Evaluation of Microscan WalkAway for determination of ceftazidime/avibactam and ceftolozane/tazobactam susceptibility in carbapenem-resistant Gram-negative bacilli

2021 ◽  
Author(s):  
Carmen Antonia Sanches Ito ◽  
Larissa Bail ◽  
Lavinia Nery Villa Stangler Arend ◽  
Kleber Oliveira Silva ◽  
Simone Sebold Michelotto ◽  
...  
Keyword(s):  
Error Rate ◽  
Reference Method ◽  
Multidrug Resistant ◽  
Error Rates ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Testing Error ◽  
Microscan Walkaway ◽  
Clinically Significant

Background: We evaluated the performance of ceftazidime/avibactam and ceftolozane/tazobactam MicroScan Neg multidrug-resistant MIC 1 NMR1 panel for clinical carbapenem-nonsusceptible Gram-negative bacilli isolates. Methods: We evaluated 212 clinically significant carbapenem-nonsusceptible Gram-negative bacilli 139 Pseudomonas aeruginosa and 73 KPC-producing Enterobacterales from 71 Brazilian hospitals 2013-2020. Ceftazidime/avibactam and ceftolozane/tazobactam MICs from the panel were compared with broth microdilution BMD test as the reference method. Essential agreement EA and categorical agreement CA were assessed. For P. aeruginosa , antimicrobial susceptibility testing error rates were calculated using the error-rate bound method. Results: Discrepancies were initially observed with 11 isolates, 4 resolved after retesting, 2 in favor of the NMR1 and 2 in favor of the BMD method. The ceftazidime/avibactam EA overall and evaluable was 100% for P. aeruginosa and Enterobacterales. CA was 100% for Enterobacterales , and 98.6% for P. aeruginosa . The ceftolozane/tazobactam EA was 98.6% and 100% overall and evaluable, respectively, and CA was 96.4% for P. aeruginosa . For ceftazidime/avibactam, no VME was found, and the ME rate was 4.2% 2/48. For ceftolozane/tazobactam and P. aeruginosa , using the CLSI breakpoints, the minor error mE was 11.4% and no VME or ME was found. While using EUCAST breakpoints, VME was 11.4% with no ME. The mE becomes ME or VME in the absence of the intermediate category. All categorical errors were also within 1 log of MIC variation, and the adjusted error rate for CLSI/EUCAST was 0% 0/212. Conclusions: The NMR1 panel is an option to test ceftazidime–avibactam for KPC-producing Enterobacterales and carbapenem-nonsusceptible P. aeruginosa . When ceftolozane–tazobactam MIC 4 mg/L are obtained using this method, an alert could be created, and the results could be confirmed by alternative method.

scholarly journals Performance of ceftazidime/avibactam susceptibility testing methods against clinically relevant Gram-negative organisms

2018 ◽  
Vol 74 (3) ◽  
pp. 633-638 ◽  
Author(s):  
E Wenzler ◽  
M Lee ◽  
T J Wu ◽  
K A Meyer ◽  
R K Shields ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Drug Application ◽  
Error Rates ◽  
Testing Methods ◽  
Suitable Alternative ◽  
Gram Negative ◽  
Treatment Regimens ◽  
Carbapenem Resistant ◽  
Gram Negative Organisms ◽  
New Drug Application

