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1.
Emerg Med J ; 37(2): 112-113, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31980552

ABSTRACT

A shortcut review was carried out to establish whether the degree of breathlessness in patients with an acute exacerbation of COPD is indicative of the severity of the exacerbation. Three hundred and forty-seven papers were found using the reported searches, of which five presented the best available evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these five papers are tabulated. It is concluded that increased shortness of breath is associated with a worse prognosis in patients with acute exacerbations of COPD. Dyspnoea assessment should be included in the triage process.


Subject(s)
Dyspnea/etiology , Patients/psychology , Perception , Pulmonary Disease, Chronic Obstructive/complications , Triage/standards , Dyspnea/physiopathology , Humans , Patients/statistics & numerical data , Triage/methods , Triage/statistics & numerical data
3.
Genes (Basel) ; 9(8)2018 Jul 31.
Article in English | MEDLINE | ID: mdl-30065230

ABSTRACT

B chromosomes (Bs) are enigmatic additional elements in the genomes of thousands of species of plants, animals, and fungi. How do these non-essential, harmful, and parasitic chromosomes maintain their presence in their hosts, making demands on all the essential functions of their host genomes? The answer seems to be that they have mechanisms of drive which enable them to enhance their transmission rates by various processes of non-mendelian inheritance. It is also becoming increasingly clear that the host genomes are developing their own mechanisms to resist the impact of the harmful effects of the Bs.

4.
J Clin Microbiol ; 56(8)2018 08.
Article in English | MEDLINE | ID: mdl-29848564

ABSTRACT

Delafloxacin, a recently approved anionic fluoroquinolone, was tested within an international resistance surveillance program. The in vitro susceptibilities of 7,914 indicated pathogens causing acute bacterial skin and skin structure infections (ABSSSI) were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution MIC testing methods. The U.S. Food and Drug Administration (FDA) susceptibility testing breakpoints and quality control ranges for routine broth microdilution and disk diffusion methods were confirmed. The delafloxacin MIC50/90 (% susceptibility) results were as follows: Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), 0.008/0.25 µg/ml (92.8%); Staphylococcus lugdunensis, 0.016/0.03 µg/ml (99.3%); Streptococcus pyogenes, 0.016/0.03 µg/ml (100.0%); Streptococcus anginosus group, 0.008/0.016 µg/ml (100.0%); Enterococcus faecalis, 0.12/1 µg/ml (66.2%); and Enterobacteriaceae, 0.12/4 µg/ml (69.5%). The FDA clinical breakpoints were used to assess intermethod test agreement between delafloxacin MIC and disk diffusion methods for the indicated pathogens. The intermethod susceptibility test categorical agreement for delafloxacin was acceptable, with only 0.4% very major, false-susceptible errors among S. aureus strains. Across all FDA-indicated species, the selected breakpoints produced only 0.0 to 1.7% rates of serious (very major and major errors) intermethod error. Quality control ranges for these standardized delafloxacin susceptibility test methods were calculated from three multilaboratory (12 total sites) studies for six control organisms. In conclusion, the application of FDA MIC breakpoints for delafloxacin against contemporary (2014 to 2016) isolates of ABSSSI pathogens provides additional support for the use of delafloxacin in the treatment of adults with ABSSSI. Delafloxacin MIC and disk diffusion susceptibility testing methods have been standardized for clinical application, achieving high intermethod categorical agreement.


Subject(s)
Anti-Bacterial Agents/pharmacology , Fluoroquinolones/pharmacology , Microbial Sensitivity Tests/standards , Enterobacteriaceae/drug effects , Humans , Microbial Viability/drug effects , Quality Control , Staphylococcus/drug effects
5.
BMC Infect Dis ; 17(1): 534, 2017 08 02.
Article in English | MEDLINE | ID: mdl-28764660

