Determinants of Clostridium difficile infection in elderly frail patients with multiple chronic comorbidities: not only a matter of antibiotic therapy

Background – Clostridium difficile enterocholitis is rapidly emerging as the leading nosocomial infection in Italy. Previous antibiotic therapy is traditionally considered as a major risk factor, but the growing incidence in elderly frail patients with multiple comorbidities and complex drug therapies suggests that other factors may be involved. Aims – The aim of our study was to identify the possible role of specific chronic comorbidities, degree of clinical complexity and therapies with anti-bacteric and anti-fungal antibiotics or proton pump inhibitors (PPIs) as risk factors for Clostridium difficile infection in a cohort of hospitalized elderly frail subjects. Materials and methods – At Internal Medicine and Critical Subacute Care Unit of Parma University Hospital (94 beds managed by care intensity) we carried out a retrospective evaluation of 505 consecutive clinical records of patients transferred to Critical Subacute Care Ward from other units of the hospital (505 patients, 238 M, 268 F, mean age 81±10 years old). For each patient we recorded age, transferring unit, length of stay, outcome, main diagnosis, comorbidities, Clostridium difficile status, antibiotic and PPI therapy. For each patient we calculated indexes of clinical complexity such as CIRS (Cumulative Index Rating Scale) Comorbidity Score and CIRS Severity Index. Statistical analysis was performed with chi-square test, Mann-Whitney’s U test, odds ratio and binary logistic regression whenever appropriate. Results – 43 patients out of 505 (8.5%) developed Clostridium difficile enterocholitis. Mortality was not different among positive (CL+) and negative (CL-) patients (16% vs 22%, p=0.582). However, overall hospital stay was longer for CL+ than CL- (median 52 days [IQR 29.5-73] vs 29 days [IQR 18-45.3]). The risk of developing Clostridium difficile infection was 21-fold higher for patients with more than 2 than for patients with two or less chronic comorbidities (OR 21.2 IC95% 8.2-55.1). Other relevant risk factors were: a CIRS comorbidity score ≥3 (OR 3.8 IC95% 1.5-9.8), previous antifungal therapy (OR 2.2 IC95% 1.0-4.6), admission in a specialized medical ward or an intensive care ward (OR 2.1 IC95% 1.0-4.4), chronic renal failure (OR 2.0 IC95% 1.0-4.1) and previous anti-bacteric therapy (OR 2.0 IC95%1.0-4.1). In the multivariate logistic regression model, significant variables were chronic renal failure, anti-bacteric and antifungal therapy and length of stay. Gender and therapy with PPIs were unrelated to Clostridium difficile infection. Conclusions – In frail hospitalized elderly with multiple comorbidities the most relevant risk factor for Clostridium difficile infection seems to be high number and severity of chronic comorbidities. Exposure to antibiotic therapy seems to play a minor role in this category of patients. Further studies are needed to clarify the physio-pathology of this infection in geriatric patients.