Introduction: Infections involving bacteria in the bloodstream pose a significant public health risk, potentially progressing to sepsis, which is often fatal. Staphylococcus aureus and Escherichia coli are recurrent pathogens in these infections, and effective treatment depends on the proper choice of antibiotics due to the growing issue of antimicrobial resistance. Objectives: The aim of this study was to evaluate the clinical management of bacteremias caused by E. coli and S. aureus. Methodology: This is a literature review study that used the PubMed and Virtual Health Library (VHL) databases, employing the following descriptors: bacteremia AND antibiotics AND Staphylococcus aureus OR Escherichia coli. Results: The search yielded a total of 394 articles, and after applying the selection and exclusion criteria, 9 articles were deemed eligible. It was observed that the treatment for methicillin-sensitive S. aureus includes penicillinase-resistant semi-synthetic penicillins, first-generation cephalosporins, and daptomycin. Beta-lactam anti-staphylococcal therapy is effective for methicillin-sensitive S. aureus, but combining it with daptomycin did not show additional benefits, as it did not reduce mortality or recurrence. For methicillin-resistant S. aureus cases, vancomycin or daptomycin is recommended. The combination of daptomycin with fosfomycin showed a 12% higher success rate, but without statistical significance. Ceftobiprole showed efficacy similar to that of daptomycin in treating complicated S. aureus bacteremias, with a success rate of 69.8%, making it an effective alternative. In bacteremias caused by E. coli producing extended-spectrum β-lactamases, carbapenems such as meropenem are the standard treatment. Fosfomycin is an alternative, but it is not superior to meropenem. Piperacillin–tazobactam demonstrated comparable efficacy to carbapenems, provided that the co-production of OXA-1 by E. coli was rare. Conclusions: The management of bacteremias caused by S. aureus and E. coli requires continuous monitoring of antimicrobial resistance and therapeutic efficacy. New treatments and approaches are crucial to address the growing threat of these infections.