Stewardship / Resistance Scan for Nov 01, 2017

MRSA vaccine candidate
MCR-1 in pigs
MRSA and patient-sharing
Pneumonia overprescribing

CARB-X awards $168,000 for development of novel MRSA vaccine

CARB-X announced today that it's awarding $168,000 to Integrated Biotherapeutics to develop a vaccine for the prevention of infections caused by methicillin-resistant Staphylococcus aureus (MRSA).

According to a statement from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), IBT-V02 is the first multivalent S aureus vaccine entirely based on rationally designed toxoids, including seven attenuated toxoids protective against three large families of toxins secreted by S aureus. The project has completed the discovery stage and proof of concept efficacy in animal models of MRSA.

M. Javad Aman, PhD, president and chief scientific officer of Maryland-based Integrated Biotherapeutics, said in the statement that the award will help the company complete the preclinical studies and the phase 1 clinical trial for IBT-V02. The company could receive up to $8.3 million from CARB-X based on achievement of milestones.

IBT-V02 is the first vaccine candidate in the CARB-X portfolio, which now includes 22 projects in the early stages of research and development. A public-private partnership funded by the Biomedical Advanced Research and Development Authority (BARDA), UK-based charity the Wellcome Trust, and the National Institute of Allergy and Infectious Diseases (NIAID), CARB-X was launched in 2016 to address gaps in development and funding of new antibiotics, diagnostics, and vaccines to treat the most serious gram-negative bacterial infections.

With today's announcement, the group has now awarded more than $52 million to fund the 22 projects, plus an additional $72 million if project milestones are met.
Nov 1 CARB-X press release


Study finds high-rate of MCR-1-producing bacteria in Portuguese pigs

Prospective screening of pigs in Portugal revealed an extremely high rate of Enterobacteriaceae harboring the colistin-resistance gene MCR-1, European researchers reported yesterday in Emerging Infectious Diseases.

In June 2016, the researchers collected a total of 100 rectal swab samples from two pig farms in Portugal, 30 kilometers apart. Of the 108 colistin-resistant isolates recovered, 90 were Escherichia coli, 17 were Klebsiella pneumoniae, and 1 was Proteus mirabilis. Molecular analysis identified the MCR-1 gene in 98 of the isolates and showed that all MCR-1 producing isolates also harbored the blaTEM-1 gene, with 10 showing an extended-spectrum beta-lactamase phenotype. Pulsed-field gel electrophoresis identified 15 different sequence types (STs) among the non-clonally related E coli isolates, and 2 different K pneumoniae STs.

Further analysis showed that the MCR-1 gene was carried on three different plasmids—IncHI2 (54%), IncP (38%), and IncX4 (8%). IncHI2 and IncP carried other resistance determinants associated with MCR-1, but IncX4 carried only MCR-1.

Because the pigs received colistin in their feed in the 6 weeks before sampling, the authors of the study suspect that use of the drug created selective pressure for MCR-1 acquisition. They believe that their data, along with a recent study in Germany that identified pig farms as a potential source of environmental contamination for MCR-1 producing E coli, indicate the need for screening farm environments in Portugal.  
Oct 31 Emerg Infect Dis study


Patient sharing spreads MRSA between UK hospitals

Though hospital transmission of MRSA has declined in UK hospitals that have implemented infection control measures, there is still little known about existing transmission paths. A study yesterday in Clinical Infectious Diseases, however, shows that frequent patient admissions to multiple hospitals is behind many MRSA cases recorded in London.

Study authors conducted a cross-sectional observational study of 610 hospitalized MRSA patients in southeast London. A large proportion (40.7%) of the cases was linked to 90 transmission clusters, 27 of which spanned multiple hospitals. Analysis of one 32-patient cluster showed that 26 (81.6%) of the patients were linked by hospital stay, suggesting inter-ward transmission.

"This is significant because it indicates that current endemic levels are explained by recent transmission on hospital wards that may be missed by a single hospital centric view, and not elsewhere as has been implied by other studies," the authors wrote.

The authors suggest inter-hospital sharing of MRSA data as a way to halt transmission among patients who are frequently hospitalized.
Oct 31 Clin Infect Dis study


Empiric pneumonia treatment with MRSA drugs more common in the US

Empiric treatment of MRSA-related community-acquired pneumonia (CAP) is most common in the United States and is rarely prescribed in other countries, an international research group based at South Texas Veterans Health Care and University of Texas Health in San Antonio reported yesterday at the annual meeting of the American College of Chest Physicians annual meeting in Toronto.

The scientists based their findings on a review of adult patients hospitalized with CAP over 4 nonconsecutive days at 222 facilities from 54 countries, according to the study abstract published yesterday in a Chest supplement. The study group included patients who had submitted respiratory or blood samples, and the authors considered anti-MRSA therapy as treatment administered according to clinical guidelines when it included vancomycin or linezolid within the first 24 hours of admission.

Of 3,193 patients hospitalized with CAP, 12% (436) were treated for MRSA, with the United States accounting for 52% of all prescriptions. Vancomycin was the most commonly prescribed MRSA therapy (12%), followed by linezolid (2%). Five or more MRSA-therapy prescriptions were reported by 10 countries, while 40 countries had three or fewer during the study period.

Of all the patients prescribed anti-MRSA treatment, only 12% actually had MRSA pneumonia.

The researchers concluded that non-US countries rarely use empiric anti-MRSA therapies for CAP and that more efforts are needed to prevent the empiric overuse of antibiotics, especially regarding anti-MRSA therapy. They added that clinicians should rely more on specific MRSA risk factors before exposing patients to unneeded treatments.
Oct 31 Chest abstract

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