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

2015 ◽  
Vol 59 (6) ◽  
pp. 3656-3659 ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
David J. Farrell ◽  
...  

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.

2013 ◽  
Vol 57 (12) ◽  
pp. 6305-6310 ◽  
Author(s):  
David J. Farrell ◽  
Robert K. Flamm ◽  
Helio S. Sader ◽  
Ronald N. Jones

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.


2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Dee Shortridge ◽  
Rodrigo E. Mendes ◽  
Robert K. Flamm

ABSTRACT The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa isolates. The isolates were consecutively collected from 94 U.S. hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥ 16 μg/ml) were evaluated for the presence of genes encoding extended-spectrum β-lactamases and carbapenemases. Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the susceptible breakpoint of ≤8 μg/ml and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/ml; 99.2% susceptible), extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/ml; 97.8% susceptible), and CRE (n = 513; MIC50/90, 0.5/2 μg/ml; 97.5% susceptible) isolates. Only 82.2% of MDR Enterobacteriaceae (n = 2,953) and 64.2% of ceftriaxone-nonsusceptible Klebsiella pneumoniae (n = 1,063) isolates were meropenem susceptible. Among Enterobacter cloacae (22.2% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.3% of the ceftazidime-nonsusceptible isolates, were ceftazidime-avibactam susceptible. Only 23 of 36,380 Enterobacteriaceae (0.06%) isolates were ceftazidime-avibactam nonsusceptible, including 9 metallo-β-lactamase producers and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. Ceftazidime-avibactam showed potent activity against P. aeruginosa (MIC50/90, 2/4 μg/ml; 97.1% susceptible), including MDR (MIC50/90, 4/16 μg/ml; 86.5% susceptible) isolates, and inhibited 71.8% of isolates nonsusceptible to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628). In summary, ceftazidime-avibactam demonstrated potent activity against a large collection (n = 44,248) of contemporary Gram-negative bacilli isolated from U.S. patients, including organisms resistant to most currently available agents, such as CRE and meropenem-nonsusceptible P. aeruginosa.


2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Helio S. Sader ◽  
Glenn E. Dale ◽  
Paul R. Rhomberg ◽  
Robert K. Flamm

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.


2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Dee Shortridge ◽  
Mariana Castanheira ◽  
Michael A. Pfaller ◽  
Robert K. Flamm

ABSTRACT The activity of ceftolozane-tazobactam was compared to the activities of 7 antimicrobials against 3,851 Pseudomonas aeruginosa isolates collected from 32 U.S. hospitals in the Program to Assess Ceftolozane-Tazobactam Susceptibility from 2012 to 2015. Ceftolozane-tazobactam and comparator susceptibilities were determined using the CLSI broth microdilution method at a central monitoring laboratory. For ceftolozane-tazobactam, 97.0% of the isolates were susceptible. Susceptibilities of the other antibacterials tested were: amikacin, 96.9%; cefepime, 85.9%; ceftazidime, 85.1%; colistin, 99.2%; levofloxacin, 76.6%; meropenem, 81.8%; and piperacillin-tazobactam, 80.4%. Of the 699 (18.1%) meropenem-nonsusceptible P. aeruginosa isolates, 87.6% were susceptible to ceftolozane-tazobactam. Six hundred seven isolates (15.8%) were classified as multidrug resistant (MDR), and 363 (9.4%) were classified as extensively drug resistant (XDR). Only 1 isolate was considered pandrug resistant, which was resistant to all tested agents, including colistin. Of the 607 MDR isolates, 84.9% were ceftolozane-tazobactam susceptible, and 76.9% of XDR isolates were ceftolozane-tazobactam susceptible. In vitro activity against drug-resistant P. aeruginosa indicates ceftolozane-tazobactam may be an important agent in treating serious bacterial infections.


2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Michael A. Pfaller ◽  
Rodrigo E. Mendes ◽  
Leonard R. Duncan ◽  
Robert K. Flamm ◽  
Helio S. Sader

ABSTRACT We evaluated trends in Streptococcus pneumoniae antimicrobial susceptibility in United States hospitals in the 2010 to 2016 period. A total of 8,768 clinical isolates from 47 medical centers were tested for susceptibility by broth microdilution methods. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) rates decreased from 25.7% and 12.4%, respectively, in 2010 to 17.7% and 3.6%, respectively, in 2016. The susceptibilities to most comparator antimicrobial agents increased, whereas the susceptibilities to ceftaroline, levofloxacin, linezolid, and tigecycline remained stable. Ceftaroline retained potent activity against S. pneumoniae (>99.9%) with no marked variations.


2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Cecilia G. Carvalhaes ◽  
Mariana Castanheira

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.


