In this episode, we discuss six newer antibiotics that target multidrug resistant gram negative bacteria with Dr. Christie Bertram, PharmD, BCIDP. We review common resistance mechanisms, particularly to carbapenems, and highlight the current role in therapy for the following antibiotics: ceftolozane/tazobactam (Zerbaxa®), ceftazidime/avibactam (Avycaz®), meropenem/vaborbactam (Vabomere®), imipenem/cilastatin/relebactam (Recarbrio®), cefiderocol (Fetroja®), and eravacycline (Xerava®).

Key Concepts

1. Ceftolozane/tazobactam (Zerbaxa®) is primarily used for multidrug resistant Pseudomonas; it does not cover carbapenemase-producing organisms and (despite the tazobactam) needs metronidazole for intra-abdominal anaerobic coverage.
2. Ceftazidime/avibactam (Avycaz®) is primarily used to cover CRE (Carbapenem-resistant Enterobacterales) but also has activity for many other gram negatives except Acinetobacter.
3. Meropenem/vaborbactam (Vabomere®) has similar coverage to Avycaz® but may provide coverage for certain KPCs (Klebsiella pneumoniae carbapenemase). Vaborbactam does not restore activity for meropenem-resistant Pseudomonas.
4. Imipenem/cilastatin/relebactam (Recarbrio®) has similar coverage to Avycaz® and Vabomere®; true niche in therapy is not yet well defined.
5. Cefiderocol (Fetroja®) uses a unique mechanism to enter gram negative bacteria and has a broad spectrum of activity against carbapenemase-producing bacteria and many other multidrug resistant gram negatives. It has no gram positive activity.
6. Eravacycline (Xerava®) is a tigecycline-like tetracycline with a broad spectrum of activity against carbapenemase-producing gram negative, gram positive, an anaerobic bacteria EXCEPT it lacks coverage for Pseudomonas.

References

• Yusuf E, Bax HI, Verkaik NJ, van Westreenen M. An Update on Eight "New" Antibiotics against Multidrug-Resistant Gram-Negative Bacteria. J Clin Med. 2021;10(5):1068. Published 2021 Mar 4. doi:10.3390/jcm10051068
• CDC Antibiotic Resistance Threats in the United States, 2019 report. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf