Stewardship / Resistance Scan for Sep 15, 2017

Promising novel assay
Transmissible Enterobacteriaceae
Additional FMT benefits

Novel assay could help physicians differentiate viral, bacterial infections

Results from a new study in Pediatrics confirmed high performance of a novel diagnostic test to distinguish bacterial from viral infection in febrile children.

The test is a host-signature assay that measures the levels of three proteins in the blood—tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon y-induced protein 10 (IP10), and C-reactive protein (CRP)—then calculates a bacterial/viral likelihood score.

Although a previous study had indicated that the assay could differentiate bacterial from viral infections with high sensitivity and specificity, the aim of this investigation was to independently validate performance in a double-blind, multi-center clinical study focusing on pediatric patients and emergency department arrivals aged 3 months to 18 years old. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results.

In total, 597 serum samples were collected from children at five pediatric emergency departments, but after exclusion of patients who failed to meet inclusion criteria, the test was performed on 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The infectious cohort was sex-balanced, with an average age of 4.1 years and a wide range of fever temperatures, times from symptom onset, and clinical syndromes.

Of the 361 patients in the infectious cohort, the assay classified 209 patients with a viral outcome, 99 patients with a bacterial outcome, and 53 patients with an equivocal outcome. Primary analysis of the 307 patients with either a viral or bacterial reference standard diagnosis showed that the assay distinguished between viral and bacterial patients with 93.8% sensitivity and 89.8% specificity.

When compared with laboratory parameters and diagnostic markers routinely used in clinical practice to distinguish bacterial from viral infections, the assay outperformed white blood cell count and demonstrated significantly improved sensitivity and comparable specificity to absolute neutrophil count, while also outperforming CRP and procalcitonin tests.

"Taken together with the high performance observed in other independent studies, these data support a new effective tool to help clinicians avoid missing bacterial infections or overusing antibiotics," the authors write.
Sep 13 Pediatrics abstract


Non-E coli Enterobacteriaceae found to be more transmissible in ICUs

Non–Escherichia coli Enterobacteriaceae (non-EcE) such as Klebsiella pneumoniae are nearly four times more transmissible than E coli in intensive care units (ICUs), Dutch scientists report in Clinical Infectious Diseases.

In the post-hoc analysis of a multicenter study conducted in 13 European ICUs, the researchers used prospective surveillance data from more than 11,000 patients and a mathematical model to estimate the transmission capacities of extended-spectrum cephalosporin-resistant E coli and non-EcE, which have become an increasing problem in hospitals in recent years. Understanding the transmission dynamics of these pathogens is considered essential for designing effective infection control measures.

Among the 11,420 patients in the study with at least one culture result, 637 patients were found to be colonized with E coli and 1,184 with non-EcE (including Klebsiella, Enterobacter, Serratia, and Citrobacter species). The admission prevalence was 3.8% for non-EcE (74% of which were K pneumoniae). Acquisition rates were 7.4 and 2.6 per 100 admissions at risk for non-EcE and E coli, respectively. The estimated transmission capacity of non-EcE was 3.7 times higher than that of E coli, with single admission reproduction numbers of 0.17 for non-EcE and 0.047 for E coli.

The authors of the study say the finding that the reproduction numbers were below the critical threshold of 1 suggests that outbreaks in ICUs typically remain small with current infection control policies. But they warn that if problems emerge, such as an outbreak of colistin-resistant Enterobacteriaceae, "more measures are needed to control a K pneumoniae outbreak than are needed to control an E coli outbreak."
Sep 15 Clin Infect Dis abstract


Study finds FMT may have additional benefits for gut microbiome

In another study yesterday in Clinical Infectious Diseases, Canadian investigators report that fecal microbiota transplantation (FMT), a non-pharmacologic approach to treating recurrent Clostridium difficile infection (CDI), may be a novel strategy for removing additional drug-resistant bacteria from the gut microbiome.

For the study, the researchers performed whole-metagenome DNA sequencing on stool specimens from eight donor-recipient pairs, both prior to FMT and at six visits following FMT. They were looking to characterize changes in microbiota composition and antimicrobial resistance gene carriage following the procedure, in which healthy donor feces is transplanted into the intestinal tract of patients who have recurrent CDI. The purpose of the investigation was to replicate previous reports of several types of multidrug-resistant bacterial pathogens being eliminated in patients who had undergone FMT for recurrent CDI.

Sequencing of the 64 total metagenomics data sets indicated significant changes in the intestinal microbiota of the FMT recipients. Normal commensal bacteria (Bacteroides, Eubacterium) increased in abundance, while opportunistic pathogens like K pneumoniae decreased. In addition, the researchers found that a total of 95 resistance genes—including clinically relevant quinolone, beta-lactamase, extended-spectrum beta-lactamase (ESBL), and vancomycin-resistant genes—were depleted in the FMT recipients.

They also, however, found evidence that 37 resistance genes (conferring ESBL and quinolone resistance) had been transferred from donors to recipients via FMT. The authors say this finding is not surprising, since some resistance genes are endogenous to commensal bacteria, but they note that it underscores the importance of selecting and screening for healthy FMT donors.

"FMT may be a non-pharmacologic approach to managing patients colonized with or at risk from infections due to multidrug-resistant bacteria," the authors write. "It is still not clear how effective or durable this approach could be, but it seems promising."
Sep 15 Clin Infect Dis abstract

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