This study, conducted over a three-year period at 49 hospitals across the United States, aimed to monitor nosocomial bloodstream infections (BSIs). The study detected over 10,000 BSIs, with gram-positive organisms accounting for 64% of cases, gram-negative organisms for 27%, and fungi for 8%. Coagulase-negative staphylococci, Staphylococcus aureus, and enterococci were the most common pathogens. Enterobacter, Serratia, coagulase-negative staphylococci, and Candida were more prevalent in critical care units, while viridans streptococci were more common in patients with neutropenia. Methicillin resistance was detected in 29% of S. aureus isolates and 80% of coagulase-negative staphylococci, and vancomycin resistance in enterococci varied by species, with 3% of E. faecalis and 50% of E. faecium isolates showing resistance. These findings highlight the importance of targeted empirical therapy for hospital-acquired bacteremia. The study also noted the increasing resistance of pathogens to antimicrobials, particularly methicillin and vancomycin, and the geographic variation in resistance rates.This study, conducted over a three-year period at 49 hospitals across the United States, aimed to monitor nosocomial bloodstream infections (BSIs). The study detected over 10,000 BSIs, with gram-positive organisms accounting for 64% of cases, gram-negative organisms for 27%, and fungi for 8%. Coagulase-negative staphylococci, Staphylococcus aureus, and enterococci were the most common pathogens. Enterobacter, Serratia, coagulase-negative staphylococci, and Candida were more prevalent in critical care units, while viridans streptococci were more common in patients with neutropenia. Methicillin resistance was detected in 29% of S. aureus isolates and 80% of coagulase-negative staphylococci, and vancomycin resistance in enterococci varied by species, with 3% of E. faecalis and 50% of E. faecium isolates showing resistance. These findings highlight the importance of targeted empirical therapy for hospital-acquired bacteremia. The study also noted the increasing resistance of pathogens to antimicrobials, particularly methicillin and vancomycin, and the geographic variation in resistance rates.