Prescripción de fármacos cardiotóxicos en pacientes con enfermedades cardiovasculares

Introducción: El uso de fármacos con potencial cardiotóxico para tratar enfermedades no cardiovasculares coexistentes resulta un agravante evitable. Objetivo: Evaluar la prescripción de 5 fármacos cardiotóxicos en pacientes con enfermedades cardiovasculares. Métodos: Se realizó un estudio descriptivo transversal (enmarcado en los estudios de utilización de medicamentos) de marzo a diciembre de 2020 en el Policlínico Santa Cruz (Artemisa, Cuba), en una población de 234 sujetos con enfermedades cardiovasculares que habían sido tratados con domperidona, azitromicina, ciprofloxacina, ibuprofeno y diclofenaco. Las variables estudiadas fueron: sexo, edad, consumo de fármacos cardiotóxicos, motivo de indicación, enfermedades cardiovasculares, forma farmacéutica, dosis diaria, intervalo de las dosis y duración del tratamiento. Se realizó un análisis estadístico descriptivo. Resultados: Los fármacos más prescritos fueron la azitromicina (n= 63), el ibuprofeno (n= 59) y la ciprofloxacina (n= 57). Sus principales motivos de indicación fueron, respectivamente, la neumonía adquirida en la comunidad (38,1 %), las infecciones de piel y tejidos blandos (28,8 %), y las infecciones del tracto urinario (43,8 %). La principal enfermedad cardiovascular fue la hipertensión arterial. Para los 5 fármacos seleccionados se reportó su esquema terapéutico (forma farmacéutica, dosis diaria, intervalo de dosis y duración del tratamiento). Conclusiones: Aunque en todos los casos el motivo de indicación es el adecuado, los fármacos pueden sustituirse por otros de menor riesgo cardiovascular. En su mayoría, los esquemas terapéuticos son correctos, salvo en los casos de la domperidona (duración prolongada) y el diclofenaco (altas dosis).

Introduction: The use of drugs with cardiotoxic potential to treat coexisting noncardiovascular diseases results in avoidable aggravation. Objective: To assess the prescription of 5 cardiotoxic drugs in patients with cardiovascular disease. Methods: A cross-sectional descriptive study (framed in the studies of drug utilization) was carried out from March to December 2020 in the Policlínico Santa Cruz (Artemisa, Cuba), in a population of 234 subjects with cardiovascular diseases who had been treated with domperidone, azithromycin, ciprofloxacin, ibuprofen and diclofenac. The variables studied were: sex, age, consumption of cardiotoxic drugs, reason for indication, cardiovascular disease, pharmaceutical form, daily dose, dose interval, and duration of treatment. Descriptive statistical analysis was performed. Results: The most prescribed drugs were azithromycin (n= 63), ibuprofen (n= 59) and ciprofloxacin (n= 57). Their main reasons for indication were, respectively, community-acquired pneumonia (38.1%), skin and soft tissue infections (28.8%), and urinary tract infections (43.8%). The main cardiovascular disease was arterial hypertension. For the 5 selected drugs, their therapeutic scheme (pharmaceutical form, daily dose, dose interval and duration of treatment) was reported. Conclusions: Although in all cases the reason for indication was adequate, the drugs can be substituted by others of lower cardiovascular risk. For the most part, the therapeutic regimens are correct, except in the cases of domperidone (prolonged duration) and diclofenac (high doses).

Paediatric ocular rosacea: diagnosis and management with an eyelid-warming device and topical azithromycin 1.5.

