More Days, More Resistance: Time to Rethink Antibiotics

Medscape

9 hours ago

'One of the most universally accepted beliefs around the world,' said Brad Spellberg, MD, chief medical officer at Los Angeles General Medical Center, 'is that when you take antibiotics, you must complete the prescribed course — 7, 10, or 14 days — even after you start feeling better, in order to eliminate every last bacterium and prevent a future relapse.'
'But that recommendation doesn't make sense. There's no data to support it,' Spellberg noted in a virtual lecture at the 2025 Argentine Society of Infectious Diseases Congress, held in Mar del Plata from June 12 to 14.
'That's not how antibiotics work. Every additional day you take an antibiotic increases resistance,' he emphasized.
Spellberg cited two quotes from Louis Rice, MD, chair of the Department of Medicine at the Warren Alpert Medical School of Brown University, Providence, Rhode Island, and former president of the Infectious Diseases Society of America:
'The most viable strategy for reducing antimicrobial selective pressure is to treat infections only for as long as is necessary.'
'[Completing the prescribed antibiotic regimen] may be excellent advice when one wants to have patients take an adequate course to treat an infection, but it is poor advice for preventing resistance.'
'We should tell patients: 'If you're taking antibiotics, and you feel better but still have a few days left, call me, and we'll decide whether to stop,'' Spellberg advised.
He added that if you prescribe 14 days of antibiotics for an infection, the patient is still taking them for a week after symptoms resolve. 'But if you prescribe 5-7 days, stopping early isn't a problem. So, we can resolve everything simply by switching to short-course therapy.'
'Shorter Is Better'
Spellberg's stance isn't new. A decade ago, he coined the mantra 'shorter is better,' challenging the dogma that longer antibiotic regimens are more effective — a notion since disproven by dozens of clinical trials. As he told Medscape's Spanish edition in 2016, 'Providing short antibiotic courses based on evidence reduces the risk that patients will feel better before completing therapy and minimizes leftover pills.'
He reported that over 150 randomized controlled trials across 24 infection types have demonstrated that short antibiotic courses yield the same clinical outcomes as longer ones. For example, in cases of community-acquired pneumonia, 14 studies have shown that 3-5 days of antibiotic therapy are as effective as 5-14 days. Similarly, for urinary tract infections or pyelonephritis, 13 studies indicate that 5-7 days of treatment are just as effective as 10-14 days. In intra-abdominal infections, three studies have found that 4 days of antibiotics are comparable in efficacy to 8-10 days of treatment.
However, in suspected cases of ventilator-associated pneumonia (not microbiologically confirmed), a retrospective study could not establish a difference between 'ultrashort' 3-day regimens and those lasting 2-3 weeks. 'If you're going to treat patients without infection with antibiotics,' he added, 'at least keep it brief.'
Paradigm Shift in Practice
Ezequiel Córdova, MD, session moderator and infectious diseases specialist at Hospital Cosme Argerich and HIV clinical investigator at Fundación IDEAA in Buenos Aires, Argentina, noted that Spellberg's message challenges a long-standing dogma passed down through generations regarding standard antibiotic durations.
'Lately, we've seen that shorter treatments can be just as effective,' Córdova told Medscape's Spanish edition . 'That not only reduces adverse effects but also limits resistance. Treatments should be as long as necessary — no more, no less.'
He noted that soft tissue infections were once routinely treated with 14-day courses, 'but today, if we see clinical improvement after 5 days, the treatment can be safely stopped. The same applies to pneumonia. Previously it was 10-14 days of antibiotics, but now 5 days is often enough if the patient improves.'
When asked whether further shortening is feasible in current practice, Córdova replied, 'There may be a limit where shorter durations compromise clinical outcomes — but we haven't reached it yet. We need to keep educating.'
Spellberg and Córdova declared having no relevant financial conflicts of interest.