age among low-birth-weight infants and increases among infants born more than 2500 g. Identifying strategies to prevent HOB and programs to decrease HOB risk are urgently needed to reduce infant mortality.