Treatment of High Dose Multi-Drug Resistant (MDR) Klebsiella Infections
For severe MDR Klebsiella infections, meropenem-vaborbactam or ceftazidime-avibactam should be used as first-line therapy if the isolate is susceptible to these agents. 1
First-Line Treatment Options Based on Infection Type
- For severe infections due to carbapenem-resistant Enterobacterales (CRE), including MDR Klebsiella, meropenem-vaborbactam or ceftazidime-avibactam are recommended if active in vitro 1
- For bloodstream infections: Ceftazidime-avibactam 2.5g IV q8h or meropenem-vaborbactam 4g IV q8h for 7-14 days 1
- For complicated intra-abdominal infections: Ceftazidime-avibactam 2.5g q8h plus metronidazole 500mg q6h 1
- For complicated urinary tract infections: Ceftazidime-avibactam 2.5g IV q8h or meropenem-vaborbactam 4g IV q8h for 5-7 days 1
Treatment for Specific Resistance Mechanisms
For KPC-producing Klebsiella (most common in US):
- Meropenem-vaborbactam shows excellent activity with 98.9% susceptibility against KPC-producing isolates 2
- Ceftazidime-avibactam is also highly effective against KPC-producing strains 1
For metallo-β-lactamase (MBL) producers (NDM, VIM):
- For patients with severe infections due to MBL-producing CRE, ceftazidime-avibactam plus aztreonam combination is recommended 1
- Cefiderocol is conditionally recommended for CRE carrying metallo-β-lactamases resistant to other antibiotics 1
Combination Therapy vs. Monotherapy
- For patients treated with newer agents (ceftazidime-avibactam, meropenem-vaborbactam, or cefiderocol), combination therapy is NOT recommended 1
- For patients with severe infections caused by CRE susceptible only to polymyxins, aminoglycosides, tigecycline or fosfomycin, treatment with more than one drug active in vitro is suggested 1
- For non-severe infections, monotherapy with an in vitro active agent is appropriate 1
Special Considerations for High-Dose Meropenem
- For CRE infections with meropenem MIC ≤8 mg/L, high-dose extended-infusion meropenem (2g IV q8h as 3-hour infusion) may be used as part of combination therapy 1
- Continuous infusion of high-dose meropenem has been successfully used to treat bacteremia caused by KPC-producing Klebsiella 3
- Carbapenem-based combination therapy should be avoided unless the meropenem MIC is ≤8 mg/L 1
Treatment for Pan-Resistant Strains
- For pan-resistant CRE (resistant to polymyxins and all other agents), treatment with the least resistant antibiotic/s based on MICs relative to the breakpoints is considered good clinical practice 1
- High-dose combination therapy with imipenem and amikacin with continuous venovenous hemodiafiltration has been reported successful in treating extensively drug-resistant Klebsiella 4
Important Caveats and Pitfalls
- Tigecycline should not be used for bloodstream infections or hospital-acquired/ventilator-associated pneumonia due to poor outcomes; if necessary in patients with pneumonia, high-dose tigecycline should be considered 1
- For urinary tract infections, aminoglycosides (including plazomicin) are suggested over tigecycline 1
- Inappropriate use of carbapenems should be avoided to reduce selective pressure and association with increasing carbapenem-resistant Enterobacteriaceae 1
- Susceptibility testing is essential before initiating therapy, as resistance patterns vary widely 5
- Prolonged infusion (3 hours) of ceftazidime-avibactam and appropriate renal adjustment are associated with improved 30-day survival 1