scholarly journals Comparative Evaluation of the In Vitro Activities of WCK 5222 (Cefepime-Zidebactam) and Combination Antibiotic Therapies against Carbapenem-Resistant Pseudomonas aeruginosa

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Elias M. Mullane ◽  
Lindsay M. Avery ◽  
David P. Nicolau
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Comparative Evaluation ◽  
Combination Therapies ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Gradient Diffusion

ABSTRACT The in vitro activity of WCK 5222 (cefepime-zidebactam) was compared to that of several available combination therapies among 30 clinical carbapenem-resistant Pseudomonas aeruginosa (CRP) strains using gradient diffusion strips. The combinations included nonsusceptible β-lactams (cefepime, ceftolozane-tazobactam, and meropenem) with amikacin and fosfomycin. WCK 5222 MICs ranged from 2 to 32 mg/liter, and 97% were ≤16 mg/liter, while 105/146 (72%) combinations demonstrated inhibition below established susceptibility breakpoints. WCK 5222 monotherapy may be preferred over the combinations assessed for CRP infections.

In vitro synergy of ceftolozane/tazobactam in combination with fosfomycin or aztreonam against MDR Pseudomonas aeruginosa

2020 ◽  
Vol 75 (7) ◽  
pp. 1874-1878 ◽  
Author(s):  
Gabriel T Cuba ◽  
Gerlan Rocha-Santos ◽  
Rodrigo Cayô ◽  
Ana Paula Streling ◽  
Carolina S Nodari ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistance Mechanisms ◽  
Density Reduction ◽  
Carbapenem Resistant ◽  
Gradient Diffusion ◽  
Fold Reduction ◽  
The Face ◽  
Antimicrobial Synergy ◽  
Time Kill

Abstract Objectives Carbapenem-resistant Pseudomonas aeruginosa (CR-PSA) imposes great limitations on empirical therapeutic choices, which are further complicated by metallo-β-lactamase production. This study evaluated in vitro antimicrobial synergy of ceftolozane/tazobactam in combination with aztreonam and fosfomycin against MDR PSA. Methods MICs were determined by broth microdilution and gradient strips. The effect of ceftolozane/tazobactam+aztreonam and ceftolozane/tazobactam+fosfomycin combinations were tested against 27 MDR PSA isolates carrying blaSPM-1 (n = 13), blaIMP (n = 4), blaVIM (n = 3), blaGES-1 (n = 2) and blaCTX-M-like (n = 2), and 3 isolates with no acquired β-lactamase production detected by gradient diffusion strip crossing (GDSC). Six genetically unrelated SPM-1-producing isolates were also evaluated by time–kill analysis (TKA). Results All CR-PSA isolates harbouring blaSPM-1, blaGES-1 and blaIMP-1 were categorized as resistant to ceftolozane/tazobactam, meropenem and fosfomycin, with 70% being susceptible to aztreonam. Synergism for ceftolozane/tazobactam+fosfomycin and ceftolozane/tazobactam+aztreonam combinations was observed for 88.9% (24/27) and 18.5% (5/27) of the isolates by GDSC, respectively. A 3- to 9-fold reduction in ceftolozane/tazobactam MICs was observed, depending on the combination. Ceftolozane/tazobactam+fosfomycin was synergistic by TKA against one of six SPM-1-producing isolates, with additional non-synergistic bacterial density reduction for another isolate. Aztreonam peak concentrations alone demonstrated a ≥3 log10 cfu/mL reduction against all six isolates, but all strains were within the susceptible range for the drug. No antagonism was observed. Conclusions In the context of increasing CR-PSA and the genetic diversity of resistance mechanisms, new combinations and stewardship strategies may need to be explored in the face of increasingly difficult to treat pathogens.

scholarly journals Results from the China Antimicrobial Surveillance Network (CHINET) in 2017 of the In Vitro Activities of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Dandan Yin ◽  
Shi Wu ◽  
Yang Yang ◽  
Qingyu Shi ◽  
Dong Dong ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Isolates ◽  
Surveillance Network ◽  
Content Type ◽  
Highly Active ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Antimicrobial Surveillance ◽  
Broth Microdilution Method

