Gaps in the continuum of care in HIV-positive adults and the need for caution in those returning to care after loss to follow-up.

Loss to follow-up (LTFU) and interruption of antiretroviral therapy (ART) are associated with worse outcomes in people with HIV (PWH). Little is known about gaps in the continuum of care. We conducted a retrospective cohort study including adult PWH with at least one clinical visit during 2000-2017. Three groups of care were defined: those constantly retained in care (constantly-RIC), definitively LTFU (dLTFU), and those who returned to care (RTC) after being LTFU for 1 year. We analyzed characteristics of individuals at enrollment. Among 2967 patients, 1565 (53%) were constantly-RIC, 826 (28%) dLTFU, and 576 (19%) RTC. CD4+ ≥350 cells/µL at enrollment was more frequent in RTC patients (43% vs 28% in both constantly-RIC and dLTFU groups, p < 0.01). Time since enrollment to ART initiation was longer in dLTFU (3.3 weeks) and RTC groups (6.0 weeks) in comparison with constantly-RIC patients (2.0 weeks, p < 0.01). Multivariate analysis showed significant differences between groups. Older and ART-naïve patients at enrollment were less likely to have gaps in the continuum of care. Those with non-MSM transmission were less likely to RTC. Patients with CD4+ ≥350 cells/µL at enrollment were more likely to reengage in care. Interventions should be tailored for those at risk of LTFU.

Predictors of Poor Outcomes in Young Non-Comorbid Patients with COVID-19.

Background: Prognostic factors in previously healthy young patients with COVID-19 remained understudied. Objectives: The objective of the study was to identify factors associated with in-hospital death or need for invasive mechanical ventilation (IMV) in young (aged ≤ 65 years) and previously healthy patients with COVID-19. Methods: We conducted a prospective cohort study that included patients admitted with COVID-19. The primary outcome was in-hospital death/need for IMV. Secondary outcomes included need for IMV during follow-up, days on IMV, length of stay (LOS), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and pulmonary embolism (PE). Bivariate and multivariate analyses were performed. Results: Among 92 patients, primary outcome occurred in 16 (17%), death in 12 (13%), need for IMV in 16 (17%), HAP/VAP in 7 (8%), and PE in 2 (2%). Median LOS and IMV duration were 7 and 12 days, respectively. Independent associations were found between the primary outcome and male sex (Adjusted odds ratio [aOR] 7.1, 95%CI 1.1-46.0, p < 0.05), D-dimer levels > 1000ng/mL (aOR 9.0, 95%CI 1.6-49.1, p < 0.05), and RT-PCR Ct-value ≤ 24 on initial swab samples (aOR 14.3, 95%CI 2.0-101.5, p < 0.01). Conclusions: In young and non-comorbid COVID-19 patients, male sex, higher levels of D-dimer, and low SARS-CoV-2 RT-PCR Ct-value on an initial nasopharyngeal swab were independently associated with increased in-hospital mortality or need for IMV. (Rev Invest Clin. 2022;74(5):268-75).

Effect of Tocilizumab in Mortality among Patients with Severe and Critical Covid-19: Experience in a Third-Level Medical Center.

BACKGROUND: Trials evaluating safety and efficacy of tocilizumab in coronavirus disease 19 (COVID-19) show contradictory results. OBJECTIVE: The objective of the study was to evaluate the effect of tocilizumab in hospital mortality among patients with severe COVID-19 in a third-level medical center. METHODS: This prospective cohort study included patients with severe and critical COVID-19. Primary outcome was death during hospitalization. Secondary outcomes included invasive mechanical ventilation (IMV), days on IMV, ventilator-free days (VFDs), length of hospital stay (LOS), and development of hospitalacquired infections (HAIs). Bivariate, multivariate, and propensity score matching analysis were performed. RESULTS: During the study period, 99/794 (12%) patients received tocilizumab. Male patients, health care workers, and patients with increased inflammatory markers received tocilizumab more frequently. No difference in hospital mortality was observed between groups (34% vs. 34%, p = 0.98). Tocilizumab was not independently associated with mortality. No significant treatment effects were observed in propensity score analysis. IMV was more frequent (46% vs. 11%, p < 0.01) and LOS was longer (12 vs. 7 days, p < 0.01) in the tocilizumab group, reflecting increased severity. Although HAIs were more frequent in the tocilizumab group (22% vs. 10%, p < 0.01), no difference was seen after adjusting for IMV (38% vs. 40%, p = 0.86). CONCLUSIONS: In our study, tocilizumab was not associated with decreased hospital mortality among patients with severe COVID-19.

