Emergence of Staphylococcus argenteus in pediatrics: Molecular insights from a hospital in East China.

Staphylococcus argenteus is a novel species within the Staphylococcus aureus complex and can cause serious bloodstream infections (BSIs) in humans, which have been mainly reported in adults, especially the elderly. In this study, we analyzed the molecular characterization of a strain of S. argenteus (22WJ8192) isolated from the peripheral vein blood sample of a seven-month-old female infant in Eastern China. The 22WJ8192 belonged to sequence type (ST)2250 and harbored six antibiotic-resistance genes and 53 virulence genes and was resistant to penicillin. Additionally, we conducted a comparative analysis of the molecular characteristics of S. argenteus sourced from various origins within the dataset, predominantly from the National Center for Biotechnology Information Collection (NCBI) genome database. Antibiotic-resistance genes blaR1, blaI_of_Z, blaZ, fosB-Saur, tet(L), aph(3")-IIIa, mecA, and dfrG were more prevalent among the strains of human origin. Virulence genes lukF-PV, sak, sdrE, scn, sdrC, and sdrD were more prevalent among strains of human origin. The presence of antibiotic-resistance genes blaR1, blaI_of_Z, blaZ, fosB-Saur, and aph(3")-IIIa in strain 22WJ8192 was also more common among strains of human origin in the dataset. Conversely, the antibiotic-resistance genes tet(L), mecA, and dfrG, typically found in strains of human origin, were not detected in 22WJ8192. Additionally, virulence genes lukF-PV, sak, sdrE, scn, sdrC, and sdrD present in 22WJ8192 exhibited a higher prevalence among strains of human origin in the dataset. In conclusion, this study emphasizes the potential of S. argenteus ST2250 to induce severe bloodstream infections in infants, shedding light on the molecular characteristics of this strain.

Impact of central-line-associated bloodstream infections and catheter-related bloodstream infections: a systematic review and meta-analysis.

OBJECTIVE: Accurate effect estimates are needed to inform input parameters of health economic models. Central-line-associated bloodstream infections (CLABSIs) and catheter-related bloodstream infections (CRBSIs) are different definitions used for central-line bloodstream infections and may represent dissimilar patients, but previous meta-analyses did not differentiate between CLABSIs/CRBSIs. In this meta-analysis, we provided outcome effect estimates in CLABSI and CRBSI patients, compared to uninfected patients. METHODS: We searched PubMed, EMBASE and CINAHL from January 2000 to March 2024 for full-text studies reporting all-cause mortality and/or hospital length of stay (LOS) in adult inpatients with and without CLABSI/CRBSI. Two investigators independently reviewed all potentially relevant studies and performed data extraction. Odds ratio for mortality and mean difference in LOS were pooled using random-effects models. Risk of study bias was assessed using ROBINS-E. RESULTS: We included 36 studies. Sixteen CLABSI and 12 CRBSI studies reported mortality. The mortality odds ratios of CLABSIs and CRBSIs, compared to uninfected patients, were 3.19 (95% CI, 2.44, 4.16, I2=49%) and 2.47 (95% CI, 1.51, 4.02, I2=82%) respectively. Twelve CLABSI and eight CRBSI studies reported hospital LOS; only three CLABSI studies and two CRBSI studies accounted for the time-dependent nature of CLABSIs/CRBSIs. The mean differences in LOS for CLABSIs and CRBSIs compared to uninfected patients were 16.14 days (95% CI, 9.27, 23.01, I2=91%) and 16.26 days (95% CI, 10.19, 22.33, I2=66%) respectively. CONCLUSION: CLABSIs and CRBSIs increase mortality risk and hospital LOSs. Few published studies accounted for the time-dependent nature of CLABSIs/CRBSIs, which can result in overestimation of excess hospital LOS.

Intestinal mucositis, systemic inflammation and bloodstream infections following high-dose methotrexate treatment in childhood acute lymphoblastic leukaemia: Comparison between the NOPHO ALL 2008 protocol and the ALLTogether1 protocol.

