Antimicrobial Susceptibility Among Gram-Negative Isolates in Pediatric Patients in Latin America, Africa-Middle East, and Asia From 2016-2020 Compared to 2011-2015: Results From the ATLAS Surveillance Study.

BACKGROUND: Antimicrobial resistance (AMR) data in the pediatric population are limited, particularly in developing countries. This study assessed the AMR profile and key resistance phenotypes and genotypes for Gram-negative bacteria (GNB) isolates collected as part of the Antimicrobial Testing Leadership and Surveillance program from pediatric patients in Latin America, Africa-Middle East, and Asia in 2016-2020 versus 2011-2015. METHODS: Minimum inhibitory concentrations by broth microdilution methodology were interpreted per the Clinical and Laboratory Standards Institute. European Committee on Antimicrobial Susceptibility Testing breakpoints were used for interpreting colistin activity. ß-lactamase genes were screened by polymerase chain reaction and sequencing. RESULTS: For Acinetobacter baumannii, low susceptibility (<60.0%) was observed for all antimicrobials, except colistin (≥92.9%), across regions and year periods. Ceftazidime-avibactam, amikacin, colistin, and meropenem were mostly active (78.6%-100.0%) against Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae. For Pseudomonas aeruginosa, susceptibility to ceftazidime-avibactam, amikacin, and colistin was ≥85.9%. Among resistance phenotypes, carbapenem-resistant (CR, ≥44.8%) and difficult-to-treat resistant (DTR, ≥37.1%) rates were the highest in A. baumannii. A consistent increase in CR and DTR K. pneumoniae was noted across regions over time. Extended-spectrum ß-lactamases (ESBL)-producing K. pneumoniae (32.6%-55.6%) were more frequent than ESBL-producing E. coli (25.3%-37.1%). CTX-M was the dominant ESBL among Enterobacterales. NDM-positive Enterobacterales species and VIM-positive P. aeruginosa were identified across regions. CONCLUSIONS: This study identified high susceptibility to few agents for key GNB in pediatric patients. Continued surveillance of resistance phenotypes and genotypes at regional levels may help to guide appropriate treatment decisions.

Comparison of Lateral Flow Immunochromatography and Phenotypic Assays to PCR for the Detection of Carbapenemase-Producing Gram-Negative Bacteria, a Multicenter Experience in Mexico.

The identification of carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa is important for treating and controlling hospital infections. The recommended methods for their identification require a long waiting time, technical training, and expertise. Lateral flow immunoassays such as NG-Test CARBA 5® overcome these needs. We analyzed 84 clinical isolates of carbapenem-resistant Enterobacterales and P. aeruginosa from four different hospitals in a two-year period. Antimicrobial resistance patterns were confirmed with the broth dilution method. Evaluation of KPC, VIM, NDM, IMP, and OXA-48-like enzymes was performed and compared to NG-Test CARBA 5 and phenotypic assays. Enterobacterales represented 69% of isolates and P. aeruginosa represented 31%. Carbapenemase-producing strains were 51 (88%) of Enterobacterales and 23 (88.4%) of P. aeruginosa; 20 (34%) and 23 (88%) were Class B ß-lactamases, respectively. The NG-Test CARBA 5® assay for Enterobacterales showed high sensitivity (98%), specificity (100%), and PPV (100%); however, it did not for P. aeruginosa. The Kappa concordance coefficient was 0.92 for Enterobacterales and 0.52 for P. aeruginosa. NG-Test CARBA 5® is a fast and easy-to-use assay. In Enterobacterales, we found excellent agreement in our comparison with molecular tests. Despite the low agreement in P. aeruginosa, we suggest that this test could be used as a complementary tool.

Metabolic Reprogramming in SARS-CoV-2 Infection Impacts the Outcome of COVID-19 Patients.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

Outpatient surveillance programme for health workers with COVID 19 in Mexico: an observational study of ambulatory treatment and early hospitalization.

Introduction: International guidelines recommend hospital care for patients with severe Coronavirus disease (COVID-19), but fragile health care systems struggle to cope with high number of admissions, placing patients at risk of receiving substandard care. We describe an outpatient ambulatory surveillance and treatment strategy (OPAT) for health care workers (HCWs) with severe COVID-19 during low hospital bed availability periods in Mexico City. Methods: In this observational, descriptive, retrospective study, we included HCWs with severe disease for whom there were no hospital beds available at the time of evaluation. We provided daily assessments by infectious disease specialists, daily ambulatory steroid, oral thromboprophylaxis and domiciliary low-dose oxygen. We recorded the number of patients who recovered, were hospitalized or died on follow-up. Results: From 18 March 2020 to 16 July 2021, 1739 HCWs attended our service. A total of 540 were diagnosed with COVID-19. Seventy-four had severe COVID-19 and needed hospitalization. Immediate hospitalization was not possible in 56 patients who were sent to the OPAT and included in our study. Twenty-four patients subsequently required hospitalization and 32 recovered as outpatients. Conclusions: We describe a feasible and safe outpatient management strategy for HCWs with severe COVID-19 in a low-resource setting.

