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Background Antimicrobial susceptibility testing (AST) is not routinely performed for Clostridioides difficile and data evaluating minimum inhibitory concentrations (MICs) are limited. We performed AST and whole genome sequencing (WGS) for 593 C. difficile isolates collected between 2012 and 2017 through the Centers for Disease Control and Prevention's Emerging Infections Program. Methods MICs to 6 antimicrobial agents (ceftriaxone, clindamycin, meropenem, metronidazole, moxifloxacin, and vancomycin) were determined using the reference agar dilution method according to Clinical and Laboratory Standards Institute guidelines. Whole genome sequencing was performed on all isolates to detect the presence of genes or mutations previously associated with resistance. Results Among all isolates, 98.5% displayed a vancomycin MIC ≤2 μg/mL and 97.3% displayed a metronidazole MIC ≤2 μg/mL. Ribotype 027 (RT027) isolates displayed higher vancomycin MICs (MIC50: 2 μg/mL; MIC90: 2 μg/mL) than non-RT027 isolates (MIC50: 0.5 μg/mL; MIC90: 1 μg/mL) (P <.01). No vanA/B genes were detected. RT027 isolates also showed higher MICs to clindamycin and moxifloxacin and were more likely to harbor associated resistance genes or mutations. Conclusions Elevated MICs to antibiotics used for treatment of C. difficile infection were rare, and there was no increase in MICs over time. The lack of vanA/B genes or mutations consistently associated with elevated vancomycin MICs suggests there are multifactorial mechanisms of resistance. Ongoing surveillance of C. difficile using reference AST and WGS to monitor MIC trends and the presence of antibiotic resistance mechanisms is essential. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Enterobacterales (CRE) are a growing public health concern due to resistance to multiple antibiotics and potential to cause health care-associated infections with high mortality. Carbapenemase-producing CRE are of particular concern given that carbapenemase-encoding genes often are located on mobile genetic elements that may spread between different organisms and species. In this study, we performed phenotypic and genotypic characterization of CRE collected at eight U.S. sites participating in active population- and laboratory-based surveillance of carbapenem-resistant organisms. Among 421 CRE tested, the majority were isolated from urine (n = 349, 83%). Klebsiella pneumoniae was the most common organism (n = 265, 63%), followed by Enterobacter cloacae complex (n = 77, 18%) and Escherichia coli (n = 50, 12%). Of 419 isolates analyzed by whole genome sequencing, 307 (73%) harbored a carbapenemase gene; variants of blaKPC predominated (n = 299, 97%). The occurrence of carbapenemase-producing K. pneumoniae, E. cloacae complex, and E. coli varied by region; the predominant sequence type within each genus was ST258, ST171, and ST131, respectively. None of the carbapenemase-producing CRE isolates displayed resistance to all antimicrobials tested; susceptibility to amikacin and tigecycline was generally retained. [ABSTRACT FROM AUTHOR]

Enterococcus faecalis and faecium with resistance to daptomycin and/or linezolid are emerging globally. We present the genomic characterization of daptomycin- and linezolid-resistant E. faecalis and E. faecium surveillance isolates from the United States, 2013–2016. Daptomycin resistance was low among E. faecalis (2/364, 0.5%) and E. faecium (17/344, 5%). The majority (71%, 12/17) of daptomycin-resistant E. faecium isolates belonged to the emerging ST736 clone and contained mutations in liaFSR and cls previously associated with resistance. However, 1/2 E. faecalis and 3/17 E. faecium did not contain these mutations previously associated with daptomycin resistance. Linezolid resistance was rare among E. faecalis (1/364, 0.3%) and E. faecium (2/344, 0.6%). These two E. faecium isolates, one of which was also resistant to daptomycin and vancomycin, contained the 23S rRNA nucleotide mutation (G2576T) associated with linezolid resistance. Long-read sequencing revealed the linezolid-resistant E. faecalis isolate contained chromosomal- and plasmid-encoded copies of optrA. The chromosomal optrA was located on the recently described Tn 6674 multiresistance transposon. The second copy of optrA was encoded on an ∼65 kb mosaic plasmid, with component regions sharing high sequence identity to optrA -encoding multiresistance plasmids of animal origin. The optrA -encoding plasmid contained open reading frames predicted to encode proteins associated with a pheromone-responsive plasmid transfer system, and filter mating experiments confirmed the plasmid was conjugative. Continued surveillance of enterococci is necessary to assess the prevalence and trends of daptomycin and linezolid resistance in the United States, characterize resistance mechanisms and how they transfer, and monitor for emerging sequence types associated with resistance. [ABSTRACT FROM AUTHOR]

