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Background: Polymyxin B (PMB)-based combination therapies are used to treat severe carbapenem-resistant gram-negative bacterial (CR-GNB) infections. This observational study investigated the relationship between clinical factors, including PMB concentration, and clinical efficacy and safety. Patients and Methods: Polymyxin B regimens were optimized through therapeutic drug monitoring (TDM) and area under the concentration-time curve (AUC). In all, 382 samples were tested from 130 patients. Logistic regression was used to analyze the relationships between variables with clinical efficacy and 30-day mortality factors were analyzed by Cox regression. The sensitivity and specificity of Cmin and AUC for the occurrence of acute kidney injury (AKI) were determined by ROC curve analysis. Results: The clinical effectiveness of PMB was 65.4%. Multivariate logistic regression analysis revealed that lung infection, continuous renal replacement therapy, and C-reactive protein were independent factors significantly associated with efficacy. AKI occurred in 14.6% of the patients during treatment; age > 73 years (OR: 3.63; 95% CI: 1.035– 12.727; P = 0.044), Cmin greater than 2.3 μg/mL (OR: 7.37; 95% CI: 1.571– 34.580; P = 0.011), combined vancomycin (OR: 9.47; 95% CI: 1.732– 51.731; P = 0.009), and combined piperacillin-tazobactam (OR: 21.87; 95% CI: 3.139– 152.324; P = 0.002) were independent risk factors. The identified PMB cut-offs for predicting AKI were Cmin = 2.3 μg/mL and AUC = 82.0 mg h/L. Conclusion: Polymyxin B-based combination regimens are effective in treating CR-GNB infections, particularly bloodstream infections, but have shown unsatisfactory for lung infections. Cmin ≥ 2.3 μg /mL and AUC ≥ 82.0 mg h/L may increase PMB-associated AKI incidence. PMB dose should be adjusted based on TDM to ensure efficacy. [ABSTRACT FROM AUTHOR]

In this report, we describe recovery of multiple drug resistance organism resistant to most of the antibiotics with coexistence of ESBL, Carbapenam and AmpC ß-lactamase genes isolated from the bovine clinical endometritisin the Mathura region of India.Sampling involvesuterine discharge collected from 70 postpartum cattle diagnosed with metritis. Out of 62 bacterial isolates recovered, seven were showing carbapenamase resistant phenotype baseddisc diffusion test. MIC testing and phenotypic detection methodconfirmed resistance to imepenam for isolates of Pseudomonas aeruginosa (n=1),E. coli (n=2) and Enterobacter agglomerance (n=1). Multiplex PCR based genotyping confirmed presence Ambler class B Carbapenemase (VIM and IMP), along with TEM and CTX-M type ESBL respectively. All four isolates were phenotypically confirmed as AmpC β-lactamase producers. [ABSTRACT FROM AUTHOR]

Background: With the difficulties in choosing colistin sulfate and polymyxin B sulfate (PBS) for carbapenem-resistant gram-negative bacteria (CR-GNB), we compared the efficacy and safety of these two old polymyxins in treatment of critically ill patients infected with CR-GNB infection. Methods: One hundred four patients infected with CR-GNB in ICU were retrospectively grouped by PBS (68 patients) or colistin sulfate (36 patients). Clinical efficacy including symptoms, inflammatory parameters, defervescence, prognosis and microbial efficacy were analyzed. Hepatotoxicity, nephrotoxicity, and hematotoxicity were evaluated by TBiL, ALT, AST, creatinine, and thrombocytes. Results: Demographic characteristics between colistin sulfate and PBS were not significantly different. Most of the CR-GNB were cultured in respiratory tract (91.7% vs 86.8%), and almost all were polymyxin-sensitive (98.2% vs 100%, MIC ≤ 2 μg/ml). The microbial efficacy in colistin sulfate (57.1%) was significantly higher than PBS (30.8%) (p = 0.022), however, no significant difference in clinical success was seen in both groups (33.8% vs 41.7%), as well as mortality, defervescence, imaging remission, days in the hospital, microbial reinfections, and prognosis, and almost all patients defervesce within 7 days (95.6% vs 89.5%). Conclusions: Both polymyxins can be administrated in critically ill patients infected with CR-GNB and colistin sulfate is superior to PBS in microbial clearance. These results highlight the necessity of identifying CR-GNB patients who may benefit from polymyxin and who are at higher risk of mortality. [ABSTRACT FROM AUTHOR]

Background: Adverse reactions, especially nephrotoxicity, are great concerns of intravenous colistin treatment. The role of substitutive nebulized colistin in treating nosocomial pneumonia caused by carbapenem-resistant Gram-negative bacterial (CR-GNB) in critically ill patients remains unknown. Methods: This retrospective study enrolled patients with nosocomial pneumonia caused by colistin-susceptible CRGNB in the intensive care unit (ICU) without intravenous colistin treatment. Patients were categorized based on whether substitutive nebulized colistin was used alongside other intravenous antibiotics. Clinical responses and mortality rates were compared between the two groups in the original and propensity score (PS)-matched cohorts. This study aimed to investigate the clinical effectiveness of substitutive nebulized colistin in treatment outcomes of nosocomial pneumonia caused by CR-GNB. The impact of dosing strategy of nebulized colistin was also explored. Results: In total, 343 and 214 patients with and without substitutive nebulized colistin, respectively, were enrolled for analysis. In the PS-matched cohort, clinical failure rates on day 7 (22.6 vs. 42.6%, p = 0.001), day 14 (27.0 vs. 42.6%, p = 0.013), and day 28 (27.8 vs. 41.7%, p = 0.027) were significantly lower in patients with nebulized colistin. In multivariate analysis, nebulized colistin was an independent factor associated with lower day 14 clinical failure (Original cohort: adjusted odds ratio (aOR) 0.45, 95% confidence interval (CI) 0.30–0.67; PS-matched cohort: aOR 0.48, 95% CI 0.27–0.87). There were no differences in clinical failure rate and mortality rate between patients receiving high (> 6 MIU/day) and low (≤ 6 MIU/day) dose nebulized colistin in the PS-matched cohort. Conclusions: In ICU-admitted patients with nosocomial pneumonia caused by colistin-susceptible CRGNB, substitutive nebulized colistin was associated with better clinical outcomes. [ABSTRACT FROM AUTHOR]