Abstract Objectives To ensure the accuracy of susceptibility testing methods for ceftazidime/avibactam. Methods The performances of the Etest (bioMérieux), 30/20 μg disc (Hardy diagnostics) and 10/4 μg disc (Mast Group) were evaluated against the reference broth microdilution (BMD) method for 102 clinically relevant Gram-negative organisms: 69 ceftazidime- and meropenem-resistant Klebsiella pneumoniae and 33 MDR non-K. pneumoniae. Essential and categorical agreement along with major and very major error rates were determined according to CLSI guidelines. Results A total of 78% of isolates were susceptible to ceftazidime/avibactam. None of the three methods met the defined equivalency threshold against all 102 organisms. The Etest performed the best, with categorical agreement of 95% and major errors of 6.3%. Against the 69 ceftazidime- and meropenem-resistant K. pneumoniae, only the Etest and the 10/4 μg disc met the equivalency threshold. None of the three methods met equivalency for the 33 MDR isolates. There were no very major errors observed in any analysis. These results were pooled with those from a previous study of 74 carbapenem-resistant Enterobacteriaceae and data from the ceftazidime/avibactam new drug application to define optimal 30/20 μg disc thresholds using the error-rate bound model-based approaches of the diffusion breakpoint estimation testing software. This analysis identified a susceptibility threshold of ≤19 mm as optimal. Conclusions Our data indicate that the Etest is a suitable alternative to BMD for testing ceftazidime/avibactam against ceftazidime- and meropenem-resistant K. pneumoniae. The 30/20 μg discs overestimate resistance and may lead to the use of treatment regimens that are more toxic and less effective.

scholarly journals In Vitro Properties of BAL30072, a Novel Siderophore Sulfactam with Activity against Multiresistant Gram-Negative Bacilli

2010 ◽  
Vol 54 (6) ◽  
pp. 2291-2302 ◽  
Author(s):  
Malcolm G. P. Page ◽  
Clothilde Dantier ◽  
Eric Desarbre
Keyword(s):  
Multidrug Resistant ◽  
Unusual Property ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
High Affinity ◽  
Class A ◽  
Carbapenem Resistant ◽  
Lactam Antibiotic ◽  
Resistant Strains

ABSTRACT BAL30072 is a new monocyclic β-lactam antibiotic belonging to the sulfactams. Its spectrum of activity against significant Gram-negative pathogens with β-lactam-resistant phenotypes was evaluated and was compared with the activities of reference drugs, including aztreonam, ceftazidime, cefepime, meropenem, imipenem, and piperacillin-tazobactam. BAL30072 showed potent activity against multidrug-resistant (MDR) Pseudomonas aeruginosa and Acinetobacter sp. isolates, including many carbapenem-resistant strains. The MIC90s were 4 μg/ml for MDR Acinetobacter spp. and 8 μg/ml for MDR P. aeruginosa, whereas the MIC90 of meropenem for the same sets of isolates was >32 μg/ml. BAL30072 was bactericidal against both Acinetobacter spp. and P. aeruginosa, even against strains that produced metallo-β-lactamases that conferred resistance to all other β-lactams tested, including aztreonam. It was also active against many species of MDR isolates of the Enterobacteriaceae family, including isolates that had a class A carbapenemase or a metallo-β-lactamase. Unlike other monocyclic β-lactams, BAL30072 was found to trigger the spheroplasting and lysis of Escherichia coli rather than the formation of extensive filaments. The basis for this unusual property is its inhibition of the bifunctional penicillin-binding proteins PBP 1a and PBP 1b, in addition to its high affinity for PBP 3, which is the target of monobactams, such as aztreonam.

scholarly journals Multicenter Evaluation of Ceftazidime-Avibactam Susceptibility Testing of Enterobacterales and Pseudomonas aeruginosa on the VITEK® 2 System

2020 ◽  
Author(s):  
Romney Humphries ◽  
Shelley Campeau ◽  
Thomas E. Davis ◽  
Kristin J. Nagaro ◽  
Vincent J. LaBombardi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Error Rate ◽  
Susceptibility Testing ◽  
Reference Method ◽  
Error Rates ◽  
Performance Criteria ◽  
Test Results ◽  
Major Error ◽  
Overall Performance ◽  
Vitek 2

