Disease relevance of Flucloxacillin

• In this study, levofloxacin was compared to ciprofloxacin, flucloxacillin, and vancomycin for the treatment of experimental endocarditis due to two methicillin-susceptible Staphylococcus aureus (MSSA) and two methicillin-resistant S. aureus (MRSA) isolates [1].
• Early termination of a prospective, randomized trial comparing teicoplanin and flucloxacillin for treating severe staphylococcal infections [2].
• Finally, the effectiveness of this simulation of oral levofloxacin therapy was at least equivalent to that of standard treatment for MSSA or MRSA endocarditis with either flucloxacillin or vancomycin [1].
• We describe a case of severe cholestatic liver disease, which persisted for 7 years, and was probably induced by flucloxacillin [3].
• Ursodeoxycholic acid for the treatment of flucloxacillin-associated cholestasis [4].

High impact information on Flucloxacillin

• INTERVENTION: Initial debridement and 2-week intravenous course of flucloxacillin or vancomycin with rifampin or placebo, followed by either ciprofloxacin-rifampin or ciprofloxacin-placebo long-term therapy [5].
• However, encapsulation of flucloxacillin into liposomes could enable its entrance into the interior of neutrophils from two CGD patients to kill phagocytized bacteria there [6].
• Commonly used antibiotics like flucloxacillin are of limited therapeutic value, because the staphylococci are protected against their action in the interior of phagocytes [6].
• Minimum bacteriocidal concentrations of cloxacillin, flucloxacillin, cephalothin, and cephazolin in serum were much higher than conventional minimum inhibitory concentrations in the absence of serum [7].
• 3. Moreover, flucloxacillin-specific T cell clones could be generated from peripheral blood, they expressed CD4 and the alphabeta-T cell receptor, and showed a heterogeneous cytokine secretion pattern with no clear commitment to either a Th1- or Th2-type response [8].

Chemical compound and disease context of Flucloxacillin

• Study II was a double-blind comparison of phlebitis caused by intravenous infusions of either flucloxacillin or cloxacillin [9].
• The distribution of three antibiotics, ampicillin, benzylpenicillin, and flucloxacillin, in wound and adjacent tissue sites on the abdomens and legs of normal and diabetic rats was determined 30 min after intravenous administration of a single bolus containing 50 mg of all three antibiotics per kg of body weight [10].
• Phlebitis induced by parenteral treatment with flucloxacillin and cloxacillin: a double-blind study [9].
• Amikacin was given once or thrice daily alone or in combination with ceftazidime or flucloxacillin against Pseudomonas aeruginosa or Staphylococcus epidermidis [11].
• Strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes were exposed to amoxicillin, ampicillin, benzylpenicillin, carbenicillin, cefazolin, chloramphenicol, flucloxacillin, gentamicin, or oxytetracyclin [12].

Biological context of Flucloxacillin

• The pharmacokinetics of intravenously administered flucloxacillin (2.0 g to five volunteers) are described [13].
• Flucloxacillin showed good tissue penetration, considering its very high serum protein binding [13].
• Per-operative serum and wound fluid concentrations achieved by two flucloxacillin dosage regimens were measured in twelve patients undergoing open heart surgery [14].
• The absolute bioavailability of flucloxacillin from capsules was 54.4 +/- 18.8% [15].
• METHODS: This was a cohort study using data from the UK General Practice Research Database. We identified patients with a first-time prescription for flucloxacillin or, for comparison, oxytetracycline from 1992 to 2002 and cases who developed clinically documented cholestatic liver disease of uncertain origin after first-time use of these drugs [16].

Anatomical context of Flucloxacillin

• Floxacillin-induced cholestatic hepatitis with evidence of lymphocyte sensitization [17].
• Concentrations of flucloxacillin in heart valves and subcutaneous and muscle tissues of patients undergoing open-heart surgery [18].
• We report cases of amoxycillin- and flucloxacillin-induced liver damage associated with an acute vanishing bile duct syndrome [19].
• Flucloxacillin concentration in serum and wound exudate during open heart surgery [14].
• Indirect cytotoxicity of flucloxacillin toward human biliary epithelium via metabolite formation in hepatocytes [20].

Associations of Flucloxacillin with other chemical compounds

• In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin [21].
• Cefotaxime and flucloxacillin as antibiotic prophylaxis in cardiac transplantation [22].
• X-ray crystallography of flucloxacillin and nafcillin is fully described [23].
• The incidence of reported liver reactions was estimated from sales data to be 1.6-2.9 per million DDD (defined daily doses) or, for flucloxacillin 1:11,000-1:30,000 prescriptions [3].
• Antibiotic prophylaxis in cardiac surgery: serum and tissue levels of teicoplanin, flucloxacillin and tobramycin [24].

Gene context of Flucloxacillin

• These findings indicate that flucloxacillin has the potential to induce expression of both CYP3A4 as well as P-glycoprotein, most likely through activation of the nuclear hormone receptor PXR [25].
• Induction of cytochrome P450 3A4 and P-glycoprotein by the isoxazolyl-penicillin antibiotic flucloxacillin [25].
• At high concentrations, flucloxacillin activated the human Pregnane-X-Receptor, PXR, a ligand-dependent transcription factor that is the target of many drugs that induce CYP3A4, with consequences for the metabolism of other drugs [25].
• Cytotoxicity in BEC preparations (9/13) was also induced by the supernatants of human liver microsomes and of recombinant human cytochrome P450 (CYP)3A4 preincubated with flucloxacillin (500 mg/L) [20].
• These organisms produced large amounts of beta-lactamase which readily hydrolyzed flucloxacillin but they were sensitive to teicoplanin, dicloxacillin and cephalothin at 37.5 degrees C. The MRSA strains did not differ from methicillin-sensitive isolates in sensitivity to unsaturated fatty acids, survival in serum and plasma or desiccation [26].

Analytical, diagnostic and therapeutic context of Flucloxacillin

• Immunologic tests revealed evidence of in vitro sensitization to the drug as well as to the serum of a normal subject collected after ingestion of floxacillin [17].
• Flucloxacillin was assayed by high-pressure liquid chromatography, and pharmacokinetics were assayed by computerized curve fitting to accepted models [13].
• Study I compares with phlebitogenic properties of flucloxacillin after intravenous infusions when either saline or sterile water was used as a solvent [9].
• Since the overall incidence of prosthetic infection using flucloxacillin was acceptably low (0.49% of perfusions; 0.56% of valve insertions), it is concluded that narrow spectrum prophylaxis offers the better overall choice, at least until more objective comparisons are made [27].
• Concentration of flucloxacillin in femoral head and joint capsule in total hip replacement [28].

References