|Year : 2020 | Volume
| Issue : 3 | Page : 500-501
Does Xpert Carba R assay detect carbapenemase-producing organism in Gram-negative sepsis in neonates?
R Usha Devi, Thangaraj Abiramalatha, Ashok Chandrasekaran, Shaik Mohammad Shafi Jan, Prakash Amboiram, Umamaheswari Balakrishnan
Department of Neonatology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
|Date of Submission||27-Jun-2020|
|Date of Decision||13-Sep-2020|
|Date of Acceptance||23-Sep-2020|
|Date of Web Publication||4-Nov-2020|
Dr. Umamaheswari Balakrishnan
Department of Neonatology, Sri Ramachandra Institute of Higher Education and Research, Chennai - 600 116, Tamil Nadu
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Devi R U, Abiramalatha T, Chandrasekaran A, Shafi Jan SM, Amboiram P, Balakrishnan U. Does Xpert Carba R assay detect carbapenemase-producing organism in Gram-negative sepsis in neonates?. Indian J Med Microbiol 2020;38:500-1
|How to cite this URL:|
Devi R U, Abiramalatha T, Chandrasekaran A, Shafi Jan SM, Amboiram P, Balakrishnan U. Does Xpert Carba R assay detect carbapenemase-producing organism in Gram-negative sepsis in neonates?. Indian J Med Microbiol [serial online] 2020 [cited 2020 Nov 24];38:500-1. Available from: https://www.ijmm.org/text.asp?2020/38/3/500/299828
(Mis) Use of antibiotics leads to antibiotic resistance. With the increasing survival of preterm neonates, the management of hospital-acquired infections with multidrug resistance organisms, especially carbapenemase-producing organisms (CPO) is challenging. An ideal tool in detecting CPO is much-awaited aid in this era of carbapenemase resistance. Carbapenem resistance is reported in around 44% of Gram-negative infections in neonatal units in India. Antibiotics are often upgraded to polymyxins in sick neonates while awaiting sensitivity reports after Gram-negative growth. Xpert Carba R assay (XCRA) identifies genes for resistance within an hour, which could guide us in rational antibiotic usage and stewardship. Here, we share our clinical experience with XCRA in detecting CPO in culture-positive Gram-negative hospital-acquired infection in neonates in our unit.
We did XCRA during January–September 2018 for ten neonates who developed Gram-negative infection and were on carbapenem antibiotics. It was not done for infants already on polymyxin.
Once the BACTEC blood culture showed growth identified by alarm beep, the inoculum was checked for Gram-positive or Gram-negative growth. Critical alert was given to the clinician about the growth. Plating with a carbapenem disc for antimicrobial testing was done, and sensitivity pattern was reported by 24–72 h from the detection of growth. While awaiting the sensitivity pattern by routine resistance testing, the polymerase chain reaction (PCR) based XCRA was done in the inoculum showing growth. It took around 47 min and turn-around-time was 2 h. This assay can identify 5 carbapenemase-producing genes namely (a) Klebsiella pneumoniae Carbapenemases, (b) New Delhi metallo-beta-lactamase (NDM), (c) Verona integron-mediated metallo-beta-lactamase, (d) IMP type Metallo-beta lactamases, and (e) class D OXA-48 beta-lactamase.
Among 21 babies with Gram-negative infection who were on carbapenems, 10 underwent XCRA. All were late-onset hospital-acquired infection. All were preterm babies, and 7 (70%) were very low birth weight neonates. The median gestation age at birth was 29 weeks ranging between 26 and 36 weeks. The median birth weight was 1040 (range: 605–2540) grams. The median time of taking culture was 5 (range: 2–40) days. Umbilical lines or peripherally inserted catheters were present in 9 (90%) babies and hence fitting into central line-associated bloodstream infections. Four were on invasive ventilation at the time of culture. Two of them were previously operated for malrotation and tracheoesophageal fistula.
Organisms were identified as Acinetobacter in seven babies. The other three were Klebsiella, Serratia, and Escherichia coli. There were five CPOs identified by standard sensitivity report (SSR), among which the only one was identified by XCRA (NDM gene in E. coli) for which carbapenem was continued in view of clinical improvement. The other four CPOs were all Acinetobacter baumanii, and all these neonates were treated with colistin based on clinical condition and SSR. Other five neonates where XCRA was negative and SSR showed susceptibility to carbapenem, improved with carbapenem itself. One neonate, though recovered from initial Acinetobacter sepsis where XCRA showed no mutation, subsequently succumbed to polymicrobial infection. All others recovered and were discharged.
In our observation, Acinetobacter species were the most common CPO. XCRA has not been found to be useful in detecting carbapenem resistance in Acinetobacter sp., This could be potentially explained by the exhibition of multiple alternate mechanisms for resistance like porin or efflux pump by Acinetobacter sp. In 2014, the FDA approved XCRA as a rapid diagnostic method for the detection and differentiation of genes for carbapenem resistance in bacterial isolates. There are no neonatal data on the utility of this assay. It is a novel assay and can be time-saving, especially in this era of genomic medicine for executing antibiotic stewardship.
In our observation, XCRA detected an NDM. Literature shows that OXA-1 and NDM-1 were the prevalent genes in the South Indian and North Indian isolates, respectively. Even in the study done in 20 adults, sensitivity of XCRA was low (50%). Additional genes (OXA 23, GES, PER) were identified by in-house PCR testing in 70% of negative XCRA. In our unit, we have stopped using XCRA assay based on our observation.
XCRA cannot be used as a tool for detecting CPO in the present stage unless all the genes causing carbapenem resistance are included in the panel.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Sekar R, Mythreyee M, Srivani S, Sivakumaran D, Lallitha S, Saranya S. Carbapenem-resistant Enterobacteriaceae
in pediatric bloodstream infections in rural Southern India. Indian Pediatr 2017;54:1021-4.
Investigators of the Delhi Neonatal Infection Study (DeNIS) collaboration. Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: A cohort study. Lancet Glob Health 2016;4:e752-60.
Wertheim H, Van Nguyen K, Hara GL, Gelband H, Laxminarayan R, Mouton J, et al
. Global survey of polymyxin use: A call for international guidelines. J Glob Antimicrob Resist 2013;1:131-4.
Jamal S, Al Atrouni A, Rafei R, Dabboussi F, Hamze M, Osman M. Molecular mechanisms of antimicrobial resistance in Acinetobacter baumannii
, with a special focus on its epidemiology in Lebanon. J Glob Antimicrob Resist 2018;15:154-63.
Khurana S, Mathur P, Kapil A, Valsan C, Behera B. Molecular epidemiology of beta-lactamase producing nosocomial Gram-negative pathogens from North and South Indian hospitals. J Med Microbiol 2017;66:999-1004.
Cortegiani A, Russotto V, Graziano G, Geraci D, Saporito L, Cocorullo G, et al
. Use of cepheid Xpert Carba-R® for rapid detection of carbapenemase-producing bacteria in abdominal septic patients admitted to intensive care unit. PLoS One 2016;11:e0160643.