ABSTRACT

BACKGROUND: In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. However, no clinical studies have evaluated the relationship between initial vancomycin exposure and emergence of hVISA. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a non-hVISA BSI at baseline. METHODS: This was a retrospective cohort study of patients with methicillin-resistant Staphylococcus aureus (MRSA) BSIs at Albany Medical Center Hospital (AMCH) between January 2005 and June 2009. The vancomycin AUC exposure variables on day 1 (AUC0-24h) and day 2 (AUC24-48h) were estimated using the maximal a posteriori probability (MAP) procedure in ADAPT 5. RESULTS: There were 238 unique episodes of MRSA BSIs during the study period, 119 of which met inclusion criteria. Overall, hVISA emerged in 7/119 (5.9%) of patients. All 7 cases of hVISA involved patients who did not achieve area under the curve over broth microdilution minimum inhibitory concentration (AUC0-24h/MICBMD) ratio of 521 or an AUC24-48h/MICBMD ratio of 650. No associations between other day 1 and day 2 AUC variables and emergence of hVISA were noted. CONCLUSIONS: Although more data are needed to draw definitive conclusions, these findings suggest that hVISA emergence among patients with non-hVISA MRSA BSIs at baseline may be partially explained by suboptimal exposure to vancomycin in the first 1 to 2 days of therapy. At a minimum, these findings support further study of the relationship between initial vancomycin exposure and hVISA emergence among patients with MRSA BSIs in a well-powered, multi-center, prospective trial.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Bacteremia/microbiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Vancomycin/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Area Under Curve , Bacteremia/drug therapy , Disk Diffusion Antimicrobial Tests , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Pilot Projects , Prospective Studies , Retrospective Studies , Staphylococcal Infections/drug therapy , Staphylococcus aureus/pathogenicity , Vancomycin/pharmacology , Vancomycin Resistance/drug effects
6.
Diagn Microbiol Infect Dis ; 88(2): 177-183, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28341098

ABSTRACT

A total of 18,386 organisms, including 13,224 Enterobacteriaceae, 3536 Pseudomonas aeruginosa, 1254 Acinetobacter spp., and 372Stenotrophomonas maltophilia were collected from Western Europe (WEU; n=10,021), Eastern Europe (EEU; n=4957), and the Asia-Pacific region (APAC; n=3408 [1052 from China]) in 2013-2014 as part of the SENTRY Antimicrobial Surveillance Program and tested by a reference broth microdilution method for susceptibility against tigecycline, cefoperazone/sulbactam, and comparator agents. Overall, 95.3% of Enterobacteriaceae were susceptible (≤1µg/mL; EUCAST) to tigecycline (MIC50/90, 0.12/1µg/mL) with regional EUCAST susceptibility rates of 94.8-97.8% (98.9-99.6% inhibited at ≤2µg/mL [US FDA]). Among Acinetobacter spp., 66.1% (EEU) and 79.5% (WEU) were inhibited at ≤1µg/mL of tigecycline (94.9% and 97.3% inhibited at ≤2µg/mL; pan-European MIC50/90, 1/2µg/mL). For S. maltophilia, 65.4% (China) to 88.9% (EEU) of the isolates were inhibited at ≤1µg/mL of tigecycline. Cefoperazone/sulbactam inhibited 94.6/83.5/91.5% of Enterobacteriaceae at ≤16µg/mL in WEU/EEU/APAC, respectively.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cefoperazone/pharmacology , Gram-Negative Bacteria/drug effects , Minocycline/analogs & derivatives , Sulbactam/pharmacology , Acinetobacter/drug effects , Acinetobacter/isolation & purification , Asia , China , Drug Therapy, Combination , Enterobacteriaceae/drug effects , Enterobacteriaceae/isolation & purification , Europe , Gram-Negative Bacteria/isolation & purification , Humans , Microbial Sensitivity Tests , Minocycline/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Stenotrophomonas maltophilia/drug effects , Stenotrophomonas maltophilia/isolation & purification , Tigecycline
7.
J Prev Alzheimers Dis ; 3(4): 229-235, 2016.
Article in English | MEDLINE | ID: mdl-29034223

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) prevention research requires methods for measurement of disease progression not yet revealed by symptoms. Preferably, such measurement should encompass multiple disease markers. OBJECTIVES: Evaluate an item response theory (IRT) model-based latent variable Alzheimer Progression Score (APS) that uses multi-modal disease markers to estimate pre-clinical disease progression. DESIGN: Estimate APS scores in the BIOCARD observational study, and in the parallel PREVENT-AD Cohort and its sister INTREPAD placebo-controlled prevention trial. Use BIOCARD data to evaluate whether baseline and early APS trajectory predict later progression to MCI/dementia. Similarly, use longitudinal PREVENT-AD data to assess test measurement invariance over time. Further, assess portability of the PREVENT-AD IRT model to baseline INTREPAD data, and explore model changes when CSF markers are added or withdrawn. SETTING: BIOCARD was established in 1995 and participants were followed up to 20 years in Baltimore, USA. The PREVENT-AD and INTREPAD trial cohorts were established between 2011-2015 in Montreal, Canada, using nearly identical entry criteria to enroll high-risk cognitively normal persons aged 60+ then followed for several years. PARTICIPANTS: 349 cognitively normal, primarily middle-aged participants in BIOCARD, 125 high-risk participants aged 60+ in PREVENT-AD, and 217 similar subjects in INTREPAD. 106 INTREPAD participants donated up to four serial CSF samples. MEASUREMENTS: Global cognitive assessment and multiple structural, functional, and diffusion MRI metrics, sensori-neural tests, and CSF concentrations of tau, Aß42 and their ratio. RESULTS: Both baseline values and early slope of APS scores in BIOCARD predicted later progression to MCI or AD. Presence of CSF variables strongly improved such prediction. A similarly derived APS in PREVENT-AD showed measurement invariance over time and portability to the parallel INTREPAD sample. CONCLUSIONS: An IRT-based APS can summarize multimodal information to provide a longitudinal measure of pre-clinical AD progression, and holds promise as an outcome for AD prevention trials.

8.
Diagn Microbiol Infect Dis ; 82(4): 303-13, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25986029

ABSTRACT

The in vitro activities of isavuconazole, micafungin, and 8 comparator antifungal agents were determined for 1613 clinical isolates of fungi (1320 isolates of Candida spp., 155 of Aspergillus spp., 103 of non-Candida yeasts, and 35 non-Aspergillus molds) collected during a global survey conducted in 2013. The vast majority of the isolates of the 21 different species of Candida, with the exception of Candida glabrata (MIC90, 2 µg/mL), Candida krusei (MIC90, 1 µg/mL), and Candida guilliermondii (MIC90, 8 µg/mL), were inhibited by ≤0.25 µg/mL of isavuconazole. C. glabrata and C. krusei were largely inhibited by ≤1 µg/mL of isavuconazole. Resistance to fluconazole was seen in 0.5% of Candida albicans isolates, 11.1% of C. glabrata isolates, 2.5% of Candida parapsilosis isolates, 4.5% of Candida tropicalis isolates, and 20.0% of C. guilliermondii isolates. Resistance to the echinocandins was restricted to C. glabrata (1.3-2.1%) and C. tropicalis (0.9-1.8%). All agents except for the echinocandins were active against 69 Cryptococcus neoformans isolates, and the triazoles, including isavuconazole, were active against the other yeasts. Both the mold active triazoles as well as the echinocandins were active against 155 Aspergillus spp. isolates belonging to 10 species/species complex. In general, there was low resistance levels to the available systemically active antifungal agents in a large, contemporary (2013), global collection of molecularly characterized yeasts and molds. Resistance to azoles and echinocandins was most prominent among isolates of C. glabrata, C. tropicalis, and C. guilliermondii.


Subject(s)
Antifungal Agents/pharmacology , Drug Resistance, Fungal , Echinocandins/pharmacology , Fungi/drug effects , Lipopeptides/pharmacology , Mycoses/microbiology , Nitriles/pharmacology , Opportunistic Infections/microbiology , Pyridines/pharmacology , Triazoles/pharmacology , Fungi/isolation & purification , Global Health , Humans , Micafungin , Microbial Sensitivity Tests
9.
Antimicrob Agents Chemother ; 59(4): 2432-4, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25605359

ABSTRACT

Solithromycin, a next-generation macrolide and novel fluoroketolide, was tested against a 2012 collection of serotyped U.S. macrolide-resistant Streptococcus pneumoniae isolates associated with community-acquired bacterial pneumonia (CABP). Against all 272 isolates, solithromycin demonstrated high potency (MIC50/90, 0.06/0.25 µg/ml), and it inhibited all strains at MICs of ≤0.5 µg/ml, including the two most prevalent macrolide-resistant serotypes (19A and 35B). These data support the continued clinical development of solithromycin for the treatment of multidrug-resistant CABP.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/drug effects , Macrolides/pharmacology , Pneumococcal Infections/microbiology , Streptococcus pneumoniae/drug effects , Triazoles/pharmacology , Bacterial Proteins/genetics , Community-Acquired Infections/microbiology , Drug Resistance, Bacterial/genetics , Drug Resistance, Multiple, Bacterial , Humans , Microbial Sensitivity Tests , Penicillin Resistance/genetics , Protein Tyrosine Phosphatases/genetics , Streptococcus pneumoniae/genetics , United States
10.
J Antimicrob Chemother ; 69(9): 2547-55, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24840624

