About one in five patients who are prescribed antibiotics during a hospital stay experiences at least one adverse drug event (ADE), which is sometimes not apparent until after they are discharged, new research shows.

Further, in a substantial proportion of cases, the prescribed antibiotics are not clinically indicated, which means the associated ADEs (such as allergic reactions, end-organ toxic effects, or subsequent infection with antibiotic-resistant organisms or with Clostridium difficile) are avoidable.

“We wanted to pursue the current study because … harm that is caused by antibiotics prescribed to hospitalized patients, including the antibiotics they are asked to continue after leaving a hospital, has not been previously evaluated,” lead author Dr. Pranita D. Tamma, who directs the pediatric antimicrobial stewardship program at the Johns Hopkins Hospital, told Reuters Health by email.

To investigate, the researchers conducted a retrospective review of electronic medical records of nearly 1,500 patients (median age 59 years; 51% female). All patients had received antibiotics for at least 24 hours while hospitalized (for a median stay of four days) at general medicine wards at the Johns Hopkins Hospital between 2013 and 2014. ADEs included gastrointestinal, dermatologic, musculoskeletal, hematologic, hepatobiliary, renal, cardiac, and neurologic events occurring within 30 days after patients began taking the drug, as well as Clostridium difficile infections or new multidrug-resistant infections within 90 days.

A total of 1,488 patients admitted during the study period received an antibiotic for at least 24 hours and were included in the analysis. Nearly 80% received more than one antibiotic.

The most common indications for antibiotic treatment were urinary tract infections, skin and soft tissue infections, and community-acquired pneumonia. The most frequently prescribed antibiotics were third-generation cephalosporins, parenteral vancomycin, and cefepime. A fifth of the patients experienced at least one antibiotic-associated ADE, the researchers report in JAMA Internal Medicine, online June 12.

The overall rate of antibiotic-associated ADEs was 22.9 per 10,000 person-days.

Nearly all (97 percent) of the 324 documented ADEs were considered clinically significant because they resulted in new or prolonged hospitalization, additional clinic or emergency department visits, or additional diagnostic procedures. The median length of treatment per patient was seven days. For every additional 10 days of antibiotic therapy, patients experienced a 3% increase in ADE risk.

A total of 287 (19 percent) antibiotic regimens were prescribed to treat conditions for which antibiotics were not indicated, and 56 of these (20 percent) had antibiotic-associated ADEs, the authors noted. Most of the ADEs occurred during hospitalization, but nearly a quarter of them emerged after patients were discharged, including 11 cases of C. difficile and 44 multi-drug resistant infections.

When ADEs occur after discharge, patients may present to an urgent care center, an emergency department, or their primary care provider, Dr. Tamma noted.

As a result, “the (hospital’s) clinicians don’t receive the feedback that the antibiotics they prescribed – sometimes in the setting of knowing they probably weren’t necessary but recommended them ‘just in case’ – led to real harm in a patient,” she said.

Clinicians sometimes forget that antibiotics “are not risk neutral,” Dr. Tamma said. When prescribing an antibiotic, it’s important for physicians to ask themselves whether the potential benefits of the antibiotic outweigh the potential risks for the patient, she said.

In addition to the potential for causing immediate harm, “we need to be very careful in how (antibiotics) are used because if they are prescribed indiscriminately, we will continue to see bacteria evolve and develop resistance to available antibiotics,” she said.

The researchers cautioned that the findings may not reflect the frequency of antibiotic-associated adverse effects that occur elsewhere, because the study hospital’s “robust” antibiotic stewardship program likely reduced overall antibiotic prescriptions and durations of therapy.

The authors’ finding adverse drug events occurring in about one in five hospitalized patients who were exposed to an antibiotic largely confirms those of other studies which have looked at many types of drugs, Dr. David Westfall Bates, who directs the Center for Patient Safety Research and Practice at Brigham and Women’s Hospital in Boston, told Reuters Health by email.

The results “are of interest because they have been done within the era of electronic records, which probably increases the number of adverse drug events which can be found, and because broader-spectrum antibiotics are used (more often) now than previously,” said Dr. Bates, who was not involved in the study.

The study provides a comprehensive and current picture of this issue, he noted, which is important because of the constantly changing spectrum of antibiotics in use.

“More days of therapy increased the risk of adverse drug events, and more judicious use of antibiotics would reduce that risk,” he said.

The study was funded by a grant from Pfizer Independent Grants for Learning and Change and the Joint Commission, and the researchers report no conflicts of interest.