Background Previous reports suggested that US methicillin-resistant Staphylococcus aureus (MRSA) strain epidemiology has changed since the rise of USA300 MRSA. We describe invasive MRSA trends by strain type. Methods Data came from 5 Centers for Disease Control and Prevention Emerging Infections Program sites conducting population-based surveillance and collecting isolates for invasive MRSA (ie, from normally sterile body sites), 2005–2013. MRSA bloodstream infection (BSI) incidence per 100 000 population was stratified by strain type and epidemiologic classification of healthcare exposures. Invasive USA100 vs USA300 case characteristics from 2013 were compared through logistic regression. Results From 2005 to 2013, USA100 incidence decreased most notably for hospital-onset (6.1 vs 0.9/100 000 persons, P <.0001) and healthcare-associated, community-onset (10.7 vs 4.9/100 000 persons, P <.0001) BSIs. USA300 incidence for hospital-onset BSIs also decreased (1.5 vs 0.6/100 000 persons, P <.0001). However, USA300 incidence did not significantly change for healthcare-associated, community-onset (3.9 vs 3.3/100 000 persons, P =.05) or community-associated BSIs (2.5 vs 2.4/100 000 persons, P =.19). Invasive MRSA was less likely to be USA300 in patients who were older (adjusted odds ratio [aOR], 0.97 per year [95% confidence interval {CI},.96–.98]), previously hospitalized (aOR, 0.36 [95% CI,.24–.54]), or had central lines (aOR, 0.44 [95% CI,.27–.74]), and associated with USA300 in people who inject drugs (aOR, 4.58 [95% CI, 1.16–17.95]). Conclusions Most of the decline in MRSA BSIs was from decreases in USA100 BSI incidence. Prevention of USA300 MRSA BSIs in the community will be needed to further reduce burden from MRSA BSIs. [ABSTRACT FROM AUTHOR]

We report 9 ciprofloxacin-resistant Salmonella enterica serotype Typhi isolates submitted to the US National Antimicrobial Resistance Monitoring System during 1999-2008. The first 2 had indistinguishable pulsed-field gel electrophoresis patterns and identical gyrA and parC mutations. Eight of the 9 patients had traveled to India within 30 days before illness onset. [ABSTRACT FROM AUTHOR]

