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 Extremely Drug-Resistant Pseudomonas aeruginosa ST309 Harboring Tandem GES Enzymes: A Newly Emerging Threat in the United States

2019 ◽  
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 ◽  
Beta Lactamases ◽  
Extended Spectrum ◽  
Extended Spectrum Beta Lactamases ◽  
Lactamase Inhibitor

AbstractTwo ST309 Pseudomonas aeruginosa clinical isolates resistant to carbapenems and newer β-lactam/β-lactamase inhibitor combinations were found to harbor the extended spectrum beta-lactamases GES 19 and 26 genetically clustered in tandem. The combination of ceftazidime/avibactam plus aztreonam achieved cure in one patient. Phylogenetic analysis suggests that ST309 P. aeruginosa carrying tandem GES are an emerging lineage in the United States.

scholarly journals Epidemiology of Conjugative Plasmid-Mediated AmpC β-Lactamases in the United States

2004 ◽  
Vol 48 (2) ◽  
pp. 533-537 ◽  
Author(s):  
M. Alvarez ◽  
J. H. Tran ◽  
N. Chow ◽  
G. A. Jacoby
Keyword(s):  
United States ◽  
New York ◽  
Klebsiella Oxytoca ◽  
The United States ◽  
Clinical Isolates ◽  
Conjugative Plasmid ◽  
E Coli ◽  
Extended Spectrum ◽  
Plasmid Analysis ◽  
Plasmid Dissemination

ABSTRACT A sample of 752 resistant Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli strains from 70 sites in 25 U.S. states and the District of Columbia was examined for transmissibility of resistance to ceftazidime and the nature of the plasmid-mediated β-lactamase involved. Fifty-nine percent of the K. pneumoniae, 24% of the K. oxytoca, and 44% of the E. coli isolates transferred resistance to ceftazidime. Plasmids encoding AmpC-type β-lactamase were found in 8.5% of the K. pneumoniae samples, 6.9% of the K. oxytoca samples, and 4% of the E. coli samples, at 20 of the 70 sites and in 10 of the 25 states. ACT-1 β-lactamase was found at eight sites, four of which were near New York City, where the ACT-1 enzyme was first discovered; ACT-1 β-lactamase was also found in Massachusetts, Pennsylvania, and Virginia. FOX-5 β-lactamase was also found at eight sites, mainly in southeastern states but also in New York. Two E. coli strains produced CMY-2, and one K. pneumoniae strain produced DHA-1 β-lactamase. Pulsed-field gel electrophoresis and plasmid analysis suggested that AmpC-mediated resistance spread both by strain and plasmid dissemination. All AmpC β-lactamase-containing isolates were resistant to cefoxitin, but so were 11% of strains containing transmissible SHV- and TEM-type extended-spectrum β-lactamases. A β-lactamase inhibitor test was helpful in distinguishing the two types of resistance but was not definitive since 24% of clinical isolates producing AmpC β-lactamase had a positive response to clavulanic acid. Coexistence of AmpC and extended-spectrum β-lactamases was the main reason for these discrepancies. Plasmid-mediated AmpC-type enzymes are thus responsible for an appreciable fraction of resistance in clinical isolates of Klebsiella spp. and E. coli, are disseminated around the United States, and are not so easily distinguished from other enzymes that mediate resistance to oxyimino-β-lactams.

scholarly journals Activity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States during 2013 to 2015

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Mariana Castanheira ◽  
Leonard R. Duncan ◽  
Rodrigo E. Mendes ◽  
Helio S. Sader ◽  
Dee Shortridge
Keyword(s):  
United States ◽  
Pseudomonas Aeruginosa ◽  
The United States ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Encoding Genes ◽  
M 14

ABSTRACT The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae isolates susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the P. aeruginosa isolates. Ceftolozane-tazobactam inhibited 77.5 to 85.1% of isolates nonsusceptible to antipseudomonal β-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than those of other β-lactams evaluated against P. aeruginosa groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae , being less active than only meropenem (95.6% susceptible) among the β-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum-β-lactamase (ESBL)-encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly bla CTX-M-15 -like (89 isolates) and bla CTX-M-14 -like (22) genes but also bla SHV (31) and bla TEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All β-lactams displayed limited activity against bla KPC -carrying isolates. Ceftolozane-tazobactam was the most active β-lactam tested against P. aeruginosa isolates from isolates that were the probable cause of pneumonia and displayed in vitro activity against Enterobacteriaceae , including isolates resistant to cephalosporins and carrying ESBL genes.

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

In vitro susceptibility of ceftolozane/tazobactam against typhoidal, non-typhoidal and extended spectrum β-lactamase-producing Salmonella

2021 ◽  
Author(s):  
Jade L. L. Teng ◽  
Elaine Chan ◽  
Asher C. H. Dai ◽  
Gillian Ng ◽  
Tsz Tuen Li ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Agents ◽  
The United States ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Extended Spectrum ◽  
Control And Prevention ◽  
Esbl Producers

