Polymyxin B Treatment for Klebsiella pneumoniae Infections
For severe infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), combination therapy with polymyxin B plus at least one other in vitro active antibiotic is recommended over polymyxin B monotherapy to improve survival outcomes. 1
Dosing Regimen
- Loading dose: 2.5 mg/kg IV infused over 3 hours
- Maintenance dose: 1.25 mg/kg IV every 12 hours infused over 2 hours 2
- Adjust dose in patients with renal impairment (CrCl ≤50 mL/min)
- Therapeutic drug monitoring is strongly recommended when available
Treatment Algorithm
Step 1: Determine Resistance Pattern
- Confirm carbapenem resistance and polymyxin B susceptibility
- Identify specific carbapenemase type if possible (KPC, MBL, OXA-48)
- Determine MICs for all potential combination agents
Step 2: Select Treatment Based on Resistance Pattern
For KPC-producing K. pneumoniae:
- First choice: Ceftazidime-avibactam (2.5g IV q8h) if available and susceptible 3
- Second choice: Polymyxin B-based combination therapy if ceftazidime-avibactam is unavailable
For MBL-producing K. pneumoniae:
- Polymyxin B-based combination therapy (limited options for these strains)
- Consider cefiderocol if available and susceptible 1
For polymyxin-susceptible CRKP:
- Combination therapy with polymyxin B plus at least one other active agent
For polymyxin-resistant CRKP:
- Triple combination therapy may be necessary (polymyxin B + rifampin + meropenem) 4
Step 3: Select Companion Drug(s) for Polymyxin B
Preferred companion drugs (in order of preference):
- Meropenem (if MIC ≤8 mg/L): 2g IV q8h as 3-hour extended infusion 1
- Aminoglycoside (if susceptible): Particularly for urinary tract infections 1, 3
- Tigecycline (if susceptible): Avoid for urinary tract infections or bacteremia 1
- Rifampin: Consider as part of triple therapy for highly resistant strains 4, 5
Duration of Therapy
- Bloodstream infections: 10-14 days
- Complicated urinary tract infections: 7-14 days
- Pneumonia: 7-14 days
Monitoring
Efficacy Monitoring
- Daily clinical assessment for signs of improvement
- Follow-up blood cultures within 48-72 hours to document clearance
- Early administration of polymyxin B (within 48h of bacteremia diagnosis) significantly improves bacterial clearance rates (65.22% vs 29.41%) and reduces 30-day mortality (39.13% vs 70.59%) 6
Toxicity Monitoring
- Nephrotoxicity: Monitor renal function daily (occurs in ~55% of patients) 2
- Neurotoxicity: Monitor for paresthesias, dizziness, ataxia (occurs in ~55% of patients) 2
- Hyperpigmentation: Rare but reported adverse effect 2
Important Considerations
- Polymyxin B monotherapy has been associated with clinical failure rates of 27% even in susceptible isolates 7
- Baseline renal insufficiency increases risk of clinical failure by 6-fold 7
- Breakthrough infections with organisms intrinsically resistant to polymyxins occur in approximately 7.5% of patients during treatment 7
- Development of polymyxin resistance during therapy is a concern, with approximately 45% of patients developing new CRKP infections after initial treatment 7
Special Situations
For urinary tract infections:
- Aminoglycosides may be preferred over polymyxin B when susceptible, with significantly better clinical cure rates 1, 3
For critically ill patients with septic shock:
- Use of two or more in vitro active antibiotics (including polymyxin B) is independently associated with improved 30-day survival 1
For patients with meropenem MIC ≤8 mg/L:
- High-dose extended-infusion meropenem (2g IV q8h as 3-hour infusion) combined with polymyxin B improves outcomes 1
For non-severe infections:
- Consider monotherapy with the most appropriate in vitro active agent based on the source of infection and local susceptibility patterns 1
Remember that early initiation of appropriate therapy is critical for improving outcomes in CRKP infections, with early polymyxin B administration (within 48 hours) significantly reducing mortality compared to delayed administration 6.