Prospective cohort study of incidence and risk factors for catheter-associated urinary tract infections in 145 intensive care units of 9 Latin American countries: INICC findings.

PURPOSE: Identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in Latin American Countries. METHODS: From 01/01/2014 to 02/10/2022, we conducted a prospective cohort study in 145 ICUs of 67 hospitals in 35 cities in nine Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru. To estimate CAUTI incidence, we used the number of UC-days as the denominator, and the number of CAUTIs as numerator. To estimate CAUTI RFs, we analyzed the following 10 variables using multiple logistic regression: gender, age, length of stay (LOS) before CAUTI acquisition, UC-days before CAUTI acquisition, UC-device utilization (DU) ratio, UC-type, hospitalizationtype, ICU type, facility ownership, and time period. RESULTS: 31,631 patients, hospitalized for 214,669 patient-days, acquired 305 CAUTIs. The pooled CAUTI rate per 1000 UC-days was 2.58, for those using suprapubic catheters, it was 2.99, and for those with indwelling catheters, it was 2.21. The following variables were independently associated with CAUTI: age, rising risk 1% yearly (aOR = 1.01; 95% CI 1.01-1.02; p < 0.0001 female gender (aOR = 1.28; 95% CI 1.01-1.61; p = 0.04), LOS before CAUTI acquisition, rising risk 7% daily (aOR = 1.07; 95% CI 1.06-1.08; p < 0.0001, UC/DU ratio (aOR = 1.14; 95% CI 1.08-1.21; p < 0.0001, public facilities (aOR = 2.89; 95% CI 1.75-4.49; p < 0.0001. The periods 2014-2016 and 2017-2019 had significantly higher risks than the period 2020-2022. Suprapubic catheters showed similar risks as indwelling catheters. CONCLUSION: The following CAUTI RFs are unlikely to change: age, gender, hospitalization type, and facility ownership. Based on these findings, it is suggested to focus on reducing LOS, UC/DU ratio, and implementing evidence-based CAUTI prevention recommendations.

Viral reactivations and co-infections in COVID-19 patients: a systematic review.

BACKGROUND: Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses. METHODS: Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle-Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables. RESULTS: In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals. CONCLUSION: Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Screening with Anal Cytology in Colombia: Initial Experience and Need for High-Resolution Anoscopy.

BACKGROUND: Men who have sex with men (MSM) living with human immunodeficiency virus (HIV) are at increased risk of anal cancer. Anal cytology can be used to screen for dysplasia, with high-resolution anoscopy (HRA) required for diagnostic confirmation. We describe the impact lack of HRA had on management of abnormal screening results in Bogotá, Colombia. MATERIAL AND METHODS: This retrospective cohort study includes MSM with HIV who underwent anal cytology screening between January 2019February 2020, with colorectal surgery (CRS) follow-up through July 2020. Cytology results included atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). Categorical and continuous variables were compared via Fisher's exact test and Wilcoxon rank-sum, respectively. RESULTS: Of 211 MSM screened, 68 had abnormal cytology: ASC-US (n = 23), LSIL (n = 41), HSIL (n = 4). Sixty (88.2%) were referred to CRS, and 51 (75.0%) attended ≥ 1 appointment. At initial assessment, 17 were referred for anal exam under anesthesia (EUA) for tissue resection, and 21 for rectosigmoidoscopy. Having perianal condyloma was associated with recommendation for EUA (P < 0.001), while cytology grade of dysplasia was not (P = 0.308). Eleven (16.2%) underwent EUA for condyloma resection. CONCLUSIONS: Few studies have described anal cancer screening in settings without HRA. We found lack of HRA limited management of abnormal cytology in Colombia. Those with condyloma underwent resection, but HRA remains necessary to localize and treat microscopic disease. Next steps include implementation of HRA in order to further develop the anal cancer screening program for MSM with HIV in Bogotá.

Epidemiological and clinical characteristics of patients with carbapenem-resistant Enterobacterales in a university hospital of Colombia: Enzyme coproductions in rise.

