UNASSIGNED: This study aimed to delineate the characteristics and outcomes of gram-negative bacteremia (GNB) in oncology patients; analyze the risk factors for multi-drug-resistant (MDR) GNB; and assess its impact on the recurrence of bloodstream infection (BSI), hospital stay, and 30-day mortality.
UNASSIGNED: Data, including demographics, clinical features, common cancers, and microbiologic findings, were collected retrospectively from electronic medical records of patients admitted with solid tumors and BSI episodes between January and December 2022. Fisher\'s exact tests were used to determine the effect of MDR-GNB on 30-day mortality and BSI recurrence. The Wilcoxon rank-sum test assessed the differences in the length of hospital stay. Logistic regression models identified the risk factors for MDR-GNB.
UNASSIGNED: Among 1074 patients, 77 episodes of GNB bacteremia occurred in 59 individuals (47% male, median age 57.4 years). Of these, 37 (48%) were MDR-GNB. Carbapenem resistance was noted in 9.1% of GNB episodes. Previous antibiotic use was significantly associated with MDR-GNB (odds ratio 7.82; 95% confidence interval 2.52-24). MDR-GNB was linked to longer hospital stays (median 23 vs 10.5 days, P = 0.003) and higher recurrence rates than non-MDR-GNB (35.13% vs 5.0%, P <0.001). However, 30-day mortality did not significantly differ between the groups (35.14% vs 32.5%, P = 0.81).
UNASSIGNED: Previous antibiotic use predicted MDR-GNB in patients with solid tumor. MDR-GNB bacteremia increased the length of hospital stay and risk of recurrence compared with non-MDR-GNB bacteremia.

UNASSIGNED: Our objective is to determine whether prolonged infusion (PI) of beta-lactam antibiotics yields superior outcomes compared to intermittent infusion (II) in patients with Gram-Negative Bacterial (GNB) infections.
UNASSIGNED: We systematically searched papers from PubMed, the Cochrane Library, Embase, and Clinicaltrials.gov, targeting mortality as the primary outcome and looking at the clinical cure rate, hospital and intensive care unit (ICU) stay lengths, antibiotic treatment duration, and mechanical ventilation (MV) duration as secondary outcomes.
UNASSIGNED: Our meta-analysis of 18 studies, including 5 randomized control trials and 13 observational studies, with a total of 3,035 patients-1,510 in the PI group and 1,525 in the II group, revealed significant findings. PI was associated with reduced mortality (RR, 0.67; 95% CI, 0.55-0.81; p = 0.001; I2 = 4.52%) and a shorter MV duration (SMD, -0.76; 95% CI, -1.37 to -0.16; p = 0.01; I2 = 87.81%) compared to II. However, no differences were found in clinical cure rates, antibiotic treatment duration, length of hospital stay, or length of ICU stay.
UNASSIGNED: The PI approach for administering beta-lactam antibiotics in patients with suspected or confirmed GNB infections may be advantageous in reducing mortality rates and the duration of MV when compared to the II strategy.

UNASSIGNED: Although corticosteroids are recommended in the 2021 Surviving Sepsis Campaign (SSC) guidelines, evidence with respect to their effects on short-term mortality remains conflicting. We conducted this study to identify whether corticosteroids alter 28-day mortality in septic shock patients with gram-negative bacterial infection.
UNASSIGNED: A total of 621 patients with septic shock and gram-negative bacterial culture results were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching (PSM) was performed, and Kaplan-Meier survival curve analyses with log-rank tests were used to determine the relationship between corticosteroid use and the risk of 28-day mortality. Subgroup analyses were conducted to assess whether the conclusions were stable and reliable.
UNASSIGNED: Corticosteroid administration was associated with increased 28-day mortality in septic shock patients with gram-negative bacterial infection (log-rank test P = 0.028). The incidence of Stage 2 or 3 AKI and the rate of hospital mortality were higher among patients who received corticosteroids. The incidence of Stage 2 or 3 AKI in the early period significantly mediated the relationship between corticosteroid use and 28-day mortality [P =0.046 for the average causal mediation effect (ACME)]. Interaction tests indicated that the effect of corticosteroid use was maintained in patients with a neutrophil-to-lymphocyte ratio (NLR) of <20 (P-value for interaction = 0.027).
UNASSIGNED: Systemic corticosteroid use could be harmful in septic shock patients with gram-negative bacterial infection, especially in patients with relatively low NLR.