Both typhoidal and non-typhoidal salmonellae are included in the top 15 drug-resistant threats described by the Center for Disease Control and Prevention of the United States. There is an urgent need to look for alternative antibiotics for the treatment of Salmonella infections. We examined the in vitro susceptibilities of ceftolozane/tazobactam and six other antibiotics on typhoidal and non-typhoidal salmonellae, including isolates that are extended-spectrum β-lactamase (ESBL)-positive, using the broth microdilution test. Of the 313 (52 typhoidal and 261 non-typhoidal) Salmonella isolates tested, 98.7% were susceptible to ceftolozane/tazobactam. Based on the overall MIC 50/90 values, Salmonella isolates were more susceptible to ceftolozane/tazobactam (0.25/0.5 mg/L) compared to all other comparator agents: ampicillin (≥64/≥64 mg/L), levofloxacin (0.25/1 mg/L), azithromycin (4/16 mg/L), ceftriaxone (≤0.25/4 mg/L), chloramphenicol (8/≥64 mg/L) and trimethoprim/sulfamethoxazole (1/≥8 mg/L). When comparing the activity of the antimicrobial agents against non-typhoidal Salmonella isolates according to their serogroup, ceftolozane/tazobactam had the highest activity (100%) against Salmonella serogroups D, G, I and Q isolates, whereas the lowest activity (85.7%) was observed against serogroup E isolates. All the 10 ESBL-producing Salmonella (all non-typhoidal) isolates, of which 8 were CTX-M-55-producers and 2 were CTX-M-65-producers, were sensitive to ceftolozane/tazobactam albeit with a higher MIC 50/90 value (1/2 mg/L) than non-ESBL-producers (0.25/0.5 mg/L). In summary, our data indicate that ceftolozane/tazobactam is active against most strains of both typhoidal and non-typhoidal salmonellae and also active against ESBL-producing salmonellae.

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 Increasing antibiotic resistance in clinical isolates of Aeromonas strains in Taiwan.

1996 ◽  
Vol 40 (5) ◽  
pp. 1260-1262 ◽  
Author(s):  
W C Ko ◽  
K W Yu ◽  
C Y Liu ◽  
C T Huang ◽  
H S Leu ◽  
...  
Keyword(s):  
United States ◽  
Antibiotic Resistance ◽  
The United States ◽  
Clinical Isolates ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Extended Spectrum ◽  
Agar Dilution

A total of 234 clinical isolates of Aeromonas, primarily A. hydrophila, were collected for the present study. Most were isolates from blood. By the agar dilution method, more than 90% of the Aeromonas strains were found to be susceptible to moxalactam, ceftazidime, cefepime, aztreonam, imipenem, amikacin, and fluoroquinolones, but they were more resistant to tetracycline, trimethoprim-sulfamethoxazole, some extended-spectrum cephalosporins, and aminoglycosides than strains from the United States and Australia.

scholarly journals Genetic Determinants of Resistance to Extended-Spectrum Cephalosporin and Fluoroquinolone in Escherichia coli Isolated from Diseased Pigs in the United States

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Shivdeep Singh Hayer ◽  
Seunghyun Lim ◽  
Samuel Hong ◽  
Ehud Elnekave ◽  
Timothy Johnson ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
High Risk ◽  
The United States ◽  
Genetic Determinants ◽  
Content Type ◽  
E Coli ◽  
Extended Spectrum ◽  
Animal Populations ◽  
Swine Population

ABSTRACT Fluoroquinolones and cephalosporins are critically important antimicrobial classes for both human and veterinary medicine. We previously found a drastic increase in enrofloxacin resistance in clinical Escherichia coli isolates collected from diseased pigs from the United States over 10 years (2006 to 2016). However, the genetic determinants responsible for this increase have yet to be determined. The aim of the present study was to identify and characterize the genetic basis of resistance against fluoroquinolones (enrofloxacin) and extended-spectrum cephalosporins (ceftiofur) in swine E. coli isolates using whole-genome sequencing (WGS). blaCMY-2 (carried by IncA/C2, IncI1, and IncI2 plasmids), blaCTX-M (carried by IncF, IncHI2, and IncN plasmids), and blaSHV-12 (carried by IncHI2 plasmids) genes were present in 87 (82.1%), 19 (17.9%), and 3 (2.83%) of the 106 ceftiofur-resistant isolates, respectively. Of the 110 enrofloxacin-resistant isolates, 90 (81.8%) had chromosomal mutations in gyrA, gyrB, parA, and parC genes. Plasmid-mediated quinolone resistance genes [qnrB77, qnrB2, qnrS1, qnrS2, and aac-(6)-lb′-cr] borne on ColE, IncQ2, IncN, IncF, and IncHI2 plasmids were present in 24 (21.8%) of the enrofloxacin-resistant isolates. Virulent IncF plasmids present in swine E. coli isolates were highly similar to epidemic plasmids identified globally. High-risk E. coli clones, such as ST744, ST457, ST131, ST69, ST10, ST73, ST410, ST12, ST127, ST167, ST58, ST88, ST617, ST23, etc., were also found in the U.S. swine population. Additionally, the colistin resistance gene (mcr-9) was present in several isolates. This study adds valuable information regarding resistance to critical antimicrobials with implications for both animal and human health. IMPORTANCE Understanding the genetic mechanisms conferring resistance is critical to design informed control and preventive measures, particularly when involving critically important antimicrobial classes such as extended-spectrum cephalosporins and fluoroquinolones. The genetic determinants of extended-spectrum cephalosporin and fluoroquinolone resistance were highly diverse, with multiple plasmids, insertion sequences, and genes playing key roles in mediating resistance in swine Escherichia coli. Plasmids assembled in this study are known to be disseminated globally in both human and animal populations and environmental samples, and E. coli in pigs might be part of a global reservoir of key antimicrobial resistance (AMR) elements. Virulent plasmids found in this study have been shown to confer fitness advantages to pathogenic E. coli strains. The presence of international, high-risk zoonotic clones provides worrisome evidence that resistance in swine isolates may have indirect public health implications, and the swine population as a reservoir for these high-risk clones should be continuously monitored.

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