Changes in Radial Artery Pulse Pressure During a Fluid Challenge Cannot Assess Fluid Responsiveness in Patients With Septic Shock.

BACKGROUND: Arterial blood pressure is the most common variable used to assess the response to a fluid challenge in routine clinical practice. The aim of this study was to evaluate the accuracy of the change in the radial artery pulse pressure (rPP) to detect the change in cardiac output after a fluid challenge in patients with septic shock. METHODS: Prospective observational study including 35 patients with septic shock in which rPP and cardiac output were measured before and after a fluid challenge with 400 mL of crystalloid solution. Cardiac output was measured with intermittent thermodilution technique using a pulmonary artery catheter. Patients were divided between responders (increase >15% of cardiac output after fluid challenge) and nonresponders. The area under the receiver operating characteristic curve (AUROC), Pearson correlation coefficient and paired Student t test were used in statistical analysis. RESULTS: Forty-three percent of the patients were fluid responders. The change in rPP could not neither discriminate between responders and nonresponders (AUROC = 0.52; [95% confidence interval: 0.31-0.72] P = .8) nor correlate (r = .21, P = .1) with the change in cardiac output after the fluid challenge. CONCLUSIONS: The change in rPP neither discriminated between fluid responders and nonresponders nor correlated with the change in cardiac output after a fluid challenge. The change in rPP cannot serve as a surrogate of the change in cardiac output to assess the response to a fluid challenge in patients with septic shock.

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF PATIENTS DIAGNOSED WITH COVID-19 IN A TERTIARY CARE CENTER IN MEXICO CITY: A PROSPECTIVE COHORT STUDY.

BACKGROUND: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. OBJECTIVE: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). METHODS: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. RESULTS: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. CONCLUSIONS: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.

Favourable effect of clavulanic acid on the minimum inhibitory concentrations of cefixime and ceftibuten in ESBL-producing Escherichia coli and Klebsiella pneumoniae.

OBJECTIVES: The use of cephalosporins combined with clavulanate for the treatment of ESBL-harbouring Enterobacteriaceae has been scarcely described. We aimed to describe the effect of different concentrations of clavulanate in the MIC of cefixime and ceftibuten of ESBL-producing Escherichia coli and Klebsiella pneumoniae. METHODS: ESBL-producing E. coli and K. pneumoniae isolates were studied. Fixed concentrations of cefixime and ceftibuten (ranges of 32-0.25 and 64-0.5 ng/ml, respectively) were used. Combinations of cefixime/clavulanate and ceftibuten/clavulanate in different ratios (1:0, 1:1, 2:1, 4:1, 8:1, 16:1, 32:1) were tested. MIC were determined by broth microdilution. RESULTS: A total of 6 ESBL-producing E. coli, 6 ESBL-producing K. pneumoniae and 2 control E. coli were tested. When different quantities of clavulanate were added to cefixime and ceftibuten, greater than two-fold decreases in the MIC were observed. When testing the 1:1 cefixime/clavulanate ratio, 10/12 isolates were susceptible. When the ratios 2:1, 4:1, 8:1 and 16:1 were tested, susceptibility was noted for 9/12, 8/12, 4/12 and 5/12 isolates, respectively. Only 2/12 K. pneumoniae isolates were susceptible when the ratio 32:1 was tested. When testing ceftibuten/clavulanate, all isolates remained susceptible across all experiments. CONCLUSIONS: Clavulanic acid has a favourable effect in reducing the MIC of cefixime and ceftibuten in isolates of ESBL-producing E. coli and K. pneumoniae. Combining clavulanate with ceftibuten or cefixime could be a useful treatment strategy.

Clinical and Microbiological Characteristics of Febrile Neutropenia During Induction Chemotherapy in Adults With Acute Leukemia.