Severe intestinal mucositis (IM) increases the risk of bloodstream infections (BSI) and inflammatory toxicity during acute lymphoblastic leukaemia (ALL) induction treatment. However, the implications of IM in subsequent ALL therapy phases after achieving remission remain unknown. This study investigated the relationship between IM (measured by plasma citrulline and the chemokine CCL20) and the development of BSI and systemic inflammation (reflected by C-reactive protein, CRP) in children with ALL during high-dose methotrexate (HDMTX) treatment, an important part of ALL consolidation therapy. The study compared patients treated according to the NOPHO ALL 2008 protocol (n = 52) and the ALLTogether1 protocol (n = 42), both with identical HDMTX procedures but different scheduling. One week post-HDMTX, citrulline dropped to median levels of 14.5 and 16.9 µM for patients treated according to the NOPHO ALL 2008 and ALLTogether1 protocols, respectively (p = 0.11). In a protocol and neutrophil count-adjusted analysis, hypocitrullinaemia (<10 µmol/L) was associated with increased odds of BSI within 3 weeks from HDMTX (OR = 26.2, p = 0.0074). Patients treated according to the NOPHO ALL 2008 protocol exhibited increased mucosal- and systemic inflammation post-HDMTX compared to patients treated according to ALLTogether1, with increased CCL20 (14.6 vs. 3.7 pg/mL, p < 0.0001) and CRP levels (10.0 vs. 1.0 mg/L, p < 0.0001). Both citrulline and CCL20 correlated with CRP for these patients (rs = -0.44, p = 0.0016 and rs = 0.35, p = 0.016, respectively). These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol.

Phylogenetic group, antibiotic resistance, virulence gene, and genetic diversity of Escherichia coli causing bloodstream infections in Iran.

Escherichia coli is one of the most important pathogens causing bloodstream infections (BSIs) throughout the world. We sought to characterize the phylogroup classification, major human sequence types (STs), antimicrobial resistance, presence of selected antimicrobial resistance and virulence genes, and genetic diversity of E. coli isolated from patients with BSIs at the University Hospital in Iran. A total of 100 E. coli bloodstream isolates were collected between December 2020 and June 2022. This study used PCR to investigate phylogenetic groups (A, B1, B2, C, D, E, and F), four major STs (ST69, ST73, ST95, and ST131), antibiotic resistance genes (ARGs), virulence-associated genes (VAGs), and pathogenicity islands (PAIs). Antimicrobial susceptibility testing was done by disk diffusion method. Genetic diversity was analyzed by repetitive element sequence-based PCR (REP-PCR). The phylogenetic group B2 (32%) predominated, followed by phylogenetic group E (25%). ST131 (28%) was the most prevalent ST and the majority of these isolates (89.3%) were of serotype O25b. Most of E. coli isolates (75%) were categorized as multidrug resistant (MDR) with high rates of resistance (>55%) to ampicillin, trimethoprim-sulfamethoxazole, ciprofloxacin, cefazolin, and ceftriaxone. The most frequent ARGs were bla TEM (66%), sul1 (57%), and sul2 (51%). The most prevalent VAGs and PAIs were fimH (type 1 fimbriae adhesin; 85%), aer (iucC) (aerobactin; 79%), traT (serum resistance; 77%), iutA (aerobactin siderophore receptor; 69%), and PAI IV536 (75%), respectively. The highest rate of ARGs and VAGs was observed in the ST131 isolates. REP-PCR analysis showed high diversity among the studied isolates. The high prevalence of MDR septicemic E. coli with different types of ARGs, VAGs and genotypes is an extremely worrisome sign of BSIs treatment and poses a major threat for hospitalized patients. Active surveillance, stringent prescribing policies, increasing the awareness of ARGs among clinicians and re-defining the infection control measures are essential to curb the dissemination of these strains.

The utility of temporal trends of blood biomarkers as predictors for bloodstream infections in left ventricular assist device recipients.