The distribution of carbapenemases in Carbapenem-Resistant Enterobacterales (CRE) has recently undergone a change in our region. According to the Colombian National Institute of Health, there is an increasing prevalence of NDM and NDM-KPC co-producing strains. We carried-out an ambispective cohort study of adult inpatients from Hospital Universitario San Ignacio (2021-2023), infected or colonized with CRE, in which carbapenemases immunochromatographic assay was performed. Out of the 150 patients included in the study, 71.3 % presented with an infection, and carbapenemases were detected in 92.7 % of these cases. Among them, KPC predominated (54 %), while 16.7 % demonstrated enzyme coproductions, mainly KPC-NDM. CRE infected patients had an 18.7 % 30-days mortality, but we could not demonstrate an association between type of carbapenemase and mortality rate (p = 0.82). Logistic regression analysis suggested that ICU admission was independently correlated to fatality (OR 5.08; CI 1.68-16.01). NDM and KPC-NDM presence in CRE poses a public health threat and a therapeutic challenge, with unknown mortality differences according to the carbapenemases pattern. Nevertheless, there was not an association between enzyme type and mortality.

Decreasing central line-associated bloodstream infections rates in intensive care units in 30 low- and middle-income countries: An INICC approach.

BACKGROUND: Central line (CL)-associated bloodstream infections (CLABSIs) occurring in the intensive care unit (ICU) are common and associated with a high burden. METHODS: We implemented a multidimensional approach, incorporating an 11-element bundle, education, surveillance of CLABSI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CLABSI rates and clinical outcomes, and performance feedback in 316 ICUs across 30 low- and middle-income countries. Our dependent variables were CLABSI per 1,000-CL-days and in-ICU all-cause mortality rates. These variables were measured at baseline and during the intervention, specifically during the second month, third month, 4 to 16 months, and 17 to 29 months. Comparisons were conducted using a two-sample t test. To explore the exposure-outcome relationship, we used a generalized linear mixed model with a Poisson distribution to model the number of CLABSIs. RESULTS: During 1,837,750 patient-days, 283,087 patients, used 1,218,882 CL-days. CLABSI per 1,000 CL-days rates decreased from 15.34 at the baseline period to 7.97 in the 2nd month (relative risk (RR) = 0.52; 95% confidence interval [CI] = 0.48-0.56; P < .001), 5.34 in the 3rd month (RR = 0.35; 95% CI = 0.32-0.38; P < .001), and 2.23 in the 17 to 29 months (RR = 0.15; 95% CI = 0.13-0.17; P < .001). In-ICU all-cause mortality rate decreased from 16.17% at baseline to 13.68% (RR = 0.84; P = .0013) at 17 to 29 months. CONCLUSIONS: The implemented approach was effective, and a similar intervention could be applied in other ICUs of low- and middle-income countries to reduce CLABSI and in-ICU all-cause mortality rates.

Incidence and risk factors for catheter-associated urinary tract infection in 623 intensive care units throughout 37 Asian, African, Eastern European, Latin American, and Middle Eastern nations: A multinational prospective research of INICC.

OBJECTIVE: To identify urinary catheter (UC)-associated urinary tract infection (CAUTI) incidence and risk factors. DESIGN: A prospective cohort study. SETTING: The study was conducted across 623 ICUs of 224 hospitals in 114 cities in 37 African, Asian, Eastern European, Latin American, and Middle Eastern countries. PARTICIPANTS: The study included 169,036 patients, hospitalized for 1,166,593 patient days. METHODS: Data collection took place from January 1, 2014, to February 12, 2022. We identified CAUTI rates per 1,000 UC days and UC device utilization (DU) ratios stratified by country, by ICU type, by facility ownership type, by World Bank country classification by income level, and by UC type. To estimate CAUTI risk factors, we analyzed 11 variables using multiple logistic regression. RESULTS: Participant patients acquired 2,010 CAUTIs. The pooled CAUTI rate was 2.83 per 1,000 UC days. The highest CAUTI rate was associated with the use of suprapubic catheters (3.93 CAUTIs per 1,000 UC days); with patients hospitalized in Eastern Europe (14.03) and in Asia (6.28); with patients hospitalized in trauma (7.97), neurologic (6.28), and neurosurgical ICUs (4.95); with patients hospitalized in lower-middle-income countries (3.05); and with patients in public hospitals (5.89).The following variables were independently associated with CAUTI: Age (adjusted odds ratio [aOR], 1.01; P < .0001), female sex (aOR, 1.39; P < .0001), length of stay (LOS) before CAUTI-acquisition (aOR, 1.05; P < .0001), UC DU ratio (aOR, 1.09; P < .0001), public facilities (aOR, 2.24; P < .0001), and neurologic ICUs (aOR, 11.49; P < .0001). CONCLUSIONS: CAUTI rates are higher in patients with suprapubic catheters, in middle-income countries, in public hospitals, in trauma and neurologic ICUs, and in Eastern European and Asian facilities.Based on findings regarding risk factors for CAUTI, focus on reducing LOS and UC utilization is warranted, as well as implementing evidence-based CAUTI-prevention recommendations.

