tigecycline
Sources réglementaires consultées
Indications approuvées
- Infections compliquées de la peau et des tissus mous, hors pied diabétique, et infections intra-abdominales compliquées chez l’adulte et l’enfant à partir de 8 ans, uniquement lorsque les alternatives ne conviennent pas.
Contre-indications
Absolues
- Hypersensibilité à la tigécycline, aux autres tétracyclines ou aux excipients.
Mises en garde cliniques
- Mise en garde encadrée · Une mortalité toutes causes plus élevée a été observée qu’avec les comparateurs. N’utiliser la tigécycline que lorsque les alternatives ne conviennent pas. — CIMA/AEMPS, ficha técnica 84604
- Mise en garde majeure · Elle n’est pas indiquée dans la pneumonie nosocomiale, y compris la pneumonie associée à la ventilation mécanique (PAVM), l’infection du pied diabétique ni la bactériémie primaire. En cas de bactériémie, rechercher et traiter le foyer et envisager un autre traitement. — CIMA/AEMPS, ficha técnica 84604
- Mise en garde majeure · Surveiller la fonction hépatique, la pancréatite et les anomalies de coagulation, y compris le fibrinogène. — CIMA/AEMPS, ficha técnica 84604
- Mise en garde majeure · Il peut provoquer une diarrhée à Clostridioides difficile, y compris après la fin du traitement ; arrêter et traiter selon la gravité. — CIMA/AEMPS, ficha técnica 84604
- Il peut provoquer une photosensibilité. Limiter l’exposition solaire/UV et arrêter en cas d’érythème important. — CIMA/AEMPS, ficha técnica 84604
Interactions médicamenteuses
- SévèreWarfarine et autres anticoagulants
Mécanisme: Elle peut modifier les paramètres de coagulation.
Recommandation: Surveiller INR, temps de coagulation et fibrinogène.
CIMA/AEMPS, ficha técnica 84604
- SévèreTacrolimus et ciclosporine
Mécanisme: La tigécycline peut augmenter les concentrations résiduelles et la toxicité du tacrolimus ou de la ciclosporine, possiblement par la P-gp.
Recommandation: Surveiller les concentrations de l’immunosuppresseur et les signes de toxicité pendant et après le traitement ; ajuster si nécessaire.
CIMA/AEMPS, ficha técnica 84604
Effets indésirables
Communs (≥1%)
Nausées, vomissements et diarrhée
Rares mais graves
Pancréatite, insuffisance hépatique, anaphylaxie et hypofibrinogénémie
Grossesse et allaitement
Éviter pendant la grossesse, surtout à partir de la seconde moitié, en raison d’un risque d’atteinte dentaire permanente et de retard de croissance osseuse fœtale. Envisager d’interrompre l’allaitement ou le traitement.
Bibliographie récente (PubMed)
Patients with severe carbapenem-resistant Acinetobacter baumannii (CRAB) infections currently face significant treatment challenges. When patients display signs of infection and the clinical suspicion of CRAB infections is high, appropriate treatment should be immediately provided. However, current treatment plans and clinical data for CRAB are limited. Inherent and acquired resistance mechanisms, as well as host factors, significantly restrict options for empirical medication. Moreover, inappropriate drug coverage can have detrimental effects on patients. Most existing studies have limitations, such as a restricted sample size, and are predominantly observational or non-randomized, which report significant variability in patient infection severity and comorbidities. Therefore, a gold-standard therapy remains lacking. Current and future treatment options of infections due to CRAB were described in this review. The dose and considerable side effects restrict treatment options for polymyxins, and high doses of ampicillin-sulbactam or tigecycline appear to be the best option at the time of initial treatment. Moreover, new drugs such as durlobactam and cefiderocol have substantial therapeutic capabilities and may be effective salvage treatments. Bacteriophages and antimicrobial peptides may serve as alternative treatment options in the near future. The advantages of a combination antimicrobial regimen appear to predominate those of a single regimen. Despite its significant nephrotoxicity, colistin is considered a primary treatment and is often used in combination with antimicrobials, such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin. The Infectious Diseases Society of America (IDSA) has deemed high-dose ampicillin-sulbactam, which is typically combined with high-dose tigecycline, polymyxin, and other antibacterial agents, the best option for treating serious CRAB infections. A rational combination of drug use and the exploration of new therapeutic drug
Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly blaKPC, blaNDM, and blaOXA-48-like genes), CR- or MDR/XDR-Pseudomonas aeruginosa (production of VIM, IMP, or NDM carbapenemases combined with porin alteration), and Acinetobacter baumannii complex (producing mainly OXA-23, OXA-58-like carbapenemases), have gradually worsened and become a major challenge to public health because of limited antibiotic choice and high case-fatality rates. Diverse MDR/XDR-GNB isolates have been predominantly cultured from inpatients and hospital equipment/settings, but CRE has also been identified in community settings and long-term care facilities. Several CRE outbreaks cost hospitals and healthcare institutions huge economic burdens for disinfection and containment of their disseminations. Parenteral polymyxin B/E has been observed to have a poor pharmacokinetic profile for the treatment of CR- and XDR-GNB. It has been determined that tigecycline is suitable for the treatment of bloodstream infections owing to GNB, with a minimum inhibitory concentration of ≤ 0.5 mg/L. Ceftazidime-avibactam is a last-resort antibiotic against GNB of Ambler class A/C/D enzyme-producers and a majority of CR-P. aeruginosa isolates. Furthermore, ceftolozane-tazobactam is shown to exhibit excellent in vitro activity against CR- and XDR-P. aeruginosa isolates. Several pharmaceuticals have devoted to exploring novel antibiotics to combat these troublesome XDR-GNBs. Nevertheless, only few antibiotics are shown to be effective in vitro against CR/XDR-A. baumannii complex isolates. In this era of antibiotic pipelines, strict implementation of antibiotic stewardship is as important as in-time isolation cohorts in limiting the spread of CR/XDR-GNB and alleviating the worsening trends of resistance.
- Acinetobacter baumannii treatment strategies: a review of therapeutic challenges and considerations.
Antimicrobial resistance poses a major challenge in the treatment of Acinetobacter baumannii. Acinetobacter spp. are intrinsically resistant to a number of commonly used antibiotics. Over the past 3 years, the European and American Professional Societies have provided important guidelines on the treatment options for carbapenem-resistant A. baumannii (CRAB). Here, we review the recent literature on combination regimens for CRAB as well as carbapenem-susceptible A. baumannii infections. We discuss the strengths and weaknesses of various agents used in combination, depending on the site of infection and their pharmacokinetic properties. Consistent with the 2024 Infectious Diseases of America (IDSA) update, sulbactam-durlobactam, in combination with background carbapenem therapy, remains the combination with the greatest reduction in mortality for pulmonary infections and has promising outcomes in bloodstream infections with CRAB. Sulbactam-based combination therapy remains an ideal part of targeted strategies and has been shown to be associated with reduced mortality. Certain agents have been highlighted in the literature for suboptimal outcomes, primarily pulmonary infections treated with cefiderocol, tigecycline, and eravacycline. Studies including non-pulmonary infections, specifically bacteremia and central nervous system (CNS) infections, are overall limited to case series and subgroup analyses. Important areas for further research include breakpoint evaluations for eravacycline and minocycline as well as subclinical resistance in cefiderocol.
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.
Antibacterial activity can be classified as either bactericidal or bacteriostatic, using methods such as the MBC/MIC ratio and time-kill curves. However, such categorization has proven challenging in clinical practice, as these definitions only apply under specific laboratory conditions, which may differ from clinical settings. Several factors, such as the specific bacteria or infectious medium, can affect the action of antibiotics, with many antibacterials exerting both activities. These definitions have also led to the belief that bactericidal antibacterials are superior to bacteriostatic, especially in more severe cases, such as endocarditis, neutropenia and bacteraemia. Additionally, current dogma dictates against the combination of bactericidal and bacteriostatic antibacterials in clinical practice, due to potential antagonism. This review aimed to assess the differences in antibacterial activity of bactericidal and bacteriostatic antibacterials based on in vitro and in vivo studies and examine their antagonistic or synergistic effects. Our findings show that specific bacteriostatic agents, such as linezolid and tigecycline, are clinically non-inferior to bactericidals in multiple infections, including pneumonia, intra-abdominal infections, and skin and soft tissue infections. Studies also support using several bacteriostatic agents as salvage therapies in severe infections, such as neutropenic fever and endocarditis. Additionally, not all combinations of bacteriostatic and bactericidal agents appear to be antagonistic, with many combinations, such as linezolid and rifampicin, already being used. The findings should be interpreted with caution, as most evidence is from observational studies and there is a need for randomized controlled trials to assess their effectiveness and combinations, especially within the context of rising antimicrobial resistance.