scholarly journals Activities of Vancomycin, Ceftaroline, and Mupirocin against Staphylococcus aureus Isolates Collected in a 2011 National Surveillance Study in the United States

2013 ◽  
Vol 58 (2) ◽  
pp. 740-745 ◽  
Author(s):  
Sandra S. Richter ◽  
Daniel J. Diekema ◽  
Kristopher P. Heilmann ◽  
Cassie L. Dohrn ◽  
Emily K. Crispell ◽  
...  

ABSTRACTForty-two medical centers from throughout the United States participating in a longitudinal surveillance program were asked to submit 100 consecutiveStaphylococcus aureusisolates during July to December 2011. Susceptibility testing using CLSI broth microdilution andmecAdetection by PCR analysis was performed on the 4,131 isolates collected. Methods employing Etest glycopeptide resistance detection (GRD; bioMérieux) and brain heart infusion agar containing 4 μg/ml vancomycin (BHIV) were used to screen methicillin-resistantS. aureus(MRSA) isolates for heterogeneous intermediate-level resistance to vancomycin (hVISA). Isolates with positive hVISA screen results were confirmed by population analysis profiling-area under the curve (PAP-AUC) determinations. The genetic relatedness of hVISA, ceftaroline-nonsusceptible, or high-level (HL) mupirocin resistance MRSA isolates was assessed by pulsed-field gel electrophoresis (PFGE). Among 2,093 MRSA isolates, the hVISA screen results were positive with 47 isolates by Etest GRD and 30 isolates by BHIV agar screen. Twenty-five of the GRD- or BHIV screen-positive isolates were confirmed as hVISA by PAP-AUC testing. Results of the current study were compared to results obtained from prior surveillance performed in 2009. The prevalence of hVISA among MRSA isolates was higher in 2011 than in 2009 (1.2% versus 0.4%,P= 0.003), especially for isolates with a vancomycin MIC of 2 (45.4% versus 14.3%,P= 0.01). The overall rate of ceftaroline susceptibility in the current study was 99.4% (one hVISA isolate had an intermediate ceftaroline MIC). HL mupirocin resistance increased from 2.2% in 2009 to 3.2% in 2011 (P= 0.006). Although overall rates of hVISA and HL mupirocin resistance are low, they have increased since 2009.

2013 ◽  
Vol 58 (2) ◽  
pp. 1243-1247 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
Patricia A. Hogan ◽  
James E. Ross ◽  
Ronald N. Jones

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.


2011 ◽  
Vol 55 (9) ◽  
pp. 4154-4160 ◽  
Author(s):  
Sandra S. Richter ◽  
Kristopher P. Heilmann ◽  
Cassie L. Dohrn ◽  
Fathollah Riahi ◽  
Andrew J. Costello ◽  
...  

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.


2012 ◽  
Vol 57 (1) ◽  
pp. 130-136 ◽  
Author(s):  
Christine Lascols ◽  
Gisele Peirano ◽  
Meredith Hackel ◽  
Kevin B. Laupland ◽  
Johann D. D. Pitout

ABSTRACTA study was designed to characterize nonrepeat isolates of carbapenemase-producingK. pneumoniaeobtained from the SMART worldwide surveillance program during 2008 and 2009. Characterization was done by PCR and sequencing forblaVIM,blaIMP,blaNDM,blaOXA,blaKPC, and plasmid-mediated quinolone resistance and virulence factors (VFs). Genetic relatedness was determined with pulsed-field gel electrophoresis (PFGE) using XbaI and multilocus sequence typing. A total of 110 isolates were included; 47 possess genes that encodeK. pneumoniaecarbapenemases (KPCs), 26 NDMs, 19 VIMs, 13 OXA-48-like, and 5 imipenems (IMPs). We identified 3 different major sequence types (STs) among 65% of the isolates (i.e., ST11 [n= 11], ST147 [n= 23], and ST258 [n= 38]). ST11 and ST147, producing OXA-48-like and NDMs, were found in Argentina, Turkey, Greece, Italy, and India; ST258, producing KPCs, was present in the United States, Israel, Greece, and Puerto Rico. The major STs consisted of up to 4 different pulsotypes, and each pulsotype had a specific geographical distribution. A new ST, named ST903, withblaIMP-26, was identified in the Philippines, while twoblaOXA-48-positive isolates were detected in the United States. There were no significant differences in the distribution of the VFs between the isolates; all were positive forfimH,mrkD,wabG, andureA. This is the first report of OXA-48-like enzymes in North America. Our study highlights the importance of surveillance programs using molecular techniques as powerful tools to identify the importance of international sequence types.