Assessing the impact of a multidimensional approach and an 8-component bundle in reducing incidences of ventilator-associated pneumonia across 35 countries in Latin America, Asia, the Middle East, and Eastern Europe.

BACKGROUND: Ventilator associated pneumonia (VAP) occurring in the intensive care unit (ICU) are common, costly, and potentially lethal. METHODS: We implemented a multidimensional approach and an 8-component bundle in 374 ICUs across 35 low and middle-income countries (LMICs) from Latin-America, Asia, Eastern-Europe, and the Middle-East, to reduce VAP rates in ICUs. The VAP rate per 1000 mechanical ventilator (MV)-days was measured at baseline and during intervention at the 2nd month, 3rd month, 4-15 month, 16-27 month, and 28-39 month periods. RESULTS: 174,987 patients, during 1,201,592 patient-days, used 463,592 MV-days. VAP per 1000 MV-days rates decreased from 28.46 at baseline to 17.58 at the 2nd month (RR = 0.61; 95% CI = 0.58-0.65; P < 0.001); 13.97 at the 3rd month (RR = 0.49; 95% CI = 0.46-0.52; P < 0.001); 14.44 at the 4-15 month (RR = 0.51; 95% CI = 0.48-0.53; P < 0.001); 11.40 at the 16-27 month (RR = 0.41; 95% CI = 0.38-0.42; P < 0.001), and to 9.68 at the 28-39 month (RR = 0.34; 95% CI = 0.32-0.36; P < 0.001). The multilevel Poisson regression model showed a continuous significant decrease in incidence rate ratios, reaching 0.39 (p < 0.0001) during the 28th to 39th months after implementation of the intervention. CONCLUSIONS: This intervention resulted in a significant VAP rate reduction by 66% that was maintained throughout the 39-month period.

International Nosocomial Infection Control Consortium (INICC) report of health care associated infections, data summary of 45 countries for 2015 to 2020, adult and pediatric units, device-associated module.

BACKGROUND: Reporting on the International Nosocomial Infection Control Consortium study results from 2015 to 2020, conducted in 630 intensive care units across 123 cities in 45 countries spanning Africa, Asia, Eastern Europe, Latin America, and the Middle East. METHODS: Prospective intensive care unit patient data collected via International Nosocomial Infection Control Consortium Surveillance Online System. Centers for Disease Control and Prevention/National Health Care Safety Network definitions applied for device-associated health care-associated infections (DA-HAI). RESULTS: We gathered data from 204,770 patients, 1,480,620 patient days, 936,976 central line (CL)-days, 637,850 mechanical ventilators (MV)-days, and 1,005,589 urinary catheter (UC)-days. Our results showed 4,270 CL-associated bloodstream infections, 7,635 ventilator-associated pneumonia, and 3,005 UC-associated urinary tract infections. The combined rates of DA-HAIs were 7.28%, and 10.07 DA-HAIs per 1,000 patient days. CL-associated bloodstream infections occurred at 4.55 per 1,000 CL-days, ventilator-associated pneumonias at 11.96 per 1,000 MV-days, and UC-associated urinary tract infections at 2.91 per 1,000 UC days. In terms of resistance, Pseudomonas aeruginosa showed 50.73% resistance to imipenem, 44.99% to ceftazidime, 37.95% to ciprofloxacin, and 34.05% to amikacin. Meanwhile, Klebsiella spp had resistance rates of 48.29% to imipenem, 72.03% to ceftazidime, 61.78% to ciprofloxacin, and 40.32% to amikacin. Coagulase-negative Staphylococci and Staphylococcus aureus displayed oxacillin resistance in 81.33% and 53.83% of cases, respectively. CONCLUSIONS: The high rates of DA-HAI and bacterial resistance emphasize the ongoing need for continued efforts to control them.

