What is the treatment for Extended-Spectrum Beta-Lactamase (ESBL) positive blood culture?

From the Guidelines

Treatment for ESBL (Extended-Spectrum Beta-Lactamase) positive blood cultures typically requires carbapenems as first-line therapy, with meropenem (1g IV every 8 hours), imipenem (500mg IV every 6 hours), or ertapenem (1g IV daily) being the preferred options for initial treatment, as recommended by recent guidelines 1.

Key Considerations

• Therapy should continue for 7-14 days depending on the source of infection, with longer durations needed for complicated infections.
• While awaiting culture results, empiric coverage with a carbapenem is recommended if ESBL is suspected.
• Alternative options for susceptible ESBL strains include piperacillin-tazobactam (4.5g IV every 6 hours), ceftazidime-avibactam (2.5g IV every 8 hours), or fosfomycin for urinary sources.

Rationale

• ESBL enzymes hydrolyze most beta-lactam antibiotics including penicillins and cephalosporins, but cannot effectively break down carbapenems.
• The recent challenges in the management of Gram-negative MDROs infections, especially in critically ill patients, have revived the clinical use of polymyxins and fosfomycin 1.
• Ceftolozane/tazobactam and ceftazidime/avibactam have recently been approved for the treatment of IAIs, including infection by ESBLs and P. aeruginosa, and may be valuable for treating infections caused by Gram-negative MDROs in order to preserve carbapenems 1.

Special Considerations

• In patients with infections caused by metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE), ceftazidime/avibactam plus aztreonam should be preferred, as recommended by recent guidelines 1.
• Cefiderocol may also be considered as an alternative option for infections caused by MBL-producing CRE, with a conditional recommendation based on moderate certainty of evidence 1.

From the FDA Drug Label

Among Gram-negative uropathogens from both arms of Trial 2, genotypic testing identified certain ESBL groups (e.g., TEM-1, SHV-12, CTX-M-15, CTX-M-27, KPC-2, KPC-3, OXA-48) and AmpC beta-lactamases expected to be inhibited by avibactam in isolates from 273/281 (97. 2%) patients in the mMITT population. Bacteremia at baseline was present in 3. 6% of patients.

The treatment for ESBL blood culture is not directly addressed in the provided drug label. However, avibactam is expected to inhibit certain ESBL groups.

• The drug label does mention bacteremia at baseline, but it does not provide specific treatment recommendations for ESBL blood culture.
• Avibactam is used in combination with ceftazidime for the treatment of complicated urinary tract infections, including pyelonephritis 2. However, the provided information is not sufficient to draw a conclusion about the treatment of ESBL blood culture.

From the Research

ESBL Blood Culture Treatment

• The treatment of bloodstream infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) typically involves the use of carbapenems, such as meropenem and imipenem, as the antibiotics of choice 3.
• However, due to the emergence of carbapenem resistance, alternative treatments are being considered, including cephamycins, fluoroquinolones, and β-lactam/β-lactam inhibitor combinations, such as piperacillin/tazobactam 3, 4.
• Ertapenem is another carbapenem that can be used to treat ESBL-E infections, particularly in patients with less severe presentations, and is recommended to be used at high doses 3, 5.
• A systematic review and meta-analysis found that ertapenem was associated with a significantly lower 30-day mortality compared to other carbapenems, and had a similar clinical efficacy in terms of clinical cure or improvement and microbiological eradication 5.
• Pharmacodynamic profiling of imipenem, meropenem, and ertapenem against clinical isolates of ESBL-producing Escherichia coli and Klebsiella spp. found that all agents achieved high bactericidal cumulative fraction of response, although ertapenem was slightly less effective than imipenem and meropenem 6.

Treatment Options

• Carbapenems, such as meropenem and imipenem, are recommended for the treatment of serious ESBL-E infections 3.
• Alternative treatments, such as cephamycins, fluoroquinolones, and β-lactam/β-lactam inhibitor combinations, can be considered for patients with less severe presentations or for definitive treatment of patients with milder presentations 3, 4.
• Ertapenem can be used to treat ESBL-E infections, particularly in patients with less severe presentations, and is recommended to be used at high doses 3, 5.
• Other treatment options, such as piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam, and cefiderocol, may also be considered, although their use should be guided by local susceptibility patterns and the severity of the infection 4, 7.