Green solvents and Ultrasound-Assisted Extraction of bioactive orange (Citrus sinensis) peel compounds.

Byproducts such as orange peel have potential uses because of their bioactive compounds, which are important for their potential to reduce the risk factors of diseases caused by aging. The lack of effective techniques and the high levels of pollution produced by the conventional extraction of bioactive compounds using organic solvents have highlighted the need to enhance the 'green chemistry' trend. This study evaluates the use of ultrasound to extract bioactive compounds from orange peel. The antioxidant capacity, phenolic content, ascorbic acid, total carotenoids, and HPLC profile of phenolic compounds from orange peel extracts were obtained by a physicochemical evaluation. The results demonstrate that the optimal conditions for the ultrasound-assisted extraction of bioactive orange peel compounds were a power of 400 W, a time of 30 min, and 50% ethanol in water. These conditions were used to obtain a total carotenoid concentration of 0.63 mg ß-carotene/100 g, vitamin C concentration of 53.78 mg AA/100 g, phenolic concentration of 105.96 mg GAE/100 g, and antioxidant capacity of ORAC = 27.08 mM TE and TEAC = 3.97 mM TE. The major phenolic compound identified in all orange peel extracts was hesperidin, with a maximum concentration of 113.03 ± 0.08 mg/100 g.

Outpatient ertapenem therapy in an ESBL-high-prevalence area: an efficacy, safety, and cost study.

INTRODUCTION: Outpatient parenteral antimicrobial therapy is a safe, effective, and convenient way of administering antimicrobials for a wide variety of infections. So far there are no reports on the efficacy of outpatient antimicrobial therapy in Mexico. Our objective was to determine the outcomes, safety, and cost of outpatient ertapenem therapy (OET) in our hospital. PATIENTS AND METHODS: A case series of 99 patients that received intravenous OET was conducted. The primary outcomes were clinical cure, relapse, and recurrence of infection. RESULTS: Of the 99 patients who received OET the most common diagnosis was urinary tract infection in 56%. Extended-spectrum-ß-lactamase-producing Enterobacteriaceae caused 67% of infections in our population. Ninety-seven percent of the patients were cured at the completion of OET. One patient presented relapse 12 days after the end of OET; two patients presented recurrence, one with skin and soft tissue infection and one with pyelonephritis at days 35 and 34, respectively, after the end of OET. Three patients were readmitted after OET, one with an episode of phlebitis, one with recurrence, and one with relapse. A case of non-Clostridium difficile-associated diarrhea was observed. The intravascular line complications observed during OET were phlebitis in two patients. CONCLUSION: In our hospital, the OET was found to be effective, safe, and cost-saving when compared to inpatient care.

Diabetes mellitus as the major risk factor for mucormycosis in Mexico: Epidemiology, diagnosis, and outcomes of reported cases.

Mucormycosis is an emerging infectious disease with high rates of associated mortality and morbidity. Little is known about the characteristics of mucormycosis or entomophthoromycosis occurring in Mexico. A search strategy was performed of literature published in journals found in available databases and theses published online at Universidad Nacional Autónoma de México (UNAM) library website reporting clinical cases or clinical case series of mucormycosis and entomophthoromycosis occurring in Mexico between 1982 and 2016. Among the 418 cases identified, 72% were diabetic patients, and sinusitis accounted for 75% of the reported cases. Diabetes mellitus was not a risk factor for entomophthoromycosis. Mortality rate was 51% (125/244). Rhizopus species were the most frequent isolates (59%, 148/250). Amphotericin B deoxycholate was used in 89% of cases (204/227), while surgery and antifungal management as combined treatment was used in 90% (172/191). In diabetic individuals, this combined treatment approach was associated with a higher probability of survival (95% vs 66%, OR = 0.1, 95% CI, 0.02-0.43' P = .002). The most common complications were associated with nephrotoxicity and prolonged hospitalization due to IV antifungal therapy. An algorithm is proposed to establish an early diagnosis of rhino-orbital cerebral (ROC) mucormycosis based on standardized identification of warning signs and symptoms and performing an early direct microbiological exam and histopathological identification through a multidisciplinary medical and surgical team. In summary, diabetes mellitus was the most common risk factor for mucormycosis in Mexico; combined antifungal therapy and surgery in ROC mucormycosis significantly improved survival.

Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.

Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma.