Community-acquired infection (CAI) was defined as an infection detected within 48 h of hospital admission in patients who did not fit the criteria for a HCAI.
HCAI was defined using the same criteria of Friedman et al. [3
]-an infection present at the time of hospital admission or within 48 h of admission in patients that fulfilled any of the following criteria:
received intravenous therapy at home; received wound care or specialized nursing care through a healthcare agency, family or friends; or self-administered intravenous medical therapy in the 30-day period before the onset of the infection;
attended a hospital or hemodialysis clinic, or received intravenous chemotherapy in the previous 30 days;
hospitalized in an acute care hospital for 2 or more days in the previous 90 days;
resided in a nursing home or long-term care facility.
Hospital-acquired infection (HAI) was defined as a localized or systemic condition that resulted from an adverse reaction to the presence of an infectious agent(s) or its toxin(s), and that occurred 48 h or more after hospital admission and was not incubating at the time of admission . Infections in patients recently discharged from hospital within the previous 2-week period were also included in this group.
The CDC definitions were used to define infections at different anatomic sites . The definition of MDR organisms used was adopted from the CDC recommendations for the management of MDR organisms in healthcare settings that defines MDR organisms as bacteria that are resistant to one or more classes of antimicrobial agents recommended as first line therapy . Thus, enteric Gram-negative rods were considered MDR (MDR-GN) if they were resistant to amoxicillin-clavulanate, piperacillin-tazobactam, carbapenems, aztreonam, fluoroquinolones, or third-generation cephalosporins or aminoglycosides. Acinetobacter spp. and Pseudomonas spp. were considered MDR if they were resistant to piperacillin-tazobactam, imipenem/meropenem, aztreonam, ciprofloxacin, cefepime, ceftazidime, aminoglycosides or colistin.
We grouped vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species, carbapenem-hydrolyzing Klebsiella pneumonia and MDR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species into a group denominated ESKAPE, according to a previous publication of the Infectious Diseases Society of America .
The presence of ESBL production among E. coli and Klebsiella spp. strains was screened by the automatic analyzer Vitek2 (bioMérieux, France). It was confirmed by a disk diffusion test that detects synergism between the cephalosporins/monobactam and clavulanate. If the interpretation of the results was doubtful, we also performed the Etest® (AB Biodisk, Solna, Sweden); a combination of cefotaxime and cefotaxime/clavulanate and ceftazidime and ceftazidime/clavulanate indicated ESBL production whenever the ESBL ratio with antibiotic:antibiotic+inhibitor was ≥8.
The presence of carbapenemase production in Enterobacteriaceae was suspected whenever minimum inhibitory concentrations for ertapenem, imipenem and meropenem exceeded 0.5, 1 and 1 μg/mL, respectively. In such cases, a modified Hodge test was performed, and the ultimate confirmatory test was carbapenemase detection by molecular methods.
The risk factors studied for association with infection by MDR pathogens (including MDR-GN and the ESKAPE group) included age, sex, previous antibiotic therapy (in the last month prior to the current infection), previous hospitalization (in the last 12 months prior to the current infection, but not in the last 3 months), patient comorbidities and general medical condition. The comorbidities studied included immunosuppression (administration of radiation therapy in the 12 months prior to hospital admission, administration of 0.2 mg/kg/day of prednisolone for at least 3 months prior to hospital admission, administration of 1 mg/kg/day of prednisolone for 1 week in the 3 months prior to hospital admission or infection with human immunodeficiency virus), chronic liver disease , chronic heart failure , chronic respiratory disease , hematological disease , cancer (metastatic disease not under chemotherapy in the previous 12 months), diabetes mellitus requiring insulin therapy or oral hypoglycemic agents before the infection and/or atherosclerosis (defined as a previous history of a transient ischemic attack, stroke, angina, myocardial infarction or peripheral arterial disease). The patient’s general medical condition was assessed by the Karnofsky index . A score of lower than 70 implies that the patient is unable to perform normal activities or do active work.
Adequacy of initial antibiotic therapy, hospital length of stay, Simplified Acute Physiology Score (SAPS II) and hospital mortality were also compared between groups of patients with and without infection by MDR pathogens (MDR-GN and ESKAPE). The initial empirical antibiotic treatment was considered “adequate” if the response to the initial antibiotic prescribed within 24 h of diagnosis matched in vitro susceptibility of the pathogen deemed to be the likely cause of the infection, and when the dosage and route of administration were appropriate for the patient’s current medical status (focus and severity of infection); only patients with positive microbiology were considered in this analysis. SAPS II  was recorded on the first day of antibiotic therapy.
Continuous variables are described as mean and standard deviation (SD), or as median and inter-quartile range if they showed a skewed distribution. Categorical variables are described with absolute frequencies and percentages. Comparison of demographic and clinical characteristics of infected patients from the community (either with CAI or HCAI) and patients with HAI was made using the Student t-test (for continuous variables with normal distribution), the Mann–Whitney U test (for continuous variables with skewed distribution) and the Pearson χ
2 test (for categorical variables).
Comparison of inadequate antibiotic therapy, hospital length of stay, SAPS II and hospital mortality between the group of patients infected with MDR pathogens and those not infected, along with comparison of the group infected by MDR-GN with those not infected, and the group infected by ESKAPE pathogens and those not infected, was made with the same tests according to the type of variables compared (continuous with normal distribution, continuous with skewed distribution or categorical).
All variables potentially associated with MDR pathogen infection (including MDR-GN and ESKAPE pathogens) were studied among all infected patients admitted from the community, those with CAI and HCAI, and included: age, sex, previous antibiotic therapy, hospitalization in the previous year, immunosuppression, chronic hepatic disease, chronic heart failure, chronic respiratory disease, chronic hematologic disease, cancer, diabetes, atherosclerosis and decreased functional capacity (Karnofsky index <70). Those with a clear association in the univariate analysis (p < 0.1) were included in the multivariable analysis. The results of the multivariable models are expressed as odds ratio (OR) with 95% confidence interval and p-values. The calibration was tested using the Hosmer-Lemeshow goodness-of-fit test. The significance level was defined as p < 0.05. Data were analyzed using SPSS version 18 for Windows (SPSS Inc., Chicago, IL, USA).