Mariana Castanheira, PhD
CSO
JMI Laboratories
North Liberty, Iowa, United States
Disclosure information not submitted.
Lalitagauri Deshpande, PhD
Research Scientist
JMI Laboratories
North Liberty, Iowa, United States
Disclosure information not submitted.
Cheung Yee, Msc, PhD
Associate Director, Medical & Scientific Affairs
Cipla Therapeutics
Warren, New Jersey, United States
Disclosure information not submitted.
Sandhya Das
Director Medical Affairs
Cipla Therapeutics
Warren, New Jersey, United States
Disclosure information not submitted.
Jaideep Gogtay, MD
Global Chief Medical Officer
Cipla Therapeutics
Warren, New Jersey, United States
Disclosure information not submitted.
Rodrigo Mendes, PhD
Director
JMI Laboratories
North Liberty, Iowa, United States
Disclosure information not submitted.
Helio Sader, MD, PhD, FIDSA
Senior Director
JMI Laboratories, Inc.
North Liberty, IA
Disclosure information not submitted.
Title: Plazomicin In Vitro Activity Against Global KPC-producing Klebsiella pneumoniae Isolates
Introduction: Plazomicin (PLZ) is a next-generation aminoglycoside approved for the treatment of complicated urinary tract infections. PLZ was developed to overcome common aminoglycoside resistance mechanisms seen in Gram-negative bacteria. We evaluated the activity of PLZ and older aminoglycosides against KPC-producing K. pneumoniae (KPN) isolates, which often display resistance to older aminoglycosides (AMG).
Methods: KPN clinical isolates collected during 2016-2019 were susceptibility tested by reference broth microdilution methods against PLZ and comparator agents. CLSI breakpoints were applied for analysis. Carbapenem-resistant isolates were screened for KPC-encoding genes using whole genome sequencing and data analysis.
Results: A total of 339 KPC-KPN were identified. These isolates were recovered in 17 countries, most commonly in Italy, Brazil, and the US (109, 83, and 60 isolates, respectively). PLZ was active against 92.0% of the isolates. Amikacin (AMK), gentamicin, and tobramycin were active against 61.1%, 52.5%, and 14.5% of the isolates, respectively. Beta-lactam agents and levofloxacin had limited activity against these isolates (< 15% susceptible). Tigecycline inhibited 97.3% of the isolates (US-FDA breakpoint) and 78.5% of the isolates exhibited an intermediate MIC result against colistin (COL; £2 mg/L). PLZ and tigecycline were the most active agents tested against 72 COL-resistant KPC-KPN isolates, inhibiting 83.3% and 97.2% of these isolates, respectively. AMK was active against 48.6% of the isolates. Gentamicin inhibited 47.2% of the isolates. Applying AMK breakpoints (susceptible £2 mg/L) generated with similar parameters used to establish the PLZ breakpoints for other newer agents, AMK was only active against 25.4% of the KPC-KPN and 6.9% of the 72 COL-resistant KPC-producing isolates. The overall PLZ susceptibility rates were 100% in North America, 92.9% in the Asia-Pacific region, 91.4% in Europe and 88.2% in Latin America.
Conclusions: Among the studied aminoglycosides, PLZ displayed greater activity against KPC-producing K. pneumoniae. KPC-KPN are usually multidrug resistant, and infections caused by these organisms are challenging to treat. PLZ seems to be a suitable treatment option for infections caused by MDR KPN isolates given that PLZ was the most active among the AMGs studied.