ABSTRACT The in vitro activities of ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C-T), and comparators were determined for 1,774 isolates of Enterobacteriaceae and 524 isolates of Pseudomonas aeruginosa collected by 30 medical centers from the China Antimicrobial Surveillance Network (CHINET) in 2017. Antimicrobial susceptibility testing was performed by the CLSI broth microdilution method, and blaKPC and blaNDM were detected by PCR for all carbapenem-resistant Enterobacteriaceae (CRE). Ceftazidime-avibactam demonstrated potent activity against almost all Enterobacteriaceae (94.6% susceptibility; MIC50, ≤0.25 mg/liter; MIC90, ≤0.25 to >32 mg/liter) and good activity against P. aeruginosa (86.5% susceptibility; MIC50/90, 2/16 mg/liter). Among the CRE, 50.8% (189/372 isolates) were positive for blaKPC-2, which mainly existed in ceftazidime-avibactam-susceptible Klebsiella pneumoniae isolates (92.1%, 174/189). Among the CRE, 17.7% (66/372 isolates) were positive for blaNDM, which mainly existed in strains resistant to ceftazidime-avibactam (71.7%, 66/92). Ceftolozane-tazobactam showed good in vitro activity against Escherichia coli and Proteus mirabilis (MIC50/90, ≤0.5/2 mg/liter; 90.5 and 93.8% susceptibility, respectively), and the rates of susceptibility of K. pneumoniae (MIC50/90, 2/>64 mg/liter) and P. aeruginosa (MIC50/90, 1/8 mg/liter) were 52.7% and 88.5%, respectively. Among the CRE strains, 28.6% of E. coli isolates and 85% of K. pneumoniae isolates were still susceptible to ceftazidime-avibactam, but only 7.1% and 1.9% of them, respectively, were susceptible to ceftolozane-tazobactam. The rates of susceptibility of the carbapenem-resistant P. aeruginosa isolates to ceftazidime-avibactam (65.7%) and ceftolozane-tazobactam (68%) were similar. Overall, both ceftazidime-avibactam and ceftolozane-tazobactam were highly active against clinical isolates of Enterobacteriaceae and P. aeruginosa recently collected across China, and ceftazidime-avibactam showed activity superior to that of ceftolozane-tazobactam against Enterobacteriaceae, whereas ceftolozane-tazobactam showed a better effect against P. aeruginosa.

scholarly journals In Vitro Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Kellie J. Goodlet ◽  
David P. Nicolau ◽  
Michael D. Nailor
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Single Agent ◽  
Cross Resistance ◽  
Combination Therapies ◽  
Beta Lactams ◽  
Content Type ◽  
Risk Patients ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired

ABSTRACT Guidelines for the treatment of sepsis, febrile neutropenia, and hospital-acquired pneumonia caused by Pseudomonas aeruginosa include empirical regimens incorporating two antibiotics from different classes with activity against P. aeruginosa for select at-risk patients to increase the likelihood that the organism will be susceptible to at least one agent. The activity against P. aeruginosa and the rates of cross-resistance of ceftolozane-tazobactam were compared to those of the β-lactam comparators cefepime, ceftazidime, piperacillin-tazobactam, and meropenem alone and cumulatively with ciprofloxacin or tobramycin. Nonurine P. aeruginosa isolates were collected from adult inpatients at 44 geographically diverse U.S. hospitals. MICs were determined using reference broth microdilution methods. Of the 1,257 isolates collected, 29% were from patients in intensive care units and 39% were from respiratory sites. The overall rate of susceptibility to ceftolozane-tazobactam was high at 97%, whereas it was 72 to 76% for cefepime, ceftazidime, piperacillin-tazobactam, and meropenem. The rate of nonsusceptibility to all four comparator β-lactams was 11%; of the isolates nonsusceptible to the four comparator β-lactams, 80% remained susceptible to ceftolozane-tazobactam. Among the isolates nonsusceptible to the tested β-lactam comparators, less than half were susceptible to ciprofloxacin. By comparison, approximately 80% of the β-lactam-nonsusceptible isolates were susceptible to tobramycin, for overall cumulative susceptibility rates of 94 to 95%, nearly 10% higher than that of the ciprofloxacin–β-lactam combinations and approaching that of ceftolozane-tazobactam as a single agent. The rates of susceptibility to ceftolozane-tazobactam were consistently high, with little observable cross-resistance. Ceftolozane-tazobactam monotherapy performed at or above the level of commonly utilized combination therapies on the basis of in vitro susceptibilities. Ceftolozane-tazobactam should be considered for use in patients at high risk for resistant P. aeruginosa infection and as an alternative to empirical combination therapy, especially for patients unable to tolerate aminoglycosides.