BACKGROUND: Temporal trends of routinely obtained parameters may provide valuable information for predicting BSIs, but this association has not yet been established in LVAD patients. METHODS: This retrospective analysis included data from 347 consecutive recipients of three rotary LVAD types. Study endpoints included the incidence of BSI, the association of temporal trends of routinely obtained blood biomarkers with the development of BSIs, the incidence of BSIs, and survival on LVAD support. RESULTS: During follow-up, 47.8% (n = 166) of the patients developed BSI. In multivariate analyses, the development of BSI was a significant predictor of mortality (HR 5.78, 95% CI 4.08-8.19, p < 0.0001). In univariate analyses, after adjusting for potential confounders, albumin (SHR 0.94, 95% CI 0.91-0.97, p < 0.00010), creatinine (SHR 1.49, 95% CI 1.03-2.15, p = 0.033), and C-reactive protein (SHR 1.19, 95% CI 1.08-1.32, p = 0.0007) significantly predicted the development of BSIs during LVAD support. Notably, the strength of the association of parameter changes with the prediction of BSIs demonstrated a time-dependent correlation in the cases of albumin (p = 0.045) and creatinine (p = 0.003). CONCLUSION: Bloodstream infections are highly prevalent among LVAD recipients and are independent predictors of mortality. Temporal biomarker trends significantly predict the development of BSIs. These findings suggest opportunities for interventions aiming to reduce the incidence of BSIs.

Impact of the COVID-19 pandemic on the incidence and the epidemiology of catheter-related bloodstream infection two years later.

Introduction: The COVID-19 pandemic increased catheter-related bloodstream infections (C-RBSI), but its subsequent impact has not been adequately described. Our hospital has already depicted the effects of the COVID-19 pandemic in the first wave. However, we still do not know whether C-RBSI rates and aetiology are similar to those described before the COVID-19 pandemic. We aimed to evaluate the impact of the COVID-19 pandemic on the evolution of C-RBSI in a large tertiary teaching hospital two years later. Material and methods: We prospectively collected all confirmed C-RBSI episodes in a clinical microbiology laboratory database by matching blood cultures and catheter tip cultures with the isolation of the same microorganism (s). We compared our C-RBSI incidence rates and aetiology from 2018 to 2023. C-RBSI was defined as bacteremia or fungemia in a patient with clinical manifestations of infection and no other apparent source except the catheter. Results: During the study period, we collected 556 C-RBSI episodes. C-RBSI incidence rate per 1000 admissions each year was as follows: 2018: 2.2; 2019: 1.7; 2020: 3.29; 2021: 2.92; 2022: 2.69. and 2023: 2.01. Mainly, C-RBSI episodes occurring in critical care units each year were, respectively: 2018: 57 (54.8 %), 2019: 38 (45.2 %), 2020: 89 (63.6 %), 2021: 69 (60.5 %), 2022: 58 (50.9 %) and 2023 (61.4 %). The distribution of microorganisms showed an increase in Gram-negative episodes after the pandemic. Conclusion: Our study shows an increase in the incidence rate of C-RBSI during the COVID-19 pandemic, with a discrete decrease after that. C-RBSI episodes were mainly caused by coagulase-negative Staphylococci but with a rise in Gram-negative bacilli.

Impact of Implementing an Antimicrobial Stewardship Program for Optimizing Antibiotic Treatment in Gram-negative Bacilli Bacteremia.

BACKGROUND: Antibiotic Stewardship Programs (ASP) have improved empirical and directed antibiotic treatment in Gram-negative bloodstream infections. A decrease in mortality, readmission, and length of hospitalization has been reported. MATERIALS AND METHODS: A pre-post-quasi-experimental study was conducted between November and April 2015-2016 (pre-intervention period), 2016-2017, 2017-2018, and 2018-2019 (post-intervention periods), to analyse the impact of ASP on empirical, directed, and entire treatment optimization, as well as mortality, readmission, and length of hospitalization, in hospitalized patients with Gram-negative bacilli (GNB) bloodstream infections. RESULTS: One hundred seventy-four patients were included (41 in the pre-intervention group, 38 in the first-year post-intervention group, 50 in the second-year post-intervention group, and 45 in the third-year post-intervention group). There was a significant improvement in directed treatment optimization (43.9% in the pre-intervention group, 68.4% in the first-year post-intervention group, 74% in the second-year post-intervention group, and 88.9% in the third-year post-intervention group, P <0.001), as well as in entire treatment optimization (19.5%, 34.2%, 40.0%, and 46.7%, respectively, P=0.013), with increased optimal directed (adjusted odds ratio [aOR], 3.71; 95% confidence interval [CI], 1.60-8.58) and entire treatment (aOR, 3.31; 95% CI, 1.27-8.58). Although a tendency toward improvement was observed in empirical treatment after ASP implementation, it did not reach statistical significance (41.5% vs. 57.9%, P=0.065). No changes in mortality, readmission, or length of hospitalization were detected. CONCLUSION: ASP implementation improved both directed and entire treatment optimization in patients with GNB bloodstream infections over time. Nevertheless, no improvement was found in clinical outcomes such as mortality, readmission, or length of hospitalization.

