What antibiotic should be used to treat a patient with Klebsiella (Klebs)-positive urosepsis and hyperchloremic metabolic acidosis?

From the Guidelines

For Klebsiella-positive urosepsis with hyperchloremic metabolic acidosis, I strongly recommend starting with a carbapenem such as meropenem (1g IV every 8 hours) as the first-line treatment option, as suggested by the most recent and highest quality study 1. This recommendation is based on the strong evidence from the study, which suggests that meropenem/vaborbactam or ceftazidime/avibactam should be the first-line treatment options for infections caused by KPC-producing carbapenem-resistant Enterobacterales (CRE) 1. The use of meropenem is supported by its excellent coverage against Klebsiella species, including many extended-spectrum beta-lactamase (ESBL) producing strains, and its ability to achieve high epithelial lining fluid (ELF) concentrations, making it an effective option for treating urosepsis 1. Alternatively, ceftazidime/avibactam can be considered, especially if there are concerns about meropenem resistance or if the patient has a specific type of infection that may require a different antibiotic 1. It is also important to address the hyperchloremic metabolic acidosis simultaneously with IV fluids, preferably balanced crystalloids rather than normal saline, to avoid worsening the acidosis, and to monitor renal function and adjust antibiotic dosing accordingly 1. Once culture and sensitivity results are available, narrow the antibiotic therapy to the most appropriate agent, as Klebsiella infections in urosepsis can be severe and may harbor resistance mechanisms, making initial broad coverage crucial while awaiting susceptibility data 1. The acidosis may improve with both infection control and appropriate fluid management, and treatment duration should typically be 7-14 days, depending on clinical response 1.

Some key points to consider when treating Klebsiella-positive urosepsis with hyperchloremic metabolic acidosis include:

• The importance of using a broad-spectrum antibiotic, such as a carbapenem, to cover potential resistance mechanisms 1
• The need to address the hyperchloremic metabolic acidosis with IV fluids and to monitor renal function and adjust antibiotic dosing accordingly 1
• The importance of narrowing antibiotic therapy to the most appropriate agent once culture and sensitivity results are available 1
• The potential for ceftazidime/avibactam to be used as an alternative to meropenem, especially if there are concerns about meropenem resistance or if the patient has a specific type of infection that may require a different antibiotic 1.

Overall, the key to treating Klebsiella-positive urosepsis with hyperchloremic metabolic acidosis is to use a broad-spectrum antibiotic, such as a carbapenem, and to address the acidosis with IV fluids, while also monitoring renal function and adjusting antibiotic dosing accordingly 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Antibiotic Selection for Klebsiella pneumoniae Urosepsis

The selection of an appropriate antibiotic for Klebsiella pneumoniae (Klebs) urosepsis is crucial, especially in cases with hyperchloremic metabolic acidosis.

• The choice of antibiotic should be guided by local resistance patterns and the expected pathogen spectrum 2.
• Klebsiella pneumoniae can produce extended-spectrum beta-lactamases (ESBL) and carbapenemases, which can confer resistance to multiple antibiotics 3, 4.
• In cases of ESBL-producing Klebsiella pneumoniae, antibiotics such as carbapenems (e.g., imipenem) or tigecycline may be effective, but resistance can develop during therapy 4.
• The development of resistance to carbapenems and tigecycline during antimicrobial therapy is a concern, and alternative antibiotics such as aminoglycosides or fluoroquinolones may be considered, although resistance to these agents is also common 3, 4.

Considerations for Hyperchloremic Metabolic Acidosis

• Hyperchloremic metabolic acidosis can occur in the context of urosepsis, particularly if the patient has a urinary tract obstruction or is receiving certain medications.
• The choice of antibiotic should not exacerbate the metabolic acidosis, and consideration should be given to the potential effects of the antibiotic on renal function and acid-base balance.

Treatment Challenges

• The treatment of urosepsis caused by Klebsiella pneumoniae can be challenging due to the potential for antibiotic resistance and the need for early and effective antimicrobial therapy 5, 6.
• A multidisciplinary approach, including urologists, intensive care specialists, and microbiologists, is recommended for the management of urosepsis 6, 2.