Program Schedule

1671
A Fatal Outbreak of a Rare but Emerging Clone of Extensively Drug-resistant Acinetobacter baumannii with Enhanced Virulence

Session: Poster Abstract Session: Microbial and Host Factors
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Background: The virulence mechanisms of Acinetobacter baumannii(AB) are not completely understood. Also, a high degree of virulence in immunocompetent hosts is unusual for AB.   A cluster of six fatal AB infections in mostly immune-competent patients who received early infectious diseases consultation and appropriate antimicrobial therapy led us to hypothesize that isolates from these patients could possess unique traits that enhance virulence.

Methods: To test our hypothesis, we determined the health status of patients using three different co-morbidity and illness severity scoring systems, characterized isolates using comparative genomics, and evaluated the virulence of each isolate in a validated animal model.

Results: No patient had scores that indicated excessive co-morbidities or critical physiologic dysfunction. Two patients had bacteremia scores that indicated severe illness.  Genomic analysis showed that two unrelated AB clones were associated with the infections.  The clone associated with the majority (5 of 6) of patient deaths, clade B, is evolutionarily distinct from the three main international clonal complexes and is most closely related to strains isolated in the Czech Republic in 1994 and in a U.S. military hospital in Germany in 2003.  One clade B isolate, MRSN16897, is hyper-virulent in a murine pulmonary model of infection when compared to other well-known and previously tested AB isolates. Of note, MRSN16987 establishes disseminating, fatal infections, even in healthy mice when other strains of AB cannot. Clade B strains contain virulence genes whose products differ from those in the majority of AB strains, including loci involved in iron metabolism, protein secretion, and glycosylation. Using genome sequences of the fatal strains and related isolates from our repository, we developed a PCR-based assay to rapidly and specifically detect clade B isolates. (This clade is not distinguishable by multi-locus sequence typing.)

Conclusion: We identified genomic correlates of virulence (a unique gene set in the progenitor, and 4 single nucleotide changes a hypervirulent derivitave ) in the emerging AB clone. This clone is notable for a combination of resistance and higher virulence. Our findings highlight the value of combining surveillance, biobanking, and basic research.

Crystal Jones, PhD1, Megan Clancy, MD2, Shweta Singh1, Cary Honnold, DVM1, Erik Snesrud, BS1, Patrick Mcgann, PhD1, Fatma Onmus-Leone, MS1, Ana Ong1, Yoon Kwak, MS1, Paige Waterman, MD1, Daniel Zurawski, PhD1, Robert Clifford, PhD1 and Emil Lesho, DO1, (1)Walter Reed Army Institute of Research, Silver Spring, MD, (2)Providence Alaska Medical Center, Anchorage, AK

Disclosures:

C. Jones, None

M. Clancy, None

S. Singh, None

C. Honnold, None

E. Snesrud, None

P. Mcgann, None

F. Onmus-Leone, None

A. Ong, None

Y. Kwak, None

P. Waterman, None

D. Zurawski, None

R. Clifford, None

E. Lesho, None

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