Exploring the Thermal-Oxidative Stability of Azithromycin Using a Thermoactivated Sensor Based on Cerium Molybdate and Multi-Walled Carbon Nanotubes.

The chemical stability of azithromycin (AZM) may be compromised depending on the imposed thermo-oxidative conditions. This report addresses evidence of this process under varying conditions of temperature (20-80 °C), exposure time to UV radiation (1-3 h irradiation at 257 nm), and air saturation (1-3 h saturation with atmospheric air at 1.2 L min-1 and 15 kPa) through electrochemical measurements performed with a thermoactivated cerium molybdate (Ce2(MoO4)3)/multi-walled carbon nanotubes (MWCNT)-based composite electrode. Thermal treatment at 120 °C led to coordinated water elimination in Ce2(MoO4)3, improving its electrocatalytic effect on antibiotic oxidation, while MWCNT were essential to reduce the charge-transfer resistance and promote signal amplification. Theoretical-experimental data revealed remarkable reactivity for the irreversible oxidation of AZM on the working sensor using phosphate buffer (pH = 8) prepared in CH3OH/H2O (10:90%, v/v). Highly sensitive (230 nM detection limit) and precise (RSD < 4.0%) measurements were recorded under these conditions. The results also showed that AZM reduces its half-life as the temperature, exposure time to UV radiation, and air saturation increase. This fact reinforces the need for continuous quality control of AZM-based pharmaceuticals, using conditions closer to those observed during their transport and storage, reducing impacts on consumers' health.

Treating Pythiosis with Antibacterial Drugs Targeting Protein Synthesis: An Overview.

This review article explores the effectiveness of antibacterial drugs that inhibit protein synthesis in treating pythiosis, a difficult-to-treat infection caused by Pythium insidiosum. The article highlights the susceptibility of P. insidiosum to antibacterial drugs, such as macrolides, oxazolidinones, and tetracyclines. We examine various studies, including in vitro tests, experimental infection models, and clinical case reports. Based on our synthesis of these findings, we highlight the potential of these drugs in managing pythiosis, primarily when combined with surgical interventions. The review emphasizes the need for personalized treatment strategies and further research to establish standardized testing protocols and optimize therapeutic approaches.

A systematic review of Neisseria gonorrhoeae drug resistance development in South Africa.

In South Africa, basic healthcare centres treat sexually transmitted infections (STIs) using a syndromic approach. In line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a complete study of all randomised controlled trials and surveillance data relevant to N. gonorrhoeae antibiotic resistance was conducted. To discover papers published between 2002 and 2022, searches were undertaken using PubMed, EMBASE and any other relevant databases. This systematic review extracted a total of 463 articles published between 2002 and 2022 from a variety of online research sources. Seven South African provinces were represented in the studies that were assessed. Mpumalanga and the North West Province did not have any studies that described the identification and monitoring of antimicrobial resistance (AMR). This study presents data obtained from a comprehensive analysis of 2140 isolates, in which we examined the presence of one or more antibiotic resistance. Our findings revealed that out of these samples, 1891 isolates exhibited antimicrobial properties; tetracycline was the antimicrobial resistance that was found the most often (30%), followed by ciprofloxacin (19%) and penicillin (17%). The mean of the isolates was 143, the upper 95% mean was 243, and the standard deviation (SD) was 181.6. All microbiological identification and susceptibility testing processes must be standardised and improved so national organisations can monitor AMR. The nation's health community must address all identified areas of concern to avoid AMR.

Clinical significance of serum microRNA-146a and inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment.

OBJECTIVE: This study aimed to investigate the clinical significance of serum microRNA-146a and pro-inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment. microRNA-146a is known to regulate inflammatory responses, and excessive inflammation is a primary characteristic of MPP. METHODS: Children with MPP received conventional symptomatic therapy along with intravenous administration of azithromycin for one week. Serum levels of microRNA-146a and pro-inflammatory factors were measured using RT-qPCR and ELISA kits, respectively. The correlation between microRNA-146a and pro-inflammatory factors was analyzed by the Pearson method. Pulmonary function indexes were assessed using a pulmonary function analyzer, and their correlation with microRNA-146a and pro-inflammatory factors after treatment was evaluated. Children with MPP were divided into effective and ineffective treatment groups, and the clinical significance of microRNA-146a and pro-inflammatory factors was evaluated using receiver operating characteristic curves and logistic multivariate regression analysis. RESULTS: Serum microRNA-146a was downregulated in children with MPP but upregulated after azithromycin treatment, contrasting with the trend observed for pro-inflammatory factors. MicroRNA-146a showed a negative correlation with pro-inflammatory cytokines. Pulmonary function parameters were initially reduced in children with MPP, but increased after treatment, showing positive/inverse associations with microRNA-146a and pro-inflammatory factors. Higher microRNA-146a and lower pro-inflammatory factors predicted better efficacy of azithromycin treatment. MicroRNA-146a, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) were identified as independent factors influencing treatment efficacy. CONCLUSION: Azithromycin treatment in children with MPP upregulates microRNA-146a, downregulates pro-inflammatory factors, and effectively improves pulmonary function.

