Antimicrobial Activity of Murepavadin Tested against Clinical Isolates of
                    Pseudomonas aeruginosa
                    from the United States, Europe, and China

ABSTRACT Murepavadin (formerly POL7080), a 14-amino-acid cyclic peptide, and comparators were tested by the broth microdilution method against 1,219 Pseudomonas aeruginosa isolates from 112 medical centers. Murepavadin (MIC 50/90 , 0.12/0.12 mg/liter) was 4- to 8-fold more active than colistin (MIC 50/90 , 1/1 mg/liter) and polymyxin B (MIC 50/90 , 0.5/1 mg/liter) and inhibited 99.1% of isolates at ≤0.5 mg/liter. Only 4 isolates (0.3%) exhibited murepavadin MICs of >2 mg/liter. Murepavadin was equally active against isolates from Europe, the United States, and China.

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Antimicrobial Activity of Ceftolozane-Tazobactam Tested against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2011-2012)

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01802-13 ◽

2013 ◽

Vol 57 (12) ◽

pp. 6305-6310 ◽

Cited By ~ 129

Author(s):

David J. Farrell ◽

Robert K. Flamm ◽

Helio S. Sader ◽

Ronald N. Jones

Keyword(s):

Pseudomonas Aeruginosa ◽

The United States ◽

Multidrug Resistant ◽

High Rate ◽

Drug Resistant ◽

Good Activity ◽

Content Type ◽

Microdilution Method ◽

Medical Centers ◽

Broth Microdilution Method

ABSTRACTCeftolozane/tazobactam, a novel antimicrobial agent with activity againstPseudomonas aeruginosa(including drug-resistant strains) and other common Gram-negative pathogens (including most extended-spectrum-β-lactamase [ESBL]-producingEnterobacteriaceaestrains), and comparator agents were susceptibility tested by a reference broth microdilution method against 7,071Enterobacteriaceaeand 1,971P. aeruginosaisolates. Isolates were collected consecutively from patients in 32 medical centers across the United States during 2011 to 2012. Overall, 15.7% and 8.9% ofP. aeruginosaisolates were classified as multidrug resistant (MDR) and extensively drug resistant (XDR), and 8.4% and 1.2% ofEnterobacteriaceaewere classified as MDR and XDR. No pandrug-resistant (PDR)Enterobacteriaceaeisolates and only one PDRP. aeruginosaisolate were detected. Ceftolozane/tazobactam was the most potent (MIC50/90, 0.5/2 μg/ml) agent tested againstP. aeruginosaand demonstrated good activity against 310 MDR strains (MIC50/90, 2/8 μg/ml) and 175 XDR strains (MIC50/90, 4/16 μg/ml). Ceftolozane/tazobactam exhibited high overall activity (MIC50/90, 0.25/1 μg/ml) againstEnterobacteriaceaeand retained activity (MIC50/90, 4/>32 μg/ml) against many 601 MDR strains but not against the 86 XDR strains (MIC50, >32 μg/ml). Ceftolozane/tazobactam was highly potent (MIC50/90, 0.25/0.5 μg/ml) against 2,691Escherichia coliisolates and retained good activity against most ESBL-phenotypeE. coliisolates (MIC50/90, 0.5/4 μg/ml), but activity was low against ESBL-phenotypeKlebsiella pneumoniaeisolates (MIC50/90, 32/>32 μg/ml), explained by the high rate (39.8%) of meropenem coresistance observed in this species phenotype. In summary, ceftolozane/tazobactam demonstrated high potency and broad-spectrum activity against many contemporaryEnterobacteriaceaeandP. aeruginosaisolates collected in U.S. medical centers. Importantly, ceftolozane/tazobactam retained potency against many MDR and XDR strains.

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Ceftazidime-Avibactam Activity against Multidrug-Resistant Pseudomonas aeruginosa Isolated in U.S. Medical Centers in 2012 and 2013

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05024-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3656-3659 ◽

Cited By ~ 55

Author(s):

Helio S. Sader ◽

Mariana Castanheira ◽

Rodrigo E. Mendes ◽

Robert K. Flamm ◽

David J. Farrell ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Multidrug Resistant ◽

Drug Resistant ◽

Broth Microdilution ◽

Content Type ◽

Microdilution Method ◽

Medical Centers ◽

Extensively Drug Resistant ◽

Broth Microdilution Method

ABSTRACTPseudomonas aeruginosaisolates (n= 3,902) from 75 U.S. medical centers were tested against ceftazidime-avibactam and comparator agents by the reference broth microdilution method. Overall, 96.9% of the strains were susceptible (MIC, ≤8 μg/ml) to ceftazidime-avibactam, while the rates of susceptibility for ceftazidime, meropenem, and piperacillin-tazobactam were 83.8, 81.9, and 78.5%, respectively. Multidrug-resistant and extensively drug-resistant phenotypes were observed in 14.9 and 8.7% of the strains, respectively, and 81.0 and 73.7% of the strains were susceptible to ceftazidime-avibactam, respectively.

