scholarly journals Detection of a Newcfr-Like Gene,cfr(B), in Enterococcus faecium Isolates Recovered from Human Specimens in the United States as Part of the SENTRY Antimicrobial Surveillance Program

2015 ◽  
Vol 59 (10) ◽  
pp. 6256-6261 ◽  
Author(s):  
Lalitagauri M. Deshpande ◽  
Deborah S. Ashcraft ◽  
Heather P. Kahn ◽  
George Pankey ◽  
Ronald N. Jones ◽  
...  
Keyword(s):  
United States ◽  
Enterococcus Faecium ◽  
Ribosomal Proteins ◽  
Medical Center ◽  
The United States ◽  
Gene Location ◽  
Rrna Genes ◽  
23S Rrna ◽  
Surveillance Program ◽  
Content Type

ABSTRACTTwo linezolid-resistantEnterococcus faeciumisolates (MICs, 8 μg/ml) from unique patients of a medical center in New Orleans were included in this study. Isolates were initially investigated for the presence of mutations in the V domain of 23S rRNA genes and L3, L4, and L22 ribosomal proteins, as well ascfr. Isolates were subjected to pulsed-field gel electrophoresis (just one band difference), and one representative strain was submitted to whole-genome sequencing. Gene location was also determined by hybridization, andcfrgenes were cloned and expressed in aStaphylococcus aureusbackground. The two isolates had one out of six 23S rRNA alleles mutated (G2576T), had wild-type L3, L4, and L22 sequences, and were positive for acfr-like gene. The sequence of the protein encoded by thecfr-like gene was most similar (99.7%) to that found inPeptoclostridium difficile, which shared only 74.9% amino acid identity with the proteins encoded by genes previously identified in staphylococci and non-faeciumenterococci and was, therefore, denominated Cfr(B). When expressed inS. aureus, the protein conferred a resistance profile similar to that of Cfr. Two copies ofcfr(B) were chromosomally located and embedded in a Tn6218similar to thecfr-carrying transposon described inP. difficile.This study reports the first detection ofcfrgenes inE. faeciumclinical isolates in the United States and characterization of a newcfrvariant,cfr(B).cfr(B) has been observed in mobile genetic elements inE. faeciumandP. difficile, suggesting potential for dissemination. However, further analysis is necessary to access the resistance levels conferred bycfr(B) when expressed in enterococci.

scholarly journals Mutations within therplDGene of Linezolid-Nonsusceptible Streptococcus pneumoniae Strains Isolated in the United States

2014 ◽  
Vol 58 (4) ◽  
pp. 2459-2462 ◽  
Author(s):  
W. Dong ◽  
S. Chochua ◽  
L. McGee ◽  
D. Jackson ◽  
K. P. Klugman ◽  
...  
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Ribosomal Protein ◽  
Ribosomal Proteins ◽  
Structural Changes ◽  
Binding Pocket ◽  
The United States ◽  
Target Site ◽  
23S Rrna ◽  
Content Type

ABSTRACTThree invasiveStreptococcus pneumoniaestrains nonsusceptible to linezolid were isolated in the United States between 2001 and 2012 from the CDC's Active Bacterial Core surveillance. Linezolid binds ribosomal proteins where structural changes within its target site may confer resistance. Our study identified mutations and deletions near the linezolid binding pocket of two of these strains within therplDgene, which encodes ribosomal protein L4. Mutations in the 23S rRNA alleles or therplVgene were not detected.

scholarly journals Macrolide-Resistant Mycoplasma pneumoniae in the United States as Determined from a National Surveillance Program

2019 ◽  
Vol 57 (11) ◽  
Author(s):  
K. B. Waites ◽  
A. Ratliff ◽  
D. M. Crabb ◽  
L. Xiao ◽  
X. Qin ◽  
...  
Keyword(s):  
United States ◽  
Clinical Significance ◽  
Mycoplasma Pneumoniae ◽  
The United States ◽  
Antimicrobial Treatment ◽  
23S Rrna ◽  
Surveillance Program ◽  
National Surveillance ◽  
Radiographic Findings ◽  
Content Type