scholarly journals In VivoEfficacy of Plazomicin Alone or in Combination with Meropenem or Tigecycline againstEnterobacteriaceaeIsolates Exhibiting Various Resistance Mechanisms in an Immunocompetent Murine Septicemia Model

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Kamilia Abdelraouf ◽  
Aryun Kim ◽  
Kevin M. Krause ◽  
David P. Nicolau
Keyword(s):  
Survival Rates ◽  
Resistance Mechanisms ◽  
Current Data ◽  
Combination Therapies ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Improvement In Survival ◽  
Overall Survival Rates

ABSTRACTPlazomicin is a novel aminoglycoside with potentin vitroactivity against multidrug- and carbapenem-resistantEnterobacteriaceae. The objective of this study was to assess the efficacy of plazomicin exposure, alone and in combination with meropenem or tigecycline, againstEnterobacteriaceaein the immunocompetent murine septicemia model. ICR mice were inoculated intraperitoneally with bacterial suspensions. EightEnterobacteriaceaeisolates with wide ranges of plazomicin, meropenem, and tigecycline MICs were utilized. Treatment mice were administered plazomicin, meropenem, or tigecycline human-equivalent doses alone or in combinations of plazomicin-meropenem and plazomicin-tigecycline. Treatments were initiated at 1 h postinfection and continued for 24 h. Efficacy was assessed by determination of mouse survival through 96 h. Compared with the survival of the controls, plazomicin monotherapy produced a significant improvement in survival for all mice infected with the isolates (P< 0.05) and resulted in overall survival rates of 86% (n= 50) and 53.3% (n= 30) for mice infected with isolates with plazomicin MICs of ≤4 and ≥8 mg/liter, respectively (P< 0.05). The survival of the meropenem and tigecycline groups correlated well with susceptibilities of their respective isolates, with incremental increases in survival being observed at lower MIC values. For mice infected with isolateKlebsiella pneumoniae561 (plazomicin, meropenem, and tigecycline MICs, 8, >32, and 2 mg/liter, respectively), combination therapies showed a significant reduction in mortality compared with that achieved with any monotherapy (P< 0.05). Plazomicin monotherapy resulted in improved survival in the immunocompetent murine septicemia model, notably, for mice infected with isolates with plazomicin MICs of ≤4 mg/liter. As evidenced by our current data, coadministration of meropenem or tigecycline could potentially lead to a further improvement in survival. These data support a role for plazomicin in the management of septicemia due toEnterobacteriaceaewith plazomicin MICs of ≤4 mg/liter, including carbapenem-resistant isolates.

scholarly journals New β-Lactam–β-Lactamase Inhibitor Combinations

2020 ◽  
Vol 34 (1) ◽  
Author(s):  
Dafna Yahav ◽  
Christian G. Giske ◽  
Alise Grāmatniece ◽  
Henrietta Abodakpi ◽  
Vincent H. Tam ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Treatment Option ◽  
Clinical Data ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Class D ◽  
Lactamase Inhibitor

