Carbapenem Resistant Aeromonas hydrophila Carrying blacphA7 Isolated From Two Solid Organ Transplant Patients

Abstract

Aeromonas hydrophila resides in a variety of aquatic environments. Infections with A. hydrophila mainly occur after contact with fresh or brackish water. Nosocomial infections with A. hydrophila can also occur. A. hydrophila infections can be difficult to treat due to both intrinsic and acquired antimicrobial resistance (AMR) mechanisms. In 2018-19, we isolated multi-drug resistant (MDR) A. hyrodphila from two solid organ transplant patients with intra-abdominal infections. We aimed to characterize their AMR mechanisms and to determine their genetic relatedness to aid epidemiological investigation. We performed whole genome sequencing (WGS) using Illumina MiSeq and Nanopore MinIon on 3 A. hydrophila isolates, with one isolate from Patient A (blood) and two isolates from Patient B (abdominal and T-tube fluid, isolated 2 weeks apart). Phenotypic assays included: Broth Microdilution (BMD), Modified Hodge Test (MHT), Modified Carbapenem Inactivation Method (mCIM), and EDTA Carbapenem Inactivation Method (eCIM). Data analyses were performed using CLCbio and Geneious. AMR genomic analysis revealed that all three isolates possess chromosomally encoded genes including bla OXA−12 (oxacillinase), bla cepS (AmpC), and bla cphA7 (metallo-beta-lactamase). All isolates tested strongly positive by MHT and mCIM, but only Patient B's second isolate (after 2 weeks of meropenem treatment) tested positive by eCIM. More intriguingly, Patient B's first isolate (before meropenem treatment) tested falsely susceptible to carbapenems by BMD, suggesting bla cphA7 gene was not expressed constitutively. Phylogenetic analysis showed the two isolates from Patient B were highly similar with only 1 SNP difference. The isolate from Patient A only differed from Patient B's isolates by 35 and 36 SNPs, respectively, suggesting close genetic relatedness. Further epidemiological investigation is undergoing. We report the first cases of CphA-mediated carbapenem resistant A. hydrophila in the U.S. It is concerning that 1 out of 3 isolates tested falsely susceptible to carbapenems by BMD despite clear carbapenemase production shown by strongly positive MHT and mCIM. In both cases, meropenem was initially used to treat the patients. Clinicians and microbiologists in the US should be aware of the emerging MDR Aeromonas nosocomial infections and the potential false carbapenem susceptible results due to CphA-type carbapenemase, which may be induced during treatment.

Novel Insights into bla GES Mobilome Reveal Extensive Genetic Variation in Hospital Effluents

“…As a resultant, this led to increased resistance to carbapenems. The Aero28 isolate presented also showed resistance to the novel carbapenem-β-lactamase inhibitor combinations, suggesting that, unlike in Aero22, an induction of the cphA gene may have occurred ( 27 ). The absence of this gene led to the reduction of MIC to carbapenems observed in GES-7 and GES-16 transformants.…”

Characterization and Antimicrobial Resistance of Environmental and Clinical Aeromonas Species Isolated from Fresh Water Ornamental Fish and Associated Farming Environment in Sri Lanka

“…Human infections caused by Carbapenem resistant Aeromonas spp. have been reported in the recent past in Colombia and in United States [68,69]. Carbapenem resistance has been associated with the production of carbapenems hydrolyzing Aeromonas (CphA).…”

Aeromonas species isolated from aquatic organisms, insects, chicken, and humans in India show similar antimicrobial resistance profiles

“…examined in this study could be that they intrinsically are encoded in the genomes. Despite so, suffice to point out that the MBL genes detected in this study have been reported from different bacteria species isolated from humans, animals, fish, chickens, mussel and the environments in different countries ( Maravić et al, 2013 ; Bottoni et al, 2015 ; Hilt et al, 2020 ; Ramsamy et al, 2020 ; Bertran et al, 2021 ; Wang Y. et al, 2021 ). Thus, it is likely that these AMR genes exist in other bacteria species in different aquatic environments and a wide range of host species in India.…”