Antibiotics to Treat Upper Respiratory Infections Increase Risk of C Difficile Infections

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The results show female patients were more likely to be diagnosed with any adverse event.

Increased antibiotic use to treat patients with acute upper respiratory infections puts patients at a risk of developing various adverse events, with an unknown benefit.

A team, led by Harris Carmichael, MD, Division of Primary Care and Population Health, Stanford University School of Medicine, estimated adverse events by only measuring comparatively severe events that require subsequent clinical evaluation.


Current guidelines recommend avoiding antibiotics for several acute upper respiratory infections to reduce the risk of adverse events in absence of a likely benefit.

However, it is unknown what the extent of harm is from these antibiotics and prior estimates finding a number needed to harm between 8-10 generally rely on patient-reported adverse events of any severity. A better understanding could inform patient-centered decision-making.

In the study, the investigators constructed a retrospective cohort that analyzed 51 million patient encounters and determined the adjusted odds ratio of clinically detectable adverse events following antibiotic use compared with events among unexposed individuals with acute upper respiratory infections using logistic regression models.

The investigators sought outcomes on adverse events including candidiasis, diarrhea, Clostridium difficile infection (CDI), and a composite outcome.

Adverse Events

The results show 62.4% of the populations were treated with an antibiotic during an acute upper respiratory infection encounter. There were adverse events of diarrhea (aOR, 1.24) observed in 54,279 patients in the antibiotic-exposed group, 46,936 for candidiasis (aOR, 1.61) in the same group. The number needed to harm was 3126 and 1975, respectively.

The observed events of CDI in the exposed group was 30,133, with an adjusted odds ratio of isolated CDI of 1.07 and an aOR of combined adverse events of 1.30. This resulted in a number needed to harm of 17,695 and 1150 respectively.

The investigators also found that female patients were more likely to be diagnosed with any adverse event.

The overall rate of adverse events caused by antibiotics was 5.7 additional cases of CDI per 100,000 outpatient prescriptions following an upper respiratory tract infection.

“Despite higher [number needed to harm] than previous methods of analysis, we find substantial iatrogenic harm associated with prescribing antibiotics in [acute upper respiratory infections],” the authors wrote.

Pediatric CDI

Earlier this year, investigators found research on pediatric patients with clostridium difficile infections (CDI) could ultimately result in future studies identifying risk factors within the pediatric population.

A team, led by Danilo Buonsenso, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A, examined certain characteristics and risk factors for pediatric patients hospitalized with C difficile infections.

In the 5-year, retrospective study, the investigators examined 359 patients at 2 referral centers in Rome between January 2014 and December 2018. Of the 359 patients who were tested for C difficile infections, 87 were positive and 272 were negative.

The investigators found pediatric patients with CDI had a higher number of previous-day hospital admissions (P = 0.024), hospitalizations (P = 0.001), and total hospital admissions (P = 0.008).

In addition, patients with chronic comorbidities frequently tested positive for C difficile (66.7% vs. 33.3%).

The investigators also found proton pump inhibitors and antibiotic use was linked to C difficile infections (P <0.001).

However, among specific antibiotics, only fluoroquinolone use was significantly associated with C difficile infections.

Pediatric patients with CDI were also more likely exposed to antibiotics during hospitalization.

The study, “Clostridium difficile and other adverse events from overprescribed antibiotics for acute upper respiratory infection,” was published online in the Journal of Internal Medicine.