Antimicrobial agents and chemotherapy, Jan 18, 2015
In over a decade (2002-2012) of Staphylococcus aureus surveillance testing on 62,195 isolates, da... more In over a decade (2002-2012) of Staphylococcus aureus surveillance testing on 62,195 isolates, dalbavancin was demonstrated to be active against isolates that were either susceptible or non-susceptible to daptomycin-, linezolid- and tigecycline. Nearly all (99.8%) of multidrug-resistant methicillin-resistant S. aureus were inhibited by dalbavancin at ≤0.12 μg/ml (MIC50/90, 0.06/0.06 μg/ml), the current United States Food and Drug Administration (USA-FDA) breakpoint. Overall, only 0.35% of the monitored S. aureus had a dalbavancin MIC at either 0.25 or 0.5 μg/ml (non-susceptible).
International journal of antimicrobial agents, 2015
Ceftazidime/avibactam consists of ceftazidime combined with the novel non-β-lactam β-lactamase in... more Ceftazidime/avibactam consists of ceftazidime combined with the novel non-β-lactam β-lactamase inhibitor avibactam, which inhibits Ambler classes A, C and some D enzymes. Clinical isolates were collected from 71 US medical centres in 2012-2013 and were tested for susceptibility at a central laboratory by reference broth microdilution methods. Results for 4381 bacterial isolates from intensive care unit (ICU) patients as well as those from ventilator-associated pneumonia (VAP) (n=435) were analysed and compared with those of 14 483 organisms from non-ICU patients. β-Lactamase-encoding genes were evaluated for 966 Enterobacteriaceae by a microarray-based assay. Ceftazidime/avibactam was active against 99.8/100.0% of Enterobacteriaceae (MIC90, 0.25/0.25mg/L) from ICU/non-ICU patients (2948/10,872 strains), including isolates from VAP (99.1%), multidrug-resistant (MDR) strains (99.3%), extensively drug-resistant (XDR) strains (96.5%) and meropenem-non-susceptible strains (98.0%), at MIC...
Scattergrams between vancomycin and telavancin demonstrated susceptibility agreement rates of 99.... more Scattergrams between vancomycin and telavancin demonstrated susceptibility agreement rates of 99.96, 99.65 and 100.00% for Staphylococcus aureus, Enterococcus faecalis and streptococci, respectively. A single very major error was obtained against E. faecalis, while vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant and teicoplanin-susceptible (VanB-phenotype) E. faecalis were responsible for the major and minor errors. These results support the use of vancomycin to infer telavancin susceptibility among indicated pathogens, except VISA, which should be tested for telavancin susceptibility.
Journal of Cardiovascular Computed Tomography, 2015
Objective: The purpose of this study is to investigate the cost and resource utilization due to c... more Objective: The purpose of this study is to investigate the cost and resource utilization due to chest pain (CP) evaluations after initial coronary computed tomography angiography (CCTA) stratified by coronary artery disease (CAD) burden.
Pseudomonas aeruginosa is the most common pathogen infecting the lungs of patients with cystic fi... more Pseudomonas aeruginosa is the most common pathogen infecting the lungs of patients with cystic fibrosis (CF). Improved antimicrobial chemotherapy has significantly increased the life expectancy of these patients. However, accurate susceptibility testing of P. aeruginosa isolates from CF sputum may be difficult because the organisms are often mucoid and slow growing. This study of 597 CF isolates of P. aeruginosa examined the correlation of disk diffusion and Etest (AB BIODISK, Solna, Sweden) results with a reference broth microdilution method. The rates of interpretive errors for 12 commonly used antipseudomonal antimicrobials were determined. The disk diffusion method correlated well (zone diameter versus MIC) for all of the agents tested. However, for mucoid isolates, correlation coefficients (r values) for piperacillin, piperacillin-tazobactam, and meropenem were <0.80. The Etest correlation with reference broth microdilution results (MIC versus MIC) was acceptable for all of ...
