Would a urinary tract infection (UTI) with Klebsiella species resistant to cefazolin (Ancef) respond to ceftriaxone (Rocephin)?

From the Guidelines

A urinary tract infection (UTI) with Klebsiella species resistant to cefazolin may still respond to ceftriaxone, but this is not guaranteed, and the most recent guidelines from 2024 recommend using a third-generation cephalosporin as empirical treatment for complicated UTI with systemic symptoms 1. The effectiveness of ceftriaxone against Klebsiella species resistant to cefazolin depends on various factors, including the specific resistance mechanisms present in the bacteria. Ceftriaxone is a third-generation cephalosporin with broader spectrum activity against gram-negative bacteria compared to cefazolin (a first-generation cephalosporin). However, resistance mechanisms like extended-spectrum beta-lactamases (ESBLs) that affect cefazolin can sometimes affect ceftriaxone as well. Some key points to consider when treating UTIs with resistant bacteria include:

• The use of combination therapy, such as a beta-lactam antibiotic with an aminoglycoside, may be recommended in certain cases 1.
• The European Association of Urology guidelines recommend using a third-generation cephalosporin as empirical treatment for complicated UTI with systemic symptoms 1.
• Antimicrobial susceptibility testing is essential to confirm whether the specific Klebsiella isolate is susceptible to ceftriaxone.
• If susceptible, ceftriaxone can be administered at 1-2 grams intravenously once daily for 7-14 days, depending on infection severity.
• For uncomplicated cases with confirmed susceptibility, oral alternatives like trimethoprim-sulfamethoxazole or fluoroquinolones might be preferable after initial IV therapy, but this should be guided by local resistance patterns and patient-specific factors 1. It's also important to note that the European Society of Clinical Microbiology and Infectious Diseases guidelines provide recommendations for the treatment of infections caused by multidrug-resistant gram-negative bacilli, including the use of carbapenems and other antibiotics 1. In terms of specific treatment recommendations, the guidelines suggest that carbapenems, such as imipenem or meropenem, may be used as targeted therapy for patients with bloodstream infections and severe infections due to third-generation cephalosporin-resistant Enterobacterales 1. However, the use of ceftriaxone for UTIs with Klebsiella species resistant to cefazolin should be guided by antimicrobial susceptibility testing and local resistance patterns, and treatment should be individualized based on patient-specific factors and the severity of the infection.

From the FDA Drug Label

Ceftriaxone has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria. The following in vitro data are available, but their clinical significance is unknown At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ceftriaxone. Gram-negative bacteria Klebsiella pneumoniae

A UTI with Klebsiella species resistant to cefazolin may still respond to ceftriaxone, as ceftriaxone has activity against Klebsiella pneumoniae.

• Key points:
  • Ceftriaxone has a broad spectrum of activity against Gram-negative bacteria, including Klebsiella species.
  • The drug label does not provide direct information on the effectiveness of ceftriaxone against cefazolin-resistant Klebsiella species.
  • However, based on the available in vitro data, it is possible that ceftriaxone may still be effective against these bacteria 2. However, clinical significance is unknown, and the efficacy of ceftriaxone in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

From the Research

Urinary Tract Infections with Klebsiella Species

• A urinary tract infection (UTI) with Klebsiella species resistant to cefazolin (Ancef) may respond to ceftriaxone (Rocephin), as ceftriaxone has been shown to be effective against Klebsiella species in various studies 3, 4.
• However, the use of ceftriaxone may increase the risk of hospital-onset Clostridioides difficile infection (HOCDI) compared to cefazolin 4.
• Cefazolin may be a suitable alternative to ceftriaxone for the treatment of UTIs caused by Klebsiella species, especially in cases where the isolate is susceptible to cefazolin 5, 6.

Antibiotic Resistance and Treatment Implications

• Klebsiella species are known to be resistant to penicillins and can acquire resistance to third- and fourth-generation cephalosporins, including cefazolin and ceftriaxone, due to the production of extended-spectrum beta-lactamases (ESBLs) 3.
• The use of ceftriaxone may select for ESBL-producing Klebsiella species, which can limit treatment options 3, 5.
• New antibiotic drugs, such as cefiderocol, meropenem-vaborbactam, ceftazidim-avibactam, and imipenem-relebactam, may be effective against Klebsiella pneumoniae carbapenemase-producers (KPCp) UTIs, but more research is needed to determine the best treatment strategy 7.

Treatment Considerations

• The choice of antibiotic for the treatment of UTIs caused by Klebsiella species should be based on local susceptibility data and the patient's individual needs 4, 6.
• Cefazolin may be a suitable option for the treatment of UTIs caused by Klebsiella species that are susceptible to cefazolin, but ceftriaxone may be necessary in cases where the isolate is resistant to cefazolin 5, 6.
• The use of combination therapy, such as the combination of a beta-lactam antibiotic with an aminoglycoside, may be beneficial in the treatment of severe UTIs caused by Klebsiella species 3.