Relationship between plasma and bone concentrations of cefuroxime and flucloxacillin three different parenteral administrations compared in 30 arthroplasties

• (i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achieved after one intravenous (IV) administration of different dosages of cefuroxime and flucloxacillin.
• (ii) Six groups of five patients participated in the study. The first three groups (A–C) received respectively 1500 mg, 1000 mg, and 500 mg cefuroxime intravenously and the second three groups (D–F) received 2000 mg, 1500 mg, and 1000 mg flucloxacillin intravenously.
• (iii) Parenteral administration of cefuroxime and flucloxacillin resulted in measurable bone concentrations in all patients.
• (iv) Large inter-individual variation in bone concentration was observed.
• (v) The bone concentrations of IV cefuroxime were higher (1500 mg, p = 0.0057; 1000 mg, p = 0.0260) than those of flucloxacillin. The bone concentrations of cefuroxime and flucloxacillin were dose dependent.

     

Determination of certain drugs in binary mixtures formulations by second derivative ratio spectrophotometry and LC

Spectrophotometric and high-performance liquid chromatographic (HPLC) methods are developed for simultaneous determination of three binary mixtures with overlapping spectra. The spectrophotometric method is based on the use of second derivative of the ratio spectra (2DD) for resolution of three binary mixtures of indapamide with captopril (mixture 1), cinnarizine with heptaminol acefylline (mixture 2) and amoxycillin trihydrate with flucloxacillin sodium (mixture 3). The HPLC method depends on the separation of components of binary mixtures using ODS column with mobile phase consisting of acetonitrile and 5 mM aqueous heptane sulphonic acid sodium salt in ratios of (60:40, v/v, pH 5.5) for mixture 1, (50:50, v/v, pH 3.0) for mixture 2 and (35:65, v/v, pH 4.2) for mixture 3. The proposed methods are accurate, non-destructive and successfully applied for the determination of the three binary combinations in synthetic mixtures and commercial pharmaceutical products.     

氟氯西林钠与4种输液的配伍稳定性

目的考察氟氯西林钠与果糖氯化钠、果糖、5%葡萄糖、转化糖四种输液的配伍稳定性。方法氟氯西林钠分别与4种输液配伍后放置于30℃恒温水浴箱,观察配伍溶液6h内的外观、pH值及氟氯西林的含量变化。结果氟氯西林与果糖氯化钠、果糖、5%葡萄糖、转化糖4种输液的配伍液在6h内其外观性状、pH值、氟氯西林的含量均无明显改变。结论氟氯西林钠与果糖氯化钠、果糖、5%葡萄糖、转化糖4种输液的配伍液在6h内稳定。     

Ofloxacin intravenous

The physical and chemical compatibility of ofloxacin (infusion solution 100 ml=200 mg) with amoxicillin, amoxicillin+clavulanic acid, flucloxacillin, tobramycin, gentamicin, clindamycin, vancomycin, ceftazidime and piperacillin was investigated. Upon admixture with flucloxacillin a precipitate formed between 7 and 24 hours. No other physical or chemical incompatibilities were observed with any of the other combinations. Ofloxacin may be safely combined with the tested antimicrobial drugs, except for flucloxacillin.     

3-(2′-氯-6′-氟苯基)-5-甲基-4-异噁唑甲酰氯的合成

目的 研究抗生素氟氯西林钠的关键中间体3-(2'-氯-6'-氟苯基)-5-甲基-4-异噁唑甲酰氯的合成方法,使之适合工业化生产.方法 以2-氯-6-氟苯甲醛为原料,经肟化、氯化、环合、水解、酰氯化等步骤制得目标化合物.结果 合成产物的化学结构经IR,1H-NMR,13C-NMR and MS确证,总收率为60.2%.结论 此方法收率高,成本低,适合工业化生产.     

Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized,double-blind,placebo-controlled,non-inferiority trial

ObjectivesTo investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis.MethodsThis multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90.ResultsBetween August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: –15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: –8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05).ConclusionsGiven the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies.     