Comparison of the Direct Identification and Short-Term Incubation Methods for Positive Blood Cultures via MALDI-TOF Mass Spectrometry.

Timely pathogen identification in bloodstream infections is crucial for patient care. A comparison is made between positive blood culture (BC) pellets from serum separator tubes using a direct identification (DI) method and colonies on agar plates from a short-term incubation (STI) method with a matrix-assisted laser desorption/ionization Biotyper for the evaluation of 354 monomicrobial BCs. Both the DI and STI methods exhibited similar identification rates for different types of bacteria, except for Gram-positive and anaerobic bacteria. The DI method's results aligned closely with the STI method's results for Enterobacterales, glucose-non-fermenting Gram-negative bacilli (GNB), and carbapenem-resistant Enterobacterales. The DI method exhibited high concordance with the conventional method for GNB identification, achieving 88.2 and 87.5% accuracy at the genus and species levels, respectively. Compared with the STI method, the DI method showed a less successful performance for Gram-positive bacterial identification (50.5 vs. 71.3%; p < 0.01). The DI method was useful for anaerobic bacterial identification of slow-growing microorganisms without any need for colony growth, unlike in the STI method (46.7 vs. 13.3%; p = 0.04). However, both methods could not identify yeast in positive BCs. Overall, the DI method provided reliable results for GNB identification, offering many advantages over the STI method by significantly reducing the turnaround time and enabling quicker pathogen identification in positive BCs.

Piperacillin-tazobactam vs. carbapenems for treating hospitalized patients with ESBL-producing Enterobacterales bloodstream infections: a systematic review and meta-analysis.

OBJECTIVES: To meta-analyze the clinical efficacy of piperacillin-tazobactam vs. carbapenems for treating hospitalized patients affected by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales bloodstream infections (BSIs). METHODS: Two authors independently searched PubMed-MEDLINE and Scopus database up to 17 January 2024, to retrieve randomized controlled trials (RCTs) or observational studies comparing piperacillin-tazobactam vs. carbapenems for the management of hospitalized patients with ESBL-BSIs. Data were independently extracted by the two authors, and the quality of included studies was independently assessed according to ROB 2.0 or ROBINS-I tools. Mortality rate was selected as primary outcome. Meta-analysis was performed by pooling odds ratios (ORs) retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. RESULTS: After screening 3,418 articles, 10 studies were meta-analyzed (one RCT and nine retrospective observational studies; N=1,962). Mortality rate did not significantly differ between treatment with piperacillin-tazobactam vs. carbapenems (N=6; OR 1.41; 95%CI 0.96-2.07; I²=23.6%). The findings were consistent also in subgroup analyses assessing patients receiving empirical therapy (N=5; OR 1.36; 95%CI 0.99-1.85), or patients having in ≥50% of cases urinary/biliary tract as the primary BSI source (N=2; OR 1.26; 95%CI 0.84-1.89). Conversely, the mortality rate was significantly higher with piperacillin-tazobactam only among patients having in <50% of cases urinary/biliary tract as the primary source of BSI (N=3; OR 2.02; 95%CI 1.00-4.07). CONCLUSIONS: This meta-analysis showed that, after performing appropriate adjustments for confounders, mortality and clinical outcome in patients having ESBL-producing Enterobacterales BSIs did not significantly differ among those receiving piperacillin-tazobactam compared to those receiving carbapenems.

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.

Systematic review on epidemiology of Escherichia coli in bloodstream infection of patients undergoing hematopoietic stem cell transplantation.

