scholarly journals Systematic comparison of three commercially available combination disc tests and zCIM for carbapenemase detection in Enterobacterales isolates

Author(s):  
Janko Sattler ◽  
Anne Brunke ◽  
Axel Hamprecht

Detection of carbapenemases in Enterobacterales is crucial for patient treatment and infection control. Among others, combination disk tests (CDT) with different inhibitors (e.g. EDTA) and variations of the carbapenem inactivation method (CIM) are recommended by EUCAST or CLSI and are used by many laboratories as they are relatively inexpensive. In this study, we compare three commercially available CDT, faropenem disc testing (FAR) and the zinc supplemented CIM test (zCIM) for detection of carbapenemase-producing Enterobacterales (CPE). Rosco KPC/MBL and OXA-48 Confirm Kit (ROS-CDT), Liofilchem KPC&MBL&OXA-48 disc kit (LIO-CDT), Mastdiscs Combi Carba plus (MAST-CDT), FAR and zCIM were challenged with 106 molecularly characterized CPE and 47 non-CPE. Sensitivity/specificity was 86% (CI 78-92%)/98% (CI 89-100%) for MAST-CDT and ROS-CDT, 96% (CI 91-99%)/87% (CI 74-95%) for LIO-CDT and 99% (CI 95-100%)/81% (CI 67-91%) for FAR compared to 98% (CI 93-100%)/100% (CI 92-100%) for zCIM. The CDT showed great performance differences depending on the carbapenemase class, with MAST-CDT and LIO-CDT best detecting class B, ROS-CDT class A and LIO-CDT class D carbapenemases. Conclusion : The overall performance of commercially available CDTs was good but varied greatly for different carbapenemases and between manufacturers, compared with FAR and zCIM which performed well for all carbapenemase types. For reliable carbapenemase detection CDT should preferably not be used as the sole test, but can be part of a diagnostic strategy when combined with other assays (e.g. CIM-based, immunochromatographic or molecular tests).

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Jonas ◽  
Sandra Reuter ◽  
Sarah Klassen ◽  
Sabine Weber ◽  
Marion Buck ◽  
...  

AbstractRapid detection of carbapenemases as a cause of resistance is beneficial for infection control and antimicrobial therapy. The BD Phoenix NMIC-502 panel and CPO detect test identifies presence of carbapenemases in Enterobacterales such as Klebsiella pneumoniae and assigns them to Ambler classes. To evaluate the performance of the CPO detect panel, we employed a European collection of 1222 K. pneumoniae including carbapenem non-susceptible and susceptible clinical isolates from 26 countries, for which draft genomes were available after Illumina sequencing and the presence of carbapenemase genes had been identified by ARIBA gene calling. The CPO panel detected 488 out of 494 carbapenemase-encoding isolates as positive and six as negative. One-hundred and two isolates were tested positive for carbapenemase in the absence of any carbapenemase gene. The CPO panel identified 229 out of 230 KPC-positive isolates as carbapenemase producing and classified 62 of these as class A enzyme. Similarly, the CPO panel correctly specified 167 of 182 as class D. Regarding metallo-beta-lactamases, the CPO panel assigned 78 of 90 MBL positive isolates to class B enzymes. The sensitivity of the CPO panel in detecting carbapenemase activity was 99.5%, 97.7% and 98.3% for class A, B and D enzymes, respectively. The sensitivity in assignation to Ambler class A, B and D was 27%, 86% and 91%, respectively. An overall sensitivity of 98.8% and specificity of 86% in unclassified detection of carbapenemases was observed, with frequent false positive detection of carbapenemase producing organisms, thus rendering further confirmatory tests necessary.


2021 ◽  
Vol 7 ◽  
Author(s):  
Rémy A. Bonnin ◽  
Agnès B. Jousset ◽  
Cécile Emeraud ◽  
Saoussen Oueslati ◽  
Laurent Dortet ◽  
...  

Gram-negative bacteria, especially Enterobacterales, have emerged as major players in antimicrobial resistance worldwide. Resistance may affect all major classes of anti-gram-negative agents, becoming multidrug resistant or even pan-drug resistant. Currently, β-lactamase-mediated resistance does not spare even the most powerful β-lactams (carbapenems), whose activity is challenged by carbapenemases. The dissemination of carbapenemases-encoding genes among Enterobacterales is a matter of concern, given the importance of carbapenems to treat nosocomial infections. Based on their amino acid sequences, carbapenemases are grouped into three major classes. Classes A and D use an active-site serine to catalyze hydrolysis, while class B (MBLs) require one or two zinc ions for their activity. The most important and clinically relevant carbapenemases are KPC, IMP/VIM/NDM, and OXA-48. However, several carbapenemases belonging to the different classes are less frequently detected. They correspond to class A (SME-, Nmc-A/IMI-, SFC-, GES-, BIC-like…), to class B (GIM, TMB, LMB…), class C (CMY-10 and ACT-28), and to class D (OXA-372). This review will address the genetic diversity, biochemical properties, and detection methods of minor acquired carbapenemases in Enterobacterales.


