FDA approves new IV antibiotic for complicated urinary tract infections

News brief

Chicago-based drugmaker Meitheal Pharmaceuticals said yesterday that the US Food and Drug Administration (FDA) has approved its intravenous (IV) formulation of fosfomycin for treating adults with complicated urinary tract infections (cUTIs) caused by Escherichia coli and Klebsiella pneumoniae.

Marketed under the brand name Contepo, the IV antibiotic has a novel mechanism of action, has no known cross-resistance, and is the only IV-administered epoxide antibiotic approved in the United States, the company said in a press release. FDA approval was based on the results of the phase 2/3 ZEUS trial, which found that IV fosfomycin was noninferior to piperacillin/tazobactam in hospitalized patients with cUTIs, including pyelonephritis, and was generally well-tolerated.

The trial results showed that overall success—defined as clinical cure and microbiologic eradication at the test-of-cure visit—was achieved in 108 (63.5%) of 170 patients receiving IV fosfomycin and 94 (55.6%) of 169 of those receiving piperacillin/tazobactam, with a treatment difference of 7.9 percentage points.

"With an estimated three million cases of cUTIs treated in the hospital setting annually, there is a critical need for a safe and effective treatment option," said Keith Robinson, MD, Chief Medical Officer of Meitheal Pharmaceuticals. "Contepo's safety, efficacy, and novel mechanism of action makes it a favorable new treatment option."

The order of pre-COVID chronic conditions may best predict long-COVID risk

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Mary Van Beusekom, MS

Graphic of woman with long COVID — *Jobalou / iStock*

The sequence of chronic conditions before COVID-19 infection—rather than any single condition—may best predict the development of persistent symptoms, a study of Catalonians in northeastern Spain reveals.

For the study, published last week in BMC Medicine, investigators at the Germans Trias i Pujol Research Institute (IGTP) in Barcelona analyzed data from 8,322 participants aged 40 to 65 years at enrollment from the COVICAT cohort and followed them from 2020 to 2023.

The team reconstructed disease trajectories using electronic health records from 2010 to 2019, focusing on sequences of two chronic conditions (found in at least 1% of the cohort). It also assessed shared genetic makeup and risk for predictive capacity.

38 trajectories tied to higher risk of long COVID

Of the 162 trajectories analyzed, 38 were linked to a significantly higher risk of long COVID, regardless of the severity of COVID-19 infection.

It is not enough to know which diseases a person has.

Natalia Blay, MS

The most common sequences involved mental illnesses and neurologic, respiratory (eg, asthma), and metabolic or digestive diseases (eg, high blood pressure, obesity). For example, COVID-19 patients who had anxiety before depression had a different risk profile from those who had depression before anxiety.

"It is not enough to know which diseases a person has," lead author Natalia Blay, MS, said in an IGTP news release. "The order in which they appear can significantly influence risk, especially among women."

The study found no strong genetic link to long COVID, although weak relationships were identified in genetic factors tied to neurologic or musculoskeletal disorders.

The researchers say that artificial-intelligence tools could help detect complex patterns in disease-trajectory sequences in large longitudinal health datasets, improving the ability to predict risks and more precisely identify vulnerable populations that may benefit from targeted prevention and care.

The findings show that studying trajectories in longitudinal data "has value beyond COVID, as it allows us to identify population health patterns that may help predict other diseases and support a more preventive and personalised public health approach," principal investigator Rafael de Cid, PhD, said.

Study: Demographic shifts will fuel increase in drug-resistant bloodstream infections in Europe

News brief

Chris Dall, MA

Hospital patient with IV in arm — *Cunaplus_M.Faba / iStock*

A new study predicts that the rate of bloodstream infections (BSIs) caused by drug-resistant bacteria will rise sharply in Europe over the next 5 years, driven primarily by an aging population, researchers reported yesterday in PLOS Medicine.

For the modeling study, a team led by researchers at the London School of Hygiene and Tropical Medicine analyzed data from more than 12 million blood tests for bacterial infections conducted in 29 European countries from 2010 through 2019, then used the data to project BSI incidence rates by age and sex through 2050, fitting the models across 38 bacteria-antibiotic combinations. The study builds on previous work by the team showing that BSI prevalence in Europe is strongly determined by the age and sex of the patient.

"With substantial sub- and national-variation, the consistency and clear shape of some relationships provide evidence for the inclusion of age and sex in any predictions of future AMR [antimicrobial resistance] burden," the study authors wrote.

Dramatic increase in older age-groups

As with their previous study, the researchers found that the burden of drug-resistant BSIs will vary substantially by country and by drug-bug combination. They also found that BSI rates are predicted to increase more in men than in women across six of eight bacterial species and to increase dramatically in older age-groups (74-plus years) by 2030, while stabilizing or declining in younger groups. Even with strong public health actions, they found that achieving a 10% reduction in BSI incidence by 2030 was only possible for two thirds of the bacteria-antibiotic combinations

Age and sex are still rarely considered in antimicrobial resistance projections, yet they make a real difference to who is most affected.

The authors say AMR modeling studies that don't account for age and sex may miss a large part of the future burden.

"Age and sex are still rarely considered in antimicrobial resistance projections, yet they make a real difference to who is most affected," senior study author Gwenan Knight, PhD, said in a journal press release. "Combining these factors with demographic and infection trends really highlighted how challenging it will be to reverse the steady rise in bloodstream infections across Europe."

Knight and her colleagues add that future intervention strategies should consider who will be most affected by drug-resistant BSIs and how the impact may be mitigated.