Single-dose oral azithromycin prophylaxis in planned vaginal delivery for sepsis prevention: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The use of oral azithromycin (AZI) as a preventive measure against postpartum infections of planned vaginal births has garnered a lot of interest in recent years and has been the subject of many randomized controlled trials (RCTs). However, the results from these trials have not been consistent. Therefore, we aim to perform a systematic review and meta-analysis to determine whether the use of a single-dose of oral AZI is clinically significant. METHODS: We systematically searched PubMed, Embase, and Cochrane Central for RCTs from May to June 2023, comparing a single dose of oral AZI with placebo in patients undergoing planned vaginal delivery at a minimum of 28 weeks of gestational age. The main outcomes were puerperal and neonatal sepsis. Statistical analyses were performed using Review Manager 5.4.1 (Cochrane Collaboration). Heterogeneity was assessed with I2 statistics. RESULTS: Four RCTs were included (mothers, n = 42 235; newborns n = 42 492). Approximately 49.8% of mothers received a single dose of oral AZI for sepsis prophylaxis. Compared with placebo, AZI significantly reduced the incidence of puerperal sepsis (risk ratio [RR], 0.65 [95% confidence interval (CI), 0.55-0.77]; P < 0.001), mastitis or breast abscess (RR, 0.58 [95% CI, 0.42-0.79]; P < 0.001), endometritis (RR, 0.65 [95% CI, 0.54-0.77]; P < 0.001), wound infection (RR, 0.81 [95% CI, 0.69-0.96]; P = 0.013), infection rate (RR, 0.62 [95% CI, 0.51-0.76]; P < 0.001), and fever (RR, 0.50 [95% CI, 0.28-0.89]; P = 0.018) in mothers. No statistically significant differences were identified between groups regarding maternal all-cause mortality and the use of prescribed postpartum antibiotics. Similarly, no statistical differences were noted in the neonatal group regarding sepsis, infection rate, and all-cause mortality. CONCLUSION: AZI appears to be an effective preventive measure against many postpartum infections in mothers but a substantial impact on neonatal outcomes has not yet been conclusively observed.

Clinical significance of serum microRNA-146a and inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment

Abstract Objective This study aimed to investigate the clinical significance of serum microRNA-146a and pro-inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment. microRNA-146a is known to regulate inflammatory responses, and excessive inflammation is a primary characteristic of MPP. Methods Children with MPP received conventional symptomatic therapy along with intravenous administration of azithromycin for one week. Serum levels of microRNA-146a and pro-inflammatory factors were measured using RT-qPCR and ELISA kits, respectively. The correlation between microRNA-146a and pro-inflammatory factors was analyzed by the Pearson method. Pulmonary function indexes were assessed using a pulmonary function analyzer, and their correlation with microRNA-146a and pro-inflammatory factors after treatment was evaluated. Children with MPP were divided into effective and ineffective treatment groups, and the clinical significance of microRNA-146a and pro-inflammatory factors was evaluated using receiver operating characteristic curves and logistic multivariate regression analysis. Results Serum microRNA-146a was downregulated in children with MPP but upregulated after azithromycin treatment, contrasting with the trend observed for pro-inflammatory factors. MicroRNA-146a showed a negative correlation with pro-inflammatory cytokines. Pulmonary function parameters were initially reduced in children with MPP, but increased after treatment, showing positive/inverse associations with microRNA-146a and pro-inflammatory factors. Higher microRNA-146a and lower pro-inflammatory factors predicted better efficacy of azithromycin treatment. MicroRNA-146a, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) were identified as independent factors influencing treatment efficacy. Conclusion Azithromycin treatment in children with MPP upregulates microRNA-146a, downregulates pro-inflammatory factors, and effectively improves pulmonary function.

Enhanced infectivity of bovine viral diarrhoea virus (BVDV) in arginase-producing bovine monocyte-derived macrophages.