2015 ◽  
Vol 53 (11) ◽  
pp. 3543-3546 ◽  
Author(s):  
Riad Khatib ◽  
Kathleen Riederer ◽  
Mamta Sharma ◽  
Stephen Shemes ◽  
Sugantha P. Iyer ◽  
...  

BHI agars supplemented with vancomycin 4 (BHI-V4) and 3 (BHI-V3) mg/liter have been proposed for screening vancomycin intermediately susceptibleStaphylococcus aureus(VISA) and heteroresistant (hVISA) phenotypes, respectively, but growth interpretation criteria have not been established. We reviewed the growth results (CFU) during population analysis profile-area under the curve (PAP-AUC) of consecutive methicillin-resistantStaphylococcus aureus(MRSA) blood isolates, which were saved intermittently between 1996 and 2012. CFU counts on BHI-V4 and BHI-V3 plates were stratified according to PAP-AUC interpretive criteria: <0.90 (susceptible [S-MRSA]), 0.90 to 1.3 (hVISA), and >1.3 (VISA). CFU cutoffs that best predict VISA and hVISA were determined with the use of receiver operating characteristic (ROC) curves. Mu3, Mu50, and methicillin-susceptibleS. aureus(MSSA) controls were included. We also prospectively evaluated manufacturer-made BHI-V3/BHI-V4 biplates for screening of 2010-2012 isolates. The PAP-AUC of 616 clinical samples was consistent with S-MRSA, hVISA, and VISA in 550 (89.3%), 48 (7.8%), and 18 (2.9%) instances, respectively. For VISA screening on BHI-V4, a cutoff of 2 CFU/droplet provided 100% sensitivity and 97.7% specificity. To distinguish VISA from hVISA, a cutoff of 16 CFU provided 83.3% sensitivity and 94.7% specificity; the specificity was lowered to 89.5% with a 12-CFU cutoff. For detecting hVISA/VISA on BHI-V3, a 2-CFU/droplet cutoff provided 98.5% sensitivity and 93.8% specificity. These results suggest that 2-CFU/droplet cutoffs on BHI-V4 and BHI-V3 best approximate VISA and hVISA gold standard confirmation, respectively, with minimal overlap in samples with borderline PAP-AUC. Simultaneous screening for VISA/hVISA on manufacturer-made BHI-V4/BHI-V3 biplates is easy to standardize and may reduce the requirement for PAP-AUC confirmation.


2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Michael A. Pfaller ◽  
Michael D. Huband ◽  
Dee Shortridge ◽  
Robert K. Flamm

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.


2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Robert K. Flamm ◽  
Leonard R. Duncan ◽  
Kamal A. Hamed ◽  
Jennifer I. Smart ◽  
Rodrigo E. Mendes ◽  
...  

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.


2015 ◽  
Vol 59 (12) ◽  
pp. 7597-7601 ◽  
Author(s):  
Zhaowei Wu ◽  
Fan Li ◽  
Dongliang Liu ◽  
Huping Xue ◽  
Xin Zhao

ABSTRACTExcision and integration of staphylococcal cassette chromosomemec(SCCmec) are mediated by cassette chromosome recombinases (Ccr), which play a crucial role in the worldwide spread of methicillin resistance in staphylococci. We report a novelccrgene,ccrC2, in the SCCmecof aStaphylococcus aureusisolate, BA01611, which showed 62.6% to 69.4% sequence identities to all publishedccrC1sequences. A further survey found that theccrC2gene was mainly located among coagulase-negative staphylococci (CoNS) and could be found in staphylococcal isolates from China, the United States, France, and Germany. Theccrgene complex harboring theccrC2gene was designated a type 9 complex, and the SCCmecof BA01611 was considered a novel type and was designated type XII (9C2). This novel SCCmecelement in BA01611 was flanked by a pseudo-SCC element (ΨSCCBA01611) carrying a truncatedccrA1gene. Both individual SCC elements and a composite SCC were excised from the chromosome based on detection of extrachromosomal circular intermediates. We advocate inclusion of the ccrC2gene and type 9ccrgene complex during revision of the SCCmectyping method.


2016 ◽  
Vol 54 (7) ◽  
pp. 1871-1876 ◽  
Author(s):  
Pamela R. F. Adkins ◽  
John R. Middleton ◽  
Lawrence K. Fox

