scholarly journals In vitro antimicrobial susceptibility of clinical respiratory isolates to ceftazidime-avibactam and comparators (2016–2018)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
D. Piérard ◽  
G. G. Stone
Keyword(s):  
Antimicrobial Susceptibility ◽  
Multidrug Resistant ◽  
Dosing Regimen ◽  
Gram Negative ◽  
E Coli ◽  
Susceptibility Data ◽  
Antimicrobial Surveillance ◽  
Genes Encoding ◽  
Respiratory Specimens

Abstract Background This antimicrobial surveillance study reports in vitro antimicrobial activity and susceptibility data for a panel of agents against respiratory isolates of Enterobacterales and Pseudomonas aeruginosa. Methods Isolates from respiratory specimens were collected in Africa/Middle East, Asia/South Pacific, Europe and Latin America between 2016 and 2018, as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Broth microdilution methodology was used to quantify minimum inhibitory concentrations, from which rates of susceptibility were determined using EUCAST breakpoints (version 10). Rates of subsets with genes encoding β-lactamases (extended-spectrum β-lactamases [ESBLs], serine carbapenemases and metallo-β-lactamases [MBLs]) were also determined, as well as rates of multidrug-resistant (MDR) P. aeruginosa. Results Among all respiratory Enterobacterales isolates, susceptibility to ceftazidime-avibactam, meropenem, colistin and amikacin was ≥94.4% in each region. For Enterobacterales isolates that were ESBL-positive or carbapenemase-positive/MBL-negative, ceftazidime-avibactam susceptibility was 93.6 and 98.9%, respectively. Fewer than 42.7% of MBL-positive Enterobacterales isolates were susceptible to any agents, except colistin (89.0% susceptible). Tigecycline susceptibility was ≥90.0% among Citrobacter koseri and Escherichia coli isolates, including all β-lactamase-positive subsets. ESBL-positive Enterobacterales were more commonly identified in each region than isolates that were ESBL/carbapenemase-positive; carbapenemase-positive/MBL-negative; or MBL-positive. Among all respiratory P. aeruginosa isolates, the combined susceptibility rates (susceptible at standard dosing regimen plus susceptible at increased exposure) were highest to ceftazidime-avibactam, colistin and amikacin (≥82.4% in each region). Susceptibility to colistin was ≥98.1% for all β-lactamase-positive subsets of P. aeruginosa. The lowest rates of antimicrobial susceptibility were observed among MBL-positive isolates of P. aeruginosa (≤56.6%), with the exception of colistin (100% susceptible). MDR P. aeruginosa were most frequently identified in each region (18.7–28.7%), compared with the subsets of ESBL-positive; carbapenemase-positive/MBL-negative; or MBL-positive isolates. Conclusions Rates of susceptibility among the collections of respiratory Enterobacterales and P. aeruginosa isolates were highest to ceftazidime-avibactam, colistin and amikacin in each region. Tigecycline was active against all subsets of C. koseri and E. coli, and colistin was active against all subsets of P. aeruginosa. The findings of this study indicate the need for continued antimicrobial surveillance among respiratory Gram-negative pathogens, in particular those with genes encoding MBLs.

scholarly journals In vitro Susceptibility Pattern of Major Gram Negative Isolates to Selected Antimicrobial Agents

2019 ◽  
pp. 1-8
Author(s):  
Shalini Gupta ◽  
Pankaj Mandale
Keyword(s):  
Antimicrobial Susceptibility ◽  
Bacterial Infections ◽  
Therapeutic Option ◽  
Polymyxin B ◽  
Susceptibility Pattern ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
E Coli ◽  
Susceptibility Data

