Study: Antibiotic Exposure Can Predict C. difficile Resistance

Patients treated with fluoroquinolones and macrolides are most vulnerable

Exposure to specific antibiotics is linked to the development of certain strains of antibiotic-resistant Clostridium difficile, one of the fastest-growing “superbugs,” according to a new study led by Stuart Johnson, MD, of Loyola University. C. difficile now rivals methicillin-resistant Staphylococcus aureus (MRSA) as the most common antibiotic-resistant pathogen.

“This discovery takes us one step closer to preventing C. diff and supports targeting specific antibiotics for antibiotic stewardship monitoring programs in the setting of high infection rates due to specific strains of C. diff,” Johnson said.

The study findings were published in Antimicrobial Agents and Chemotherapy.

Johnson and his team performed a retrospective case-control study of 143 patients who had been infected with the BI/NAP1/027 strain of C. difficile between 2005 and 2007. Of these patients, 103 (72%) with first-episode C. difficile infections had the BI strain, as determined by restriction endonuclease analysis (REA) typing. Most of the patients received multiple antibiotics (a median of three antibiotic classes) within six weeks of the onset of infection.

The authors found that fluoroquinolone and macrolide exposure was more common among BI cases than among non–BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; P < 0.001; OR for macrolides, 5.2; P = 0.04). In contrast, clindamycin use was less frequent among the BI cases than among the controls (OR, 0.1; P = 0.001). High-level resistance to moxifloxacin and azithromycin was more frequent among BI strains (moxifloxacin, 49/102 [48%] BI versus 0/40 [0%] non-BI, P = 0.0001; azithromycin, 100/102 [98%] BI versus 22/40 [55%] non-BI, P = 0.0001). High-level resistance to clindamycin was more frequent among non-BI strains (22/40 [55%] non-BI versus 7/102 [7%] BI, P = 0.0001).

The authors concluded that fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when C. difficile infection rates were increasing nationally because of the highly fluoroquinolone-resistant BI/NAP1/027 strain.

According to the Centers for Disease Control and Prevention, more than 29,000 C. difficile-related deaths occur in the U.S. each year. The bug causes inflammation in the colon. Symptoms of infection include frequent bouts of diarrhea, abdominal pain, loss of appetite, fever, and nausea. C. difficile infections are commonly treated with specific antibiotics. The infection returns in approximately 20% of cases, largely because of ongoing disruption of the gut flora by antibiotics––both those that precipitated the infection in the first place and those used to treat it.

Sources: Medical Xpress; February 4, 2016; and Antimicrobial Agents and Chemotherapy; January 2016.