Stewardship / Resistance Scan for Oct 19, 2018

Undetected MDR-TB in South Africa
Carbapenem prescribing algorithm

Study finds current diagnostic tests missing MDR-TB cases in South Africa

An international team of researchers found that the World Health Organization (WHO)-endorsed diagnostic tests for drug-resistant tuberculosis (TB) are missing a substantial number of multidrug-resistant (MDR) TB cases in South Africa. The study appeared yesterday in Lancet Infectious Diseases.

For the study, the team of researchers from France, Belgium, and South Africa screened records of 37,644 Mycobacterium tuberculosis-positive cultures that had been detected in four South African provinces from 2013 through 2016 using standard diagnostic tests, including two rapid molecular assays endorsed by the WHO (Xpert MTB/RIF and GenoType MTBDRplus version 2.0). While these tests detect most genetic mutations conferring resistance to the first-line TB drugs rifampicin and isoniazid, they don't detect the ile491Phe mutation in the rpoB gene, which is associated with poor rifampicin-based treatment outcomes. Although the worldwide prevalence of this mutation is considered low, a 2009 study in Swaziland had found that nearly 30% of MDR-TB cases contained that mutation.

To find out how many of the TB-positive cultures contained this mutation, the researchers randomly selected 277 isolates identified as isoniazid resistant and rifampicin sensitive and tested them with two alternative diagnostic tests, one of which specifically targets the rpoB ile491Phe mutation. They also conducted whole genome sequencing. The results revealed that 37 of 249 (15%) of the isolates previously classified as isoniazid monoresistant contained the genetic mutation and therefore could be reclassified as MDR-TB. The tests also found additional mutations associated with resistance to other first-line TB drugs, including four distinct mutations associated with resistance to bedaquiline, one of the newest antibiotics for treating MDR-TB cases.

As a result, the researchers determined that 68% of patients in the study who had been infected by strains carrying these mutations had undergone at least one unsuccessful previous first-line TB treatment, and could be contributing to the spread of these strains in the community.

"A substantial number of MDR tuberculosis cases harbouring the Ile491Phe mutation in the rpoB gene in South Africa are missed by current diagnostic strategies, resulting in ineffective first-line treatment, continued amplification of drug resistance, and concurrent silent spread in the community," the authors of the study wrote.
Oct 17 Lancet Infect Dis study


Prescribing algorithm reduces carbapenem use in single-center study

A team of pharmacists and physicians at a small community hospital in California report that a carbapenem prescribing algorithm led to a threefold reduction in carbapenem use, according to a study yesterday in Infection Control and Hospital Epidemiology.

The algorithm developed at Sutter Tracy Community Hospital aimed to reduce overall carbapenem use by decreasing inappropriate use in patients. The hospital's antimicrobial stewardship committee was particularly concerned about the unrestricted use of imipenem-cilastatin, an antipseudomonal beta-lactam with an observed decrease in effectiveness against multidrug-resistant Pseudomonas aeruginosa. Using prospective audit and feedback, pharmacists evaluated all new orders for carbapenems and recommended alternative therapies when patients failed to meet the algorithm's criteria. The algorithm was implemented in December 2015.

In the quasi-experimental study, researchers collected 3 months of pre-intervention baseline data on carbapenem use, then compared carbapenem use in the immediate post-intervention period, 6 months post-intervention, and 1 year post-intervention. The primary end-points were carbapenem days of therapy adjusted per 1,000 patient-days (DOT) and the percentage of patients who met algorithm use criteria.

The researchers observed that DOT dropped from 131.8 at baseline to 40.1 in the immediate post-intervention period and remained low (42.9) at 6 months post-intervention. Although DOT climbed to 64.5 at 1 year post-intervention, it remained less than half of the baseline level. The percentage of patients who met algorithm use criteria climbed from 20% at baseline to 79% at 1 year post-intervention. The overall reduction in carbapenem use improved susceptibility to P aeruginosa and reduced pharmacy costs (compared with 2015) by $75,000 in 2016 and $65,000 in 2017.

The authors conclude, "Pharmacy-driven ASP [antimicrobial stewardship program]strategies may be particularly effective at both reducing antimicrobial utilization and improving antimicrobial susceptibility trends at small community hospitals."
Oct 17 Infect Control Hosp Epidemiol abstract

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