Background The recent discovery of carbapenemase-producing hypervirulent Klebsiella pneumoniae (CP-HvKP) has signaled the convergence of multidrug resistance and pathogenicity, with the potential for increased mortality. While previous studies of CP-HvKP isolates revealed that most carried carbapenemase genes and hypervirulence elements on separate plasmids, a 2018 report from China confirmed that both could be harbored on a single, hybrid carbapenemase-hypervirulent plasmid. As part of a project sequencing isolates carrying multiple carbapenemase genes identified through CDC's Antibiotic Resistance Laboratory Network (AR Lab Network), we discovered a bla NDM-1 -bearing hypervirulent plasmid found in a KPC- and NDM-positive K. pneumoniae from the United States. Methods Antimicrobial susceptibility testing (AST) was performed by reference broth microdilution against 23 agents. Whole-genome sequencing (WGS) was performed on Illumina MiSeq and PacBio RS II platforms. Results AST results indicated the isolate was extensively drug-resistant, as it was non-susceptible to at least one agent in all but two drug classes; it was susceptible to only tigecycline and tetracycline. Analysis of WGS data showed the isolate was ST11, the same sequence type that caused a fatal outbreak of CP-HvKP in China in 2016. The genome included two plasmids. The smaller one (129kbp) carried seven antibiotic resistance (AR) genes, including the carbapenemase gene bla KPC-2 . The larger plasmid (354kbp) harbored 11 AR genes, including the metallo-β-lactamase gene bla NDM-1 , as well as virulence factors iucABCD/iutA , peg-344 , rmpA , and rmpA2 , which comprise four of the five genes previously identified as predictors of hypervirulence in K. pneumoniae. Conclusion This is the first report of a hybrid carbapenemase-hypervirulent plasmid in the United States. The presence of both blaNDM-1 and hypervirulence elements on the same plasmid suggests that the CP-Hv pathotype could spread rapidly through horizontal transfer. This discovery demonstrates the critical role of genomic characterization of emerging resistance and virulence phenotypes by the AR Lab Network as part of US containment efforts. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

CTX-M-type β-lactamases are increasing among US Enterobacteriaceae isolates. Of 2,165 non-Typhi Salmonella isolates submitted in 2007 to the National Antimicrobial Resistance Monitoring System, 100 (4.6%) displayed elevated MICs (≥2 mg/L) of ceftriaxone or ceftiofur. Three isolates (serotypes Typhimurium, Concord, and I 4,5,12:i:--) contained blaCTX-M-5, blaCTX-M-15, and blaCTX-M-55/57, respectively. [ABSTRACT FROM AUTHOR]

We determined the prevalence of plasmid-mediated quinolone resistance mechanisms among non-Typhi Salmonella spp. isolated from humans, food animals, and retail meat in the United States in 2007. Six isolates collected from humans harbored aac(6')lb-cr or a qnr gene. Most prevalent was qnrS1. No animal or retail meat isolates harbored a plasmid-mediated mechanism. [ABSTRACT FROM AUTHOR]

