scholarly journals 179. Identification and Whole Genome Sequencing Analysis of an Oxacillinase (OXA)-48-like-producing Acinetobacter baumannii Outbreak in California, January-May 2021

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S109-S110
Author(s):  
Diana Holden ◽  
Matthew Sylvester ◽  
John Crandall ◽  
Fengfeng Xu ◽  
Emily C Schneider ◽  
...  

Abstract Background In January 2021, a California acute care hospital (ACH A), a sentinel site for Acinetobacter baumannii (AB) surveillance, identified OXA-48-like-carbapenemase producing (CP) AB in a patient admitted from a ventilator-equipped skilled nursing facility (vSNF A); OXA-48-like AB had not been previously reported in the United States. Methods Our investigation included onsite infection control (IC) assessments, contact tracing, and point prevalence surveys (PPS) at vSNF A. The Antibiotic Resistance (AR) Laboratory Network performed carbapenemase testing on AB isolates (including those from ACH A) and PPS swabs. A case was defined as a patient with an OXA-48-like AB isolate, or an epidemiologically-linked patient with an OXA-48-like gene detected via screening. We performed whole genome sequencing (WGS) of OXA-48-like AB and other CP organisms on the Illumina MiSeq and Oxford Nanopore MinION for short and long read sequencing, respectively. Results Since January 2021, we have identified five OXA-48-like AB cases (including the index), six OXA-48-like cases (no organism recovered), and six patients with other CP organisms at ACH A and vSNF A. Since August 2019, vSNF A has concurrently been experiencing an OXA-109 AB outbreak. A second vSNF A patient, Patient 2, who overlapped with the index patient, had OXA-48-like Klebsiella pneumoniae (KP) (November 2019) and OXA-109 AB (May 2020) isolates. WGS of the index patient’s AB and Patient 2’s KP isolates identified a rare OXA-48-like gene located on the AB chromosome and a KP plasmid. The OXA-48-like AB was also carrying an OXA-109 gene, and hqSNP analysis indicated it varied by 9-44 single-nucleotide polymorphisms (SNPs) from 14 OXA-109 AB isolates linked to that outbreak, and 0-3 SNPs from the other OXA-48-like AB case isolates. Figure 1. Phylogenetic Tree Comparison of OXA-109 AB and OXA-48-like AB Isolates Figure 2. Epidemic Curve of OXA-109 AB, OXA-48-like AB, and Other CP Organism Cases, 2019-2021 Conclusion The first reported case of OXA-48-like AB in the US was identified through public health sentinel laboratory surveillance, allowing prompt response to contain spread of a novel multidrug-resistant organism (MDRO). WGS detected a rare OXA-48-like gene in AB and KP and provides evidence for possible interspecies transfer of this gene from KP to AB through plasmid transfer followed by chromosomal integration. Disclosures All Authors: No reported disclosures

2015 ◽  
Vol 82 (2) ◽  
pp. 459-466 ◽  
Author(s):  
S. Zhao ◽  
G. H. Tyson ◽  
Y. Chen ◽  
C. Li ◽  
S. Mukherjee ◽  
...  

ABSTRACTThe objectives of this study were to identify antimicrobial resistance genotypes forCampylobacterand to evaluate the correlation between resistance phenotypes and genotypes usingin vitroantimicrobial susceptibility testing and whole-genome sequencing (WGS). A total of 114Campylobacterspecies isolates (82C. coliand 32C. jejuni) obtained from 2000 to 2013 from humans, retail meats, and cecal samples from food production animals in the United States as part of the National Antimicrobial Resistance Monitoring System were selected for study. Resistance phenotypes were determined using broth microdilution of nine antimicrobials. Genomic DNA was sequenced using the Illumina MiSeq platform, and resistance genotypes were identified using assembled WGS sequences through blastx analysis. Eighteen resistance genes, includingtet(O),blaOXA-61,catA,lnu(C),aph(2″)-Ib,aph(2″)-Ic,aph(2′)-If,aph(2″)-Ig,aph(2″)-Ih,aac(6′)-Ie-aph(2″)-Ia,aac(6′)-Ie-aph(2″)-If,aac(6′)-Im,aadE,sat4,ant(6′),aad9,aph(3′)-Ic, andaph(3′)-IIIa, and mutations in two housekeeping genes (gyrAand 23S rRNA) were identified. There was a high degree of correlation between phenotypic resistance to a given drug and the presence of one or more corresponding resistance genes. Phenotypic and genotypic correlation was 100% for tetracycline, ciprofloxacin/nalidixic acid, and erythromycin, and correlations ranged from 95.4% to 98.7% for gentamicin, azithromycin, clindamycin, and telithromycin. All isolates were susceptible to florfenicol, and no genes associated with florfenicol resistance were detected. There was a strong correlation (99.2%) between resistance genotypes and phenotypes, suggesting that WGS is a reliable indicator of resistance to the nine antimicrobial agents assayed in this study. WGS has the potential to be a powerful tool for antimicrobial resistance surveillance programs.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S644-S645
Author(s):  
Sarah McLeod ◽  
Samir Moussa ◽  
Meredith Hackel ◽  
Alita Miller

