What is the treatment approach for infections caused by OXA-48 (Oxacillinase-48) producing bacteria with suspected or confirmed resistance?

Treatment Approach for OXA-48 Producing Bacteria Infections

For infections caused by OXA-48-like producing carbapenem-resistant Enterobacterales (CRE), ceftazidime/avibactam should be used as the first-line treatment option. 1

Treatment Algorithm Based on Carbapenemase Type

OXA-48-like Producing CRE:

• First-line therapy: Ceftazidime/avibactam monotherapy 1, 2

  • Clinical success rates are significantly higher with ceftazidime/avibactam compared to other treatment options 2
  • Evidence shows lower 14-day mortality in patients receiving ceftazidime/avibactam compared to best available therapy 2

• Alternative options (if ceftazidime/avibactam is unavailable):

  • For isolates susceptible to carbapenems (approximately 65% of OXA-48 isolates may retain carbapenem susceptibility) 3:
    • Meropenem or imipenem at high doses 3
  • For carbapenem-resistant isolates:
    • Amikacin (if susceptible) 4
    • Tigecycline (for intra-abdominal infections, not for bloodstream infections) 4

Clinical Considerations

Susceptibility Testing

• Always perform antimicrobial susceptibility testing, as OXA-48 producers show variable resistance patterns 5
• OXA-48 has unique characteristics:
  • Low-level hydrolytic activity toward carbapenems 5
  • No intrinsic activity against expanded-spectrum cephalosporins 5
  • Often co-produces ESBLs, leading to variable resistance to cephalosporins 5

Source of Infection

• Infection source impacts outcomes and treatment decisions 3:
  • Catheter-related bloodstream infections and urinary tract infections have better prognosis 3
  • Lower respiratory tract infections and bloodstream infections are associated with higher 30-day mortality 3
  • Source control is critical and associated with improved survival (aHR: 0.35) 3

Treatment Duration

• Median duration of targeted therapy is approximately 14 days 4

Evidence Quality and Limitations

• The recommendation for ceftazidime/avibactam as first-line therapy has a CONDITIONAL strength with VERY LOW certainty of evidence 1
• Clinical data on OXA-48 treatment comes primarily from observational studies with small sample sizes 1
• Combination therapy did not demonstrate additional benefit over appropriate monotherapy in OXA-48 infections 3

Emerging Concerns

• Resistance to ceftazidime/avibactam in OXA-48 producers has been reported, though less frequently than in KPC producers 6
• Local epidemiology and resistance patterns should guide therapy decisions 1
• Newer options like cefiderocol may have a role, but clinical evidence specifically for OXA-48 infections is limited 1, 6

Important Distinctions from Other Carbapenemases

• KPC-producing CRE: Either ceftazidime/avibactam or meropenem/vaborbactam are recommended (stronger evidence base) 1
• MBL-producing CRE (e.g., NDM): Ceftazidime/avibactam plus aztreonam is strongly recommended, with cefiderocol as an alternative 1, 6