What antibiotic should be used to treat a patient in septic shock with ESBL (Extended-Spectrum Beta-Lactamase) Klebsiella infection?

From the Guidelines

For a patient in septic shock with ESBL Klebsiella infection, carbapenems are the first-line treatment, specifically meropenem (1g IV every 8 hours), imipenem-cilastatin (500mg IV every 6 hours), or ertapenem (1g IV daily). These antibiotics should be administered immediately after obtaining blood cultures. Carbapenems are recommended because ESBL-producing organisms are resistant to most beta-lactam antibiotics including penicillins and cephalosporins 1. In cases of carbapenem allergy, alternatives include ceftazidime-avibactam (2.5g IV every 8 hours) or a combination of a polymyxin (colistin or polymyxin B) with an aminoglycoside 1.

Some key points to consider in the management of septic shock with ESBL Klebsiella infection include:

• The importance of early and appropriate antibiotic therapy, with the goal of administering effective IV antimicrobials within the first hour of recognition of septic shock 1
• The need for source control through drainage of any identified infection source 1
• The importance of adjusting antibiotic therapy based on culture results and susceptibility testing, typically continuing for 7-14 days depending on clinical response 1
• The consideration of alternative antibiotics in cases of carbapenem allergy or resistance, such as ceftazidime-avibactam or combinations of polymyxins with aminoglycosides 1

It's also important to note that the management of septic shock with ESBL Klebsiella infection requires a comprehensive approach, including fluid resuscitation, vasopressor support, and other supportive care measures as needed 1.

In terms of specific antibiotic regimens, the following options may be considered:

• Meropenem (1g IV every 8 hours) or imipenem-cilastatin (500mg IV every 6 hours) as first-line therapy 1
• Ceftazidime-avibactam (2.5g IV every 8 hours) as an alternative in cases of carbapenem allergy or resistance 1
• Combinations of polymyxins (colistin or polymyxin B) with aminoglycosides as an alternative in cases of carbapenem allergy or resistance 1

Overall, the management of septic shock with ESBL Klebsiella infection requires a prompt and effective approach, with a focus on early and appropriate antibiotic therapy, source control, and supportive care measures as needed.

From the FDA Drug Label

ZERBAXA is indicated for the treatment of adult and pediatric patients (birth to less than 18 years old) with complicated intra-abdominal infections (cIAI) caused by the following susceptible Gram-negative and Gram-positive microorganisms: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius. ZERBAXA is indicated for the treatment of adult and pediatric patients (birth to less than 18 years old) with complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. ZERBAXA is indicated for the treatment of adult patients (18 years and older) with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the following susceptible Gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens.

The patient in septic shock with ESBL Klebsiella infection should be treated with ZERBAXA (ceftolozane/tazobactam), as it is effective against Klebsiella pneumoniae, which is a susceptible microorganism. The recommended dosage for an adult patient with normal renal function is 1.5 g every 8 hours for complicated intra-abdominal infections or complicated urinary tract infections, and 3 g every 8 hours for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. However, the dosage may need to be adjusted based on the patient's renal function. 2

Key points:

• ZERBAXA is effective against ESBL-producing Klebsiella pneumoniae.
• The recommended dosage varies depending on the type of infection and the patient's renal function.
• Dosage adjustments may be necessary for patients with renal impairment.

From the Research

Treatment Options for ESBL Klebsiella Infection in Septic Shock

• The choice of antibiotic for treating a patient in septic shock with ESBL (Extended-Spectrum Beta-Lactamase) Klebsiella infection should be based on sound clinical judgement and knowledge of antimicrobials used 3.
• Carbapenems are the primary treatment strategy for invasive infections caused by ESBL bacteria, but combination therapy with a carbapenem and an aminoglycoside such as amikacin may be effective against KPC-producing Klebsiella pneumoniae 4.
• Studies have shown that the combination of meropenem or imipenem with amikacin can achieve synergistic activity and bactericidal activity against KPC-3-producing K. pneumoniae isolates 4.
• The use of a definitive therapy with at least two antibiotics displaying in vitro activity against the KPC-Kp isolates was the most important determinant of favourable outcome in patients with KPC-Kp infection 5.
• High-dose combination therapy with imipenem and amikacin has been successfully used to treat a patient with septic shock due to Carbapenem-resistant Klebsiella pneumoniae carrying multiple resistance genes 6.
• Newer antibiotics such as ceftazidime/avibactam may also be effective against carbapenem-resistant Enterobacteriaceae, including KPC-producing Klebsiella pneumoniae 7.

Key Considerations

• The selection of appropriate antibiotics should be based on the type of microorganisms or suspected organism being treated, as well as knowledge of resistant organisms in the community and hospital 3.
• Combination therapy with a beta-lactam antibiotic and an aminoglycoside may be effective against ESBL-producing bacteria, but the choice of antibiotics should be guided by in vitro susceptibility testing and clinical experience 4, 5.
• The use of high-dose antibiotics and combination therapy may be necessary to achieve optimal outcomes in patients with septic shock due to resistant bacteria 6.