Prevalence of Multidrug-Resistant Organism Infections in General Adult Wards in Argentina (PREV-AR 2 - IGA)

Overview

This study measures how common infections caused by multidrug-resistant organisms (MDROs) are among adult patients hospitalized in general medical and surgical wards in Argentina, and how these infections relate to in-hospital death. Background: A 2019 national survey (ENPIHA 2019), conducted across 255 hospital units in Argentina, found that nearly 29% of hospitalized patients had a healthcare-associated infection, most often caused by Klebsiella pneumoniae, Acinetobacter species, Pseudomonas aeruginosa, E. coli, and Staphylococcus aureus. Most prior regional studies combined data from intensive care and general ward patients together, making it hard to know how much of this burden specifically affects general medical/surgical wards. This study is designed to answer that question directly. On a single day chosen by each hospital between August 4 and 6, 2026, doctors and infection-control staff at participating hospitals across Argentina will record information about every adult patient (18 years or older) who has been in a general adult ward for at least 24 hours. For each patient, the study team records basic demographics, underlying health conditions, whether the patient has an active infection that day, the site and type of that infection, the organism responsible, whether that organism is drug-resistant, and what antibiotics are being used. No study procedures, tests, or treatments are performed - the study only records information that is already part of routine hospital care. Each patient is then followed for up to 60 days after the study day, using existing hospital records, to determine whether they were discharged alive or died in the hospital. No patient names or other identifying information are collected; each patient is assigned a code known only to the local site investigator. This study is sponsored by the Sociedad Argentina de Infectología (SADI), in collaboration with the Sociedad Argentina de Terapia Intensiva (SATI) and the Sociedad Argentina de Medicina (SAM), with no external funding. It is one component of a larger multi-part project, PREV-AR 2, which separately surveys neonatal intensive care units and adult intensive care units at other points in 2026. This registration covers only the general adult ward (Internación General de Adultos, IGA) component.

