What is the choice of antibiotics for a patient with a urine culture showing heavy growth of Klebsiella, status post (s/p) left nephrectomy, sensitive to Meropenem (Meropenem) but resistant to Imipenem (Imipenem)?

From the Guidelines

For a patient with a urine culture showing heavy growth of Klebsiella who is post left nephrectomy, with sensitivity to meropenem but resistance to imipenem, the recommended antibiotic choice is meropenem. The typical dosing for meropenem in urinary tract infections is 1 gram intravenously every 8 hours for 7-14 days, depending on the severity of the infection and clinical response 1. Dose adjustment may be needed for patients with renal impairment, with typical adjustments being 500 mg every 8 hours for creatinine clearance 26-50 ml/min, and 500 mg every 12 hours for creatinine clearance 10-25 ml/min. This recommendation is based on the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines, which suggest the use of carbapenems, such as meropenem, as targeted therapy for patients with severe infections due to third-generation cephalosporin-resistant Enterobacterales (3GCephRE) 1.

Key considerations in the management of this patient include:

• Monitoring kidney function during treatment, given the patient's history of nephrectomy
• Ensuring adequate hydration
• Follow-up urine cultures after completing treatment to confirm eradication of the infection
• The discrepancy in susceptibility between meropenem and imipenem, despite both being carbapenems, can occur due to differences in their molecular structure affecting binding to bacterial penicillin-binding proteins or variations in the specific carbapenemase enzymes produced by the Klebsiella strain 1.

Given the patient's specific situation, with sensitivity to meropenem and resistance to imipenem, meropenem is the most appropriate choice, as it is effective against the isolate and aligns with current clinical guidelines for the treatment of 3GCephRE infections 1.

From the FDA Drug Label

Dosage adjustment is recommended in patients with advanced age and/or adult patients with creatinine clearance of 50 mL/min or less [ see Dosage and Administration (2. 2)]. Close adherence to the recommended dosage regimens is urged, especially in patients with known factors that predispose to convulsive activity. The patient has a urine culture showing Klebsiella heavy growth and is sensitive to Meropenem. Given the patient's sensitivity to Meropenem and resistance to Imipenem, the choice of antibiotic is Meropenem. However, it is essential to consider the patient's renal function, especially since they have undergone a left nephrectomy, and adjust the dosage accordingly as recommended in the drug label 2.

• The patient should be closely monitored for potential side effects, such as seizures, delirium, headaches, and/or paresthesias, that could interfere with mental alertness and/or cause motor impairment.
• It is also crucial to be aware of the potential for Clostridium difficile-associated diarrhea and take appropriate measures if it occurs.
• The development of drug-resistant bacteria and overgrowth of nonsusceptible organisms should also be considered, and repeated evaluation of the patient is essential.

From the Research

Urine Culture Results and Antibiotic Sensitivity

• The urine culture shows heavy growth of Klebsiella, which is sensitive to Meropenem but resistant to Imipenem.
• The patient has a history of left nephrectomy, which may increase the risk of complications from urinary tract infections.

Choice of Antibiotics

• Based on the sensitivity results, Meropenem is a suitable choice of antibiotic for treating the Klebsiella infection 3.
• However, considering the resistance to Imipenem, Meropenem-vaborbactam may be a better option, as it has shown efficacy against carbapenem-resistant Enterobacteriaceae, including Klebsiella pneumoniae carbapenemase (KPC)-producing strains 4, 5, 6, 7.
• Meropenem-vaborbactam has been approved for the treatment of complicated urinary tract infections, including acute pyelonephritis, and has shown superior treatment success and lower toxicity compared to traditional agents 4, 6, 7.

Considerations for Treatment

• The patient's history of left nephrectomy should be taken into account when selecting an antibiotic, as it may affect the pharmacokinetics and pharmacodynamics of the chosen antibiotic.
• The potential for resistance to Meropenem-vaborbactam should be monitored, and alternative treatment options should be considered if resistance develops 5, 7.