ABSTRACT

OBJECTIVES: Several phenotypic characteristics of Staphylococcus aureus have been identified as aetiological factors responsible for adverse outcomes among patients receiving vancomycin. However, characterization of the outcomes associated with these reduced vancomycin susceptibility phenotypes (rVSPs) remains largely incomplete and it is unknown if these features contribute to deleterious treatment outcomes alone or in concert. This study described the interrelationship between rVSPs and assessed their individual and combined effects on outcomes among patients who received vancomycin for a methicillin-resistant S. aureus (MRSA) bloodstream infection. METHODS: An observational study of adult, hospitalized patients with MRSA bloodstream infections who were treated with vancomycin between January 2005 and June 2009 was performed. The rVSPs evaluated included the following: (i) Etest MIC; (ii) broth microdilution MIC; (iii) MBC : MIC ratio; and (iv) heteroresistance to vancomycin by the Etest macromethod. Failure was defined as any of the following: (i) 30 day mortality; (ii) bacteraemia ≥ 7 days on therapy; or (iii) recurrence of MRSA bacteraemia within 60 days of therapy discontinuation. RESULTS: During the study period, 184 cases met the study criteria and 41.3% met the failure criteria. There was a clear linear exposure-response relationship between the number of these phenotypic markers and outcomes. As the number of phenotypes escalated, the incidence of overall failure increased incrementally by 10%-18%. CONCLUSIONS: The data suggest that rVSPs contribute to deleterious treatment outcomes in concert.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Tolerance , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/drug therapy , Vancomycin/pharmacology , Vancomycin/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/drug therapy , Bacteremia/microbiology , Cohort Studies , Female , Humans , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Middle Aged , Recurrence , Retrospective Studies , Staphylococcal Infections/microbiology , Survival Analysis , Treatment Outcome , Young Adult
11.
J Clin Microbiol ; 50(6): 2040-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22461672

ABSTRACT

Clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) have been established for several Candida spp. and the newer triazoles and echinocandins but are not yet available for older antifungal agents, such as amphotericin B, flucytosine, or itraconazole. We determined species-specific ECVs for amphotericin B (AMB), flucytosine (FC) and itraconazole (ITR) for eight Candida spp. (30,221 strains) using isolates from 16 different laboratories in Brazil, Canada, Europe, and the United States, all tested by the CLSI reference microdilution method. The calculated 24- and 48-h ECVs expressed in µg/ml (and the percentages of isolates that had MICs less than or equal to the ECV) for AMB, FC, and ITR, respectively, were 2 (99.8)/2 (99.2), 0.5 (94.2)/1 (91.4), and 0.12 (95.0)/0.12 (92.9) for C. albicans; 2 (99.6)/2 (98.7), 0.5 (98.0)/0.5 (97.5), and 2 (95.2)/4 (93.5) for C. glabrata; 2 (99.7)/2 (97.3), 0.5 (98.7)/0.5 (97.8), and 05. (99.7)/0.5 (98.5) for C. parapsilosis; 2 (99.8)/2 (99.2), 0.5 (93.0)/1 (90.5), and 0.5 (97.8)/0.5 (93.9) for C. tropicalis; 2 (99.3)/4 (100.0), 32 (99.4)/32 (99.3), and 1 (99.0)/2 (100.0) for C. krusei; 2 (100.0)/4 (100.0), 0.5 (95.3)/1 (92.9), and 0.5 (95.8)/0.5 (98.1) for C. lusitaniae; -/2 (100.0), 0.5 (98.8)/0.5 (97.7), and 0.25 (97.6)/0.25 (96.9) for C. dubliniensis; and 2 (100.0)/2 (100.0), 1 (92.7)/-, and 1 (100.0)/2 (100.0) for C. guilliermondii. In the absence of species-specific CBP values, these wild-type (WT) MIC distributions and ECVs will be useful for monitoring the emergence of reduced susceptibility to these well-established antifungal agents.


Subject(s)
Amphotericin B/pharmacology , Antifungal Agents/pharmacology , Candida/drug effects , Candidiasis/microbiology , Flucytosine/pharmacology , Itraconazole/pharmacology , Brazil , Canada , Candida/isolation & purification , Europe , Humans , Microbial Sensitivity Tests/standards , United States
12.
J Clin Microbiol ; 50(4): 1199-203, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22278842

