Can Colistin Be Used for Klebsiella pneumoniae?
Yes, colistin can be used for Klebsiella pneumoniae infections, particularly for multidrug-resistant and carbapenem-resistant strains, but it should NOT be used as monotherapy and is now considered a second-line option due to poor efficacy, high toxicity, and the availability of superior alternatives. 1, 2, 3
FDA-Approved Indication
- Colistin (colistimethate) is FDA-approved for treatment of infections caused by Klebsiella pneumoniae when the strain is susceptible. 3
- The drug demonstrates bactericidal activity by disrupting bacterial cell membranes and achieves therapeutic serum levels with a half-life of 2-3 hours. 3
When Colistin Should Be Used
For Carbapenem-Resistant K. pneumoniae (CRKP)
- Colistin is reserved for salvage therapy when newer agents (ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam) are unavailable or the strain is resistant to these first-line options. 1, 2
- Colistin monotherapy has shown poor outcomes with approximately one in three patients dying and <70% achieving clinical/microbiological response. 2
Mandatory Combination Therapy
- Colistin must ALWAYS be combined with at least one other in vitro active antibiotic—never use as monotherapy for serious infections. 1
- For critically ill patients with KPC-producing K. pneumoniae and septic shock, combination therapy with two or more active antibiotics (including colistin) was independently associated with 30-day survival (adjusted HR 0.56,95% CI 0.34-0.91). 1
Recommended Colistin-Based Combinations
High-Dose Carbapenem Plus Colistin
- For KPC-producing K. pneumoniae with meropenem MIC ≤16 mg/L, use high-dose extended-infusion meropenem (6g/day as 3-hour infusions) plus colistin. 1, 2
- This combination showed lower 14-day mortality compared to non-carbapenem containing regimens, even at elevated MICs. 1
Colistin Plus Tigecycline
- For bloodstream infections: Colistin 5 mg CBA/kg IV loading dose, then 2.5 mg CBA × (1.5 × CrCl + 30) IV q12h PLUS tigecycline 100 mg IV loading dose, then 50 mg IV q12h. 1
- This combination is NOT recommended for pneumonia due to poor tigecycline lung penetration. 1
Colistin Plus Rifampicin
- For colistin-resistant KPC-producing K. pneumoniae, colistin/rifampicin combinations demonstrated uniform synergy (FIC indices 0.1-0.4) with persistent growth inhibition lasting 3 hours. 4
- This combination may be considered when the strain shows colistin resistance but clinical data remains limited. 4, 5
Critical Dosing Parameters
- Loading dose: 5 mg colistin base activity (CBA)/kg IV 1
- Maintenance dose: 2.5 mg CBA × (1.5 × CrCl + 30) IV q12h 1
- One million international units (MIU) colistin methanesulfonate equals 33 mg colistin base activity. 1
When NOT to Use Colistin
First-Line Alternatives Are Superior
- For CRKP infections, ceftazidime-avibactam (2.5g IV q8h) or meropenem-vaborbactam (4g IV q8h) should be used first-line instead of colistin. 2
- These newer agents showed significantly lower 28-day mortality (18.3% vs 40.8%) and reduced nephrotoxicity compared to colistin. 2
Carbapenem-Susceptible Strains
- For carbapenem-susceptible K. pneumoniae, use carbapenems (meropenem, imipenem, or ertapenem) as first-line therapy—colistin is unnecessary. 2
Special Resistance Scenarios
Colistin-Resistant K. pneumoniae
- Colistin resistance in K. pneumoniae is increasingly reported, often mediated by mgrB gene disruption via insertion sequences (ISKpn26, IS5). 5, 6
- For colistin-resistant strains, use ceftazidime-avibactam, meropenem-vaborbactam, or consider colistin/rifampicin combinations based on susceptibility testing. 2, 4
Metallo-β-Lactamase (MBL) Producers
- For MBL-producing K. pneumoniae, use ceftazidime-avibactam PLUS aztreonam (70-90% efficacy)—colistin is not the preferred option. 2
Critical Pitfalls to Avoid
- Never use colistin monotherapy for serious K. pneumoniae infections—it is associated with treatment failure and high mortality. 1, 2
- Nephrotoxicity is a major concern—monitor renal function closely and adjust doses based on creatinine clearance. 1
- Heteroresistance is common—strains may appear susceptible but contain resistant subpopulations that emerge during therapy. 5
- Obtain rapid molecular testing to identify carbapenemase types (KPC vs OXA-48 vs MBL) before initiating colistin, as this guides whether colistin-based therapy is appropriate. 2
- Infectious disease consultation is highly recommended for all multidrug-resistant K. pneumoniae infections. 2