Background: Up to one-third of brucellosis patients develop focal organ involvement, contributing to increased morbidity and therapeutic failure, yet no clinically validated instrument exists to stratify risk at presentation. Methods: In this three-center retrospective cohort from Türkiye (2015–2025), 355 adults with confirmed brucellosis were enrolled. Thirty-two candidate variables spanning demographics, comorbidities, symptoms, routine laboratory values, and composite inflammation indices underwent LASSO-penalized regression with 10-fold cross-validation for predictor selection, after which a nomogram was constructed and internally validated via 1000-iteration bootstrap resampling. Results: Ninety-two patients (25.9%) developed focal complications. Five predictors were retained by LASSO—prognostic nutritional index (PNI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), chronic disease stage, and hypertension—and combined with age and sex (retained a priori) into a seven-predictor nomogram. PNI was the strongest contributor (OR = 0.901, 95% CI: 0.857–0.948). Apparent C-statistic reached 0.782 (optimism-corrected 0.762), with a calibration slope of 0.894 and Brier score of 0.154. Decision curve analysis indicated net clinical benefit over the 5–55% threshold probability range. Conclusions: This PNI-anchored LASSO nomogram offers a practical bedside risk stratification instrument for brucellosis-related focal involvement. Prospective external validation across geographically diverse endemic regions is warranted before clinical adoption.

Outpatient parenteral antimicrobial therapy (OPAT) is a well-established, cost-effective treatment modality delivered through structured, multidisciplinary