Background: The choice of choosing right anti-microbial therapy in hospitals depends on the knowledge of local anti-microbial susceptibility profile. This retrospective study was conducted to assess the in vitro susceptibility pattern of different pathogen isolates to various antibiotics including Cefepime-Amikacin-Antibiotic resistant breakers (ARBs)* in various hospitals across the Jaipur City. Methods: To characterize the antimicrobial susceptibility pattern of different isolates from various hospitals across the Jaipur City, a retrospective, observational analysis was done for antibiogram data. A total of 1201 Gram negative isolates collected during the period from January 2017 to December 2017 were included in the study. Antibiotic sensitivity testing was done in accordance with the recommendations of Clinical Laboratory Standard Institute (CLSI) guidelines. Results: Of the total 1201 Gram negative isolates included in this study, 51.6% were from wounds and pus specimens, 40.1% were from respiratory and 8.2% from blood. P. aeruginosa (49.7%) was the most frequently isolated pathogen distantly followed by A. baumannii (21.6%), K. pneumoniae (16.6%) and E. coli (12.1%). The highest susceptibility was reported to polymyxins (100%) including Colistin and Polymyxin B, among all the tested bacteria’s and system wise. Among all the antibiotic tested, (Cefepime-Amikacin-ARBs*) sensitivity ranged for 87.9% to 52% on pathogens (E. coli, K. pneumonia, P. aeruginosa) tested from samples of skin and soft tissue, respiratory tract, blood stream, followed by Meropenem ranged for 78.4% to 55% on pathogens (E. coli, K. pneumonia, P. aeruginosa), followed by ceftazidime-tazobactam ranged for 82.7% to 58% on pathogens (E. coli, K. pneumonia, P. aeruginosa) and 22.7% sensitive for A. baumannii to Cefoperazone sulbactam. Based on pathogen type, E. coli exhibited highest overall susceptibility and the lowest was reported by A. baumannii. The susceptibility of A. baumannii ranged from 1-26% to all the tested antibiotics except polymyxins with 100% susceptibility. Conclusions: This in vitro susceptibility data suggests that Cefepime-Amikacin-ARBs* can serve as important therapeutic option for the treatment of various resistant Gram-negative bacterial infections to relieve the excess pressure on last resort antibiotics, carbapenems and other drugs including Colistin and polymyxin B. Cefepime-Amikacin-ARBs*on the basis of antimicrobial susceptibility data can be considered as an effective therapeutic option for carbapenems in treating gram negative bacterial infections, and could be considered as a broad spectrum antibiotic sparer’s like carbapenem, colistin and Polymyxin B.

scholarly journals 1181. Use of the Combination Antibiogram in the Era of MDR Gram-Negative Pathogens

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S357-S357
Author(s):  
Kenneth Klinker ◽  
Kartikeya Cherabuddi ◽  
Mark Redell ◽  
Matthew Balogh ◽  
Jill Massey ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Empiric Therapy ◽  
Multidrug Resistant ◽  
In Vitro Susceptibility ◽  
University Of Florida ◽  
Gram Negative ◽  
E Coli ◽  
Susceptibility Data ◽  
The University

Abstract Background Combinations of two or more antimicrobial agents are frequently used in empiric therapy regimens to ensure at least one agent demonstrates activity against suspected pathogens. A combination antibiogram can assess the increase in empiric coverage of a particular combination vs. either of the agents alone (i.e., percent gain). These data could assist in developing empiric regimens that may be particularly useful in settings with problematic multidrug-resistant Gram-negative pathogens. Methods An Excel-based model to construct combination antibiograms was developed to assist clinicians in evaluating institutional susceptibility data. The University of Florida Health Shands Hospital microbiology laboratory supplied susceptibility data for ceftriaxone (CFX), cefepime (CEF), ciprofloxacin (CIP), and amikacin (AMI) to assess % gain achieved with combinations for E. coli all blood isolates (n = 206) and blood isolates with an ESBL phenotype (n = 35). The same laboratory provided susceptibility data for CEF, piperacillin–tazobactam (PTZ), AMI and CIP for P. aeruginosa (all, n = 250; carbapenem-resistant (CARB-R), n = 30). Results Percent gains achieved by adding AMI or CIP to CFX and CEF to capture at least one agent exhibiting in vitro susceptibility against all blood E. coli were calculated: CFX-AMI, 16%; CFTX-CIP, 3%; CEF-AMI, 10%; CEF-CIP, 1%. The percentage gain specific to E. coli blood isolates with an ESBL phenotype ranged from 9% to 86%. The combination with the greatest percent loss against blood E. coli isolates, comparing all blood isolates to those with an ESBL phenotype, was CFX-CIP (∆-66%). Percentage gain achieved against all isolates of Pa by adding AMI or CIP to PTZ and CEF were CEF-AMI, 8%; CEF-CIP, 5%; PTZ-AMI, 15%; PTZ-CIP, 9%; percent gain of the same combinations against P. aeruginosa CARB-R isolates were 23%, 10%, 47%, and 30%, respectively. Adding AMI to either β-lactam: PTZ % S increased from 47% to 77% (+CIP) and to 94% (+AMI); CEF % S increased from 60% S to 70% (+CIP) and to 83% (+AMI). Conclusion Combination antibiogram models can assist clinicians in identifying regimens which may provide improved targeting of MDR phenotypes through calculation of percent gain. Disclosures K. Klinker, Melinta Therapeutics: Consultant, Speaker honorarium. Nabriva Therapeutics: Scientific Advisor, Consulting fee. M. Redell, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. M. Balogh, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. J. Massey, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. M. Dudley, The Medicines Company: Employee, Salary.

