OXA-48 Infections: Treatment and Management

Introduction to OXA-48

OXA-48 is a Class D carbapenemase enzyme that confers resistance to carbapenems and most β-lactam antibiotics, but remains susceptible to ceftazidime-avibactam, accounting for approximately 19% of carbapenem-resistant Enterobacterales (CRE) infections globally 1
Unlike metallo-β-lactamases (MBLs), OXA-48 is a serine-based carbapenemase that can be inhibited by avibactam 2, 3
OXA-48-producing organisms frequently co-harbor extended-spectrum β-lactamases (ESBLs) like CTX-M, creating complex resistance patterns 4

The International Society for Antimicrobial Chemotherapy provides a CONDITIONAL recommendation with VERY LOW certainty of evidence for ceftazidime-avibactam as first-line therapy for OXA-48 infections 2, 3
Nearly 100% of OXA-48-producing CRE strains are susceptible to ceftazidime-avibactam 5, 6
Ceftazidime-avibactam monotherapy is appropriate for OXA-48 producers without co-production of metallo-β-lactamases 5

In a study of 57 CRE infections, the curative rate was 82.3% in 17 patients who received ceftazidime-avibactam alone for OXA-48-positive infections 7, 5
Ceftazidime-avibactam showed superior outcomes compared to older therapies, with better safety profiles than colistin-based regimens 5, 6, 2, 3

Add aztreonam 2 grams IV every 8 hours to ceftazidime-avibactam ONLY if the isolate co-produces both OXA-48 AND a metallo-β-lactamase (NDM, VIM, or IMP) 7, 5, 4
For NDM + OXA-48 co-producers, the curative rate was 77.5% with ceftazidime-avibactam plus aztreonam combination therapy 7, 5
Aztreonam is stable against metallo-β-lactamases because these enzymes cannot hydrolyze monobactam antibiotics 4

Do not use ceftazidime-avibactam monotherapy if NDM or other MBL is co-produced with OXA-48 - it will fail because avibactam has no activity against metallo-β-lactamases 4
Do not use meropenem-vaborbactam for OXA-48 infections - vaborbactam has no activity against OXA-48 carbapenemases 4
Do not delay treatment waiting for complete carbapenemase typing - initiate ceftazidime-avibactam immediately based on epidemiology or rapid molecular testing 5, 4
Monitor for emergence of ceftazidime-avibactam resistance, which ranges from 0% to 12.8% in KPC-producing isolates and can occur through OXA-48 mutations (P68A, Y211S) 6