Examining the impact of a 9-component bundle and the INICC multidimensional approach on catheter-associated urinary tract infection rates in 32 countries across Asia, Eastern Europe, Latin America, and the Middle East.

BACKGROUND: Catheter-Associated Urinary Tract Infections (CAUTIs) frequently occur in the intensive care unit (ICU) and are correlated with a significant burden. METHODS: We implemented a strategy involving a 9-element bundle, education, surveillance of CAUTI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CAUTI rates and performance feedback. This was executed in 299 ICUs across 32 low- and middle-income countries. The dependent variable was CAUTI per 1,000 UC days, assessed at baseline and throughout the intervention, in the second month, third month, 4 to 15 months, 16 to 27 months, and 28 to 39 months. Comparisons were made using a 2-sample t test, and the exposure-outcome relationship was explored using a generalized linear mixed model with a Poisson distribution. RESULTS: Over the course of 978,364 patient days, 150,258 patients utilized 652,053 UC-days. The rates of CAUTI per 1,000 UC days were measured. The rates decreased from 14.89 during the baseline period to 5.51 in the second month (risk ratio [RR] = 0.37; 95% confidence interval [CI] = 0.34-0.39; P < .001), 3.79 in the third month (RR = 0.25; 95% CI = 0.23-0.28; P < .001), 2.98 in the 4 to 15 months (RR = 0.21; 95% CI = 0.18-0.22; P < .001), 1.86 in the 16 to 27 months (RR = 0.12; 95% CI = 0.11-0.14; P < .001), and 1.71 in the 28 to 39 months (RR = 0.11; 95% CI = 0.09-0.13; P < .001). CONCLUSIONS: Our intervention, without substantial costs or additional staffing, achieved an 89% reduction in CAUTI incidence in ICUs across 32 countries, demonstrating feasibility in ICUs of low- and middle-income countries.

Emergence and circulation of azole-resistant C. albicans, C. auris and C. parapsilosis bloodstream isolates carrying Y132F, K143R or T220L Erg11p substitutions in Colombia.

Methods: Over a four-year period, 123 Candida bloodstream isolates were collected at a quaternary care hospital. The isolates were identified by MALDI-TOF MS and their fluconazole (FLC) susceptibility patterns were assessed according to CLSI guidelines. Subsequently, sequencing of ERG11, TAC1 or MRR1, and efflux pump activity were performed for resistant isolates. Results: Out of 123 clinical strains,C. albicans accounted for 37.4%, followed by C. tropicalis 26.8%, C. parapsilosis 19.5%, C. auris 8.1%, C. glabrata 4.1%, C. krusei 2.4% and C. lusitaniae 1.6%. Resistance to FLC reached 18%; in addition, a high proportion of isolates were cross-resistant to voriconazole. Erg11 amino acid substitutions associated with FLC-resistance (Y132F, K143R, or T220L) were found in 11/19 (58%) of FLCresistant isolates. Furthermore, novel mutations were found in all genes evaluated. Regarding efflux pumps, 8/19 (42%) of FLC-resistant Candida spp strains showed significant efflux activity. Finally, 6/19 (31%) of FLC-resistant isolates neither harbored resistance-associated mutations nor showed efflux pump activity. Among FLC-resistant species, C. auris 7/10 (70%) and C. parapsilosis 6/24 (25%) displayed the highest percentages of resistance (C. albicans 6/46, 13%). Discussion: Overall, 68% of FLC-resistant isolates exhibited a mechanism that could explain their phenotype (e.g. mutations, efflux pump activity, or both). We provide evidence that isolates from patients admitted to a Colombian hospital harbor amino acid substitutions related to resistance to one of the most commonly used molecules in the hospital setting, with Y132F being the most frequently detected.

Clinical and epidemiological characteristics of mpox: A descriptive cases series in Colombia.

