Stewardship / Resistance Scan for Jan 31, 2019

News brief

UK One Health report shows declines in human, animal antibiotic use

The UK government today published a One Health report on antibiotic use and antibiotic resistance in animals and humans from 2013 through 2017, noting a 40% reduction of antibiotics in food-producing animals and a 9% decline in people.

Antibiotic use declined from 62 milligrams per kilogram (mg/kg) to 37 mg/kg over the study period in food animals and from 135 mg/kg to 123 mg/kg in people, for declines of 40.3% and 8.9%, respectively. In addition, the use and sales in tons of antibiotics dropped 18.5%, from 957 to 773 tons. Of those 773 tons, 491 tons were used in people and 282 tons in livestock, pets, and other animals.

Overall, 89% of highest-priority antibiotics (17 tons) were used in people. Their use increased by 8% in people and decreased by 51% in animals.

In food-producing animals, scientists detected no resistance in Escherichia coli or Salmonella isolates to colistin, and very low or no resistance to third-generation cephalosporins. There was low resistance level to fluoroquinolones for E coli and only very low resistance level for Salmonella.

In people, E coli demonstrated moderate resistance to third-generation cephalosporins and to fluoroquinolones, while E coli had low resistance and Salmonella moderate resistance to colistin.

The report is a follow-up to a 2015 UK One Health report.
Jan 31 UK report

Greek ICU study links resistant Klebsiella colonization, blood infections

Greek researchers report that a study of intensive care unit (ICU) patients colonized with carbapenem-resistant Klebsiella pneumoniae (CRKP) found that more than 20% developed CRKP bloodstream infections (BSIs) from their colonizing strains. The findings appear in the Journal of Medical Microbiology.

For the prospective study, which was conducted in a Greek tertiary care hospital over 39 months, researchers enrolled all adults admitted to the ICU to determine the risk factors for CRKP rectal colonization and the incidence of and risk factors for subsequent BSI. CRKP isolates from blood cultures and corresponding patient rectal specimens were screened by polymerase chain reaction (PCR) for the presence of antibiotic-resistance genes, and pulsed-field gel electrophoresis (PFGE) was conducted to investigate the clonal relatedness of the isolates. The researchers also evaluated the time from admission to colonization and BSI.

Over the study period, 226 of 498 patients (45.4%) were rectally colonized with CRKP, and 48 (21.2%) developed a CRKP BSI. The median time from admission to colonization was 8 days, and the median time from colonization to BSI was 4 days. Multivariate analysis showed that the length of ICU stay, patient/nurse ratio, and prior use of antibiotics that disturb the anaerobic flora were independent risk factors for colonization, but no specific risk factors were associated with BSIs in the colonized patients.

PCR analysis of 96 isolates (48 from blood cultures, 48 from corresponding patient rectal specimens) found that all were positive for the blaKPC2 gene and all belonged to sequence type ST-258. PFGE results showed that the BSI and rectal strains from the same patients were identical.

The authors of the study conclude, "A direct correlation between colonization and the progression to BSI was demonstrated. The early detection of asymptomatic CRKP carriers in conjunction with rigorous control measures (contact precautions, hand hygiene, and patient cohorting) and the appropriate management of antibiotic therapy are crucial to prevent the spread of CRKP stains in ICUs."
Jan 28 J Med Microbiol abstract

Study shows some benefits for adding antibiotics to malaria prevention

Adding azithromycin to monthly seasonal malaria chemoprevention in children in Burkina Faso and Mali didn't decrease the incidence of death or hospital admission, but it did lower rates of certain infections, researchers from the London School of Hygiene and Tropical Medicine and their partners in Africa reported yesterday in the New England Journal of Medicine.

The team explored the potential benefits of adding azithromycin to malaria prevention treatment as a way of maximizing the delivery of other health interventions after recent studies showed mass azithromycin administration had some success at lowering childhood mortality and trachoma in sub-Saharan African children.

In July 2014, the researchers randomized children ages 3 to 59 months by household to receive either azithromycin or placebo with sulfadoxine-pyrimethamine plus amodiaquine for seasonal malaria prevention. The drugs were given in four 3-day cycles for three successive seasons. Of 19,578 children, 9,735 received the added azithromycin and 9,843 received placebo.

The researchers didn't see any difference in incidence of death or hospitalization not linked to trauma or surgery, but azithromycin treatment lowered the incidence of gastrointestinal infection, upper-respiratory tract infection, and nonmalarial febrile illness by 15%, 15%, and 21%, respectively. Malaria parasitemia and adverse events were similar among the two groups.
Jan 30 N Engl J Med abstract
Aug 14, 2018, CIDRAP News story "Study: Mass antibiotic use limits but doesn't banish trachoma"

Antifungal candidate shows positive early results in phase 3 trial

Biotechnology company Scynexis released positive interim results yesterday from an ongoing phase 3 study evaluating the novel antifungal ibrexafungerp in patients with difficult-to-treat fungal infections.

An interim efficacy analysis of the first 20 patients treated in the FURI study, which is evaluating oral ibrexafungerp in adults with documented invasive and/or severe mucocutaneous fungal disease that has been intolerant or refractory to standard-of-care treatment, showed clinical benefits in 17 out 20 patients, with 11 patients achieving a complete or partial response and 6 a stable disease response. The drug was also well tolerated.

