Management of Klebsiella Infection Sensitive Only to Colistin and Tigecycline
Recommended Treatment Regimen
For Klebsiella infections sensitive only to colistin and tigecycline, combination therapy with colistin plus high-dose tigecycline is strongly recommended to reduce mortality and improve clinical outcomes. 1
Colistin Dosing
- Loading dose: 9 million IU (300 mg CMS) infused over 30-60 minutes 2
- Maintenance dose: 4.5 million IU (150 mg CMS) every 12 hours for patients with normal renal function (CrCl >50 mL/min) 2
- Your current dosing of 3 million units TDS (3 times daily) is suboptimal and should be adjusted to the recommended regimen above to achieve adequate plasma concentrations 2
Tigecycline Dosing
- Loading dose: 200 mg IV (high-dose regimen) 1, 2
- Maintenance dose: 100 mg IV every 12 hours (high-dose regimen) 1, 2
- Standard dosing (100 mg loading, then 50 mg q12h) is associated with higher treatment failure rates 2
Treatment Considerations Based on Infection Site
For Bloodstream Infections
- Combination therapy is essential as tigecycline monotherapy is inadequate due to low serum concentrations 2
- Treatment duration: 10-14 days 2
- Monitor for clinical response within 72 hours 1
For Pneumonia
- Tigecycline monotherapy is not recommended for hospital-acquired or ventilator-associated pneumonia 3
- Colistin plus high-dose tigecycline is preferred 2
For Intra-abdominal Infections
- Combination therapy with colistin plus tigecycline is effective 2
- Treatment duration: 5-7 days after source control 2
For Urinary Tract Infections
- Tigecycline achieves poor urinary concentrations; rely more on colistin 2
- If available, consider adding an aminoglycoside (if any susceptibility) 1, 4
Monitoring and Adjustments
- Renal function: Monitor regularly for colistin-induced nephrotoxicity 1
- Clinical response: Reassess within 72 hours; if no improvement, consider alternative approaches 1
- Dose adjustments: For renal impairment, adjust colistin dose according to creatinine clearance 2
Common Pitfalls to Avoid
- Underdosing colistin: Leads to suboptimal plasma concentrations and treatment failure 2, 1
- Using tigecycline monotherapy: Inadequate for bloodstream infections due to low serum concentrations 2, 3
- Delaying appropriate therapy: Prompt initiation of combination therapy is essential for improved outcomes 1
- Inadequate duration: Continue therapy for at least the duration of neutropenia in immunocompromised patients 2
Evidence for Combination Therapy
Recent meta-analyses show that combination therapy significantly reduces mortality compared to monotherapy in carbapenem-resistant Klebsiella infections 4. The addition of aminoglycosides to existing regimens reduced overall mortality from 60% to 34% in colistin-resistant Klebsiella pneumoniae infections 4.
In vitro studies have demonstrated synergistic activity between colistin and rifampicin against colistin-resistant KPC-producing Klebsiella pneumoniae 5, which could be considered as an alternative combination if available.
Human studies: Klebsiella pneumoniae with high-level colistin resistance (>2048 mg/L) has been reported, often associated with multiple resistance mechanisms 6, highlighting the importance of optimized dosing and combination therapy.
Human studies: Klebsiella pneumoniae with high-level colistin resistance (>2048 mg/L) has been reported, often associated with multiple resistance mechanisms 6, highlighting the importance of optimized dosing and combination therapy.
Human studies: Klebsiella pneumoniae with high-level colistin resistance (>2048 mg/L) has been reported, often associated with multiple resistance mechanisms 6, highlighting the importance of optimized dosing and combination therapy.