scholarly journals Heterogeneous and Flexible Transmission ofmcr-1in Hospital-AssociatedEscherichia coli

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Yingbo Shen ◽  
Zuowei Wu ◽  
Yang Wang ◽  
Rong Zhang ◽  
Hong-Wei Zhou ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Genes Encoding

ABSTRACTThe recent emergence of a transferable colistin resistance mechanism, MCR-1, has gained global attention because of its threat to clinical treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the possible transmission route ofmcr-1amongEnterobacteriaceaespecies in clinical settings is largely unknown. Here, we present a comprehensive genomic analysis ofEscherichia coliisolates collected in a hospital in Hangzhou, China. We found thatmcr-1-carrying isolates from clinical infections and feces of inpatients and healthy volunteers were genetically diverse and were not closely related phylogenetically, suggesting that clonal expansion is not involved in the spread ofmcr-1. Themcr-1gene was found on either chromosomes or plasmids, but in most of theE. coliisolates,mcr-1was carried on plasmids. The genetic context of the plasmids showed considerable diversity as evidenced by the different functional insertion sequence (IS) elements, toxin-antitoxin (TA) systems, heavy metal resistance determinants, and Rep proteins of broad-host-range plasmids. Additionally, the genomic analysis revealed nosocomial transmission ofmcr-1and the coexistence ofmcr-1with other genes encoding β-lactamases and fluoroquinolone resistance in theE. coliisolates. These findings indicate thatmcr-1is heterogeneously disseminated in both commensal and pathogenic strains ofE. coli, suggest the high flexibility of this gene in its association with diverse genetic backgrounds of the hosts, and provide new insights into the genome epidemiology ofmcr-1among hospital-associatedE. colistrains.IMPORTANCEColistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergentmcr-1colistin resistance gene threatens the clinical utility of colistin and has gained global attention. Howmcr-1spreads in hospital settings remains unknown and was investigated by whole-genome sequencing ofmcr-1-carryingEscherichia coliin this study. The findings revealed extraordinary flexibility ofmcr-1in its spread among genetically diverseE. colihosts and plasmids, nosocomial transmission ofmcr-1-carryingE. coli, and the continuous emergence of novel Inc types of plasmids carryingmcr-1and newmcr-1variants. Additionally,mcr-1was found to be frequently associated with other genes encoding β-lactams and fluoroquinolone resistance. These findings provide important information on the transmission and epidemiology ofmcr-1and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat.

scholarly journals Volatile Oils ofNepeta tenuifolia(Jing Jie) as an Alternative Medicine against Multidrug-Resistant Pathogenic Microbes

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Hsuan Lee ◽  
Chao-Min Wang ◽  
Po-Yu Liu ◽  
Ching-Chang Cheng ◽  
Zong-Yen Wu ◽  
...  
Keyword(s):  
Essential Oils ◽  
In Vitro Study ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
E Coli ◽  
Wide Range ◽  
Main Component ◽  
Reference Strains

Essential oils from the dried spikes ofNepeta tenuifolia(Benth) are obtained by steam distillation. Pulegone was identified as the main component in the spikes ofN. tenuifoliathrough analysis, with greater than 85% purity obtained in this study. The essential oils are extremely active against all Gram-positive and some Gram-negative reference bacteria, particularlySalmonella enterica,Citrobacter freundii, andEscherichia coli. The minimum inhibitory concentration was found to be between 0.08 and 0.78% (againstS. enterica), 0.39 and 0.78% (againstC. freundii), and 0.097 and 0.39% (againstE. coli), whereas the minimum bactericidal concentration varied in range from 0.097% to 1.04%. In general, the essential oils show a strong inhibitory action against all tested reference strains and clinical isolates. However, the antibacterial activity of EOs against bothPseudomonas aeruginosareference strains and clinical isolates was relatively lower than other Gram-negative pathogens. The essential oils ofN. tenuifoliaalso displayed bactericidal activities (MBC/MIC < 4) in this study. These findings reflect the bactericidal activity of the essential oils against a wide range of multidrug-resistant clinical pathogens in an in vitro study. In addition, we propose the fragmentation pathways of pulegone and its derivatives by LC-ESI-MS/MS in this study.

