Stewardship / Resistance Scan for Aug 20, 2019

News brief

Study supports shorter parenteral antibiotics for infants with bacteremic UTIs

A study of infants who had bacteremic urinary tract infections (UTIs) indicates that short-course parenteral antibiotic therapy may be considered as a treatment option, a team of US researchers reported today in Pediatrics.

In the multicenter retrospective cohort study, conducted at 11 geographically diverse US children's hospitals, researchers with the Febrile Young Infant Research Collaborative examined the association between parenteral antibiotic duration and clinical outcomes in infants younger than 60 days who had a UTI with concomitant bacteremia. UTIs are a common bacterial infection in young infants, and approximately 8% to 10% have bacteremic UTIs. Yet no evidence-based treatment guidelines exist in this population, and infants with bacteremic UTIs frequently receive prolonged courses of parenteral antibiotics, which can lead to complications, prolonged hospitalization, and increased costs.

The primary outcome of the analysis was UTI recurrence resulting in an emergency department visit or hospitalization within 30 days of discharge. Secondary outcomes included length of hospitalization and 30-day all-cause hospital reutilization.

Among the 115 infants treated for bacteremic UTIs from 2011 through 2016, 58 received short-course parenteral antibiotic therapy (defined as 7 days or less) and 57 received long-course antibiotics (7 days or more). Six infants had a recurrent UTI, and no significant difference was found in the rates of recurrent UTI between the two treatment groups (adjusted risk difference, 3%; 95% confidence interval [CI], –5.8 to 12.7). Fifteen infants had 30-day all-cause reutilization, with no significant difference found in the rates of reutilization between the two groups (adjusted risk difference, 3%; 95% CI, –14.6 to 20.4). The adjusted mean hospital duration was significantly longer in the long-course group compared with the short-course group (adjusted mean difference, 6 days; 95% CI, 4.0 to 8.8).

The authors of the study conclude, "Our data indicates that ≤7 days of parenteral antibiotic therapy may be safe in this population. Researchers in future prospective studies should seek to establish the bioavailability and optimal dosing of oral antibiotics in young infants and assess if there are particular subpopulations of infants with bacteremic UTI who may benefit from longer courses of parenteral antibiotic therapy."
Aug 20 Pediatrics study

CARB-X awards funds for developing vaccine against resistant Klebsiella

CARB-X today said it is awarding Vaxxilon AG of Reinach, Switzerland, up to $1.4 million—and possibly more—to develop a multivalent vaccine to prevent infections caused by carbapenem-resistant Klebsiella pneumoniae, an invasive and deadly gram-negative bacterium.

Arne von Bonin, PhD, chief scientific officer and head of immunology at Vaxxilon, said in a CARB-X news release, "CARB-X's award will support the development of VXN-319, a semi-synthetic conjugate vaccine targeting multiple strains of Klebsiella pneumoniae, one of the top priority critical pathogens identified by the World Health Organization."

Vaxxilon said it expects the vaccine would protect against more than 80% of carbapenem-resistant strains of K pneumoniae. To create VXN-319, Vaxxilon scientists synthesized the carbohydrates that resemble the coating that surrounds each bacterial cell. They then combined the synthetic carbohydrates with other components to create a conjugate vaccine similar to those that have been approved to prevent infections from bacteria such as Streptococcus pneumoniae and Haemophilus influenzae type B.

"Vaccines are vital tools in the fight against disease and drug-resistant bacteria, with the potential to prevent infections and reduce the spread of life-threatening bacteria," said Kevin Outterson, JD, CARB-X executive director and professor of law at Boston University. "Vaxxilon's vaccine, if approved for use in patients, could prevent deadly infections and save the lives of thousands of patients."

Vaxxilon could receive $3.1 million in additional funding if certain project milestones are met, according to CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator). Since its inception in 2016, CARB-X has announced awards for 46 projects in seven countries exceeding $134 million total.
Aug 20 CARB-X news release

News Scan for Aug 20, 2019

News brief

DRC Ebola total grows by 10; newly affected areas linked to Beni

The rate of Ebola cases in the Democratic Republic of the Congo (DRC) outbreak shows a slight decline, with Beni and Mandima still remaining as the main hot spots, according to a weekly outbreak and emergencies report from the World Health Organization (WHO) African regional office that covers cases through Aug 17.