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Antimicrobial Susceptibility of Pseudomonas aeruginosa to Ceftazidime-Avibactam, Ceftolozane-Tazobactam, Piperacillin-Tazobactam, and Meropenem Stratified by U.S. Census Divisions: Results from the 2017 INFORM Program

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01587-18 ◽

2018 ◽

Vol 62 (12) ◽

Cited By ~ 16

Author(s):

Helio S. Sader ◽

Robert K. Flamm ◽

Cecilia G. Carvalhaes ◽

Mariana Castanheira

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Susceptibility ◽

Broth Microdilution ◽

Content Type ◽

Microdilution Method ◽

Medical Centers ◽

Broth Microdilution Method

ABSTRACT Pseudomonas aeruginosa isolates (n = 1,909) were collected from 70 U.S. medical centers, and their susceptibilities were tested using the broth microdilution method. Ceftazidime-avibactam (MIC50/MIC90, 2/8 mg/liter) and ceftolozane-tazobactam (MIC50/MIC90, 0.5/2 mg/liter) were the most active (i.e., had the highest susceptibility rates) compounds after colistin, with national susceptibility rates of 96.9% and 97.5%, respectively. Overall, piperacillin-tazobactam (MIC50/MIC90, 4/128 mg/liter) and meropenem (MIC50/MIC90, 0.5/16 mg/liter) were active against 77.5% and 76.0% of the isolates, respectively. Susceptibility variations across census divisions were documented for many antimicrobials.

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Arbekacin Activity against Contemporary Clinical Bacteria Isolated from Patients Hospitalized with Pneumonia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04839-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3263-3270 ◽

Cited By ~ 17

Author(s):

Helio S. Sader ◽

Paul R. Rhomberg ◽

David J. Farrell ◽

Ronald N. Jones

Keyword(s):

The United States ◽

Multidrug Resistant ◽

Surveillance Program ◽

Content Type ◽

Microdilution Method ◽

Medical Centers ◽

Broth Microdilution Method ◽

Mrsa Strains ◽

Infection Types

ABSTRACTArbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States. We evaluated the occurrence of organisms isolated from pneumonias in U.S. hospitalized patients (PHP), including ventilator-associated pneumonia (VAP), and thein vitroactivity 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 U.S. 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 wereStaphylococcus aureus,Pseudomonas aeruginosa,Klebsiellaspp., andEnterobacterspp. The highest arbekacin MIC amongS. aureusisolates from PHP (43% methicillin-resistantS. aureus[MRSA]) was 4 μg/ml. AmongP. aeruginosaisolates from PHP, only one had an arbekacin MIC of >16 μg/ml (MIC50and MIC90, 1 and 4 μg/ml), and susceptibility rates for gentamicin, tobramycin, and amikacin were 88.0, 90.0, and 98.0%, respectively. Arbekacin (MIC50, 2 μg/ml) and tobramycin (MIC50, 4 μg/ml) were the most potent aminoglycosides tested againstAcinetobacter baumannii. AgainstEnterobacteriaceaefrom PHP, arbekacin and gentamicin (MIC50and MIC90, 0.25 to 1 and 1 to 8 μg/ml for both compounds) were generally more potent than tobramycin (MIC50and MIC90, 0.25 to 2 and 1 to 32 μg/ml) and amikacin (MIC50and MIC90, 1 to 2 and 2 to 32 μg/ml). Arbekacin also demonstrated potentin vitroactivity against a worldwide collection of well-characterized MDR Gram-negative and MRSA strains.

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Baseline Activity of Telavancin against Gram-Positive Clinical Isolates Responsible for Documented Infections in U.S. Hospitals (2011-2012) as Determined by the Revised Susceptibility Testing Method

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04052-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 702-706 ◽

Cited By ~ 18

Author(s):

Rodrigo E. Mendes ◽

David J. Farrell ◽

Helio S. Sader ◽

Robert K. Flamm ◽

Ronald N. Jones

Keyword(s):

Staphylococcus Aureus ◽

Susceptibility Testing ◽

The United States ◽

Broth Microdilution ◽

Content Type ◽

Testing Method ◽

Microdilution Method ◽

Baseline Activity ◽

Broth Microdilution Method ◽

Vancomycin Resistant

ABSTRACTTelavancin had MIC50and MIC90values of 0.03 and 0.06 μg/ml (100.0% susceptible), respectively, against methicillin-resistant and -susceptibleStaphylococcus aureus. Telavancin was active against vancomycin-susceptibleEnterococcus faecalis(MIC50/90, 0.12/0.12 μg/ml; 100% susceptible) andEnterococcus faecium(MIC50/90, 0.03/0.06 μg/ml), while higher MIC values were obtained against vancomycin-resistantE. faecium(MIC50/90, 1/2 μg/ml) andE. faecalis(MIC50/90, >2/>2 μg/ml). Streptococci showed telavancin modal MIC results of ≤0.015 μg/ml, except againstStreptococcus agalactiae(i.e., 0.03 μg/ml). This study reestablishes the telavancin spectrum of activity against isolates recovered from the United States (2011-2012) using the revised broth microdilution method.

