What is the recommended treatment for complicated urinary tract infection (UTI) caused by Gram-negative Klebsiella pneumoniae?

From the Guidelines

For complicated UTIs caused by gram-negative Klebsiella, ceftazidime-avibactam or meropenem-vaborbactam are recommended as first-line treatments, with a strong recommendation and moderate certainty of evidence 1. The choice of antibiotic treatment for complicated UTIs caused by gram-negative Klebsiella should be guided by the severity of the infection, the susceptibility of the organism, and the patient's underlying health status.

• For patients with severe infections, ceftazidime-avibactam or meropenem-vaborbactam are recommended as first-line treatments, with a strong recommendation and moderate certainty of evidence 1.
• For patients with less severe infections, alternative options such as piperacillin-tazobactam or cefepime may be considered, with a conditional recommendation and low certainty of evidence 1.
• For patients with infections caused by carbapenem-resistant Enterobacterales (CRE), meropenem-vaborbactam or ceftazidime-avibactam are recommended as first-line treatments, with a conditional recommendation and moderate to low certainty of evidence 1.
• The use of imipenem-relebactam or cefiderocol may also be considered as alternative options, with a conditional recommendation and low certainty of evidence 1. It is essential to note that the treatment of complicated UTIs caused by gram-negative Klebsiella requires careful consideration of the patient's individual needs and the susceptibility of the organism, and should be guided by culture and sensitivity results. Patients should complete the full course of antibiotics even after symptoms improve, maintain adequate hydration, and follow up to ensure resolution of the infection.

From the FDA Drug Label

1. 2 Complicated Urinary Tract Infections, Including Pyelonephritis 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.

Ceftolozane (ZERBAXA) is a suitable option for the treatment of complicated urinary tract infections (cUTI) caused by Gram-negative Klebsiella 2.

• The recommended dosage is 1.5 g (ceftolozane 1 g and tazobactam 0.5 g) administered every 8 hours by intravenous infusion over 1 hour.
• The duration of therapy should be guided by the severity and site of infection and the patient’s clinical and bacteriological progress, with a recommended treatment duration of 7 days for cUTI.

Alternatively, Avibactam (AVYCAZ) in combination with ceftazidime can also be used to treat cUTI caused by Gram-negative Klebsiella 3.

• The recommended dosage is 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered every 8 hours by intravenous infusion over 2 hours.
• The duration of therapy should be guided by the severity and site of infection and the patient’s clinical and bacteriological progress, with a recommended treatment duration of 7 to 14 days for cUTI.

From the Research

Treatment Options for Complicated UTI Caused by Gram-Negative Klebsiella

• The recommended treatment options for complicated UTI caused by Gram-negative Klebsiella include:
  • Nitrofurantoin, fosfomycin, pivmecillinam, fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems 4
  • Ceftazidime-avibactam, meropenem/vaborbactam, imipenem/cilastatin-relebactam, colistin, fosfomycin, aztreonam, and cefiderocol for carbapenem-resistant Enterobacteriales (CRE) 4
• A study compared the efficacy and safety of cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infection caused by Gram-negative uropathogens, including Klebsiella pneumoniae, and found that cefiderocol was non-inferior to imipenem-cilastatin 5
• Another study presented a case of a patient with recurrent, complicated urinary tract infections caused by carbapenem-resistant K. pneumoniae and P. aeruginosa, and discussed the changes in the epidemiology, mechanisms involved, and means of detecting carbapenem resistance in Gram-negative bacilli 6
• A review emphasized the challenge of treating complicated urinary tract infections caused by antimicrobial drug-resistant Gram-negative uropathogens, including Klebsiella 7
• A prospective, investigator-blinded, randomized study compared the efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults, and found that ceftazidime-avibactam may be similar to imipenem-cilastatin in terms of efficacy and safety 8