scholarly journals Microbial Profile of Various Catheter Tips among Hospitalized Patients

2018 ◽  
Vol 5 ◽  
pp. 32-38
Author(s):  
Pushpa Man Shrestha ◽  
Nisha Thapa ◽  
Navraj Dahal ◽  
Nabaraj Adhikari ◽  
Upendra Thapa Shrestha
Keyword(s):  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Descriptive Analysis ◽  
Multidrug Resistant ◽  
Antimicrobial Susceptibility Testing ◽  
Resistance Pattern ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Klebsiella Spp

Objectives: This study aimed to identify the microbiological profile of various catheter tips, and multidrug resistance pattern of extended spectrum β-lactamase (ESBL) producing E. coli and Klebsiella spp. isolates. Methods: A descriptive analysis of 263 catheter tip specimens processed for culture and antimicrobial susceptibility testing was carried out in B&B Hospital, Lalitpur. Five different types of catheter tips were analyzed for microbiological growth and antimicrobial susceptibility testing. Results: Among catheter tips, the highest percentage of microbial growth was observed in tracheostomy tip. Monomicrobial growth was recorded in 82.9% catheter tips and polymicrobial growth was observed in 17.1% tip samples. Of 180 isolates, gram negative rods (76.6%) followed by yeast (19.4%) and gram-positive cocci (3.9%) were isolated. Gram negative Acinetobacter spp. (25%) and Pseudomonas spp. (23.3%) and gram-positive Enterococcus spp. (2.2%) were the most frequently isolated bacteria. However, carbapenam was the most effective antibiotic for both groups. Conclusion: Of the total isolates tested, 61.4% were found to be multidrug resistant (MDR). Among gram negative rods, 22.2% E. coli and 27.3% Klebsiella spp. were confirmed as ESBL producer. It is recommended to apply standard protocol during insertion and removal of catheter which may help in managing nosocomial infection associated with catheters.

scholarly journals 698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S315-S316
Author(s):  
Joel Goldberg ◽  
Christopher Bethel ◽  
Andrea M Hujer ◽  
Kristine Hujer ◽  
Steven Marshall ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
E Coli ◽  
New Class ◽  
Resistant Strains ◽  
Gram Negative Organisms ◽  
New Generation ◽  
Hospital Acquired

Abstract Background Multidrug-resistant Gram-negative bacilli (MDRGNB) are emerging as a challenging cause of hospital-acquired infections and represent a critical need for innovative antibacterial development. New oxopyrazole agents targeting penicillin-binding proteins (PBPs) based on a non-β-lactam core and incorporating a siderophore moiety (Figure 1) which facilitates transport to the periplasm are being developed that show promise against Gram-negative organisms including multidrug-resistant strains of E. coli, K. pneumoniae and P. aeruginosa. Methods YU253434, an example of this new class of antibacterials, was investigated in vitro. Minimum inhibitory concentrations (MICs) were determined by broth microdilution against a representative panel comprising 15 strains each of E. coli, K. pneumoniae and P. aeruginosa, which contain extended-spectrum β-lactamase (ESBL) and/or carbapenemases genes.All studies were performed according to current Clinical & Laboratory Standards Institute (CLSI) guidelines using iron-depleted media. Ceftazidime breakpoints were arbitrability chosen as a reference for YU253434 (susceptibilities ≤4 μg/mL for Enterobacteriaceae and ≤8 μg/mL for P. aeruginosa). Results MIC testing (Figures 2–4) against E. coli showed 11 strains were YU253434 susceptible (compared with 6 for ceftazidime, and 3 for imipenem); against K. pneumoniae 13 strains were YU253434 susceptible (compared with 2 for ceftazidime and 6 for imipenem); against P. aeruginosa 10 strains were YU253434 susceptible (compared with 0 for both ceftazidime and imipenem). There appeared to be no correlation between YU253434 resistance and the presence of specific lactamase genes. Conclusion YU253434, a new generation oxopyrazole antibiotic, demonstrated promising in vitro potency against a panel of E. coli, K. pneumonia, and P. aeruginosa strains which contain ESBL and/or carbapenemases genes. Disclosures All authors: No reported disclosures.

