Systemic treatment of rhinosinusitis in children

Systemic acute rhinosinusitis therapy consists mostly of antibiotic treatment because pathogens play a major role. Amoxicillin is the drug of choice for treatment of acute rhinosinusitis, with second- and third- generation cephalosporins, azythromycin, clarithromycin, and telithromycin as possible options, especially in the case of allergy to amoxicillin. If the clinical course suggests that an anaerobic pathogen is more likely, clindamycin or metronidazole can be considered in combination with a broad-spectrum drug. In antimicrobial treatment of chronic sinusitis there is no consensus on treatment length, organism coverage, or which antibiotics are most effective because the bacteriology is variable with polymicrobial anaerobic and aerobic organisms present. Adjuvant therapies need to be proven by additional studies. Chronic rhinosinusitis is heterogeneous and treatment should vary according to the causative factor involved. Short courses of systemic steroids have been found very useful to decrease mucosal swelling and inflammation in chronic rhinosinusitis. However, no randomized controlled studies have been performed to validate their efficacy in children. A variety of other agents are used in the treatment of chronic rhinosinusitis including antihistamines, decongestants, and leukotriene modifiers. To date, there is no good evidence from randomized controlled studies to support the use of any of these agents in the treatment of this disease in either children or adults.     

Amoxicillin and clavulanic acid concentrations in gingival crevicular fluid

Abstract The β-lactams are bactericidal antibiotics, but some of them may be inactivated by bacterial β-lactamases which destroy the β-lactam ring. The inactivation of amoxicilhn by β-Iactamases of gram negative anaerobic bacteria can be circumvented by the addition of clavulanic acid, a β-lactamases inhibitor. Thus, most of these bacteria are susceptible to this combination. The aim of this study was to investigate the concentrations of amoxicillin and clavulanic acid in gingival crevicular fluid (GCF). These concentrations were measured in 20 patients with rapidly progressive periodontitis 1 h after a dose of 500 mg (1 tablet Augmentin®) on day 0 and 1 h after the 10th intake on day 3. For the sampling of GCF, Periopapers® were introduced in 16 gingival sites per subject and time. The GCF volumes collected were estimated using the Periotron 6000®. A high performance liquid chromatography method has been developed for the determination of amoxicillin and clavulanic acid in microsamples (1 to 10 μl) of GCF. The concentrations of amoxicillin and clavulanic acid were respectively, 14.05 μg ml^-1 and 0.40 μg ml^-1 at day 0.13.93 μg ml^-1 and 0.37 μg ml^-1 at day 3. Effective levels of amoxicillin and clavulanic acid, well above the minimal inhibitory concentrations of some susceptible periodontal anaerobes (P. intermedia) involved in destructive periodontal diseases, are achieved following the multiple administration of amoxicillin combined with clavulanic acid.     

* Immediate allergic reactions to amoxicillin

A large group of patients with suspected allergic reactions to (β-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to β-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to β-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.     

Immediate hypersensitivity to penicillins. Studies on Italian subjects

The IgE response, the involvement of the different penicillins available for therapeutic use, and the specificity of the IgE antibodies found in a group of penicillin-allergic subjects from Italy were studied. Thirty subjects with a history of allergic reactions to penicillins were studied. In vivo and in vitro specific IgE antibodies were determined to different penicillin determinants. Fifteen subjects developed anaphylactic responses and the remainder urticaria and angioedema. The drug most frequently involved in the patients' allergic reactions was ampicillin (AMP). The benzylpenicilloyl (BPO) skin test was positive in 16 (53.3%) patients, whereas 23 (76.6%) patients were positive to minor determinant mixture (MDM), benzylpenicillin (PG), AMP, or amoxicillin (AX). When classified according to initial reaction type, most anaphylactic patients (93.3%) were associated with minor determinant reactivity, whereas most urticaria patients (80%) reacted to BPO. RAST results for the anaphylactic and urticaria subgroups were similar. RAST inhibition showed that most sera contained highly cross-reactive IgE antibodies. There was evidence of a specific response to AX and PG (one patient each). These data show that in a population of penicillin-allergic patients from Italy, AMP was the main drug inducing the allergic reaction. In skin tests and RAST, patients exhibited heterogeneous IgE responses with little indication of specific reactivity to AMP.     

Nanoarchitectures for efficient IgE cross-linking on effector cells to study amoxicillin allergy

Background

Amoxicillin (AX) is nowadays the β-lactam that more frequently induces immediate allergic reactions. Nevertheless, diagnosis of AX allergy is occasionally challenging due to risky in vivo tests and non-optimal sensitivity of in vitro tests. AX requires protein haptenation to form multivalent conjugates with increased size to be immunogenic. Knowing adduct structural features for promoting effector cell activation would help to improve in vitro tests. We aimed to identify the optimal structural requirement in specific cellular degranulation to AX using well-precised nanoarchitectures of different lengths.

