EVIDENCE-BASED ANSWER
CERTAIN ANTIBIOTICS AND USING 3 OR MORE ANTIBIOTICS AT ONE TIME are associated with Clostridium difficile-associated diarrhea (CDAD) (strength of recommendation [SOR]: B, 1 heterogeneous systematic review and several good-quality cohort studies).
Hospital risk factors include proximity to other patients with C difficile and longer length of stay (SOR: B, several good-quality cohort studies).
Patient risk factors include advanced age and comorbid conditions (SOR: B, several good-quality cohort studies).
Acid suppression medication is also a risk factor for CDAD (SOR: B, 1 heterogeneous systematic review and 2 good-quality cohort studies).
Evidence summary
One systematic review found increased risk of CDAD in patients taking cephalosporins, penicillin, or clindamycin (TABLE 1).1 A subsequent retrospective cohort investigation of 5619 patients during a CDAD epidemic in Quebec, Canada reported that quinolone antibiotics were most strongly associated with CDAD, whereas other antibiotics posed an intermediate risk.2
A prospective cohort study of 101,796 admissions over a 5-year period at a tertiary medical center defined a group of high-risk antibiotics before starting research.3 They included fluoroquinolones, cephalosporins, intravenous β-lactam/β-lactamase inhibitors, macrolides, clindamycin, and carbapenems. All other antibiotics were considered low risk. High-risk antibiotics were associated with a 3-fold increase in CDAD compared with low-risk drugs (odds ratio [OR]=3.37; 95% confidence interval [CI], 2.64-4.31); number needed to harm [NNH]= 10).3
TABLE 1
Medications associated with C difficile diarrhea
| Medication | Reported ratio* (95% CI) | NNH† |
|---|---|---|
| Antibiotics | ||
| β-Lactam/β-lactamase inhibitor, intraveneous2 | aHR=1.88 (1.35-2.63) | 25 |
| Cephalosporins1 | RR=2.07 (1.06-6.62) | 21 |
| Cephalosporins, first generation2 | aHR=1.78 (1.28-2.46) | 28 |
| Cephalosporins, second generation2 | aHR=1.89 (1.45-2.46) | 25 |
| Cephalosporins, third generation2 | aHR=1.56 (1.15-2.12) | 39 |
| Clindamycin1 | OR=4.22 (2.11-8.45) | 8 |
| Clindamycin2 | aHR=1.77 (1.06-2.96) | 28 |
| Macrolides2 | aHR=1.65 (1.15-2.39) | 33 |
| Penicillins1 | RR=3.62 (1.28-8.42) | 9 |
| Quinolones2 | aHR=3.44 (2.65-4.47) | 10 |
| Acid suppression medication | ||
| Histamine2-receptor antagonist3 | aOR=1.53 (1.12-2.10) | 41 |
| Proton-pump inhibitor daily3 | aOR=1.74 (1.29-2.18) | 30 |
| Proton-pump inhibitor more often than daily3 | aOR=2.36 (1.79-3.11) | 17 |
| aHR, adjusted hazard ratio; aOR, adjusted odds ratio; CI, confidence interval; NNH, number needed to harm; OR, odds ratio; RR, risk ratio. *Because the incidence of C difficile diarrhea is low, each reported adjusted hazard ratio or risk ratio is approximately equal to the odds ratio used to calculate number needed to harm. †Assuming an event rate of 5%. | ||