Macrophages are important cells of the innate immunity that play a major role in Bovine Viral Diarrhea Virus (BVDV) pathogenesis. Macrophages are not a homogenous population; they exist in different phenotypes, typically divided into two main categories: classically (pro-inflammatory) and alternatively activated (anti-inflammatory) or M1 and M2, respectively. The role of bovine macrophage phenotypes on BVDV infection is still unclear. This study characterized the interaction between BVDV, and monocyte-derived macrophages (Mo-Mφ) collected from healthy cattle and polarized to an M1 or M2 state by using LPS, INF-γ, IL-4 or azithromycin. Arginase activity quantitation was utilized as a marker of the M2 Mo-Mφ spectrum. There was a significant association between arginase activity and the replication rate of BVDV strains of different genotypes and biotypes. Inhibition of arginase activity also reduced BVDV infectivity. Calves treated with azithromycin induced Mo-Mφ of the M2 state produced high levels of arginase. Interestingly, azithromycin administered in vivo increased the susceptibility of macrophages to BVDV infection ex vivo. Mo-Mφ from pregnant dams and calves produced higher arginase levels than those from non-pregnant adult animals. The increased infection of arginase-producing alternatively activated bovine macrophages with BVDV supports the need to delve into a possible leading role of M2 macrophages in establishing the immune-suppressive state during BVDV convalescence.

Review of Analytical Methods for Evaluating Azithromycin in the Context of Green Analytical Chemistry.

BACKGROUND: Azithromycin (AZT) is an antimicrobial available in different pharmaceutical forms and many people can have access to this medicine. Therefore, the existence of adequate and reliable analytical methods for evaluating the quality of AZT and AZT-based products is essential. OBJECTIVE/METHODS: The purpose of this review is to discuss the analytical methods for evaluating AZT present in the literature and official compendia in the context of Green Analytical Chemistry (GAC). RESULTS: Among the methods found in the literature for evaluating AZT, the most used method is HPLC (62%) followed by TLC (14%) and the microbiological method by agar diffusion (14%). Even pharmacopoeias recommend the analysis of AZT by HPLC or agar diffusion. Acetonitrile and methanol account for 35% of the most used solvents in the analyses, followed by buffer. CONCLUSION: AZT lacks analytical methods in the context of GAC. Both physical-chemical and microbiological methods can contemplate the environmentally friendly way to analyze AZT and AZT-based products, depending only on the chosen conditions. Ethanol, purified water, acetic acid instead of methanol, acetonitrile, buffer, formic acid in the physical-chemical methods are excellent alternatives. However, in the microbiological method, turbidimetry is a great option instead of agar diffusion.

Quantum chemical investigation of predominant conformation of the antibiotic azithromycin in water and DMSO solutions: thermodynamic and NMR analysis.

Azithromycin (AZM) is a macrolide-type antibiotic used to prevent and treat serious infections (mycobacteria or MAC) that significantly inhibit bacterial growth. Knowledge of the predominant conformation in solution is of fundamental importance for advancing our understanding of the intermolecular interactions of AZM with biological targets. We report an extensive density functional theory (DFT) study of plausible AZM structures in solution considering implicit and explicit solvent effects. The best match between the experimental and theoretical nuclear magnetic resonance (NMR) profiles was used to assign the preferred conformer in solution, which was supported by the thermodynamic analysis. Among the 15 distinct AZM structures, conformer M14, having a short intramolecular C6-OH … N H-bond, is predicted to be dominant in water and dimethyl sulfoxide (DMSO) solutions. The results indicated that the X-ray structure backbone is mostly conserved in solution, showing that large flexible molecules with several possible conformations may assume a preferential spatial orientation in solution, which is the molecular structure that ultimately interacts with biological targets.

Epidemiología y prevalencia de Mycoplasma genitalium y resistencia a azitromicina en el Área Norte de Tenerife, Islas Canarias / Epidemiology and prevalence of Mycoplasma genitalium and resistance to azithromycin in the North Area of Tenerife, Canary Islands

