Clarithromycin, as an adjunct to non surgical periodontal therapy for chronic periodontitis: a double blinded, placebo controlled, randomized clinical trial

Objective

Along with conventional non-surgical periodontal therapy (NSPT) systemic antimicrobials may provide more effective treatment for chronic periodontitis by targeting tissue-invasive bacteria. The aim of this randomized, placebo-controlled, double-masked clinical trial was to evaluate the adjunctive effects of oral clarithromycin (CLM) to non-surgical periodontal therapy for chronic periodontitis.

Methods

40 patients were categorized into two groups: test group – scaling and root planing (SRP) plus CLM (500 mg b.i.d. for 3 days) and control group – SRP plus placebo. Clinical parameters were recorded at baseline and at 1, 3, 6, and 9 months. They included gingival index (GI), probing depth (PD), and clinical attachment level (CAL). Also microbial analysis of dental plaque was done at baseline, 3 and 9 months to estimate the levels of periodontopathic organisms using polymerase chain reaction. ANOVA, Chi-square and Bonferroni tests were used for statistical analysis.

Results

Thirty-seven subjects completed the study and the results demonstrated that both groups displayed clinical improvements. Using a subject-based analysis, patients treated with SRP + CLM showed enhanced reductions in PD and gains in CAL (p < 0.001) over time, as compared to control group. Also significant reductions in periodontopathic organisms were noticed in the test group compared to control group. However, no statistically significant differences were noted for Tannerella forsythia levels between the groups during the course of the study.

Conclusions

The utilisation of CLM in combination with SRP improves the efficacy of NSPT in reducing PD, improving CAL and in lessening microbial loads. Hence, CLM may be beneficial in the non-surgical treatment regimen of chronic periodontitis.     

腹腔镜胆囊切除术100例预防性应用抗菌药物调查分析

目的评价某二甲医院腹腔镜胆囊切除术围术期预防性应用抗菌药物情况。方法采用回顾性方法对该院腹腔镜胆囊切除术患者100例的住院时间、用药时间、用药种类、费用等指标进行统计分析。结果本组患者抗菌药物预防性应用率为100%,平均用药时间为5.49d,最长用药时间为22d;预防性应用抗菌药物共涉及4类10种,应用频次排序前3位的依次为奥硝唑、头孢孟多、头孢地嗪。单一用药33例,联合用药67例。术后预防性应用抗菌药物费用占总药费的45%。结论该院腹腔镜胆囊切除术围术期预防性应用抗菌药物仍存在较严重的不规范现象,亟待采取相关措施加以干预。     

Ⅰ类切口手术围手术期抗菌药物预防应用的调查分析

目的调查分析Ⅰ类切口手术围手术期抗菌药物应用情况。方法选出住院Ⅰ类切口手术病历179份（例）,并对其围手术期抗菌药物的选择、用药时间、疗程、用法用量和联合用药等方面的合理性进行分析。结果Ⅰ类切口手术不合理使用抗菌药物的病历共67份（例）,占抽查病历的37．4％,其中,选药不合理占13．4％,用药时间不准确占12．3％,病程记录不完整占7．8％,用法用量不合理占2．8％,联合用药不合理占1．1％。结论Ⅰ类切口围手术期抗菌药物预防应用仍存在一些不合理现象,需继续加强管理。     

临床药师干预围手术期抗菌药物应用的意义及模式

目的评价本院围手术期抗菌药物应用的合理性。方法对我院普通外科Ⅰ、Ⅱ类手术切口围手术期病历176份进行回顾性分析。结果围手术期抗菌药物应用中存在着范围过广、时间过长、起点过高等问题。结论对围手术期抗菌药物的合理应用进行干预是临床药师的重要工作。     

Simultaneous determination and validation of antimicrobials in plasma and tissue of actinomycetoma by high-performance liquid chromatography with diode array and fluorescence detection