Antimicrobial agents and chemotherapy, Jan 23, 2015
Arbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinica... more Arbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States (USA). We evaluated the occurrence of organisms isolated from pneumonias in USA hospitalized patients (PHP), including ventilator-associated pneumonia (VAP), and the in vitro activity of arbekacin. Organism frequency was evaluated from a collection of 2,203 bacterial isolates (339 from VAP) consecutively collected from 25 medical centers in 2012 through the SENTRY Antimicrobial Surveillance Program. Arbekacin activity was tested against 904 isolates from PHP collected in 2012 from 62 USA medical centers and 303 multidrug-resistant (MDR) organisms collected worldwide in 2009 and 2010 from various infection types. Susceptibility to arbekacin and comparator agents was evaluated by the reference broth microdilution method. The four most common organisms from PHP were Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella spp. an...
Antimicrobial agents and chemotherapy, Jan 17, 2015
S. aureus and coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human... more S. aureus and coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human infections. The investigational antibacterial Debio 1450 (previously AFN-1720), a prodrug of Debio 1452 (previously AFN-1252) specifically targets staphylococci without significant activity against other Gram-positive or Gram-negative species. Debio 1452 inhibits FabI, an enzyme critical to fatty acid biosynthesis in staphylococci. The activity of Debio 1452 against CoNS, methicillin-susceptible (MSSA) and -resistant (MRSA) S. aureus, including significant clones, was determined. A globally diverse collection of 574 patient isolates from 35 countries was tested that included CoNS (6 species, 103 strains), MSSA (154), MRSA (163) and molecularly characterized strains (including spa typed MRSA clones; 154). Isolates were susceptibility tested by CLSI broth microdilution methods against Debio 1452 and 10 comparators. Susceptibility rates for comparators were determined using CLSI and EUCAST...
Pexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3 clinical trials as... more Pexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3 clinical trials as a topical antimicrobial agent for the treatment of mild infections associated with diabetic foot ulcers. Bacterial isolates from the 2013 SENTRY Antimicrobial Surveillance Program designated as pathogens from diabetic foot infections (DFI) and Gram-negative and -positive pathogens from various infection types that harbored selected resistance mechanisms/phenotypes were tested against pexiganan in reference cation-adjusted Mueller-Hinton broth. The MIC50 and MIC90 against all organisms tested from DFI were 16 and 32 μg/ml, respectively. Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter cloacae, Acinetobacter species, and Pseudomonas aeruginosa MIC values ranged from 8 to 16 μg/ml. Pexiganan MIC values among Staphylococcus aureus (methicillin-resistant S. aureus [MRSA] and methicillin-susceptible S. aureus [MSSA]), beta-hemolytic streptococci, and Enterococcus faec...
The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada, 2014
In the absence of clinical resistance, breakpoints for many antimicrobial agents are often set hi... more In the absence of clinical resistance, breakpoints for many antimicrobial agents are often set high. Clinical failures following use of the agents over time requires re-evaluation of breakpoints. This is based on patient response, pharmacokinetic/pharmacodynamic information and in vitro minimal inhibitory concentration data. Data from the SENTRY Antimicrobial Surveillance Program has shown that Clinical and Laboratory Standards Institute breakpoint changes for carbapenems that occurred between 2008 and 2012 in North America have resulted in decreased levels of susceptibility for some species. In particular, reduced susceptibility to imipenem was observed for Proteus mirabilis (35%) and Morganella morganii (80%). Minor decreases in susceptibility were also noted for Enterobacter species with ertapenem (5%) and imipenem (4.3%), and Serratia species with imipenem (6.4%). No significant decreases in susceptibility were observed for meropenem following the breakpoint changes. There were ...
We evaluated doripenem-resistant Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ACB... more We evaluated doripenem-resistant Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ACB; n = 411) and Enterobacteriaceae (n = 92) isolates collected from patients from 14 European and Mediterranean countries during 2009 to 2011 for the presence of carbapenemase-encoding genes and clonality. Following susceptibility testing, carbapenem-resistant (doripenem MIC, >2 μg/ml) isolates were screened for carbapenemases. New β-lactamase genes were expressed in a common background and susceptibility was tested. Class 1 integrons were sequenced. Clonality was evaluated by pulsed-field gel electrophoresis and multilocus sequence typing (Pasteur scheme). Relative expression of β-lactam intrinsic resistance mechanisms was determined for carbapenemase-negative Enterobacteriaceae. ACB and Enterobacteriaceae displayed 58.9 and 0.9% doripenem resistance, respectively. bla(OXA-23), bla(OXA-58), and bla(OXA-24/OXA-40) were detected among 277, 77, and 29 ACB, respectively (in 8, 6, and 5 co...