Method

We constructed eight Bidendron Antigens (BiAns) based on polyethylene glycol (PEG) linkers of different lengths (600–12,000 Da), end-coupled with polyamidoamine dendrons that were terminally multi-functionalized with amoxicilloyl (AXO). In vitro IgE recognition was studied by competitive radioallergosorbent test (RAST) and antibody–nanoarchitecture complexes by transmission electron microscopy (TEM). Their allergenic activity was evaluated using bone marrow-derived mast cells (MCs) passively sensitized with mouse monoclonal IgE against AX and humanized RBL-2H3 cells sensitized with polyclonal antibodies from sera of AX-allergic patients.

Results

All BiAns were recognized by AX-sIgE. Dose-dependent activation responses were observed in both cellular assays, only with longer structures, containing spacers in the range of PEG 6000–12,000 Da. Consistently, greater proportion of immunocomplexes and number of antibodies per complex for longer BiAns were visualized by TEM.

Conclusions

BiAns are valuable platforms to study the mechanism of effector cell activation. These nanomolecular tools have demonstrated the importance of the adduct size to promote effector cell activation in AX allergy, which will impact for improving in vitro diagnostics.

     

思密达四联疗法对幽门螺杆菌阳性的消化性溃疡42例疗效分析

目的 观察思密达四联疗法对幽门螺杆菌（Hp)阳性的消化性溃疡（Pu0的临床应用价值。方法：对42例经胃镜证实Hp阳性的Pu病人用思密达,雷尼替丁,阿莫西林,甲硝唑,四联治疗,与38例予枸橼酸铋钾,奥美拉唑,阿莫西林,甲硝唑四联疗法治疗进行对照。结果：治疗组与对照组停药4周后胃复查溃疡愈合率分别为86％及90％,Hp根除率分别为90％及95％,不良反应发生率分别为19％及24％,两组比较差异无显性。而两组药价差异有显性,治疗组价廉。结论：以思密达为中心的四联疗法能有效治疗Hp阳性的Pu,且相对价廉,无严重不良反应,值得进一步推广应用。     

盐酸溴己新阿莫西林胶囊的一般药理学和毒理学研究

目的 :探讨盐酸溴己新阿莫西林胶囊对动物神经、心血管和呼吸系统的影响及毒性。方法 :小鼠一次性口服 (ig)药物后 ,测定其对神经系统的影响和耐受性 ;腹腔注射 (ip)测其LD50;记录给猫灌药后不同时间的心电图和呼吸变化 ;大鼠按不同剂量ig2个月作长期毒性研究。结果 :本品对小鼠的自主活动无影响 ,与安钠咖和戊巴比妥钠均无协同作用和抑制作用 ;对猫的心血管系统和呼吸均无影响 ;小鼠ig的最大耐受量大于24g/kg;ip的LD50 为3842.82mg/kg;给大鼠ig2个月 ,对动物的各项检查指标均无影响。结论 :本品对动物的神经、心血管和呼吸系统均无影响 ,长期服用本品无明显毒副作用 ,服用安全     

丙磺舒对阿莫西林在家兔体内的药动学影响

目的:观察丙磺舒对阿莫西林在健康家兔体内药动学的影响.方法:采用微生物杯碟法测定兔血清中阿莫西林的浓度.结果:阿莫西林单剂量肌内注射后,吸收迅速,Tmax=(0.78±0.09)h,Cmax=(0.87±0.30)μg·mL-1,其代谢模型为一级速率一房室模型.当阿莫西林和丙磺舒等剂量伍用时丙磺舒对阿莫西林药动学参数的影响达到最大值:阿莫西林的t1/2由(2.06±0.09)h延长至(5.50±0.52)h,AUC由(4.07±0.05)μg·mL-1·h增加至(13.75±3.09)μg·mL-1·h,Cmax由(0.87±0.30)μg·mL-1增加至(6.30±1.46)μg·mL-1,且三者统计学差异极显著(P<0.01).结论:丙磺舒对阿莫西林的药动学参数的影响呈S型,当两者等剂量伍用时影响最大.     

高效液相色谱衍生化法同时测人血清中阿莫西林和克拉维酸浓度

 目的 建立同时测定人血清中阿莫西林和克拉维酸农度的高效液相色谱法。方法 血清样品经笨甲醛衍生，荧光检测,波长λex=386mm，λem=460nm，采用Discovery C₁₈柱，流动相甲醇-水=55:45,流速为1.0 mL·min^-1，柱温为29℃。结果 克拉维酸和阿莫西林的保留时间分别为5.10,6.20 min左右。克拉維酸在0.062~4.968mg·L^-1内线性良好（r=0.999 9);阿莫西林在0.089~35.718 mg·L^-1内线性良好（r=0.999 9)。加样回收率均在90.0%~105.0%范围内，日内和日间RSD均小于15.0%(n=5)。结论 本法灵敏度和精密度高、重复性好，适于阿莫西林克拉维酸钾复方制剂的药动学研究。