AAP issues guidance on alternatives to in-shortage amoxicillin

News brief

Amid a shortage of the antibiotic amoxicillin, the American Academy of Pediatrics (AAP) has issued guidance on alternatives to the oral powder formulation for suspension in its Red Book Online.

The shortage, which is expected to last several months, is being fueled by increased demand as many US children are ill with respiratory diseases such as the flu, COVID-19, and respiratory syncytial virus (RSV), according to amoxicillin manufacturers reporting shortages to the US Food and Drug Administration (FDA). Though antibiotics aren't indicated for these viral illnesses, clinicians may prescribe them presumptively.

The AAP first urges clinicians not to prescribe antibiotics to patients with viral illnesses, because overprescribing can lead to antibiotic resistance. If antibiotics are indicated, pediatricians can use alternative amoxicillin formulations not in shortage (eg, tablets, capsules, chewable tablets), rounding doses to within 10% of 125, 250, 500, 750, 875, or 1,000 milligrams, the AAP said.

To use tablets in pediatric patients, clinicians can split or crush them, and they can open capsules and split chewable formulations and mix them with liquid or a semisolid such as applesauce to be given by mouth or tube.

If amoxicillin isn't available or can't be used in a patient owing to hypersensitivity, the guidance said, pediatricians can treat ear infections with amoxicillin/clavulanate or intramuscular ceftriaxone, community-acquired pneumonia or sinusitis with amoxicillin/clavulanate, and pharyngitis caused by group A Streptococcus with Penicillin VK, intramuscular penicillin G benzathine x 1, or cephalexin. Penicillin VK can be used for infection prevention after spleen removal.

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Clinical trial will examine early transition from IV to oral antibiotics

News brief

Researchers at Johns Hopkins University have received $10 million to conduct a clinical trial that will investigate whether early transition to oral antibiotic therapy from intravenous (IV) administration improves outcomes in patients with gram-negative bloodstream infections.

The funding from the Patient-Centered Outcomes Research Institute will support a randomized controlled trial that will involve roughly 1,200 patients with bloodstream infections at eight US hospitals. The patients will be randomly assigned to two groups—one that receives IV antibiotics for the entire duration of therapy and one that starts on IV therapy, followed by an early transition to oral antibiotics.

Patients with bloodstream infections caused by gram-negative bacteria, such as Escherichia coli, have been traditionally treated with IV antibiotics. If patients are discharged home or to a skilled nursing facility, a vascular catheter is required to continue the treatment.

"However, because vascular catheters used to place IV lines can pose a risk of a secondary infection and other complications, and because IV therapy imposes limitations on patient mobility and quality of life, we want to see if oral antibiotic treatment—pills—given at an early stage in the process could achieve outcomes on par with those of IV antibiotics," co-principal investigator Pranita Tamma, MD, MHS, who directs the Pediatric Antimicrobial Stewardship Program at Johns Hopkins Children's Center, said in a university press release.

Tamma and her colleagues say they will use a novel analytical approach to determine efficacy and safety.

Small UK study shows 78% protection from 1 dose of monkeypox vaccine

News brief

New UK Health Security Agency (HSA) data that are not yet peer-reviewed indicate that a single Jynneos vaccine dose provides 78% protection against monkeypox 14 days or more after vaccination, but the number of vaccinated men in the study was small.

For the study, published yesterday, HSA scientists and their UK colleagues analyzed monkeypox cases in England from Jul 4 to Nov 3 involving men who have sex with men at high risk for the disease. Of the 363 monkeypox patients during this period, 8 had been vaccinated at least 14 days before, and 32 had been vaccinated between 0 to 13 days before. The other 323 had not received a Jynneos vaccine.

The authors said the estimated vaccine effectiveness (VE) 14 or more days after a single dose was 78% (95% confidence interval [CI], 54% to 89%). For men vaccinated 13 days or less, VE was -4% (95% CI, -50% to 29%).

