Prevalence of mutations associated with macrolide and fluoroquinolone resistance in Neisseria gonorrhoeae with Allplex™ NG&DR Assay (Seegene®) in a tertiary hospital from Madrid, Spaina / Prevalencia de mutaciones asociadas a resistencia a macrólidos y fluoroquinolonas en Neisseria gonorrhoeae con el kit Allplex™ NG&DR Assay (Seegene®) en un hospital terciario de la Comunidad de Madrid, España

Background. The prevalence of drug-resistant Neisseria gonorrhoeae (NG) infections is increasing. Studies report the prevalence of NG strains presenting A2059G/C2611T (rRNA 23S) and S91F (parC) mutations conferring resistance to azith romycin and ciprofloxacin. Material and methods. We conducted a prospective cohort study evaluating first void-urine urines, rectal, and oropharyngeal swabs collected from a cohort of patients in a tertiary hospital in Madrid between October 2022 and January 2023. Samples were screened by Allplex™ 7-STI Essential As say (Seegene®). Drug resistances were performed by Allplex™ NG&DR Assay (Seegene®). Results. A total of 1,415 patients were included, of which 112 had a positive sample for NG infection. One patient had a C2611T mutation (0.9%) and neither patient showed A2059G mutation. We found 67 (59.8%) S91F-positive patients. For ty-four patients (39.3%) not had any mutations. Conclusions. We report a low-prevalence of mutations A2059G/C2611T to macrolides and a high-prevalence to S91F in NG infections. Molecular methods for the detection of NG resistance could be useful in direct non-culturable samples (AU)

Introducción. La infección por Neisseria gonorrhoeae (NG) resistente está aumentando. Se ha descrito la prevalencia de cepas de NG con mutaciones A2059G/C2611T (rRNA 23S) y S91F (parC) que confieren resistencia a azitromicina y cipro floxacino. Material y métodos. Realizamos un estudio prospecti vo evaluando orinas de primera micción, hisopos anales y fa ríngeos recogidos de una cohorte de pacientes en un hospital terciario de Madrid entre octubre de 2022 y enero de 2023. El cribado de las muestras se realizó mediante Allplex™ 7-STI Es sential Assay (Seegene®). Las resistencias a macrólidos y fluo roquinolonas se realizaron mediante Allplex™ NG&DR Assay (Seegene®). Resultados. Se incluyeron 1.415 pacientes, de los cua les 112 fueron positivos para NG. Un paciente presentaba una mutación C2611T (0,9%) y en ningún paciente se detec tó A2059G. Encontramos 67 pacientes (59,8%) positivos pa ra S91F. Cuarenta y cuatro pacientes (39,3%) no presentaban mutaciones. Conclusiones. Reportamos una baja prevalencia de mu taciones A2059G/C2611T a macrólidos y una alta prevalencia de S91F en NG. Los métodos moleculares para la detección de resistencias en NG podrían ser útiles en muestras directas no cultivables (AU)

Epidemiología y prevalencia de Mycoplasma genitalium y resistencia a azitromicina en el Área Norte de Tenerife, Islas Canarias

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.

Epidemiology and prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium in a tertiary hospital from Madrid, Spain / Epidemiología y prevalencia de mutaciones asociadas a la resistencia a macrólidos y fluoroquinolonas en Mycoplasma genitalium en un hospital terciario de Madrid, España

Objectives: Mycoplasma genitalium causes persistent sexually transmitted infections. The aims of this study were to estimate the prevalence of resistances to macrolides and fluoroquinolones in M. genitalium and the sexually transmitted coinfections in patients at Hospital Universitario La Paz (Madrid, Spain). Material and methods: Patients attended between January and October 2021 were studied. Screening for sexually transmitted pathogens and detection of 23S rRNA and parC genes mutations were performed by real-time PCR (Allplex,SeegeneTM). Results: A total of 1,518 females and 1,136 males were studied. The prevalence of M. genitalium was 2.1%. The macrolides resistance rate was 51.8%. The mutations found were A2059G, A2058T and A2058G. The rate of resistance to fluoroquinolones was 17.8% being the G248T mutation (S83I) the most frequent. Seven males had some sexual transmitted coinfection. Conclusions: Although the percentage of M. genitalium infections is low, the high rate of resistance to macrolides makes it necessary to revise the protocols for diagnosis and empirical treatment of sexually transmitted infections. The use of fluoroquinolones is appropriate after screening of macrolide resistance profile. (AU)

Objetivos: Mycoplasma genitalium causa infecciones de transmisión sexual persistentes. Los objetivos de este trabajo fueron estimar la prevalencia de resistencias a macrólidos y fluoroquinolonas en M. genitalium así como las coinfecciones de transmisión sexual en pacientes del Hospital Universitario La Paz (Madrid, España). Material y métodos: Se estudiaron pacientes atendidos entre enero y octubre de 2021. El cribado de patógenos de transmisión sexual y la detección de mutaciones de los genes ARNr 23S y parC se realizaron por PCR en tiempo real (Allplex, SeegeneTM). Resultados: Se estudiaron 1.518 mujeres y 1.136 hombres. La prevalencia de M. genitalium fue del 2,1%. La tasa de resistencia a macrólidos fue del 51.8%. Las mutaciones encontradas fueron A2059G, A2058T y A2058G. La tasa de resistencias a fluoroquinolonas fue del 17.8% siendo la mutación G248T (S83I) la más frecuente. Siete hombres presentaron alguna coinfección de transmisión sexual. Conclusiones: Aunque el porcentaje de infecciones por M. genitalium es bajo, la elevada tasa de resistencias frente a macrólidos hace necesario modificar los protocolos de diagnóstico y tratamiento empírico de las infecciones de transmisión sexual. El uso de fluoroquinolonas es adecuado tras testar previamente el perfil de resistencia a macrólidos. (AU)

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.

Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil / Real-Life Data on Hydroxychloroquine or Chloroquine with or Without Azithromycin in COVID-19 Patients: A Retrospective Analysis in Brazil

Resumo Fundamento Apesar da ausência de evidência mostrando benefícios da hidroxicloroquina e da cloroquina combinadas ou não à azitromicina no tratamento da covid-19, esses medicamentos têm sido amplamente prescritos no Brasil. Objetivos Avaliar desfechos, incluindo moralidade hospitalar, alterações eletrocardiográficas, tempo de internação, admissão na unidade de terapia intensiva, e necessidade de diálise e de ventilação mecânica em pacientes hospitalizados com covid-19 que receberam cloroquina ou hidroxicloroquina, e comparar os desfechos entre aqueles pacientes e seus controles pareados. Métodos Estudo multicêntrico retrospectivo do tipo coorte que incluiu pacientes com diagnóstico laboratorial de covid-19 de 37 hospitais no Brasil de março a setembro de 2020. Escore de propensão foi usado para selecionar controles pareados quanto a idade, sexo, comorbidades cardiovasculares, e uso de corticosteroides durante a internação. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados Dos 7850 pacientes com covid-19, 673 (8,6%) receberam hidroxicloroquina e 67 (0,9%) cloroquina. A idade mediana no grupo de estudo foi 60 (46-71) anos e 59,1% eram mulheres. Durante a internação, 3,2% dos pacientes apresentaram efeitos adversos e 2,2% necessitaram de interromper o tratamento. Alterações eletrocardiográficas foram mais prevalentes no grupo hidroxicloroquina/cloroquina (13,2% vs. 8,2%, p=0,01), e o prolongamento do intervalo QT corrigido foi a principal diferença (3,6% vs. 0,4%, p<0,001). O tempo mediano de internação hospitalar foi maior no grupo usando CQ/HCQ em relação aos controles (9,0 [5,0-18,0] vs. 8,0 [4,0-14,0] dias). Não houve diferenças estatisticamente significativas entre os grupos quanto a admissão na unidade de terapia intensiva (35,1% vs. 32,0%; p=0,282), ventilação mecânica invasiva (27,0% vs. 22,3%; p=0,074) ou mortalidade (18,9% vs. 18,0%; p=0,682). Conclusão Pacientes com covid-19 tratados com cloroquina ou hidroxicloroquina apresentaram maior tempo de internação hospitalar, em comparação aos controles. Não houve diferença em relação a admissão em unidade de terapia intensiva, necessidade de ventilação mecânica e mortalidade hospitalar.

Abstract Background Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. Objectives To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. Methods A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. Results From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 - 71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). Conclusion COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and in-hospital mortality were similar.

Efectividad de antimicrobianos como coadyuvantes del raspado y alisado radicular en el tratamiento de la periodontitis del adulto

Fundamento: existen escasos estudios que evalúen la aplicación subgingival de antimicrobianos en el tratamiento de la periodontitis del adulto. Objetivo: evaluar la efectividad de antimicrobianos como coadyuvantes del raspado y alisado radicular en el tratamiento de la periodontitis leve y moderada del adulto. Métodos: estudio cuasiexperimental de intervención terapéutica, realizado en la Clínica Estomatológica de Santiago de Cuba, entre noviembre 2018 y septiembre 2021, sobre 144 pacientes con diagnóstico de periodontitis crónica leve y moderada. Mediante el método probabilístico aleatorio simple, se conformaron tres grupos con 48 integrantes, de forma voluntaria. El grupo control tratado con el raspado y alisado radicular y dos grupos de estudio en que, además, se aplicó una concentración subgingival de tetraciclina y azitromicina, respectivamente. Los pacientes fueron examinados y evaluados a los siete días, al mes y tres meses. Se empleó el análisis de varianza ANOVA para evaluar la igualdad de medias y la prueba ji-cuadrado para la efectividad de curación con un 95 % de confiabilidad. Resultados: hubo reducción de profundidad de sondaje y mayor ganancia de inserción clínica en los tres grupos, pero a favor de los grupos de estudio. Todas las terapias fueron efectivas, pero obtuvo mayor curación el grupo dos (RAR + Tetraciclina) con 97,9 %. Conclusiones: las aplicaciones subgingivales de tetraciclina y azitromicina resultaron efectivas como coadyuvantes del raspado y alisado radicular en el tratamiento de la periodontitis leve y moderada del adulto; con la tetraciclina se logró mayor mejoramiento de parámetros clínicos, disminución de profundidad de sondaje, ganancia de inserción clínica y menor tiempo de curación.

