Stewardship / Resistance Scan for Oct 16, 2019

News brief

FDA advisory committee reviewing new drug application for cefiderocol

The US Food and Drug Administration (FDA) Antimicrobial Drugs Advisory Committee is meeting today to discuss the new drug application (NDA) for cefiderocol, an investigational antibiotic developed by Shionogi, Inc, a US-based subsidiary of Japanese pharmaceutical company Shionogi & Co. The company is seeking FDA approval of the drug for the treatment of complicated urinary tract infections (cUTIs) caused by gram-negative bacteria in patients with limited or no alternative treatment options.

As reported by Endpoint News, a website that covers the pharmaceutical industry, one of the questions the committee will be discussing is an imbalance in deaths in the CREDIBLE-CR trial, a phase 3 study that compared cefiderocol against the best available therapy (BAT) in patients with cUTIs, hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), and bloodstream infections or sepsis caused by carbapenem-resistant infections. According to the FDA's briefing document, an independent adjudication committee found that a greater percentage of patients in the cefiderocol group had infection-related death with treatment failure than in the BAT group (15.8% vs 8.2%), but also noted an imbalance in deaths due to underlying comorbidities (9.9% vs 4.1%).

"Whether this difference in mortality is a chance finding or truly reflects a deficit in the activity of cefiderocol in critically ill patients is unclear," the FDA wrote.

The committee will also review the results of two other clinical trials: a phase 2 trial that tested cefiderocol against imipenem-cilastatin for treating cUTIs with or without pyelonephritis caused by gram-negative bacteria, and a phase 3 trial that tested cefiderocol against meropenem for the treatment of HABP caused by gram-negative bacteria.

Cefiderocol is a siderophore cephalosporin with a novel method of penetrating the tough outer membrane of gram-negative bacteria, including carbapenem-resistant pathogens. The drug was designated as a Qualified Infectious Disease Product (QIDP) by the FDA, a designation given to antibacterial or antifungal products that treat serious or life-threatening infections and address unmet medical needs. QIDPs are eligible to be fast-tracked for FDA approval.

The FDA has assigned an action date of Nov 14 to the drug.
Oct 14 Endpoint News story
Oct 16 FDA briefing document
Oct 26, 2018, CIDRAP News story "Fast-tracked antibiotic shows promise in phase 2 trial"
Oct 3 CIDRAP Stewardship/Resistance scan on HABP data

Study analyzes infections, antibiotic use in emergency departments

New data from 145 US emergency departments (EDs) indicates that antibiotic prescribing patterns for the most commonly diagnosed infections generally align to treatment guidelines, according to a study yesterday in the American Journal of Health-System Pharmacy. But researchers also found areas for improvement based on local susceptibility patterns.

For the study, researchers from HCA Healthcare—a large multistate network of hospitals—and Harvard Medical School used electronic medical records to examine ED encounters at 145 HCA hospitals from July 2016 through June 2017. Their aim was to assess the most common diagnoses of infectious origin seen in non-admitted ED patients, the most commonly administered antibiotics in the ED, and the unique patterns of resistance and susceptibility in the 14 geographic areas covered by the network. The generalizability of the results to the national population was assessed using patient demographic data.

Overall, more than 627,000 unique patient encounters and 780,000 antibiotic administrations were assessed. The five most frequently identified infections were UTI, cellulitis, pneumonia, Streptococcal pharyngitis, and otitis media (ear infection). The five most commonly administered antibiotics were ceftriaxone, azithromycin, clindamycin, levofloxacin, and cephalexin. While patterns of treatment generally adhered to treatment guidelines, the analysis found possible overuse of ceftriaxone—which accounted for 30.6% of all antibiotics administered—across all indications.

In addition, the assessment of resistance and susceptibility patterns determined that clindamycin—the antibiotic most commonly used for cellulitis—is becoming less viable for treating Staphylococcus-suspected cellulitis, and that resistance is developing in Escherichia coli to sulfamethoxazole-trimethoprim in regions where the drug is used to treat UTIs.

"The results of this study can be applied to health-system EDs of varying sizes to assess current antimicrobial stewardship program practices and to identify opportunities to optimize empiric antibiotic selection based on susceptibility patterns and evidence-based treatment recommendations," the authors of the study write.
Oct 15 Am J Health Syst Pharm study

News Scan for Oct 16, 2019

News brief

Three major health associations issue joint flu shot recommendation

Yesterday three of the nation's biggest health organizations—the American Lung Association, the American Diabetes Association, and the American Heart Association—recommended that Americans living with chronic health conditions get this year's seasonal influenza vaccine.

"Getting the flu can lead to complications with very serious consequences for people with cardiovascular disease, including hospitalization, increased risk for other major health events like heart attacks or strokes, and death," said the American Heart Association Chief Medical Officer for Prevention Eduardo Sanchez, MD, in an American Lung Association press release. "Flu vaccination is a good idea for all and has actually been associated with lower rates of some cardiac events."

This is the first time the three groups have made a joint statement on the flu vaccine. They said the 117 million Americans currently living with chronic diseases are at increased risk of complications from the flu. Last flu season, 93% of adults hospitalized for flu reported at least one underlying medical condition, the groups said.

According to the news release, getting an annual flu shot reduces the chance of hospitalization by 37% and the risk of admission to the intensive care unit by 82% for patients with chronic health conditions.
Oct 15 American Lung Association press release

Avian flu outbreaks strike poultry in Vietnam, Dominican Republic

Vietnam's agriculture ministry recently reported another highly pathogenic H5N6 avian flu outbreak in poultry, according to a notification today from the World Organization for Animal Health (OIE), and the Dominican Republic detailed outbreaks involving a low-pathogenic strain.

The event began on Oct 15 in village birds in Kon Tum province in the central part of the country. The virus infected all 980 susceptible birds, which were then euthanized to contain the outbreak. Vietnam's last H5N6 outbreak occurred in August, affecting village birds in Ben Tre province in the south.

H5N6 has been implicated in poultry outbreaks in China and a few other Asian countries, but China is the only one to report human cases, which are often severe or fatal.
Oct 16 OIE report on H5N6 in Vietnam

The Dominican Republic reported 11 more outbreaks involving low-pathogenic H5N2 in poultry, according to a separate OIE report. The outbreak start dates range from Nov 2, 2018, to Jun 2, 2019.

The virus struck birds in seven different provinces: Puerto Plata, Espaillat, Distrito Nacional, Salcedo, La Vega, San Jose De Ocoa, and Santiago. Two outbreaks involved backyard birds and the others occurred at farms. Poultry types included layers, fighting hens, broilers, and Israeli-bred hens.

In total, the virus killed 5,573 of 500,456 susceptible birds, and the surviving ones were culled. The country's last outbreaks involving H5N2 occurred in April in Espaillat province.
Oct 16 OIE report on low-path H5N2 in the Dominican Republic

Samoa declares measles epidemic with 7 cases, 1 fatality

Government officials in Samoa have declared a measles epidemic after two adults and five children have tested positive for the virus. Measles is also highly suspected in the death of a 1-year-old last week, officials said, Radio New Zealand (RNZ) reported.

None of the seven confirmed case-patients were vaccinated.

Helen Petousis-Harris, PhD, a vaccinologist with Auckland University in New Zealand, said measles vaccination coverage in Samoa is low, around 31%. A coverage rate of 95% is needed to confer herd immunity, because measles is a highly contagious disease.

New Zealand has also recently reported a measles outbreak, and travel between Samoa and New Zealand is likely implicated in Samoa's epidemic.
Oct 16 RNZ report