SUMMARY The limited armamentarium against drug-resistant Gram-negative bacilli has led to the development of several novel β-lactam–β-lactamase inhibitor combinations (BLBLIs). In this review, we summarize their spectrum of in vitro activities, mechanisms of resistance, and pharmacokinetic-pharmacodynamic (PK-PD) characteristics. A summary of available clinical data is provided per drug. Four approved BLBLIs are discussed in detail. All are options for treating multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa. Ceftazidime-avibactam is a potential drug for treating Enterobacterales producing extended-spectrum β-lactamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC), AmpC, and some class D β-lactamases (OXA-48) in addition to carbapenem-resistant Pseudomonas aeruginosa. Ceftolozane-tazobactam is a treatment option mainly for carbapenem-resistant P. aeruginosa (non-carbapenemase producing), with some activity against ESBL-producing Enterobacterales. Meropenem-vaborbactam has emerged as treatment option for Enterobacterales producing ESBL, KPC, or AmpC, with similar activity as meropenem against P. aeruginosa. Imipenem-relebactam has documented activity against Enterobacterales producing ESBL, KPC, and AmpC, with the combination having some additional activity against P. aeruginosa relative to imipenem. None of these drugs present in vitro activity against Enterobacterales or P. aeruginosa producing metallo-β-lactamase (MBL) or against carbapenemase-producing Acinetobacter baumannii. Clinical data regarding the use of these drugs to treat MDR bacteria are limited and rely mostly on nonrandomized studies. An overview on eight BLBLIs in development is also provided. These drugs provide various levels of in vitro coverage of carbapenem-resistant Enterobacterales, with several drugs presenting in vitro activity against MBLs (cefepime-zidebactam, aztreonam-avibactam, meropenem-nacubactam, and cefepime-taniborbactam). Among these drugs, some also present in vitro activity against carbapenem-resistant P. aeruginosa (cefepime-zidebactam and cefepime-taniborbactam) and A. baumannii (cefepime-zidebactam and sulbactam-durlobactam).

scholarly journals Multicenter Evaluation of Ceftazidime-Avibactam and Ceftolozane-Tazobactam Inhibitory Activity against Meropenem-Nonsusceptible Pseudomonas aeruginosa from Blood, Respiratory Tract, and Wounds

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Mordechai Grupper ◽  
Christina Sutherland ◽  
David P. Nicolau
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Activity ◽  
Clinical Utility ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACT The recent escalation of occurrences of carbapenem-resistant Pseudomonas aeruginosa has been recognized globally and threatens to erode the widespread clinical utility of the carbapenem class of compounds for this prevalent health care-associated pathogen. Here, we compared the in vitro inhibitory activity of ceftazidime-avibactam and ceftolozane-tazobactam against 290 meropenem-nonsusceptible Pseudomonas aeruginosa nonduplicate clinical isolates from 34 U.S. hospitals using reference broth microdilution methods. Ceftazidime-avibactam and ceftolozane-tazobactam were active, with ceftolozane-tazobactam having significantly higher inhibitory activity than ceftazidime-avibactam. The heightened inhibitory activity of ceftolozane-tazobactam was sustained when the site of origin (respiratory, blood, or wound) and nonsusceptibility to other β-lactam antimicrobials was considered. An extensive genotypic search for enzymatically driven β-lactam resistance mechanisms revealed the exclusive presence of the VIM metallo-β-lactamase among only 4% of the subset of isolates nonsusceptible to ceftazidime-avibactam, ceftolozane-tazobactam, or both. These findings suggest an important role for both ceftazidime-avibactam and ceftolozane-tazobactam against carbapenem-nonsusceptible Pseudomonas aeruginosa. Further in vitro and in vivo studies are needed to better define the clinical utility of these novel therapies against the increasingly prevalent threat of multidrug-resistant Pseudomonas aeruginosa.

scholarly journals In Vitro Activity of Cefepime-Zidebactam, Ceftazidime-Avibactam, and Other Comparators against Clinical Isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii: Results from China Antimicrobial Surveillance Network (CHINET) in 2018

2020 ◽  
Vol 65 (1) ◽  
pp. e01726-20
Author(s):  
Yang Yang ◽  
Yan Guo ◽  
Dandan Yin ◽  
Yonggui Zheng ◽  
Shi Wu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Clinical Isolates ◽  
Surveillance Network ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Carbapenem Resistant ◽  
Almost All