Background: there are few studies that evaluate the subgingival application of antimicrobials in adult periodontitis. Objective: to evaluate the effectiveness of antimicrobials as contributing for scaling and root planing in the treatment of mild and moderate periodontitis in adults. Methods: quasi-experimental study of therapeutic intervention, carried out at the Santiago de Cuba Stomatological Clinic, between November 2018 and September 2021, on 144 patients diagnosed with mild and moderate chronic periodontitis. Using the simple random probabilistic method, three groups with 48 members were formed voluntarily. The control group treated with scaling and root planing and two study groups in which, in addition, a subgingival concentration of tetracycline and azithromycin, respectively, was applied. The patients were examined and evaluated at seven days, one month and three months. ANOVA analysis of variance was used to evaluate the equality of means and the chi-square test for the effectiveness of healing with 95% reliability. Results: there was a reduction in probing depth and greater gain in clinical attachment in the three groups, but in favor of the study groups. All therapies were effective, but group two (RAR + Tetracycline) obtained a greater cure with 97.9%. Conclusions: subgingival applications of tetracycline and azithromycin were effective as adjuvants for scaling and root planing in mild and moderate periodontitis in adults; Tetracycline achieved greater improvement in clinical parameters, decreased probing depth, gain in clinical attachment, and shorter healing time.

Tratamiento de COVID-19 en Panamá. La historia del inicio, estudio PanaCovid2020

Antecedentes En Panamá, durante los primeros cinco meses de pandemia, se reportaron 65,256 casos y 1,421 fallecimientos por COVID-19. Los tratamientos utilizados en pacientes hospitalizados durante este periodo fueron variando en la medida que surgía evidencia científica. Metodología Presentamos un estudio multicéntrico observacional, descriptivo, de corte transversal y retrospectivo de la terapéutica administrada en pacientes hospitalizados con COVID-19 en siete centros estatales de la República de Panamá, entre el 1 de marzo al 31 de julio de 2020. Se analizó el resultado de recuperado o fallecido en relación al uso de hidroxicloroquina, heparinas y esteroides. Resultados Se revisaron 837 expedientes. 60.7% pacientes eran hombres y la mediana de edad fue 53.6 años. Los tratamientos más utilizados fueron heparinas 84.7%, esteroides sistémicos 76.5%, azitromicina 65.5% e hidroxicloroquina en 41.1%. La frecuencia de uso de oxigenoterapia fue de cánula nasal 73,2%, máscara facial con reservorio 39%, cánula de alto flujo 8.9%, ventilación mecánica no invasiva 11.1% y ventilación invasiva en el 15.3%. Los esteroides mostraron mayor tasa de recuperación (OR 1.72 [1.16-2.54). Conclusiones El reto de abordar una nueva enfermedad, sin tratamiento conocido, con evolución y desenlace variable, llevó a la comunidad médica a utilizar medicamentos empíricos con potencial terapéutico incierto. Destacamos que desde muy temprano se administró esteroides sistémicos, heparinas y tocilizumab; actualmente con beneficios para pacientes con requerimientos de hospitalización. Además, se empleó técnicas de oxigenación, como la cánula de alto flujo y ventilación mecánica no invasiva, con dudosa efectividad; pero que hoy ya tienen un rol estudiado en la falla respiratoria por COVID-19. (provisto por Infomedic International)

Background: In Panama, during the first five months of the pandemic, 65,256 cases and 1,421 deaths due to COVID-19 were reported. The treatments used in hospitalized patients during this period varied as scientific evidence emerged. Methodology: We present a retrospective, descriptive, cross-sectional, observational, descriptive, multicenter study of the therapeutics administered in hospitalized patients with COVID-19 in seven state centers in the Republic of Panama, between March 1 and July 31, 2020. The outcome of recovered or deceased was analyzed in relation to the use of hydroxychloroquine, heparins and steroids. Results: A total of 837 files were reviewed. 60.7% of patients were men and the median age was 53.6 years. The most commonly used treatments were heparins 84.7%, systemic steroids 76.5%, azithromycin 65.5% and hydroxychloroquine in 41.1%. The frequency of oxygen therapy use was nasal cannula 73.2%, face mask with reservoir 39%, high-flow cannula 8.9%, noninvasive mechanical ventilation 11.1% and invasive ventilation in 15.3%. Steroids showed higher recovery rate (OR 1.72 [1.16-2.54). Conclusions: The challenge of dealing with a new disease, without known treatment, with variable evolution and outcome, led the medical community to use empirical drugs with uncertain therapeutic potential. We highlight the early administration of systemic steroids, heparins and tocilizumab; currently with benefits for patients requiring hospitalization. In addition, oxygenation techniques were used, such as high-flow cannula and noninvasive mechanical ventilation, with doubtful effectiveness, but which today have a studied role in respiratory failure due to COVID-19.   (provided by Infomedic International)

Effect of periodontal debridement plus systemic azithromycin in subjects with stage III periodontitis: a randomized controlled clinical trial / Efecto del desbridamiento periodontal más azitromicina sistémica en sujetos con periodontitis estadio III: un ensayo clínico controlado aleatorio