1983 ◽  
Vol 92 (2) ◽  
pp. 113-118 ◽  
Author(s):  
Gershon J. Spector ◽  
Peter G. Smith

An endolymphatic-mastoid Silastic shunt procedure was performed in 122 cases of Menière's disease having a mean follow-up period of three years. In accordance with American Academy of Ophthalmology and Otolaryngology 1972 criteria, there were 43 % class A, 20% class B, 21% class C, and 17% class D results. Analysis of 35 recent cases having a mean follow-up period of nine months revealed 57% class A, 25% class B, 9% class C, and 9% class D results. Sixteen percent of the patients who experienced classes A, B or C results complained of other fluctuating symptoms which were not relieved by surgery. Moreover, three new eases of otolithic crisis were found in the postoperative group. Seven of ten patients who experienced a class A or B result had either a recrudescence of their vertigo or a significant decrement in hearing in response to a postoperative salt-loading test. It is concluded that the surgical success rate decreases with time and that the procedure appears to alter the symptom complex but does not cure Menière's disease.


2007 ◽  
Vol 51 (9) ◽  
pp. 3089-3095 ◽  
Author(s):  
Anne Marie Queenan ◽  
Wenchi Shang ◽  
Malgosia Kania ◽  
Malcolm G. P. Page ◽  
Karen Bush

ABSTRACT The interactions of ceftobiprole with purified β-lactamases from molecular classes A, B, C, and D were determined and compared with those of benzylpenicillin, cephaloridine, cefepime, and ceftazidime. Enzymes were selected from functional groups 1, 2a, 2b, 2be, 2d, 2e, and 3 to represent β-lactamases from organisms within the antibacterial spectrum of ceftobiprole. Ceftobiprole was refractory to hydrolysis by the common staphylococcal PC1 β-lactamase, the class A TEM-1 β-lactamase, and the class C AmpC β-lactamase but was labile to hydrolysis by class B, class D, and class A extended-spectrum β-lactamases. Cefepime and ceftazidime followed similar patterns. In most cases, the hydrolytic stability of a substrate correlated with the MIC for the producing organism. Ceftobiprole and cefepime generally had lower MICs than ceftazidime for AmpC-producing organisms, particularly AmpC-overexpressing Enterobacter cloacae organisms. However, all three cephalosporins were hydrolyzed very slowly by AmpC cephalosporinases, suggesting that factors other than β-lactamase stability contribute to lower ceftobiprole and cefepime MICs against many members of the family Enterobacteriaceae.


2018 ◽  
Vol 56 (8) ◽  
Author(s):  
Menglan Zhou ◽  
Danchen Wang ◽  
Timothy Kudinha ◽  
Qiwen Yang ◽  
Shuying Yu ◽  
...  

ABSTRACT The objective of this study was to evaluate the performance of four phenotypic methods in the detection of carbapenemase-producing Enterobacteriaceae (CPE) in China. We evaluated the performance of four carbapenemase detection methods, the modified Hodge test (MHT), the Carba NP test, the meropenem hydrolysis assay (MHA) with 1- and 2-h incubation, and the modified carbapenem inactivation method (mCIM) with meropenem, imipenem, and ertapenem, on 342 carbapenem-resistant Enterobacteriaceae isolates (CRE) in China. PCR was used as the gold standard. The 2-h-incubation MHA performed the best in carbapenemase detection (overall sensitivity, specificity, positive predictive value, and negative predictive value all 100%). Second was the Carba NP test, with a sensitivity of 99.6%. The 1-h-incubation MHA performed poorly in Klebsiella pneumoniae carbapenemase (KPC) detection (sensitivity, 71.3%). For mCIM, the best performance was observed with the meropenem disk. The MHT exhibited the worst performance, with a specificity of 88.8%. All assays except 1-h-incubation MHA, which failed to identify 68 KPC-2s, had a sensitivity of >98% in the detection of 172 KPCs. Likewise, all assays had a sensitivity of >95% in the detection of 70 class B carbapenemases, except for MHT (82.9%). The 2-h-incubation MHA significantly improved the accuracy in CPE detection compared with that for 1-h incubation and performed the best in the detection of class A and B carbapenemases. Our findings suggest that the MHA is the most practical assay for carbapenemase detection. For those who cannot afford the associated equipment, both the Carba NP test and mCIM are good alternatives with regard to the practical requirements of time and cost.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S376-S376 ◽  
Author(s):  
Sandra Boyd ◽  
Karen Anderson ◽  
Valerie Albrecht ◽  
Davina Campbell ◽  
Maria S Karlsson ◽  
...  