BACKGROUND: Ocular rosacea is a chronic inflammatory disorder with periods of exacerbation and remission, often underdiagnosed in children. When diagnosed, its management is challenging because of a lack of effective long-term treatment options. OBJECTIVE: To report our experience in cases of pediatric ocular rosacea treated with moist heat therapy and topical azithromycin 1.5%. METHODS: The medical records of six children diagnosed with ocular rosacea based on a careful medical history and slit-lamp examination of the eyelids and ocular surface were reviewed. Previous treatments were discontinued, and children/parents were instructed to use the eyelid-warming device for 1 or 2 sessions of 10minutes each day, followed by eyelid massage and cleansing, in combination with azithromycin 1.5% eye drops. RESULTS: The diagnosis of ocular rosacea in these children was delayed for several months or years from the first identifiable clinical sign or symptom. All the children presented with corneal sequelae and decreased vision. Ocular manifestations included meibomian gland disease, recurrent chalazia, and phlyctenular keratoconjunctivitis. Cutaneous signs were not always associated with the condition. Ocular rosacea was usually resistant to initial treatments with antibiotics and topical corticosteroids. Treatment with the eyelid-warming device in combination with azithromycin 1.5% led to a rapid improvement in the clinical signs and was well tolerated by all patients. CONCLUSIONS: Childhood ocular rosacea is potentially sight threatening. Practitioners should consider this condition in order to minimise diagnostic delay and subsequent complications. Combined therapy of eyelid hygiene (including an eyelid warming device) and azithromycin 1.5% eye drops was effective in treating ocular rosacea in children.

Effect of adding azithromycin to the antimalarials used for seasonal malaria chemoprevention on the nutritional status of African children.

OBJECTIVES: Mass administration of azithromycin has reduced mortality in children in sub-Saharan Africa but its mode of action is not well characterised. A recent trial found that azithromycin given alongside seasonal malaria chemoprevention was not associated with a reduction in mortality or hospital admissions in young children. We investigated the effect of azithromycin on the nutritional status of children enrolled in this study. METHODS: A total of 19 578 children in Burkina Faso and Mali were randomised to receive either azithromycin or placebo alongside seasonal malaria chemoprevention with sulfadoxine-pyrimethamine plus amodiaquine monthly for three malaria transmission seasons (2014-2016). After each transmission season, anthropometric measurements were collected from approximately 4000 randomly selected children (2000 per country) at a cross-sectional survey and used to derive nutritional status indicators. Binary and continuous outcomes between treatment arms were compared by Poisson and linear regression. RESULTS: Nutritional status among children was poor in both countries with evidence of acute and chronic malnutrition (24.9-33.3% stunted, 15.8-32.0% underweight, 7.2-26.4% wasted). There was a suggestion of improvement in nutritional status in Burkina Faso and deterioration in Mali over the study period. At the end of each malaria transmission season, nutritional status of children did not differ between treatment arms (seasonal malaria chemoprevention plus azithromycin or placebo) in either the intention-to-treat or per-protocol analyses (only children with at least three cycles of SMC in the current intervention year). CONCLUSIONS: The addition of azithromycin to seasonal malaria chemoprevention did not result in an improvement of nutritional outcomes in children in Burkina Faso and Mali.

OBJECTIFS: L'administration massive d'azithromycine a réduit la mortalité infantile en Afrique subsaharienne mais son mode d'action n'est pas bien caractérisé. Un essai récent a révélé que l'azithromycine administrée parallèlement à la chimioprévention du paludisme saisonnier n'était pas associée à une réduction de la mortalité ou des hospitalisations chez les jeunes enfants. Nous avons étudié l'effet de l'azithromycine sur l'état nutritionnel des enfants inscrits à cette étude. MÉTHODES: 19.578 enfants au Burkina Faso et au Mali ont été randomisés pour recevoir soit de l'azithromycine soit un placebo parallèlement à une chimioprévention du paludisme saisonnier avec du sulfadoxine-pyriméthamine plus de l'amodiaquine par mois pendant trois saisons de transmission du paludisme (2014-2016). Après chaque saison de transmission, des mesures anthropométriques ont été recueillies auprès d'environ 4.000 enfants sélectionnés au hasard (2.000 par pays) lors d'une enquête transversale et utilisées pour dériver des indicateurs de l'état nutritionnel. Les résultats binaires et continus entre les bras de traitement ont été comparés par la régression linéaire et de Poisson. RÉSULTATS: L'état nutritionnel des enfants était médiocre dans les deux pays avec des signes de malnutrition aiguë et chronique (24,9 à 33,3% de retard de croissance, 15,8 à 32,0% d'insuffisance pondérale, 7,2 à 26,4% d'émaciation). Il a été suggéré une amélioration de l'état nutritionnel au Burkina Faso et une détérioration au Mali au cours de la période d'étude. A la fin de chaque saison de transmission du paludisme, l'état nutritionnel des enfants ne différait pas entre les bras de traitement (chimioprévention contre le paludisme saisonnier plus azithromycine ou placebo) dans les analyses en intention de traiter ou selon le protocole (seulement les enfants avec au moins trois cycles de chimioprévention dans l'année d'intervention en cours). CONCLUSIONS: L'ajout d'azithromycine à la chimioprévention du paludisme saisonnier n'a pas entraîné d'amélioration des résultats nutritionnels chez les enfants au Burkina Faso et au Mali.

