What clues on an antibiotic sensitivity report can indicate the type of carbapenemase (carbapenem-resistant enzyme) present in a patient's infection?

Identifying Carbapenemase Type from Antibiotic Sensitivity Reports

The most critical clue on antibiotic sensitivity reports is the pattern of resistance to specific beta-lactam/beta-lactamase inhibitor combinations: resistance to ceftazidime/avibactam and meropenem/vaborbactam with retained susceptibility to aztreonam strongly suggests metallo-beta-lactamase (MBL) production, while susceptibility to ceftazidime/avibactam or meropenem/vaborbactam indicates KPC or OXA-48-like carbapenemases. 1, 2

Key Resistance Patterns by Carbapenemase Class

Class A Carbapenemases (KPC)

• KPC producers typically show susceptibility to ceftazidime/avibactam and meropenem/vaborbactam, as these novel beta-lactam/beta-lactamase inhibitor combinations effectively inhibit Class A enzymes 1, 2
• KPC remains the most common carbapenemase globally, accounting for 47.4% of meropenem-resistant Enterobacterales 1, 2
• Some KPC-producing strains may have MICs that remain within the susceptible range for carbapenems, making them difficult to detect without confirmatory testing 1

Class B Metallo-Beta-Lactamases (NDM, VIM, IMP)

• MBL producers show resistance to ceftazidime/avibactam and meropenem/vaborbactam but retain susceptibility to aztreonam, as MBLs cannot hydrolyze monobactams 1, 2, 3
• MBLs represent approximately 20.6% of carbapenem-resistant Enterobacterales 1, 2
• These organisms typically show resistance to all beta-lactams except aztreonam, which is the defining characteristic 1, 2
• Colistin and tigecycline may show retained activity, though resistance rates vary 3, 4

Class D Carbapenemases (OXA-48-like)

• OXA-48-like enzymes account for approximately 19% of carbapenemases in Enterobacterales 1, 2
• OXA-48 producers typically show susceptibility to ceftazidime/avibactam, similar to KPC producers 1
• These organisms may demonstrate variable carbapenem MICs, sometimes remaining in the susceptible range 1

Additional Sensitivity Pattern Clues

Aminoglycoside Susceptibility

• Amikacin susceptibility may be preserved in some carbapenemase producers, with resistance rates as low as 19% in certain populations 4
• This can provide a treatment option while awaiting definitive carbapenemase identification 4

Polymyxin and Tigecycline Activity

• Colistin typically shows the lowest resistance rates (2.7-11%) among carbapenem-resistant organisms, making it a potential empiric option 1, 4
• Tigecycline resistance rates range from 11% in some studies, though clinical efficacy data are limited 4

Critical Diagnostic Considerations

Elevated but "Susceptible" MICs

• Carbapenem-susceptible Enterobacterales with elevated MICs or reduced disk diffusion zone sizes should undergo modified Hodge test (MHT) for carbapenemase detection, as some carbapenemase producers remain technically susceptible by standard breakpoints 1
• The MHT demonstrates sensitivity and specificity exceeding 90% for identifying carbapenemase-producing Enterobacterales 1

Co-Production of Multiple Beta-Lactamases

• Most carbapenem-resistant organisms carry combinations of beta-lactamases, with 76% of strains in one study carrying OXA-48, SHV, TEM, and CTX-M-type enzymes simultaneously 4
• The presence of ESBL genes (CTX-M, SHV, TEM) is nearly universal (97-100%) in carbapenem-resistant isolates 4

Common Pitfalls and How to Avoid Them

Assuming All Carbapenem Resistance is KPC

• Geographic and institutional epidemiology varies significantly—while KPC predominates in the United States (47.4% of cases), MBL producers are increasingly detected and represent 20.6% of carbapenem-resistant isolates 1, 2, 5
• Using ceftazidime/avibactam monotherapy for an unrecognized MBL producer will result in treatment failure, as avibactam does not inhibit metallo-enzymes 5

Misinterpreting Novel Agent Susceptibility

• Resistance to both ceftazidime/avibactam AND meropenem/vaborbactam is the hallmark of MBL production and should trigger consideration of aztreonam-based combination therapy 1, 2, 3
• Cefiderocol may show activity against MBL producers when other options fail 6, 7

Overlooking Infection Control Implications

• All carbapenem-resistant Enterobacterales require contact precautions regardless of carbapenemase type, as the resistance genes are carried on mobile genetic elements with high transmission potential 1

Algorithmic Approach to Sensitivity Report Interpretation

1. First, check carbapenem susceptibility: If intermediate or resistant, proceed to step 2 1

2. Evaluate novel beta-lactam/inhibitor combinations:

   • If susceptible to ceftazidime/avibactam OR meropenem/vaborbactam → likely KPC or OXA-48 1, 2
   • If resistant to BOTH ceftazidime/avibactam AND meropenem/vaborbactam → likely MBL 1, 2, 3

3. Check aztreonam susceptibility:

   • If aztreonam susceptible with resistance to ceftazidime/avibactam → confirms MBL 1, 2, 3
   • If aztreonam resistant → likely KPC with co-production of ESBL 4

4. Request rapid molecular testing to definitively identify carbapenemase family (KPC, NDM, VIM, OXA-48), as treatment efficacy depends entirely on the specific enzyme present 1, 5