Abstract
Background Sickle cell disease (SCD) is highly prevalent among India's tribal populations, with infections being a major cause of morbidity and mortality. Current data on causative pathogens, antimicrobial resistance patterns, and clinical predictors of outcomes in Indian SCD patients remain limited. This study aims to characterize the clinical and microbiological profile of infections in hospitalized SCD patients and identify predictors of adverse outcomes. Methods An ambispective observational study was conducted at a tertiary care center in central India from December 2018 to December 2021 (retrospective phase, n=61) and January 2022 to June 2023 (prospective phase, n=150), totaling 211 SCD patients with confirmed infections. Data were analyzed using IBM SPSS Statistics software, version 25.0 (IBM Corp., Armonk, NY). An exploratory secondary analysis developed a preliminary risk score for predicting adverse outcomes using multivariate logistic regression and receiver operating characteristic (ROC) curve analysis. Results Among 211 hospitalized SCD patients (median age 21 years, range two to 65 years), respiratory infections were most common (34.6%), followed by acute undifferentiated febrile illness (19.9%), bone and joint infections (9.5%), and bloodstream infections (9%). Among 32 gram-negative isolates, 50% were extended-spectrum β-lactamase (ESBL) producers with 100% susceptibility to polymyxins. Fever was present in 86.7% of patients. Procalcitonin levels >2 ng/mL were significantly associated with adverse outcomes (p=0.04). Overall mortality was 6.6% (14 deaths), with respiratory infections accounting for the highest number of deaths (8/73, 11.0%). An exploratory SCD Infection Risk Score (SCD-IRS) incorporating age, hemoglobin level, total leucocyte count, and procalcitonin demonstrated moderate discriminative ability with an area under the curve (AUC) of 0.78 (95% CI: 0.65-0.91, p<0.001) but lacks internal validation due to sample size constraints. Conclusions Respiratory infections predominate among hospitalized SCD patients in central India. High antimicrobial resistance poses significant treatment challenges. Elevated procalcitonin levels (>2 ng/mL) are significantly associated with adverse outcomes. The preliminary SCD-IRS shows potential for risk stratification but is strictly exploratory and requires validation in larger, multi-institutional studies before any clinical application. Strengthening vaccination coverage, implementing antimicrobial stewardship programs, and developing validated risk assessment tools are essential to reduce infection-related morbidity and mortality in this vulnerable population.