The company, which is based in Jersey City, N.J., says the results demonstrate the drug's ability to treat fungal infections in vulnerable patients who've failed other therapies.

"The positive results of this interim analysis reassure us of oral ibrexafungerp's clinical benefits in this difficult-to-treat patient population, warranting continued enrollment in the FURI study," Scynexis chief medical officer David Angulo, MD, said in a statement.

Ibrexafungerp is currently in development for treatment of fungal infections cause by Apergillus and Candida species, including Candida auris, and has demonstrated in vivo and in vitro activity against multidrug-resistant pathogens. The drug has been granted qualified infectious disease product (QIDP) and Fast Track designations from the US Food and Drug Administration for treatment of invasive candidiasis, invasive aspergillosis, and vulvovaginal candidiasis.
Jan 30 Scynexis press release

News Scan for Jan 31, 2019

News brief

Two new MERS cases reported in Saudi Arabia

Today Saudi Arabia's Ministry of Health (MOH) reported two new MERS-CoV cases, both in Wadi Al Dawasir, a town in south-central Saudi Arabia.

In an update to its epidemiologic week 5 report, the MOH said the patients were a 44-year-old man and a 62-year-old women, both hospitalized for their MERS-CoV (Middle East respiratory syndrome coronavirus) infections.

Their cases were designated as secondary, community acquired. Neither patient had camel contact.

In the World Health Organization's most recent MERS-CoV update, it said that, as of Dec 31, it had received reports of 2,279 MERS-CoV cases since 2012, at least 806 of them fatal. The Saudi MOH has reported 14 MERS cases this month.
Jan 31 MOH report

Study notes 90% flu vaccine protection against hospitalization in HK kids

An early-season estimate of flu vaccine effectiveness (VE) against hospitalization for influenza in children in Hong Kong has found 90% VE, according to a report today in Eurosurveillance.

Researchers enrolled 2,016 children 6 months to 17 years old from three public hospitals from Sep 2, 2018, through Jan 11, 2019, 180 of whom (8.9%) had been immunized. The investigators used a test-negative design for the study.

Of the children studied, 344 (17.1%) tested positive for influenza A or B. Among those, 85% (292/344) were positive for 2009 H1N1 and 13% (45/344) for the H3N2 strain. Among the 180 vaccinated children, 160 (89%) received the quadrivalent (four-strain) flu vaccine.

Ten of 344 children (2.9%) who tested positive for influenza had been vaccinated, compared with 170 of 1,672 (10.2%) who had not received the vaccine. That amounts to a flu VE of 90% (95% confidence interval, 80% to 95%).

The authors conclude, "Our findings were consistent with previous estimates against influenza A(H1N1)pdm09 in children in Hong Kong from 2012/13 to 2016/17."
Jan 31 Eurosurveill study

Merck gets FDA breakthrough tag for 15-valent pneumococcal vaccine

Merck yesterday announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for V114, its investigational 15-valent (15-strain) pneumococcal conjugate vaccine.

The step helps speed the development and review of drugs for serious or life-threatening conditions for products that have been shown in early clinical trials to provide substantial improvement over currently available therapies.

In a press release, Merck said the designation applies to the prevention of invasive pneumococcal disease in children ages 6 weeks to 18 years. It added that the vaccine is also being developed for preventing the disease in adults and that both indications are currently under evaluation in phase 3 clinical trials.

The FDA based its breakthrough therapy decision partly on immunogenicity data from two studies, one a phase 1 / 2 study to evaluate safety, tolerability, and immunogenicity of four different lots of a new formulation of V114 in healthy adults and infants and another to confirm the first study in a larger population of infants. For both, the vaccine prompted an immune response in infants for two disease serotypes (22F and 33F) not included in the current 13-valent vaccines and showed a similar protection against the serotypes contained in the current vaccine.
Jan 30 Merck press release

Positive phase 1 Lyme vaccine data noted, including booster-dose benefits

Valneva, a biotechnology company based in France, today reported promising early findings for a booster dose regimen and final phase 1 data for its experimental Lyme disease vaccine, VLA15, the only one of its kind in clinical development.

In 2018 the company amended its phase 1 study protocol to add a booster dose to a subgroup, and during the same time it completed follow-up of all people who received all doses, providing the final phase 1 data.

In a press release, Valneva, based in France, said the trial confirmed the safety and tolerability it saw in the interim results for VLA15, a multivalent protein subunit vaccine that targets the outer surface protein A (OspA) of the Lyme disease bacterium, Borrelia burgdorferi. Final findings showed the alum-adjuvanted formulation elicited higher immune responses. As expected, antibody titers dropped after day 84 in all groups, reaching baseline at about 1 year after initial vaccination.

To gauge the benefit of a booster dose, 64 participants in the two higher-dose groups received a booster dose 12 to 15 months after the first dose, which the company said resulted in a significant immune response with antibody titers 2.7- to 5.8-fold higher than the titers at day 84, which it says is consistent with other Lyme vaccines in development that target OspA.

Last month, Valneva announced that the vaccine had entered a phase 2 trial at study sites in the United States and Europe.
Jan 31 Valneva press release
Dec 18, 2018, CIDRAP News scan on phase 2 announcement