2015 ◽  
Vol 59 (6) ◽  
pp. 3263-3270 ◽  
Author(s):  
Helio S. Sader ◽  
Paul R. Rhomberg ◽  
David J. Farrell ◽  
Ronald N. Jones

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.


2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Helio S. Sader ◽  
Rodrigo E. Mendes ◽  
Michael A. Pfaller ◽  
Dee Shortridge ◽  
Robert K. Flamm ◽  
...  

ABSTRACT A total of 10,451 contemporary (2016) Enterobacteriaceae isolates from 84 U.S. medical centers and 116 metallo-β-lactamase- and/or OXA-48-like-producing Enterobacteriaceae isolates from other countries were tested against aztreonam-avibactam and comparators. All U.S. isolates were inhibited at aztreonam-avibactam MICs of ≤8 μg/ml (MIC50, ≤0.03 μg/ml; MIC90, 0.12 μg/ml), including Klebsiella pneumoniae carbapenemase-producing isolates (n = 102; MIC50, 0.25 μg/ml; MIC90, 0.5 μg/ml), multidrug-resistant isolates (n = 876; MIC50, 0.06 μg/ml; MIC90, 0.25 μg/ml), and extensively drug-resistant isolates (n = 111; MIC50, 0.12 μg/ml; MIC90, 0.5 μg/ml). The highest aztreonam-avibactam MIC value among ex-U.S. isolates was 4 μg/ml.


2013 ◽  
Vol 57 (7) ◽  
pp. 3178-3181 ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Ronald N. Jones

ABSTRACTVancomycin, linezolid, and daptomycin are very active against staphylococci, but isolates with decreased susceptibility to these antimicrobial agents are isolated sporadically. A total of 19,350Staphylococcus aureusisolates (51% methicillin resistant [MRSA]) and 3,270 coagulase-negative staphylococci (CoNS) were collected consecutively from 82 U.S. medical centers from January 2008 to December 2011 and tested for susceptibility against ceftaroline and comparator agents by the reference broth microdilution method. AmongS. aureusstrains, 14 isolates (0.07%) exhibited decreased susceptibility to linezolid (MIC, ≥8 μg/ml), 18 (0.09%) to daptomycin (MIC, ≥2 μg/ml), and 369 (1.9%) to vancomycin (MIC, ≥2 μg/ml; 368 isolates at 2 μg/ml and 1 at 4 μg/ml). Fifty-one (1.6%) CoNS were linezolid resistant (MIC, ≥8 μg/ml), and four (0.12%) were daptomycin nonsusceptible (MIC, ≥2 μg/ml). Ceftaroline was very active againstS. aureusoverall (MIC50/90, 0.5/1 μg/ml; 98.5% susceptible), including MRSA (MIC50/90, 0.5/1 μg/ml; 97.2% susceptible). All daptomycin-nonsusceptible and 85.7% of linezolid-resistantS. aureusisolates were susceptible to ceftaroline. AgainstS. aureusisolates with a vancomycin MIC of ≥2 μg/ml, 91.9, 96.2, and 98.9% were susceptible to ceftaroline, daptomycin, and linezolid, respectively. CoNS strains were susceptible to ceftaroline (MIC50/90, 0.25/0.5 μg/ml; 99.1% inhibited at ≤1 μg/ml), including methicillin-resistant (MIC50/90, 0.25/0.5 μg/ml), linezolid-resistant (MIC50/90, 0.5/0.5 μg/ml), and daptomycin-nonsusceptible (4 isolates; MIC range, 0.03 to 0.12 μg/ml) strains. In conclusion, ceftaroline demonstrated potentin vitroactivity against staphylococci with reduced susceptibility to linezolid, daptomycin, or vancomycin, and it may represent a valuable treatment option for infections caused by these multidrug-resistant staphylococci.


2012 ◽  
Vol 56 (4) ◽  
pp. 2129-2131 ◽  
Author(s):  
Fabio Silvio Taccone ◽  
Frédéric Cotton ◽  
Sandrine Roisin ◽  
Jean-Louis Vincent ◽  
Frédérique Jacobs

ABSTRACTA patient with septic shock due to extensively drug resistant (XDR)Pseudomonas aeruginosawas cured by optimizing the meropenem (MEM) regimen to obtain at least 40% of the time between two administrations in which drug levels were four times higher than the MIC of the pathogen. As the standard drug dose did not achieve these optimal concentrations, the MEM regimen was progressively increased up to 12 g/day (3 g every 6 h in a 3-h extended infusion), which eventually resulted in sepsis resolution. High MEM dosage may represent a valuable therapeutic option for infection due to multidrug-resistant (MDR) strains, and drug monitoring would allow rapid regimen adjustment in clinical practice.


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