Can oxa (oxacillinase) enzymes exhibit sensitivity to some carbapenems while showing resistance to others?

OXA Enzymes Can Show Differential Sensitivity to Different Carbapenems

Yes, OXA (oxacillinase) enzymes can definitely show sensitivity to some carbapenems while exhibiting resistance to others, as their hydrolytic activity varies significantly across different carbapenem molecules.

Mechanism of OXA-Mediated Carbapenem Resistance

OXA enzymes belong to Class D β-lactamases in the Ambler classification system 1. These enzymes have diverse hydrolytic profiles that vary considerably between different OXA variants:

• OXA-48-like enzymes primarily hydrolyze penicillins at high levels and carbapenems at lower levels, while generally sparing broad-spectrum cephalosporins 2
• Different OXA variants show significant variation in their ability to hydrolyze specific carbapenems 3
• The coefficient of activity for imipenem among OXA-48 variants ranges from 550 mM^-1·s^-1 to as low as 0.02 mM^-1·s^-1, demonstrating vast differences in hydrolytic capability 3

Evidence of Differential Carbapenem Susceptibility

The differential activity of OXA enzymes against various carbapenems is well-documented:

• OXA-48 variants can hydrolyze some carbapenems while having minimal activity against others 3
• OXA-40 (found in Acinetobacter baumannii) shows variable hydrolytic activity against different β-lactams, including carbapenems 4
• OXA-163 (an OXA-48 variant) has reduced carbapenem-hydrolyzing activity but increased activity against broad-spectrum cephalosporins 2

Clinical Implications

This differential susceptibility has important clinical implications:

• Rapid testing to identify specific carbapenemase families (including OXA-48-like) is strongly recommended to guide appropriate antibiotic selection 5
• Knowledge of the specific OXA variant is crucial because each enzyme confers variable susceptibility profiles that require different treatment strategies 5
• Some OXA-producing organisms may appear susceptible to certain carbapenems in standard susceptibility tests while being resistant to others 1

Factors Affecting Carbapenem Resistance

The level of resistance conferred by OXA enzymes can be influenced by:

1. Specific amino acid substitutions: Even single amino acid changes can significantly alter the hydrolytic profile 4
2. Expression levels: Increased expression due to upstream insertion sequences can enhance resistance 6
3. Additional resistance mechanisms: When combined with porin defects or other β-lactamases, OXA producers may exhibit higher levels of resistance to carbapenems 2

Detection Challenges

The variable activity of OXA enzymes against different carbapenems creates diagnostic challenges:

• Many OXA-48-like producers may not exhibit resistance to broad-spectrum cephalosporins or show only decreased susceptibility to carbapenems 2
• This can make their recognition and detection challenging in clinical settings 2
• Specialized testing methods may be needed to accurately identify these resistance mechanisms 1

Therapeutic Considerations

When treating infections caused by OXA-producing organisms:

• Carbapenems may still be effective against some OXA-producing organisms depending on the specific variant and its hydrolytic profile 1
• Alternative treatment options may include newer β-lactam/β-lactamase inhibitor combinations like ceftazidime-avibactam for certain OXA variants 1
• Combination therapy may be necessary in some cases 1

The differential susceptibility of OXA enzymes to various carbapenems underscores the importance of accurate identification of the specific carbapenemase type to guide optimal antimicrobial therapy and improve clinical outcomes.