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The FDA has approved a new drug for certain UTIs. Getty Images
  • A new drug called cefiderocol (Fetroja) has been approved by the FDA to treat certain UTIs.
  • The drug is only to be used as a last resort when other antibiotics have failed.
  • A lack of new antibiotics has led the CDC to warn that antibiotic-resistant infections are on the rise and a danger to public health.

Bacterial infections that are resistant to treatment are on the rise in the United States, with an estimated 2.8 million antibiotic-resistant infections occurring each year, according to the Centers for Disease Control and Prevention (CDC).

Now the Food and Drug Administration (FDA) has announced there’s another drug available that may help stop even drug-resistant urinary tract infections.

The FDA approved the antibiotic cefiderocol (Fetroja) this month.

The drug was approved for adults with complicated urinary tract infections, including kidney infections caused by susceptible gram-negative microorganisms. The patients otherwise have limited treatment options or none at all, as some gram-negative bacteria have been more likely to be resistant to antibiotic medications.

Cefiderocol (Fetroja) was tested in a study of 448 patients with complicated urinary tract infections. Of those who took cefiderocol, 72.6 percent of them had symptoms resolve about 7 days into treatment. Of those who received another antibiotic, 54.6 percent had the same results.

There’s a warning label on the drug, as higher all-cause mortality was observed in patients who used cefiderocol compared to other antibiotics. Some of the reasons people died were due to the infection getting worse or other comorbidities. Patients who died included those with hospital-acquired/ventilator-associated pneumonia, bloodstream infections, and sepsis.

“This drug shows that we are able to overcome many common mechanisms of resistance, but there are likely to be other bacteria that can overcome this, so continued research and development by both academia and pharma is required,” Dr. Robert A. Bonomo, chief of medical service at the Louis Stokes Cleveland Department of Veteran Affairs Medical Center.

Most patients on cefiderocol had side effects including diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion site reactions, candidiasis (yeast infection), cough, headache, and hypokalemia (low potassium). Patients who have a history of severe hypersensitivity to beta-lactam antibacterial drugs are advised not to take it.

Cefiderocol has the FDA’s Qualified Infectious Disease Product (QIDP) designation, which means it can treat serious infections. It was approved under the Priority Review protocol that offers expedited review. Shionogi & Co. will be producing the drug.

“Complicated UTIs due to multidrug-resistant bacteria can be very hard to treat, especially in hospitalized patients that are very ill,” Bomono said.

Patients with multidrug-resistant UTIs, which can be due to certain bacteria like Pseudomonas, Acinetobacter, or Klebsiella pneumoniae, have few options as far as treatment.

Currently, drugs such as colistin are used as last resort options.

But it’s been problematic to estimate the potency of multiple drugs, as the pharmacological and toxicity parameters are difficult to measure.

“In the trials using colistin, not enough patients were studied correctly, Bonomo said.

Some new testing has found potentially positive news about some of these drugs, which is a good thing, Bomono said, because doctors are scrambling for solutions.

“Physicians have rapidly escalated to therapies that are unproven and of questionable merit, as their choices often are very limited,” he said.

Much of the time, complicated UTIs cannot be treated with a simple course of regular antibiotics because there is another underlying issue. Often, urinary obstruction or undrained abscesses are to blame, noted Dr. Nicolas Cortes-Penfield, an assistant professor at University of Nebraska Medical Center.

This is why he’s “cautious” about being an early adopter of cefiderocol.

The FDA labeling for cefiderocol was specifically approved for complicated urinary tract infections in gram-negative organisms with limited or no treatment options.

“In other words, they recommend it be used only as a drug of last resort,” he explained.

Cefiderocol did well in a trial last year, and was not inferior to a high-dose antibiotic called meropenem in another trial. But another study that’s still incomplete pitted it against the best-available therapy for gram-negative organisms across a wide variety of infections. There was reportedly a strong signal toward increased all-cause mortality among the cefiderocol recipients, Cortes-Penfield said.

“This gives me pause, because of course the truth of antibiotic approvals is that every new gram-negative drug gets labeled for complicated urinary tract infections and then in practice we infectious disease docs start using it for everything under the sun,” Cortes-Penfield explained.

Cortes-Penfield said it’s possible that cefiderocol may go the way of another antibiotic called tigecycline, which was also developed to treat drug-resistant infections.

He wants to wait to read more about the final study mentioned and hear about more real-world applications before he starts using it.

“I certainly think it’s too soon to call cefiderocol our savior from the post-antibiotic era, although I do think that with its activity against carbapenem-resistant Acinetobacter and metallo beta-lactamase carpabenemases [two superbugs] it’s an important step forward in a way that previous new gram-negative antimicrobials were not,” he added.