Multicenter Evaluation of the BD Phoenix CPO Detect Test for Detection and Classification of Carbapenemase-Producing Organisms in Clinical Isolates

Abstract

265words) 32 Background: 33 Limited treatment options contribute to high morbidity/mortality rates with carbapenem-resistant, 34 gram-negative bacterial infections. New approaches for carbapenemase-producing organism 35 (CPO) detection may help inform clinician decision-making on patient treatment and infection 36 control. BD Phoenix™ CPO detect ("CPO detect") detects and classifies carbapenemases in 37 Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa during susceptibility 38 testing. The clinical performance for CPO detect is reported here. 40Methods: 41 Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates were 42 evaluated across three sites using CPO detect and a composite reference method (RM); the latter 43 comprised of the modified carbapenem inactivation method and minimal inhibitory 44 concentration (MIC) screen for ertapenem, imipenem, and meropenem. Multiplex PCR testing 45 was also utilized for Ambler class determination. Positive/negative percent agreements (PPA and 46 NPA) between CPO detect and RM were determined. 47 48 Results: 49 PPA and NPA for Enterobacterales were 98.5% [96.6, 99.4] and 97.2% [95.8, 98.2], 50 respectively. A. baumannii PPA and NPA, respectively, were 97.1% [90.2, 99.2] and 97.1% 51 [89.9, 99.2]. P. aeruginosa PPA and NPA, respectively, were 95.9% [88.6, 98.6] and 92.3% 52 [86.7, 95.6]. PPA for carbapenemase class designation for all organisms combined and 53 Enterobacterales alone, respectively, were 95.3% [90.2, 97.8] and 94.6% [88.8, 97.5] for Class 54 on July 4, 2020 by guest http://jcm.asm.org/ Downloaded from Clinical performance for CPO detection-Whitley et al., 2020-JCM 3 A, 94.0% [88.7, 96.6] and 96.4% [90.0, 98.8] for Class B, and 95.0% [90.1, 97.6] and 99.0% 55 [94.4, 99.8] for Class D. NPA values for all organisms, and Enterobacterales alone, ranged from 56 98.5% to 100%. 57 58 Conclusions: 59 CPO detect provided accurate detection and classification of CPOs for the majority of isolates of 60 Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa tested. 61 62 KEY WORDS: Carbapenem resistance; Carbapenemase-producing organisms; Ambler class 63 carbapenemase; Carbapenemase-resistant Enterobacterales; Phoenix CPO detect 64 on July 4, 2020 by guest http://jcm.asm.org/ Downloaded from Clinical performance for CPO detection-Whitley et al., 2020-JCM 65 Approximately 2.8 million people are infected with antibiotic-resistant bacteria each year in the 66 USA; at least 35,000 die as a result of antibiotic resistance.(1) A large number of these 67 mortalities are caused by multidrug-resistant (MDR), gram-negative organisms,(2, 3) which 68 continue to represent a major health concern-especially in hospital settings,(4-6) where 69 mortality rates due to MDR range from 30-70%. (7, 8) Recent data suggest that anywhere from 5-70 60% of infections involve antibiotic resistant organisms.(9, 10) Carbapenems are among a 71 diminishing list of effective antibiotic classes for the treatment of MDR in...

Evaluation of the BD Phoenix CPO detect panel for prediction of Ambler class carbapenemases

“…Of note, most false positive reported strains had an MIC against meropenem of 1-8 mg/L, which could lead to false conclusions regarding infection control. In 50% of cases, broad spectrum beta-lactamases and/or a loss of porins could be detected genetically (data not shown), which was also discussed in another similar study as a source of possible undercount bias 28 . Due to the large number of strains of diverse European origin local effects and peculiarities could be largely excluded.…”

“…Few previous studies have investigated the performance of the CPO detect test [25][26][27][28][29][30] . These studies are mainly based on smaller collections of locally or regionally collected/sampled CPO-positive strains and just some 30-50 CPO-negative control strains selected on the basis of resistance without carbapenemase activity-which has already been discussed as a limitation in assessment of test specificity.…”

Sağlık Hizmetiyle İlişkili Enfeksiyon Etkeni Enterobacterales Suşlarında Karbapenemaz Direnç Genlerinin Araştırılması

“…Gram negatif organizmalara bağlı enfeksiyonların tedavisinde en uygun antibiyotiğin seçiminde antimikrobiyal duyarlılık test sonucu önemlidir, ancak zaman alıcıdır. Önceden karbapenemaz üretiminin ve karbapenemaz enzim sınıfının belirlenmesi tedaviye yön verebilir 18 . Ayrıca, karbapenem dirençli bir organizmada erkenden karbapenemaz varlığının tanımlanması hızla enfeksiyon kontrol önlemlerinin alınması ve dolayısıyla direnç genlerinin yayılmasının önlenmesine yardımcı olabilir 18 .…”

“…Önceden karbapenemaz üretiminin ve karbapenemaz enzim sınıfının belirlenmesi tedaviye yön verebilir 18 . Ayrıca, karbapenem dirençli bir organizmada erkenden karbapenemaz varlığının tanımlanması hızla enfeksiyon kontrol önlemlerinin alınması ve dolayısıyla direnç genlerinin yayılmasının önlenmesine yardımcı olabilir 18 . Çalışmamızda, meropeneme doza bağlı duyarlı veya d�rençl� olarak saptanan toplam 79 K. pneumoniae ve E. coli izolatında, yaygın karbapenemaz kodlayan OXA-48, NDM, KPC, IMP ve VIM direnç genleri araştırıldı.…”

“…Bununla birlikte, maliyetlidirler ve genellikle en yaygın karbapenemazları kodlayan genleri hedef alırlar. Fenotipik testler ise, daha önce tanımlanmamış karbapenemazları tespit edebilme avantajına sahiptirler, ancak karbapenemaz enzimlerini düşük seviyelerde eksprese eden bazı genleri tespit edemeyebilirler 18 . Bir çalışmada BD Phoenix CPO detect paneli ile yanlış pozitiflik oranı %20.51 olarak bulunmuş, çift karbapenemaz üreticisi suşlardan ise hepsinin doğru olarak tanımlandığı, bunlardan yalnız birinin Ambler sınıflamasına göre sınıflandırılamamış olduğu gösterilmiştir 22 .…”