ABSTRACT There are sparse data to indicate the extent that macrolide-resistant Mycoplasma pneumoniae (MRMp) occurs in the United States or its clinical significance. Between 2015 and 2018, hospitals in 8 states collected and stored respiratory specimens that tested positive for M. pneumoniae and sent them to the University of Alabama at Birmingham, where real-time PCR was performed for detection of 23S rRNA mutations known to confer macrolide resistance. MRMp was detected in 27 of 360 specimens (7.5%). MRMp prevalence was significantly higher in the South and East (18.3%) than in the West (2.1%). A2063G was the predominant 23S rRNA mutation detected. MICs for macrolide-susceptible M. pneumoniae (MSMp) were ≤0.008 μg/ml, whereas MICs for MRMp were 16 to 32 μg/ml. Patients with MRMp infection were more likely to have a history of immunodeficiency or malignancy. Otherwise, there were no other significant differences in the clinical features between patients infected with MRMp and those infected with MSMp, nor were there any differences in radiographic findings, hospitalization rates, viral coinfections, the mean duration of antimicrobial treatment, or clinical outcomes. There was no significant change in MRMp incidence over time or according to age, sex, race/ethnicity, or status as an inpatient or an outpatient. Patients with MRMp were more likely to have received a macrolide prior to presentation, and their treatment was more likely to have been changed to a fluoroquinolone after presentation. This is the first national surveillance program for M. pneumoniae in the United States. Additional surveillance is needed to assess the clinical significance of MRMp and to monitor changes in MRMp prevalence.

scholarly journals Linezolid Surveillance Results for the United States (LEADER Surveillance Program 2014)

2016 ◽  
Vol 60 (4) ◽  
pp. 2273-2280 ◽  
Author(s):  
Robert K. Flamm ◽  
Rodrigo E. Mendes ◽  
Patricia A. Hogan ◽  
Jennifer M. Streit ◽  
James E. Ross ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Ribosomal Proteins ◽  
The United States ◽  
23S Rrna ◽  
Surveillance Program ◽  
Coagulase Negative Staphylococci ◽  
Content Type ◽  
Mrsa Strains ◽  
Viridans Group Streptococci

ABSTRACTThelinezolidexperience andaccuratedetermination ofresistance (LEADER) surveillance program has monitored linezolid activity, spectrum, and resistance since 2004. In 2014, a total of 6,865 Gram-positive pathogens from 60 medical centers from 36 states were submitted. The organism groups evaluated wereStaphylococcus aureus(3,106), coagulase-negative staphylococci (CoNS; 797), enterococci (855),Streptococcus pneumoniae(874), viridans group streptococci (359), and beta-hemolytic streptococci (874). Susceptibility testing was performed by reference broth microdilution at the monitoring laboratory. Linezolid-resistant isolates were confirmed by repeat testing. PCR and sequencing were performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins and acquired genes (cfrandoptrA). The MIC50/90forStaphylococcus aureuswas 1/1 μg/ml, with 47.2% of isolates being methicillin-resistantStaphylococcus aureus. Linezolid was active against allStreptococcus pneumoniaestrains and beta-hemolytic streptococci with a MIC50/90of 1/1 μg/ml and against viridans group streptococci with a MIC50/90of 0.5/1 μg/ml. Among the linezolid-nonsusceptible MRSA strains, one strain harboredcfronly (MIC, 4 μg/ml), one harbored G2576T (MIC, 8 μg/ml), and one containedcfrand G2576T with L3 changes (MIC, ≥8 μg/ml). Among CoNS, 0.75% (six isolates) of all strains demonstrated linezolid MIC results of ≥4 μg/ml. Five of these were identified asStaphylococcus epidermidis, four of which containedcfrin addition to the presence of mutations in the ribosomal proteins L3 and L4, alone or in combination with 23S rRNA (G2576T) mutations. Six enterococci (0.7%) were linezolid nonsusceptible (≥4 μg/ml; five with G2576T mutations, including one with an additionalcfrgene, and one strain withoptrAonly). Linezolid demonstrated excellent activity and a sustained susceptibility rate of 99.78% overall.

scholarly journals Summary of Linezolid Activity and Resistance Mechanisms Detected during the 2012 LEADER Surveillance Program for the United States

2013 ◽  
Vol 58 (2) ◽  
pp. 1243-1247 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
Patricia A. Hogan ◽  
James E. Ross ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Susceptibility Testing ◽  
The United States ◽  
Resistance Mechanisms ◽  
Regulatory Approval ◽  
Surveillance Program ◽  
Gram Positive ◽  
Content Type