Impact of the addition of azithromycin to antimalarials used for seasonal malaria chemoprevention on antimicrobial resistance of Streptococcus pneumoniae.

OBJECTIVE: A trial was conducted in Burkina Faso and Mali to investigate whether addition of azithromycin to the antimalarials used for seasonal malaria chemoprevention reduces mortality and hospital admissions of children. We tested the sensitivity of nasal isolates of Streptococcus pneumoniae obtained during this trial to azithromycin and other antibiotics. METHODS: Azithromycin or placebo was administered monthly, in combination with the antimalarials used for seasonal malaria chemoprevention, for four months, over the annual malaria transmission seasons of 2014, 2015, and 2016. Nasopharyngeal swabs were collected from 2773 Burkinabe and 2709 Malian children on seven occasions: in July and December each year prior to and after drug administration, and at a final survey in early 2018. Pneumococci were isolated from nasopharyngeal swabs and tested for sensitivity to azithromycin and other antibiotics. RESULTS: A total of 5482 samples were collected. In Burkina Faso, the percentage of pneumococcal isolates resistant to azithromycin among children who had received it increased from 4.9% (95% CI: 2.4%, 9.9%) before the intervention to 25.6% (95% CI: 17.6%, 35.7%) afterward. In Mali, the increase was from 7.6% (95% CI: 3.8%, 14.4%) to 68.5% (95% CI: 55.1%, 79.4%). The percentage of resistant isolates remained elevated (17.7% (95% CI: 11.1%, 27.1%) in Burkina Faso and 19.1% (95% CI: 13.5%, 26.3%) in Mali) among children who had received azithromycin 1 year after stopping the intervention. An increase in resistance to azithromycin was also observed in children who had received a placebo but it was less marked. CONCLUSION: Addition of azithromycin to the antimalarial combination used for seasonal malaria chemoprevention was associated with an increase in resistance of pneumococci to azithromycin and erythromycin, which persisted 1 year after the last administration of azithromycin.

