Tigecycline Might Protect Against C. difficile
Major Finding: The risk of hospital-onset Clostridium difficile pseudomembranous colitis in tigecycline-treated patients was one-fifth that of patients not on the antibiotic.
Data Source: Case-control retrospective study that included 1,454 adults with laboratory-confirmed CDI at least 72 hours after admission to 74 hospitals in the Cerner Corp.'s proprietary Health Facts database.
Disclosures: The studies were sponsored by Cerner LifeSciences, where Dr. Emons is employed.
VIENNA — Treatment with the antibiotic tigecycline was associated with a sharply decreased risk of hospital-onset Clostridium difficile pseudomembranous colitis in a large case-control study.
This apparent protective effect has not been previously described, Dr. Matthew F. Emons said at the annual European Congress of Clinical Microbiology and Infectious Diseases.
The unexpected finding requires confirmation, given that exposure to other classes of antibiotics has consistently been shown to be a strong risk factor for C. difficile infection (CDI).
But the protective effect is biologically plausible. Tigecycline (Tygacil) has broad-spectrum in vitro activity against gram-positive and gram-negative agents as well as anaerobic organisms, and it reportedly has activity against toxicogenic strains of C. difficile.
The retrospective study involved 1,454 adults who developed laboratory-confirmed CDI at least 72 hours after admission to 74 hospitals of various sizes included in the Cerner Corp.'s proprietary Health Facts database. The control group consisted of 32,807 inpatients who did not develop CDI during hospital stays of 72 hours or longer.
The risk of hospital-onset CDI in tigecycline-treated patients was one-fifth that of patients not on the antibiotic. Exposure to tigecycline prior to onset of CDI was the only protective factor identified in the study, according to Dr. Emons of Cerner LifeSciences, Beverly Hills, Calif.
In contrast, exposure to carbapenems was associated with a 2.1-fold increased risk of CDI in a multivariate regression analysis, and third-or fourth-generation cephalosporins conferred a 1.6-fold increased risk. Patients who received two systemic antibiotics had a 1.5-fold greater risk than did those who hadn't received any systemic antibiotics, while those who got three or more antibiotics were at 1.8-fold increased risk.
Session chair Dr. Edward J. Kuijper deemed the tigecycline findings “very interesting.”
“Based on this and other data, I think tigecycline is now a reasonable option with C. difficile infection resistant to first-line therapy,” said Dr. Kuijper of University Medical Center Utrecht (the Netherlands).
The single most potent risk factor for hospital-onset CDI in the case-control study was impaired immune function, which was prevalent in 19.5% of cases and 4.3% of controls and was associated with a 4.8-fold increased risk.
Other notable risk factors included hospital admission from a skilled nursing facility, with a 3.5-fold increased risk, and acute renal failure, cardiac arrhythmia, heart failure, or cerebrovascular disease within 12 months prior to admission, each of which was associated with a 1.7- to 2.7-fold increased risk of CDI. Advanced age and a high burden of comorbidity were also risk factors, as previously reported by others.
Proton pump inhibitor therapy was associated with a 1.6-fold risk. The PPI/CDI link was confirmed—with a twist—in a separate study presented at the congress by Dr. Paul Cleary of the U.K. Health Protection Agency, Liverpool. In this study, which included 296 patients with CDI and 296 controls, prior PPI therapy was associated with a threefold increased risk of CDI, but only in cases involving C. difficile ribotype 106, which accounted for 27% of all infections. Histamine2-blocker therapy was associated with a significantly decreased risk of CDI in the British study.
Dr. Emons presented a second study that highlighted the impact of CDI on hospital resource utilization. It involved 1,312 patients with hospital-onset CDI and an equal number of hospitalized control subjects matched for comorbidity burden and demographic characteristics. The CDI group's in-hospital mortality rate of 8.7% was not significantly different from that of the matched controls. However, the mean hospital length of stay among CDI survivors was 20.8 days, compared with 9.9 days for controls. Moreover, 33% of patients discharged after CDI were readmitted within the next 90 days, a rate 56% higher than controls.
The risk of hospital-onset CDI in tigecycline-treated patients was one-fifth that of patients not on the antibiotic.
Source DR. EMONS