International journal of antimicrobial agents, 2014
In this study, 1717 fungal clinical isolates causing invasive fungal infections were evaluated ag... more In this study, 1717 fungal clinical isolates causing invasive fungal infections were evaluated against nine antifungal agents using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods. The isolates comprised 1487 Candida spp., 109 Aspergillus spp., 86 non-Candida yeasts (including 52 isolates of Cryptococcus neoformans) and 35 rare moulds obtained during 2012 from 72 hospitals worldwide. Echinocandin resistance among Candida spp. was low, and resistance rates to anidulafungin, caspofungin and micafungin varied from 0.0% to 2.8% among different species. Echinocandin-resistant Candida glabrata were shown to have fks mutations (fks2 HS1 F659Y, F659del, S663F and S663P), and fluconazole resistance was also observed in those strains. One Candida krusei and one Candida dubliniensis had L701M or S645P fks1 mutations, respectively. Candida tropicalis and C. glabrata had higher fluconazole resistance rates of 6.1% and 6.9%, respectively, compared with oth...
Diagnostic microbiology and infectious disease, 2014
Ceftazidime-avibactam, a combination of ceftazidime and the non-β-lactam β-lactamase inhibitor av... more Ceftazidime-avibactam, a combination of ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam, is in advanced clinical development. In this study, we report results of in vitro testing of ceftazidime-avibactam and comparator agents against a collection of urinary tract infection (UTI) isolates from the United States (USA), Europe and Mediterranean region (EMR), Latin America (LATAM), and the Asia-Pacific/South Africa regions (APAC). Clinical isolates (1 per patient episode) were collected from patients with a UTI during 2011. A total of 1797 isolates were collected from 159 medical centers. Isolates were processed at the medical centers and forwarded to a central monitoring laboratory for confirmatory identification and reference susceptibility testing. Ceftazidime-avibactam was highly active against Enterobacteriaceae and Pseudomonas aeruginosa. The MIC90 values for ceftazidime-avibactam against Enterobacteriaceae in the USA, EMR, and LATAM regions ranged from 0.25 to 0....
This study addressed the application of anidulafungin as a surrogate marker to predict the suscep... more This study addressed the application of anidulafungin as a surrogate marker to predict the susceptibility of Candida to caspofungin due to unacceptably high interlaboratory variation of caspofungin MIC values. CLSI reference broth microdilution methods and species-specific interpretive criteria were used to test 4,290 strains of Candida (eight species), including 71 strains with documented fks mutations. Caspofungin MIC values were compared with those of anidulafungin to determine the percentage of categorical agreement (CA) and very major (VME), major (ME), and minor error rates, as well as the ability to detect fks mutants. For all 4,290 isolates the CA was 97.1% (0.2% VME and ME, 2.5% minor errors) using anidulafungin as the surrogate. Among the 62 isolates of Candida albicans (4 isolates), C. tropicalis (5 isolates), C. krusei (4 isolates), C. kefyr (2 isolates), and C. glabrata (47 isolates) that were nonsusceptible (NS; either intermediate [I] or resistant [R]) to both caspofu...
Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired ... more Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired pneumonia (HAP) (excluding patients with ventilator-associated pneumonia but including ventilated HAP patients) and community-acquired pneumonia in adults. The aim of this study was to evaluate the in vitro antimicrobial activity of ceftobiprole against prevalent Gram-positive and -negative pathogens isolated in Europe, Turkey, and Israel during 2005 through 2010. A total of 60,084 consecutive, nonduplicate isolates from a wide variety of infections were collected from 33 medical centers. Species identification was confirmed, and all isolates were susceptibility tested using reference broth microdilution methods. Ceftobiprole had high activity against methicillin-susceptible Staphylococcus aureus (MSSA) (100.0% susceptible), methicillin-susceptible coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci, and Streptococcus pneumoniae (99.3% susceptible), with MIC90 values of ...
