What is the recommended treatment and dose adjustment for a patient with Multi-Drug Resistant (MDR) Klebsiella infection and Chronic Kidney Disease (CKD)?

From the Guidelines

For patients with Multi-Drug Resistant (MDR) Klebsiella infection and Chronic Kidney Disease (CKD), the recommended treatment involves using Ceftazidime/Avibactam 2.5 g 8-hourly, with dose adjustment based on renal function, as it is effective against carbapenemase-producing Klebsiella pneumoniae 1.

Key Considerations

• The choice of antibiotic should be guided by antimicrobial susceptibility testing, as MDR Klebsiella resistance patterns can vary significantly.
• In patients with CKD, dose adjustment is crucial to avoid nephrotoxicity and ensure adequate drug levels.
• Combination therapy may be necessary, but the choice of additional antibiotics should be based on the patient's specific infection and renal function.
• Regular monitoring of renal function is essential, as these patients face dual risks of nephrotoxicity from both the medication and the infection itself.

Dose Adjustment in CKD

• For patients with severe CKD (GFR <30 mL/min), dose reduction may be necessary to avoid accumulation of the drug and its metabolites.
• The use of Ceftazidime/Avibactam in patients with CKD requires careful monitoring of renal function and adjustment of the dose based on the patient's creatinine clearance.

Additional Therapies

• Vancomycin or Teicoplanin may be added to the treatment regimen, but their use should be guided by the patient's specific infection and renal function.
• In patients at risk for invasive candidiasis, Echinocandins or Amphotericin B Liposomal may be considered as additional therapies.

Monitoring and Treatment Duration

• Regular monitoring of renal function and clinical response is essential to guide therapy and adjust the treatment regimen as needed.
• Treatment duration typically ranges from 7-14 days, depending on the severity of the infection and the patient's clinical response.

From the FDA Drug Label

The recommended dosage of FETROJA is 2 grams administered every 8 hours by intravenous (IV) infusion over 3 hours in adults with a creatinine clearance (CLcr) of 60 to 119 mL/min Dosage adjustment of FETROJA is recommended for patients with CLcr less than 60 mL/min, including patients receiving intermittent hemodialysis (HD) or continuous renal replacement therapy (CRRT), and for patients with CLcr 120 mL/min or greater For patients with CLcr 30 to 59 mL/min, the recommended dose is 1.5 grams every 8 hours For patients with CLcr 15 to 29 mL/min, the recommended dose is 1 gram every 8 hours For patients with CLcr less than 15 mL/min, with or without intermittent HD, the recommended dose is 0.75 grams every 12 hours

The recommended treatment and dose adjustment for a patient with Multi-Drug Resistant (MDR) Klebsiella infection and Chronic Kidney Disease (CKD) is as follows:

• Dose adjustment: The dose of cefiderocol (FETROJA) should be adjusted based on the patient's creatinine clearance (CLcr)
• CLcr 30 to 59 mL/min: 1.5 grams every 8 hours
• CLcr 15 to 29 mL/min: 1 gram every 8 hours
• CLcr less than 15 mL/min: 0.75 grams every 12 hours
• Intermittent HD: Start the dosing of FETROJA immediately after the completion of HD
• CRRT: The dosage of FETROJA should be based on the effluent flow rate in CRRT, as shown in Table 2 2

From the Research

Treatment Options for MDR Klebsiella Infection

• The treatment of Multi-Drug Resistant (MDR) Klebsiella infection requires careful consideration of the patient's underlying health conditions, including Chronic Kidney Disease (CKD) 3, 4, 5.
• Promising drugs for the treatment of MDR Klebsiella infection include cefiderocol, aztreonam, ceftazidime/avibactam, and meropenem/vaborbactam 3, 4.
• In patients with CKD, dose adjustment may be necessary to avoid nephrotoxicity and ensure effective treatment 5, 6.

Dose Adjustment in CKD

• Patients with CKD may require dose adjustment of certain antibiotics, such as plazomicin, to avoid accumulation and toxicity 5.
• Therapeutic drug monitoring may be necessary to ensure safe and effective use of certain antibiotics in patients with severe renal dysfunction 5.
• The use of combination therapy, such as aztreonam, ceftazidime/avibactam, and colistin, may be effective in treating MDR Klebsiella infection, but requires careful consideration of potential interactions and toxicity 6, 7.

Considerations for Treatment

• Susceptibility testing is essential to guide antibiotic therapy and ensure effective treatment of MDR Klebsiella infection 3, 4, 7.
• Automated systems may overestimate the susceptibility profile of MDR Gram-negative bacilli, highlighting the importance of careful interpretation of susceptibility results 7.
• Combination therapy and synergy using polymyxin may be effective treatment strategies for MDR Gram-negative bacilli, but require careful consideration of potential interactions and toxicity 7.