ABSTRACTThis study evaluated the in vitro activity of cefepime-zidebactam in comparison with that of ceftazidime-avibactam and other comparators against clinically significant Gram-negative bacillus isolates. A total of 3,400 nonduplicate Gram-negative clinical isolates were collected from 45 medical centers across China in the CHINET Program in 2018, including Enterobacterales (n = 2,228), Pseudomonas aeruginosa (n = 657), and Acinetobacter baumannii (n = 515). The activities of cefepime-zidebactam and 20 comparators were determined by broth microdilution as recommended by the Clinical and Laboratory Standards Institute. Cefepime-zidebactam demonstrated potent activity against almost all Enterobacterales (MIC50/90, 0.125/1 mg/liter) and good activity against P. aeruginosa (MIC50/90, 2/8 mg/liter). Among the 373 carbapenem-resistant Enterobacteriaceae isolates, 57.3% (213/373) and 15.3% (57/373) were positive for blaKPC-2 and blaNDM, respectively. Cefepime-zidebactam showed a MIC of ≤2 mg/liter for 92.0% (196/213) of blaKPC-2 producers and 79.7% (47/59) of blaNDM producers. Ceftazidime-avibactam showed good in vitro activity against Enterobacterales (MIC50/90, 0.25/2 mg/liter; 94.0% susceptible) and P. aeruginosa (MIC50/90, 4/16 mg/liter; 86.9% susceptible). Ceftazidime-avibactam was active against 9.1% of carbapenem-resistant Escherichia coli isolates (63.6% were blaNDM producers) and 84.6% of Klebsiella pneumoniae isolates (74.3% were blaKPC producers). Most (90.1%) blaKPC-2 producers were susceptible to ceftazidime-avibactam. Cefepime-zidebactam demonstrated limited activity (MIC50/90, 16/32 mg/liter) against the 515 A. baumannii isolates (79.2% were carbapenem resistant), and ceftazidime-avibactam was less active (MIC50/90, 64/>64 mg/liter). Cefepime-zidebactam was highly active against clinical isolates of Enterobacterales and P. aeruginosa, including blaKPC-2-positive Enterobacterales and blaNDM-positive Enterobacterales and carbapenem-resistant P. aeruginosa. And ceftazidime-avibactam was highly active against blaKPC-2-positive Enterobacterales and carbapenem-resistant P. aeruginosa.

scholarly journals Potency of Vaborbactam Is Less Affected than That of Avibactam in Strains Producing KPC-2 Mutations That Confer Resistance to Ceftazidime-Avibactam

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ruslan Tsivkovski ◽  
Olga Lomovskaya
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Concentration ◽  
Fold Increase ◽  
Clinical Settings ◽  
Bacterial Cells ◽  
Wild Type ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

ABSTRACT Resistance to ceftazidime-avibactam due to mutations in KPC genes has been reported both in vitro and in clinical settings. The most frequently reported mutation leads to the amino acid substitution D179Y in the Ω loop of the enzyme. Bacterial cells that carry mutant KPC acquire a higher level of ceftazidime resistance, become more sensitive to other cephalosporins, and almost completely lose resistance to carbapenems. In this study, we demonstrated that two substitutions in KPC-2, D179Y and L169P, reduce the ability of avibactam to enhance the activity of ceftazidime, cefepime, or piperacillin against isogenic efflux-deficient strains of Pseudomonas aeruginosa, 8- to 32-fold and 4- to 16-fold for the D179Y and L169P variants, respectively, depending on the antibiotic. In contrast, the potency of vaborbactam, the structurally unrelated β-lactamase inhibitor that was recently approved by the FDA in combination with meropenem, is reduced no more than 2-fold. Experiments with purified enzymes demonstrate that the D179Y substitution causes an ∼20-fold increase in the 50% inhibitory concentration (IC50) for inhibition of ceftazidime hydrolysis by avibactam, versus 2-fold for vaborbactam, and that the L169P substitution has an ∼4.5-fold-stronger effect on the affinity for avibactam than for vaborbactam. In addition, the D179Y and L169P variants hydrolyze ceftazidime with 10-fold and 4-fold-higher efficiencies, respectively, than that of wild-type KPC-2. Thus, microbiological and biochemical experiments implicate both decreased ability of avibactam to interact with KPC-2 variants and an increase in the efficiency of ceftazidime hydrolysis in resistance to ceftazidime-avibactam. These substitutions have a considerably lesser effect on interactions with vaborbactam, making the meropenem-vaborbactam combination a valuable agent in managing infections due to KPC-producing carbapenem-resistant Enterobacteriaceae.

