scholarly journals In VitroActivity of CEM-102 (Fusidic Acid) against Prevalent Clones and Resistant Phenotypes of Staphylococcus aureus

2013 ◽  
Vol 57 (9) ◽  
pp. 4535-4536 ◽  
Author(s):  
D. F. Sahm ◽  
J. Deane ◽  
C. M. Pillar ◽  
P. Fernandes
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Oral Treatment ◽  
The United States ◽  
Content Type ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

ABSTRACTClinical development of CEM-102 (fusidic acid) has recently begun in the United States for chronic oral treatment of prosthetic joint infections. To support this development, thein vitroactivity of fusidic acid against importantStaphylococcus aureusclones and resistance phenotypes was determined. Against 51 such isolates, the modal fusidic acid MIC was 0.12 μg/ml (range, 0.06 to 0.25 μg/ml for 49 isolates). This level ofin vitrofusidic acid activity underscores the potential clinical utility of this compound in the United States.

scholarly journals USA300 and USA500 Clonal Lineages of Staphylococcus aureus Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the cap5 Locus

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Susan Boyle-Vavra ◽  
Xue Li ◽  
Md Tauqeer Alam ◽  
Timothy D. Read ◽  
Julia Sieth ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Capsular Polysaccharide ◽  
The United States ◽  
Whole Genome Sequence ◽  
Content Type ◽  
Capsule Production ◽  
Usa300 Strain

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.

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 JNJ-Q2, a New Fluoroquinolone with PotentIn VitroActivity against Staphylococcus aureus, Including Methicillin- and Fluoroquinolone-Resistant Strains

2011 ◽  
Vol 55 (7) ◽  
pp. 3631-3634 ◽  
Author(s):  
David J. Farrell ◽  
Lisa C. Liverman ◽  
Douglas J. Biedenbach ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Broad Spectrum ◽  
The United States ◽  
Gram Positive ◽  
Content Type ◽  
Skin Structure ◽  
Resistant Strains

ABSTRACTJNJ-Q2 is a broad-spectrum bactericidal fluoroquinolone with potent activity against Gram-positive and -negative pathogens. In this study, thein vitroactivity of JNJ-Q2 was evaluated against 511 selectedStaphylococcus aureussamples isolated in 2008-2009 from patients with acute bacterial skin and skin structure infections in the United States by using reference methodology. JNJ-Q2 was the most potent fluoroquinolone tested overall (MIC50and MIC90, 0.12 and 0.5 μg/ml, respectively) and against methicillin- and fluoroquinolone-resistant subgroups in direct comparisons to moxifloxacin, levofloxacin, and ciprofloxacin (each being ≥16-fold less potent than JNJ-Q2).

scholarly journals Comparative Efficacies of Cloxacillin-Daptomycin and the Standard Cloxacillin-Rifampin Therapies against an Experimental Foreign-Body Infection by Methicillin-Susceptible Staphylococcus aureus

2014 ◽  
Vol 58 (9) ◽  
pp. 5576-5580 ◽  
Author(s):  
Cristina El Haj ◽  
Oscar Murillo ◽  
Alba Ribera ◽  
Mireia Vivas ◽  
Dolors Garcia-Somoza ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Foreign Body ◽  
Early Treatment ◽  
Infection Model ◽  
Content Type ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Mssa Infection

ABSTRACTWe compared the efficacies of daptomycin (doses equivalent to 8 to 10 mg/kg of body weight/day in humans) and cloxacillin alone with those of cloxacillin-rifampin and cloxacillin-daptomycin combinations, using a tissue cage methicillin-susceptibleStaphylococcus aureus(MSSA) infection model. Monotherapies were less effective than combinations (P< 0.05), and daptomycin resistance emerged. Cloxacillin-daptomycin proved as effective as cloxacillin-rifampin and prevented the appearance of resistance; this combination may be an alternative anti-MSSA therapy, which may offer greater benefits in the early treatment of prosthetic joint infections (PJI).