BACKGROUND: Few studies regarding infectious causes of febrile neutropenia (FN) in Mexico are available. AIMS: We aimed to describe clinical and microbiological characteristics of FN episodes during induction chemotherapy in adults with acute leukemia. METHODS AND RESULTS: This retrospective cohort from a Mexican tertiary care center included adults with newly diagnosed acute leukemia between January 2014, and December 2018. Clinical and microbiological characteristics were summarized using descriptive statistics. Univariate analyses for associations between clinical characteristics and FN and/or death were made; logistic regression analysis was performed to assess relationships with FN. Kaplan-Meier survival estimates were modeled for antimicrobial prophylaxis and FN. Ninety-five patients were included. Median age was 28 (IQR 20-43), 49 (52%) were males, and 74 (78%) developed FN (74/95). Among these, 98% had an identified source of infection (73/74) and 65% had >1. Common infections were urinary tract infection (24%), bacterial sinusitis (20%), and bacterial pneumonia (19%). Gram-negatives were the most frequently isolated microorganisms (69%), followed by Gram-positives (21%), and fungi (9%). Antimicrobial prophylaxis was inversely associated with FN (aOR = 0.07, CI 0.008-0.060, p = 0.02). Invasive fungal diseases were associated with 30-day mortality (aOR = 9.46, 95% CI 1.66-54.05). CONCLUSION: Infections caused 98% of the FN episodes. Gram-negative bacteria are the most common pathogens.

Cephalotin Versus Dicloxacillin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteraemia: A Retrospective Cohort Study.

BACKGROUND: First-line treatments for methicillin-susceptible S. aureus (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to use other options like dicloxacillin and cephalotin. This study aims to describe and compare the safety and efficacy of cephalotin and dicloxacillin for the treatment of MSSA bacteraemia. METHODS: This retrospective study was conducted in a referral centre in Mexico City. We identified MSSA isolates in blood cultures from 1 January 2012 to 31 December 2022. Patients ≥ 18 years of age, with a first episode of MSSA bacteraemia, who received cephalotin or dicloxacillin as the definitive antibiotic treatment, were included. The primary outcome was in-hospital all-cause mortality. RESULTS: We included 202 patients, of which 48% (97/202) received cephalotin as the definitive therapy and 52% (105/202) received dicloxacillin. In-hospital all-cause mortality was 20.7% (42/202). There were no differences in all-cause in-hospital mortality between patients receiving cephalotin or dicloxacillin (20% vs. 21%, p = 0.43), nor in 30-day all-cause mortality (14% vs. 18%, p = 0.57) or 90-day all-cause mortality (24% vs. 22%, p = 0.82). No severe adverse reactions were associated with either antibiotic. CONCLUSIONS: Cephalotin and dicloxacillin were equally effective for treating MSSA bacteraemia, and both showed an adequate safety profile.

Histoplasmosis Beyond Human Immunodeficiency Virus (HIV): Clinical Characteristics and Outcomes in a Non-HIV Population.

Histoplasmosis is an endemic and invasive mycosis caused by Histoplasma capsulatum. We conducted a retrospective study comparing immunosuppressed patients without human immunodeficiency virus (HIV) with a historical cohort of people with HIV and histoplasmosis. We included 199 patients with proven or probable histoplasmosis, of which 25.1% were people without HIV. Diabetes mellitus, chronic kidney disease, hematologic neoplasms, rheumatologic diseases, and transplantations were more frequent among people without HIV (P < .01). Forty-four percent of immunocompromised patients without HIV died within the first 6-week period following their diagnosis. A high suspicion index for histoplasmosis should be kept in immunosuppressed patients.

Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients to prevent hospitalization or death during the Omicron era: a propensity score-matched study.

Background: Even though worldwide death rates from coronavirus disease 2019 (COVID-19) have decreased, the threat of disease progression and death for high-risk groups continues. Few direct comparisons between the available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals have been made. Objective: We aimed to compare two SARS-CoV-2 antivirals (nirmatrelvir/ritonavir and remdesivir) against all-cause hospitalization or death. Design: This is a propensity score-matched cohort study. Methods: We included all high-risk outpatients with COVID-19 in a tertiary referral center in Mexico City from 1 January 2022 to 31 July 2023. The primary outcome was all-cause hospitalization or death 28 days after symptom onset. The secondary outcome was COVID-19-associated hospitalization or death 28 days after symptom onset. Logistic regression analysis for characteristics associated with the primary outcome and a multi-group comparison with Kaplan-Meier survival estimates were performed. Results: Of 1566 patients analyzed, 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. The median age was 60 years (interquartile range: 46-72), 62.5% were female and 97.8% had at least one comorbidity. The use of nirmatrelvir/ritonavir was associated with an absolute risk reduction of 8.8% and a relative risk reduction of 90% for all-cause hospitalization or death. The use of remdesivir was associated with an absolute risk reduction of 6.4% and a relative risk reduction of 66% for all-cause hospitalization or death. In multivariable analysis, both antivirals reduced the odds of 28-day all-cause hospitalization or death [nirmatrelvir/ritonavir odds ratio (OR) 0.08 - 95% confidence interval (CI): 0.03-0.19, remdesivir OR 0.29 - 95% CI: 0.18-0.45]. Conclusion: In high-risk COVID-19 outpatients, early antiviral treatment with nirmatrelvir/ritonavir or remdesivir was associated with lower 28-day all-cause hospitalization or death.

Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients In this study, we included high-risk non-hospitalized patients with confirmed mild COVID-19. We compared those who received antiviral treatment (nirmatrelvir/ritonavir or remdesivir) against those who only received symptomatic treatment. The aim was to detect differences in hospitalization or death 28 days after symptom onset. We analyzed 1566 patients: 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. Most patients were female and over 60 years old. The most common comorbidities were chronic hypertension (44%), diabetes mellitus (26%), and autoimmune diseases (25%); systemic immunosuppression was registered in 35% of patients. Hospitalization or death 28 days after symptom onset occurred in 168 patients (136 in the symptomatic treatment group, 27 in the remdesivir group, and 5 in the nirmatrelvir/ritonavir group). Considering multiple variables like age, sex, comorbidities, and previous vaccination, both antivirals significantly reduced the odds of hospitalization or death (nirmatrelvir/ritonavir odds ratio 0.08, 95% confidence interval 0.03-0.19; remdesivir odds ratio 0.29, 95% confidence interval 0.18-0.45).

Delivering acute stroke care in a middle-income country. The Mexican model: "ResISSSTE Cerebro".

Introduction: Founded in 2019, the "ResISSSTE Cerebro" program is the first and only stroke network within the Mexican public health system. One advanced stroke center (ASC) and seven essential stroke centers (ESC) provide acute stroke (AS) care through a modified hub-and-spoke model. This study describes the workflow, metrics, and outcomes in AS obtained during the program's third year of operation. Materials and methods: Participants were adult beneficiaries of the ISSSTE health system in Mexico City with acute focal neurological deficit within 24 h of symptom onset. Initial evaluation could occur at any facility, but the stroke team at the ASC took all decisions regarding treatment and transfers of patients. Registered variables included demographics, stroke risk factors, AS treatment workflow time points, and clinical outcome measures. Results: We analyzed data from 236 patients, 104 (44.3%) men with a median age of 71 years. Sixty percent of the patients were initially evaluated at the ESC, and 122 (85.9%) were transferred to the ASC. The median transfer time was 123 min. The most common risk factor was hypertension (73.6%). Stroke subtypes were ischemic (86.0%) and hemorrhagic (14.0%). Median times for onset-to-door, door-to-imaging, door-to-needle, and door-to-groin were: 135.5, 37.0, 76.0, and 151.5 min, respectively. The rate of intravenous thrombolysis was 35%. Large vessel occlusion was present in 63 patients, from whom 44% received endovascular therapy; 71.4% achieved early clinical improvement (median NIHSS reduction of 11 points). Treatment-associated morbimortality was 3.4%. Conclusion: With the implementation of a modified hub-and-spoke model, this study shows that delivery of AS care in low- and middle-income countries is feasible and achieves good clinical outcomes.

Fungal Infections in the ICU during the COVID-19 Pandemic in Mexico.

