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IntroductionFounded 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 methodsParticipants 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.ResultsWe 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%.ConclusionWith 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.

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%).

Background: Antimalarial drugs were widely used as experimental therapies against COVID-19 in the initial stages of the pandemic. Despite multiple randomized controlled trials demonstrating unfavorable outcomes in both efficacy and adverse effects, antimalarial drugs are still prescribed in developing countries, especially in those experiencing recurrent COVID-19 crises (India and Brazil). Therefore, real-life experience and pharmacovigilance studies describing the use and side effects of antimalarials for COVID-19 in developing countries are still relevant.Objective: To describe the adverse effects associated with the use of antimalarial drugs in hospitalized patients with COVID-19 pneumonia at a reference center in Mexico City.Methods: We integrated a retrospective cohort with all adult patients hospitalized for COVID-19 pneumonia from March 13th, 2020, to May 17th, 2020. We compared the baseline characteristics (demographic and clinical) and the adverse effects between the groups of patients treated with and without antimalarial drugs. The mortality analysis was performed in 491 patients who received optimal care and were not transferred to other institutions (210 from the antimalarial group and 281 from the other group).Results: We included 626 patients from whom 38% (n = 235) received an antimalarial drug. The mean age was 51.2 ± 13.6 years, and 64% were males. At baseline, compared with the group treated with antimalarials, the group that did not receive antimalarials had more dyspnea (82 vs. 73%, p = 0.017) and cyanosis (5.3 vs. 0.9%, p = 0.009), higher respiratory rate (median of 28 vs. 24 bpm, p < 0.001), and lower oxygen saturation (median of 83 vs. 87%, p < 0.001). In the group treated with antimalarials, 120 patients had two EKG evaluations, from whom 12% (n = 16) prolonged their QTc from baseline in more than 50 ms, and six developed a ventricular arrhythmia. Regarding the trajectories of the liver function tests over time, no significant differences were found for the change in the mean value per day between the two groups. Among patients who received optimal care, the mortality was 16% (33/210) in those treated with antimalarials and 15% (41/281) in those not receiving antimalarials (RR 1.08, 95% 0.75–1.64, and adjusted RR 1.12, 95% CI 0.69–1.82).Conclusion: The adverse events in patients with COVID-19 treated with antimalarials were similar to those who did not receive antimalarials at institutions with rigorous pharmacological surveillance. However, they do not improve survival in patients who receive optimal medical care.

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.

ABSTRACT: 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.

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.

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.

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.