tobramycin
Sources réglementaires consultées
Indications approuvées
- Infections graves dues à des bacilles à Gram négatif sensibles, notamment septicémie et infections respiratoires, urinaires, intra-abdominales, cutanées, osseuses et du système nerveux central, généralement en association.
Contre-indications
Absolues
- Hypersensibilité à tobramicina ou à d’autres aminosides.
Mises en garde cliniques
- Il peut provoquer une néphrotoxicité, une ototoxicité cochléaire ou vestibulaire irréversible et un bloc neuromusculaire ; surveiller la fonction rénale, l’audition, l’équilibre et les concentrations sériques. — DailyMed, set_id 02b48684-168c-4cd9-8375-794206eff23e
- Mise en garde majeure · Le risque augmente avec les fortes doses, les traitements prolongés, la déshydratation, l’âge avancé, l’insuffisance rénale et les autres médicaments néphrotoxiques ou ototoxiques. — DailyMed, set_id 02b48684-168c-4cd9-8375-794206eff23e
Interactions médicamenteuses
- SévèreAutres médicaments néphrotoxiques ou ototoxiques
Mécanisme: La toxicité rénale, cochléaire et vestibulaire peut être additive.
Recommandation: Éviter l’association si possible ; si elle est indispensable, intensifier le suivi pharmacologique, la créatinine et l’audiométrie.
DailyMed, set_id 02b48684-168c-4cd9-8375-794206eff23e
- SévèreDiurétiques de l’anse
Mécanisme: Ils peuvent augmenter l’ototoxicité, surtout lors d’une administration intraveineuse rapide.
Recommandation: Éviter l’association ou surveiller étroitement l’audition et la fonction rénale.
DailyMed, set_id 02b48684-168c-4cd9-8375-794206eff23e
- SévèreBloquants neuromusculaires et anesthésiques
Mécanisme: Le bloc neuromusculaire peut être potentialisé et provoquer une apnée.
Recommandation: Surveiller la fonction respiratoire et disposer d’une assistance ventilatoire ainsi que de calcium ou de néostigmine.
DailyMed, set_id 02b48684-168c-4cd9-8375-794206eff23e
Effets indésirables
Communs (≥1%)
Nausées, élévation de la créatinine et réaction au site d’administration
Rares mais graves
Insuffisance rénale, perte auditive irréversible, toxicité vestibulaire et bloc neuromusculaire avec apnée
Grossesse et allaitement
Les aminosides peuvent provoquer une atteinte fœtale ; utiliser pendant la grossesse uniquement si le bénéfice l’emporte clairement sur le risque. Décider de l’allaitement selon le besoin maternel et la surveillance du nourrisson.
Bibliographie récente (PubMed)
Cystic fibrosis, a genetic disorder defined by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, affects more than 30 000 individuals in the US and approximately 89 000 worldwide. Absent or decreased function of the CFTR protein is associated with multiorgan dysfunction and shortened life expectancy. CFTR is an anion channel in the apical membrane of epithelial cells. Loss of function leads to obstructed exocrine glands. Of people with cystic fibrosis in the US, approximately 85.5% have the gene variant F508del. Manifestations of cystic fibrosis in patients with the F508del gene variant begin in infancy with steatorrhea, poor weight gain, and respiratory symptoms (coughing, wheezing). As people with cystic fibrosis age, chronic respiratory bacterial infections cause loss of lung function and bronchiectasis. With the availability of universal newborn screening in multiple countries including the US, many people with cystic fibrosis are asymptomatic at diagnosis. With multidisciplinary care teams that included dietitians, respiratory therapists, and social workers, treatment of cystic fibrosis can slow disease progression. Median survival has improved from 36.3 years (95% CI, 35.1-37.9) in 2006 to 53.1 years (95% CI, 51.6-54.7) in 2021. Pulmonary therapies for patients with cystic fibrosis consist of mucolytics (eg, dornase alfa), anti-inflammatories (eg, azithromycin), and antibiotics (such as tobramycin delivered by a nebulizer). Four small molecular therapies, termed CFTR modulators, that facilitate CFTR production and/or function have received regulatory approval. Examples are ivacaftor and elexacaftor-tezacaftor-ivacaftor. For example, in patients with 1 F508del variant, the combination of ivacaftor, tezacaftor, and elexacaftor improved lung function from -0.2% in the placebo group to 13.6% (difference, 13.8%; 95% CI, 12.1%-15.4%) and decreased the annualized estimated rate of pulmonary exacerbations from 0.98 to 0.37 (rate ratio, 0
Inhaled antibiotics have been incorporated into contemporary European and British guidelines for bronchiectasis, yet no inhaled antibiotics have been approved in the United States or Europe for the treatment of bronchiectasis not related to cystic fibrosis. Pseudomonas aeruginosa infection is common in patients with bronchiectasis, contributing to a cycle of progressive inflammation, exacerbations, and airway remodelling. The aim of the current study was to identify and evaluate published studies of inhaled tobramycin solution or powder in patients with bronchiectasis and P. aeruginosa infection not associated with cystic fibrosis. A literature review was conducted utilising the PubMed and Cochrane databases. Studies published in the English language that reported safety and/or efficacy outcomes of inhaled tobramycin either alone or in combination with other antibiotics were included. Seven clinical trials published between 1999 and 2021 were identified that met inclusion criteria. Inhaled tobramycin therapy was effective in reducing P. aeruginosa microbial density in the sputum of patients with bronchiectasis. Several studies demonstrated favourable impacts on hospitalisations, number and severity of exacerbations, and symptoms. Other studies were underpowered for these clinical outcomes or were exploratory in nature. Although tobramycin was generally well tolerated, some evidence of treatment-associated wheezing was reported. In patients with bronchiectasis and chronic P. aeruginosa infection, inhaled tobramycin was effective in reducing the density of bacteria in sputum, which may be associated with additional clinical benefits. Definitive phase 3 trials of inhaled tobramycin in patients with bronchiectasis are indicated to determine clinical efficacy and long-term safety.
Hypersensitivity reactions including IgE-mediated and delayed cell-mediated reactions to aminoglycosides, clindamycin, linezolid, and metronidazole are rare. For aminoglycosides, allergic contact dermatitis is the most frequent reaction for which patch testing can be a useful step in evaluation. For clindamycin, delayed maculopapular exanthems are the most common reactions. There are case reports of clindamycin associated with drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), acute febrile neutrophilic dermatosis, and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). For linezolid, cases of hypersensitivity were exceedingly rare and included urticaria, angioedema, anaphylaxis, delayed rashes, and DRESS. For metronidazole, only rare cases were found across a broad spectrum of reactions including allergic contact dermatitis, fixed drug eruption, angioedema, anaphylaxis, serum sickness-like reaction, SJS/TEN, AGEP, SDRIFE, and a possible case of DRESS. IgE-mediated reactions and anaphylaxis to these types of antibiotics are uncommon, and reports of skin testing concentrations and desensitization protocols are largely limited to case reports and series. Non-irritating skin testing concentrations have been reported for gentamycin, tobramycin, and clindamycin. Published desensitization protocols for intravenous and inhaled tobramycin, oral clindamycin, intravenous linezolid, and oral and intravenous metronidazole have also been reported and are reviewed.
Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks). To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021. We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA). We applied standard Cochrane methodology. We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED. Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (med