What is a suitable antibiotic for a patient with sepsis and a urinary tract infection (UTI) caused by gram-negative rods?

From the Guidelines

For a patient with sepsis and a UTI with gram-negative rods on culture, I recommend starting with a carbapenem, such as imipenem or meropenem, as targeted therapy, as suggested by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines 1. This approach is based on the strongest and most recent evidence, which prioritizes the use of carbapenems for patients with bloodstream infections (BSI) and severe infections due to third-generation cephalosporin-resistant Enterobacterales (3GCephRE). The guidelines suggest that for patients with BSI and severe infection due to 3GCephRE, a carbapenem (imipenem or meropenem) should be used as targeted therapy, with a strong recommendation and moderate level of evidence 1. Some key points to consider when treating a patient with sepsis and a UTI with gram-negative rods on culture include:

• The importance of starting with a broad-spectrum antibiotic, such as a carbapenem, to rapidly control the infection before the specific pathogen is identified
• The need to narrow therapy to a more targeted antibiotic once culture and sensitivity results are available
• The consideration of antibiotic stewardship principles to minimize the risk of resistance and optimize treatment outcomes
• The use of combination therapy in certain cases, such as for patients with severe infections caused by carbapenem-resistant Enterobacterales (CRE) carrying metallo-b-lactamases and/or resistant to all other antibiotics It is also important to note that the ESCMID guidelines suggest that ertapenem may be used instead of imipenem or meropenem for patients with BSI due to 3GCephRE without septic shock, with a conditional recommendation and moderate level of evidence 1. Additionally, the guidelines recommend against the use of tigecycline for infections caused by 3GCephRE, with a strong recommendation and very low level of evidence 1. Overall, the choice of antibiotic therapy for a patient with sepsis and a UTI with gram-negative rods on culture should be guided by the most recent and highest-quality evidence, with consideration of the specific clinical context and the principles of antibiotic stewardship.

From the FDA Drug Label

Gentamicin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species and Staphylococcus species (coagulase-positive and coagulase-negative) Clinical studies have shown gentamicin injection to be effective in bacterial neonatal sepsis; bacterial septicemia and serious bacterial infections of the central nervous system (meningitis), urinary tract, respiratory tract, gastrointestinal tract (including peritonitis), skin, bone and soft tissue (including burns) Gentamicin injection may be considered as initial therapy in suspected or confirmed gram-negative infections, and therapy may be instituted before obtaining results of susceptibility testing

Gentamicin may be a suitable antibiotic for a patient with sepsis and a UTI with gram-negative rods on culture, as it is effective against serious infections caused by susceptible strains of gram-negative microorganisms, including those that can cause UTIs and sepsis 2.

• It is essential to obtain specimens for bacterial culture to determine the susceptibility of the causative organisms to gentamicin.
• The decision to continue therapy with gentamicin should be based on the results of susceptibility tests, the severity of the infection, and other important considerations.

From the Research

Antibiotic Options for Sepsis and UTI with Gram-Negative Rods

• For a patient with sepsis and a urinary tract infection (UTI) caused by gram-negative rods, the choice of antibiotic is crucial 3, 4.
• The latest evidence suggests that new antimicrobials, including β-lactam/β-lactamase inhibitor combinations, such as ceftolozane-tazobactam, imipenem-relebactam, or meropenem-vaborbactam, and cephalosporins, such as cefiderocol, can be effective against gram-negative bacteria 3.
• Piperacillin-tazobactam is also an option for treating Pseudomonas aeruginosa infections, and extended-infusion dosing strategies may improve clinical outcomes 5.

Considerations for Antibiotic Choice

• The decision to use empirical anti-pseudomonal treatment should be based on the patient's risk factors, such as severe immunodeficiency, age, recent antimicrobial therapy, and the presence of a central venous catheter or urinary device 6.
• Biomarkers, such as procalcitonin, can provide decision support for antibiotic use and may help identify patients with a low likelihood of infection 4.
• Antimicrobial stewardship, including de-escalation and short duration of antimicrobial therapy, is essential to minimize the risk of resistance and overuse of broad-spectrum antibiotics 3, 4.

Specific Antibiotic Recommendations

• Ceftolozane-tazobactam, imipenem-relebactam, or meropenem-vaborbactam may be considered for patients with sepsis and UTI caused by gram-negative rods, including Pseudomonas aeruginosa 3.
• Piperacillin-tazobactam, with extended-infusion dosing, may be an alternative option for patients with Pseudomonas aeruginosa infections 5.
• Cefiderocol may also be considered for patients with gram-negative infections, including those caused by Pseudomonas aeruginosa 3.