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Antibiotics with high C. difficile risk may increase severe sepsis risk
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Patients exposed to antibiotics associated with increased risk for Clostridium difficile infection have a significantly higher risk for severe sepsis compared with those not exposed to any antibiotics, according to researchers.
Patients who receive drugs from four or more antibiotic classes also have a much higher risk for severe sepsis, they wrote in Clinical Infectious Diseases.
“We found a significant association between antibiotic exposure in the hospital and severe sepsis and septic shock either as the cause of or occurring during a subsequent hospitalization within 90 days of discharge,” James Baggs, PhD, of the CDC Division of Healthcare Quality Promotion, and colleagues wrote. “Our findings support, but do not prove, the hypothesis that microbiota disruption is associated with an increased risk of severe sepsis and septic shock within 90 days of discharge from a hospital stay.”
To test the hypothesis, the researchers conducted a retrospective cohort study of records for about 12.7 million patients treated at roughly 500 hospitals. Of those patients, severe sepsis or septic shock was diagnosed in 21,247 (0.17%) within 90 days of a hospital stay.
Baggs and colleagues stratified the antibiotic exposures into three groups — high-risk, low-risk and control antibiotics. The groupings were based on how strongly the antibiotics are associated with C. difficile infection, which is considered a marker for disruption of intestinal microbiota.
Antibiotics deemed high risk were third- and fourth-generation cephalosporins, fluoroquinolones, lincosamides, beta-lactam/beta-lactamase inhibitor combinations, oral vancomycin and carbapenems. Those considered low risk were first- and second-generation cephalosporins, macrolides, tetracyclines, metronidazole and sulfonamides without the use of high-risk antibiotics.
Control exposures included use of antibiotics that cause minimal gastrointestinal flora disruption, specifically aminoglycocides, penicillin or intravenous vancomycin. The researchers compared sepsis risk in patients given antibiotics with that in patients who received no antibiotics.
They found that the use of high-risk antibiotics was associated with an increased risk for severe sepsis within 90 days of hospital discharge (OR = 1.65). Low-risk and control antibiotics were less significantly associated with severe sepsis (OR = 1.07 and 1.22, respectively).
In addition, exposure to four or more antibiotic classes, as well as 14 or more days of antibiotic therapy, was associated with a more than twofold increase in the risk for severe sepsis, compared with no antibiotic exposure (OR = 2.23 and2.17, respectively).
The researchers said their study adds to evidence that thoughtful use of antibiotics may reduce several types of morbidities.
“Given that a significant proportion of inpatient antimicrobial use may be unnecessary,” they wrote, citing previous studies, “this study builds on a growing evidence base suggesting that increased stewardship efforts in hospitals may not only prevent antimicrobial resistance, C. difficile infection and other adverse effects, but also reduce other unwanted outcomes potentially related to disruption of the microbiota, including sepsis.” – by Joe Green
Disclosures: The authors report no relevant financial disclosures.
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