What antibiotics are recommended for sepsis of unknown origin in a patient with a penicillin (Penicillin) allergy?

From the Guidelines

For sepsis of unknown origin in a patient with penicillin allergy, I recommend using a combination of vancomycin plus either aztreonam or a fluoroquinolone (such as ciprofloxacin or levofloxacin). Vancomycin typically dosed at 15-20 mg/kg IV every 8-12 hours provides coverage against gram-positive organisms including MRSA, while aztreonam (1-2g IV every 6-8 hours) or a fluoroquinolone covers gram-negative pathogens 1. For patients with severe penicillin allergies (anaphylaxis), avoid cephalosporins due to potential cross-reactivity. In critically ill patients, consider adding an aminoglycoside like gentamicin (5-7 mg/kg IV daily) for broader gram-negative coverage. Alternatively, linezolid (600mg IV twice daily) can replace vancomycin, particularly in patients with renal impairment. Carbapenems like meropenem may be used in less severe penicillin allergies. These regimens should be initiated immediately after obtaining blood cultures and before source identification. Once culture results return, narrow therapy appropriately. This broad-spectrum approach ensures coverage of most potential pathogens while avoiding beta-lactams in penicillin-allergic patients.

Some key points to consider:

• The Surviving Sepsis Campaign guidelines recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage) 1.
• The guidelines also recommend daily assessment for de-escalation of antimicrobial therapy in patients with sepsis and septic shock 1.
• For patients with severe penicillin allergies, a combination of ciprofloxacin plus clindamycin or aztreonam plus vancomycin is recommended 1.
• The use of procalcitonin levels can be used to support shortening the duration of antimicrobial therapy in sepsis patients 1.

The recommended regimen should be based on the most recent and highest quality evidence, which in this case is the Surviving Sepsis Campaign guidelines from 2016 1.

From the Research

Antibiotic Recommendations for Sepsis of Unknown Origin in Penicillin-Allergic Patients

• For patients with a penicillin allergy, most beta-lactams may be safely used, with the possible exception of first-generation and second-generation cephalosporins 2.
• Vancomycin can be used to treat sepsis, especially in cases where methicillin-resistant Staphylococcus aureus (MRSA) is suspected, and a high dose may be required to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets 3.
• In patients with penicillin allergy, alternative antibiotics such as doxycycline can be effective in treating certain infections, including those caused by Eikenella corrodens and Actinomyces odontolyticus 4.
• Initial empiric therapy for sepsis should be directed against the resident flora of the organ primarily involved in the infectious process, and monotherapy with an antibiotic of the appropriate spectrum is often adequate 5.
• The selection of antibiotics should consider the risk of multidrug-resistant (MDR) pathogens, and individualized dosing should be used to optimize treatment outcomes 6.

Considerations for Antibiotic Selection

• The degree of organ dysfunction, underlying medical conditions, and physiologic abnormalities are important prognostic factors, but are not crucial in initial antibiotic selection 5.
• Blood cultures should be obtained in all patients to guide antibiotic therapy, and methods should be employed for the early detection of septicemia 5.
• Reevaluation of duration and appropriateness of treatment at regular intervals is necessary, and de-escalation and shortened courses of antimicrobials should be considered for most patients 6.