INTRODUCCIÓN: La infección y resistencia antimicrobiana de Mycoplasma genitalium está infradiagnósticada en nuestra comunidad ya que no es una Enfermedad de Declaración Obligatoria y requiere técnicas de biología molecular, no siempre disponibles. OBJETIVO: Estudiar la epidemiología y prevalencia de M. genitalium y la tasa de resistencia frente a azitromicina en nuestra Área de Salud. MÉTODOS: Estudio retrospectivo, desde abril de 2019 a julio de 2020, realizado en el Área de Salud del Norte de Tenerife, la cual atiende el Hospital Universitario Canarias. Para el diagnóstico de las infecciones de transmisión sexual (ITS) se utilizó la RT-PCR Allplex™ STI Essential Assay (Seegene, South Korea). Las muestras en las que se detectó M. genitalium fueron congeladas a −80°C para posteriormente realizar estudio de resistencia a azitromicina con la RT-PCR Allplex™ MG y AziR Assay (Seegene, South Korea). RESULTADOS: Se identificaron 111/3.849 (prevalencia de 2,8%) pacientes con M. genitalium, de los cuales la mayoría, 59(53,1%) eran hombres con una mediana de 32 años (15-74) y cuyas muestras procedían principalmente de Atención Primaria: 55 (49,5%). Para la detección de resistencia a azitromicina, de los 111 pacientes solo se pudo analizar las muestras de 79, detectándose resistencia in vitro en 15(18,3%): 10 con A2059G, 4 con A2058G y 1 con ambas. La resistencia a azitromicina fue más frecuente en hombres 12 (15,8%). DISCUSIÓN Y CONCLUSIONES: Con este estudio se pone de manifiesto la importancia de la prevalencia de M. genitalium en nuestro entorno, así como su alta tasa de resistencia a azitromicina por lo que se hace necesario vigilar dicha resistencia en nuestro Área de Salud para su adecuado tratamiento.

BACKGROUND: Infection and antimicrobial resistance of Mycoplasma genitalium is under-diagnosed in our community as it is not a Notifiable Infectious Disease and requires for its detection molecular biology techniques, which are not always available. AIM: To study the epidemiology and prevalence of M. genitalium and the rate of resistance to azithromycin in our Health Care Area. METHODS: We conducted a retrospective study from April 2019 to July 2020 in the Northern Health Care Area of Tenerife, which is attended to the Universitary Hospital Complex of the Canary Islands. The RT-PCR Allplex™ STI Essential Assay (Seegene, South Korea) to diagnose Sexually Transmitted Infections (STI) was used. Samples in which M. genitalium was detected were stored at −80°C for subsequent diagnosis of resistance to azithromycin with the RT-PCR Allplex™ MG and AziR Assay (Seegene, South Korea). RESULTS: Of a total of 111/3,849 (2.8% prevalence) patients diagnosed with M. genitalium, 59 (53.1%) were male with a mean age of 30 (19-61) years and mainly from Primary Care 55 (49.5%). Only 79 samples of the 111 patients could be tested to detect azithromycin resistance, of which 15 (18.3%) were resistant in vitro: 10 with A2059G, 4 with A2058G and 1 with both. Azithromycin resistance was more frequent in men 12 (15.8%) and detected mainly in urine samples 6 (60%). Discussion and CONCLUSIONS: This study highlights the prevalence of M. genitalium in our setting as well as the high rate of resistance to azithromycin, making it necessary to detect resistance to azithromycin in M. genitalium for its appropriate treatment in our Health Care Area.

Antibiotic dispensing during first year of COVID-19 pandemic in Brazilian public hospitals.

Aim: To evaluate the impact of the first year of the COVID-19 pandemic on antibiotic dispensation in three Brazilian hospitals. Methods: Stock movement was accessed from pharmacy databases and microbiological reports from 2018 to 2021. Results: Reduced antibiotic dispensation occurred during 2020 in all hospitals. The most significant reduction was in April at Hospital Doutor Jayme dos Santos Neves (∼58%), and in May at Hospital Doutor Roberto Arnizaut Silvares (∼66%) and Hospital Doutor Dório Silva (∼29%). However, azithromycin dispensation increased in all hospitals in 2020. Macrolide-resistant bacterial isolates rose from 66.6% in 2019 to 77.1% in 2020 and 88.3% in 2021. Conclusion: Despite reduced antibiotic dispensation, the increase in azithromycin consumption in 2020 highlights the urgency to monitor macrolide resistance after the pandemic and improve stewardship activities.

Increase in veterinary prescriptions of azithromycin during the COVID-19 pandemic in Brazil.

