Lecture on Carbapenem Resistance and IDSA Guidelines

Overview

• Carbapenem-resistant Enterobacteriaceae (CRE) cause thousands of deaths annually worldwide.
• Defined by CDC as Enterobacteriaceae resistant to at least one carbapenem antibiotic or producing a carbapenemase enzyme.
• Classification:
  • Carbapenemase-producing
  • Non-carbapenemase-producing groups (due to amplification of non-carbapenemase genes and disruption of the outer membrane).

Prevalence

• High prevalence: 35-60% of CRE cases in the US are carbapenemase-producing.

Common Carbapenemases

• KPCs (Klebsiella pneumoniae carbapenemase)
• NDMs (New Delhi metallo-beta-lactamase)
• VIMs (Verona integron-encoded metallo-beta-lactamase)
• IMI (imipenemase)
• OXA-48-like enzymes

Importance in Treatment

• Carbapenems are crucial antibiotics for sepsis and are broad-spectrum.
• Resistance necessitates changes in therapy.

Diagnostic Testing

• Phenotypic testing: differentiation between carbapenemase and non-carbapenemase-producing CRE.
• Molecular testing is also useful.

Treatment Guidelines

General Recommendations

• Clinical labs should perform phenotypic or genotypic testing to guide treatment.

Meropenem and Imipenem

• For isolates susceptible to meropenem/imipenem but resistant to ertapenem:
  • Extended infusion of meropenem/imipenem is recommended.
  • Standard infusion may be used for uncomplicated cystitis.
  • Consider severity and infection site for treatment decisions.

Antibiotics for Uncomplicated Cystitis

• Options: nitrofurantoin, trimethoprim-sulfamethoxazole, fosfomycin, colistin, ceftazidime-avibactam.

Treatment for Pyelonephritis and Complicated UTI

• Options: trimethoprim-sulfamethoxazole, ciprofloxacin, levofloxacin, aminoglycosides.

Treatment for Infections Outside UTI

• Consider patient's medical history and regional organism prevalence.
• Cefiderocol or ceftazidime-avibactam as monotherapy.
• Avoid extended carbapenem infusions due to mortality and nephrotoxicity risks.

KPC-Producing Infections

• Preferred: meropenem-vaborbactam.
• Ceftazidime-avibactam as second choice.

NDM-Producing Infections

• Preferred: ceftazidime-avibactam/aztreonam combination.
• Sepidicerol monotherapy as alternative.

OXA-48 Producing Organisms

• Preferred: ceftazidime-avibactam.
• Alternatives: tigecycline or eravacycline.

Resistance Emergence

• Resistance mechanisms vary based on genetic mutations and changes in permeability.
• Estimated resistance: 10-20% for ceftazidime-avibactam, 3% for meropenem-vaborbactam.

Role of Tetracyclines

• Not recommended for UTI or bloodstream infections.
• Suitable for intra-abdominal, skin, soft tissue, osteomyelitis, and respiratory infections.

Antibiotic Combination Therapy

• Empirical combination for initial treatment.
• Prolonged use can lead to adverse effects.
• Studies show no significant benefit of combination over monotherapy.

Conclusion

• IDSA recommendations emphasize monotherapy with preferred agents.
• Future sessions will cover other organisms and treatments.