What are the recommendations for colistin (Colistimethate) and other alternative treatments for a patient with neutropenia, stage 3 Acute Kidney Injury (AKI) on Chronic Kidney Disease (CKD), and septic shock?

From the Guidelines

Colistin and alternative treatments for a patient with neutropenia, stage 3 Acute Kidney Injury (AKI) on Chronic Kidney Disease (CKD), and septic shock are recommended to be used with caution and close monitoring of renal function.

Key Considerations

• The patient's condition requires prompt initiation of effective IV antimicrobials within the first hour of recognition of septic shock 1.
• Empiric broad-spectrum therapy with one or more antimicrobials is recommended to cover all likely pathogens, including bacterial and potentially fungal or viral coverage 1.
• Colistin-based treatment is recommended in infections due to multidrug-resistant organisms, such as carbapenem-resistant Pseudomonas aeruginosa (CRPA) 1.
• A loading dose of 9 MU (5 mg/kg) of colistin followed by a maintenance dose of 4.5 MU (2.5 mg) twice daily is suggested in critically ill patients 1.
• Renal function should be closely monitored during colistin treatment, and dose adjustment may be necessary in patients with acute kidney injury or chronic kidney disease 1.
• Combination therapy with colistin and other antimicrobials may be considered in certain cases, but the evidence is limited and controversial 1.

Dosing and Monitoring

• The optimal dose of colistin is 9 MU of colistin methanesulfonate (CMS) initially followed by 4.5 MU CMS twice a day as the maintenance dose 1.
• Pharmacodynamic studies have shown that this regimen is effective in critically ill patients, but individualized dose adjustment may be necessary based on renal function and other factors 1.
• Close monitoring of renal function is essential during colistin treatment, and dose adjustment may be necessary to prevent nephrotoxicity 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION ... The daily dose and frequency should be reduced for the patients with renal impairment Suggested modifications of dosage schedule for patients with renal impairment are presented in Table 1. TABLE 1 Suggested Modification of Dosage Schedules of Colistimethate for Injection, USP for Adults with Impaired Renal Function Degree of Renal Impairment Normal Mild Moderate Severe Creatinine Clearance (mL/min) ≥80 50-79 30-49 10-29 Dosage Schedule 2.5 to 5 mg/kg, divided into 2 to 4 doses per day 2.5 to 3.8 mg/kg, divided into 2 doses per day 2.5 mg/kg, once daily or divided into 2 doses per day 1.5 mg/kg every 36 hours In the presence of impaired renal function, reduce the infusion rate depending on the degree of renal impairment.

For a patient with stage 3 Acute Kidney Injury (AKI) on Chronic Kidney Disease (CKD), the creatinine clearance is likely to be between 30-49 mL/min, which corresponds to moderate renal impairment. According to the dosage schedule, the recommended dose for moderate renal impairment is 2.5 mg/kg, once daily or divided into 2 doses per day. However, for a patient with septic shock and neutropenia, the clinical decision should be made with caution, considering the potential risks and benefits of the treatment. The use of colistin (Colistimethate) should be carefully monitored, and the dosage should be adjusted according to the patient's renal function and clinical response 2. Alternative treatments should also be considered, but there is no information in the provided drug labels to support a specific alternative treatment for this patient.

From the Research

Patient Considerations

• The patient has neutropenia, stage 3 Acute Kidney Injury (AKI) on Chronic Kidney Disease (CKD), and septic shock, which are significant considerations for treatment with colistin (Colistimethate) 3, 4, 5, 6, 7.
• Colistin-induced nephrotoxicity is a major concern, and the risk of nephrotoxicity varies between different formulations of colistin 3.
• The presence of septic shock and inappropriate colistin dosage are clinical factors associated with colistin-induced nephrotoxicity 3.

Treatment Recommendations

• Colistin is widely used in the treatment of nosocomial infections caused by carbapenem-resistant gram-negative bacilli (CR-GNB), but its use requires careful consideration of the risk of nephrotoxicity 3, 4, 5, 6, 7.
• The development of AKI in patients treated with colistin should not be considered a sufficient reason for discontinuing colistin treatment, especially in the absence of alternative therapies 4.
• Patients with CKD may be at risk of underdosing with colistin, and therapeutic drug monitoring is advised to optimize treatment 6, 7.
• Higher dosing regimens may be necessary for patients with reduced kidney function, especially those receiving renal replacement therapy (RRT) such as dialysis or hemofiltration 7.

Alternative Treatments

• There are limited alternative treatments for multidrug-resistant Gram-negative bacterial infections, and colistin may be the only viable option for some patients 4, 7.
• The use of alternative treatments should be considered on a case-by-case basis, taking into account the patient's individual circumstances and the potential risks and benefits of each treatment option 3, 4, 5, 6, 7.