INTRODUCTION: With the advent of the pandemic in 2020 and the lack of perspectives on the treatment of COVID-19, numerous therapeutic proposals have emerged, including hydroxychloroquine and azithromycin. Therefore, some studies have shown that in many countries, the demand for azithromycin has increased during the pandemic. In Brazil, antibiotics can only be purchased with a medical, dental, or veterinary prescription. This study aimed to determine whether the number of prescriptions made by veterinarians (which could be used by humans) has increased during the pandemic. METHODOLOGY: Data on the purchase of antibiotics made under veterinary prescriptions in Brazilian pharmacies between 2014 and 2021 were collected. To assess the changes in monthly trends in the use of the selected antibiotics, we applied the Joinpoint regression. RESULTS: The most prescribed antibiotic in all years was cephalexin (35%), followed by amoxicillin (24%). During the pandemic, sales of azithromycin substantially increased. Regression analysis showed that since 2014, azithromycin prescriptions grew by an average of 0.67% per month. At the beginning of the pandemic, the monthly growth rate became 12.64%. When comparing azithromycin sales during the pandemic with the historical average (2014-2019), the increase was 41%. CONCLUSIONS: During the pandemic, there was no animal health situation in Brazil that required the use of this antibiotic. Veterinary prescriptions may have been an instrument for human access to azithromycin for the treatment of COVID-19. Stricter enforcement policies are needed to address this problem to avoid antimicrobial resistance.

Sustained Transmission of Neisseria gonorrhoeae Strains with High-Level Azithromycin Resistance (MIC ≥ 256 µg/mL) in Argentina, 2018 to 2022.

Azithromycin combined with ceftriaxone is the recommended dual therapy for uncomplicated gonorrhea in many countries. Nevertheless, the increasing prevalence of azithromycin resistance compromises the effectiveness of this treatment strategy. From 2018 to 2022, we collected 13 gonococcal isolates with high-level azithromycin resistance (MIC ≥ 256 µg/mL) across Argentina. Whole-genome sequencing revealed that these isolates were mainly represented by the internationally spreading Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup G12302, containing the 23S rRNA A2059G mutation (in all four alleles) together with mosaic mtrD and mtrR promoter 2 loci. This information is important to develop targeted public health policies to control the spread of azithromycin-resistant N. gonorrhoeae in Argentina and internationally. IMPORTANCE Azithromycin resistance in Neisseria gonorrhoeae has been increasing in numerous populations worldwide, which is of concern, as azithromycin is part of the recommended dual treatment in many countries. Here, we report 13 N. gonorrhoeae isolates with high-level azithromycin resistance (MIC ≥ 256 µg/mL). This study observed that high-level azithromycin-resistant gonococcal strains have shown sustained transmission in Argentina and are related to the successful international clone NG-MAST G12302. Genomic surveillance together with real-time tracing and data-sharing networks will be crucial in controlling the spread of azithromycin resistance in gonococcus.

Adsorption of azithromycin in agricultural soils of the Bogotá savanna, Colombia.

Azithromycin is one of the most widely used macrolide antibiotics in medical treatment. However, there is little information on studies of the ecotoxicity, persistence and mobility of this type of compounds in the environment, although their presence in surfaces and wastewater has already been detected (Hernández et al., 2015). Based on this approach, the present research performs an analysis of the behavior of the adsorption process of azithromycin in soils of different textural classes, with the intention of establishing a first approach to assess the destination and transport of such substances in the biosphere. From the results of the evaluation of the conditions of adsorption of azithromycin, it is established that the Langmuir model has a better fit for clay soils with correlation coefficients R2 between 0.998 and 0.961. In contrast, the Freundlich model fits the soil with higher sand fraction with a higher correlation, R2 of 0.9892. Finally, based on a correlation analysis between the clay content, the percentage of organic matter and the adsorption coefficient K, it was evident that the adsorption of azithromycin is mainly related to the inorganic fraction of the soil.

Pharmacotherapy and clinical outcomes of hospitalized COVID-19 patients in Chile during the first wave of pandemic / Farmacoterapia y desenlaces clínicos de pacientes de COVID-19 hospitalizados en Chile durante la primera ola de pandemia