OBJECTIF: Un essai a été mené au Burkina Faso et au Mali pour investiguer si l'addition d'azithromycine aux antipaludéens utilisés dans le cadre de la chimioprévention du paludisme saisonnier réduisait la mortalité et les hospitalisations d'enfants. Nous avons testé la sensibilité à l'azithromycine et à d'autres antibiotiques pour les isolats nasaux de Streptococcus pneumoniae obtenus lors de cet essai. MÉTHODES: L'azithromycine ou un placebo a été administré mensuellement, en association avec les antipaludéens utilisés pour la chimioprévention du paludisme saisonnier, pendant 4 mois, durant les saisons de transmission annuelle du paludisme de 2014, 2015 et 2016. Des échantillons nasopharyngés ont été prélevés sur écouvillons chez 2.773 enfants burkinabés et 2.709 enfants maliens lors de 7 occasions: en juillet et en décembre chaque année avant et après l'administration du médicament, ainsi que lors d'une surveillance finale au début de 2018. Les pneumocoques ont été isolés à partir d'écouvillons nasopharyngés et soumis à des tests de sensibilité à l'azithromycine et à d'autres antibiotiques. RÉSULTATS: 5.482 échantillons ont été collectés. Au Burkina Faso, le pourcentage d'isolats de pneumocoque résistants à l'azithromycine chez les enfants qui l'avaient reçu était passé de 4,9% (IC95%: 2,4%, 9,9%) avant l'intervention à 25,6% (IC95%: 17,6-35,7%) après. Au Mali, l'augmentation est passée de 7,6% (IC95%: 3,8-14,4%) à 68,5% (IC95%: 55,1-79,4%). Le pourcentage d'isolats résistants est resté élevé (17,7% (IC95%: 11,1-27,1%) au Burkina Faso et 19,1% (IC95%: 13,5-26,3%) au Mali) chez les enfants ayant reçu l'azithromycine un an après arrêter l'intervention. Une augmentation de la résistance à l'azithromycine a également été observée chez les enfants ayant reçu un placebo, mais elle était moins marquée. CONCLUSION: L'ajout d'azithromycine à la combinaison antipaludique utilisée pour la chimioprévention du paludisme saisonnier était associé à une augmentation de la résistance du pneumocoque à l'azithromycine et à l'érythromycine, qui persistait un an après la dernière administration d'azithromycine.

Evaluation of 3-day azithromycin or 5-day cefaclor in comparison with 10-day amoxicillin for treatment of tonsillitis in children.

To evaluate the clinical efficacy of azithromycin, cefaclor, and amoxicillin in treatment of pediatric tonsillitis, a total of 256 children with Group A ß-hemolytic streptococcus (GAS) tonsillitis were randomly divided into 3 groups. Only patients assessed with streptococcus-positive tonsillitis, considered to be compliant with treatment and complete clinical and microbiological evaluations at the end of therapy (day 14) and follow-up (day 30) were included in the efficacy analysis. Our study demonstrated that 96.4% of patients in the azithromycin group, 92.4% of patients in the cefaclor group, and 91.0% of patients in the amoxicillin group were recorded as clinical success at the end of therapy. Bacteriological eradication rates of the 3 groups at the end of therapy were 94.0%, 89.9%, and 88.5%, respectively. A pathogen recurrence rate was evaluated as 2.6%, 7.0%, and 5.9% at the follow-up. Treatment-stimulated adverse events occurred in 2.4% of patients in the azithromycin group, 11.3% in the cefaclor group, and 11.4% in the amoxicillin group. In summary, azithromycin showed an effective tendency for the treatment of pediatric tonsillitis with lower occurrence rate of adverse reactions, although there is no statistical significance for the clinical and bacteriological eradication efficacy between these 3 groups.

[Azithromycine and chronic bronchial diseases: For which patients? For which benefits? With what modalities?] / Azithromycine et pathologies bronchiques chroniques : quels patients ? Quels bénéfices ? Quelles modalités ?

Azithromycin is a macrolide widely used in chronic bronchial diseases due to its anti-inflammatory properties. This treatment is prescribed to patients with bronchiectasis, asthma and severe chronic obstructive pulmonary disease who present more than 3 exacerbations per year or a deterioration of respiratory function despite an optimal treatment. Macrolides decrease the number of exacerbation but azythromycine must be prescribed carefully. Indeed, it involves potential cardiovascular and otological toxicities and the emergence of resistant bacteria. In addition, studies remain insufficient to establish the optimal dosage and duration of azithromycine.

[What's new in dermatological treatment?] / Quoi de neuf en thérapeutique dermatologique ?