Introduction: We aimed to conduct a systematic review of the epidemiology of Escherichia coli in bloodstream infections (BSI) of hematopoietic stem cell transplantation patients. Methods: For a comprehensive search of studies that reported the prevalence of E. coli and antibiotic resistance in bloodstream infections from 2000 to January 1, 2024, databases such as PubMed, EMBASE, Google Scholar, Scopus, and Web of Science were searched. The main keywords used were: Escherichia coli, epidemiology, bloodstream infection, microbial resistance, antibiotic resistance, hematopoietic malignancy, hematopoietic stem cell transplantation. After applying eligibility criteria, and quality assessment of studies, data analysis was done by comprehensive meta-analysis (CMA) software. Results: The prevalence of bacterial bloodstream infections amongst different studies varied between 8-51%. Also, bloodstream infections caused by E. coli varied between 2.5-57%. Prevalence of extended-spectrum ß-lactamases (ESBLs) of Escherichia coli in bloodstream infections varied between 15-80%. As well, the mortality rate caused by Escherichia coli strains in bloodstream infection varied between 6.7-27.3%. Resistance to ciprofloxacin, cefepime, third- and fourth-generation cephalosporins, was reported to be the highest (prevalence of 100%), and the lowest was against amikacin, with a prevalence between 13-38%. Conclusions: The high prevalence of Escherichia coli-related BSI, and subsequent mortality, especially by multidrug resistance and ESBL strains, in patients undergoing hematopoietic stem cell transplantation, requires essential measures to prevent the spread of microbial resistance.

Urgent call for attention to diabetes-associated hospital infections.

In this editorial, we discuss the recent article by Zhao et al published in the World Journal of Diabetes, which highlights the importance of recognizing the risk indicators associated with diabetes mellitus (DM). Given the severe implications of healthcare-associated infections (HAIs) in hospitalized individuals- such as heightened mortality rates, prolonged hospitalizations, and increased costs- we focus on elucidating the connection between DM and nosocomial infections. Diabetic patients are susceptible to pathogenic bacterial invasion and subsequent infection, with some already harboring co-infections upon admission. Notably, DM is an important risk factor for nosocomial urinary tract infections and surgical site infections, which may indirectly affect the occurrence of nosocomial bloodstream infections, especially in patients with DM with poor glycemic control. Although evidence regarding the impact of DM on healthcare-associated pneumonias remains inconclusive, attention to this potential association is warranted. Hospitalized patients with DM should prioritize meticulous blood glucose management, adherence to standard operating procedures, hand hygiene pra-ctices, environmental disinfection, and rational use of drugs during hospitalization. Further studies are imperative to explore the main risk factors of HAIs in patients with DM, enabling the development of preventative measures and mitigating the occurrence of HAIs in these patients.

Prevalence and impact of multidrug-resistant bacteria in solid cancer patients with bloodstream infection: a 25-year trend analysis.

The study aimed to describe the epidemiology of multidrug-resistant (MDR) bacteria among solid cancer (SC) patients with bloodstream infections (BSIs), evaluating inappropriate empiric antibiotic treatment (IEAT) use and mortality trends over a 25-year period. All BSI occurrences in adult SC patients at a university hospital were analyzed across five distinct five-year intervals. MDR bacteria were classified as extended-spectrum beta-lactamases (ESBL)-producing and/or Carbapenem-resistant Enterobacterales, non-fermenting Gram-negative bacilli (GNB) resistant to at least three antibiotic classes, methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococci. A multivariate regression model identified the risk factors for MDR BSI. Of 6,117 BSI episodes, Gram-negative bacilli (GNB) constituted 60.4% (3,695/6,117), being the most common are Escherichia coli with 26.8% (1,637/6,117), Klebsiella spp. with 12.4% (760/6,117), and Pseudomonas aeruginosa with 8.6% (525/6,117). MDR-GNB accounted for 644 episodes (84.8% of MDR or 644/759), predominantly ESBL-producing strains (71.1% or 540/759), which escalated significantly over time. IEAT was administered in 24.8% of episodes, mainly in MDR BSI, and was associated with higher mortality (22.9% vs. 14%, P < 0.001). Independent factors for MDR BSI were prior antibiotic use [odds ratio (OR) 2.93, confidence interval (CI) 2.34-3.67], BSI during antibiotic treatment (OR 1.46, CI 1.18-1.81), biliary (OR 1.84, CI 1.34-2.52) or urinary source (OR 1.86, CI 1.43-2.43), admission period (OR) 1.28, CI 1.18-1.38, and community-acquired infection (OR 0.57, CI 0.39-0.82). The study showed an increase in MDR-GNB among SC patients with BSI. A quarter received IEAT, which was linked to increased mortality. Improving risk assessment for MDR infections and the judicious prescription of empiric antibiotics are crucial for better outcomes. IMPORTANCE: Multidrug-resistant (MDR) bacteria pose a global public health threat as they are more challenging to treat, and they are on the rise. Solid cancer patients are often immunocompromised due to their disease and cancer treatments, making them more susceptible to infections. Understanding the changes and trends in bloodstream infections in solid cancer patients is crucial, to help physicians make informed decisions about appropriate antibiotic therapies, manage infections in this vulnerable population, and prevent infection. Solid cancer patients often require intensive and prolonged treatments, including surgery, chemotherapy, and radiation therapy. Infections can complicate these treatments, leading to treatment delays, increased healthcare costs, and poorer patient outcomes. Investigating new strategies to combat MDR infections and researching novel antibiotics in these patients is of paramount importance to avoid these negative impacts.