BACKGROUND: The largest growth in cases of COVID-19 worldwide during 2020 was in the Americas, and Chile was one of the most affected countries. AIM: To describe, characterize, and evaluate the use of drugs as treatment for COVID-19 in hospitalized patients in Chile during the first wave of the pandemic. METHODS: We performed a multicenter, observational study that included 442 patients with confirmed SARS-CoV-2 infection admitted in Chilean hospitals between March 21 and September 22, 2020. The analysis included demographics, comorbidities, specific drug therapy, and outcomes over a 28-day follow-up period. RESULTS: The median age of patients was 68 years (IQR 55-73), and 38.9% were women. The most common comorbidities were hypertension (57.7%) and diabetes (36.9%). Fifty-seven (12.9%) patients died. Hypertension (HR 2.99; CI 95% 1.43-6.26) and age ≥; 65 (2.14; CI 95% 1.10- 4.17) were the main predictors of mortality. Primary drugs were azithromycin (58.8%) and corticosteroids (51.1%). In this sample, azithromycin was a protective factor regarding mortality (HR 0.53; CI 95% 0.31-0.90), increasing clinical improvement and avoiding progression. CONCLUSIONS: The patterns of use of drugs to treat COVID-19 in Chile during the first wave of the pandemic were very dynamic and followed the international, evidence-based guidelines. The low mortality rate indicates that the clinical management of hospitalized patients was adequate.

ANTECEDENTES: Durante 2020, el mayor incremento de casos de COVID-19 se observó en el continente americano, donde Chile fue uno de los países más afectados. Objetivos: Describir, caracterizar y evaluar el uso de fármacos indicados para tratar el COVID-19 en pacientes hospitalizados en Chile durante la primera ola de pandemia. PACIENTES Y MÉTODOS: Un estudio multicéntrico observacional incorporó a 442 pacientes con infección confirmada por SARS- CoV-2 admitidos en hospitales chilenos entre el 21 de marzo y el 22 de septiembre de 2020. Se analizaron variables demográficas, comorbilidades, terapia farmacológica específica y desenlaces clínicos para un período de seguimiento de 28 días. Resultados: La mediana de la edad fue de 68 años (RIC 55-73), y un 38,9% fueron mujeres. Las comorbilidades más comunes fueron hipertensión (57,7%) y diabetes (36,9%). Cincuenta y siete (12,9%) de los pacientes murieron. Los principales predictores de mortalidad fueron la hipertensión (HR 2,99; IC 95% 1,43-6,26) y la edad ≥ 65 años (2,14; IC 95% 1,10- 4,17). Los fármacos más utilizados fueron azitromicina (58,8%) y corticosteroides (51,1%). En esta muestra, la azitromicina fue un factor de protección respecto a la mortalidad (HR 0,53; IC 95% 0,31-0,90), incrementando igualmente la mejoría y evitando la progresión. CONCLUSIONES: Los patrones de uso de fármacos para tatar COVID-19 en Chile durante la primera ola de pandemia fueron muy dinámicos y siguieron las directrices internacionales basadas en la evidencia. La baja mortalidad sugiere que el manejo de los pacientes hospitalizados fue adecuado.

Outpatient treatment of COVID-19: an experience with 552 cases in Mexico.

INTRODUCTION: The impact of the coronavirus disease 2019 (COVID-19) pandemic has globally challenged health services, especially because when the pandemic first reached Mexico, in February 2020, there was no known effective and safe treatment. A treatment scheme was offered by the Institute for the Integral Development of Health (IDISA) in Mexico City from March 2020 to August 2021 when there were many patients with COVID-19. This report summarizes the experience managing COVID-19 with this scheme. MATERIALS AND METHODS: This is a descriptive, retrolective study. The data was obtained from the case files of the patients who attended the IDISA from March 2020 to August 2021 with COVID-19. All the cases were treated with the scheme consisting of nitazoxanide, azithromycin, and prednisone. Various laboratory blood tests and chest computerized tomography scan were done. When indicated, supplementary oxygen, and another specific treatment were used. A standardized clinical recording was conducted for 20 days based on symptoms and systemic symptoms. RESULTS: Based on the World Health Organization criteria, the patients were classified according to the disease severity: 170 mild, 70 moderate, and 312 severe cases. The outcome was the discharge of 533 patients after their recovery, 16 were excluded from the study, and 6 died. CONCLUSIONS: The use of nitazoxanide, azithromycin, and prednisone proved to be effective as it resulted in improvement of symptoms and in successful outcomes for the management of COVID-19 outpatients.

Association between self-reported evidence-based medicine competencies and prescribing of drugs without scientific evidence against mild COVID-19 among recently graduated physicians in Peru.

