Antimicrobial activity of POL7306 tested against clinical isolates of Gram-negative bacteria collected worldwide

2020 ◽  
Vol 75 (6) ◽  
pp. 1518-1524 ◽  
Author(s):  
Helio S Sader ◽  
Paul R Rhomberg ◽  
Leonard R Duncan ◽  
Hans H Locher ◽  
Glenn E Dale ◽  
...  
Keyword(s):  
Protein Targeting ◽  
Treatment Options ◽  
Asia Pacific ◽  
Surveillance Program ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
The Usa

Abstract Background POL7306 belongs to a new class of peptidomimetic outer-membrane-protein-targeting antibiotics with a novel mechanism of action. POL7306 is in development for the treatment of infections caused by antimicrobial-resistant Gram-negative bacteria and has demonstrated low cytotoxicity and nephrotoxicity. Methods A total of 891 isolates were collected by the SENTRY Antimicrobial Surveillance Program from 134 medical centres in Europe (n = 424; 41 centres in 18 nations), the USA (n = 411 isolates from 67 centres), the Asia-Pacific region (n = 24; 15 centres in 6 nations) and Latin America (n = 32; 11 centres in 9 nations) and included 558 Enterobacterales, 310 non-fermenters and 23 fastidious organisms. Susceptibility testing was performed using the reference broth microdilution method and the medium was supplemented with 0.002% polysorbate-80 for testing POL7306. Resistant subsets were characterized by WGS. Results POL7306 demonstrated potent in vitro activity against Enterobacterales [including carbapenem-resistant (MIC50/90, 0.06/0.25 mg/L), ESBL-producing (MIC50/90, 0.06/0.12 mg/L), KPC-producing (MIC50/90, 0.12/0.25 mg/L), MBL-producing (MIC50/90, 0.06/0.25 mg/L), colistin-non-susceptible, mcr-negative (MIC50/90, 0.5/2 mg/L) and mcr-positive (MIC50/90, 0.12/0.25 mg/L) Enterobacterales], Pseudomonas aeruginosa (MIC50/90, 0.25/0.25 mg/L), Acinetobacter baumannii (MIC50/90, 0.06/0.12 mg/L) and Stenotrophomonas maltophilia (MIC50/90, 0.06/0.25 mg/L). Conclusions POL7306 demonstrated potent activity against a large collection of Gram-negative organisms collected worldwide that included colistin-resistant, XDR and ESBL- and carbapenemase-producing isolates for which there are currently limited treatment options.

scholarly journals Susceptibility trends of ceftolozane/tazobactam and comparators when tested against European Gram-negative bacterial surveillance isolates collected during 2012–18

2020 ◽  
Vol 75 (10) ◽  
pp. 2907-2913 ◽  
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
Leonard R Duncan ◽  
Robert K Flamm ◽  
Dee Shortridge
Keyword(s):  
Eastern Europe ◽  
Active Compound ◽  
Western Europe ◽  
Antimicrobial Agents ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Systemic Infections

Abstract Background The Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) monitors the in vitro activity of ceftolozane/tazobactam and numerous antimicrobial agents against Gram-negative bacteria worldwide. Objectives To evaluate the activity of ceftolozane/tazobactam and resistance trends among Pseudomonas aeruginosa and Enterobacterales isolates in Europe between 2012 and 2018. Methods P. aeruginosa (7503) and Enterobacterales (30 582) isolates were collected from 53 medical centres in 26 countries in Europe and the Mediterranean region and tested for susceptibility by reference broth microdilution method in a central laboratory. MIC results were interpreted using EUCAST criteria. Results Ceftolozane/tazobactam was the most active compound tested against P. aeruginosa isolates after colistin, with overall susceptibility rates of 94.1% in Western Europe and 80.9% in Eastern Europe. Moreover, ceftolozane/tazobactam retained activity against 75.2% and 59.2% of meropenem-non-susceptible P. aeruginosa isolates in Western and Eastern Europe, respectively. Tobramycin was the third most active compound tested against P. aeruginosa, with susceptibility rates of 88.6% and 70.9% in Western and Eastern Europe, respectively. Ceftolozane/tazobactam was active against 94.5% of all Enterobacterales and 96.1% of meropenem-susceptible isolates from Western Europe. In Eastern Europe, ceftolozane/tazobactam was active against 79.4% of Enterobacterales overall and 86.2% of meropenem-susceptible isolates. Discussion Antimicrobial susceptibility rates for agents commonly used to treat serious systemic infections varied widely among nations and geographic regions and were generally lower in Eastern Europe compared with Western Europe. Ceftolozane/tazobactam demonstrated potent activity against P. aeruginosa, including MDR strains, and retained activity against most meropenem-susceptible Enterobacterales causing infection in European medical centres.

