What is the recommended treatment for a patient with an Extended-Spectrum Beta-Lactamase (ESBL)-positive culture?

From the Guidelines

The recommended treatment for a patient with an Extended-Spectrum Beta-Lactamase (ESBL)-positive culture is typically a carbapenem antibiotic, such as meropenem or imipenem-cilastatin, due to their reliability in treating serious ESBL infections.

Key Considerations

• Carbapenems, including meropenem (1g IV every 8 hours) and imipenem-cilastatin (500mg IV every 6 hours), are the preferred choice for treating ESBL-positive infections because ESBL enzymes cannot hydrolyze carbapenems 1.
• For less severe infections, alternatives may include fosfomycin, nitrofurantoin, or pivmecillinam, but these should be chosen based on susceptibility testing and the specific infection site and severity.
• Other options, such as amikacin, tigecycline, or ceftazidime-avibactam, may be considered in certain cases, especially when susceptibility testing indicates their effectiveness against the specific ESBL-producing organism 1.

Treatment Duration and Stewardship

• Treatment duration typically ranges from 7-14 days, depending on the infection site and severity.
• It is essential to obtain cultures and susceptibility testing before initiating therapy when possible to guide the choice of antibiotic and to practice antimicrobial stewardship by de-escalating to narrower-spectrum agents if susceptibility allows 1.

Resistance and Therapy

• ESBL-producing organisms are resistant to most penicillins, cephalosporins, and aztreonam due to their ability to hydrolyze the beta-lactam ring in these antibiotics, which is why carbapenems remain the most reliable option for serious infections 1.

Newer Antibiotics

• Newer antibiotics like ceftolozane/tazobactam and ceftazidime/avibactam have been approved for treating complicated intra-abdominal infections, including those caused by ESBL-producing Enterobacteriaceae and P. aeruginosa, and may offer valuable alternatives to carbapenems in preserving their effectiveness 1.

From the FDA Drug Label

1. 1 Intra-abdominal Infections Piperacillin and Tazobactam for Injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of appendicitis (complicated by rupture or abscess) and peritonitis caused by beta-lactamase producing isolates of Escherichia coli
2. 2 Nosocomial Pneumonia Piperacillin and Tazobactam for Injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of nosocomial pneumonia (moderate to severe) caused by beta-lactamase producing isolates of Staphylococcus aureus and by piperacillin and tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.

The recommended treatment for a patient with an ESBL-positive culture is to use piperacillin-tazobactam if the isolate is susceptible to it.

• The dosage for adult patients with indications other than nosocomial pneumonia is 3.375 grams every six hours.
• The dosage for adult patients with nosocomial pneumonia is 4.5 grams every six hours plus an aminoglycoside. 2

From the Research

Treatment Options for ESBL-Positive Cultures

The recommended treatment for a patient with an Extended-Spectrum Beta-Lactamase (ESBL)-positive culture depends on various factors, including the type of infection, the causative organism, and the patient's medical history.

• Carbapenems, such as meropenem and imipenem, are often considered the primary treatment option for invasive infections caused by ESBL-producing bacteria 3.
• However, some studies suggest that ertapenem, a carbapenem, can be used as an alternative to group 2 carbapenems for the treatment of infections caused by ESBL-producing gram-negative organisms 4, 5.
• Combination therapy, such as meropenem or imipenem with amikacin, may also be effective against ESBL-producing bacteria, particularly in cases where carbapenem resistance is a concern 3, 6.
• Piperacillin-tazobactam, in combination with amikacin, may be a potential carbapenem-sparing regimen for the treatment of urosepsis caused by ESBL-producing Escherichia coli 6.
• For non-bacteremic urinary tract infections (UTIs) due to ESBL-producing Enterobacteriaceae, piperacillin-tazobactam may be an effective alternative to carbapenems 7.

Key Considerations

• The choice of treatment should be guided by the results of antimicrobial susceptibility testing and the patient's clinical response to therapy.
• Combination therapy may be necessary to achieve synergistic activity against ESBL-producing bacteria.
• The potential for carbapenem resistance should be considered when selecting a treatment regimen.
• Further studies are needed to fully evaluate the efficacy of alternative treatment regimens, such as piperacillin-tazobactam, for the treatment of ESBL-positive infections.