Treatment of Multidrug-Resistant Klebsiella Bone Infections

Primary Recommendation

The Infectious Diseases Society of America recommends using ceftazidime-avibactam alone for KPC-producing or OXA-48-producing strains, but using ceftazidime-avibactam combined with aztreonam for metallo-β-lactamase (MBL)-producing strains for multidrug-resistant Klebsiella bone infections 1, 2, 3

Ascertain the carbapenemase type before initiating treatment whenever possible through phenotypic testing or genotypic PCR testing for MBL genes 3
Use ceftazidime-avibactam monotherapy at 2.5 g IV every 8 hours as a prolonged 3-hour infusion for KPC-producing or OXA-48-producing Klebsiella 1, 3
Nearly 100% of KPC-producing and OXA-48-producing strains are susceptible to ceftazidime-avibactam 3
Prolonged 3-hour infusions are associated with improved 30-day survival compared to standard infusions 1
Use ceftazidime-avibactam 2.5 g IV every 8 hours PLUS aztreonam 2 g IV every 6 hours for MBL-producing Klebsiella (NDM, VIM, IMP) 1, 2, 3
This combination demonstrates synergistic activity in 90% of MBL-producing strains and achieves significantly lower 30-day mortality and clinical failure rates compared to other antimicrobial therapies 1, 2, 3

Treat bone and musculoskeletal infections for a minimum of 4-6 weeks, though specific duration data for ceftazidime-avibactam in osteomyelitis is limited 4, 5

Emergence of ceftazidime-avibactam resistance occurs in 3.8-10.4% of KPC-producing CRE infections 1
The combination with aztreonam provides resistance suppression that monotherapy does not achieve for MBL-producing strains 1, 2, 3
Do NOT add polymyxin or fosfomycin routinely for MBL-producers, as the ceftazidime-avibactam plus aztreonam combination alone demonstrates superior outcomes compared to colistin-containing regimens 2, 3
There are currently no standardized antimicrobial susceptibility testing methods or clinical breakpoints approved for the ceftazidime-avibactam plus aztreonam combination 1

Monitor for clinical improvement within 48-72 hours and obtain repeat cultures if clinical deterioration occurs to assess for resistance development 1, 4, 5