Continued Intravenous Versus First Week Transition to Oral Antibiotic Therapy in Bloodstream Infections: A Systematic Review and Meta-Analysis.

Bloodstream infections (BSIs) are a major public health concern worldwide, requiring prompt and effective antibiotic therapy. Traditionally, intravenous (IV) antibiotics have been preferred for their rapid action and consistent absorption. However, interest is growing in transitioning to oral (PO) antibiotics when suitable, due to similar pharmacokinetics, improved patient outcomes, and reduced healthcare costs. This meta-analysis aims to evaluate the clinical effectiveness of switching from IV to PO antibiotics for both gram-negative and gram-positive BSIs. Scopus, Embase, and PubMed databases were comprehensively searched until March 2023. The review included randomized controlled trials and cohort studies comparing continued IV therapy with early transition from IV to PO antibiotics within the first week of admission. Inclusion criteria encompassed studies involving adult patients (≥18 years) and reporting specific outcomes such as treatment success, mortality, and hospital readmissions. Meta-analysis of 17 studies comprising 11,245 patients demonstrated higher treatment success rates overall (OR: 1.40, P=0.04), particularly in gram-negative infections (OR: 1.42, P=0.05). However, this effect was not statistically significant in the gram-positive subgroup (OR: 1.41, P=0.036). Oral switch significantly reduced all-cause mortality overall (OR: 0.35, P=0.003), especially in gram-negative infections (OR: 0.22, P=0.008), but not significantly in gram-positive infections (OR: 0.60, P=0.09). Both gram-negative and gram-positive infections benefited from shorter hospital stays (P<0.0001), despite significant heterogeneity. Hospital readmission rates did not significantly differ between IV and oral switch groups (P=0.53). Our meta-analysis suggests potential benefits of early transition from IV to PO antibiotics for BSIs, including improved treatment outcomes and shorter hospital stays without an increased risk of readmission. However, these findings are subject to selection bias, and further standardized randomized trials are essential to validate these results.

Risk Factors and Mortality Outcomes in Elderly Patients With Bloodstream Infections: A Retrospective Analysis.

Background The objective of our investigation was to evaluate the mortality rate and predictor factors that are associated with bloodstream infections (BSIs) in elderly patients who are admitted to the internal medicine ward. Materials and methods A retrospective cross-sectional analysis was conducted at a 550-bed tertiary care hospital in Peshawar, Pakistan, from January 2021 to June 2022. The study involved elderly inpatients aged 65 and older with positive culture results detected within two days of admission. Data collection involved demographic and patient-related risk variables, BSI-related risk factors, and environmental risk factors, with statistical analysis performed using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 26.0, Armonk, NY). Results Of the total study sample (n=186), 103 (55.4%) survived while 83 (44.6%) did not. The non-survivor group had a higher median Sequential Organ Failure Assessment (SOFA) score (6 vs. 2, p<0.0001) and Charlson Comorbidity Index (5 ± 2 vs. 3 ± 2, p<0.0001), with more frequent immunosuppression (25.3% vs. 8.7%, p=0.001). Additionally, gram-positive bacteria were more common in non-survivors (42% vs. 10%, p<0.0001), while gram-negative bacteria were more prevalent in survivors (73% vs. 36%, p=0.002). Conclusions Our research validates that BSI in older adults is a serious condition that is linked to a substantial death rate during hospitalization. The biggest determinant of death in older patients with BSI is the severity of clinical symptoms evaluated by the SOFA score upon admission. It is imperative to acknowledge that respiratory-induced BSIs are the most fatal, and patients who are hospitalized and admitted to the intensive care unit (ICU) are at an elevated risk.