Background: Invasive Fungal Infections (IFI) are emergent complications of COVID-19. In this study, we aim to describe the prevalence, related factors, and outcomes of IFI in critical COVID-19 patients. Methods: We conducted a nested case-control study of all COVID-19 patients in the intensive care unit (ICU) who developed any IFI and matched age and sex controls for comparison (1:1) to evaluate IFI-related factors. Descriptive and comparative analyses were made, and the risk factors for IFI were compared versus controls. Results: We found an overall IFI prevalence of 9.3% in COVID-19 patients in the ICU, 5.6% in COVID-19-associated pulmonary aspergillosis (CAPA), and 2.5% in invasive candidiasis (IC). IFI patients had higher SOFA scores, increased frequency of vasopressor use, myocardial injury, and more empirical antibiotic use. CAPA was classified as possible in 68% and 32% as probable by ECMM/ISHAM consensus criteria, and 57.5% of mortality was found. Candidemia was more frequent for C. parapsilosis Fluconazole resistant outbreak early in the pandemic, with a mortality of 28%. Factors related to IFI in multivariable analysis were SOFA score > 2 (aOR 5.1, 95% CI 1.5-16.8, p = 0.007) and empiric antibiotics for COVID-19 (aOR 30, 95% CI 10.2-87.6, p = <0.01). Conclusions: We found a 9.3% prevalence of IFIs in critically ill patients with COVID-19 in a single center in Mexico; factors related to IFI were associated with higher SOFA scores and empiric antibiotic use for COVID-19. CAPA is the most frequent type of IFI. We did not find a mortality difference.

Evaluation of the BD Phoenix Carbapenemase-Producing Organism Panels for the Detection of Carbapenemase Producers in Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.

The classification of carbapenemases can help guide therapy. The present study evaluated the performance of the CPO detection test, included in the BD Phoenix™ NMIC-501 panel for the detection and classification of carbapenemases on the representative molecularly characterized strains collection from Mexico. Carbapenem non-susceptible isolates collected in Mexico were included. The clinical isolates (n = 484) comprised Klebsiella pneumoniae (n = 154), Escherichia coli (n = 150), and P. aeruginosa (n = 180). BD Phoenix CPO NMIC-504 and NMIC-501 panels were used for the identification of species, antimicrobial susceptibility tests, and detection of CPOs. For the detection of carbapenemase-encoding genes, E. coli and K. pneumoniae were evaluated using PCR assays for blaNDM-1, blaKPC, blaVIM, blaIMP, and blaOXA-48-like. For P. aeruginosa, blaVIM, blaIMP, and blaGES were detected using PCR. Regarding E. coli, the CPO panels had a sensitivity of 70% and specificity of 83.33% for the detection of a class B carbapenemase (blaNDM in the molecular test). Regarding K. pneumoniae, the panels had a sensitivity of 75% and specificity of 100% for the detection of a class A carbapenemase (blaKPC in the molecular test). The Phoenix NMIC-501 panels are reliable for detecting class B carbapenemases in E. coli. The carbapenemase classification in K. pneumoniae for class A carbapenemases has a high specificity and PPV; thus, a positive result is of high value.

Risk Factors Associated with the Development of Hospital-Acquired Infections in Hospitalized Patients with Severe COVID-19.

Recognition of risk factors for hospital-acquired infections (HAI) in patients with COVID-19 is warranted. We aimed to describe factors associated with the development of HAI in patients with severe COVID-19. We conducted a retrospective cohort study including all adult patients admitted with severe COVID-19 between March 2020 and November 2020. The primary outcome was HAI development. Bivariate and multiple logistic regression models were constructed. Among 1540 patients, HAI occurred in 221 (14%). A total of 299 episodes of HAI were registered. The most common HAI were hospital-acquired/ventilation-associated pneumonia (173 episodes) and primary bloodstream infection (66 episodes). Death occurred in 387 (35%) patients and was more frequent in patients with HAI (38% vs. 23%, p < 0.01). Early mechanical ventilation (aOR 18.78, 95% CI 12.56-28.07), chronic kidney disease (aOR 3.41, 95% CI 1.4-8.27), use of corticosteroids (aOR 2.95, 95% CI 1.92-4.53) and tocilizumab (aOR 2.68, 95% CI 1.38-5.22), age ≥ 60 years (aOR 1.91, 95% CI 1.27-2.88), male sex (aOR 1.52, 95% CI 1.03-2.24), and obesity (aOR 1.49, 95% CI 1.03-2.15) were associated with HAI. In patients with severe COVID-19, mechanical ventilation within the first 24 h upon admission, chronic kidney disease, use of corticosteroids, use of tocilizumab, age ≥ 60 years, male sex, and obesity were associated with a higher risk of HAI.

Predictors of Mortality in Patients with Infections Due to Carbapenem-Resistant Gram-Negative Bacteria.