ABSTRACTThis study summarizes the linezolid susceptibility testing results for 7,429 Gram-positive pathogens from 60 U.S. sites collected during the 2012 sampling year for the LEADER Program. Linezolid showed potent activity when tested against 2,980Staphylococcus aureusisolates, inhibiting all but 3 at ≤2 μg/ml. Similarly, linezolid showed coverage against 99.5% of enterococci, as well as for all streptococci tested. These results confirm a long record of linezolid activity against U.S. Gram-positive isolates since regulatory approval in 2000.

scholarly journals Surveillance of Omadacycline Activity Tested against Clinical Isolates from the United States and Europe as Part of the 2016 SENTRY Antimicrobial Surveillance Program

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Michael A. Pfaller ◽  
Michael D. Huband ◽  
Dee Shortridge ◽  
Robert K. Flamm
Keyword(s):  
United States ◽  
Moraxella Catarrhalis ◽  
The United States ◽  
Surveillance Program ◽  
Bacterial Isolates ◽  
Content Type ◽  
Medical Centers ◽  
Antimicrobial Surveillance ◽  
Serious Infections ◽  
Viridans Group Streptococci

ABSTRACTOmadacycline was tested against 21,000 bacterial isolates collected prospectively from medical centers in Europe and the United States during 2016. Omadacycline was active againstStaphylococcus aureus(MIC50/MIC90, 0.12/0.25 mg/liter), including methicillin-resistantS. aureus(MRSA); streptococci (MIC50/MIC90, 0.06/0.12 mg/liter), includingStreptococcus pneumoniae, viridans group streptococci, and beta-hemolytic streptococci;Enterobacteriaceae, includingEscherichia coli(MIC50/MIC90, 0.5/2 mg/liter);Haemophilus influenzae(MIC50/MIC90, 1/1 mg/liter); andMoraxella catarrhalis(MIC50/MIC90, 0.25/0.25 mg/liter). Omadacycline merits further study in serious infections where resistant pathogens may be encountered.

scholarly journals Ceftobiprole Activity against Bacteria from Skin and Skin Structure Infections in the United States from 2016 through 2018

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Robert K. Flamm ◽  
Leonard R. Duncan ◽  
Kamal A. Hamed ◽  
Jennifer I. Smart ◽  
Rodrigo E. Mendes ◽  
...  
Keyword(s):  
United States ◽  
The United States ◽  
Generation Cephalosporin ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Content Type ◽  
Skin Structure ◽  
Highly Active

ABSTRACT Ceftobiprole medocaril is an advanced-generation cephalosporin prodrug that has qualified infectious disease product status granted by the US FDA and is currently being evaluated in phase 3 clinical trials in patients with acute bacterial skin and skin structure infections (ABSSSIs) and in patients with Staphylococcus aureus bacteremia. In this study, the activity of ceftobiprole and comparators was evaluated against more than 7,300 clinical isolates collected in the United States from 2016 through 2018 from patients with skin and skin structure infections. The major species/pathogen groups were S. aureus (53%), Enterobacterales (23%), Pseudomonas aeruginosa (7%), beta-hemolytic streptococci (6%), Enterococcus spp. (4%), and coagulase-negative staphylococci (2%). Ceftobiprole was highly active against S. aureus (MIC50/90, 0.5/1 mg/liter; 99.7% susceptible by EUCAST criteria; 42% methicillin-resistant S. aureus [MRSA]). Ceftobiprole also exhibited potent activity against other Gram-positive cocci. The overall susceptibility of Enterobacterales to ceftobiprole was 84.8% (>99.0% susceptible for isolate subsets that exhibited a non-extended-spectrum β-lactamase [ESBL] phenotype). A total of 74.4% of P. aeruginosa, 100% of beta-hemolytic streptococci and coagulase-negative staphylococci, and 99.6% of Enterococcus faecalis isolates were inhibited by ceftobiprole at ≤4 mg/liter. As expected, ceftobiprole was largely inactive against Enterobacterales that contained ESBL genes and Enterococcus faecium. Overall, ceftobiprole was highly active against most clinical isolates from the major Gram-positive and Gram-negative skin and skin structure pathogen groups collected at U.S. medical centers participating in the SENTRY Antimicrobial Surveillance Program during 2016 to 2018. The broad-spectrum activity of ceftobiprole, including potent activity against MRSA, supports its further evaluation for a potential ABSSSI indication.

