What is the management for a patient with Polymyxin B (Polymyxin B) induced Bartter's like syndrome, with a history of infection or sepsis, and impaired renal function?

Management of Polymyxin B-Induced Bartter's-Like Syndrome

Immediately discontinue polymyxin B when Bartter's-like syndrome is suspected, as this drug-induced tubulopathy resolves completely within 7-31 days after stopping the offending agent, and continuing therapy risks severe electrolyte-related complications including cardiac arrhythmias. 1, 2

Immediate Recognition and Drug Discontinuation

The cornerstone of management is prompt discontinuation of polymyxin B. 1, 2 This is critical because:

• Polymyxin B-induced Bartter's-like syndrome typically manifests after a median of 10 days (range 7-18 days) of drug exposure 2
• The syndrome presents with hypokalemia (100% of cases), hypomagnesemia (100%), hypocalcemia (92.5%), and metabolic alkalosis (97.2%) despite normal serum creatinine 2
• Complete resolution occurs within a median of 14 days (range 7-31 days) after drug cessation 2
• One documented case showed normalization of electrolytes rapidly after polymyxin B discontinuation 1

Monitor for life-threatening cardiac complications immediately, as hypokalemia and hypomagnesemia can cause QT prolongation and ventricular arrhythmias. 3 Obtain an ECG to assess QT interval. 3, 4

Acute Electrolyte Replacement Strategy

While awaiting resolution after drug discontinuation, aggressive electrolyte replacement is essential:

Potassium Replacement

• Use potassium chloride exclusively—never potassium citrate or other alkalinizing potassium salts, as these will worsen the metabolic alkalosis. 3, 5
• Target serum potassium of 3.0 mmol/L is reasonable; avoid aiming for complete normalization 4
• Divide supplementation into as many doses as tolerable to maintain steady levels rather than causing large fluctuations 6

Magnesium Replacement

• Aggressive magnesium supplementation is required given 100% incidence of hypomagnesemia in antibiotic-induced Bartter's-like syndrome 2
• Magnesium replacement is essential for cardiac stability and potassium repletion 1

Sodium Chloride Supplementation

• Provide sodium chloride supplementation (5-10 mmol/kg/day) to address the salt-wasting tubulopathy 3
• This addresses the underlying pathophysiology of defective salt reabsorption 2

Monitoring During Recovery Phase

Establish a systematic monitoring protocol given the context of impaired renal function:

• Monitor acid-base status (blood gas or venous total CO2), serum electrolytes (including bicarbonate, chloride, magnesium), and renal function closely during the recovery period 6, 3
• Assess for signs of dehydration, polyuria, muscular weakness, fatigue, and palpitations at each evaluation 6
• Continue monitoring until electrolytes normalize and remain stable 1, 2

Critical Pitfall: Dose Adjustment in Renal Impairment

A crucial error to avoid: The FDA label for polymyxin B explicitly states that dosage "should be reduced from 15,000 units/kg downward for individuals with kidney impairment" and warns that "patients with renal damage and nitrogen retention should have reduced dosage." 7 In your patient with impaired renal function, polymyxin B likely accumulated to toxic levels, causing the tubular dysfunction. 7

The FDA warns that "nephrotoxicity due to polymyxin B sulfate usually shows albuminuria, cellular casts, and azotemia" and that "diminishing urine output and a rising BUN are indications for discontinuing therapy." 7

Alternative Antibiotic Considerations

If ongoing antimicrobial therapy is still required for the underlying infection:

• Avoid concurrent or sequential use of other nephrotoxic drugs (aminoglycosides, colistin, amphotericin B) which are also associated with Bartter's-like syndrome 7, 2
• Gentamicin is the most common antimicrobial causing acquired Bartter's-like syndrome (41.8% of cases), followed by colistin (32.5%) 2
• Consult infectious disease specialists for alternative antimicrobial strategies that avoid nephrotoxic agents

Long-Term Follow-Up

After resolution of the acute episode:

• Patients should be monitored every 6-12 months if any residual tubular dysfunction persists 6, 3
• Perform renal ultrasound every 12-24 months to monitor for nephrocalcinosis or kidney stones, which can develop from the hypercalciuria associated with Bartter's-like syndrome 6, 3
• Continue daily potassium and magnesium supplements only if deficiencies persist after drug discontinuation 1

What NOT to Do

• Do not use NSAIDs (indomethacin, ibuprofen, celecoxib) in this drug-induced form, as these are reserved for genetic Bartter syndrome and can cause nephrotoxicity, especially with pre-existing renal impairment 6, 8
• Do not use potassium-sparing diuretics in the acute phase of drug-induced disease—these are for chronic genetic Bartter syndrome management 3
• Do not continue polymyxin B even at reduced doses, as the tubular damage will persist and potentially worsen 1, 2