The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases
A total of 2484 target bacterial pathogens were collected (one per patient episode) from patients... more A total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 Latin American medical centers located in seven nations during 2011. Isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. A total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary tract and 11.3% from other sites. Ceftaroline was active against Staphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at ≤ 1 mg/L and all isolates at ≤ 2 mg/L (MIC5090, 0.25/2mg/L). National MRSA rates ranged from a low of 28.8% in Colombia to a high of 68.1% in Chile. All Streptococcus pyogenes and Streptococcus agalactiae were susceptible to ceftaroline (MIC50/90 values were at ≤ 0.015/≤ 0.015 mg/L for both). All Streptococcus pneumoniae were susceptible to ceftaroline, linezolid,...
Time-kill curves were determined for three isolates of Candida albicans tested against fluconazol... more Time-kill curves were determined for three isolates of Candida albicans tested against fluconazole and amphotericin B at multiples of the MIC. Fluconazole produced fungistatic activity, with concentration-related growth effects observed over a narrow range of concentrations. Amphotericin B exhibited fungicidal activity, with enhancement of activity over a broader range of concentrations.
The spectrum of antibacterial activity of cefixime was defined by reviewing data from two multice... more The spectrum of antibacterial activity of cefixime was defined by reviewing data from two multicenter studies and three independent studies that we performed within the past 3 years. Microdilution tests were performed with 16,016 bacterial isolates. An isolate was considered susceptible to cefixime if the minimal inhibitory concentration was less than or equal to 1.0 microgram/ml and resistant if the minimal inhibitory concentration was greater than or equal to 4.0 micrograms/ml. Cefixime was effective against the Enterobacteriaceae (87.7% susceptible to 1.0 microgram/ml) as well as against pathogenic Neisseria spp. (including penicillin-resistant gonococci), Haemophilus influenzae (including ampicillin-resistant strains), penicillin-susceptible Streptococcus pneumoniae and other Streptococcus species (minimal concentration inhibiting 90% of organisms less than or equal to 0.25 micrograms/ml). Species resistant to cefixime included penicillin-resistant pneumococci, Staphylococcus sp...
Background: Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gr... more Background: Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gram-positive bacteria currently used for the treatment of complicated skin and skin structure infections and bacteremia, including right sided endocarditis. We evaluated the in vitro activity of this compound and selected comparator agents tested against clinical strains of staphylococci and enterococci collected in European medical centers in 2005.
Antimicrobial agents and chemotherapy, Jan 18, 2015
In over a decade (2002-2012) of Staphylococcus aureus surveillance testing on 62,195 isolates, da... more In over a decade (2002-2012) of Staphylococcus aureus surveillance testing on 62,195 isolates, dalbavancin was demonstrated to be active against isolates that were either susceptible or non-susceptible to daptomycin-, linezolid- and tigecycline. Nearly all (99.8%) of multidrug-resistant methicillin-resistant S. aureus were inhibited by dalbavancin at ≤0.12 μg/ml (MIC50/90, 0.06/0.06 μg/ml), the current United States Food and Drug Administration (USA-FDA) breakpoint. Overall, only 0.35% of the monitored S. aureus had a dalbavancin MIC at either 0.25 or 0.5 μg/ml (non-susceptible).
International journal of antimicrobial agents, 2015
Ceftazidime/avibactam consists of ceftazidime combined with the novel non-β-lactam β-lactamase in... more Ceftazidime/avibactam consists of ceftazidime combined with the novel non-β-lactam β-lactamase inhibitor avibactam, which inhibits Ambler classes A, C and some D enzymes. Clinical isolates were collected from 71 US medical centres in 2012-2013 and were tested for susceptibility at a central laboratory by reference broth microdilution methods. Results for 4381 bacterial isolates from intensive care unit (ICU) patients as well as those from ventilator-associated pneumonia (VAP) (n=435) were analysed and compared with those of 14 483 organisms from non-ICU patients. β-Lactamase-encoding genes were evaluated for 966 Enterobacteriaceae by a microarray-based assay. Ceftazidime/avibactam was active against 99.8/100.0% of Enterobacteriaceae (MIC90, 0.25/0.25mg/L) from ICU/non-ICU patients (2948/10,872 strains), including isolates from VAP (99.1%), multidrug-resistant (MDR) strains (99.3%), extensively drug-resistant (XDR) strains (96.5%) and meropenem-non-susceptible strains (98.0%), at MIC...
Scattergrams between vancomycin and telavancin demonstrated susceptibility agreement rates of 99.... more Scattergrams between vancomycin and telavancin demonstrated susceptibility agreement rates of 99.96, 99.65 and 100.00% for Staphylococcus aureus, Enterococcus faecalis and streptococci, respectively. A single very major error was obtained against E. faecalis, while vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant and teicoplanin-susceptible (VanB-phenotype) E. faecalis were responsible for the major and minor errors. These results support the use of vancomycin to infer telavancin susceptibility among indicated pathogens, except VISA, which should be tested for telavancin susceptibility.
Journal of Cardiovascular Computed Tomography, 2015
Objective: The purpose of this study is to investigate the cost and resource utilization due to c... more Objective: The purpose of this study is to investigate the cost and resource utilization due to chest pain (CP) evaluations after initial coronary computed tomography angiography (CCTA) stratified by coronary artery disease (CAD) burden.
Pseudomonas aeruginosa is the most common pathogen infecting the lungs of patients with cystic fi... more Pseudomonas aeruginosa is the most common pathogen infecting the lungs of patients with cystic fibrosis (CF). Improved antimicrobial chemotherapy has significantly increased the life expectancy of these patients. However, accurate susceptibility testing of P. aeruginosa isolates from CF sputum may be difficult because the organisms are often mucoid and slow growing. This study of 597 CF isolates of P. aeruginosa examined the correlation of disk diffusion and Etest (AB BIODISK, Solna, Sweden) results with a reference broth microdilution method. The rates of interpretive errors for 12 commonly used antipseudomonal antimicrobials were determined. The disk diffusion method correlated well (zone diameter versus MIC) for all of the agents tested. However, for mucoid isolates, correlation coefficients (r values) for piperacillin, piperacillin-tazobactam, and meropenem were <0.80. The Etest correlation with reference broth microdilution results (MIC versus MIC) was acceptable for all of ...
Antimicrobial agents and chemotherapy, Jan 23, 2015
Arbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinica... more Arbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States (USA). We evaluated the occurrence of organisms isolated from pneumonias in USA hospitalized patients (PHP), including ventilator-associated pneumonia (VAP), and the in vitro activity of arbekacin. Organism frequency was evaluated from a collection of 2,203 bacterial isolates (339 from VAP) consecutively collected from 25 medical centers in 2012 through the SENTRY Antimicrobial Surveillance Program. Arbekacin activity was tested against 904 isolates from PHP collected in 2012 from 62 USA medical centers and 303 multidrug-resistant (MDR) organisms collected worldwide in 2009 and 2010 from various infection types. Susceptibility to arbekacin and comparator agents was evaluated by the reference broth microdilution method. The four most common organisms from PHP were Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella spp. an...
Antimicrobial agents and chemotherapy, Jan 17, 2015
S. aureus and coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human... more S. aureus and coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human infections. The investigational antibacterial Debio 1450 (previously AFN-1720), a prodrug of Debio 1452 (previously AFN-1252) specifically targets staphylococci without significant activity against other Gram-positive or Gram-negative species. Debio 1452 inhibits FabI, an enzyme critical to fatty acid biosynthesis in staphylococci. The activity of Debio 1452 against CoNS, methicillin-susceptible (MSSA) and -resistant (MRSA) S. aureus, including significant clones, was determined. A globally diverse collection of 574 patient isolates from 35 countries was tested that included CoNS (6 species, 103 strains), MSSA (154), MRSA (163) and molecularly characterized strains (including spa typed MRSA clones; 154). Isolates were susceptibility tested by CLSI broth microdilution methods against Debio 1452 and 10 comparators. Susceptibility rates for comparators were determined using CLSI and EUCAST...
Pexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3 clinical trials as... more Pexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3 clinical trials as a topical antimicrobial agent for the treatment of mild infections associated with diabetic foot ulcers. Bacterial isolates from the 2013 SENTRY Antimicrobial Surveillance Program designated as pathogens from diabetic foot infections (DFI) and Gram-negative and -positive pathogens from various infection types that harbored selected resistance mechanisms/phenotypes were tested against pexiganan in reference cation-adjusted Mueller-Hinton broth. The MIC50 and MIC90 against all organisms tested from DFI were 16 and 32 μg/ml, respectively. Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter cloacae, Acinetobacter species, and Pseudomonas aeruginosa MIC values ranged from 8 to 16 μg/ml. Pexiganan MIC values among Staphylococcus aureus (methicillin-resistant S. aureus [MRSA] and methicillin-susceptible S. aureus [MSSA]), beta-hemolytic streptococci, and Enterococcus faec...
