Background
Despite many efforts, the control of nosocomial antibiotic-resistant infections is still a permanent and unresolved issue in healthcare institutions worldwide facing increased morbidity, mortality and hospital costs. Selective pressure exerted by antibiotics plays a central role on the acquisition, selection, persistence and transmission of resistant pathogens which may include the following effects: (1) eradication of the susceptible skin and gut flora will increase the likelihood of acquisition of antibiotic-resistant organisms, especially in settings with endemic resistance; (2) antibiotics select for pre-existing antibiotic-resistant bacteria (ARB) in carriers and enhance the likelihood of spread; (3) antibiotic selection pressure may transform low-level carriers to high-level spreaders; (4) antibiotics active against antibiotic-susceptible bacteria may convert carriers of susceptible bacteria to non-carriers, indirectly promoting acquisition and spread of ARB; (5) antibiotic exposure may increase the risk of endogenous infection with ARB related to changes in colonisation resistance and bacterial virulence at the individual host level. Numerous papers demonstrated that prior antimicrobial drug exposure is a strong risk factor for colonisation and infection due to a drug resistant pathogen. A meta-analysis that included 76 studies for a total of 24,230 patients documented that the risk of acquiring methicillin-resistant Staphylococcus aureus (MRSA) was increased by 1.8-fold in patients who had taken antibiotics. Antibiotic exposure was determined in the 126 days preceding MRSA isolation. Such risk was almost 3-fold greater after using quinolones or glycopeptides and 2-fold for cephalosporins. A multicentre prospective cohort study conducted in several Italian hospitals showed that 5% of patients were newly colonised by ARB including MRSA in nasal samples, after starting antibiotic therapy. Nine percent of those patients developed an infection by the same strain over the 30-day follow-up. The use of carbapenems was associated with the highest incidence of colonisation with eight new cases of MRSA colonisation for 1,000 antibiotic-day.
The likelihood of acquisition of nosocomial ARB during or shortly after therapy with different antibiotic agents is still unclear and is often confounded by scarce data on antibiotic usage at the individual patient level. Study design, selection bias, definition of control groups and failure to control for confounding variables might account for conflicting results. No prospective multi-centre cohort study has been conducted defining, in countries with varying baseline antimicrobial resistance rates, the impact of antibiotic exposure on the development and acquisition of nosocomial carriage by ARB, after accounting for individual and group-level confounding variables, such as case-mix and colonisation pressure.