Aim: To evaluate the effect of the systemic administration of azi-thromycin (AZM) as an adjunct to non-surgical periodontal therapy (NSPT) on the clinical and microbiological variables of patients with periodontitis. Material and Methods: Eighteen volunteers received NSPT combined with placebo or AZM (500 mg/day) for 3 days (n=9/group). They were monitored clinically for probing pocket depth (PPD), clinical attachment level (CAL), O'Leary index (OI), bleeding on probing (BoP) at baseline and during the first, third and sixth month and microbiologically, at baseline and at 3 and 6 months after therapy, by conventional polymerase chain reaction tests. Results: Fourteen patients completed the study (n=7/group). Differences statistically significant were observed among both groups. The experimental group presented: A PPD mean (p=0.04) significantly lower and PPD reduction (p=0.02), at 6-months post NSPT. Regarding changes (∆), at the third month post NSPT, there was a significant increase in the number of shallow sites (p<0.001) and a decrease in the intermediate sites (p<0.001). In addition, a significant decrease in the mean number of deep sites (p=0.04) was detected at 6 months post treatment. There was also a significant decrease in periodontal index BoP at 1 (p=0.01), 3 (p<0.001) and 6 (p=0.01) months and OI at 3- and 6-months (p<0.001), post treatment. Regarding the presence of periodontal pathogens, no significant differences were observed, intra and inter groups. Conclusion: AZM as an adjuvant to NSPT provides additional beneficial effects for PPD and BoP compared to NSPT alone.

Objetivo: Evaluar el efecto de la administración sistémica de azitromicina (AZM) como coadyuvante de la terapia periodontal no quirúrgica (TPNQ) en las variables clínicas y microbiológicas de pacientes con periodontitis. Material y Métodos: Dieciocho voluntarios recibieron TPNQ combinado con placebo o AZM (500 mg/día) durante 3 días (n=9/grupo). Fueron monitoreados clínicamente para determinar Profundidad de Sondaje del Saco (PSS), Nivel de Inserción Clínica (NIC), Índice de O'Leary (IO), Sangrado al sondaje (SS) al inicio y durante el primer, tercer y sexto mes y microbiológicamente, al inicio y a los 3 y 6 meses después de la terapia, mediante la reacción en cadena de la polimerasa convencional. Resultados: Catorce pacientes completaron el estudio (n=7/grupo). Se observaron diferencias estadísticamente significativas entre ambos grupos. El grupo experimental presentó una media de PSS significativamente menor (p=0,04) y una reducción de PSS (p=0,02), a los 6 meses post TPNQ. En cuanto al delta (∆) pre y post tratamiento, al tercer mes post TPNQ, hubo un aumento significativo en el número de sitios poco profundos (p<0.001) y una disminución en los sitios intermedios (p<0.001). Además, se detectó una disminución significativa en la media de los sitios profundos (p=0.04) a los 6 meses post tratamiento. También hubo una disminución significativa en el índice SS al primer (p=0.01), tercer (p<0. 0 01) y sexto mes (p=0.01) post TPNQ y del IO al tercer y sexto mes (p<0.001), post tratamiento. En cuanto a la presencia de patógenos periodontales, no se observaron diferencias significativas tanto intra como ínter grupos. Conclusión: AZM como adyuvante a TPNQ proporciona efectos benéficos adicionales en la PSS y SS en comparación a TPNQ solo.

Indicación y prescripción de macrólidos en una población colombiana / Study of the indications for macrolide prescriptions in a Colombian population

Introducción. El uso inadecuado de antibióticos se asocia con aumento de la resistencia antimicrobiana, mayores costos de atención médica, más efectos adversos y peores resultados clínicos. Objetivo. Determinar los patrones de prescripción y las indicaciones aprobadas y no aprobadas para macrólidos en un grupo de pacientes en Colombia. Materiales y métodos. Se hizo un estudio de corte transversal sobre las indicaciones de uso de macrólidos en pacientes ambulatorios a partir de una base de datos de dispensación de medicamentos de 8,5 millones, aproximadamente, de personas afiliadas al sistema de salud de Colombia. Se consideraron variables sociodemográficas, farmacológicas y clínicas. Resultados. Se encontraron 9.344 pacientes que habían recibido prescripción de macrólidos; su mediana de edad era de 40,1 años (rango intercuartílico: 27,1-53,3 años) y el 58,3 % correspondía a mujeres. El macrólido más prescrito fue la azitromicina (38,8 %) y los usos más frecuentes fueron el tratamiento de la infección por Helicobacter pylori (15,9 %) y la neumonía (15,8 %). El 31,3 % de las prescripciones correspondía a indicaciones no aprobadas, destacándose el resfriado común (7,8 %), la Covid-19 (4,0 %) y la bronquitis aguda (3,5 %). La residencia en la región Caribe (OR=1,17; IC95% 1,05-1,31), las prescripciones odontológicas (OR=2,75; IC95% 1,91-3,96), las comorbilidades respiratorias crónicas (OR=1,30; IC95% 1,08-1,56), y la prescripción de eritromicina (OR=3,66; IC95% 3,24-4,14) o azitromicina (OR=2,15; IC95% 1,92 2,41), se asociaron con una mayor probabilidad de recibir macrólidos para indicaciones no aprobadas, en tanto que tener entre 18 y 64 años (OR=0,81; IC95% 0,71-0,93), 65 o más años (OR=0,77; IC95% 0,63-0,94) y residir en Bogotá-Cundinamarca (OR=0,74; IC95% 0,65 0,85) reducían dicho riesgo. Conclusiones. La mayoría de los pacientes recibieron macrólidos para infecciones del sistema respiratorio; la eritromicina y la azitromicina se prescribieron en indicaciones no aprobadas en menores de 18 años y en quienes presentaban enfermedades respiratorias crónicas.