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Multicenter Study of Anidulafungin and Micafungin MIC Distributions and Epidemiological Cutoff Values for Eight Candida Species and the CLSI M27-A3 Broth Microdilution Method

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02020-13 ◽

2013 ◽

Vol 58 (2) ◽

pp. 916-922 ◽

Cited By ~ 32

Author(s):

M. A. Pfaller ◽

A. Espinel-Ingroff ◽

B. Bustamante ◽

E. Canton ◽

D. J. Diekema ◽

...

Keyword(s):

Acquired Resistance ◽

The United States ◽

Resistance Mechanisms ◽

Broth Microdilution ◽

Wild Type ◽

Content Type ◽

Microdilution Method ◽

Cutoff Values ◽

Broth Microdilution Method ◽

Species Specific

ABSTRACTSince epidemiological cutoff values (ECVs) using CLSI MICs from multiple laboratories are not available forCandidaspp. and the echinocandins, we established ECVs for anidulafungin and micafungin on the basis of wild-type (WT) MIC distributions (for organisms in a species-drug combination with no detectable acquired resistance mechanisms) for 8,210Candida albicans, 3,102C. glabrata, 3,976C. parapsilosis, 2,042C. tropicalis, 617C. krusei, 258C. lusitaniae, 234C. guilliermondii, and 131C. dubliniensisisolates. CLSI broth microdilution MIC data gathered from 15 different laboratories in Canada, Europe, Mexico, Peru, and the United States were aggregated to statistically define ECVs. ECVs encompassing 97.5% of the statistically modeled population for anidulafungin and micafungin were, respectively, 0.12 and 0.03 μg/ml forC. albicans, 0.12 and 0.03 μg/ml forC. glabrata, 8 and 4 μg/ml forC. parapsilosis, 0.12 and 0.06 μg/ml forC. tropicalis, 0.25 and 0.25 μg/ml forC. krusei, 1 and 0.5 μg/ml forC. lusitaniae, 8 and 2 μg/ml forC. guilliermondii, and 0.12 and 0.12 μg/ml forC. dubliniensis. Previously reported single and multicenter ECVs defined in the present study were quite similar or within 1 2-fold dilution of each other. For a collection of 230 WT isolates (nofksmutations) and 51 isolates withfksmutations, the species-specific ECVs for anidulafungin and micafungin correctly classified 47 (92.2%) and 51 (100%) of thefksmutants, respectively, as non-WT strains. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin and micafungin due tofksmutations.

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Multicenter Study of Isavuconazole MIC Distributions and Epidemiological Cutoff Values for Aspergillus spp. for the CLSI M38-A2 Broth Microdilution Method

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00636-13 ◽

2013 ◽

Vol 57 (8) ◽

pp. 3823-3828 ◽

Cited By ~ 60

Author(s):

A. Espinel-Ingroff ◽

A. Chowdhary ◽

G. M. Gonzalez ◽

C. Lass-Flörl ◽

E. Martin-Mazuelos ◽

...

Keyword(s):

Species Complex ◽

Acquired Resistance ◽

Resistance Mechanism ◽

The United States ◽

Resistance Mechanisms ◽

Broth Microdilution ◽

Content Type ◽

Microdilution Method ◽

Cutoff Values ◽

Broth Microdilution Method

ABSTRACTEpidemiological cutoff values (ECVs) were established for the new triazole isavuconazole andAspergillusspecies wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) that were defined with 855Aspergillus fumigatus, 444A. flavus, 106A. nidulans, 207A. niger, 384A. terreus, and 75A. versicolorspecies complex isolates; 22AspergillussectionUstiisolates were also included. CLSI broth microdilution MIC data gathered in Europe, India, Mexico, and the United States were aggregated to statistically define ECVs. ECVs were 1 μg/ml for theA. fumigatusspecies complex, 1 μg/ml for theA. flavusspecies complex, 0.25 μg/ml for theA. nidulansspecies complex, 4 μg/ml for theA. nigerspecies complex, 1 μg/ml for theA. terreusspecies complex, and 1 μg/ml for theA. versicolorspecies complex; due to the small number of isolates, an ECV was not proposed forAspergillussectionUsti. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to isavuconazole due tocyp51A(anA. fumigatusspecies complex resistance mechanism among the triazoles) or other mutations.