scholarly journals Investigation of in vitro activity of colistin and tygecyclin against Stenotrophomonas maltophilia isolates

2021 ◽  
Vol 38 (4) ◽  
pp. 529-532
Author(s):  
Yeliz TANRIVERDİ ÇAYCI ◽  
İlknur BIYIK ◽  
Gonca YILMAZ ◽  
Kemal BİLGİN ◽  
Asuman BİRİNCİ
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Inhibitory Concentration ◽  
Treatment Options ◽  
Opportunistic Pathogen ◽  
Diffusion Method ◽  
Colistin Resistance ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
The Usa

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen, causing infections whose management is often problematic due to its inherent resistance to many antibiotics. In this study, we aimed to investigate the antimicrobial susceptibility of colistin and tygecyclin as an alternative treatment options for S. maltophilia infections. A total of 122 S. maltophilia isolates were tested. Minimum inhibitory concentration (MIC) values of colistin and tygecycline were determined by broth microdilution method. Susceptibility of TMP/SMX and levofloxacin (LVX) were determined by disc diffusion method and MIC value of ceftazidime (CAZ) was determined by using E-test. Out of 122 S. maltophilia isolates, 5 (4%) of them were resistant to TMP-SXM. MIC range was 0.125- >512 μg/ml and MIC50 64 μg/ml, MIC90 512 μg/ml for colistin. MIC range for tygecyclin was detected as 0.5- >8, MIC50 2 μg/ml and MIC90 8 μg/ml. Tygecyclin resistance was detected as 66.4% according to the EUCAST guideline and 13.1% according to the USA-FDA breakpoints. And colistin resistance was determined as 86.9% according to both guidelines.

scholarly journals Cefepime-Zidebactam (WCK 5222) Activity Tested against Gram-negative Organisms Causing Bloodstream Infections Worldwide

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S374-S375 ◽  
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Jennifer M Streit ◽  
Leonard R Duncan ◽  
Robert K Flamm
Keyword(s):  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Asia Pacific ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Research Grant

Abstract Background Zidebactam (ZID), a bicyclo-acyl hydrazide, is a β-lactam enhancer with a dual mechanism of action involving selective and high binding affinity to Gram-negative (GN) PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime (FEP) combined with ZID against GN organisms causing bloodstream infections (BSI) in hospitals worldwide. Methods A total of 2,094 isolates from 105 medical centers were evaluated. Isolates were collected from Europe (1,050), USA (331), Latin America (LA; 200) and the Asia-Pacific region (AP; 393) in 2015, and China (120) in 2013 by the SENTRY Program. Susceptibility (S) testing was performed by reference broth microdilution method against FEP-ZID (1:1 ratio) and comparators. The collection included 1,809 Enterobacteriaceae (ENT), 170 P. aeruginosa (PSA) and 115 Acinetobacter spp. (ASP). Results FEP-ZID was very active against ENT (MIC50/90 of ≤0.03/0.12 μg/mL) with 99.9 and 100.0% of isolates inhibited at ≤4/4 and ≤8/8 μg/mL, respectively, and retained potent activity against carbapenem-resistant (CRE; n = 44; MIC50/90, 1/4 μg/mL), multidrug-resistant (MDR), and extensively drug-resistant (XDR) isolates (Table). Amikacin (AMK; MIC50/90, 2/4 μg/mL; 97.7% S) was also very active against ENT, and colistin (COL; MIC50/90, 0.12/>8 μg/mL) inhibited only 87.3% of isolates at ≤2 μg/mL. FEP-ZID was highly active against PSA, including isolates resistant to other antipseudomonal β-lactams, MDR (MIC50/90, 4/8 μg/mL) and XDR (MIC50/90, 4/8 μg/mL) isolates. Among the comparators, COL (MIC50/90 of ≤0.5/1 μg/mL; 100.0% S) and AMK (MIC50/90, 4/16 μg/mL; 91.2% S) were the most active agents against PSA. FEP-ZID (MIC50/90, 16/32 μg/mL) was 4-fold more active than FEP against ASP. Conclusion FEP-ZID (WCK 5222) exhibited potent in vitro activity against a large worldwide collection of GN isolates from BSI, including MDR and XDR isolates. These results support further clinical development of WCK 5222 for treating BSI. Disclosures H. S. Sader, Wockhardt Bio Ag: Research Contractor, Research grant; M. Castanheira, Wockhardt Bio Ag: Research Contractor, Research grant; J. M. Streit, Wockhardt Bio Ag: Research Contractor, Research grant; L. R. Duncan, Wockhardt Bio Ag: Research Contractor, Research grant; R. K. Flamm, Wock: Research Contractor, Research support