INTRODUCTION: Colombia is the fifth most affected country by the global monkeypox outbreak and the second in LAC after Brazil. We describe the clinical and epidemiological characteristics of 521 patients with mpox in the country. METHODS: We conducted an observational analysis of laboratory-confirmed Mpox cases between June 29 and November 16, 2022. RESULTS: Most cases were young men living with HIV. The clinical evolution was primarily benign, with two deaths reported. We found some differences between women and men regarding their BMI, presence of lymphadenopathies, localization of lesions, and the antecedent of HIV infection. CONCLUSION: Although it seems that the epidemic curve for this outbreak of Mpox is decreasing not only in Colombia but globally, it could remain endemic. Therefore, it is necessary to maintain very close surveillance.

Comparative outcomes of direct-acting antiviral treatment in patients with HIV-Hepatitis C co-infection: insights from a single center experience in Colombia.

Background: Direct-acting antivirals (DAA) were introduced to Latin America with the aim of eliminating hepatitis C (HCV) in the region. There are scarce data on the outcomes of people living with HIV and HCV treated with these medications in Colombia. This study compares the outcomes of patients with HIV-HCV co-infection and HCV mono-infection treated with DAAs. Methods: Retrospective observational study including patients ≥18 years old with HCV infection treated with DAAs from August 2017 to December 2019 in a comprehensive center in Colombia. The main outcome was sustained virologic response (SVR). Secondary outcomes included reinfection, relapse and adverse events. Results: We included 223 individuals with HCV treated with DAAs; 142 (63.6%) individuals were mono-infected and 81 (36.3%) co-infected. Genotypes 1b (49.7%) and 4 (33.9%) were the most common. Overall SVR after DAA treatment was 96.8%. Relapse rate was 2.24%, reinfection rate was 6.28% and adverse events occurred in 27.8% of cases. SVR was comparable in patients with co- and mono-infection (95% vs 97.8%, p=0.245). Conclusion: DAA were effective in mono-infected (HCV) and co-infected (HCV/HIV) patients and reinfection was high in this last group.

Reasons for antiretroviral switching in Colombia: A retrospective cohort study.

INTRODUCTION: Long-term use of antiretroviral therapy (ART) for HIV infection might lead to the necessity of switching regimens. We aimed to analyze the reasons for the ART switch, the time-to-switch of ART, and its associated factors in a Colombian cohort. METHODS: We conducted a retrospective cohort in 20 HIV clinics, including participants ≥18 years old with confirmed HIV infection who underwent an ART switch from January 2017 to December 2019 with at least 6 months of follow-up. A time-to-event analysis and an exploratory Cox model were performed. RESULTS: 796 participants switched ART during the study period. The leading cause of ART switch was drug intolerance (n = 449; 56.4%) with a median time-to-switch of 12.2 months. The longest median time-to-switch was due to regimen simplification (42.4 months). People ≥50 years old (HR = 0.6; 95% CI (0.5-0.7) and CDC stage 3 at diagnosis (HR = 0.8; 95% CI (0.6-0.9) had less hazard for switching ART over time. CONCLUSIONS: In this Colombian cohort, drug intolerance was the main cause of the ART switch, and the time-to-switch is shorter than reports from other countries. In Colombia, it is crucial to apply current recommendations for ART initiation to choose regimens with a better tolerability profile.

Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population.

The SARS CoV-2 antibody and CD4+ T cell responses induced by natural infection and/or vaccination decline over time and cross-recognize other viral variants at different levels. However, there are few studies evaluating the levels and durability of the SARS CoV-2-specific antibody and CD4+ T cell response against the Mu, Gamma, and Delta variants. Here, we examined, in two ambispective cohorts of naturally-infected and/or vaccinated individuals, the titers of anti-RBD antibodies and the frequency of SARS-CoV-2-specific CD4+ T cells up to 6 months after the last antigen exposure. In naturally-infected individuals, the SARS-CoV-2 antibody response declined 6 months post-symptoms onset. However, the kinetic observed depended on the severity of the disease, since individuals who developed severe COVID-19 maintained the binding antibody titers. Also, there was detectable binding antibody cross-recognition for the Gamma, Mu, and Delta variants, but antibodies poorly neutralized Mu. COVID-19 vaccines induced an increase in antibody titers 15-30 days after receiving the second dose, but these levels decreased at 6 months. However, as expected, a third dose of the vaccine caused a rise in antibody titers. The dynamics of the antibody response upon vaccination depended on the previous SARS-CoV-2 exposure. Lower levels of vaccine-induced antibodies were associated with the development of breakthrough infections. Vaccination resulted in central memory spike-specific CD4+ T cell responses that cross-recognized peptides from the Gamma and Mu variants, and their duration also depended on previous SARS-CoV-2 exposure. In addition, we found cross-reactive CD4+ T cell responses in unexposed and unvaccinated individuals. These results have important implications for vaccine design for new SARS-CoV-2 variants of interest and concern.