Senior author Jamie Lopez-Bernal, MBBS, MScPH, consultant HSA epidemiologist, said in an agency news release, "We now know that a single vaccine dose provides strong protection against monkeypox, which shows just how important vaccination is to protect yourself and others. A second dose is expected to offer even greater and longer lasting protection."

The authors note that the results are similar to findings from an Israeli study in late September that was also not peer-reviewed. Also, US data published around the same time showed that at-risk unvaccinated people have a 14-times-greater risk of contracting the disease. VE data published so far, however, have not factored in people's changing behavior.

At the time of the US study, Michael T. Osterholm, PhD, MPH, director of the University of Minnesota's Center for Infectious Disease Research and Policy, publisher of CIDRAP News, said there were too many unaccounted-for variables in the data. "People who seek out vaccines may be behaving differently from people who don't," he explained. "Did they also take a pause on sexual behavior?"

In fact, the authors of the new study write, "Behavioural changes post-vaccination may also have affected VE estimates; for example, if vaccinated individuals were less likely to abstain from high-risk sexual activity as a result of having received the vaccine then the pharmacological effectiveness would be underestimated."

Antibiotic sales are rising on Canadian farms, report finds

News brief

Canada saw an increase in the sales of antibiotics for use in food production animals in 2020, according to a report released this week by the Canadian government.

Data from the Canadian Integrated Program for Antimicrobial Resistance and Surveillance (CIPARS) show that the overall sales of antibiotics intended for use in production animals (food animals and horses) rose by 6.5% from 2019 to 2020, and by 7.5% when accounting for the number of animals and their weights (animal biomass). The increase was primarily driven by increased sales of antibiotics for use in beef cattle, pigs, and veal calves, as sales of antibiotics for use in poultry and aquaculture declined and sales of antibiotics for dairy cattle, horses, dogs, and cats remained stable.

The report notes that, after adjusting for the underlying biomass, there were approximately 1.8 times more antibiotics sold for use in production animals than for people.

Antimicrobial resistance surveillance on Canadian farms revealed a mixed picture. In poultry and grower-finisher pigs, the trend in resistance to three or more antibiotic classes declined in Escherichia coli, and Salmonella and Campylobacter from pigs also showed lower rates of multidrug resistance. But resistance to ciprofloxacin continued to rise in Campylobacter from broiler chickens and healthy feedlot cattle.

CIPARS also detected colistin-resistant E coli and Salmonella isolates from three surveillance sources.

Study ties Paxlovid to lower COVID-19 hospitalization rate

News brief

Adult US COVID-19 patients who received the antiviral drug Paxlovid within 5 days after diagnosis had a 51% lower hospitalization rate than nonrecipients, according to an observational study yesterday in Morbidity and Mortality Weekly Report.

Researchers from the Centers for Disease Control and Prevention (CDC) and Epic Research in Verona, Wisconsin, analyzed the electronic health records of 699,848 high-risk COVID-19 outpatients eligible to receive nirmatrelvir-ritonavir (Paxlovid) amid Omicron variant predominance, from Apr 1 to Aug 31, 2022. Of that number, 28.4% received Paxlovid within 5 days after diagnosis.

Many patients had previous COVID-19 infections or were vaccinated against the virus. A total of 92.4% of Paxlovid recipients had at least one chronic condition.

In the 30 days after diagnosis, 0.75% of the total population were hospitalized, 63.3% of them people 65 and older. Of the 198,927 Paxlovid recipients, 0.47% were hospitalized, compared with 0.86% of 500,921 nonrecipients.

Among the 5,229 hospitalized patients, 17.8% received Paxlovid within 5 days of diagnosis. A total of 211 in-hospital deaths occurred, for a death rate among Paxlovid recipients of 0.01%, compared with 0.04% of nonrecipients.