Abstract Background Acinetobacter baumannii-calcoaceticus complex (ABC) causes severe infections that are difficult to treat due to increasing resistance to antibacterial therapy. Sulbactam (SUL) has intrinsic antibacterial activity against ABC, but its clinical utility has been compromised by the prevalence of serine β-lactamases. Durlobactam (DUR, previously ETX2514) is a diazabicyclooctenone β-lactamase inhibitor with potent activity against Ambler classes A, C and D serine β-lactamases that effectively restores SUL activity against ABC isolates. SUL-DUR is an antibiotic designed to treat serious infections caused by Acinetobacter, including multidrug-resistant strains, which is currently in Phase 3 clinical testing. The potency of SUL-DUR against geographically diverse ABC isolates collected in 2018 was measured. Methods 929 ABC isolates, including 698 A. baumannii, 13 A. calcoaceticus, 54 A. nosocomialis, and 164 A. pittii, were collected in 2018 from geographically diverse medical centers in the United States, Europe, Latin America, Israel and the Asia-Pacific region. Susceptibility testing was performed according to CLSI guidelines. Data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Select isolates were subjected to whole genome sequencing with an Illumina MiSeq V2 instrument and analysis using CLCBio Genomics Workbench v6.5. Results In surveillance of 929 global isolates from 2018, the SUL-DUR MIC90 was 2 mg/L compared with 64 mg/L for SUL alone. This level of potency was consistent across species, regions, source of infection and subsets of resistance phenotypes. Fifty percent of the isolates were non-susceptible to carbapenems. Only 7 isolates (0.75%) had SUL-DUR MIC values >4 mg/L. Whole genome sequencing of these 7 isolates revealed that they either encoded the metallo-β-lactamase NDM-1, which DUR does not inhibit, or single amino acid substitutions near the active site of PBP3, the primary target of SUL. Conclusion SUL-DUR demonstrated potent antibacterial activity against recent, geographically diverse clinical isolates of ABC, including MDR isolates. These data support the potential utility of SUL-DUR for the treatment of antibiotic-resistant infections caused by ABC. Disclosures Sarah McLeod, PhD, Entasis Therapeutics (Employee) Samir Moussa, PhD, Entasis Therapeutics (Employee) Alita Miller, PhD, Entasis Therapeutics (Employee)


Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 201
Author(s):  
Sang Mee Hwang ◽  
Hee Won Cho ◽  
Tae Yeul Kim ◽  
Jeong Su Park ◽  
Jongtak Jung ◽  
...  

Carbapenem-resistant Acinetobacter baumannii (CRAB) outbreaks in hospital settings challenge the treatment of patients and infection control. Understanding the relatedness of clinical isolates is important in distinguishing outbreak isolates from sporadic cases. This study investigated 11 CRAB isolates from a hospital outbreak by whole-genome sequencing (WGS), utilizing various bioinformatics tools for outbreak analysis. The results of multilocus sequence typing (MLST), single nucleotide polymorphism (SNP) analysis, and phylogenetic tree analysis by WGS through web-based tools were compared, and repetitive element polymerase chain reaction (rep-PCR) typing was performed. Through the WGS of 11 A. baumannii isolates, three clonal lineages were identified from the outbreak. The coexistence of blaOXA-23, blaOXA-66, blaADC-25, and armA with additional aminoglycoside-inactivating enzymes, predicted to confer multidrug resistance, was identified in all isolates. The MLST Oxford scheme identified three types (ST191, ST369, and ST451), and, through whole-genome MLST and whole-genome SNP analyses, different clones were found to exist within the MLST types. wgSNP showed the highest discriminatory power with the lowest similarities among the isolates. Using the various bioinformatics tools for WGS, CRAB outbreak analysis was applicable and identified three discrete clusters differentiating the separate epidemiologic relationships among the isolates.


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