Corrigendum: Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population.

[This corrects the article DOI: 10.3389/fimmu.2023.1241038.].

Multinational prospective cohort study of rates and risk factors for ventilator-associated pneumonia over 24 years in 42 countries of Asia, Africa, Eastern Europe, Latin America, and the Middle East: Findings of the International Nosocomial Infection Control Consortium (INICC).

Objective: Rates of ventilator-associated pneumonia (VAP) in low- and middle-income countries (LMIC) are several times above those of high-income countries. The objective of this study was to identify risk factors (RFs) for VAP cases in ICUs of LMICs. Design: Prospective cohort study. Setting: This study was conducted across 743 ICUs of 282 hospitals in 144 cities in 42 Asian, African, European, Latin American, and Middle Eastern countries. Participants: The study included patients admitted to ICUs across 24 years. Results: In total, 289,643 patients were followed during 1,951,405 patient days and acquired 8,236 VAPs. We analyzed 10 independent variables. Multiple logistic regression identified the following independent VAP RFs: male sex (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.16-1.28; P < .0001); longer length of stay (LOS), which increased the risk 7% per day (aOR, 1.07; 95% CI, 1.07-1.08; P < .0001); mechanical ventilation (MV) utilization ratio (aOR, 1.27; 95% CI, 1.23-1.31; P < .0001); continuous positive airway pressure (CPAP), which was associated with the highest risk (aOR, 13.38; 95% CI, 11.57-15.48; P < .0001); tracheostomy connected to a MV, which was associated with the next-highest risk (aOR, 8.31; 95% CI, 7.21-9.58; P < .0001); endotracheal tube connected to a MV (aOR, 6.76; 95% CI, 6.34-7.21; P < .0001); surgical hospitalization (aOR, 1.23; 95% CI, 1.17-1.29; P < .0001); admission to a public hospital (aOR, 1.59; 95% CI, 1.35-1.86; P < .0001); middle-income country (aOR, 1.22; 95% CI, 15-1.29; P < .0001); admission to an adult-oncology ICU, which was associated with the highest risk (aOR, 4.05; 95% CI, 3.22-5.09; P < .0001), admission to a neurologic ICU, which was associated with the next-highest risk (aOR, 2.48; 95% CI, 1.78-3.45; P < .0001); and admission to a respiratory ICU (aOR, 2.35; 95% CI, 1.79-3.07; P < .0001). Admission to a coronary ICU showed the lowest risk (aOR, 0.63; 95% CI, 0.51-0.77; P < .0001). Conclusions: Some identified VAP RFs are unlikely to change: sex, hospitalization type, ICU type, facility ownership, and country income level. Based on our results, we recommend focusing on strategies to reduce LOS, to reduce the MV utilization ratio, to limit CPAP use and implementing a set of evidence-based VAP prevention recommendations.

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. FINDINGS: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING: National Institutes of Health.

Multinational prospective cohort study of incidence and risk factors for central line-associated bloodstream infections in ICUs of 8 Latin American countries.