A simple, precise, and reliable chromatographic method was developed for the simultaneous determination in plasma and infected tissue of five antimicrobials proposed for the treatment of actinomycotic mycetoma: amoxicillin, trimethoprim, linezolid, sulfamethoxazole and garenoxacin. Separation of the analytes was achieved on an Atlantis dC18 column (150 mm × 4.6 mm, ID 5 μm) with a mobile phase composed of acetonitrile and trifluoroacetic acid (ATF) 0.1% (v/v) using a gradient program. The detection was carried out using a diode array detector at 254 nm and in a fluorescence detector at wavelengths of excitation and emission of 292 nm and 392 nm for linezolid and sulfamethoxazole, and 292 nm and 408 nm for garenoxacin, respectively. The intraday precision was in the range of 0.7–15% of relative standard deviations (%R.S.D.) for plasma and 1–18% for tissue. Linearity range was from 2.4 to 20 μg/ml for amoxicillin, 0.3 to 20 μg/ml for trimethoprim, sulfamethoxazole and linezolid, and 0.3 to 10 μg/ml for garenoxacin. Acetonitrile was used to precipitate proteins from plasma. Recoveries in plasma ranged from 71% to 118% and in infected tissue from 78% to 122%. Limits of detection (LODs) were 1.2 and 0.5 μg/ml for amoxicillin in plasma and tissue, respectively and 0.15 and 1.2 μg/ml in plasma and tissue, respectively for the other antimicrobials. The method can be applied for individual or simultaneous determination of the antimicrobials in plasma and tissue of mouse infected with actinomycetoma.     

我院腹腔感染患者抗菌药应用分析

目的：调查分析我院腹腔感染患者的抗菌药使用情况,指导临床合理应用抗菌药物治疗腹腔感染。方法：抽查我院2014年1~7月份腹腔感染出院患者病历共220份,对抗菌药使用情况进行统计分析。结果：220份病历均使用了抗菌药,共涉及10类24种：单一用药92例（占41.8%）,二联用药126例（占57.3%）,三联用药2例（占0.91%）。应用的抗菌药物以头孢菌素类（含加酶抑制剂复合制剂）的使用率最高;其次为青霉素类（含加酶抑制剂复合制剂）;排在第三位的是硝基咪唑类。以两联用药为主,联用类别主要为β-内酰胺类联合硝基咪唑类及β-内酰胺类联合喹诺酮类。平均用药时间5.57 d。进行细菌培养及药敏试验的病例有47例,检出的致病菌主要是革兰阴性菌,有大肠埃希菌、铜绿假单胞菌及肺炎克雷伯菌。结论：我院腹腔感染患者抗菌药应用基本合理,但也存在联合用药不合理、疗程超长等情况,应进一步加强管理。     

临床药师干预眼科清洁手术围术期抗菌药物应用效果分析

目的:评价临床药师对眼科清洁手术围术期抗菌药物预防用药的干预效果。方法:通过行政干预与技术干预相结合的综合干预策略,对对照组(2011年1-8月清洁手术患者出院病历401份)、干预组1(2012年1-8月清洁手术患者出院病历417份)和干预组2(2013年1-8月清洁手术患者出院病历437份)围术期预防使用抗菌药物情况进行合理性评价及统计学分析。结果:经过综合干预,3个阶段围术期抗菌药物用药指标均有明显改善,抗菌药物预防使用率从对照组的20.70%下降至干预组的5.76%和12.13%(P<0.05);无适应证用药率从4.20%下降至0.48%和1.14%(P<0.01);抗菌药物品种选择不合理率从16.21%下降至1.68%和0.46%(P<0.01);用药时机不合理率从13.22%下降至1.92%和0(P<0.05);平均用药疗程从(2.80±2.70)d下降至(2.56±1.56)d(P>0.05)和(1.52±1.39)d(P<0.05)。结论:通过综合干预措施,可有效提高眼科清洁手术围术期抗菌药物应用的合理性。     

Typical antimicrobials induce mast cell degranulation and anaphylactoid reactions via MRGPRX2 and its murine homologue MRGPRB2