Objective: To evaluate the association between self-rated evidence-based medicine (EBM) competencies and the prescription of drugs without scientific evidence against mild COVID-19 (present with any of the signs and symptoms of COVID-19 but who do not have shortness of breath, dyspnea, or abnormal chest imaging) among recently graduated physicians in Peru. Methods: We conducted an analytical cross-sectional study where we evaluated a non-probability sample of recently graduated physicians during June and July 2021 (end of second wave of COVID-19 in Peru). Self-rated EBM competencies were assessed by four domains (formulation of a clinical question, search, analysis, and application) using a Likert scale with scores from zero to four ("Very inadequate" = 0, to "Very Adequate" = 4), it was considered as "Adequate" if the score was three or four. In addition, the variable "General competence on EBM" was rated as "Adequate" if in all domains evaluated it presented an adequate self-rating. For the outcome, drug prescription, we considered the use of ivermectin, azithromycin, other antibiotics, hydroxychloroquine, dexamethasone, and anticoagulants (drugs with no efficacy demonstrated for patients with mild COVID-19). To assess the association, we used Poisson regression models with robust variances and obtaining crude (cPR) and adjusted (aPR) prevalence ratios with their 95% confidence intervals (95%CI). Results: Of a total of 239 physicians included 70.7% prescribed at least one drug without scientific evidence. A total of 51.1% reported adequate ratings in all evaluated domains of EBM. Self-rating the "Clinical Question Formulation" competency as adequate was associated with a lower frequency of prescribing medications for mild COVID-19 (aPR: 0.93; 95% CI: 0.91-0.95). While self-rating as adequate the competency of "Identify possible implications of investigations" was associated with an increase in the prescription of such drugs (aPR: 1.14; 95% CI: 1.09-1.20). Additionally, self-rating all domains as adequate were associated with less prescription (aPR: 0.93; 95% CI: 0.90-0.96). Conclusion: Seven out of ten recently graduated physicians prescribed some type of medication without scientific evidence to treat patients with mild COVID-19. Having adequate self-perceived EBM competencies was associated with a lower frequency of prescribing medications without scientific evidence to manage patients with mild COVID-19.

Mycoplasma genitalium prevalence, antimicrobial resistance-associated mutations, and coinfections with non-viral sexually transmitted infections in high-risk populations in Guatemala, Malta, Morocco, Peru and South Africa, 2019-2021.

The prevalence of Mycoplasma genitalium (MG) and MG antimicrobial resistance (AMR) appear to be high internationally, however, prevalence data remain lacking globally. We evaluated the prevalence of MG and MG AMR-associated mutations in men who have sex with men (MSM) in Malta and Peru and women at-risk for sexually transmitted infections in Guatemala, South Africa, and Morocco; five countries in four WHO regions mostly lacking MG prevalence and AMR data, and estimated MG coinfections with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Male urine and anorectal samples, and vaginal samples were tested for MG, CT, NG, and TV (only vaginal samples) using Aptima assays (Hologic). AMR-associated mutations in the MG 23S rRNA gene and parC gene were identified using ResistancePlus MG kit (SpeeDx) or Sanger sequencing. In total, 1,425 MSM and 1,398 women at-risk were recruited. MG was detected in 14.7% of MSM (10.0% in Malta and 20.0% Peru) and in 19.1% of women at-risk (12.4% in Guatemala, 16.0% Morocco, 22.1% South Africa). The prevalence of 23S rRNA and parC mutations among MSM was 68.1 and 29.0% (Malta), and 65.9 and 5.6% (Peru), respectively. Among women at-risk, 23S rRNA and parC mutations were revealed in 4.8 and 0% (Guatemala), 11.6 and 6.7% (Morocco), and 2.4 and 3.7% (South Africa), respectively. CT was the most frequent single coinfection with MG (in 2.6% of MSM and 4.5% of women at-risk), compared to NG + MG found in 1.3 and 1.0%, respectively, and TV + MG detected in 2.8% of women at-risk. In conclusion, MG is prevalent worldwide and enhanced aetiological MG diagnosis, linked to clinical routine detection of 23S rRNA mutations, in symptomatic patients should be implemented, where feasible. Surveillance of MG AMR and treatment outcome would be exceedingly valuable, nationally and internationally. High levels of AMR in MSM support avoiding screening for and treatment of MG in asymptomatic MSM and general population. Ultimately, novel therapeutic antimicrobials and/or strategies, such as resistance-guided sequential therapy, and ideally an effective MG vaccine are essential.

Macrolides at Clinically-Relevant Concentrations May Induce Biofilm Formation in Macrolide-Resistant Staphylococcus aureus.