scholarly journals Activity of Ceftaroline and Epidemiologic Trends in Staphylococcus aureus Isolates Collected from 43 Medical Centers in the United States in 2009

2011 ◽  
Vol 55 (9) ◽  
pp. 4154-4160 ◽  
Author(s):  
Sandra S. Richter ◽  
Kristopher P. Heilmann ◽  
Cassie L. Dohrn ◽  
Fathollah Riahi ◽  
Andrew J. Costello ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Surveillance Program ◽  
Content Type ◽  
Type Iv ◽  
Medical Centers ◽  
High Level ◽  
Resistance Rates

ABSTRACTAStaphylococcus aureussurveillance program was initiated in the United States to examine thein vitroactivity of ceftaroline and epidemiologic trends. Susceptibility testing by Clinical and Laboratory Standards Institute broth microdilution was performed on 4,210 clinically significant isolates collected in 2009 from 43 medical centers. All isolates were screened formecAby PCR and evaluated by pulsed-field gel electrophoresis. Methicillin-resistantS. aureus(MRSA) were analyzed for Panton-Valentine leukocidin (PVL) genes and the staphylococcal cassette chromosomemec(SCCmec) type. All isolates had ceftaroline MICs of ≤2 μg/ml with an MIC50of 0.5 and an MIC90of 1 μg/ml. The overall resistance rates, expressed as the percentages of isolates that were intermediate and resistant (or nonsusceptible), were as follows: ceftaroline, 1.0%; clindamycin, 30.2% (17.4% MIC ≥ 4 μg/ml; 12.8% inducible); daptomycin, 0.2%; erythromycin, 65.5%; levofloxacin, 39.9%; linezolid, 0.02%; oxacillin, 53.4%; tetracycline, 4.4%; tigecycline, 0%; trimethoprim-sulfamethoxazole, 1.6%; vancomycin, 0%; and high-level mupirocin, 2.2%. ThemecAPCR was positive for 53.4% of the isolates. The ceftaroline MIC90s were 0.25 μg/ml for methicillin-susceptibleS. aureusand 1 μg/ml for MRSA. Among the 2,247 MRSA isolates, 51% were USA300 (96.9% PVL positive, 99.7% SCCmectype IV) and 17% were USA100 (93.4% SCCmectype II). The resistance rates for the 1,137 USA300 MRSA isolates were as follows: erythromycin, 90.9%; levofloxacin, 49.1%; clindamycin, 7.6% (6.2% MIC ≥ 4 μg/ml; 1.4% inducible); tetracycline, 3.3%; trimethoprim-sulfamethoxazole, 0.8%; high-level mupirocin, 2.7%; daptomycin, 0.4%; and ceftaroline and linezolid, 0%. USA300 is the dominant clone causing MRSA infections in the United States. Ceftaroline demonstrated potentin vitroactivity against recentS. aureusclinical isolates, including MRSA, daptomycin-nonsusceptible, and linezolid-resistant strains.

scholarly journals Summary of Ceftaroline Activity against Pathogens in the United States, 2010: Report from the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Surveillance Program

2012 ◽  
Vol 56 (6) ◽  
pp. 2933-2940 ◽  
Author(s):  
Robert K. Flamm ◽  
Helio S. Sader ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Bloodstream Infections ◽  
The United States ◽  
Surveillance Program ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Medical Centers ◽  
Therapeutic Decision Making ◽  
Tract Infections