Mast cells are unique immune cells that function as sentinels in host defence reactions, including immediate hypersensitivity responses and allergic responses. The mast cell‐specific receptor named MAS‐related G protein‐coupled receptor X2 (MRGPRX2) triggers mast‐cell degranulation, a key process in anaphylactoid reactions. It is widely observed that antimicrobials can induce pseudo‐allergic reactions (i.e. IgE‐independent mechanism) with symptoms ranging from skin inflammation to life‐threatening systemic anaphylaxis. However, their direct involvement and the mechanisms underlying anaphylactoid reactions caused by antimicrobials have not been demonstrated. Structurally different antimicrobials were screened by Ca²⁺ imaging using MRGPRX2 overexpressing HEK293 cells. MRGPRX2 related anaphylactoid reactions induced by these components were investigated by body temperature drop and mast cell degranulation assays. We showed that MRGPRX2 is involved in allergic‐like reactions to three types of antimicrobials in a dose‐dependent manner. However, mast cells lacking the receptor show reduced degranulation. Furthermore, mice without MAS‐related G protein‐coupled receptor B2 (the orthologous gene of MRGPRX2) exhibited reduced substance‐induced inflammation. Interestingly, β‐lactam and antiviral nucleoside analogues did not induce anaphylactic reactions, which were also observed in vitro. These results should alarm many clinicians that such drugs might induce anaphylactoid reactions and provide guidance on safe dosage of these drugs.     

A case of recovery from aphasia following dose reduction of cefepime by bayesian prediction-based therapeutic drug monitoring

Cefepime is known to exert bactericidal activity against Pseudomonas aeruginosa. Cefepime-induced neurotoxicity, most likely caused by increased exposure, has recently become a major concern in clinical practice; therefore, appropriate dose reduction of cefepime should be applied with respect to patients with low cefepime clearance (mostly eliminated by the kidneys). Here, we report a case in which Bayesian prediction-based therapeutic drug monitoring (Bayes-TDM) was effectively used to reduce the dose of cefepime in a patient with pneumonia to prevent neurotoxic complications. A woman (age: 59 years, body weight: 32.5 kg, serum creatinine concentration: 1.02 mg/dL) developed pneumonia caused by P. aeruginosa while receiving treatment for scleroderma and systemic lupus erythematosus. She started treatment with a dosing regimen of 1.0 g of cefepime every 8 h (day X). On day X+5, aphasia developed, and the serum cefepime concentration was 71.3 mg/L at trough. This concentration was twice or thrice higher than the reported safe concentration of cefepime (22 or 35 mg/L at trough). Therefore, we reduced the dose of cefepime to 0.5 g every 12 h using Bayes-TDM from day X+7. As a result, the severity of aphasia decreased by day X+10, and this dose was successfully continued up to day X+13 without further adjustment. In conclusion, individualizing doses by Bayes-TDM may be useful in preventing adverse effects associated with cefepime treatment.     

Enhanced bactericidal activity of enterocin AS-48 in combination with essential oils, natural bioactive compounds and chemical preservatives against Listeria monocytogenes in ready-to-eat salad

Enterocin AS-48 (30–60 μg/g) significantly reduced viable counts of Listeria monocytogenes in Russian-type salad during one week storage at 10 °C. Antilisterial activity of AS-48 (30 μg/g) in salad was strongly enhanced by essential oils (thyme verbena, thyme red, Spanish oregano, ajowan, tea tree, clove, and sage oils tested at 1%, as well as with 2% rosemary oil). Antilisterial activity also increased in combination with bioactive components from essential oils and plant extracts, with other related antimicrobials of natural origin or derived from chemical synthesis (carvacrol, eugenol, thymol, terpineol, tyrosol, hydroxytyrosol, caffeic, ferulic and vanillic acid, luteolin, geranyl butyrate, geranyl phenylacetate, pyrocatechol, hydrocinnamic acid, tert butylhydroquinone, phenylphosphate, isopropyl methyl phenol, coumaric acid, and 2-nitropropanol), and with food preservatives (citric and lactic acid, sucrose palmitate, sucrose stearate, p-hydroxybenzoic methylester acid – PHBME, and Nisaplin). AS-48 acted synergistically with citric, lactic acid, and PHBME. A mixed population of two L. monocytogenes strains was markedly reduced for one week in salads treated with AS-48 (30 μg/g) in combination with lactic acid, PHBME or Nisaplin. The increased bactericidal activity of these combinations is interesting to improve protection against L. monocytogenes during salad storage.