Staphylococcus aureusis one of the most important pathogens causing contagious mastitis in dairy cattle worldwide. The objectives of this study were to determine if recently describedS. aureusgenotype B was present among previously characterized isolates from cases of bovine intramammary infection in the United States and to compare pulsed-field gel electrophoresis (PFGE) to the combination of ribosomal spacer PCR (RS-PCR) and virulence gene identification for typing ofS. aureusstrains. The hypothesis was that isolates that were previously characterized as contagious would be identified as genotype B and that the results of the two strain-typing methods would be comparable. Isolates were selected from a collection ofS. aureusisolates from eight dairy farms. Mammary quarter milk somatic cell count (SCC) andN-acetyl-β-d-gluconaminidase (NAGase) activity data were known and used to evaluate strain pathogenicity. RS-PCR was performed with conventional gel electrophoresis, and PCR was used for toxin gene identification. RS-PCR patterns were associated with a specific virulence gene pattern, as previously reported. Five RS-PCR banding patterns were identified. None of the isolates were characterized as genotype B. No association between RS-PCR types and milk SCC was found; however, NAGase activity was significantly higher in milk from mammary glands infected with RS-PCR banding type 1 (RSP type 1) than in milk from those infected with RSP type 2. The discriminatory power values were 1.0 and 0.46 for PFGE and RS-PCR, respectively. These data suggest that genotype B may have a limited geographic distribution and that PFGE is more discriminatory than RS-PCR performed with conventional gel electrophoresis for typing ofS. aureusisolates of bovine origin.


mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Susan Boyle-Vavra ◽  
Xue Li ◽  
Md Tauqeer Alam ◽  
Timothy D. Read ◽  
Julia Sieth ◽  
...  

ABSTRACTThe surface capsular polysaccharide (CP) is a virulence factor that has been used as an antigen in several successful vaccines against bacterial pathogens. A vaccine has not yet been licensed againstStaphylococcus aureus, although two multicomponent vaccines that contain CP antigens are in clinical trials. In this study, we evaluated CP production in USA300 methicillin-resistantS. aureus(MRSA) isolates that have become the predominant community-associated MRSA clones in the United States. We found that all 167 USA300 MRSA and 50 USA300 methicillin-susceptibleS. aureus(MSSA) isolates were CP negative (CP−). Moreover, all 16 USA500 isolates, which have been postulated to be the progenitor lineage of USA300, were also CP−. Whole-genome sequence analysis of 146 CP−USA300 MRSA isolates revealed they all carry acap5locus with 4 conserved mutations compared with strain Newman. Genetic complementation experiments revealed that three of these mutations (in thecap5promoter,cap5Dnucleotide 994, andcap5Enucleotide 223) ablated CP production in USA300 and that Cap5E75 Asp, located in the coenzyme-binding domain, is essential for capsule production. All but three USA300 MSSA isolates had the same fourcap5mutations found in USA300 MRSA isolates. Most isolates with a USA500 pulsotype carried three of these four USA300-specific mutations, suggesting the fourth mutation occurred in the USA300 lineage. Phylogenetic analysis of thecaploci of our USA300 isolates as well as publicly available genomes from 41 other sequence types revealed that the USA300-specificcap5mutations arose sequentially inS. aureusin a common ancestor of USA300 and USA500 isolates.IMPORTANCEThe USA300 MRSA clone emerged as a community-associated pathogen in the United States nearly 20 years ago. Since then, it has rapidly disseminated and now causes health care-associated infections. This study shows that the CP-negative (CP−) phenotype has persisted among USA300 isolates and is a universal and characteristic trait of this highly successful MRSA lineage. It is important to note that a vaccine consisting solely of CP antigens would not likely demonstrate high efficacy in the U.S. population, where about half of MRSA isolates comprise USA300. Moreover, conversion of a USA300 strain to a CP-positive (CP+) phenotype is unlikelyin vivoorin vitrosince it would require the reversion of 3 mutations. We have also established that USA300 MSSA isolates and USA500 isolates are CP−and provide new insight into the evolution of the USA300 and USA500 lineages.


mBio ◽  
2012 ◽  
Vol 3 (3) ◽  
Author(s):  
Veronica N. Kos ◽  
Christopher A. Desjardins ◽  
Allison Griggs ◽  
Gustavo Cerqueira ◽  
Andries Van Tonder ◽  
...  

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistantS. aureus(VRSA) infection in the United States—all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift indprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition.IMPORTANCEInvasive methicillin-resistantStaphylococcus aureus(MRSA) infection now ranks among the leading causes of death in the United States. Vancomycin is a key last-line bactericidal drug for treating these infections. However, since 2002, vancomycin resistance has entered this species. Of the now 12 cases of vancomycin-resistantS. aureus(VRSA), each was believed to represent a new acquisition of the vancomycin-resistant transposon Tn1546from enterococcal donors. All acquisitions of Tn1546so far have occurred in MRSA strains of the clonal cluster 5 genetic background, the most common hospital lineage causing hospital-acquired MRSA infection. To understand the nature of these strains, we determined and examined the nucleotide sequences of the genomes of all available VRSA. Genome comparison identified candidate features that position strains of this lineage well for acquiring resistance to antibiotics in mixed infection.


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