scholarly journals 603. Identification of a Carbapenemase-Producing, Extensively Drug-Resistant Klebsiella pneumoniae Isolate Carrying a blaNDM-1-Bearing, Hypervirulent Plasmid, United States 2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S282-S283
Author(s):  
Richard A Stanton ◽  
Gillian A McAllister ◽  
Amelia Bhatnagar ◽  
Maria Karlsson ◽  
Allison C Brown ◽  
...  
Keyword(s):  
United States ◽  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Critical Role ◽  
Illumina Miseq ◽  
The United States ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Drug Classes ◽  
Carbapenemase Gene

Abstract 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 blaNDM-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 blaKPC-2. The larger plasmid (354kbp) harbored 11 AR genes, including the metallo-β-lactamase gene blaNDM-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.

scholarly journals Case Report of an Extensively Drug-Resistant Klebsiella pneumoniae Infection With Genomic Characterization of the Strain and Review of Similar Cases in the United States

2018 ◽  
Vol 5 (5) ◽  
Author(s):  
Fiorella Krapp ◽  
Egon A Ozer ◽  
Chao Qi ◽  
Alan R Hauser
Keyword(s):  
United States ◽  
Case Report ◽  
Klebsiella Pneumoniae ◽  
Genome Sequencing ◽  
The United States ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Genomic Characterization

Abstract Reports of extensively drug-resistant and pan-drug-resistant Klebsiella pneumoniae (XDR-KP and PDR-KP) cases are increasing worldwide. Here, we report a case of XDR-KP with an in-depth molecular characterization of resistance genes using whole-genome sequencing, and we review all cases of XDR-KP and PDR-KP reported in the United States to date.

scholarly journals First Report on a Hyperepidemic Clone of KPC-3-Producing Klebsiella pneumoniae in Israel Genetically Related to a Strain Causing Outbreaks in the United States

2008 ◽  
Vol 53 (2) ◽  
pp. 818-820 ◽  
Author(s):  
Shiri Navon-Venezia ◽  
Azita Leavitt ◽  
Mitchell J. Schwaber ◽  
J. Kamile Rasheed ◽  
Arjun Srinivasan ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
The United States ◽  
Drug Resistant ◽  
Resistant Clone ◽  
Bacterial Strains ◽  
First Report ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Global Spread

ABSTRACT A highly epidemic carbapenem-resistant clone of KPC-3-producing Klebsiella pneumoniae emerged in Israel in 2006, causing a nationwide outbreak. This clone was genetically related to outbreak strains from the United States isolated in 2000 but differed in KPC-carrying plasmids. The threat of the global spread of hyperepidemic, extensively drug-resistant bacterial strains should be recognized and confronted.

scholarly journals 1675. Epidemiology of Urinary Tract Infections in the United States, 2009 - 2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S823-S823
Author(s):  
Kendra Foster ◽  
Linnea A Polgreen ◽  
Brett Faine ◽  
Philip M Polgreen
Keyword(s):  
United States ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Antibiotic Use ◽  
The United States ◽  
Drug Resistant ◽  
E Coli ◽  
Tract Infections

Abstract Background Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting. Methods We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization. Results There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively. Conclusion E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common. Disclosures All Authors: No reported disclosures

scholarly journals Activity of Plazomicin Tested against Enterobacterales Isolates Collected from U.S. Hospitals in 2016–2017: Effect of Different Breakpoint Criteria on Susceptibility Rates among Aminoglycosides

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Mariana Castanheira ◽  
Helio S. Sader ◽  
Rodrigo E. Mendes ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
16S Rrna ◽  
The United States ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant

ABSTRACT Plazomicin was active against 97.0% of 8,783 Enterobacterales isolates collected in the United States (2016 and 2017), and only 6 isolates carried 16S rRNA methyltransferases conferring resistance to virtually all aminoglycosides. Plazomicin (89.2% to 95.9% susceptible) displayed greater activity than amikacin (72.5% to 78.6%), gentamicin (30.4% to 45.9%), and tobramycin (7.8% to 22.4%) against carbapenem-resistant and extensively drug-resistant isolates. The discrepancies among the susceptibility rates for these agents was greater when applying breakpoints generated using the same stringent contemporary methods applied to determine plazomicin breakpoints.

scholarly journals Extensively Drug-Resistant Pseudomonas aeruginosa ST309 Harboring Tandem Guiana Extended Spectrum β-Lactamase Enzymes: A Newly Emerging Threat in the United States

2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Ayesha Khan ◽  
Truc T Tran ◽  
Rafael Rios ◽  
Blake Hanson ◽  
William C Shropshire ◽  
...  
Keyword(s):  
United States ◽  
Pseudomonas Aeruginosa ◽  
Phylogenetic Analysis ◽  
The United States ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Class 1 Integron ◽  
E Coli ◽  
Extensively Drug Resistant ◽  
Extended Spectrum