scholarly journals Inhibition of Multidrug-Resistant Gram-Positive and Gram-Negative Bacteria by a Photoactivated Porphyrin

2017 ◽  
Vol 66 (4) ◽  
pp. 533-536 ◽  
Author(s):  
Moreno Bondi ◽  
Anna Mazzini ◽  
Simona de Niederhäusern ◽  
Ramona Iseppi ◽  
Patrizia Messi
Keyword(s):  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
In Vitro Antibacterial Activity

The authors studied the in vitro antibacterial activity of the photo-activated porphyrin meso-tri(N-methyl-pyridyl), mono(N-tetradecyl-pyridyl)porphine (C14) against four multidrug-resistant bacteria: Staphylococcus aureus, Enterococcus faecalis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative). Using 10 μg/ml of porphyrin and 60 sec irradiation we observed the remarkable susceptibility of S. aureus and E. faecalis to treatment while, under the same conditions, E. coli and P. aeruginosa showed very low susceptibility. In a later stage, suspensions of Gram-negative bacteria were processed with EDTA before photo-activation, obtaining a significant decrease in viable counts. In view of the results, if the combination of low porphyrin concentrations and short irradiation times will be effective in vivo also, this approach could be a possible alternative to antibiotics, in particular against localized infections due to multidrug-resistant microorganisms.

scholarly journals Cefepime/tazobactam as a new treatment option for multidrug resistant gram negative bacilli

2019 ◽  
Vol 7 (6) ◽  
pp. 2278
Author(s):  
Roshni Agarwal ◽  
Vaibhav Agarwal ◽  
Anjali Tewari ◽  
Parwati Upadhyay
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Resistant Bacteria ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
E Coli ◽  
New Treatment

Background: Every time an antibiotic is used, whether appropriately or not, the probability of the development and spread of antibiotic resistant bacteria is increased. Thus, multidrug resistant bacteria particularly ESBL (Extended spectrum β­lactamase), Amp C and carbapenemases producing gram negative bacilli have emerged as a major health problem all over the world. Considering new treatment options as a carbapenems sparing and resistance prevention modality, this study was aimed to know the in vitro susceptibility pattern of Cefepime/Tazobactam (CPM/TZ) in comparison to other β-Lactam/ β-Lactamase inhibitors (BL/BLI) and carbapenems against GNB.Methods: A prospective study was conducted on all clinical samples received for a period of about 1 year. Identification and susceptibility of all isolates was done by Vitek 2 Compact system. Susceptibility of CPM/ TZ was done by disc diffusion method on the basis of CLSI guidelines. Both fermenters (E. coli and Klebsiella pneumoniae) and non-fermenters (Acintobacter baumanii and Pseudomonas aeruginosa) were included in the study.Results: Out of 550 GNB isolates the most common was E. coli (61.8%), Acintobacter baumanii (16%), Klebsiella pneumoniae (14.9%) and Pseudomonas aeruginosa (7.3%). Cefepime/tazobactam had a much higher susceptibility of 68% compared to cefepime (28%). Among the BL/BLI combinations tested cefepime/tazobactam (68%) showed the maximum percentage of susceptibility followed by cefoperazone/sulbactam (61.5%) and piperacillin/tazobactam (57.6%). Amongst all GNB isolates cefepime/tazobactam (68%) sensitivity was very much comparable to imipenem (71.8%) and meropenem (69.6%).Conclusions: CPM/TZ exhibited the best in vitro activity in comparison to the other BL/BLI. This new combination of cefepime/tazobactam appears to be a promising alternative therapeutic option to carbapenems. Clinical studies are needed to confirm this in vitro study result.

scholarly journals In Vitro Activity of Ceftaroline Alone and in Combination against Clinical Isolates of Resistant Gram-Negative Pathogens, Including β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa

2009 ◽  
Vol 53 (6) ◽  
pp. 2360-2366 ◽  
Author(s):  
Céline Vidaillac ◽  
Steve N. Leonard ◽  
Helio S. Sader ◽  
Ronald N. Jones ◽  
Michael J. Rybak
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Therapeutic Option ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Clinical Value ◽  
Gram Negative ◽  
E Coli ◽  
Time Kill