Introduction: The inappropriate use of antibiotics is associated with a greater risk for antimicrobial resistance, high health care costs, adverse events, and worse clinical outcomes. Objective: To determine the prescription patterns and approved and nonapproved indications for macrolides in a group of patients from Colombia. Materials and methods: This was a cross-sectional study on the indications for the use of macrolides in outpatients registered in a drug-dispensing database of approximately 8.5 million people affiliated with the Colombian health system. Sociodemographic, pharmacological, and clinical variables were considered. Results: A total of 9.344 patients had received a macrolide prescription; their median age was 40.1 years (interquartile range: 27.1-53.3 years) and 58.3% were women. The most commonly prescribed macrolide was azithromycin (38.8%) most frequently for Helicobacter pylori infection (15.9%) and pneumonia treatment (15.8%). A total of 31.3% of the prescriptions were used for unapproved indications: common cold (7.8%), COVID-19 (4.0%), and acute bronchitis (3.5%). Residence in the Caribbean region (OR=1.17; 95%CI 1.05-1.31), dental prescriptions (OR=2.75; 95%CI 1.91-3.96), presence of chronic respiratory comorbidities (OR=1.30; 95%CI 1.08-1.56), and prescription of erythromycin (OR=3.66; 95%CI 3.24-4.14) or azithromycin (OR=2.15; 95%CI 1,92-2.41) were associated with a higher probability of macrolide use for unapproved indications while being 18-64 years old (OR=0.81; 95%CI 0.71-0.93) or 65 years or older (OR=0.77; 95%CI 0.63-0.94) and residing in Bogotá-Cundinamarca (OR=0.74; 95%CI 0.65-0.85) were associated with reduced risk. Conclusions: Most patients received macrolides for respiratory tract infections; erythromycin and azithromycin were used for unapproved indications in people under 18 years of age and those with chronic respiratory diseases.

Pharmacological treatment of COVID-19: an opinion paper / Tratamiento farmacológico del COVID-19: un documento de opinión

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation. (AU)

La precocidad y la eficacia de las vacunas desarrolladas hasta ahora frente al COVID-19, ha sido el avance más significativo y salvador frente a la pandemia. El desarrollo vacunal no ha impedido, durante todo el periodo de la pandemia, la búsqueda constante de remedios terapéuticos, tanto entre los medicamentos ya existentes y con indicaciones diversas, como en el desarrollo de nuevos fármacos. Sobre estos nuevos fármacos, sobre las novedades en la inmunoterapia y sobre lo aprendido de los moduladores de la respuesta inmune ya conocidos y que se han mostrado eficaces frente al virus, el Comité Científico del COVID-19 del Ilustre Colegio de Médicos de Madrid ha querido ofrecer una aproximación precoz, simplificada y critica que pueda ayudar a comprender la situación actual. (AU)

Evolución del intervalo QTc en pacientes con infección SARS-CoV-2 tratados con fármacos antivirales / QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs

Introducción: Muchos antivirales, como la hidroxicloroquina, se han utilizado para el tratamiento de COVID-19. La prolongación del QTc es un efecto adverso preocupante, escasamente estudiado en pediatría. Pacientes y métodos: Los pacientes pediátricos con COVID-19 que recibieron tratamiento antiviral se emparejaron (1:2) con controles no infectados ni expuestos al tratamiento. Se analizaron prospectivamente los electrocardiogramas basales, en las primeras 72 horas de tratamiento y posterior a 72 horas. Resultados: Once (22,9%) de 48 pacientes pediátricos ingresados por COVID-19 (marzo a julio del 2020) recibieron terapia antiviral. Todos presentaban patologías de base; destacando cardiopatías (4/11; 36,4%) e inmunosupresión (3/11; 27,3%); 5/11 (45,5%) recibían tratamiento de base con potencial efecto sobre el QTc. No hubo diferencias en el QTc basal entre casos y controles: 414,8 ms (49,2) vs. 416,5 ms (29,4) (p = 0,716). Se observó QTc prolongado basal en 2/11 casos y 2/22 controles. De los casos, 10/11 (90,9%) recibieron hidroxicloroquina, principalmente asociada a azitromicina (8/11; 72,7%); tres recibieron lopinavir/ritonavir, uno remdesivir. La mediana de incremento del QTc tras 72 horas fue de 28,9 ms (IQR 48,7) (p = 0,062); 4/11 (36,4%) presentaron un QTc largo, de los cuales en tres ≥ 500 ms. En uno se paró el tratamiento (QTc 510 ms) pero no se documentaron arritmias ventriculares. Conclusiones: El uso de fármacos antivirales causó un incremento del QTc tras 72 horas de tratamiento, considerándose un QTc largo en el 36,4% de los pacientes, aunque no se objetivaron eventos arrítmicos. El uso de hidroxicloroquina y antivirales requiere monitorización activa del QTc y se recomienda suspender el tratamiento si el QTc > 500 ms. (AU)

Introduction: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. Patients and methods: Pediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h in treatment and after 72 h. Results: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March–July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs. 416.5 ms (29.4) (p = 0.716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms (IQR 48.7) (p = 0.062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. Conclusions: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc >500 ms. (AU)

QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs.