Imipenem/cilastatin/relebactam is approved for the treatment of serious gram-negative bacterial infections in adults. This study assessed the pharmacokinetics (PK), safety, and tolerability of a single dose of imipenem/cilastatin/relebactam (with a fixed 2:1 ratio of imipenem/cilastatin to relebactam, and with a maximum dose of 15 mg/kg imipenem and 15 mg/kg cilastatin [≤500 mg imipenem and ≤500 mg cilastatin] and 7.5 mg/kg relebactam [≤250 mg relebactam]) in children with confirmed/suspected gram-negative bacterial infections receiving standard-of-care antibacterial therapy. In this phase 1, noncomparative study (ClinicalTrials.gov identifier, NCT03230916), PK parameters from 46 children were analyzed using both population modeling and noncompartmental analysis. The PK/pharmacodynamic (PD) target for imipenem was percent time of the dosing interval that unbound plasma concentration exceeded the minimum inhibitory concentration (%fT>MIC) of ≥30% (MIC = 2 mcg/mL). For relebactam, the PK/PD target was a free drug area under the plasma concentration-time curve (AUC) normalized to MIC (at 2 mcg/mL) of ≥8.0 (equivalent to an AUC from time zero extrapolated to infinity of ≥20.52 mcg·h/mL). Safety was assessed up to 14 days after drug infusion. For imipenem, the ranges for the geometric mean %fT>MIC and maximum concentration (Cmax ) across age cohorts were 56.5%-93.7% and 32.2-38.2 mcg/mL, respectively. For relebactam, the ranges of the geometric mean Cmax and AUC from 0 to 6 hours across age cohorts were 16.9-21.3 mcg/mL and 26.1-55.3 mcg·h/mL, respectively. In total, 8/46 (17%) children experienced ≥1 adverse events (AEs) and 2/46 (4%) children experienced nonserious AEs that were deemed drug related by the investigator. Imipenem and relebactam exceeded plasma PK/PD targets; single doses of imipenem/cilastatin/relebactam were well tolerated with no significant safety concerns identified. These results informed imipenem/cilastatin/relebactam dose selection for further pediatric clinical evaluation.

To explore the diagnostic performance of interleukin (IL)-6 and IL-10 in discriminating Gram bacteria types and predicting disease severity in intensive care unit (ICU)-hospitalized pediatric sepsis patients.
We retrospectively collected Th1/Th2 cytokine profiles of 146 microbiologically documented sepsis patients. Patients were categorized into Gram-positive (G+) or Gram-negative (G-) sepsis groups, and cytokine levels were compared. Subgroup analysis was designed to eliminate the influence of other inflammatory responses on cytokine levels.
After propensity score matching, 78 patients were matched and categorized according to Gram bacteria types. Compared with G+ sepsis, IL-6 and IL-10 were significantly elevated in G- sepsis (p < 0.05). Spearman test proved the linear correlation between IL-6 and IL-10 (r = 0.654, p < 0.001), and their combination indicators (ratio and differences) were effective in identifying G- sepsis. In the subgroup analysis, such cytokine elevation was significant regardless of primary infection site. However, for patients with progressively deteriorating organ function [new or progressive multiple organ dysfunction syndrome (NPMODS)], differences in IL-6 and IL-10 levels were less significant between G+ and G- sepsis. In the receiver operating characteristic (ROC) curves of the G- sepsis group, the area under the curve (AUC) value for IL-6 and IL-10 was 0.679 (95% CI 0.561-0.798) and 0.637 (95% CI 0.512-0.762), respectively. The optimal cutoff value for diagnosing G- sepsis was 76.77 pg/ml and 18.90 pg/ml, respectively. While for the NPMODS group, the AUC for IL-6 and IL-10 was 0.834 (95% CI 0.766-0.902) and 0.781 (95% CI 0.701-0.860), respectively.
IL-6 and IL-10 are comparably effective in discriminating G+/G- sepsis in pediatric intensive care unit (PICU) patients. The deteriorated organ function observed in ICU patients reveals that complex inflammatory responses might have contributed to the cytokine pattern observed in severe sepsis patients, therefore confounding the discriminating efficacy of Th1/Th2 cytokines in predicting Gram bacteria types.

Probability of target attainment (PTA) analyses were conducted to support the recommended ceftolozane/tazobactam dosing regimens, adjusted for renal function, in patients with hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). Previously published population pharmacokinetic models describing the disposition of ceftolozane and tazobactam in plasma and epithelial lining fluid (ELF) in patients with HABP/VABP were used to simulate ceftolozane and tazobactam concentration-time profiles in plasma and ELF over the course of 14 days. The simulations were conducted for patients with normal renal function and for patients receiving adjusted doses for mild, moderate, and severe renal impairment. PTA was calculated using established pharmacokinetic/pharmacodynamic targets for ceftolozane and tazobactam. Across renal function groups, plasma PTA was 100% for ceftolozane and >99% for tazobactam; ELF PTA was >99% for ceftolozane and >87% for tazobactam. These results provided support for the currently recommended ceftolozane/tazobactam dosing regimens for HABP/VABP, which were efficacious and well tolerated in the Ceftolozane-Tazobactam Versus Meropenem for Treatment of Nosocomial Pneumonia (ASPECT-NP) trial.

