NEW YORK (GenomeWeb) – Determining whether rapid molecular testing changes prescribing is critical, particularly with respect to antibiotic stewardship programs. Now, a new study has demonstrated the clinical utility of molecular testing for bloodstream pathogens in pediatric patients.
The research, which was published in Infectious Diseases and Therapy last week, retrospectively evaluated the consequences of using BioFire Diagnostics' FilmArray Blood Culture ID (BCID) and a fluorescent in situ hybridization test in children.
The data was collected over about a three-year period during which the Primary Children’s Hospital in Salt Lake City, Utah had an antibiotic stewardship program and was switching between blood infection detection methods.
Anne Blaschke, corresponding author on the study, told GenomeWeb in an email that pediatric centers have typically been early adopters of syndromic panels.
"The first panels to be released were for upper respiratory tract infection, a syndrome for which etiologic testing is much more common in pediatric care," Blaschke said. "Adult centers came on board when the blood culture panels were released, but many pediatric centers already had the testing platforms in place."
Blaschke, a pediatric infectious diseases expert at the University of Utah School of Medicine, said that, having introduced rapid molecular testing for identification for bloodstream pathogens into the laboratory algorithm for blood cultures, "We felt a responsibility to show that it had a positive impact on patient care."
Having an active antimicrobial stewardship program in place gave the researchers the opportunity to evaluate the added impact of rapid testing, Blaschke added.
During the initial baseline period of the study the hospital used blood culture, and no rapid diagnostic methods were employed to diagnose blood infections.
Over a period of two years, however, the lab first phased in a peptide nucleic acid fluorescent in situ hybridization (PNAFISH) test called QuickFISH from AvanDx, followed by the BioFire FilmArray BCID. Over all three periods, a Gram stain was performed immediately when a blood culture signaled positive and physicians were notified within one hour as part of the stewardship program.
The study found that both PNAFISH and BCID reduced the time it took to identify Gram-positive pathogens.
Both methods were associated with decreased use of vancomycin — an IV antibiotic — for kids with blood cultures positive for coagulase-negative staphylococci (CoNS).
Vancomycin is the appropriate treatment for pathogenic CoNS, but many positive tests turn out to be from contamination, Blaschke said. The researchers excluded patients with positive CoNS tests who had multiple positive blood cultures, infants hospitalized in the neonatal ICU, and patients with central venous catheters, to identify a population where a positive blood culture was likely to represent contamination, according to the study.
The duration of vancomycin use for CoNS was reduced from a mean of 31 hours in the baseline period, to 12 and 14 hours for PNAFISH and BCID periods, respectively.
However, the researchers noted that for Staphylococcus aureus blood infection, which requires additional identification of resistance markers for optimal treatment, only BCID reduced the use of vancomycin for methicillin-susceptible S. aureus. This was attributed to the fact that one of the targets in the BCID assay is the mecA gene.
Although BCID also decreased the time it took to identify Gram-negative pathogens, the researchers did not see a change in the use of broad-spectrum gram-negative antibiotics associated with the introduction of the test.
"Hypotheses for this finding included our low, but non-trivial institutional rate of gram-negative resistance ... as well as ASP activities resulting in well-controlled use of broad-spectrum agents prior to the start of the study," Blaschke said.
Overall, the study concluded that resistance testing is particularly useful and important.
PCH uses standard antimicrobial susceptibility testing methods to evaluate drug resistance in Gram-negative organisms, Blaschke said, but she noted that the central lab in the hospital system uses a panel from Verigene that has more Gram-negative resistance targets.
"Without data on resistance, both the ability and the desire of clinicians to rapidly de-escalate therapy for bloodstream infection is limited," she said. Furthermore, with low resistance rates among Gram-negative organisms in children’s hospitals in general, and lower mortality from pediatric sepsis compared to adults, "the opportunity for early de-escalation and reduction in selection pressure is great."
BioFire's senior product marketing manager for commercial products, Art Seguin, noted in an email that with the increase in prevalence of antimicrobial resistance, the firm is "diligent about staying current ... monitoring the trends to ensure we develop next-generation products that can detect the most common resistance genes."
Interestingly, a previous study of BCID in an adult patient population suggested that the clinical benefits of rapid diagnostic microbiological tools may be enhanced when there is also a concurrent antibiotic stewardship program, particularly one that includes things like templated comments to guide physician prescribing based on test results.
Blaschke also pointed out that no molecular test can impact care if the result is not acted upon at the time it becomes available. "Antibiotic stewardship programs have been shown in many studies to increase the impact of rapid testing by acting as a link between the result, the provider, and the rapid implementation of clinical change," she said.
Although microbiology labs serving pediatric populations tend to be early adopters of syndromic panels, Blaschke said the pediatric population per se does not require many special considerations with respect to molecular testing — the same tests that work on adults usually work on kids, and many validation studies include both populations.
However, the epidemiology of bloodstream infection in children is slightly different than in adults, Blaschke said. Children are somewhat less likely to be infected with antibiotic-resistant organisms, particularly Gram-negative ones, and so there may be less of a need for rapid resistance testing to combat inadequate empiric therapy, she added.
Seguin affirmed that sepsis occurs in all patient populations, including children, and that a number of previous FilmArray BCID panel studies have been done in pediatric patients.
"Our marketing materials thus far have not targeted pediatrics specifically, but include all populations susceptible to sepsis," Seguin said, noting that in the future the firm may consider directing more targeted campaigns to the unique risks and diagnostic needs in pediatric populations.
Separate preliminary work on the clinical utility of BioFire's Gastrointestinal (GI) panel in pediatric patients was recently presented at ID Week.
The firm's global product marketing manager, Maggie Anderson, noted in an email that this work was the first multi-center study of the panel that included pediatric patients only, although it was not the first evaluation of the GI panel on kids.
That evaluation showed a marked increase in overall pathogen detection, detection of pathogens that are usually treated with antimicrobials, and detection of pathogens for which antimicrobial treatment can be harmful. The study also found that the ability to detect additional pathogens alongside Clostridium difficile prevented unnecessary treatment of children who happened to be C. diff colonized.
Preliminary analysis did not find a reduction in subsequent healthcare encounters, however.
In general, Blaschke said she sees increasing use of syndromic molecular panels in pediatrics going forward. "More panels have become available, and as systems are already in place at many hospitals it is relatively easy to add new panels to the test menu," she said.
But, she said, "It is important to make sure we are improving the care we give our patients, not just increasing cost," particularly in cases where a single pathogen test would be sufficient.
"The increasing availability of syndromic testing for a range of diseases states compels us to perform outcome studies ... to demonstrate that we are appropriately using these tests and improving the care of our patients," she said, further noting that a formal economic analysis to determine the value and cost-effectiveness of using these platforms is also vital.