Cefazolin versus anti-staphylococcal penicillins for the treatment of patients with Staphylococcus aureus bacteraemia

BackgroundFor patients with bacteraemia caused by methicillin-sensitive Staphylococcus aureus anti-staphylococcal penicillins (ASPs) or cefazolin are agents of choice. While ASPs are potentially nephrotoxic, cefazolin may be less effective in some S. aureus strains due to an inoculum effect.ObjectivesTo perform a systematic literature review and meta-analysis assessing current evidence comparing cefazolin with ASPs for patients with S. aureus bacteraemia (SAB).MethodsWe searched MEDLINE, ISI Web of Science (Science Citation Index Expanded) and the Cochrane Database as well as clinicaltrials.gov from inception to 26 June 2018. All studies investigating the effects of cefazolin versus ASP in patients with methicillin-sensitive SAB were eligible for inclusion regardless of study design, publication status or language. Additional information was requested by direct author contact. A meta-analysis to estimate relative risks (RRs) with the corresponding 95% confidence intervals (CIs) was performed. Statistical heterogeneity was estimated using I². The primary endpoint was 90-day all-cause mortality. The Newcastle–Ottawa Scale (NOS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used for study and data quality assessment.ResultsFourteen non-randomized studies were included. Seven reported the primary endpoint (RR 0.71 (0.50, 1.02), low quality of evidence). Cefazolin treatment may be associated with lower 30-day mortality rates (RR 0.70 (0.54, 0.91), low quality of evidence) and less nephrotoxicity (RR 0.36 (0.21, 0.59), (low quality of evidence)). We are uncertain whether cefazolin and ASP differ regarding treatment failure/relapse as the quality of the evidence has been assessed as very low (RR of 0.84 (0.59, 1.18)). For patients with endocarditis (RR 0.71 (0.12, 4.05)) or abscesses (RR 1.17 (0.30, 4.63)), cefazolin treatment may be associated with equal 30-day and 90-day mortality (low quality of evidence).ConclusionsCefazolin seemed to be at least equally as effective as ASPs while being associated with less nephrotoxicity.     

均匀设计在氟氯西林钠工艺优化中的应用

均匀设计适用于多因素多水平的实验设计。本文采用均匀设计对氟氯西林酰胺缩合单元工艺参数进行优化，运用U10(1010) 均匀设计表对反应温度、加入丙酮体积和反应pH值3个因素进行了10个水平的筛选，考察反应率、杂质1~3与因素水平之间的关系。运用SPSS软件对数据进行回归分析，得到反应率、杂质1~3与因素水平之间的线性回归方程，预测了氟氯西林酰胺缩合单元最佳工艺参数范围。最后对回归方程进行了试验验证，预测值与实测值有良好的吻合。     

氟氯西林联合碘伏外擦治疗成人化脓性扁桃体炎疗效观察

目的探讨氟氯西林联合碘伏外擦治疗成人化脓性扁桃体炎的疗效。方法将临床确诊的56例急性化脓性扁桃体炎患者随机分成治疗组和对照组各28例，2组均使用氟氯西林1g 静脉滴注，每8小时1次，治疗组加用0,5％碘伏外擦，每天1~2次，对咽痛好转时间、体温正常时间等临床症状及体征观察疗效。结果治疗组平均住院天数4,9d，有效率达96,4％；对照组平均住院天数6,1d，有效率为89,3％，2组平均住院时间、有效率比较差异有统计学意义（p ＜0,05）。结论氟氯西林联合碘伏外擦治疗成人化脓性扁桃体炎，治疗效果更高、更快，值得临床推广，特别适合在成人中应用。     

Flucloxacillin in the treatment of infectious conditions in children

Summary

A multi-centre study was carried out in 107 children with skin and soft-tissue infections (46) or upper respiratory tract infections (61) to assess the effectiveness of flucloxacillin (125?mg. q.d.s. for 5 days). Swabs were taken from the lesion sites before and after treatment for bacteriological assessment and sensitivity of the isolated organisms.

The clinical success rate achieved was 93% in skin and soft-tissue infections and 94% in upper respiratory tract infections and these results correlate closely with the bacteriological findings. The main causative organism in the skin and soft-tissue infections was Staph, aureus which was resistant to benzyl penicillin and to ampicillin in all but 2 cases. All strains proved sensitive to flucloxacillin. Minimal side-effects were reported and the syrup presentation was well accepted.