Are infections caused by bacteria producing oxacillinase (OXA) carbapenemases susceptible to cephalosporins?

Susceptibility of OXA Carbapenemase-Producing Bacteria to Cephalosporins

Bacteria producing OXA-48-like carbapenemases can be susceptible to certain cephalosporins, particularly when they do not co-produce extended-spectrum beta-lactamases (ESBLs). 1

Characteristics of OXA-48 Carbapenemases

OXA-48 carbapenemases have unique hydrolytic properties that distinguish them from other carbapenemases:

• They have low-level hydrolytic activity against carbapenems
• They have poor intrinsic hydrolytic activity against cephalosporins 2, 3
• They are primarily found in Enterobacteriaceae, especially Klebsiella pneumoniae and Escherichia coli 2

Susceptibility to Cephalosporins

The susceptibility pattern of OXA-48 producers to cephalosporins depends on several factors:

1. Co-production of other beta-lactamases:

   • OXA-48 producers that do not co-produce ESBLs may remain susceptible to cephalosporins 4
   • Co-production with CTX-M-15 or other ESBLs leads to resistance to cephalosporins 2

2. Specific OXA-48 variants:

   • Most OXA-48-like enzymes have poor hydrolytic activity against cephalosporins
   • Exception: OXA-163 effectively hydrolyzes cephalosporins 2

Treatment Options for OXA-48 Producers

First-line Treatment

According to clinical guidelines, ceftazidime-avibactam should be the first-line treatment option for infections caused by OXA-48-like producing carbapenem-resistant Enterobacteriaceae (CRE). 1

• This recommendation has a conditional strength with very low certainty of evidence
• Clinical studies have shown promising results with ceftazidime-avibactam in treating OXA-48 infections 5

Alternative Options for ESBL-negative OXA-48 Producers

For OXA-48 producers that do not co-produce ESBLs:

• Cephalosporins could be considered as an alternative treatment in selected patients 4
• Clinical case reports have documented successful treatment with:
  • Cefepime (alone or in combination)
  • Ceftriaxone 4

Newer Treatment Options

• Cefepime-enmetazobactam has shown high in vitro activity against OXA-48 producers (96.7% susceptibility), similar to ceftazidime-avibactam (99.5%) 6

Clinical Implications and Pitfalls

Diagnostic Challenges

• The poor hydrolytic profile of OXA-48-like enzymes against cephalosporins can obscure their detection in routine diagnostics 2
• This may lead to inappropriate treatment selection if the presence of OXA-48 is not identified

Treatment Considerations

• Always assess for co-production of ESBLs before considering cephalosporin therapy
• Susceptibility testing is crucial for guiding treatment decisions
• The plasmid-mediated nature of OXA-48 facilitates rapid spread and inter-species dissemination 2

Monitoring and Follow-up

• Monitor for emergence of resistance during treatment
• Be aware that recurrence of infection can occur (reported in 35% of patients within 90 days after treatment with ceftazidime-avibactam) 5

Algorithm for Treatment Decision

1. Identify the presence of OXA-48-like carbapenemase
2. Test for co-production of ESBLs or other beta-lactamases
3. If OXA-48 producer without ESBL co-production:
   • Consider ceftazidime-avibactam as first-line therapy 1
   • In selected cases with confirmed susceptibility, cephalosporins may be an option 4
4. If OXA-48 producer with ESBL co-production:
   • Use ceftazidime-avibactam as first-line therapy 1
   • Avoid cephalosporins due to likely resistance

In conclusion, while OXA-48 producers have intrinsically poor hydrolytic activity against cephalosporins, treatment decisions should be based on comprehensive susceptibility testing and assessment for co-production of other resistance mechanisms.