BACKGROUND: Our objective was to identify central line (CL)-associated bloodstream infections (CLABSI) rates and risk factors in Latin-America. METHODS: From January 1, 2014 to February 10, 2022, we conducted a multinational multicenter prospective cohort study in 58 ICUs of 34 hospitals in 21 cities in 8 Latin American countries (Argentina, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama). We applied multiple-logistic regression. Outcomes are shown as adjusted-odds ratios (aOR). RESULTS: About 29,385 patients were hospitalized during 92,956 days, acquired 400 CLABSIs, and pooled CLABSI rate was 4.30 CLABSIs per 1,000 CL-days. We analyzed following 10 variables: Gender, age, length of stay (LOS) before CLABSI acquisition, CL-days before CLABSI acquisition, CL-device utilization (DU) ratio, CL-type, tracheostomy use, hospitalization type, intensive care unit (ICU) type, and facility ownership, Following variables were independently associated with CLABSI: LOS before CLABSI acquisition, rising risk 3% daily (aOR=1.03;95%CI=1.02-1.04; P < .0001); number of CL-days before CLABSI acquisition, rising risk 4% per CL-day (aOR=1.04;95%CI=1.03-1.05; P < .0001); publicly-owned facility (aOR=2.33;95%CI=1.79-3.02; P < .0001). ICU with highest risk was medical-surgical (aOR=2.61;95%CI=1.41-4.81; P < .0001). CL with the highest risk were femoral (aOR=2.71;95%CI=1.61-4.55; P < .0001), and internal-jugular (aOR=2.62;95%CI=1.82-3.79; P < .0001). PICC (aOR=1.25;95%CI=0.63-2.51; P = .52) was not associated with CLABSI risk. CONCLUSIONS: Based on these findings it is suggested to focus on reducing LOS, CL-days, using PICC instead of femoral or internal-jugular; and implementing evidence-based CLABSI prevention recommendations.

Multinational prospective study of incidence and risk factors for central-line-associated bloodstream infections in 728 intensive care units of 41 Asian, African, Eastern European, Latin American, and Middle Eastern countries over 24 years.

OBJECTIVE: To identify central-line (CL)-associated bloodstream infection (CLABSI) incidence and risk factors in low- and middle-income countries (LMICs). DESIGN: From July 1, 1998, to February 12, 2022, we conducted a multinational multicenter prospective cohort study using online standardized surveillance system and unified forms. SETTING: The study included 728 ICUs of 286 hospitals in 147 cities in 41 African, Asian, Eastern European, Latin American, and Middle Eastern countries. PATIENTS: In total, 278,241 patients followed during 1,815,043 patient days acquired 3,537 CLABSIs. METHODS: For the CLABSI rate, we used CL days as the denominator and the number of CLABSIs as the numerator. Using multiple logistic regression, outcomes are shown as adjusted odds ratios (aORs). RESULTS: The pooled CLABSI rate was 4.82 CLABSIs per 1,000 CL days, which is significantly higher than that reported by the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC NHSN). We analyzed 11 variables, and the following variables were independently and significantly associated with CLABSI: length of stay (LOS), risk increasing 3% daily (aOR, 1.03; 95% CI, 1.03-1.04; P < .0001), number of CL days, risk increasing 4% per CL day (aOR, 1.04; 95% CI, 1.03-1.04; P < .0001), surgical hospitalization (aOR, 1.12; 95% CI, 1.03-1.21; P < .0001), tracheostomy use (aOR, 1.52; 95% CI, 1.23-1.88; P < .0001), hospitalization at a publicly owned facility (aOR, 3.04; 95% CI, 2.31-4.01; P <.0001) or at a teaching hospital (aOR, 2.91; 95% CI, 2.22-3.83; P < .0001), hospitalization in a middle-income country (aOR, 2.41; 95% CI, 2.09-2.77; P < .0001). The ICU type with highest risk was adult oncology (aOR, 4.35; 95% CI, 3.11-6.09; P < .0001), followed by pediatric oncology (aOR, 2.51;95% CI, 1.57-3.99; P < .0001), and pediatric (aOR, 2.34; 95% CI, 1.81-3.01; P < .0001). The CL type with the highest risk was internal-jugular (aOR, 3.01; 95% CI, 2.71-3.33; P < .0001), followed by femoral (aOR, 2.29; 95% CI, 1.96-2.68; P < .0001). Peripherally inserted central catheter (PICC) was the CL with the lowest CLABSI risk (aOR, 1.48; 95% CI, 1.02-2.18; P = .04). CONCLUSIONS: The following CLABSI risk factors are unlikely to change: country income level, facility ownership, hospitalization type, and ICU type. These findings suggest a focus on reducing LOS, CL days, and tracheostomy; using PICC instead of internal-jugular or femoral CL; and implementing evidence-based CLABSI prevention recommendations.