scholarly journals 696. Cefiderocol Susceptibility Against Molecularly Characterized Carbapenemase-Producing Gram-Negative Bacteria in North America and Europe Between 2014 and 2017: SIDERO-WT-2014 to -2016 Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S315-S315
Author(s):  
Takafumi Sato ◽  
Masakatsu Tsuji ◽  
Krystyna M Kazmierczak ◽  
Meredith M Hackel ◽  
Roger Echols ◽  
...  
Keyword(s):  
North America ◽  
Antibiotic Susceptibility ◽  
Treatment Options ◽  
The United States ◽  
Detection Rates ◽  
Gram Negative ◽  
Surveillance Studies ◽  
Microdilution Method ◽  
Broth Microdilution Method

Abstract Background Antibiotic susceptibility surveillance is the foundation for selecting treatment options as well as immediate and long-term strategies for combating antimicrobial resistance. We have conducted three surveillance studies SIDERO-WT-2014/-2015/-2016 with approximately 30,000 Gram-negative strains isolated in North America and Europe between 2014 and 2017. Here, we present the latest data of molecular analysis on acquired carbapenemase genes and antibiotic susceptibility of 3691 meropenem-nonsusceptible strains in the surveillance studies. Methods Meropenem-nonsusceptible strains isolated in North America (n = 1009) and Europe (n = 2,682), consisting of 1,897 Acinetobacter baumannii, 1,154 Pseudomonas aeruginosa, 447 Klebsiella pneumoniae, and 193 other Enterobacteriaceae were tested. Conventional PCR was used to detect known carbapenemases. Cefiderocol MICs were determined by broth microdilution method using iron-depleted cation-adjusted Mueller–Hinton broth. Results The percentages of known carbapenemases detected in 3 main pathogens are shown in the Table. In A. baumannii complex, OXA-23 was predominant followed by OXA-24 in most countries. The detection rates of VIM in P. aeruginosa were ≥40% in Greece and Russia, but none of the strains in the United States carried VIM. In K. pneumoniae, the predominant carbapenemase varied among the countries, with KPC predominating in the USA, Greece and Italy, while OXA-48-like was dominant in Russia, Spain and Turkey. Cefiderocol MIC90 were ≤4 μg/mL against these 3 pathogens in all 6 countries, except for A. baumannii strains in Russia. Conclusion Carbapenemase detection rates, especially in P. aeruginosa and K. pneumoniae, were quite different among the countries. Cefiderocol demonstrated potent in vitro activity against meropenem-nonsusceptible strains irrespective of the presence of specific carbapenemases. Disclosures All authors: No reported disclosures.

scholarly journals Formation in vitro of colistin resistance in carbapenem-resistant Gram-negative bacteria and its biological cost

2021 ◽  
Author(s):  
D. V. Tapalski ◽  
T. A. Petrovskaya ◽  
A. E. Kozlov
Keyword(s):  
Broth Culture ◽  
Exponential Growth Phase ◽  
Lag Phase ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Broth Microdilution Method ◽  
Resistant Mutants ◽  
Biological Cost

