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Microbiology’s shifting role in war on sepsis

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Anne Paxton

August 2018—If you were casting about for the severest test of a laboratory’s capabilities, day in and day out, sepsis admissions at a pediatric hospital might fit the bill.

At Children’s Hospital of Philadelphia, and at other hospitals, waging war on sepsis requires battles on multiple fronts and clinical pathways that rely on an agile and highly equipped microbiology laboratory.

Three main categories of patients ensure there is no shortage of sepsis cases at CHOP, says Erin H. Graf, PhD, D(ABMM), director of the infectious disease diagnostics laboratory. “We’re a very large oncology center with a lot of children with hematologic malignancies as patients, who are certainly at high risk for sepsis.”


The hospitals treating adults see much more carba­penem-resistant Enterobacteriaceae than the pediatric hospitals, “and it’s just a matter of time before they become more common in our community,” says Dr. Erin Graf of Children’s Hospital of Philadelphia. [Bob Williams]

A large neonatal population makes up the second category, since the 546-bed hospital is also the major center to which other hospitals send their most premature babies. “Low-birthweight infants are at increased risk for sepsis, and we see that fairly often,” Dr. Graf notes. The third population consists of patients with community-acquired sepsis, including, among others, infants with group B strep or E. coli acquired from the mother.

Community-acquired infections have gradually declined, thanks to vaccination and successful group B strep screening programs, but the populations of low-birthweight neonates and the immunocompromised continue to grow and help keep the roughly 40 FTEs of the CHOP microbiology laboratory busy. Performing more than 200,000 tests a year, the lab is constantly looking for ways to identify bacteria in the bloodstream faster.

The laboratory uses BD Bactec instruments to run blood cultures, and when a blood culture is positive, there are two mechanisms by which to rapidly identify the organisms, Dr. Graf says. “We run the Luminex Verigene for Gram-positive organisms and find within a couple of hours whether it’s Staph aureus that might be resistant, or MRSA or coagulase-negative staphylococci versus a group A or B strep.” A new Accelerate Pheno instrument, soon to go live, will provide rapid identification within an hour and susceptibility testing within eight hours. “That will speed up the process significantly,” she says.

Also on deck, though still in a research phase, is next-generation sequencing. “The beauty of NGS is you can look for everything, so we don’t have to bias what we’re looking for.” That is one reason her lab has not been as excited about the T2 Biosystems bacteria panel, which the FDA approved this spring, and Candida panel. “They only cover five bacteria and Candida, but we do not see a lot of Candida bacteremia here.”

She would be pleased to see NGS testing become more cost-effective. “Right now it’s not fast enough and not cheap enough, but I think we’ll get there. There is newer technology on its way that is promising at picking up bacteria in the bloodstream. And we can start asking questions about genetic resistance determinants that are present.” She is optimistic, for example, that Oxford Nanopore Technologies instruments will soon bring speed at lower cost.

Pathologists at CHOP have expressed interest in total lab automation, but Dr. Graf is a bit wary. “There’s a large validation that goes along with that because pediatric samples can be so different from adults’. Considering our volume and collection and sample types, that would mean devoting brainpower that we’re currently using on other important projects.”

The laboratory testing that goes along with the several clinical pathways for sepsis includes blood culture and testing of isolates on a MALDI-TOF mass spectrometer, although with the Accelerate Pheno, she notes, it’s not necessary to confirm the identification. Then the lab may run flu or other viral PCRs if there is a need to rule out a viral cause. “The PCRs could include herpes virus, CMV, and EBV, in addition to the standard respiratory viruses that can cause fever and other sepsis-like symptoms,” all of which are laboratory-developed assays, she notes.


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