Paxlovid was tied to an overall lower hospitalization rate within the next 30 days than that of nonrecipients (adjusted hazard ratio [aHR], 0.49). aHRs among recipients were lower in recipients of at least three doses of mRNA vaccine (0.50), in all age-groups (18 to 49 years aHR, 0.59; 50 to 64 aHR, 0.40; and 65 and older aHR, 0.53). In the total population, Paxlovid was linked to a lower rate of all-cause hospitalization (aHR, 0.45) and hospitalization for acute respiratory illness (aHR, 0.48).

The authors noted that the initial Paxlovid clinical trial, which showed an 89% reduction in severe COVID-19, was conducted in unvaccinated, COVID-naïve people before Omicron.

"The ease of oral administration, short duration of therapy, and lower likelihood for resistance make Paxlovid a useful antiviral," they wrote. "Paxlovid should be offered to eligible adults irrespective of vaccination status, especially in groups with the highest risk for severe COVID-19 outcomes, such as older adults and those with multiple underlying health conditions."

Novel malaria combination drug to be tested in phase 3 trial

News brief

Pharmaceutical company Novartis and the Medicines for Malaria Venture (MMV) announced today that they are moving forward with a phase 3 trial for a novel combination drug for patients with uncomplicated malaria.

The phase 3 trial will test the efficacy of ganaplacide/lumefantrine-solid dispersion formulation (SDF) against the current standard treatment, artemether-lumefantrine, in patients with acute uncomplicated malaria caused by the Plasmodium falciparum parasite. The hope is that the drug could be an alternative to artemisinin-based treatments, which are being increasingly challenged by artemisinin-resistant strains of malaria.

Ganaplacide is a novel agent with a new mechanism of action, while lumefantrine-SDF is an optimized formulation that allows for once-daily administration. The combination has shown the potential to clear malaria infections, including those caused by artemisinin-resistant strains, and block the transmission of the malaria parasite.

Artemisinin-resistant malaria is widespread in the Greater Mekong Subregion of Southeast Asia, and in recent years has shown evidence of emergence in Africa, where 90% of malaria cases and deaths are reported.

"We are increasingly seeing parasites with decreased sensitivity to artemisinin, even in Africa," MMV Chief Scientific Officer Timothy Wells, PhD, said in a Novartis press release. "If the Phase 3 trial is successful, this new combination will increase the number of options available to countries and help save the lives of children at risk of this devastating disease."

Ganaplacide/lumefantrine-SDF was granted Fast Track and Orphan Drug designations by the US Food and Drug Administration in August 2022.

The trial will be conducted at clinical sites in Burkina Faso, Mali, Gabon, Niger, and other sub-Saharan African countries.

US high-path avian flu poultry losses reach 2015 record

News brief

Over the past few days, the US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) reported more highly pathogenic avian flu outbreaks in five states, which put the nation's poultry losses for the year at 50.5 million, which ties the record set in the outbreaks of 2015.

One of the latest outbreaks involved a turkey farm housing 29,200 birds in South Dakota's Beadle County. In Utah, the virus struck a petting zoo and exhibition farm in Utah County that houses 270 birds. Elsewhere, outbreaks affected backyard birds in Missouri, Maine, South Dakota, and North Carolina.

The outbreaks involve a Eurasian H5N1 strain that first cropped up in US poultry in February, eventually spreading to 46 states so far.

The virus has fueled outbreaks in multiple world regions. The World Organization for Animal Health (WOAH) in its latest monthly situation report, which covers avian flu outbreaks Oct 12 through Nov 10, reported 140 outbreaks in poultry and 110 outbreaks in wild birds. Most were in Europe and the Americas, but some were reported from Africa and Asia. The predominant subtype was H5N1.

WOAH noted the first H5N1 detection in Colombia, which marked the first appearance of high path avian flu in South America in about two decades. The group warned that outbreak activity is expected to rise in the coming months, and it urged countries to maintain their surveillance efforts and for producers to beef up their biosecurity practices.

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