The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada, 2014
In the absence of clinical resistance, breakpoints for many antimicrobial agents are often set hi... more In the absence of clinical resistance, breakpoints for many antimicrobial agents are often set high. Clinical failures following use of the agents over time requires re-evaluation of breakpoints. This is based on patient response, pharmacokinetic/pharmacodynamic information and in vitro minimal inhibitory concentration data. Data from the SENTRY Antimicrobial Surveillance Program has shown that Clinical and Laboratory Standards Institute breakpoint changes for carbapenems that occurred between 2008 and 2012 in North America have resulted in decreased levels of susceptibility for some species. In particular, reduced susceptibility to imipenem was observed for Proteus mirabilis (35%) and Morganella morganii (80%). Minor decreases in susceptibility were also noted for Enterobacter species with ertapenem (5%) and imipenem (4.3%), and Serratia species with imipenem (6.4%). No significant decreases in susceptibility were observed for meropenem following the breakpoint changes. There were ...
We evaluated doripenem-resistant Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ACB... more We evaluated doripenem-resistant Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ACB; n = 411) and Enterobacteriaceae (n = 92) isolates collected from patients from 14 European and Mediterranean countries during 2009 to 2011 for the presence of carbapenemase-encoding genes and clonality. Following susceptibility testing, carbapenem-resistant (doripenem MIC, >2 μg/ml) isolates were screened for carbapenemases. New β-lactamase genes were expressed in a common background and susceptibility was tested. Class 1 integrons were sequenced. Clonality was evaluated by pulsed-field gel electrophoresis and multilocus sequence typing (Pasteur scheme). Relative expression of β-lactam intrinsic resistance mechanisms was determined for carbapenemase-negative Enterobacteriaceae. ACB and Enterobacteriaceae displayed 58.9 and 0.9% doripenem resistance, respectively. bla(OXA-23), bla(OXA-58), and bla(OXA-24/OXA-40) were detected among 277, 77, and 29 ACB, respectively (in 8, 6, and 5 co...
International journal of antimicrobial agents, 2014
In this study, 1717 fungal clinical isolates causing invasive fungal infections were evaluated ag... more In this study, 1717 fungal clinical isolates causing invasive fungal infections were evaluated against nine antifungal agents using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods. The isolates comprised 1487 Candida spp., 109 Aspergillus spp., 86 non-Candida yeasts (including 52 isolates of Cryptococcus neoformans) and 35 rare moulds obtained during 2012 from 72 hospitals worldwide. Echinocandin resistance among Candida spp. was low, and resistance rates to anidulafungin, caspofungin and micafungin varied from 0.0% to 2.8% among different species. Echinocandin-resistant Candida glabrata were shown to have fks mutations (fks2 HS1 F659Y, F659del, S663F and S663P), and fluconazole resistance was also observed in those strains. One Candida krusei and one Candida dubliniensis had L701M or S645P fks1 mutations, respectively. Candida tropicalis and C. glabrata had higher fluconazole resistance rates of 6.1% and 6.9%, respectively, compared with oth...
Diagnostic microbiology and infectious disease, 2014
Ceftazidime-avibactam, a combination of ceftazidime and the non-β-lactam β-lactamase inhibitor av... more Ceftazidime-avibactam, a combination of ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam, is in advanced clinical development. In this study, we report results of in vitro testing of ceftazidime-avibactam and comparator agents against a collection of urinary tract infection (UTI) isolates from the United States (USA), Europe and Mediterranean region (EMR), Latin America (LATAM), and the Asia-Pacific/South Africa regions (APAC). Clinical isolates (1 per patient episode) were collected from patients with a UTI during 2011. A total of 1797 isolates were collected from 159 medical centers. Isolates were processed at the medical centers and forwarded to a central monitoring laboratory for confirmatory identification and reference susceptibility testing. Ceftazidime-avibactam was highly active against Enterobacteriaceae and Pseudomonas aeruginosa. The MIC90 values for ceftazidime-avibactam against Enterobacteriaceae in the USA, EMR, and LATAM regions ranged from 0.25 to 0....