In this multisite study, VITEK® 2 AST-Gram-Negative Ceftazidime-Avibactam (CZA) test results for 1073 isolates (866 Enterobacterales and 207 Pseudomonas aeruginosa) were compared to the Clinical & Laboratory Standards Institute (CLSI) broth microdilution (BMD) reference method. The results were analyzed for essential agreement (EA), category agreement (CA), major error rates, and very major error rates following FDA/ISO performance criteria using the FDA-recognized CLSI/EUCAST breakpoints (S ≤8/4 μg/ml and R ≥16/4 μg/ml). The overall EA was 94.5% (1014/1073) and CA was 98.7% (1059/1073). No very major errors were reported. The major error rate was 1.4% (14/998). Out of 14 major errors, 9 were within EA. Based on the EA and lack of an intermediate category for CZA, the adjusted major error rate for FDA criteria was 0.5% (5/998). The performance for ISO criteria after error resolutions included EA 94.5% (1014/1073), CA 98.9% (1061/1073), major error 1.2% (12/998), and no very major error. Vitek 2 met the ISO and FDA criteria of ≥95% reproducibility and ≥95% quality control (QC) results within acceptable ranges for QC organisms. Vitek 2 overall performance for Enterobacterales and P. aeruginosa met or exceeded the FDA and ISO performance criteria and thus is a reliable alternative to BMD reference method for routine CZA susceptibility testing.

scholarly journals Using Molecular Diagnostics to Develop Therapeutic Strategies for Carbapenem-Resistant Gram-Negative Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Fred C. Tenover
Keyword(s):  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Therapeutic Strategies ◽  
Beta Lactam ◽  
Gram Negative ◽  
Molecular Tests ◽  
Negative Results ◽  
Carbapenem Resistant ◽  
Class B ◽  
Global Threat

Infections caused by multidrug-resistant Gram-negative organisms have become a global threat. Such infections can be very difficult to treat, especially when they are caused by carbapenemase-producing organisms (CPO). Since infections caused by CPO tend to have worse outcomes than non-CPO infections, it is important to identify the type of carbapenemase present in the isolate or at least the Ambler Class (i.e., A, B, or D), to optimize therapy. Many of the newer beta-lactam/beta-lactamase inhibitor combinations are not active against organisms carrying Class B metallo-enzymes, so differentiating organisms with Class A or D carbapenemases from those with Class B enzymes rapidly is critical. Using molecular tests to detect and differentiate carbapenem-resistance genes (CRG) in bacterial isolates provides fast and actionable results, but utilization of these tests globally appears to be low. Detecting CRG directly in positive blood culture bottles or in syndromic panels coupled with bacterial identification are helpful when results are positive, however, even negative results can provide guidance for anti-infective therapy for key organism-drug combinations when linked to local epidemiology. This perspective will focus on the reluctance of laboratories to use molecular tests as aids to developing therapeutic strategies for infections caused by carbapenem-resistant organisms and how to overcome that reluctance.

Determination of carbapenemase genes in clinical isolates using Cepheid Xpert Carba-R

2021 ◽  
pp. 16-19
Author(s):  
N. I. Gabrielyan ◽  
V. G. Kormilitsyna ◽  
V. K. Zaletaeva ◽  
A. V. Krotevich ◽  
I. A. Miloserdov ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Infection Control ◽  
Resistance Genes ◽  
Carbapenem Resistance ◽  
Critical Issue ◽  
Sensitivity Study ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant

Detection of carbapenem resistance genes is a critical issue for hospitals due to possible recommendations for infection control and targeted therapy. The Cepheid Xpert instrument, a Carba-R test for the detection and differentiation of five common carbapenemase genes, was tested from September 2020 to February 2021. As part of the approbation, 20 tests were provided. This review presents the results of the approbation of a relatively regular sensitivity study on Siemens WalkAway‑96 plus. Cepheid Xpert Carba-R analysis has been shown to be an accurate and fast tool for detecting colonization by carbapenem-resistant gram-negative bacteria, which can help limit the spread of these organisms in hospitals.

