Abstract
Background
MV is a newly approved β-lactam/β-lactamase inhibitor combination (BLIC) for the treatment of complicated urinary tract infections (cUTI). Vaborbactam is a cyclic boronic acid BLI that was mainly developed as a potent inhibitor of KPC carbapenemases and other Ambler class A&C enzymes. Vaborbactam is inactive against metallo-β-lactamases (MBL) and certain Class D enzymes (e.g. OXA-2 and OXA-48). We encountered a case of MV-resistant Klebsiella pneumoniae (MVRKP)and sought to explore the various mechanisms of MV resistance within KP.
Methods
A 65-year-old nursing home resident with multiple prior hospitalizations and recent exposure to antibiotics (Timeline) developed sepsis secondary to carbapenem-resistant Klebsiella pneumoniae (CRKP) cUTI. WGS of the patient’s isolate was performed. This was followed by random screening for MV resistance and WGS of other isolates from a historical database.
Results
Results of WGS are seen in the table below. Sequencing of our patient’s isolate revealed strain ST258 with a premature stop in aa89 of OmpK35 as well as insertions at Gly134 and Asp135 (i.e., the GD repeat) of OmpK36. Furthermore, the KPC plasmid’s copy number was approximately five times higher than the chromosome. No mutations encoding efflux system AcrAB-TolC were found.
Conclusion
Resistance to MV in KP was found in isolates that predate the drug’s availability. Notably, resistance occurred in the absence of MBLs and OXAs. The mechanism seems to involve outer membrane porin mutations in OmpK35 and/or OmpK36. WGS is a useful tool in identifying the mechanism of resistance especially for newer agents.
Table: Characterization of MVRKP by WGS
| Typing Enzymes Efflux | Outer Membrane Porin Variant | |||||||
|---|---|---|---|---|---|---|---|---|
| Strain | Date | MV MIC (mg/mL) | MLST | β-Lactamase |
Multidrug Transporters and Regulators
|
OmpK35 | OmpK36 | Notes |
| 1 | 2-1-12 | 16 | ST258 | KPC-2 & SHV-160 | Emr, mexk, oqxAB, smeD | FS 121insG | S to CZA and TGC | |
| 2 | 4-3-12 | 16 | ST258 | KPC-2 & SHV-160 | Emr, mexk, oqxAB, smeD | FS 121insG | S to CZA and TGC | |
| 3 | 2013 | 16 | ST258 | KPC-2 & SHV-160 | Emr, mexk, oqxAB, smeD | FS 121insG | S to CZA and TGC | |
| 4 | 2013 | 4 | ST258 | KPC-2 & SHV-160 | Emr, mexk, oqxAB, smeD | FS 121insG | S to CZA and TGC | |
| 5 | 2017 | 32 | ST258 | KPC-2, SHV-11, SHV-12 | N/A | STOP aa89 | 134-135 GD ins | CZA MIC 8 |
Disclosures
All authors: No reported disclosures.
Session: 67. Resistance Mechanisms: Gram-Negative
Thursday, October 4, 2018: 12:30 PM