Monoclonal antibodies (MAbs) are gaining significant momentum as novel therapeutics for infections caused by antibiotic-resistant bacteria. We evaluated the mechanism by which anti-bacterial MAb therapy protects against Acinetobacter baumannii infections. Anti-capsular MAb enhanced macrophage opsonophagocytosis and rescued mice from lethal infections by harnessing complement, macrophages, and neutrophils, yet the degree of bacterial burden did not correlate with survival. Furthermore, MAb therapy reduced pro-inflammatory (IL-1β, IL-6, TNFα) and anti-inflammatory (IL-10) cytokines, which correlated inversely with survival. Although disrupting IL-10 abrogated the survival advantage conferred by the MAb, IL-10-knockout mice treated with MAb could still survive if TNFα production was suppressed directly (via anti-TNFα neutralizing antibody) or indirectly (via macrophage depletion). Thus, even for a MAb that enhances microbial clearance via opsonophagocytosis, clinical efficacy required modulation of pro- and anti-inflammatory cytokines. These findings may inform future MAb development targeting bacteria that trigger the sepsis cascade.

OBJECTIVE: Neonatal sepsis is a clinical condition that results in serious morbidity and mortality unless urgently diagnosed and treated. Obtaining the results of blood cultures to determine the causative agent in sepsis is a time-consuming process. The CRP/albumin ratio is an inflammatory marker that has started to be used in recent years. The aim of our study was to investigate the relationship between CRP/albumin and Gram-negative bacterial sepsis in neonates.
METHODS: This study was conducted on 112 premature neonates with sepsis. The patients were divided into two groups according to culture results as Gram-negative and Gram-positive bacterial sepsis. The laboratory and demographic features of the patients were obtained from the hospital records. A receiver operating characteristic curve was plotted to evaluate the predictive value of the CRP/albumin ratio for Gram-negative sepsis.
RESULTS: CRP/albumin was significantly higher in the Gram-negative group (p<0.001). According to the receiver operating characteristic curve, the optimal cut-off value of CRP/albumin for the prediction of Gram-negative sepsis was >35.17, which had a specificity of 97% and sensitivity of 56% (AUC=0.839; 95% CI: 0.743-0.944; p<0.001). A multivariate logistic regression analysis revealed that CRP/albumin (OR=1.082, 95% CI: 1.033-1.134, p=0.001) and absolute neutrophil count (OR=1.145, 95% CI: 1.000-1.312, p=0.049) were still associated with Gram-negative sepsis after adjustment for variables found to be statistically significant in univariate analysis and correlated with Gram-negative sepsis.
CONCLUSIONS: The CRP/albumin ratio is independently related to Gram-negative sepsis in neonatal sepsis and may be useful in predicting Gram-negative bacteremia.

Novel cyclic peptide derivatives based on ogipeptins A, B, C, and D were synthesized. Starting with a mixture of ogipeptins A-D, a practical four-step synthetic procedure was followed to prepare novel derivatives with various kinds of acyl side chains. Among the 45 new synthetic derivatives identified, the antibacterial activities of compounds 8-3 and 8-38 were comparable with those of ogipeptin A. In in vitro nephrotoxicity screening using LLC-PK1 cells, compounds 8-3 and 8-38 showed significantly lower cytotoxicity (LD20 > 480 μM) than colistin (LD20 = 44.2 μM).

BACKGROUND: Neisseria elongata (NE), a Gram-negative, rod-shaped organism, was previously thought to be non-pathogenic. However, in recent years it has become increasingly recognized as a rare cause of infective endocarditis. In this paper, we report a case of NE infective endocarditis and provide a review of the literature.
OBJECTIVE: To describe a case of NE endocarditis, and to review the literature in search of any similar cases of this rare condition.
METHODS: Our patient is a 77-year-old, otherwise healthy female patient who was found to have mitral valve endocarditis with valve regurgitation.
CONCLUSIONS: NE endocarditis is a rare condition that typically affects the left cardiac chambers and is associated with high risk of embolization. A literature review retrieved 35 other cases.
CONCLUSIONS: Our report underlines the rarity of NE endocarditis, insofar as relatively few cases have been reported. The bacterium presents similarities with HACEK organisms and can potentially cause infective endocarditis.