ABSTRACT

The echinocandin class of antifungal agents is considered to be the first-line treatment of bloodstream infections (BSI) due to Candida glabrata. Recent reports of BSI due to strains of C. glabrata resistant to both fluconazole and the echinocandins are of concern and prompted us to review the experience of two large surveillance programs, the SENTRY Antimicrobial Surveillance Program for the years 2006 through 2010 and the Centers for Disease Control and Prevention population-based surveillance conducted in 2008 to 2010. The in vitro susceptibilities of 1,669 BSI isolates of C. glabrata to fluconazole, voriconazole, anidulafungin, caspofungin, and micafungin were determined by CLSI broth microdilution methods. Fluconazole MICs of ≥64 µg/ml were considered resistant. Strains for which anidulafungin and caspofungin MICs were ≥0.5 µg/ml and for which micafungin MICs were ≥0.25 µg/ml were considered resistant. A total of 162 isolates (9.7%) were resistant to fluconazole, of which 98.8% were nonsusceptible to voriconazole (MIC > 0.5 µg/ml) and 9.3%, 9.3%, and 8.0% were resistant to anidulafungin, caspofungin, and micafungin, respectively. There were 18 fluconazole-resistant isolates that were resistant to one or more of the echinocandins (11.1% of all fluconazole-resistant isolates), all of which contained an acquired mutation in fks1 or fks2. By comparison, there were no echinocandin-resistant strains detected among 110 fluconazole-resistant isolates of C. glabrata tested in 2001 to 2004. These data document the broad emergence of coresistance over time to both azoles and echinocandins in clinical isolates of C. glabrata.


Subject(s)
Antifungal Agents/pharmacology , Candida glabrata/drug effects , Candidemia/microbiology , Drug Resistance, Multiple, Fungal/genetics , Echinocandins/pharmacology , Fluconazole/pharmacology , Adult , Aged , Candida glabrata/genetics , Candida glabrata/isolation & purification , Female , Fungal Proteins/genetics , Glucosyltransferases/genetics , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mutation, Missense , Sentinel Surveillance , Young Adult
13.
J Chemother ; 23(4): 200-6, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21803696

ABSTRACT

Daptomycin is a cyclic lipopeptide approved by the European medicines Agency (EMEA) for the treatment of complicated skin and soft tissue infections (cSSTI) and Staphylococcus aureus bacteremia and endocarditis. We evaluated the in vitro activity of daptomycin and comparators tested against clinical isolates from european hospitals over a 7-year period (2003-2009). A total of 36,769 consecutive isolates were collected in 34 medical centers located in 13 European countries, Turkey and Israel. the collection included S. aureus (18,352; 27.2% oxacillin-resistant [MRSA]); coagulase-negative staphylococci (CoNS; 6,874), Enterococcus spp. (7,241; 9.4% vancomycin-resistant), ß-hemolytic (3,009), viridans group streptococci (1,176), and Streptococcus bovis/gallolyticus (107). The organisms were isolated mainly from patients with bloodstream infection (56%) or cSSTI (23%). Daptomycin was very active against S. aureus and CoNS (MIC(50/90), 0.25/0.5 mg/l for both organisms), and its activity was not adversely influenced by oxacillin resistance. All Enterococcus faecalis strains were susceptible to daptomycin (MIC(50/90), 1/1 mg/l). Daptomycin (MIC(50/90), 2/2 mg/l; 100.0% susceptible) and linezolid (MIC(50/90), 1/2 mg/l; 99.7% susceptible) were the most active agents tested against vancomycin-resistant E. faecium. Vancomycin- resistant and -susceptible enterococcal strains were equally susceptible to daptomycin. Daptomycin was also active against ß-hemolytic streptococci (MIC(50/90), 0.06/0.25 mg/l; 100.0% susceptible), viridans group streptococci (MIC(50/90), 0.25/0.5 mg/l; 99.8% susceptible) and S. bovis (MIC(50/90), 0.06/0.12 mg/l; 100.0% susceptible).In summary, daptomycin was very potent against this large collection (36,769) of Gram-positive organisms isolated in european hospitals, and its activity remained stable across the 7-year period evaluated (2003-2009), using reference methods and interpretive criteria. Decreases in daptomycin potency were not observed since EMEA approval and widespread clinical use, and emerging resistance to other compounds did not adversely influence daptomycin activity against contemporary Gram-positive species.


Subject(s)
Anti-Bacterial Agents/pharmacology , Daptomycin/pharmacology , Gram-Positive Bacteria/drug effects , Gram-Positive Bacterial Infections/microbiology , Bacteremia/microbiology , Gram-Positive Bacteria/isolation & purification , Hospitals , Humans , Microbial Sensitivity Tests/methods , Soft Tissue Infections/microbiology , Vancomycin/pharmacology
14.
J Chemother ; 23(2): 71-6, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21571621