INTRODUCTION: Infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) are a significant cause of mortality and represent a serious challenge to health systems. The early identification of mortality predictors could guide appropriate treatment and follow-up. We aimed to identify the factors associated with 90-day all-cause mortality in patients with CR-GNB infections. METHODS: We conducted a cohort study from 1 January 2019 to 30 April 2022. The primary outcome was death from any cause during the first 90 days after the date of the first CR-GNB-positive culture. Secondary outcomes included infection relapse, invasive mechanical ventilation during follow-up, need for additional source control, acute kidney injury, Clostridioides difficile infection, and all-cause hospital admission after initial discharge. Bivariate and multivariate Cox-proportional hazards models were constructed to identify the factors independently associated with 90-day all-cause mortality. RESULTS: A total of 225 patients with CR-GNB infections were included. Death occurred in 76 (34%) cases. The most-reported comorbidities were immunosuppression (43%), arterial hypertension (35%), and COVID-19 (25%). The median length of stay in survivors was 18 days (IQR 10-34). Mechanical ventilation and ICU admission after diagnosis occurred in 8% and 11% of cases, respectively. Both infection relapse and rehospitalisation occurred in 18% of cases. C. difficile infection was diagnosed in 4% of cases. Acute kidney injury was documented in 22% of patients. Mechanical ventilation after diagnosis, ICU admission after diagnosis, and acute kidney injury in the first ten days of appropriate treatment were more frequently reported among non-survivors. In the multivariate analysis, age (HR 1.19 (95%CI 1.00-1.83)), immunosuppression (HR 1.84 (95%CI 1.06-3.18)), and septic shock at diagnosis (HR 2.40 (95% 1.41-4.08)) had an independent association with death during the first 90 days after the CR-GNB infection diagnosis. Receiving antibiogram-guided appropriate treatment was independently associated with a lower risk of death (HR 0.25 (95%CI 0.14-0.46)). CONCLUSIONS: The presence of advanced age, immunosuppression, septic shock at diagnosis, and inappropriate treatment are associated with higher 90-day all-cause mortality in hospitalised patients with infections due to CR-GNB. Recognition of the risk factors for adverse outcomes could further assist in patient care and the design of interventional studies that address the severe and widespread problem that is carbapenem resistance.

Whole genome analysis of Gram-negative bacteria using the EPISEQ CS application and other bioinformatic platforms.

OBJECTIVES: To determine genomic characteristics and molecular epidemiology of carbapenem non-susceptible Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa from medical centres of Mexico using whole genome sequencing data analysed with the EPISEQⓇ CS application and other bioinformatic platforms. METHODS: Clinical isolates collected from 28 centres in Mexico included carbapenem-non-susceptible K. pneumoniae (n = 22), E. coli (n = 24), A. baumannii (n = 16), and P. aeruginosa (n = 13). Isolates were subjected to whole genome sequencing using the Illumina (MiSeq) platform. FASTQ files were uploaded to the EPISEQⓇ CS application for analysis. Additionally, the tools Kleborate v2.0.4 and Pathogenwatch were used as comparators for Klebsiella genomes, and the bacterial whole genome sequence typing database was used for E. coli and A. baumannii. RESULTS: For K. pneumoniae, both bioinformatic approaches detected multiple genes encoding aminoglycoside, quinolone, and phenicol resistance, and the presence of blaNDM-1 explained carbapenem non-susceptibility in 18 strains and blaKPC-3 in four strains. Regarding E. coli, both EPISEQⓇ CS and bacterial whole genome sequence typing database analyses detected multiple virulence and resistance genes: 20 of 24 (83.3%) strains carried blaNDM, 3 of 24 (12.4%) carried blaOXA-232, and 1 carried blaOXA-181. Genes that confer resistance to aminoglycosides, tetracyclines, sulfonamides, phenicols, trimethoprim, and macrolides were also detected by both platforms. Regarding A. baumannii, the most frequent carbapenemase-encoding gene detected by both platforms was blaOXA-72, followed by blaOXA-66. Both approaches detected similar genes for aminoglycosides, carbapenems, tetracyclines, phenicols, and sulfonamides. Regarding P. aeruginosa, blaVIM, blaIMP, and blaGES were the more frequently detected. Multiple virulence genes were detected in all strains. CONCLUSION: Compared to the other available platforms, EPISEQⓇ CS enabled a comprehensive resistance and virulence analysis, providing a reliable method for bacterial strain typing and characterization of the virulome and resistome.

Active Surveillance of Antimicrobial Resistance and Carbapenemase-Encoding Genes According to Sites of Care and Age Groups in Mexico: Results from the INVIFAR Network.