Abstract Background Treatment of serious infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa remains a challenge, despite the introduction of novel therapeutics. In this study, we report 2 extensively drug-resistant clinical isolates of sequence type (ST) 309 P aeruginosa resistant to all β-lactams, including the novel combinations ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. Methods Isolates were sequenced using both short-read (Illumina) and long-read technology to identify resistance determinants, polymorphisms (compared with P aeruginosa PAO1), and reconstruct a phylogenetic tree. A pair of β-lactamases, Guiana extended spectrum β-lactamase (GES)-19 and GES-26, were cloned and expressed in a laboratory strain of Escherichia coli to examine their relative impact on resistance. Using cell lysates from E coli expressing the GES genes individually and in tandem, we determined relative rates of hydrolysis for nitrocefin and ceftazidime. Results Two ST309 P aeruginosa clinical isolates were found to harbor the extended spectrum β-lactamases GES-19 and GES-26 clustered in tandem on a chromosomal class 1 integron. The presence of both enzymes in E coli was associated with significantly elevated minimum inhibitory concentrations to aztreonam, cefepime, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam, compared with those expressed individually. The combination of ceftazidime/avibactam plus aztreonam was active in vitro and used to achieve cure in one patient. Phylogenetic analysis revealed ST309 P aeruginosa are closely related to MDR strains from Mexico also carrying tandem GES. Conclusions The presence of tandem GES-19 and GES-26 is associated with resistance to all β-lactams, including ceftolozane/tazobactam. Phylogenetic analysis suggests that ST309 P aeruginosa may be an emerging threat in the United States.

scholarly journals 484. Metallo-β-Lactamase-Positive Carbapenem-Resistant Enterobacteriaceae and Pseudomonas aeruginosa in the Antibiotic Resistance Laboratory Network, 2017–2018

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S237-S237
Author(s):  
Allison C Brown ◽  
Sarah Malik ◽  
Jennifer Huang ◽  
Amelia Bhatnagar ◽  
Rocio Balbuena ◽  
...  
Keyword(s):  
United States ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
The United States ◽  
New Drugs ◽  
Carbapenem Resistant ◽  
Laboratory Network ◽  
Therapeutic Decisions ◽  
Carbapenemase Gene ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract 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 blaKPC, blaNDM, blaOXA-48-like, blaVIM, and blaIMP 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 blaNDM gene was detected most often (81%; 551/686). blaNDM were most common among Klebsiella spp. (47%; 261/551), blaIMP were most common among Providencia spp. (53%; 40/75), blaVIM 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 blaVIM 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.

scholarly journals 165. Emergence of Extensively Drug-Resistant Salmonella enterica Serotype Typhi Infections—United States, 2008–2020

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S99-S100
Author(s):  
Felicita Medalla ◽  
Louise Francois Watkins ◽  
Michael Hughes ◽  
Meseret Birhane ◽  
Layne Dorough ◽  
...  
Keyword(s):  
United States ◽  
Typhoid Fever ◽  
The United States ◽  
Empiric Therapy ◽  
Salmonella Typhi ◽  
International Travel ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Large Outbreak ◽  
Control And Prevention

Abstract Background Typhoid fever, caused by Salmonella Typhi, is fatal in 12%–30% of patients not treated with appropriate antibiotics. In 2016, a large outbreak of extensively drug-resistant (XDR) Typhi infections began in Pakistan with cases reported globally, including the United States. In 2021, the Centers for Disease Control and Prevention (CDC) issued a health advisory on XDR infections among U.S. residents without international travel. We describe resistance of Typhi infections diagnosed in the United States to help guide treatment decisions. Methods Typhoid fever is a nationally notifiable disease. Health departments report cases to CDC through the National Typhoid and Paratyphoid Fever Surveillance system. Isolates are submitted to the National Antimicrobial Resistance Monitoring System for antimicrobial susceptibility testing (AST) using broth microdilution. AST results are categorized by Clinical and Laboratory Standards Institute criteria. We defined XDR as resistant to ceftriaxone, ampicillin, chloramphenicol, and co-trimoxazole, and nonsusceptible to ciprofloxacin. Results During 2008–2019, of 4,637 Typhi isolates, 52 (1%) were ceftriaxone resistant (axo-R); 71% were ciprofloxacin nonsusceptible, 1 azithromycin resistant (azm-R), and none meropenem resistant. XDR was first detected in 2018, in 2% of 474 isolates and increased to 7% of 535 in 2019. Of the 52 axo-R isolates, 46 were XDR, of which 45 were from travelers to Pakistan, and one from a non-traveler; 6 were not XDR, of which 4 were linked to travel to Iraq. In preliminary 2020 reports, 23 isolates were XDR; 14 were from travelers to Pakistan, 8 from non-travelers, and 1 from someone with unknown travel status. Among those with XDR infection, median age was 11 years (range 1–62), 54% were female, and 62% were from 6 states. Conclusion Ceftriaxone-resistant Typhi infections, mostly XDR, are increasing. Clinicians should ask patients with suspected Typhi infections about travel and adjust treatment based on susceptibility results. Carbapenem, azithromycin, or both may be considered for empiric therapy of typhoid fever among travelers to Pakistan or Iraq and in uncommon instances when persons report no international travel. Ceftriaxone is an empiric therapy option for travelers to countries other than Pakistan and Iraq. Disclosures All Authors: No reported disclosures

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