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Antimicrobial Activity of Ceftolozane-Tazobactam and Comparators against Clinical Isolates of Haemophilus influenzae from the United States and Europe

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00211-20 ◽

2020 ◽

Vol 64 (5) ◽

Author(s):

Helio S. Sader ◽

Cecilia G. Carvalhaes ◽

Leonard R. Duncan ◽

Dee Shortridge

Keyword(s):

United States ◽

Antimicrobial Activity ◽

Haemophilus Influenzae ◽

Infection Type ◽

The United States ◽

Clinical Isolates ◽

Broth Microdilution ◽

Content Type ◽

Medical Centers ◽

Mic Value

ABSTRACT Nine hundred Haemophilus influenzae clinical isolates from 83 U.S. and European medical centers were tested for susceptibility by reference broth microdilution methods against ceftolozane-tazobactam and comparators. Results were stratified by β-lactamase production and infection type. Overall, ceftolozane-tazobactam MIC50/90 values were 0.12/0.25 mg/liter, and 99.0% of isolates were inhibited at the susceptible breakpoint of ≤0.5 mg/liter; the highest MIC value was only 2 mg/liter. Our results support using ceftolozane-tazobactam to treat H. influenzae infections.

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Wild-Type MIC Distributions and Epidemiological Cutoff Values for Amphotericin B and Aspergillus spp. for the CLSI Broth Microdilution Method (M38-A2 Document)

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00686-11 ◽

2011 ◽

Vol 55 (11) ◽

pp. 5150-5154 ◽

Cited By ~ 74

Author(s):

A. Espinel-Ingroff ◽

M. Cuenca-Estrella ◽

A. Fothergill ◽

J. Fuller ◽

M. Ghannoum ◽

...

Keyword(s):

Amphotericin B ◽

Acquired Resistance ◽

The United States ◽

Resistance Mechanisms ◽

Broth Microdilution ◽

Wild Type ◽

Content Type ◽

Microdilution Method ◽

Cutoff Values ◽

Broth Microdilution Method

ABSTRACTAlthough clinical breakpoints have not been established for mold testing, epidemiological cutoff values (ECVs) are available forAspergillusspp. versus the triazoles and caspofungin. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for sixAspergillusspp. and amphotericin B. Two sets (CLSI/EUCAST broth microdilution) of available MICs were evaluated: those forA. fumigatus(3,988/833),A. flavus(793/194),A. nidulans(184/69),A. niger(673/140),A. terreus(545/266), andA. versicolor(135/22). Three sets of data were analyzed: (i) CLSI data gathered in eight independent laboratories in Canada, Europe, and the United States; (ii) EUCAST data from a single laboratory; and (iii) the combined CLSI and EUCAST data. ECVs, expressed in μg/ml, that captured 95%, 97.5%, and 99% of the modeled wild-type population (CLSI and combined data) were as follows: forA. fumigatus, 2, 2, and 4; forA. flavus, 2, 4, and 4; forA. nidulans, 4, 4, and 4; forA. niger, 2, 2, and 2; forA. terreus, 4, 4, and 8; and forA. versicolor, 2, 2, and 2. Similar to the case for the triazoles and caspofungin, amphotericin B ECVs may aid in the detection of strains with acquired mechanisms of resistance to this agent.

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Comparative activity of newer β-lactam/β-lactamase inhibitor combinations against Pseudomonas aeruginosa from patients hospitalized with pneumonia in European medical centers in 2020

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-021-04363-7 ◽

2021 ◽

Author(s):

Helio S. Sader ◽

Cecilia G. Carvalhaes ◽

Dee Shortridge ◽

Mariana Castanheira

Keyword(s):

Pseudomonas Aeruginosa ◽

Eastern Europe ◽

Western Europe ◽

Broth Microdilution ◽

Active Compounds ◽

Microdilution Method ◽

Medical Centers ◽

Broth Microdilution Method ◽

Lactamase Inhibitor ◽

Comparative Activity

Abstract Pseudomonas aeruginosa isolates were consecutively collected from patients with pneumonia in 29 medical centers in 2020 and susceptibility tested by broth microdilution method. Ceftazidime-avibactam (95.5% susceptible), imipenem-relebactam (94.3% susceptible), and ceftolozane-tazobactam (93.3% susceptible) were the most active compounds after colistin (99.5% susceptible). Susceptibility rates for the β-lactam/β-lactamase inhibitor combinations (BL/BLIs) varied against isolates resistant to piperacillin-tazobactam, meropenem, imipenem, and/or ceftazidime. Ceftazidime-avibactam was the most active BL/BLI against resistant subsets from Western Europe, whereas imipenem-relebactam was slightly more active than other BL/BLIs against resistant subsets from Eastern Europe. Susceptibility rates were markedly lower in Eastern Europe than Western Europe.

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