Safe and effective use of colistin requires robust pharmacokinetic (PK) and pharmacodynamic (PD) data to guide dosing. To evaluate the pharmacokinetics of colistimethate sodium and colistin in critically ill patients and correlate with clinical efficacy and renal function. Twenty critically ill adult patients with colistin-susceptible multidrug-resistant (MDR) infections and normal renal function treated with intravenous colistimethate sodium - at a 9 million units (270 mg CBA) loading dose followed by maintenance (MD) of 3 million units t.i.d, 24 hours later - were evaluated for clinical cure (CC) at the end of therapy. Patient characteristics and plasma colistin levels at 0, 0.5, 1, 2, 4, 8 and 12 hours after the loading dose and at 1, 2 and 8 hours after the eighth and ninth infusion of MD were evaluated. Colistimethate sodium and colistin levels were measured by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Among the 20 patients who were evaluated, 60% had pneumonia. Predominant pathogens were Klebsiella pneumoniae and Acinetobacter spp. Clinical cure was 50% (10/20). Mean peak loading dose concentrations were 3 ± 1.1 mg/L (1.75-5.14) and 2.37 ± 1.2 mg/L (1.52-5.54) for 'cure' and 'failure' groups, respectively (p = 0.13), while mean steady-state (Cssavg) concentrations were 2.25 ± 1.3 mg/L and 1.78 ± 1.1 mg/L in 'cure' and 'failure' groups, respectively (p = 0.19). Nephrotoxicity was 5% on day 7 of therapy. However, bacteriological cure could not be correlated with PK/PD. Subtherapeutic Cssavg with clinical failure and lower efficacy without significant nephrotoxicity highlights the need for therapeutic drug monitoring to guide colistin dosing.

The study aims to characterize community-acquired sepsis patients admitted to our 1300-bedded tertiary care hospital in South India from the Surviving Sepsis Campaign (SSC) guideline-compliant e-sepsis registry stratified by focus of infection. The prospective observational study recruited 1009 adult sepsis patients presenting to the emergency department at the center based on Sepsis-2 criteria for a period of three years. Of the patients, 41% were between 61 and 80 years with a mean age of 57.37 ± 13.5%. A total of 13.5% (136) was under septic shock and in-hospital mortality for the study cohort was 25%. The 3 h and 6 h bundle compliance rates observed were 37% and 49%, respectively, without significant survival benefits. Predictors of mortality among patients with bloodstream infections were septic shock (p = 0.01, OR 2.4, 95% CI 1.23–4.79) and neutrophil-to-lymphocyte ratio (p = 0.008, OR 1.01, 95% CI 1.009–1.066). The presence of Acinetobacter (p = 0.005, OR 4.07, 95% CI 1.37–12.09), Candida non-albicans (p = 0.001, OR16.02, 95% CI 3.0–84.2) and septic shock (p = 0.071, OR 2.5, 95% CI 0.97–6.6) were significant predictors of mortality in patients with community-acquired pneumonia. The registry has proven to be a key data source detailing regional microbial etiology and clinical outcomes of adult sepsis patients, enabling comprehensive evaluation of regional community-acquired sepsis to tailor institutional sepsis treatment protocols.

Background: Sepsis, a life-threatening condition characterized by a dysregulated immune response to infection, remains a significant clinical challenge globally. This study aims to enhance the predictive accuracy of existing sepsis severity scores by developing augmented versions of the SOFA and SAPS-III models, termed Pro-SOFA and Pro-SAPS, through the integration of biomarkers procalcitonin (PCT), neutrophil-tolymphocyte ratio (NLR), and C-reactive protein (CRP). Methods: This prospective observational study was conducted in the medical ICU of a tertiary care hospital in southern India from August 2022 to December 2023. A total of 301 adult patients suspected or confirmed to have sepsis were assessed for eligibility, with 171 patients completing the study. Demographic and clinical data were collected; SOFA and SAPS-III scores were calculated and augmented with PCT, NLR, and CRP to develop Pro-SOFA and Pro-SAPS models. The performance of these models was evaluated using Brier scores, AUC, and net reclassification index (NRI). Results: The augmented Pro-SOFA and Pro-SAPS models demonstrated superior predictive accuracy compared to their original counterparts. The Brier scores for Pro-SOFA and Pro-SAPS were 0.181 and 0.165, respectively, indicating better calibration than the original scores. The Pro- SAPS showed significant improvement over the original SAPS-III score (NRI = 0.50, SE = 0.14, p < 0.01). Similarly, Pro-SOFA outperformed the original SOFA (NRI = 0.49, SE = 0.13, p < 0.01). Conclusion and clinical significance: Integrating PCT, CRP, and NLR with SOFA and SAPS-III scores to develop Pro-SOFA and Pro-SAPS significantly improves the predictive accuracy for sepsis mortality and can thus potentially improve sepsis outcomes.