Multidrug-resistant acinetobacter baumannii - plasmid-borne carbapenem and aminoglycoside co-resistance causing outbreak in Southwest Virginia.

Background: Multidrug-resistant (MDR) Gram-negative bacterial pathogens, often resistant to more than one class of antibiotics including carbapenems and aminoglycosides, pose serious threats in healthcare settings worldwide. A 2015 White House task force issued guidelines to combat antibiotic-resistant strains in the United States, which the Center for Diseases Center has termed "nightmare bacteria". MDR pathogens cause at least two million illnesses and 23,000 deaths annually in the U.S. MDR A. baumannii (MDR-Ab) cause 10% of hospital-acquired infections (HAI) with 70% patient mortality. A mini-outbreak of carbapenem-resistant (CR)MDR-Ab (CR-MDR-Ab) occurred during a 2009-2010H1N1epidemic at Carilion Medical Center (CMC) in Virginia, U.S; three of the nine patients died. To develop effective strategies for prevention, control and treatment of MDR infections, we are performing whole genome analysis of the clinical isolates of CR-MDR-Ab. Methods & Materials: To date, we have analyzed 68 Ab clinical isolates, including five CR-MDR-Ab outbreak strains. We have sequenced and analyzed whole genomes of the following MDRAb isolates: an isolate from outbreak patients (CMC-MDR-Ab4); a carbapenem-sensitive isolate (CMC-MDR-Ab59); and a CR-MDR-Ab (CMC-MDR-Ab66) isolate from sporadic cases. The sequencing was performed on the PacBioRSII platform. Results: The CR CMC-MDR-Ab strains were found to carry two plasmids, pCMCVTAb1 and pCMCVTAb2. The latter is conjugative type and carried two transposons: Tn2008-like, containing a beta-lactamase gene (blaOXA23) and conferring CR, and a TnaphA6 element causing aminoglycoside resistance and further reducing treatment choices. Their chromosomes carried five bla genes and an aphA1 gene. A PCR analysis based upon the resistant determinants showed that all outbreak isolates (100%) carried pCMCVTAb2 containing the two transposons. Fourteen of the remaining 63 isolates (22.22%) carried pCMCVTAb2 and of these, six (42.85%) carried Tn2008-like, and two (14.28%) carried TnaphA6. These differences are statistically significant using Fisher's exact, two-tailed p = 0.0011, p = 0.0445 and p = 0.0018. Conclusion: The results suggested that pCMCVTAb2 was responsible for the CR-MDR outbreak. A PCR analysis based on the antibiotic-resistant genes of pCMCVTAb2 could be used for rapid identification of CR-MDR-Ab strains, thereby helping to prevent the spread and providing guidance for identification and treatment of hospitalized patients with CR-MDR-Ab infections. [ABSTRACT FROM AUTHOR]