INTRODUCTION: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. PATIENTS AND METHODS: Paediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h of treatment and after 72 h. RESULTS: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March-July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs 416.5 ms (29.4), (P = .716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms [IQR 48.7] (P = .062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. CONCLUSIONS: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc > 500 ms.

Chlamydia infection resembling ulcerative colitis: case report / Infecção por clamídia lembrando retocolite ulcerativa: relato de caso

Introduction: The diagnosis of ulcerative colitis is relatively complex because the symptoms are similar to those seen in several other diseases. Objective: To report a case of rectal chlamydial infection whose initial symptoms resembled ulcerative colitis. Case report: A 50-year-old male patient presented with diarrhea, blood and mucus in the stools, and an ulcer in the rectum. The histopathological exam pointed to chronic, unspecified inflammation. After a broad serological screening, with Immunoglobulin M positive for Chlamydia and a high titer of immunoglobulin G, the patient was treated with antibiotics and is clinically cured. Later, he remained Immunoglobulin M positive, but the titers of immunoglobulin G lowered considerably. Chlamydia has been shown to live in the gut microbiota, which could explain the case. Conclusion: It is important to search for chlamydial infection as a differential diagnosis of ulcerative colitis.

Introdução: A retocolite ulcerativa é uma condição clínica de diagnóstico relativamente complexo, uma vez que apresenta sinais e sintomas comuns a muitas outras doenças. Objetivo: Relatar um caso de infecção anorretal por clamídia, cujos sintomas iniciais se pareciam com os de retocolite ulcerativa. Relato de caso: Paciente de 50 anos, do sexo masculino, apresentou-se com diarreia, muco e sangue nas fezes, e úlcera no canal anorretal. O exame histopatológico mostrou um processo inflamatório crônico e inespecífico, então procedeu-se a amplo rastreamento sorológico, que revelou Imunoglobulina M positivo para clamídia e altos títulos de Imunoglobulina G. O paciente foi tratado com antibióticos e encontra-se clinicamente curado. No seguimento, permanece com Imunoglobulina M positivo, mas os títulos de Imunoglobulina G decresceram consideravelmente. Bactérias do gênero Chlamydia têm sido reportadas como parte da microbiota intestinal, o que poderia explicar tal comportamento sorológico. Conclusão: É importante rastrear por clamídia como diagnóstico diferencial das suspeitas de retocolite ulcerativa

Sales of "COVID kit" drugs and adverse drug reactions reported by the Brazilian Health Regulatory Agency / Vendas de "kit-COVID" e reações adversas a esses medicamentos relatadas pela Agência Nacional de Vigilância Sanitária / Ventas de medicamentos del "kit-COVID" y reacciones adversas a los medicamentos notificadas por la Agencia Nacional de Vigilancia Sanitaria

Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.

No Brasil, o uso off label de azitromicina, hidroxicloroquina e ivermectina (o "kit-COVID") foi sugerido para tratar COVID-19 sem que tivéssemos evidências clínicas ou científicas de sua eficácia. Estas drogas têm causado reações adversas (RA) em quem as tomam. Este estudo almejou analisar se a venda dos medicamentos que compõem o "kit-COVID" correlaciona-se com o número relatado de RAs após o início da pandemia da COVID-19. Os dados sobre vendas e RA associados a azitromicina, hidroxicloroquina e ivermectina foram obtidos no site da Agência Nacional de Vigilância Sanitária (Anvisa) para todos os estados brasileiros. Comparamos o período entre março de 2019 e fevereiro de 2020 (antes da pandemia) ao de março de 2020 a fevereiro de 2021 (durante a pandemia). Ajustamos tendências para os dados de séries temporais e as análises de correlação cruzada para investigar a correlação entre vendas e RA em um mesmo mês (lag 0) e nos seguintes (lag 1 e 2). O coeficiente de correlação de Spearman foi utilizado para avaliar a magnitude das correlações. Após o início da pandemia, as vendas de todos os medicamentos investigados aumentaram significativamente (69,75% para azitromicina, 10.856.481,39% para hidroxicloroquina e 12.291.129,32% para ivermectina). Os níveis de RAs de todos os medicamentos (com exceção de azitromicina) eram zero antes da pandemia mas aumentaram após seu início. A análise de correlação cruzada foi significativa no lag 1 para todas as drogas em todo o país. A correlação de Spearman foi moderada para azitromicina e hidroxicloroquina, mas ausente para ivermectina. Os dados devem ser interpretados com cautela, uma vez que não realizamos uma busca ativa por RA. Nossos resultados mostram que o uso aumentado e indiscriminado do "kit-COVID" durante a pandemia se correlaciona com uma ocorrência aumentada de RAs.