ABSTRACT Ceftaroline is a novel broad-spectrum cephalosporin that exhibits bactericidal activity against many gram-positive and -negative pathogens. However, the activity of ceftaroline cannot be solely relied upon for eradication of multidrug-resistant gram-negative isolates, such as Pseudomonas aeruginosa and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, which represent a current clinical concern. As drug combinations might be beneficial by potential synergy, we evaluated the in vitro activity of ceftaroline combined with meropenem, aztreonam, cefepime, tazobactam, amikacin, levofloxacin, and tigecycline. Susceptibility testing was performed for 20 clinical P. aeruginosa isolates, 10 ESBL-producing Escherichia coli isolates, 10 ESBL-producing Klebsiella pneumoniae isolates, and 10 AmpC-derepressed Enterobacter cloacae isolates. Time-kill experiments were performed for 10 isolates using antimicrobials at one-fourth the MIC. Ceftaroline exhibited a MIC range of 0.125 to 1,024 μg/ml and was reduced 2- to 512-fold by combination with tazobactam (4 μg/ml) for ESBL-producing strains. In time-kill experiments, ceftaroline plus amikacin was synergistic against 90% of the isolates (and indifferent for one P. aeruginosa isolate). Ceftaroline plus tazobactam was indifferent for E. cloacae and P. aeruginosa strains but synergistic against 100% of E. coli and K. pneumoniae isolates. Combinations of ceftaroline plus meropenem or aztreonam were also synergistic for all E. coli and E. cloacae isolates, respectively, but indifferent against 90% of the other isolates. Finally, combinations of ceftaroline plus either tigecycline, levofloxacin, or cefepime were indifferent for 100% of the isolates. No antagonism was observed with any combination. Ceftaroline plus amikacin appeared as the most likely synergistic combination. This represents a promising therapeutic option, and further studies are warranted to elucidate the clinical value of ceftaroline combinations against resistant gram-negative pathogens.

scholarly journals In Vitro Activity of Plazomicin Compared to Amikacin, Gentamicin, and Tobramycin against Multidrug-Resistant Aerobic Gram-Negative Bacilli

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Wim A. Fleischmann ◽  
Kerryl E. Greenwood-Quaintance ◽  
Robin Patel
Keyword(s):  
Public Health ◽  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
In Vitro Activity ◽  
Gram Negative ◽  
European Committee ◽  
The U.S

ABSTRACT The worldwide spread of multidrug-resistant Enterobacterales is a serious threat to public health. Here, we compared the MICs of plazomicin, amikacin, gentamicin, and tobramycin against 303 multinational multidrug-resistant Gram-negative bacilli. We followed Clinical and Laboratory Standards Institute (CLSI) guidelines and applied CLSI breakpoints as well as those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for amikacin, gentamicin, and tobramycin and of the U.S. Food and Drug Administration for plazomicin. Overall, the highest percentage of susceptible isolates (80.2%) was demonstrated for plazomicin, which had the lowest MIC50 (1 μg/ml) of the aminoglycosides studied. Of the 42 isolates resistant to plazomicin, 34 had MICs of ≥128 μg/ml, with 33 of the 34 having MICs of >128 μg/ml for amikacin, gentamicin, and tobramycin. Among the 42 blaNDM-positive isolates, 35.7% were plazomicin susceptible, with the percentage of isolates susceptible to amikacin being 38.1% or 35.7% when applying the CLSI or EUCAST breakpoint, respectively. The 20 blaOXA-48-like-positive isolates showed 50.0% susceptibility to plazomicin. Among 35 isolates with blaCTX-M as their only characterized resistance mechanism, 68.6% were plazomicin susceptible, while the percentage susceptible to amikacin was 74.3% or 62.9% when applying the CLSI or EUCAST breakpoint, respectively. Among the 117 blaKPC-positive isolates, 94.9% were susceptible to plazomicin, whereas when the CLSI and EUCAST breakpoints were applied, 43.6% and 25.6%, respectively, were susceptible to amikacin; 56.4% and 44.4%, respectively, were susceptible to gentamicin; and 5.1% and 4.3%, respectively, were susceptible to tobramycin.

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