nafcillin
Sources réglementaires consultées
Indications approuvées
- Infections dues à des staphylocoques producteurs de pénicillinase sensibles à la nafcilline ; ne pas utiliser contre le SARM.
Contre-indications
Absolues
- Hypersensibilité à la nafcilline ou antécédent d’hypersensibilité à une pénicilline.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer une hypersensibilité sévère ou une anaphylaxie. Rechercher tout antécédent de réaction immédiate aux bêta-lactamines avant l’emploi et arrêter en cas de réaction allergique. — FDA, set_id 0556378a-b794-4235-ba09-ebdc295e9092
- Mise en garde majeure · Il peut provoquer une diarrhée associée à Clostridioides difficile pendant ou après le traitement ; évaluer toute diarrhée importante et éviter les antipéristaltiques si une colite est suspectée. — FDA, set_id 0556378a-b794-4235-ba09-ebdc295e9092
Interactions médicamenteuses
- SévèreWarfarine
Mécanisme: La nafcilline à forte dose peut réduire l’effet anticoagulant ; l’interaction peut persister jusqu’à 30 jours après.
Recommandation: Surveiller étroitement le temps de prothrombine/INR et ajuster la warfarine pendant le traitement et après l’arrêt de la nafcilline.
FDA, set_id 0556378a-b794-4235-ba09-ebdc295e9092
- SévèreCiclosporine
Mécanisme: La nafcilline peut réduire les concentrations et l’efficacité de la ciclosporine.
Recommandation: Surveiller les concentrations et la réponse et ajuster la ciclosporine.
FDA, set_id 0556378a-b794-4235-ba09-ebdc295e9092
- ModéréeTétracyclines
Mécanisme: Elles peuvent antagoniser l’activité bactéricide de la nafcilline.
Recommandation: Éviter l’association.
FDA, set_id 0556378a-b794-4235-ba09-ebdc295e9092
Effets indésirables
Communs (≥1%)
Nausées, diarrhée et éruption cutanée
Rares mais graves
Anaphylaxie, colite à C. difficile et cytopénies sévères
Grossesse et allaitement
Utiliser pendant la grossesse uniquement en cas d’indication claire. De faibles quantités passent dans le lait ; surveiller diarrhée, candidose ou sensibilisation chez le nourrisson et réévaluer la poursuite selon le produit.
Bibliographie récente (PubMed)
Infections of the central nervous system (CNS) are complex to treat and associated with significant morbidity and mortality. Historically, antistaphylococcal penicillins such as nafcillin were recommended for the treatment of methicillin-susceptible staphylococcal CNS infections. However, the use of antistaphylococcal penicillins presents challenges, such as frequent dosing administration and adverse events with protracted use. This narrative reviews available clinical and pharmacokinetic/pharmacodynamic (PK/PD) data for cefazolin in CNS infections and produces a recommendation for use. Based on the limited available evidence analyzed, dose optimized cefazolin is likely a safe and effective alternative to antistaphylococcal penicillins for a variety of CNS infections due to methicillin-susceptible Staphylococcus aureus. Given the site of infection and wide therapeutic index of cefazolin, practitioners may consider dosing cefazolin regimens of 2 g IV every 6 h or a continuous infusion of 8-10 g daily instead of 2 g IV every 8 h to optimize PK/PD properties.