Se ha sugerido el uso fuera de lo establecido de azitromicina, hidroxicloroquina e ivermectina (el "kit-COVID") para el tratamiento de la COVID-19 en Brasil sin evidencia clínica o científica de su eficacia. Estos medicamentos tienen reacciones adversas (RAM) conocidas. Este estudio pretendía analizar si las ventas de medicamentos del "kit-COVID" están correlacionadas con el número de reacciones adversas notificadas tras el inicio de la pandemia de COVID-19. Los datos se obtuvieron del sitio web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa) sobre las ventas y las RAM notificadas para la azitromicina, la hidroxicloroquina y la ivermectina para todos los estados brasileños. Se comparó el periodo de marzo de 2019 a febrero de 2020 (antes de la pandemia) con el de marzo de 2020 a febrero de 2021 (durante la pandemia). Se realizó un ajuste de tendencia para los datos de las series de tiempo y un análisis de correlación cruzada para investigar la correlación entre las ventas y la RAM dentro del mismo mes (lag 0) y en los meses siguientes (lag 1 y lag 2). Se utilizó el coeficiente de correlación de Spearman para evaluar la magnitud de las correlaciones. Tras el inicio de la pandemia, las ventas de todos los medicamentos investigados aumentaron significativamente (69,75% para la azitromicina, 10.856.481,39% para la hidroxicloroquina y 12.291.129,32% para la ivermectina). Los niveles de RAM de todos los medicamentos, excepto la azitromicina, eran nulos antes de la pandemia, pero aumentaron tras su inicio. El análisis de correlación cruzada fue significativo en el lag 1 para todos los medicamentos a nivel nacional. La correlación de Spearman fue moderada para la azitromicina y la hidroxicloroquina, pero no para la ivermectina. Los datos deben interpretarse con cautela, ya que no se realizó una búsqueda activa de RAM. Nuestros resultados muestran que el uso creciente e indiscriminado del "kit-COVID" durante la pandemia se correlaciona con una mayor aparición de las RAM.

Interacciones farmacocinéticas de la azitromicina e implicación clínica / Pharmacokinetic interactions of azithromycin and clinical implication

Introducción: El síndrome respiratorio agudo grave (por la COVID-19) es en la actualidad la primera causa de muerte en el Perú, por lo que se requiere de fármacos eficaces y seguros para mitigar la enfermedad. Se realizó una búsqueda bibliográfica en SciELO y PubMed/ Medline; se seleccionaron 37 de 58 artículos sobre el tema. Objetivos: Revisar e integrar la información sobre las interacciones farmacocinéticas de la azitromicina que se prescriben en el tratamiento ambulatorio de la COVID-19 en el Perú, y evaluar su implicación clínica. Desarrollo: La azitromicina es usada en la COVID-19, por su actividad antiinflamatoria, al inhibir a las interleucinas (IL1, 6, 8 y TNF-α), y a las moléculas de adhesión intracelular 1 (ICAM1); y por inducir la producción de interferón tipo I (IFN-α, IFN-β) y III (IFN-λ) en células de pacientes con enfermedad pulmonar obstructiva crónica. Los estudios de tres brazos, aleatorizado y abierto, indican que la azitromicina no genera cambios en los parámetros farmacocinéticos de la ivermectina, sildenafilo, rupatadina y desloratadina; los estudios de un solo centro, abierto, sin ayuno y de dos períodos, evidencian que la azitromicina influye en los parámetros farmacocinéticos de venetoclax y de los psicotrópicos. Conclusiones: Basado en la evidencia de los estudios clínicos revisados e integrados, se concluye que estas son limitadas y de poca relevancia clínica, sin embargo, se propone usar el antibiótico bajo el criterio científico del médico, para evitar las interacciones farmacocinéticas y las reacciones adversas de los fármacos(AU)

Introduction: The severe acute respiratory syndrome (due to COVID-19) is currently the leading cause of death in Peru, so effective and safe drugs are required to mitigate the disease. A bibliographic search was carried out in SciELO and PubMed/Medline; 37 of 58 articles on the topic were selected. Objectives: Review and integrate the information on the pharmacokinetic interactions of azithromycin that are prescribed in the outpatient treatment of COVID-19 in Peru, and evaluate their clinical implication. Development: Azithromycin is used in COVID-19, due to its anti-inflammatory activity, by inhibiting interleukins (IL1, 6, 8 and TNF-α), and intracellular adhesion molecules 1 (ICAM1); and by inducing the production of type I interferon (IFN-α, IFN-β) and III (IFN-λ) in cells of patients with chronic obstructive pulmonary disease. The three-arm, randomized and open-label studies indicate that azithromycin does not cause changes in the pharmacokinetic parameters of ivermectin, sildenafil, rupatadine, and desloratadine; single-center, open-label, non-fasting, and two-period studies show that azithromycin influences the pharmacokinetic parameters of venetoclax and psychotropics. Conclusions: Based on the evidence from the reviewed and integrated clinical studies, it is concluded that these are limited and of little clinical relevance, however, it is proposed to use the antibiotic under the scientific criteria of the doctor, to avoid pharmacokinetic interactions and adverse reactions of drugs(AU)

Mortalidad por hidroxicloroquina y azitromicina en pacientes con COVID-19 en ventilación mecánica de una unidad de cuidados intensivos de Lima