scholarly journals In Vitro Activity of Aztreonam-Avibactam against Enterobacteriaceae and Pseudomonas aeruginosa Isolated by Clinical Laboratories in 40 Countries from 2012 to 2015

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
James A. Karlowsky ◽  
Krystyna M. Kazmierczak ◽  
Boudewijn L. M. de Jonge ◽  
Meredith A. Hackel ◽  
Daniel F. Sahm ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Medical Center ◽  
Treatment Options ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Fixed Concentration ◽  
Serious Infections ◽  
Clinically Significant

ABSTRACT The combination of the monobactam aztreonam and the non-β-lactam β-lactamase inhibitor avibactam is currently in clinical development for the treatment of serious infections caused by metallo-β-lactamase (MBL)-producing Enterobacteriaceae, a difficult-to-treat subtype of carbapenem-resistant Enterobacteriaceae for which therapeutic options are currently very limited. The present study tested clinically significant isolates of Enterobacteriaceae (n = 51,352) and Pseudomonas aeruginosa (n = 11,842) collected from hospitalized patients in 208 medical center laboratories from 40 countries from 2012 to 2015 for in vitro susceptibility to aztreonam-avibactam, aztreonam, and comparator antimicrobial agents using a standard broth microdilution methodology. Avibactam was tested at a fixed concentration of 4 μg/ml in combination with 2-fold dilutions of aztreonam. The MIC90s of aztreonam-avibactam and aztreonam were 0.12 and 64 μg/ml, respectively, for all Enterobacteriaceae isolates; >99.9% of all isolates and 99.8% of meropenem-nonsusceptible isolates (n = 1,498) were inhibited by aztreonam-avibactam at a concentration of ≤8 μg/ml. PCR and DNA sequencing identified 267 Enterobacteriaceae isolates positive for MBL genes (NDM, VIM, IMP); all Enterobacteriaceae carrying MBLs demonstrated aztreonam-avibactam MICs of ≤8 μg/ml and a MIC90 of 1 μg/ml. Against all P. aeruginosa isolates tested, the MIC90 of both aztreonam-avibactam and aztreonam was 32 μg/ml; against MBL-positive P. aeruginosa isolates (n = 452), MIC90 values for aztreonam-avibactam and aztreonam were 32 and 64 μg/ml, respectively. The current study demonstrated that aztreonam-avibactam possesses potent in vitro activity against a recent, sizeable global collection of Enterobacteriaceae clinical isolates, including isolates that were meropenem nonsusceptible, and against MBL-positive isolates of Enterobacteriaceae, for which there are few treatment options.

scholarly journals In VitroandIn VivoActivities of Tigecycline-Colistin Combination Therapies against Carbapenem-Resistant Enterobacteriaceae

2014 ◽  
Vol 58 (6) ◽  
pp. 3541-3546 ◽  
Author(s):  
Jonathan W. Betts ◽  
Lynette M. Phee ◽  
Michael Hornsey ◽  
Neil Woodford ◽  
David W. Wareham
Keyword(s):  
Escherichia Coli ◽  
Animal Model ◽  
Klebsiella Pneumoniae ◽  
Galleria Mellonella ◽  
Combination Therapies ◽  
Viable Option ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACTWe assessed the activity of tigecycline (TGC) combined with colistin (COL) against carbapenem-resistant enterobacteria. Synergy occurredin vitroagainst the majority of isolates, with the exception ofSerratia marcescens. In a simple animal model (Galleria mellonella), TGC-COL was superior (P< 0.01) in treatingEscherichia coli,Klebsiella pneumoniae, andEnterobacterinfections, including those with TGC-COL resistance. Clinical studies are needed to determine whether TGC-COL regimens may be a viable option.

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