We analyzed the antimicrobial resistance (AMR) data of 6519 clinical isolates of Escherichia coli (n = 3985), Klebsiella pneumoniae (n = 775), Acinetobacter baumannii (n = 163), Pseudomonas aeruginosa (n = 781), Enterococcus faecium (n = 124), and Staphylococcus aureus (n = 691) from 43 centers in Mexico. AMR assays were performed using commercial microdilution systems (37/43) and the disk diffusion susceptibility method (6/43). The presence of carbapenemase-encoding genes was assessed using PCR. Data from centers regarding site of care, patient age, and clinical specimen were collected. According to the site of care, the highest AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from ICU patients. In contrast, in A. baumannii, higher AMR was observed in isolates from hospitalized non-ICU patients. According to age group, the highest AMR was observed in the ≥60 years age group for E. coli, E. faecium, and S. aureus, and in the 19-59 years age group for A. baumannii and P. aeruginosa. According to clinical specimen type, a higher AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from blood specimens. The most frequently detected carbapenemase-encoding gene in E. coli was blaNDM (84%).

Early Outpatient Treatment With Remdesivir in Patients at High Risk for Severe COVID-19: A Prospective Cohort Study.

Background: Early treatment of coronavirus disease 2019 (COVID-19) with remdesivir in high-risk patients, including those with immunosuppression of different causes, has not been evaluated. The objective of this study was to assess the clinical effectiveness of early remdesivir treatment among patients with mild to moderate COVID-19 at high risk of progression. Methods: This prospective cohort comparative study was conducted in a tertiary referral center in Mexico City. Patients with mild to moderate COVID-19 at high risk for progression were treated with an ambulatory 3-day course of remdesivir. The primary efficacy composite outcome was hospitalization or death at 28 days after symptom onset. A Cox proportional hazards regression model was used to identify associations with the primary outcome. Results: From December 1, 2021, to April 30, 2022, a total of 196 high-risk patients were diagnosed with COVID-19, of whom 126 were included in this study (43%, 54/126, received remdesivir; 57%, 72/126, did not receive remdesivir). Baseline clinical characteristics were similar between groups; autoimmune diseases (39/126), solid organ transplant (31/126), and malignant neoplasms (24/126) were the most common immunocompromising conditions. Diabetes mellitus was strongly associated with the primary outcome in both groups. Prior severe acute respiratory syndrome coronavirus 2 infection or vaccination was not independently associated with COVID-19 progression. Treatment with remdesivir significantly reduced the odds of hospitalization or death (adjusted hazard ratio, 0.16; 95% CI, 0.06-0.44; P < .01). Conclusions: Early outpatient treatment with remdesivir significantly reduces hospitalization or death by 84% in high-risk, majority immunosuppressed patients with Omicron variant COVID-19.

Outcomes of patients with severe and critical COVID-19 treated with dexamethasone: a prospective cohort study.

Dexamethasone implementation for COVID-19 management represented a milestone but data regarding its impact and safety have not been consistently reproduced. We aimed to evaluate in-hospital mortality before and after the implementation of corticosteroid treatment (CS-T) for severe and critical COVID-19. We conducted a cohort study that included patients admitted with severe and critical COVID-19. The primary outcome was death during hospitalization. Secondary outcomes included the length of stay (LOS), need for invasive mechanical ventilation (IMV), time to IMV initiation, IMV duration, and development of hospital-acquired infections (HAIs). Bivariate, multivariate, and propensity-score matching analysis were performed. Among 1540 patients, 688 (45%) received CS-T. Death was less frequent in the CS-T group (18 vs 31%, p < .01). Among patients on IMV, death was also less frequent in the CS-T group (25 vs 55%, p < .01). The median time to IMV was longer in the CS-T group (5 vs 3 days, p < .01). HAIs occurred more frequently in the CS-T group (20 vs 10%, p < .01). LOS, IMV, and IMV duration were similar between groups. Multivariate analysis revealed an independent association between CS-T and lower mortality (aOR 0.26, 95% CI 0.19-0.36, p < .001). Propensity-score matching analysis revealed that CS-T was independently associated with lower mortality (aOR 0.33, 95% CI 0.22-0.50, p < .01). Treatment with corticosteroids was associated with reduced in-hospital mortality among patients with severe and critical COVID-19, including those on IMV.