Molecular Detection of Carbapenem Resistant Gram Negative Bacterial Isolates from Dogs 

2021 ◽  
Author(s):  
Surya Sankar ◽  
Thresia . ◽  
Anu Bosewell ◽  
M. Mini
Keyword(s):  
Companion Animals ◽  
Multidrug Resistant ◽  
Beta Lactam ◽  
Gram Negative ◽  
Extended Spectrum Beta Lactamase ◽  
Beta Lactam Antibiotics ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Line Of Therapy ◽  
Encoding Genes

Background: Carbapenems are beta-lactam antibiotics that are considered as the last line of therapy against multidrug resistant extended spectrum beta-lactamase. The resistance to carbapenems predominantly through carbapenemase is one of the most important emerging health problems worldwide in the therapy of clinical infections. The objective of the present study is to determine the presence of carbapenemase encoding genes among Gram- negative bacterial spp. associated with clinical infections in dogs. Methods: 30 Escherichia coli, 11 Klebsiella pneumoniae and three Pseudomonas aeruginosa isolated from urine, swabs from lesional skin and anterior vagina of dogs presented with different clinical ailments formed the samples for the study. Polymerase chain reaction was carried out to detect the presence of carbapenemase encoding genes viz., KPC, NDM, OXA, VIM and IMP among the isolates.Result: Out of the 44 Gram- negative isolates tested, 28 (76.3%) were positive for at least one tested carbapenemase gene. The highest frequency of carbapenemase recorded was for NDM followed by OXA-181, KPC, OXA-48 and VIM. Our study identified a high prevalence of carbapenemases among companion animals like dogs which could act as potential source of transmission of these resistance bacteria or their genomes to humans.

scholarly journals Synergistic Activity of Colistin-Containing Combinations against Colistin-ResistantEnterobacteriaceae

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Thea Brennan-Krohn ◽  
Alejandro Pironti ◽  
James E. Kirby
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Bacterial Outer Membrane ◽  
Time Kill ◽  
Synergistic Combinations

ABSTRACTResistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistantEnterobacteriaceae(CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistantEnterobacteriaceaeisolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.

scholarly journals Clinical Experience of Colistin-Glycopeptide Combination in Critically Ill Patients Infected with Gram-Negative Bacteria

2013 ◽  
Vol 58 (2) ◽  
pp. 851-858 ◽  
Author(s):  
Nicola Petrosillo ◽  
Maddalena Giannella ◽  
Massimo Antonelli ◽  
Mario Antonini ◽  
Bruno Barsic ◽  
...  
Keyword(s):  
Protective Factor ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Causative Agents ◽  
Treatment Onset ◽  
Cox Analysis

ABSTRACTA colistin-glycopeptide combination (CGC) has been shownin vitroto be synergistic against multidrug-resistant Gram-negative bacteria (MDR GNB), especiallyAcinetobacter baumannii, and to prevent further resistance. However, clinical data are lacking. We carried out a retrospective multicenter study of patients hospitalized in intensive care units (ICUs) who received colistin for GNB infection over a 1-year period, to assess the rates of nephrotoxicity and 30-day mortality after treatment onset among patients treated with and without CGC for ≥48 h. Of the 184 patients treated with colistin, GNB infection was documented for 166. The main causative agents were MDRA. baumannii(59.6%), MDRPseudomonas aeruginosa(18.7%), and carbapenem-resistantKlebsiella pneumoniae(14.5%); in 16.9% of patients, a Gram-positive bacterium (GPB) coinfection was documented. Overall, 68 patients (40.9%) received CGC. Comparison of patients treated with and without CGC showed significant differences for respiratory failure (39.7% versus 58.2%), ventilator-associated pneumonia (54.4% versus 71.4%), MDRA. baumanniiinfection (70.6% versus 52%), and GPB coinfection (41.2% versus 0%); there were no differences for nephrotoxicity (11.8% versus 13.3%) and 30-day mortality (33.8% versus 29.6%). Cox analysis performed on patients who survived for ≥5 days after treatment onset showed that the Charlson index (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.44;P= 0.001) and MDRA. baumanniiinfection (HR, 2.51; 95% CI, 1.23 to 5.12;P= 0.01) were independent predictors of 30-day mortality, whereas receiving CGC for ≥5 days was a protective factor (HR, 0.42; 95% CI, 0.19 to 0.93;P= 0.03). We found that CGC was not associated with higher nephrotoxicity and was a protective factor for mortality if administered for ≥5 days.

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