This study addressed the application of anidulafungin as a surrogate marker to predict the suscep... more This study addressed the application of anidulafungin as a surrogate marker to predict the susceptibility of Candida to caspofungin due to unacceptably high interlaboratory variation of caspofungin MIC values. CLSI reference broth microdilution methods and species-specific interpretive criteria were used to test 4,290 strains of Candida (eight species), including 71 strains with documented fks mutations. Caspofungin MIC values were compared with those of anidulafungin to determine the percentage of categorical agreement (CA) and very major (VME), major (ME), and minor error rates, as well as the ability to detect fks mutants. For all 4,290 isolates the CA was 97.1% (0.2% VME and ME, 2.5% minor errors) using anidulafungin as the surrogate. Among the 62 isolates of Candida albicans (4 isolates), C. tropicalis (5 isolates), C. krusei (4 isolates), C. kefyr (2 isolates), and C. glabrata (47 isolates) that were nonsusceptible (NS; either intermediate [I] or resistant [R]) to both caspofu...
Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired ... more Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired pneumonia (HAP) (excluding patients with ventilator-associated pneumonia but including ventilated HAP patients) and community-acquired pneumonia in adults. The aim of this study was to evaluate the in vitro antimicrobial activity of ceftobiprole against prevalent Gram-positive and -negative pathogens isolated in Europe, Turkey, and Israel during 2005 through 2010. A total of 60,084 consecutive, nonduplicate isolates from a wide variety of infections were collected from 33 medical centers. Species identification was confirmed, and all isolates were susceptibility tested using reference broth microdilution methods. Ceftobiprole had high activity against methicillin-susceptible Staphylococcus aureus (MSSA) (100.0% susceptible), methicillin-susceptible coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci, and Streptococcus pneumoniae (99.3% susceptible), with MIC90 values of ...
The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases
A total of 2484 target bacterial pathogens were collected (one per patient episode) from patients... more A total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 Latin American medical centers located in seven nations during 2011. Isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. A total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary tract and 11.3% from other sites. Ceftaroline was active against Staphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at ≤ 1 mg/L and all isolates at ≤ 2 mg/L (MIC5090, 0.25/2mg/L). National MRSA rates ranged from a low of 28.8% in Colombia to a high of 68.1% in Chile. All Streptococcus pyogenes and Streptococcus agalactiae were susceptible to ceftaroline (MIC50/90 values were at ≤ 0.015/≤ 0.015 mg/L for both). All Streptococcus pneumoniae were susceptible to ceftaroline, linezolid,...
Time-kill curves were determined for three isolates of Candida albicans tested against fluconazol... more Time-kill curves were determined for three isolates of Candida albicans tested against fluconazole and amphotericin B at multiples of the MIC. Fluconazole produced fungistatic activity, with concentration-related growth effects observed over a narrow range of concentrations. Amphotericin B exhibited fungicidal activity, with enhancement of activity over a broader range of concentrations.
The spectrum of antibacterial activity of cefixime was defined by reviewing data from two multice... more The spectrum of antibacterial activity of cefixime was defined by reviewing data from two multicenter studies and three independent studies that we performed within the past 3 years. Microdilution tests were performed with 16,016 bacterial isolates. An isolate was considered susceptible to cefixime if the minimal inhibitory concentration was less than or equal to 1.0 microgram/ml and resistant if the minimal inhibitory concentration was greater than or equal to 4.0 micrograms/ml. Cefixime was effective against the Enterobacteriaceae (87.7% susceptible to 1.0 microgram/ml) as well as against pathogenic Neisseria spp. (including penicillin-resistant gonococci), Haemophilus influenzae (including ampicillin-resistant strains), penicillin-susceptible Streptococcus pneumoniae and other Streptococcus species (minimal concentration inhibiting 90% of organisms less than or equal to 0.25 micrograms/ml). Species resistant to cefixime included penicillin-resistant pneumococci, Staphylococcus sp...
Background: Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gr... more Background: Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gram-positive bacteria currently used for the treatment of complicated skin and skin structure infections and bacteremia, including right sided endocarditis. We evaluated the in vitro activity of this compound and selected comparator agents tested against clinical strains of staphylococci and enterococci collected in European medical centers in 2005.
Uploads
Papers by Ronald Jones