ABSTRACTTheAssessingWorldwideAntimicrobialResistanceEvaluation (AWARE) surveillance program is a sentinel resistance monitoring system designed to track the activity of ceftaroline and comparator agents. In the United States, a total of 8,434 isolates were collected during the 2010 surveillance program from 65 medical centers distributed across the nine census regions (5 to 10 medical centers per region). All organisms were isolated from documented infections, including 3,055 (36.2%) bloodstream infections, 2,282 (27.1%) respiratory tract infections, 1,965 (23.3%) acute bacterial skin and skin structure infections, 665 (7.9%) urinary tract infections, and 467 (5.5%) miscellaneous other infection sites. Ceftaroline was the most potent β-lactam agent tested against staphylococci. The MIC90values were 1 μg/ml for methicillin-resistantStaphylococcus aureus(MRSA; 98.4% susceptible) and 0.5 μg/ml for methicillin-resistant coagulase-negative staphylococci (CoNS). Ceftaroline was 16- to 32-fold more potent than ceftriaxone against methicillin-susceptible staphylococcal strains. All staphylococcus isolates (S. aureusand CoNS) were inhibited at ceftaroline MIC values of ≤2 μg/ml. Ceftaroline also displayed potent activity against streptococci (MIC90, 0.015 μg/ml for beta-hemolytic streptococci; MIC90, 0.25 μg/ml for penicillin-resistantStreptococcus pneumoniae). Potent activity was also shown against Gram-negative pathogens (Haemophilus influenzae,Haemophilus parainfluenzae, andMoraxella catarrhalis). Furthermore, wild-type strains ofEnterobacteriaceae(non-extended-spectrum β-lactamase [ESBL]-producing strains and non-AmpC-hyperproducing strains) were often susceptible to ceftaroline. Continued monitoring through surveillance networks will allow for the assessment of the evolution of resistance as this new cephalosporin is used more broadly to provide clinicians with up-to-date information to assist in antibiotic stewardship and therapeutic decision making.

scholarly journals Complete Genome Sequences of Two Avilamycin-Resistant Enterococcus faecium Strains Isolated from Chicken in the United States

2019 ◽  
Vol 8 (47) ◽  
Author(s):  
S. Zhao ◽  
C. Li ◽  
S. Mukherjee ◽  
C. H. Hsu ◽  
R. Singh ◽  
...  
Keyword(s):  
United States ◽  
Enterococcus Faecium ◽  
Complete Genome ◽  
The United States ◽  
Multidrug Resistant ◽  
Genome Sequences ◽  
Content Type ◽  
Young Chicken

Avilamycin-resistant Enterococcus spp. have never been reported in the United States. Here, we report the complete genome sequences of two avilamycin-resistant (Avir) Enterococcus faecium strains isolated from a retail chicken and a cecal sample from a young chicken. Both isolates are multidrug resistant (MDR) and carry emtA on MDR plasmids.

scholarly journals Molecular Testing for Mycoplasma genitalium in the United States: Results from the AMES Prospective Multicenter Clinical Study

2019 ◽  
Vol 57 (11) ◽  
Author(s):  
Charlotte A. Gaydos ◽  
Lisa E. Manhart ◽  
Stephanie N. Taylor ◽  
Rebecca A. Lillis ◽  
Edward W. Hook ◽  
...  
Keyword(s):  
United States ◽  
Clinical Study ◽  
Reference Method ◽  
Mycoplasma Genitalium ◽  
The United States ◽  
23S Rrna ◽  
Molecular Testing ◽  
Content Type ◽  
Vaginal Swabs ◽  
Multicenter Clinical Study

ABSTRACT A prospective multicenter clinical study involving subjects from 21 sites across the United States was conducted to validate the performance of a new in vitro diagnostic nucleic acid amplification test (NAAT) for the detection of Mycoplasma genitalium. Seven urogenital specimen types (n = 11,556) obtained from 1,778 females, aged 15 to 74 years, and 1,583 males, aged 16 to 82 years, were tested with the Aptima Mycoplasma genitalium assay, an investigational transcription-mediated amplification (TMA) NAAT for the detection of M. genitalium 16S rRNA. Infected status for enrolled subjects was established using results obtained from testing either self-collected vaginal swab or clinician-collected male urethral swab specimens with a composite reference method consisting of three transcription-mediated amplification NAATs targeting unique regions of M. genitalium 16S or 23S rRNA. M. genitalium prevalence was 10.2% in females and 10.6% in males; prevalence was high in both symptomatic and asymptomatic subjects for both sexes. Compared to the subject infected status standard, the investigational test had sensitivity and specificity estimates, respectively, of 98.9% and 98.5% for subject-collected vaginal swabs, 92.0% and 98.0% for clinician-collected vaginal swabs, 81.5% and 98.3% for endocervical swabs, 77.8% and 99.0% for female urine, and 98.2% and 99.6% for male urethral swabs, 88.4% and 97.8% for self-collected penile meatal swabs, and 90.9% and 99.4% for male urine specimens. For all seven specimen types, within-specimen positive and negative agreements between the investigational test and the composite reference standard ranged from 94.2% to 98.3% and from 98.5 to 99.9%, respectively. These results provide clinical efficacy evidence for the first FDA-cleared NAAT for M. genitalium detection in the United States.

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