The Estimated Magnitude and Direct Hospital Costs of Prosthetic Joint Infections in the United States, 1997 to 2004

2010 ◽  
Vol 25 (5) ◽  
pp. 766-771.e1 ◽  
Author(s):  
Matthew Hellmann ◽  
Supriya D. Mehta ◽  
David M. Bishai ◽  
Simon C. Mears ◽  
Jonathan M. Zenilman
Keyword(s):  
United States ◽  
Hospital Costs ◽  
The United States ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

scholarly journals In vitro susceptibility of Staphylococcus aureus and Staphylococcus epidermidis isolated from prosthetic joint infections

2012 ◽  
Vol 65 (10) ◽  
pp. 505-508 ◽  
Author(s):  
Diana Molina-Manso ◽  
Gema del Prado ◽  
Alberto Ortiz-Pérez ◽  
Miguel Manrubia-Cobo ◽  
Enrique Gómez-Barrena ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
In Vitro Susceptibility ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

scholarly journals Five-Year Summary of In Vitro Activity and Resistance Mechanisms of Linezolid against Clinically Important Gram-Positive Cocci in the United States from the LEADER Surveillance Program (2011 to 2015)

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Michael A. Pfaller ◽  
Rodrigo E. Mendes ◽  
Jennifer M. Streit ◽  
Patricia A. Hogan ◽  
Robert K. Flamm
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Resistance Mechanisms ◽  
23S Rrna ◽  
Rrna Gene ◽  
Gram Positive ◽  
Content Type ◽  
Linezolid Resistance

ABSTRACT This report describes linezolid susceptibility testing results for 6,741 Gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the report summarizes linezolid in vitro activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid showed potent activity in testing against Staphylococcus aureus, inhibiting >99.9% of 3,031 isolates at ≤2 µg/ml. Similarly, linezolid showed coverage against 99.2% of coagulase-negative staphylococci, 99.7% of enterococci, and 100.0% of Streptococcus pneumoniae, virdans group, and beta-hemolytic streptococcus isolates tested. The overall linezolid resistance rate remained a modest <1% from 2011 to 2015. Staphylococci, especially Staphylococcus epidermidis, showed a range of linezolid resistance mechanisms. Increased annual trends for the presence of cfr among Staphylococcus aureus isolates were not observed, but 64.3% (9/14) of the isolates with decreased susceptibility (MIC, ≥4 µg/ml) to linezolid carried this transferrable gene (2011 to 2015). The cfr gene was detected in 21.9% (7/32) of linezolid-resistant staphylococci other than S. aureus from 2011 to 2015. The optrA gene was noted in half (2/4) of the population of linezolid-nonsusceptible Enterococcus faecalis isolates from 2011 to 2015, while linezolid-nonsusceptible Enterococcus faecium isolates showed alterations predominantly (16/16) in the 23S rRNA gene (G2576T). This report confirms a long record of linezolid activity against Gram-positive isolates in the United States since regulatory approval in 2000 and reports the oxazolidinones evolving resistance mechanisms.

scholarly journals Antibiotics in Bone Cements Used for Prosthesis Fixation: An Efficient Way to Prevent Staphylococcus aureus and Staphylococcus epidermidis Prosthetic Joint Infection

2021 ◽  
Vol 7 ◽  
Author(s):  
Andréa Cara ◽  
Mathilde Ballet ◽  
Claire Hemery ◽  
Tristan Ferry ◽  
Frédéric Laurent ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Joint Infection ◽  
Bone Cements ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Prosthesis Fixation

