plazomicin
Sources réglementaires consultées
Indications approuvées
- Infections urinaires compliquées, y compris pyélonéphrite, dues à des germes à Gram négatif sensibles chez l’adulte avec des options limitées.
Contre-indications
Absolues
- Hypersensibilité à plazomicina 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 eccf9fd9-53ac-4252-a106-5567b3a82a70
- 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 eccf9fd9-53ac-4252-a106-5567b3a82a70
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 eccf9fd9-53ac-4252-a106-5567b3a82a70
- 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 eccf9fd9-53ac-4252-a106-5567b3a82a70
- 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 eccf9fd9-53ac-4252-a106-5567b3a82a70
Effets indésirables
Communs (≥1%)
Diminution de la fonction rénale, diarrhée, hypertension, céphalées, nausées, vomissements et hypotension
Rares mais graves
Insuffisance rénale, perte auditive irréversible, toxicité vestibulaire et bloc neuromusculaire avec apnée
Grossesse et allaitement
Il peut provoquer une atteinte fœtale ; informer du risque et éviter pendant la grossesse sauf si le bénéfice l’emporte clairement. Les données dans le lait sont insuffisantes ; envisager d’arrêter l’allaitement ou le traitement.
Bibliographie récente (PubMed)
Pneumonia is frequently encountered in clinical practice, and Gram-negative bacilli constitute a significant proportion of its aetiology, especially when it is acquired in a hospital setting. With the alarming global rise in multidrug resistance in Gram-negative bacilli, antibiotic therapy for treating patients with pneumonia is challenging and must be guided by in vitro susceptibility results. In this review, we provide an overview of antibiotics newly approved for the treatment of pneumonia caused by Gram-negative bacilli. Ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam have potent activity against some of the carbapenem-resistant Enterobacterales, especially Klebsiella pneumoniae carbapenemase producers. Several novel antibiotics have potent activity against multidrug-resistant Pseudomonas aeruginosa, such as ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relabactam and cefiderocol. Cefiderocol may also play an important role in the management of pneumonia caused by Acinetobacter baumannii, along with plazomicin and eravacycline. Plazomicin is an aminoglycoside antibiotic similar to gentamicin and amikacin. No information is available on the use of plazomicin during breastfeeding. However, based on the excretion of other aminoglycoside antibiotics, amounts in milk are expected to be low. Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (e.g., thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.
Klebsiella pneumoniae is a Gram-negative opportunistic pathogen responsible for a variety of community and hospital infections. Infections caused by carbapenem-resistant K. pneumoniae (CRKP) constitute a major threat for public health and are strongly associated with high rates of mortality, especially in immunocompromised and critically ill patients. Adhesive fimbriae, capsule, lipopolysaccharide (LPS), and siderophores or iron carriers constitute the main virulence factors which contribute to the pathogenicity of K. pneumoniae. Colistin and tigecycline constitute some of the last resorts for the treatment of CRKP infections. Carbapenemase production, especially K. pneumoniae carbapenemase (KPC) and metallo-β-lactamase (MBL), constitutes the basic molecular mechanism of CRKP emergence. Knowledge of the mechanism of CRKP appearance is crucial, as it can determine the selection of the most suitable antimicrobial agent among those most recently launched. Plazomicin, eravacycline, cefiderocol, temocillin, ceftolozane-tazobactam, imipenem-cilastatin/relebactam, meropenem-vaborbactam, ceftazidime-avibactam and aztreonam-avibactam constitute potent alternatives for treating CRKP infections. The aim of the current review is to highlight the virulence factors and molecular pathogenesis of CRKP and provide recent updates on the molecular epidemiology and antimicrobial treatment options.
Carbapenem resistant Enterobacterales (CRE) are a major threat to global health and hospital-onset CRE infections have risen during the COVID-19 pandemic. Novel antimicrobials are now available for the treatment of CRE infections. There remains an urgent need for new antimicrobials for CRE, especially for those producing metallo-β-lactamases. This article discusses previously published research supporting currently available novel antimicrobials for the treatment of CRE infections. Newer compounds currently being evaluated in clinical trials are covered. A literature search was conducted in PubMed over all available dates for relevant published papers and conference abstracts with the search terms, 'CRE,' 'carbapenem-resistant Enterobacterales,' 'β-lactam-β-lactamase inhibitor,' 'KPC,' 'NDM,' 'metallo-β-lactamase,' 'ceftazidime-avibactam,' 'meropenem-vaborbactam,' 'imipenem-cilastatin-relebactam,' 'cefiderocol,' 'eravacycline,' 'plazomicin,' 'taniborbactam,' 'zidebactam,' and 'nacubactam.' Novel antimicrobials for CRE infections have been developed, most notably the β-lactam-β-lactamase inhibitor combinations, though treatment options for infections with metallo-β-lactamase producing Enterobacterales remain few and have limitations. Development of antibiotics with activity against metallo-β-lactamase producing Enterobacterales is eagerly awaited, and there are promising new compounds in clinical trials. Finally, more clinical research is needed to optimize and individualize treatment approaches, which will help guide antimicrobial stewardship initiatives aimed at reducing the spread of CRE and development of further resistance.
Aim: Compared with uncomplicated urinary tract infections (UTIs), complicated UTIs (cUTIs) including acute pyelonephritis (AP) present with significant morbidity, a higher risk of treatment failure and typically require longer courses of treatment, or alternative antibiotics. The emergence of drug-resistant organisms represents a considerable challenge in the treatment of patients with cUTIs/AP and has limited antibiotic options. Carbapenems are considered the current last line of therapy, however, carbapenem resistance represents a growing problem. Although several established and novel treatment options are available, direct comparative evidence is lacking. Methods: Randomized controlled trials (RCTs) were identified by systematic literature review of Embase®, MEDLINE® and Cochrane databases (database inception to 15th June 2022). Relevant conference proceedings (2020-2022) were also reviewed. Following feasibility assessment to verify network connectivity at an overall level, outcome specific networks were prepared. Bayesian network meta-analysis (NMA) was performed (using R version 4.2.1) to determine the relative efficacy of various treatments for cUTI/AP, including cefepime + enmetazobactam. Convergence was assessed by visual inspection of trace plots. The accuracy of the posterior estimates was assessed using the Monte Carlo error for each parameter. Published study results were included in the synthesis of the relative risk (RR) of efficacy end points, using a logit link with binomial likelihood distribution. Results: Feasibility assessment was conducted for 40 RCTs identified, to assess the viability of constructing a network of interlinked RCTs. Of those, 28 studies were included in the master NMA network. A fixed effects model (FEM) was selected due to low statistical heterogeneity, according to I2 values. For composite outcome at test of cure (TOC), ceftolozane + tazobactam, cefepime + enmetazobactam, cefiderocol, levofloxacin and plazomicin demonstrated