ABSTRACT

The linezolid surveillance network (ZAAPS program) has been monitoring linezolid activity and susceptibility rates for eight years (2002-2009) in european medical centers. Samples from 12-24 sites annually in 11 countries were monitored by a central laboratory design using reference MIC methods with international and regional interpretations (EUCAST). A total of 13,404 gram-positive pathogens were tested from 6 pathogen groups. Linezolid remained without documented resistance from 2002 through 2005, but beginning in 2006 resistant strains emerged at very low rates among Staphylococcus aureus (G2576T mutant in ireland, 2007), coagulase-negative staphylococci (CoNS; usually Staphylococcus epidermidis, France and Italy in 2006-2009) and enterococci (Enterococcus faecium in Germany [2006, 2008, 2009] and E. faecalis in Sweden [2008], United Kingdom [2008] and Germany [2009]); all but one strain having a target mutation. A mobile cfr was detected in an italian CoNS strain (2008 and 2009), and clonal spread was noted for linezolid-resistant strains (PFGE results). Overall the linezolid susceptibility rates were >99.9, 99.7 and 99.6% for S. aureus, CoNS and enterococci, respectively; and all streptococcal strains were susceptible (MIC(90), 1 mg/l). In conclusion, the ZAAPS program surveillance confirmed high, sustained levels of linezolid activity from 2002-2009 and without evidence of MIC creep or escalating resistance in gram-positive pathogens across monitored european nations.


Subject(s)
Acetamides/therapeutic use , Anti-Bacterial Agents/therapeutic use , Oxazolidinones/therapeutic use , Product Surveillance, Postmarketing/methods , Acetamides/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Europe , Gram-Positive Cocci/drug effects , Humans , Linezolid , Microbial Sensitivity Tests , Oxazolidinones/pharmacology , Product Surveillance, Postmarketing/standards
15.
J Clin Microbiol ; 49(7): 2568-71, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21543581

ABSTRACT

Although Clinical and Laboratory Standards Institute (CLSI) disk diffusion assay standard conditions are available for susceptibility testing of filamentous fungi (molds) to antifungal agents, quality control (QC) disk diffusion zone diameter ranges have not been established. This multicenter study documented the reproducibility of tests for one isolate each of five molds (Paecilomyces variotii ATCC MYA-3630, Aspergillus fumigatus ATCC MYA-3626, A. flavus ATCC MYA-3631, A. terreus ATCC MYA-3633, and Fusarium verticillioides [moniliforme] ATCC MYA-3629) and Candida krusei ATCC 6258 by the CLSI disk diffusion method (M51-A document). The zone diameter ranges for selected QC isolates were as follows: P. variotii ATCC MYA-3630, amphotericin B (15 to 24 mm), itraconazole (20 to 31 mm), and posaconazole (33 to 43 mm); A. fumigatus ATCC MYA-3626, amphotericin B (18 to 25 mm), itraconazole (11 to 21 mm), posaconazole (28 to 35 mm), and voriconazole (25 to 33 mm); and C. krusei, amphotericin B (18 to 27 mm), itraconazole (18 to 26 mm), posaconazole (28 to 38 mm), and voriconazole (29 to 39 mm). Due to low testing reproducibility, zone diameter ranges were not proposed for the other three molds.


Subject(s)
Antifungal Agents/pharmacology , Culture Media/chemistry , Fungi/drug effects , Mycology/methods , Mycology/standards , Microbial Sensitivity Tests/methods , Microbial Sensitivity Tests/standards , Quality Control , Reproducibility of Results
16.
J Chemother ; 22(5): 304-11, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21123152

ABSTRACT

Telavancin is approved in the United States and Canada for the treatment of complicated skin and skin structure infections (cSSSI) in adults caused by susceptible Gram-positive organisms. The antimicrobial activity of telavancin and comparators was evaluated against 5,027 (2007-2008) Gram-positive bacteria responsible for SSSI in medical centers in Asia-Pacific, European, Latin American, and North American regions. Telavancin was active against Staphylococcus aureus (MIC50(/)90, 0.12/0.25 mg/l; 100.0% susceptible) and coagulase-negative staphylococci (MIC50(/)90, 0.12/0.25 mg/l). telavancin inhibited all Enterococcus faecalis, including four strains displaying a VanB phenotype, at ≤ 1 mg/L (MIC50(/)90, 0.25/0.5 mg/l), except for two isolates with a VanA phenotype (MIC, >2 mg/l). Vancomycin-susceptible and VanB vancomycin-resistant E. faecium were inhibited by telavancin at ≤ 0.25 mg/L, while this drug exhibited elevated MIC values (≥ 0.5 mg/l) against E. faecium of VanA phenotype (MIC50(/)90, 2/>2 mg/l). Telavancin was potent against ß-haemolytic streptococci (MIC50(/)90, 0.03/0.12 mg/l; 100.0% susceptible) and viridans group streptococci (MIC50(/)90, 0.03/0.06 mg/l; 100.0% susceptible). These in vitro data document the activity of telavancin against contemporary Gram-positive isolates and support its clinical use for the treatment of cSSSI caused by the indicated pathogens.


Subject(s)
Aminoglycosides/pharmacology , Anti-Bacterial Agents/pharmacology , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Gram-Positive Bacterial Infections/microbiology , Skin Diseases, Bacterial/microbiology , Bacterial Toxins/metabolism , Drug Resistance, Bacterial/genetics , Enterococcus/drug effects , Enterococcus/isolation & purification , Exotoxins/metabolism , Gram-Positive Bacterial Infections/drug therapy , Humans , Leukocidins/metabolism , Lipoglycopeptides , Microbial Sensitivity Tests , Population Surveillance , Skin/drug effects , Skin/microbiology , Skin Diseases, Bacterial/drug therapy , Staphylococcal Skin Infections/drug therapy , Staphylococcal Skin Infections/microbiology , Staphylococcus/drug effects , Staphylococcus/isolation & purification , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification , Streptococcus/drug effects , Streptococcus/isolation & purification , Vancomycin/therapeutic use
17.
Cytogenet Genome Res ; 129(1-3): 64-71, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20501974

ABSTRACT

Biologists have been fascinated for more than 2 centuries about how the nucleus in eukaryotes is organised. Certain of the component parts are well known, but the overall picture is blurred and often confusing. Small genome species have chromosomes in their interphase nuclei disposed in diffuse chromosome territories, without any Rabl arrangement, while in large genomes the chromosomes run string-like through the nucleus with a Rabl orientation following through the cell cycle. What happens in genomes of intermediate size is either a bit of both, depending on the tissue being studied, or still remains to be determined. The centromeres are the most dynamic and least well understood part of the nucleus, subject to rapid evolutionary change and with an epigenetic mark based on a special form of histone CENH3. Nonetheless, the centromere epigenetic mark has been inherited for millions of years by a process that is a complete mystery. Centromeres are involved with the dynamic interactions between chromosomes and other parts of the nuclear environment, such as the nuclear matrix and inner nuclear membrane, and they also engage with the spindle when the order within the nucleus changes during its division. The nucleolus organizer regions have likewise posed tantalising problems about their massive amplification of rDNA sequences, and how they are regulated and expressed. Some of these issues are now becoming clearer with advances in the science and the ongoing development of new molecular tools. These developments are discussed in this contribution, with particular reference to the centromere and the nucleolus organizer.


Subject(s)
Heterochromatin/genetics , Plants/genetics , Arabidopsis/genetics , Cell Nucleus/genetics , Centromere/genetics , Epigenesis, Genetic , Genome, Plant , Interphase/genetics , Nucleolus Organizer Region/genetics , Triticum/genetics
18.
J Chemother ; 22(1): 13-6, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20227986

ABSTRACT

Tigecycline, a glycylcycline, has been approved by the United States Food and Drug Administration (USA-FDA) for the treatment of complicated skin and skin structure infections, intra-abdominal infections and community-acquired bacterial pneumonia. based on broth microdilution minimum inhibitory concentration (MIC) testing, tigecycline demonstrated sustained high activity (MIC(50/90), 0.12/0.25 mg/L) against a contemporary collection (10,242) of methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA) collected from 32 USA hospitals over a 5-year period (2004-2008). Tigecycline MIC distribution did not vary significantly during the study period and only three isolates (0.03%) were non-susceptible at USA-FDA breakpoints. Vancomycin (MIC(90), 1 mg/L), trimethoprim/sulfamethoxazole (MIC( 90), <0.5 mg/L) and linezolid (MIC(90), 2 mg/L) were also very active. The results of this study indicate that tigecycline potency and spectrum against MRSA have not changed since its initial regulatory approval by the USA-FDA.


Subject(s)
Anti-Bacterial Agents/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Minocycline/analogs & derivatives , Microbial Sensitivity Tests , Minocycline/pharmacology , Tigecycline , Time Factors
19.
J Clin Microbiol ; 48(5): 1592-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20335424

ABSTRACT

The antifungal broth microdilution (BMD) method of the European Committee on Antibiotic Susceptibility Testing (EUCAST) and the Etest agar diffusion method were compared with the Clinical and Laboratory Standards Institute (CLSI) BMD method M27-A3 for anidulafungin, caspofungin, and micafungin susceptibility testing of 133 clinical isolates of Candida species. The isolates were characterized for the presence or absence of fks1 and/or fks2 gene mutations and included 34 isolates of C. glabrata (4 mutant strains), 32 of C. albicans (1 mutant strain), 25 of C. parapsilosis, 19 of C. guilliermondii, 12 of C. tropicalis (2 mutant strains), and 11 of C. krusei. Excellent essential agreement (EA; within 2 dilutions) between the CLSI and EUCAST and CLSI and Etest MIC results was observed. The overall EA between the EUCAST and CLSI results ranged from 89.5% (caspofungin) to 99.2% (micafungin), whereas the EA between the Etest and CLSI results ranged from 90.2% (caspofungin) to 93.2% (anidulafungin). The categorical agreement (CA) between methods for each antifungal agent was assessed using previously determined epidemiological cutoff values (ECVs). Excellent CA (>90%) was observed for all comparisons between the EUCAST and CLSI results with the exceptions of C. glabrata and caspofungin (85.3%) and C. krusei and caspofungin (54.5%). The CA between the Etest and CLSI results was also excellent for all comparisons, with the exception of C. krusei and caspofungin (81.8%). All three methods were able to differentiate wild-type (WT) strains from those with fks mutations. With anidulafungin as the test reagent, the CLSI method identified 5 of 7 mutant strains, whereas the EUCAST method and the Etest identified 6 of 7 mutant strains. With either caspofungin or micafungin as the test reagent, the CLSI method identified all 7 mutant strains and the EUCAST method identified 6 of 7 mutant strains. The Etest identified all 7 mutant strains using caspofungin as the reagent. All three test methods showed a high level of agreement and of ability to distinguish fks mutant strains of Candida species from WT strains using each of the echinocandins.


Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Echinocandins/pharmacology , Lipopeptides/pharmacology , Anidulafungin , Candida/isolation & purification , Candidiasis/microbiology , Caspofungin , Humans , Micafungin , Microbial Sensitivity Tests/methods
20.
J Clin Microbiol ; 48(1): 52-6, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19923478

ABSTRACT

We tested a global collection of Candida sp. strains against anidulafungin, caspofungin, and micafungin, using CLSI M27-A3 broth microdilution (BMD) methods, in order to define wild-type (WT) populations and epidemiological cutoff values (ECVs). From 2003 to 2007, 8,271 isolates of Candida spp. (4,283 C. albicans, 1,236 C. glabrata, 1,238 C. parapsilosis, 996 C. tropicalis, 270 C. krusei, 99 C. lusitaniae, 88 C. guilliermondii, and 61 C. kefyr isolates) were obtained from over 100 centers worldwide. The modal MICs (in microg/ml) for anidulafungin, caspofungin, and micafungin, respectively, for each species were as follows: C. albicans, 0.03, 0.03, 0.015; C. glabrata, 0.06, 0.03, 0.015; C. tropicalis, 0.03, 0.03, 0.015; C. kefyr, 0.06, 0.015, 0.06; C. krusei, 0.03, 0.06, 0.06; C. lusitaniae, 0.05, 0.25, 0.12; C. parapsilosis, 2, 0.25, 1; and C. guilliermondii, 2, 0.5. 05. The ECVs, expressed in microg/ml (percentage of isolates that had MICs that were less than or equal to the ECV is shown in parentheses) for anidulafungin, caspofungin, and micafungin, respectively, were as follows: 0.12 (99.7%), 0.12 (99.8%), and 0.03 (97.7%) for C. albicans; 0.25 (99.4%), 0.12 (98.5%), and 0.03 (98.2%) for C. glabrata; 0.12 (98.9%), 0.12 (99.4%), and 0.12 (99.1%) for C. tropicalis; 0.25(100%), 0.03 (100%), and 0.12 (100%) for C. kefyr; 0.12 (99.3%), 0.25 (96.3%), and 0.12 (97.8%) for C. krusei; 2 (100%), 0.5 (98.0%), and 0.5 (99.0%) for C. lusitaniae; 4 (100%), 1 (98.6%), and 4 (100%) for C. parapsilosis; 16 (100%), 4 (95.5%), and 4 (98.9%) for C. guilliermondii. These WT MIC distributions and ECVs will be useful in surveillance for emerging reduced echinocandin susceptibility among Candida spp. and for determining the importance of various FKS1 or other mutations.


Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Candidiasis/microbiology , Echinocandins/pharmacology , Lipopeptides/pharmacology , Anidulafungin , Candida/isolation & purification , Caspofungin , Humans , Micafungin , Microbial Sensitivity Tests
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