Prosthetic joint infections (PJIs) are one of the most frequent reasons for arthroplasty revision. These infections are mostly associated with the formation of biofilm, notably by staphylococci, such as Staphylococcus aureus and Staphylococcus epidermidis. To minimize the rates of PJIs following primary or revision total joint arthroplasty, antibiotic-loaded bone cements (ALBCs) can be used for prosthesis fixation. However, its use is still debated. Indeed, various studies reported opposite results. In this context, we aimed to compare the prophylactic anti-biofilm activity of ALBCs loaded with two antibiotics with ALBC loaded with only one antibiotic. We compared commercial ready-to-use cements containing gentamicin alone, gentamicin plus vancomycin, and gentamicin plus clindamycin to plain cement (no antibiotic), investigating staphylococcal biofilm formation for 10 strains of S. aureus and S. epidermidis with specific resistance to gentamicin, vancomycin, or clindamycin. Firstly, we performed disk diffusion assays with the elution solutions. We reported that only the cement containing gentamicin and clindamycin was able to inhibit bacterial growth at Day 9, whereas cements with gentamicin only or gentamicin and vancomycin lost their antibacterial activity at Day 3. Then, we observed that all the tested ALBCs can inhibit biofilm formation by methicillin-susceptible staphylococci without other antibiotic resistance ability. Similar results were observed when we tested vancomycin-resistant or clindamycin-resistant staphylococci, with some strain-dependent significant increase of efficacy for the two antibiotic ALBCs when compared with gentamicin-loaded cement. However, adding vancomycin or clindamycin to gentamicin allows a better inhibition of biofilm formation when gentamicin-resistant strains were used. Our in vitro results suggest that using commercially available bone cements loaded with gentamicin plus vancomycin or clindamycin for prosthesis fixation can help in preventing staphylococcal PJIs following primary arthroplasties, non-septic revisions or septic revisions, especially to prevent PJIs caused by gentamicin-resistant staphylococci.

scholarly journals Bactericidal Action of Daptomycin against Stationary-Phase and Nondividing Staphylococcus aureus Cells

2007 ◽  
Vol 51 (12) ◽  
pp. 4255-4260 ◽  
Author(s):  
Carmela T. M. Mascio ◽  
Jeff D. Alder ◽  
Jared A. Silverman
Keyword(s):  
Staphylococcus Aureus ◽  
Stationary Phase ◽  
Bactericidal Activity ◽  
Direct Action ◽  
Metabolic Inhibitor ◽  
Log Reduction ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Lipopeptide Antibiotic

ABSTRACT Most antibiotics with bactericidal activity require that the bacteria be actively dividing to produce rapid killing. However, in many infections, such as endocarditis, prosthetic joint infections, and infected embedded catheters, the bacteria divide slowly or not at all. Daptomycin is a lipopeptide antibiotic with a distinct mechanism of action that targets the cytoplasmic membrane of gram-positive organisms, including Staphylococcus aureus. Daptomycin is rapidly bactericidal against exponentially growing bacteria (a 3-log reduction in 60 min). The objectives of this study were to determine if daptomycin is bactericidal against nondividing S. aureus and to quantify the extent of the bactericidal activity. In high-inoculum methicillin-sensitive S. aureus cultures in stationary phase (1010 CFU/ml), daptomycin displayed concentration-dependent bactericidal activity, requiring 32 μg/ml to achieve a 3-log reduction. In a study comparing several antibiotics at 100 μg/ml, daptomycin demonstrated faster bactericidal activity than nafcillin, ciprofloxacin, gentamicin, and vancomycin. In experiments where bacterial cell growth was halted by the metabolic inhibitor carbonyl cyanide m-chlorophenylhydrazone or erythromycin, daptomycin (10 μg/ml) achieved the bactericidal end point (a 3-log reduction) within 2 h. In contrast, ciprofloxacin (10 μg/ml) did not produce bactericidal activity. Daptomycin (2 μg/ml) remained bactericidal against cold-arrested S. aureus, which was protected from the actions of ciprofloxacin and nafcillin. The data presented here suggest that, in contrast to that of other classes of antibiotics, the bactericidal activity of daptomycin does not require cell division or active metabolism, most likely as a consequence of its direct action on the bacterial membrane.

scholarly journals In VitroEfficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

2013 ◽  
Vol 57 (11) ◽  
pp. 5717-5720 ◽  
Author(s):  
Hung-Jen Tang ◽  
Chi-Chung Chen ◽  
Kuo-Chen Cheng ◽  
Kuan-Ying Wu ◽  
Yi-Chung Lin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Antibacterial Activities ◽  
Methicillin Resistant ◽  
Content Type ◽  
Biofilm Model ◽  
Rifampin Resistance ◽  
Combination Regimens ◽  
Resistant Mutation

ABSTRACTTo compare thein vitroantibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistantStaphylococcus aureus(MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.

Sign in / Sign up

Export Citation Format

Share Document