There is debate on whether cefazolin or antistaphylococcal penicillins should be the first-line treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Ongoing trials are investigating whether cefazolin is non-inferior to (flu)cloxacillin, but it remains uncertain whether these findings apply to other antistaphylococcal penicillins. We conducted a systematic review and meta-analysis comparing cefazolin with each of the individual antistaphylococcal penicillins for MSSA bacteraemia. Data sources: We updated a 2019 systematic review but specifically focused on evaluating outcomes by individual antistaphylococcal penicillins. Study eligibility criteria include comparative observational studies. Participants include patients with MSSA bacteraemia. Interventions include cefazolin vs. the antistaphylococcal penicillins. Assessment of risk of bias involved the risk of bias in non-randomized studies of interventions tool. The primary outcome was 30-day all-cause mortality and we assessed for non-inferiority of cefazolin using a pre-specified non-inferiority margin of a pooled OR <1.2 using raw unadjusted data. Secondary outcomes were 90-day mortality, treatment-related adverse events (TRAEs), discontinuation due to toxicity, and nephrotoxicity. No randomized data have been published. A total of 30 observational studies at moderate or high risk of bias were included, which comprised 3869 patients who received cefazolin and 11 644 patients who received antistaphylococcal penicillins (flucloxacillin = 6721, unspecified = 2440, nafcillin = 1305, cloxacillin = 1258, and oxacillin = 120). Cefazolin was associated with a reduced odds of 30-day all-cause mortality (OR = 0.73, 95% CI: 0.62-0.85) compared with antistaphylococcal penicillins, meeting pre-specified non-inferiority. This effect was consistent vs. flucloxacillin (OR = 0.92, 95% CI: 0.73-1.16), nafcillin (OR = 0.58, 95% CI: 0.28-1.17), cloxacillin (OR = 0.42, 95% CI: 0.11-1.58), and oxacillin (OR =
To compare the efficacy of antimicrobial therapies used in the management of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. A literature search using the PubMed database (inception to December 2022) was conducted using the search terms "Staphylococcus aureus bacteremia," "methicillin-susceptible Staphylococcus aureus bacteremia," "persistent methicillin-susceptible Staphylococcus aureus bacteremia," and "refractory methicillin-susceptible Staphylococcus aureus bacteremia ." In addition, therapeutic agents which could be used as treatment for MSSA including "nafcillin," "oxacillin," "cefazolin," "ceftaroline," "gentamicin," "rifampin," and "daptomycin" were also combined with the aforementioned search terms to capture data using these agents. Clinical data were limited to those published in the English language. Articles and abstracts were considered for inclusion in addition to ongoing trials identified through ClinicalTrials.gov. A total of 78 articles were reviewed including 17 in vitro or animal model studies and 39 studies including patient data. The remaining 22 articles included guidelines, review articles, and editorials. Recent data evaluating use of dual β-lactam regimens for persistent MSSA bacteremia were limited to 8 case reports or case series. At present, there is little guidance on how to best manage patients with persistent MSSA bacteremia. This narrative review collates the available data to assist clinicians in selecting the best possible antimicrobial regimen when facing this clinical conundrum. Modification of antimicrobial therapy, in conjunction with source control and infectious diseases consultation, may all be necessary to sterilize blood cultures in patients with persistent MSSA bacteremia.
Anti-staphylococcal penicillins (ASPs) are among the most commonly prescribed antibiotics in children and are associated with a risk of drug-induced liver injury (DILI). Despite the frequent use of ASPs in children, there is no consensus on whether liver function tests (LFTs) should be routinely monitored during treatment. To review the literature on the frequency of ASP-related DILI in children to determine the incidence, risk factors and outcomes of hepatotoxicity. PubMed, MEDLINE and Embase were searched in January 2022 for original studies of children who received cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin or oxacillin that included ≥10 children aged up to 18 years, and presented data on the incidence of DILI in children exposed to ASPs. Overall, two studies of oral flucloxacillin, two of intravenous (IV) methicillin, three of IV nafcillin and four of IV oxacillin were included. The mean onset of DILI ranged between 7.0 and 19.0 days following commencement of antibiotic treatment and all episodes resolved between 14.2 and 16.0 days after drug discontinuation, with no specific treatment required. This review found that the incidence of DILI in children was 1 in 50 000 for oral flucloxacillin and ranged from 1 in 3 to 13 for IV oxacillin, methicillin and nafcillin. This review found that routine LFT monitoring is not required in children receiving low dose oral flucloxacillin in a primary care setting, although pharmacovigilance is critical. For IV preparations, the existing data support routine LFT monitoring in those receiving treatment for at least 7 days.