On a therapeutic point of view, 2017 in dermatology could be summarized in one disease, one pathway and in one number : atopic dermatitis, JAK inhibitors and 23. 2017 will be the year of the first registration of a biologic treatment in atopic dermatitis, dupilumab, with numerous other drugs currently in development. JAK inhibitors show promising results in several difficult-to-treat conditions, such as alopecia areata, vitiligo or atopic dermatitis, but still warrant confirmation in upcoming controlled trials. Monoclonal antibodies targeting IL-23 have confirmed in phase III studies their great efficacy in controlling psoriasis and will be soon available in practice, illustrating well the optimal link between bench side and bed in this emblematic inflammatory dermatological condition.

Azithromycin assay in drug formulations: Validation of a HPTLC method with a quadratic polynomial calibration model using the accuracy profile approach.

Many different assaying high performance thin layer chromatography (HPTLC) methods have been developed and validated in order to be used in routine analysis in different analytical fields. Validation often starts by the evaluation of the linearity of the calibration curve. Frequently, if the correlation coefficient is close to one, the linear calibration curve model is considered to be proper to predict the unknown concentration in the sample. But is this simple model effective to assess the behavior of the response of an HPTLC method as a function of concentration. To answer this question, a method for the determination of azithromycin by HPTLC has been developed and validated following both the classical approach and that based on the accuracy profile. Silica gel plates with fluorescence indicator F254 and chloroform - ethanol - 25% ammonia 6:14:0.2 (v/v/v) as mobile phase were used. Analysis was carried out in reflectance mode at 483nm. The RF of azithromycin was 0.53. The validation based on the classical approach, shows that the behavior is not linear, even though r2=0.999 because the lack of fit test is significant (P<0.05). Validation based on the accuracy profile approach considering both the straight line and the quadratic regression model, show that the former results is a ß-expectation tolerance interval outside the acceptance limits, while with the latter, this interval is within the limits of ±5% acceptability for a range which extends from 0.2 to 1.0µg/zone. With the quadratic model, the method showed to be precise and accurate.

Enteric fever in India: current scenario and future directions.

Enteric fever is a major cause of morbidity and mortality in tropical areas worldwide. The Indian subcontinent bears the brunt of the disease, both in terms of absolute case numbers and drug-resistant strains. Recent phylogenetic studies suggest that the multidrug-resistant clade H58 originated in India and subsequently expanded through Asia and Africa. In Africa, it caused unrecognised outbreaks in areas previously considered free of the disease. In this study, we discuss the current status of enteric fever in India, the factors preventing its control and its future directions in this rapidly developing nation.

[National consensus regarding azithromycin use in cystic fibrosis]. / Consensus national sur la prescription de l'azithromycine dans la mucoviscidose.

AIM: To propose a formalized consensus agreement regarding the prescription of azithromycin in cystic fibrosis (CF). MATERIAL AND METHODS: Application of the Delphi method in 5 thematic fields: indications, contra-indications, dosage, precautions for use and treatment follow-up. RESULTS: Thirty identified French CF centers participated in the process on 49 (61%), which comprised 3 rounds. Experts validated azithromycin as a long-term anti-inflammatory agent in children aged over 6 years, presenting with the classical form of CF, irrespective of the bacteriological status of the patient (except for non-tuberculous mycobacteria). Azithromycin administration should not be routine in the milder forms of the disease, and avoided in the presence of severe hepatic or renal involvement. In children whose weight is below 40 kg, a strong consensus recommended a single daily oral dose, administered three times weekly. However, in adults, the level of agreement was weaker. Minimal duration of treatment is 6 months, after which the drug should be discontinued if no observable effect is noted on clinical parameters, exacerbation rate and/or FEV1. Clinical monitoring of treatment tolerance is recommended (nausea, diarrhea, skin rash, tinnitus, deafness, arthropathy), without increasing the frequency of surveillance of sputum bacteria. However, it is essential to monitor sputum for fungi (expectoration, Aspergillus, broncho-pulmonary allergic aspergillosis). CONCLUSION: This consensus statement defines an area for the prescription of azithromycin in CF, with the aim of better harmonization of its use.