OXA Enzymes Can Be Resistant to Ertapenem While Susceptible to Meropenem
Yes, OXA (oxacillinase) enzymes can confer resistance to ertapenem while maintaining susceptibility to meropenem due to their variable hydrolytic activity against different carbapenems. 1
Mechanism of Differential Carbapenem Resistance
OXA-type β-lactamases (Class D carbapenemases) demonstrate variable activity against different carbapenems due to several factors:
Enzyme-specific hydrolytic profiles: OXA enzymes have different hydrolytic capabilities against various carbapenems, with many showing preferential hydrolysis of ertapenem over meropenem 2
Structural differences: Ertapenem's molecular structure makes it more susceptible to hydrolysis by certain OXA variants compared to meropenem 1
Porin channel interactions: The combination of OXA enzymes with porin channel mutations (particularly OmpK35/OmpK36 in Klebsiella) can create differential resistance patterns 3
Clinical Evidence
A 2019 study demonstrated this phenomenon clearly with OXA-232 (an OXA-48-like enzyme):
- Initial isolates showed ertapenem MIC of 0.5 μg/ml and meropenem MIC of 0.125 μg/ml
- After ertapenem therapy, resistance developed with ertapenem MIC increasing to 512 μg/ml while meropenem MIC increased to only 32 μg/ml 4
Similarly, a 2022 study found that in certain Klebsiella pneumoniae isolates:
- High-level ertapenem resistance (MIC = 64 mg/L) occurred while the isolates remained susceptible to meropenem and imipenem
- This differential resistance was linked to RamA downregulation of OmpK35 through micF, affecting ertapenem more significantly than other carbapenems 3
Diagnostic Implications
This differential resistance pattern creates diagnostic challenges:
Screening challenges: Meropenem-based screening alone may miss OXA-producing organisms that are resistant to ertapenem but susceptible to meropenem 5
Improved detection: Including both ertapenem and temocillin in screening can enhance detection of OXA-48-producing organisms 5
Rapid testing importance: The International Society for Antimicrobial Chemotherapy strongly recommends rapid testing to identify specific carbapenemase families, as each enzyme confers variable susceptibility profiles requiring different treatment strategies 1
Treatment Considerations
For infections caused by OXA-48-like producing CRE:
First-line treatment: Ceftazidime/avibactam is recommended as the first-line option for OXA-48-like producing CRE 2
Carbapenem selection: When using carbapenems, meropenem may remain effective against some OXA-producing organisms that show resistance to ertapenem 1
Resistance development risk: Be aware that exposure to ertapenem can trigger development of resistance to other carbapenems in initially susceptible OXA-producing organisms 4
Clinical Implications
Susceptibility testing: Test susceptibility to multiple carbapenems rather than assuming class-wide resistance or susceptibility
Treatment selection: For OXA-producing organisms, meropenem may be preferred over ertapenem when carbapenem therapy is indicated
Monitoring: Close monitoring for resistance development is essential when treating infections caused by OXA-producing organisms with any carbapenem
This differential resistance pattern highlights the importance of accurate identification of resistance mechanisms and appropriate selection of antimicrobial agents based on specific enzyme characteristics rather than assuming class-wide activity.