Phenotypic screening and molecular characterization of carbapenemase-producing Gram-negative bacilli recovered from febrile neutropenic pediatric cancer patients in Egypt.

Noha A Kamel,Wafaa N El-Tayeb,Mona R El-Ansary,Mohamed T Mansour,Khaled M Aboshanab,Ashraf B Abdel-Naim

doi:10.1371/journal.pone.0202119

Abstract

AimInfections with carbapenem-resistant Gram-negative bacteria (GNB) are among the most frequent complications in the immunocompromised cancer patients because of their considerable morbidity and mortality. Therefore, the aim of the current study was to characterize the prevalence of carbapenemase-producing GNB recovered from febrile neutropenic pediatric cancer patients in Egypt.MethodsStandard methods were used for identification, sensitivity testing (Kirby-Bauer and broth microdilution method according to CLSI guidelines). Standard methods were applied for both phenotypic and genotypic detection of the carbapenemase-producing GNB.ResultsA total of 185 GNB were recovered from different clinical specimens, Escherichia (E.) coli (86; 46.48%), followed by Klebsiella spp. (71; 38.37%), Acinetobacter (A.) baumannii (7; 3.78%) and others including Pseudomonas spp., Enterobacter (Ent.) cloacae and Proteus spp. (21; 11.35%). It is a matter of concern that 116 out of 171 enterobacterial isolates (94.15%) showed resistance to three or more antimicrobial classes and were considered multidrug resistant. Additionally, the rate of carbapenem-resistance displayed a worrisome trend as 113 out of 171 enterobacterial isolates (66.08%) and 12 out of 14 non fermenting bacilli (85.71%) showed resistance pattern to at least one of the tested carbapenems. After performing a series of phenotypic tests for initial screening of potential carbapenemase producers, molecular characterization to the 29 extracted plasmids were subjected to PCR (using 5 common carbapenemase primers). The results revealed that blaOXA-48 was the most prevalent 17 (58.62%), followed by blaNDM 8(27.58%), then blaVIM 3 (10.3%) and blaKPC 2 (6.89%).ConclusionThese results are an alarming threat to public health that calls for urgent application of antimicrobial stewardship programs along with routine surveillance for controlling outbreaks.

Highlights

Immunodeficiency is a common problem among cancer patients that results from the underlying disease itself, chemotherapy that induce neutropenia, and/or radiation therapy[1]
The results revealed that blaOXA-48 was the most prevalent 17 (58.62%), followed by blaNDM 8(27.58%), blaVIM 3 (10.3%) and blaKPC 2 (6.89%)
These results are an alarming threat to public health that calls for urgent application of antimicrobial stewardship programs along with routine surveillance for controlling outbreaks

Summary

Introduction

Immunodeficiency is a common problem among cancer patients that results from the underlying disease itself, chemotherapy that induce neutropenia, and/or radiation therapy[1]. There has been a dramatic increase in the proportion of bloodstream infections among cancer patients caused by non fermenting bacilli including Pseudomonas aeruginosa, A. baumannii and St. maltophilia along with the evolution of multiple drug resistant phenotype (MDR) [2,3].Of particular concern is the emergence of carbapenem-resistant Enterobacteriaceae (CRE), MDR Pseudomonas and Acinetobacter species[4]. The ability to produce class A, B and D carbapenemases remain by far the most clinically important carbapenem-resistance mechanism[5,6,7,8]. There are 5 main carbapenemase enzymes that are widely involved in nosocomial outbreak including, Klebsiella pneumoniae carbapenemase (KPC), Verona integron encoded metallo-β-lactamase (VIM), New Delhi metallo-β-lactamase (NDM) and for activity on imipenem(IMP) and oxacillinases due to their ability to hydrolyze oxacillin at a relatively high rate (OXA-48)[9]. The present study aimed to determine the prevalence of CP-GNB among children with malignancy by using phenotypic screening test in addition to molecular assays

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Results

Conclusion