What are the empiric antibiotics for sepsis of unknown source?

From the Guidelines

For sepsis of unknown source, empiric antibiotic therapy should include broad-spectrum coverage targeting both gram-positive and gram-negative organisms, including potential resistant pathogens, as recommended by the Surviving Sepsis Campaign guidelines 1. A recommended regimen is a combination of vancomycin (15-20 mg/kg IV every 8-12 hours, adjusted based on renal function and targeting trough levels of 15-20 μg/mL) plus either piperacillin-tazobactam (4.5g IV every 6 hours), cefepime (2g IV every 8 hours), or a carbapenem such as meropenem (1g IV every 8 hours) 1. For patients with beta-lactam allergies, aztreonam (2g IV every 8 hours) plus vancomycin is an alternative 1. In critically ill patients or those with risk factors for resistant organisms, consider adding an aminoglycoside like gentamicin (5-7 mg/kg IV once daily) or amikacin (15-20 mg/kg IV once daily) 1. Therapy should be initiated within one hour of recognizing sepsis, after obtaining appropriate cultures 1. De-escalation should occur within 48-72 hours based on culture results and clinical response 1. This broad initial approach is necessary because delayed appropriate antimicrobial therapy increases mortality in sepsis, while the specific regimen may need adjustment based on local resistance patterns, patient risk factors, recent antibiotic exposure, and organ dysfunction 1. Some key considerations in selecting empiric antimicrobial therapy include the anatomic site of infection, prevalent pathogens within the community and hospital, resistance patterns of those pathogens, and the presence of specific immune defects or risk factors for resistant organisms 1. The use of local and unit-specific antibiograms or infectious diseases consultation can also help guide empiric therapy 1. Ultimately, the goal is to provide effective antimicrobial coverage while minimizing the risk of resistance and adverse effects, and to de-escalate therapy as soon as possible based on clinical response and microbiologic data 1.

From the FDA Drug Label

FORTAZ may be used alone in cases of confirmed or suspected sepsis. Ceftazidime has been used successfully in clinical trials as empiric therapy in cases where various concomitant therapies with other antibacterial drugs have been used FORTAZ may also be used concomitantly with other antibacterial drugs, such as aminoglycosides, vancomycin, and clindamycin; in severe and life-threatening infections; and in the immunocompromised patient. Gentamicin injection may be administered as initial therapy in conjunction with a penicillin-type or cephalosporin-type drug before obtaining results of susceptibility testing In serious infections when the causative organisms are unknown, gentamicin injection may be administered as initial therapy in conjunction with a penicillin-type or cephalosporin-type drug before obtaining results of susceptibility testing

Empiric antibiotics for sepsis of unknown source can include:

• Ceftazidime alone or in combination with other antibacterial drugs
• Gentamicin in conjunction with a penicillin-type or cephalosporin-type drug 2 3

From the Research

Empiric Antibiotics for Sepsis of Unknown Source

• The use of broad-spectrum antimicrobials is essential in the treatment of sepsis, and should be initiated as soon as possible, within the first hour of diagnosis 4, 5.
• The selection of antimicrobial agents should be based on a combination of patient factors, predicted infecting organism(s), and local microbial resistance patterns 5.
• Initial drugs should have activity against typical gram-positive and gram-negative causative micro-organisms, and anaerobic coverage should be provided for intra-abdominal infections or others where anaerobes are significant pathogens 5.
• Empiric antifungal or antiviral therapy may be warranted in certain cases, such as healthcare-associated infections or suspected fungal or viral pathogens 6, 5.
• De-escalation of antimicrobial therapy should be considered as soon as possible, to reduce the risk of antimicrobial resistance and adverse effects 4, 6, 5.
• Specific antimicrobial agents, such as meropenem and piperacillin-tazobactam, have been studied in the treatment of sepsis, and may be effective in certain cases 7, 8.
• The use of biomarkers, such as procalcitonin, may provide decision support for antibiotic use and guide duration of antibiotic therapy 6.