Abstract Background Few options remain for treatment of infections caused by multi-drug resistant (MDR), carbapenemase-producing gram-negative pathogens. Cefiderocol (CFDC; Shionogi & Co. Ltd), is a novel parenteral siderophore cephalosporin that enters the bacterial cell through the iron–siderophore uptake system. Here we report on the in vitro activity of CFDC against a set of well-characterized MDR gram-negative isolates collected by the Centers for Disease Control and Prevention. Methods Minimum inhibitory concentrations (MIC) values for CFDC in iron-depleted cation-adjusted Mueller Hinton broth were determined using reference broth microdilution. Study isolates (n = 315) included Enterobacteriaceae (59%), Pseudomonas aeruginosa (19%), Acinetobacter baumannii (17%), Stenotrophomonas maltophilia (4%), and Burkholderia cepacia complex (1%). Of these, 229 (73%) were carbapenemase-producers including Ambler Class A- (37%), Class B- (29%) and Class D- type (29%) enzymes. The remaining isolates included 51 β-lactam-resistant isolates that were non-carbapenemase-producers, and 35 β-lactam-susceptible isolates. Results were interpreted using suggested CFDC breakpoints of Sensitive ≤4 μg/mL and Resistant ≥16 μg/mL. Results The majority of the isolates (90.8%) were categorized as CFDC susceptible; the percentage of isolates with a CFDC MIC ≤4 μg/mL among Enterobacteriaceae, P. aeruginosa, and A. baumannii was 87.5%, 100%, and 89%, respectively. Percentage of isolates with a CFDC MIC ≤4 μg/mL that harbored a carbapenemase of the Class A-, Class B-, and Class D-type was 91.8%, 74.8%, 98.0%, respectively. By applying suggested breakpoints, 12 isolates were categorized as intermediate and 17 as resistant. The resistant isolates included 11 NDM-, 2 OXA-23- and 4 KPC-positive organisms. Conclusion Cefiderocol showed potent activity against MDR gram-negative pathogens including Class A, B, and D carbapenemase-producing isolates. Of note, all P. aeruginosa, including Class B metallo-β-lactamase producers, were susceptible to CFDC. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 10 (1) ◽  
pp. 57-60
Author(s):  
F. I. Belialov

New classification divides medications on five classes by influence on comorbid diseases and conditions and rates drug’s effects as favourable (A), possible (B), neutral (C), undesirable (D), and unfavourable (X). Class A includes drugs used in treatment of comorbid disease, class B embraced drugs with positive influence, class C includes drugs without significant influence or contradictory influence, class D consist of drugs with possible nonsevere adverse effects, and class X includes drugs with severe adverse effects. The more universal drug classification according to influence on comorbid diseases can include and unite other classifications. Classification may help unify marks of positive and negative influences drugs on comorbidity and help practitioners in selection of effective and safe treatment.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rémy A. Bonnin ◽  
Delphine Girlich ◽  
Agnès B. Jousset ◽  
Lauraine Gauthier ◽  
Gaëlle Cuzon ◽  
...  

Abstract In Enterobacterales, the most common carbapenemases are Ambler’s class A (KPC-like), class B (NDM-, VIM- or IMP-like) or class D (OXA-48-like) enzymes. This study describes the characterization of twenty-four OXA-23 or OXA-58 producing-Proteus mirabilis isolates recovered from human and veterinary samples from France and Belgium. Twenty-two P. mirabilis isolates producing either OXA-23 (n = 21) or OXA-58 (n = 1), collected between 2013 and 2018, as well as 2 reference strains isolated in 1996 and 2015 were fully sequenced. Phylogenetic analysis revealed that 22 of the 24 isolates, including the isolate from 1996, belonged to a single lineage that has disseminated in humans and animals over a long period of time. The blaOXA-23 gene was located on the chromosome and was part of a composite transposon, Tn6703, bracketed by two copies of IS15∆II. Sequencing using Pacbio long read technology of OXA-23-producing P. mirabilis VAC allowed the assembly of a 55.5-kb structure encompassing the blaOXA-23 gene in that isolate. By contrast to the blaOXA-23 genes, the blaOXA-58 gene of P. mirabilis CNR20130297 was identified on a 6-kb plasmid. The acquisition of the blaOXA-58 gene on this plasmid involved XerC-XerD recombinases. Our results suggest that a major clone of OXA-23-producing P. mirabilis is circulating in France and Belgium since 1996.


2013 ◽  
Vol 119 (1) ◽  
pp. 131-138 ◽  
Author(s):  
Anthony C. Wang ◽  
Steven B. Chinn ◽  
Khoi D. Than ◽  
H. Alexander Arts ◽  
Steven A. Telian ◽  
...  

Object The middle cranial fossa (MCF) approach is a microsurgical technique described as a primary option in the treatment of small, intracanalicular schwannomas involving the eighth cranial nerve. Excellent rates of complete tumor resection, hearing preservation, preservation of facial nerve function, and low complication rates have been reproduced using this technique. However, the durability of hearing preservation attained using the various treatment options has not been adequately assessed. The purpose of this study was to evaluate the durability of long-term hearing preservation in patients with vestibular schwannoma (VS) treated via the MCF approach. The authors hypothesize that hearing preservation in these patients will prove to be durable years after treatment in a high percentage of cases. Methods Retrospective medical chart review was performed in 103 consecutive patients undergoing resection of VS via a modified MCF approach between 1999 and 2008. Patients in whom surgical goals were gross-total resection and hearing preservation were included. Preoperative and postoperative hearing assessment was performed using standard audiometric testing, and classified according to American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) guidelines as a primary outcome measure. Outcomes and neurological complications initially, and at 1, 3, and 5 years following operation were analyzed. Results Initial hearing preservation rates were in keeping with the best previously published results. At initial postoperative audiometric follow-up, of the patients presenting with Class A hearing, 67% remained Class A, 17% were Class B, 1% were Class C, and 15% were Class D. Of patients presenting with Class B hearing, 24% were Class A, 53% remained Class B, 6% were Class C, and 18% were Class D. Of patients presenting with Class C hearing, 100% remained Class C. To assess the durability of hearing preservation in our patients, the authors evaluated hearing function at regular intervals after the initial postoperative audiometric follow-up. Audiometric data were available for 56 patients at 5-year follow-up. Of the 20 patients with Class A hearing at initial postoperative follow-up with 5-year follow-up, 13 (65%) remained Class A, 6 (30%) were Class B, and 1 (5%) was Class C. Of the 12 patients with Class B hearing at initial postoperative follow-up with 5-year follow-up, 4 (33%) were Class A, 4 (33%) remained Class B, and 4 (33%) were Class C. Of the 3 patients with Class C hearing at initial postoperative follow-up with 5-year follow-up, all 3 (100%) remained Class C. Conclusions A majority of patients with preserved hearing following the MCF approach for treatment of VS experience durability of their preserved hearing at 5-year follow-up. The initial AAO-HNS classification was preserved in 13 (65%) of the 20 patients who had Class A hearing at 5 years, and in 8 (67%) of the 12 who had Class B hearing at 5 years. Overall, a decline in AAO-HNS classification was noted in 15% of patients with preserved Class A hearing, and in 33% of those with preserved Class B hearing. Facial nerve function was preserved in 91% of cases. Superior hearing preservation as well as good outcomes in facial nerve function and few serious complications can be accomplished using the MCF approach for resection of small VSs.


2002 ◽  
Vol 46 (12) ◽  
pp. 3837-3842 ◽  
Author(s):  
Ellen Smith Moland ◽  
Jennifer A. Black ◽  
Jason Ourada ◽  
Mark D. Reisbig ◽  
Nancy D. Hanson ◽  
...  

ABSTRACT Despite the discovery of novel β-lactamases such as extended-spectrum β-lactamases (ESBLs), imported AmpC, and carbapenem-hydrolyzing β-lactamases at least a decade ago, there remains a low level of awareness of their importance and how to detect them. There is a need to increase the levels of awareness of clinical laboratories about the detection of newer β-lactamases. Therefore, a study was conducted in 2000 to investigate the occurrence of these β-lactamases in Klebsiella pneumoniae isolates at 24 U.S. medical centers. To enhance the likelihood of detecting imported AmpC and carbapenem-hydrolyzing β-lactamases, participating laboratories were permitted to include archived strains (1996 to 2000) that were intermediate or resistant to either cefoxitin or imipenem. The β-lactamase production of 408 isolates positive by screening of 1,123 isolates was investigated by ESBL phenotypic confirmation tests; and for AmpC and carbapenem-hydrolyzing β-lactamases, three-dimensional tests, isoelectric focusing, β-lactamase inhibitor studies, spectrophotometric assays, induction assays, and molecular tests were used. ESBL-producing isolates were detected at 18 of the 24 sites (75%), imported AmpC-producing isolates were detected at 10 sites (42%), inducible imported AmpC-producing isolates were detected at 3 sites (12.5%), and a molecular class A carbapenem-hydrolyzing enzyme was detected at 1 site (4%). No class B or D carbapenem-hydrolyzing enzymes were detected. ESBLs and imported AmpC β-lactamases were detected at a significant number of sites, indicating widespread penetration of these enzymes into U.S. medical institutions. Because these enzymes may significantly affect therapeutic outcomes, it is vital that clinical laboratories be aware of them and be able to detect their occurrence.


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