Macrolides inhibit biofilm formation in several Gram-negative, intrinsically-resistant bacterial species. However, the effect of macrolides upon biofilm formation by susceptible Gram-positive bacteria has been much less explored as such concentrations also inhibit cell growth. To circumvent this problem, the effect of macrolides (erythromycin, clarithromycin and azithromycin) at 0.5-2 µg/mL, upon biofilm formation, was explored on macrolide-resistant Staphylococcus aureus isolates, using the crystal violet assay with 96-well plates. Early (4 h) biofilm formation by strains having constitutive target-modification resistance was consistently induced by all macrolides but not in azithromycin-treated cells in longer (8 and 12 h) incubation. In inducible-resistance isolates, early biofilm formation was enhanced by some macrolide treatments, compared to similar cell growth in the absence of antibiotics; but the typical decay of biofilms at longer incubation appeared prematurely in macrolide-treated cultures. Biofilm formation in an efflux-mediated resistant isolate was not affected by macrolides. These results indicate that macrolides induce the formation of biofilm by resistant S. aureus isolates, especially during the early stages. This suggests that the empirical use of macrolides against infections caused by resistant S. aureus strains could not only result in clinical failure but even in the enhancement of biofilms, making further treatment difficult.

Caracterización de eventos adversos a hidroxicloroquina, ivermectina, azitromicina y tocilizumab en pacientes hospitalizados por COVID-19 en un hospital del Seguro Social de Salud del Perú / Characterization of adverse events to hydroxychloroquine, ivermectin, azithromycin and tocilizumab in patients hospitalized due to COVID-19 in a Peruvian Social Health Insurance hospital

Objetivos. Caracterizar los eventos adversos (EA) asociados a hidroxicloroquina (HQ), azitromicina (AZI), tocilizumab (TOB) e ivermectina (IVM) prescritos como «fuera de etiqueta» en el tratamiento de pacientes hospitalizados por la COVID-19. Materiales y métodos. Se realizó un análisis secundario transversal de la base de datos del sistema de farmacovigilancia del Seguro Social de Salud del Perú (EsSalud) de las notificaciones de EA a HQ, AZI, TOB e IVM provenientes del Hospital Nacional Edgardo Rebagliati Martins de abril a octubre del 2020. Se revisaron las historias clínicas digitales, se estimaron las tasas de reporte de EA y se evaluaron sus características por tipo de fármaco, tiempo de aparición, tipo por órgano-sistema afectado, gravedad y causalidad. Resultados. Se identificaron 154 notificaciones que describen un total de 183 EA posiblemente relacionados con HQ, AZI, TOB e IVM, siendo 8% la tasa de reporte de EA. La mediana de tiempo de aparición de EA fue de 3 días (RIC: 2-5). La mayoría fueron cardiovasculares, destacándose la prolongación del intervalo QT. Se observaron EA hepatobiliares principalmente asociados a TOB. La mayoría de los casos fueron moderados, no obstante, el 10,4% fue grave. Conclusiones. Se identificaron EA potencialmente asociados al uso de HQ, AZI, TOB e IVM contra la COVID-19, siendo los más frecuentes los de tipo cardiovasculares. A pesar de que la AZI, HQ e IVM poseen perfiles conocidos de seguridad, su empleo en la COVID-19 podría incrementar la aparición de EA por los factores de riesgo propios de esta infección. Se sugiere reforzar la vigilancia, especialmente, de TOB.

Objective. To characterize the adverse events (AEs) related to the off-label use of hydroxychloroquine (HQ), azithromycin (AZI), tocilizumab (TOB) and ivermectin (IVM) for the treatment of COVID-19 in hospitalized patients. Materials and Methods. We conducted a secondary cross-sectional analysis of the Peruvian Social Health Insurance (EsSalud) pharmacovigilance system database of AE notifications to HQ, AZI, TOB and IVM in the Edgardo Rebagliati Martins National Hospital from April to October 2020. Information was collected from digital medical records. We estimated AE reporting rates and evaluated their characteristics by drug type, time of occurrence, type by the affected organ-system, severity and causality. Results. We identified 154 notifications describing a total of 183 AE possibly related to HQ, AZI, TOB and IVM; the reporting rate was 8%. The median time of AE occurrence was 3 days (IQR: 2-5). Most were cardiovascular events; prolongation of the QT interval was the most frequent. Hepatobiliary AEs were mainly associated with TOB. Most cases were moderate, however, 10.4% were severe. Conclusions. We found AEs potentially associated with the use of HQ, AZI, TOB and IVM against COVID-19; cardiovascular events were the most frequent. Although AZI, HQ and IVM have known safety profiles, their use against COVID-19 could increase the occurrence of AE due to the risk factors inherent to this infection. Surveillance systems must be improved, especially those for TOB.