1. Background and rationale The 2019 National Healthcare-Associated Infection Prevalence Study (ENPIHA 2019), conducted by Argentina's National Institute of Epidemiology across 255 units in 140 healthcare institutions, found an overall healthcare-associated infection (HAI) rate of 28.80%, with Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus as the leading pathogens. Regional literature on non-critical (general ward) inpatient populations remains limited, as most existing studies pool data from critical and non-critical care areas together, which obscures the true prevalence, predominant resistance phenotypes, and mortality impact specific to general internal medicine wards. Available evidence nonetheless suggests that infections caused by multidrug-resistant organisms (MDROs) are associated with substantially higher mortality - one recent analysis found an unadjusted MDRO-related mortality rate of 45%, with an adjusted risk of death 1.93 times higher than for infections caused by non-resistant organisms, an effect that is further amplified when empirical antibiotic treatment is inadequate. PREV-AR 2 was designed to close this evidence gap by generating Argentina-specific, ward-level data on MDRO prevalence and its association with mortality, with the goal of informing infection prevention and control strategies, antimicrobial stewardship programs, and resource allocation (e.g., availability of appropriate antibiotics for MDRO treatment). Periodic, standardized prevalence measurement also creates a comparable baseline over time, enabling trend surveillance and future evaluation of the impact of prevention interventions. 2. Study objectives General objective: To estimate the prevalence of, and factors associated with, MDRO infection among adult patients hospitalized in general medical/surgical wards (IGA) in healthcare institutions across Argentina. Specific objectives: To calculate in-hospital mortality at day 28 and identify its independent predictors. To identify risk factors associated with MDRO infection. To characterize infections by microbiological isolate, resistance mechanism (MDRO vs. non-MDRO), and site of infection. To compare patients with and without MDRO infection with respect to risk factors, mortality, and length of hospital stay. To describe the overall prevalence of infection (MDRO and non-MDRO) in this population. 3. Study design This is a multicenter, observational, analytical, cross-sectional prevalence study with prospective longitudinal follow-up for in-hospital mortality, conducted in public, social-security, and private-sector hospitals throughout Argentina. For the general adult ward (IGA) component, each participating site selects a single 24-hour data-collection window (beginning 8:00 AM local time) within August 4-6, 2026. Sampling is consecutive and non-probabilistic: all patients who have been hospitalized in a general adult ward for at least 24 hours before 8:00 AM on the chosen day are included. No intervention of any kind is performed, and no predefined sample size was set, as the design is a census-style prevalence cut rather than a hypothesis-driven comparison - the goal is to include as many eligible patients as possible. 4. Setting and eligible sites Eligible hospitals must (a) sign an institutional commitment letter guaranteeing data collection support throughout the study, and (b) have on-site microbiology laboratory capability to detect antimicrobial resistance mechanisms using phenotypic, molecular, and/or immunochromatographic methods. Sites are recruited through SADI, SATI, and SAM via direct member outreach and public announcements. Institution-level data collected include hospital type (public/private/community/social-security), total and ward-level bed capacity, presence of an infection control committee, presence of an antimicrobial stewardship program (PROA), reporting to Argentina's national HAI surveillance system (VIHDA), and MDRO colonization-surveillance practices and methodology. 5. Study population Target population: All patients hospitalized in general adult wards (IGA) in Argentine hospitals during the study period. Accessible population: All patients hospitalized in the participating unit at the time of the study cut, at sites that agree to participate. Unit of analysis: Each patient hospitalized in the surveyed unit on the study day. 6. Data collected Data are captured on a structured case report form (CRF) with three sections: (1) institutional/unit-level characteristics, (2) patient demographics and study-day variables, and (3) follow-up data. Patient-level variables include: age and sex; hospital and ward admission/discharge dates; admission type (medical or surgical); baseline severity via the McCabe classification (non-fatal, ultimately fatal, rapidly fatal within 1 month, unknown); comorbidities and risk factors (asthma/COPD, diabetes, obesity, alcohol use disorder, smoking, ischemic heart disease, chronic liver disease, chronic kidney disease, immunosuppressive treatment, bone marrow or solid-organ transplant, oncohematologic malignancy, chemotherapy in the prior 6 months, HIV, antibiotic use in the prior 3 months, hospitalization in the prior 6 months, and abdominal surgery); and prior MDRO colonization or infection within the previous 3 months. For the study day itself, clinical status is classified as: no infection; active infection without sepsis; confirmed/probable sepsis; or septic shock (per Sepsis-3-type criteria: vasopressor requirement to maintain MAP ≥65 mmHg after adequate fluid resuscitation plus lactate \>2 mmol/L). For patients with active infection, the CRF records the origin (community-acquired, hospital-acquired outside the ward, or hospital-acquired within the general ward, including patients transferred from a higher level of care), infection site/syndrome (e.g., community/hospital-acquired pneumonia, catheter-associated or community urinary tract infection, primary or CVC-associated bacteremia, surgical site infection, C. difficile diarrhea, skin/soft-tissue, cardiovascular, osteoarticular, gynecologic/obstetric, nosocomial meningitis, or infection without a clear source), culture results, and up to two isolated organisms per infection episode. Organisms are classified as MDRO or non-MDRO according to the WHO priority pathogen list for antibiotic research and development: MDRO categories include carbapenem-resistant Acinetobacter baumannii (ABRC), difficult-to-treat Pseudomonas aeruginosa (DT-PAE, resistant to antipseudomonal cephalosporins, aztreonam, piperacillin-tazobactam, imipenem, meropenem, and fluoroquinolones simultaneously), carbapenem-resistant Enterobacterales (EPC), extended-spectrum beta-lactamase-producing Enterobacterales (E-BLEE), vancomycin-resistant Enterococcus faecium (EVR), methicillin-resistant Staphylococcus aureus (MRSA), and S. aureus with intermediate (VISA) or full (VRSA) vancomycin resistance, plus Stenotrophomonas maltophilia. Fungi, parasites, and viruses are excluded. Resistance mechanisms recorded for gram-negative MDROs include KPC, MBL, OXA, ESBL, and combinations thereof. Antibiotic treatment is classified as empirical vs. targeted, traditional vs. novel agent (e.g., ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, aztreonam-avibactam), and by WHO AWaRe category (Access, Watch, Reserve). 7. Follow-up and outcome ascertainment Each patient is followed through existing hospital records until hospital discharge, transfer, or death. Data are censored 60 days after the prevalence cut date; patients still hospitalized at that point are classified as survivors for analysis. In-hospital mortality at day 28 is a co-primary outcome, together with the discharge date and vital status at discharge (alive or deceased, with date of death if applicable). 8. Primary and secondary outcome measures Primary outcomes: (1) Prevalence of MDRO infection, calculated as the number of patients with active MDRO infection divided by the total number of patients hospitalized in the surveyed unit on the study day, ×100; (2) In-hospital mortality at day 28. Secondary outcomes: Overall infection prevalence (MDRO and non-MDRO); distribution of infection sites and causative organisms; distribution of MDRO type and resistance mechanism by infection site; and comparison of risk factors, mortality, and length of hospital stay between patients with and without MDRO infection. 9. Data management and quality control Data are entered into REDCap (Research Electronic Data Capture), a validated platform for multicenter research, with built-in range, format, and mandatory-field validation to reduce transcription errors. All site investigators and coordinators complete mandatory centralized training on the CRF and REDCap use, including practice data entry with simulated ("dummy") patient cases, prior to study initiation. A SADI-appointed study coordinator performs active monitoring of the database to identify logical inconsistencies (e.g., a patient coded with sepsis but no documented infection source, or atypical severity scores) and issues data queries to local investigators for timely resolution. Missing data are categorized as missing-by-design versus missing-by-omission; multiple imputation may be applied to key variables in the final statistical analysis if deemed appropriate, with full documentation in the statistical analysis section of the final report. Data access is role-based and site-specific; patients are identified only by an internally generated code (initials-based), and no direct identifiers (name, national ID, or medical record number) are transmitted to the coordinating data center at any point. 10. Statistical analysis As this is a no-risk observational study with no predefined sample size, the analysis includes all patients enrolled. Prevalence is calculated as described above. Categorical variables are summarized as absolute numbers and percentages; continuous variables as means with standard deviations or medians with interquartile ranges \[P25-P75\], depending on distribution normality. Between-group comparisons use the chi-square or Fisher's exact test for categorical variables, and Student's t-test or Wilcoxon rank-sum test for continuous variables. A two-tailed p-value \<0.05 is considered statistically significant, with Bonferroni correction applied for multiple comparisons where appropriate. 11. Ethics The study was granted a waiver of individual informed consent by participating institutional ethics/research committees, based on its non-interventional, no-risk, descriptive design and the use of fully de-identified, code-based data. Conduct of the study follows the Declaration of Helsinki and applicable Argentine national regulations (Resolución 1480/11, Ministerio de Salud de la Nación; Disposición 6677/10, ANMAT). 12. Relationship to the broader PREV-AR 2 project This registration corresponds specifically to the general adult ward (Internación General de Adultos, IGA) component of PREV-AR 2, a national multi-society project (SADI, SATI, SAM) that separately conducts prevalence cuts in neonatal intensive care units (April 8-9, 2026) and adult intensive care units (November 25-27, 2026), each registered and analyzed independently.