Introduction. The spread of resistance to carbapenems among gram-negative bacteria have led to an increase in the consumption of polymyxins and the emergence of certain strains resistant to them. Polymyxin resistance is mainly associated with mutations in chromosomal genes. The development of mutational resistance to antibiotics can lead to a decrease in the viability of bacteria, which is manifested by an increase in the duration of the cell cycle, a decrease in virulence and competitive fitness. The purpose of the study was to assess in vitro the intensity of the formation of colistin resistance in carbapenemresistant clinical isolates of gram-negative bacteria, the stability of the formed emerged resistance and its biological cost.Materials and methods. For 46 strains of Klebsiella pneumoniae, 77 strains of Pseudomonas aeruginosa and 42 strains of Acinetobacter baumannii, real time polymerase chain reaction (PCR) was used to detect the genes of carbapenemases, the minimum inhibitory concentrations (MIC) of meropenem and colistin were determined by broth microdilution method. The selection of resistant subpopulations on Muller–Hinton agar with the addition of 16 mg/l colistin was carried out. For colistin-resistant mutants and their isogenic sensitive strains, the kinetic parameters of growth in broth culture were determined. Incubation and result recording were performed on an Infinite M200 microplate reader for 18.5 hours at 35°C with measurement of light scatter in the wells every 15 minutes.Results. The production of carbapenemases MBL VIM in P. aeruginosa, MBL NDM, KPC and OXA-48 in K. pneumoniae, OXA-23 and OXA-40 in A. baumannii was observed. All strains were sensitive to colistin (MIC varied from 0.062 to 2 mg/l). The colony growth on a selective medium with16 mg/l colistin was observed for 97.8% of K. pneumoniae strains, 16.9% of P. aeruginosa strains, and 61.9% of A. baumannii strains. The mutational nature of colistin resistance was confirmed for 21.7% of K. pneumoniae strains. For colistin-resistant mutants of K. pneumoniae, a significant increase in the duration of the lag phase (Tlag) was observed: 225.6 ± 7.037 min in the wild-type susceptible strains and 245.5 ± 8.726 in resistant mutants, p = 0.037. The indicators of the doubling time of the number of microbial cells in the exponential growth phase (Tdoubling) and the area under the bacterial growth curve did not differ significantly.Conclusion. A high frequency of formation of colistin resistance in vitro in carbapenemase-producing strains of K. pneumoniae was observed. The absence of significant changes in the kinetics of microbial growth in resistant strains makes it possible to predict the further spread of mutational resistance to colistin, as well as its preservation in microbial populations of K. pneumoniae even in the case of limiting the use of this antibiotic. 

scholarly journals Case Commentary: the Need for Cefiderocol Is Clear, but Are the Supporting Clinical Data?

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ryan K. Shields
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Salvage Therapy ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Potential Utility ◽  
Gram Negative

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.

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

2015 ◽  
Vol 59 (6) ◽  
pp. 3263-3270 ◽  
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.

scholarly journals In VitroActivity of Plazomicin against Gram-Negative and Gram-Positive Bacterial Pathogens Isolated from Patients in Canadian Hospitals from 2013 to 2017 as Part of the CANWARD Surveillance Study

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Andrew Walkty ◽  
James A. Karlowsky ◽  
Melanie R. Baxter ◽  
Heather J. Adam ◽  
George G. Zhanel
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Pathogens ◽  
Multidrug Resistant ◽  
Surveillance Study ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method

ABSTRACTThe Clinical and Laboratory Standards Institute (CLSI) broth microdilution method was used to evaluate thein vitroactivities of plazomicin and comparator antimicrobial agents against 7,712 Gram-negative and 4,481 Gram-positive bacterial pathogens obtained from 2013 to 2017 from patients in Canadian hospitals as part of the CANWARD Surveillance Study. Plazomicin demonstrated potentin vitroactivity againstEnterobacteriaceae(MIC90≤ 1 µg/ml for all species tested exceptProteus mirabilisandMorganella morganii), including aminoglycoside-nonsusceptible, extended-spectrum β-lactamase (ESBL)-positive, and multidrug-resistant (MDR) isolates. Plazomicin was equally active against methicillin-susceptible and methicillin-resistant isolates ofStaphylococcus aureus.

Chemical composition and antimicrobial activity of Erodium species: E. ciconium L., E. cicutarium L., and E. absinthoides Willd. (Geraniaceae)

2010 ◽  
Vol 64 (3) ◽  
Author(s):  
Zorica Stojanović-Radić ◽  
Ljiljana Čomić ◽  
Niko Radulović ◽  
Milan Dekić ◽  
Vladimir Ranđelović ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Chemical Composition ◽  
Essential Oils ◽  
Palmitic Acid ◽  
Gram Negative Bacteria ◽  
Broth Microdilution ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Microdilution Method ◽  
Broth Microdilution Method

AbstractThe present study gives results of chemical composition analyses and antimicrobial activity testing of three Erodium species: E. ciconium L., E. cicutarium L., and E. absinthoides Willd. Essential oils were obtained by hydro-distillation from air-dried entire plants and analyzed by GC and GC-MS. A total of 209 different compounds were identified: 162 for E. cicutarium, 107 for E. ciconium, and 79 for E. absinthoides. Antimicrobial activity (broth microdilution method) of the oils was screened against a panel of Gram positive and Gram negative bacteria and a number of fungi. Moderate susceptibility of all tested strains was observed. Determined MIC values were 0.156–5 mg mL−1 (bacterial strains) and 0.039–0.325 mg mL−1 (fungal strains). Major component of the most active oil, palmitic acid, was also tested for activity together with stearic and myristic acids.

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