Background Infections with metallo-β-lactamase (MBL)-producing organisms are emerging in the United States. Treatment options for these infections are limited. We describe MBL genes among carbapenemase positive carbapenem-resistant Enterobacteriaceae (CP-CRE) and Pseudomonas aeruginosa (CP-CRPA) isolates tested during the first two years of the Antibiotic Resistance Laboratory Network (AR Lab Network). Methods State and local public health laboratories tested CRE and CRPA isolates for organism identification, antimicrobial susceptibility, and PCR-based detection of bla KPC, bla NDM, bla OXA-48-like, bla VIM, and bla IMP carbapenemase genes. All testing results were sent to CDC at least monthly. Results Since January 2017, the AR Lab Network tested 21,733 CRE and 14,141 CRPA. CP-CRE were detected in 37% of CRE; 2% of CRPA were CP-CRPA. Among CP-CRE, 9% (686/8016) were MBL-producers (NDM, VIM, or IMP). Among MBL-producers, a bla NDM gene was detected most often (81%; 551/686). bla NDM were most common among Klebsiella spp. (47%; 261/551), bla IMP were most common among Providencia spp. (53%; 40/75), bla VIM was most common among Enterobacter spp. (19%; 25/62). Twelve percent (96) of MBL CP-CRE contained more than one carbapenemase gene. Among CP-CRPA, 73% (218/300) were MBL producers and bla VIM was the most common gene (62%; 186). Three (1%) MBL CP-CRPA contained more than one carbapenemase. Conclusion Increased testing of CRE and CRPA isolates through the AR Lab Network has facilitated early and rapid detection of hard-to-treat infections caused by MBL-producing organisms across the United States. The widespread distribution of MBL genes highlights the continued need for containment strategies that help prevent transmission between patients and among healthcare facilities. To support therapeutic decisions for severe infections caused by MBL-producing organisms, the AR Lab Network is now offering rapid susceptibility testing against aztreonam/avibactam, using digital dispenser technology. This testing program aims to close the gap between the availability of new drugs or drug combinations and the availability of commercial AST methods, thereby improving patient safety and antimicrobial stewardship. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background In 2009, the Centers for Disease Control and Prevention (CDC) implemented Clostridioides difficile infection (CDI) surveillance through the Emerging Infections Program (EIP) to monitor the incidence and evolving epidemiology of CDI in the United States. Since 2012, ribotypes (RTs) 027, 106, 002, 014, and 020 have constituted the top five strain types among both US community- and healthcare-associated isolates. Here we describe the changes in molecular epidemiology of C. difficile isolates collected in the United States in 2017. Methods In 2017, CDI surveillance was conducted at 10 EIP sites (CA, CO, CT, GA, MD, MN, NM, NY, OR, and TN). A convenience sample of clinical laboratories across EIP sites submitted C. difficile -positive stool specimens to the MN Department of Health Public Health Laboratory and Hines VA Hospital (IL) for culture. Isolates were forwarded to CDC and characterized by capillary-based PCR-ribotyping and PCR detection of tcdA , tcdB , cdtA , cdtB , and deletions in tcdC. Results In 2017, 1,051 C. difficile isolates were submitted; the total number of isolates received from each site ranged from 11 to 286 with a median of 85.5. In total, 143 RTs were observed, with the majority of isolates harboring toxin genes tcdA and tcdB (95%) and a wild-type tcdC sequence (71%). Among 556 healthcare-associated isolates, RT 027 was the most prevalent and the top RT at 5 sites (CA, GA, MD, NM, TN). Ribotype 106 was the most prevalent among 495 community-associated CA isolates and the top RT at 6 sites (CO, CT, GA, MD, MN, TN). Ribotype 027 significantly decreased from 2012 to 2017 among both healthcare-associated (21% vs 15%; p = 0.02) and community-associated isolates (17% vs 6%; P < 0.0001). Among healthcare-associated isolates, RT 076, which was observed in 8 EIP sites, increased from 2% in 2016 to 5% in 2017 (p = 0.05) and replaced RT 020 as one of the top 5 healthcare-associated RTs in 2017. Conclusion Despite an overall decline since 2012, RT 027 remained the most prevalent RT among healthcare-associated isolates submitted in 2017. The increased frequency of RT 076 among healthcare-associated isolates submitted in 2017 highlights the evolving molecular epidemiology of C. difficile and the need for continued surveillance to monitor potential emerging strains. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

A three-center study was performed to see if Etest gradient diffusion minimum inhibitory concentration (MIC) methodology correlated with reference broth microdilution (BMD) for antimicrobial susceptibility testing of Burkholderia pseudomallei against six antimicrobial agents known to be usually effective against B. pseudomallei. This study was performed to assist in the decision-making process for possible deployment of the Etest method for antimicrobial susceptibility testing of B. pseudomallei into several regional public health laboratories in the United States. Three laboratories each tested a challenge set of 30 genotypically diverse isolates collected from 15 different countries. MICs were performed by both Etest gradient diffusion and reference BMD for amoxicillin/clavulanate, ceftazidime, doxycycline, imipenem, tetracycline, and trimethoprim/sulfamethoxazole. Etest results for amoxicillin/clavulanate, ceftazidime, doxycycline, and imipenem correlated well with reference BMD by both category interpretation (≥97%) and essential agreement of MIC (≥93%). Tetracycline and trimethoprim/sulfamethoxazole Etests yielded poor correlation with BMD by category interpretation (80%) and essential agreement (70%), respectively. In conclusion, Etest gradient diffusion represents a valid option for antimicrobial susceptibility testing of B. pseudomallei against amoxicillin/clavulanate, ceftazidime, doxycycline, and imipenem. Tetracycline and trimethoprim/sulfamethoxazole Etest results showed some concerning lack of correlation with the corresponding reference BMD results. [ABSTRACT FROM AUTHOR]