Assessing the burden of disease of gram-negative bloodstream infections in a Brazilian hospital: A retrospective cohort study from 2015 to 2019.

Objectives: This study aimed to estimate the disease burden of BSIs caused by gram-negative bacteria (GNB-BSIs) in a Brazilian hospital from 2015 to 2019, measured in disability-adjusted life-years (DALYs). Methods: A retrospective cohort study of adult patients with GNB-BSI was conducted from April 01, 2015 to March 31, 2019. This study was carried out in a 356-bed private hospital with a 68-bed medical intensive care unit located in Salvador, Brazil. Demographic and clinical data were collected through a review of medical records. DALYs were estimated using Monte Carlo Simulations, using life tables for Brazilians estimated for 2020 and the Global Burden of Diseases 2010 (GBD 2010). Results: A total of 519 GNB-BSI episodes in 498 individuals were identified. The mean age was 59.92 ± 17.97 years, with 61.1% being male. The most common bacterial infections were Klebsiella pneumoniae and Escherichia coli (66.5%), whereas carbapenem-resistant gram-negative bacteria (CR-GNB) accounted for 32.7% of cases. The highest overall DALYs were observed in 2018 (752, 95% confidence interval [CI]: 520-1021 with Brazilian Life Tables and 782, 95% CI: 540-1062 with GBD 2010). Infections due to CR-GNB had the highest DALYs, particularly, in 2017, reaching 7050 (95% CI: 3200-12,150 with Brazilian Life Tables and 7350, 95% CI: 3350-12,700 with GBD 2010) DALYs per 1000 patient days and an estimated mortality rate of 40% per 1000 patient days. Conclusions: The persistently high DALYs associated with CR-GNB raise alarming concerns, potentially leading to over 300 deaths per 1000 patient days in the coming years. These findings underscore the urgency of addressing GNB-BSI as a significant public health issue in Brazil. These results are expected to provide helpful information for public health policymakers to prioritize interventions for infections due to antibiotic-resistant bacteria.

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.

Prospective Clinical Follow-Up Results of Infective Endocarditis.

Objective: Infective endocarditis incidence has been rising in recent years, with high mortality. Risk factors such as underlying heart diseases, chronic diseases, healthcare-associated infections, advanced age, and intravenous (IV) drug use have gained importance in the incidence, the treatment approach, and the disease course. The aim of this study is to contribute to Türkiye's data on infective endocarditis epidemiology and risk factors. Materials and Methods: This study examined risk factors, diagnostic and treatment approaches, and prognosis of infective endocarditis cases at Pamukkale University Faculty of Medicine Hospital. It was carried out prospectively for 28 months. Results: During this period, 67 endocarditis cases were detected in 65 patients. Among cardiac diseases, the rate of congenital heart diseases (41%), degenerative heart diseases (37%), and acute rheumatic fever (ARF) related valvular heart disease (31%) were found to be high. Hospitalization in the last six months (53.7%), history of cardiac surgery (41.8%), use of IV catheters (22.4%), hemodialysis (14.9%) and IV drug use (7.5%) were also determined. Staphylococci, streptococci, and enterococci were the primary agents. The most used empirical treatments were ampicillin, ampicillin-sulbactam, and gentamicin. Natural valve endocarditis was most determined. Surgical treatment was applied in 56.7% of endocarditis cases. Septic embolism and cardiac failure were the most common complications. Conclusion: This study's findings regarding the epidemiology and prognosis of infective endocarditis pointed out that it is still a disease with a high mortality rate.

Brucella as a cause of severe sepsis: Case series and brief review.

Brucellosis is a serious public health problem worldwide and can affect any organ system. Due to brucellosis's variable clinical presentation, ranging from subclinical to fully symptomatic, and limited available information, it poses a diagnostic challenge. In this study, we reported a case series of patients with diverse presentations. In addition, we briefly described the pathophysiology and mechanisms of Brucella in the body. These case presentations will be valuable in increasing the awareness of physicians. A prompt diagnosis is crucial, as detecting some clues of the infection in its early stages can help avoid misdiagnoses.

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.