Recent spread to South Kivu province and Pinga health zone in North Kivu province are linked to Beni, which officials have said continues to seed the virus to other areas.

The WHO said it is critical that local transmission in the newly affected areas is curbed with robust control measures, as was done recently in Goma, the capital of North Kivu province.

In other outbreak developments, the DRC confirmed 10 new cases, pushing the overall outbreak total to 2,909, according to the WHO's online Ebola dashboard today, which reflects cases reported as of Aug 18. Health officials are still investigating 301 suspected cases. The number of deaths remained at 1,934.
Aug 20 WHO African regional office weekly outbreak and emergencies report
WHO online Ebola dashboard

WHO: Flu activity still brisk in parts of Australia

Flu levels have peaked in most Southern Hemisphere countries, except for parts of Australia, the WHO said yesterday in its latest global flu update.

Australia's flu season started earlier than previous seasons. Though activity seems to have peaked in Southern Australia, Victoria, New South Wales, and Tasmania, so far Queensland's levels haven't peaked. H3N2 is the main strain, followed by influenza B.

In New Zealand, flu levels are dropping, but activity is still elevated, with both H3N2 and influenza B strains detected. In both countries, markers for severe infections such as hospitalizations and intensive care unit admissions have been low. Meanwhile, in temperate parts of South America, flu levels declined with all strains circulating except in Uruguay, which reported a slight uptick in 2009 H1N1 detections.

Elsewhere in the world, flu levels remained low except for Myanmar, where activity is still high, led by 2009 H1N1 and in Madagascar, which is experiencing a rise in influenza B illnesses.

Globally, influenza A made up 63.9% of detections reported for the week ending Aug 4. Of the subtyped influenza A strains, 61.1% were H3N2 and 38.9% H1N1.
Aug 19 WHO global flu update

NIAID awards $2.2 million for broadly protective flu patch vaccine candidate

The National Institute of Allergy and Infectious Diseases (NIAID) awarded the developers of the MIMIX flu vaccine up to $2.2 million in funding yesterday.

Scientists from Vaxess Technologies, Inc. of Cambridge, Massachusetts, the maker of MIMIX, use smart release technology in the flu vaccine patch, designed to be worn for an extended period. Vaxess says the patch delivery system more closely replicates a natural flu infection and thus triggers a more protective immune response. The makers of the patch also say the vaccine will protect against both vaccine-included and drifted influenza strains.

"The MIMIX smart release patch has demonstrated to increase existing flu vaccine efficacy and advancing toward the creation of a universal flu vaccine quickly," said Vaxess vice president of policy and strategy, Livio Valenti in a Vaxess news release. "Moreover, the patch does not require refrigeration, is painless, and can be easily administered at home; additional benefits that will increase immunization rates here in the US and globally."

The NIAID funding will help launch the phase 1 trail of MIMIX.
Aug 19 Vaxess press release

FDA gives fast-track designation to Zika vaccine

Yesterday Moderna, Inc., also of Cambridge, announced that the US Food and Drug Administration (FDA) has granted "Fast Track" designation for its investigational Zika vaccine, mRNA-1893, currently being evaluated in a phase 1 study in healthy adults.

Fast Track designation helps expedite the review of vaccines and medications for unmet medical needs.

"Protecting against Zika virus transmission, particularly in women during pregnancy, continues to be an area of high unmet need. Fast Track designation supports our belief in the clinical potential of mRNA-1893 and the importance of developing an effective vaccine that can be rapidly developed and deployed," said Tal Zaks, MD, PhD, chief medical officer at Moderna, in a company press release.

"Our Zika program is part of Moderna's broader commitment to improving global public health through developing mRNA vaccines to prevent the spread of infectious diseases."

In mouse studies, mRNA-1893 was protective against Zika in pregnancy. It contains an mRNA sequence encoding for the structural proteins of Zika virus and is designed to cause cells to secrete virus-like particles, Moderna said in the release.
Aug 19 Moderna press release