Objetivo : Estimar la mortalidad relacionada a hidroxicloroquina y azitromicina en pacientes con Covid-19 en ventilación mecánica de una unidad de cuidados intensivos. Material y métodos : Cohorte analítica retrospectiva. Se incluyeron 105 pacientes con Covid-19 en ventilación mecánica invasiva que ingresaron con el diagnóstico de Insuficiencia Respiratoria Aguda a la unidad de cuidados intensivos del Hospital Cayetano Heredia durante el año 2020. Resultados : La mortalidad global fue 38 %; el 79 % fueron varones, la edad media fue 50±13 años, el 65 % no tuvo comorbilidades; al ingreso la puntuación en la escala APACHE II fue 12±6 puntos y en la escala SOFA 5±3 puntos; el 30 % recibió hidroxicloroquina, el 32 % azitromicina y 32 % la combinación de los mismos. La mortalidad fue significativamente mayor en pacientes que recibieron hidroxicloroquina (p=0.001), azitromicina (p=0.03), y la combinación hidroxicloroquina más azitromicina (p=0.001). Sin embargo, en la regresión de Cox se evidenció que los pacientes que fallecieron tuvieron mayor probabilidad de exposición a hidroxicloroquina (p=0.001) (HR: 21, IC: 3.4-131.3), no ocurrió lo mismo con azitromicina (p=0.22) (HR: 0.43, IC: 0.11-1.6). Conclusión : La mortalidad en los pacientes con Covid-19 en ventilación mecánica invasiva fue significadamente mayor en pacientes que recibieron hidroxicloroquina.

Objective : To estimate mortality rates associated with hydroxichloroquine and azithromycin use in Covid-19 patients undergoing mechanical ventilation in an intensive care unit in Lima. Material and methods : This is a retrospective analytical cohort. One hundred and five patients with Covid-19 undergoing invasive mechanical ventilation who were admitted with a diagnosis of acute respiratory insufficiency to the intensive care unit of Cayetano Heredia Hospital in Lima during 2020. Results : The overall mortality rate was 38%. Most patients (79%) were male, their mean age was 50 ± 13 years, two thirds (65%) did not have comorbidities; APACHE II and SOFA scores were 12 ± 6 points and 5 ± 3 points, respectively. Thirty percent of all patients received hydroxichloroquine, 32% received azithromycin, and 32% received both drugs. Mortality was significantly higher in those patients who received hydroxichloroquine (p= 0.001), azithromycin (p= 0.03), and the combination of hydroxichloroquine and azithromycin (p= 0.001). However, when a Cox regression analysis was performed, it was evidenced that deceased patients were more likely to have been exposed to hydroxichloroquine (p= 0.001) (HR: 21, CI: 3.4-131.3), but this was not the case with azithromycin (p= 0.22) (HR: 0.43, CI: 0.11-1.6). Conclusion : Mortality in Covid-19 patients undergoing invasive mechanical ventilation was higher in those who received hydroxichloroquine.

[QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs]. / Evolución del intervalo QTc en pacientes con infección SARS-CoV-2 tratados con fármacos antivirales.

INTRODUCTION: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. PATIENTS AND METHODS: Pediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h in treatment and after 72 h. RESULTS: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March-July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs. 416.5 ms (29.4) (p = 0.716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms (IQR 48.7) (p = 0.062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. CONCLUSIONS: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc >500 ms.

Eficacia y seguridad de la cloroquina, la hidroxicloroquina y la azitromicina en pacientes con COVID-19. Resumen de evidencia / Efficacy and safety of chloroquine, hydroxychloroquine and azithromycin in patients with COVID-19: Summary of evidence

Resumen Introducción: hasta el momento, no se ha demostrado la efectividad de ningún tratamiento para afrontar la emergencia sanitaria por COVID-19. Objetivo: presentar la evidencia disponible respecto a la eficacia y seguridad del uso de cloroquina, hidroxicloroquina y azitromicina en la profilaxis y el manejo de pacientes con COVID-19. Materiales y métodos: se realizó una revisión de la literatura en las bases de datos MEDLINE, Scopus y PubMed sobre publica- ciones que registraran el uso de cloroquina, hidroxicloroquina y azitromicina en pacientes con COVID-19. Resultados: se seleccionaron 12 publicaciones que incluyeron revisiones rápidas de literatura, estudios observacionales y ensayos clínicos. No se encontró información sobre la profilaxis con cloroquina, hidroxicloroquina ni azitromicina para SARS-CoV-2. Los eventos adversos reportados incluyeron emesis, dolor abdominal, náuseas, diarrea, erupción cutánea y picazón. Conclusiones: según la evidencia recopilada el uso de hidroxicloroquina o de cloroquina sola o en combinación con azitromicina en pacientes con COVID-19 no ha mostrado beneficio. Además, cada uno de estos esquemas de tratamiento se asocia con un mayor riesgo de muerte y de episodios de arritmias. En síntesis, la efectividad de estos medicamentos sigue sin estar esclarecida, por lo cual se sugiere evitar su uso en el tratamiento de personas con infección por SARS-CoV-2/COVID-19.

Abstract Introduction: The COVID-19 disease is a health emergency; treatment has not yet been proven. Objective: To present the available evidence of efficacy and safety of the use of hydroxychloroquine and azithromycin in the prophylaxis and management of patients with COVID-19. Methods: A rapid literature review was performed; we consulted Medline, scopus and pubmed databases. Results: Eleven publications were included including rapid literature reviews, observational studies, and clinical trials. No data were found studying prophylaxis with hydroxychloroquine and azithromycin for SARS-CoV-2. Reports of adverse events include episodes of emesis, abdominal pain, nausea, diarrhea, rash, and itching. Conclusions: The evidence collected suggests that the use of hydroxychloroquine and azithromycin in patients with COVID-19, could abnormal electrocardiogram and increased risk of mortality in-hospital. The effectiveness remains unclear.