Metronidazole for the treatment of vaginal infections

Introduction: Metronidazole, undoubtedly the most widely known and used member of the nitroimidazole drug class, remains not only first line therapy for bacterial vaginosis (BV) and trichomoniasis, but serves as drug of first choice. Available and used both orally and topically with high efficacy rates, especially for trichomoniasis, nevertheless numerous unanswered questions remain regarding mechanism of action. Given the extraordinary global frequency of vaginitis due to BV and trichomoniasis, especially the high recurrence rate observed in BV, it is timely to critically examine the therapeutic role of metronidazole in management decisions.

Areas covered: Search methodology used PUBMED literature review. In spite of many years of successful use, multiple questions exist regarding optimal dose and duration of therapy especially in the management of BV. Antimicrobial drug resistance remains uncommon in spite of extensive use. The use of metronidazole for vaginitis is reviewed in this article together with challenges to improving its more effective administration.

Expert opinion: Currently metronidazole or the family of nitroimidazoles, represent the drugs of first choice for trichomonas vaginitis and first line therapy for BV. Drug resistance for both entities remains uncommon; however, in contrast to trichomoniasis where relapse is rare, high recurrence rates are common in women with BV. Metronidazole appears to allow persistence of vaginal microbiome microorganisms which translate into frequent relapses. In the absence of new therapeutic alternatives, strategies are being developed to enhance drug cure rates.     

Experimental acute alcohol pancreatitis‐related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect

OBJECTIVE: The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. METHODS: Sprague–Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full‐blown, rats were fed an alcohol‐rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. RESULTS: Synbiotics but not metronidazole improved the acute pancreatitis‐induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic‐treated group, while metronidazole had a negative effect on liver damage. CONCLUSIONS: Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.     

Estrogen Activation of G-Protein–Coupled Estrogen Receptor 1 Regulates Phosphoinositide 3-Kinase and mTOR Signaling to Promote Liver Growth in Zebrafish and Proliferation of Human Hepatocytes

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雷贝拉唑、阿莫西林联合甲硝唑对幽门螺旋杆菌的临床效果观察

目的 探讨雷贝拉唑、阿莫西林联合甲硝唑对幽门螺旋杆菌的临床效果。方法 选取2016年1月—2017年12月于中国人民解放军第464医院诊治的幽门螺旋杆菌患者90例进行前瞻性研究,采用随机数字法分为观察组（45例）和对照组（45例）,对照组患者给予奥美拉唑、阿莫西林联合甲硝唑,观察组患者给予雷贝拉唑、阿莫西林联合甲硝唑,两组患者均接受治疗4周。比较两组患者临床治疗有效率,腹胀、腹痛、反酸及嗳气的缓解时间及不良反应发生率。结果 观察组患者的有效率为91.11%,对照组患者的治疗有效率为73.33%,差异具有统计学意义（P<0.05）。与对照组相比,观察组患者的腹胀、腹痛、反酸及嗳气缓解时间均显著缩短,差异具有统计学意义（P<0.05）。观察组患者的不良反应发生率为13.33%,对照组患者的不良反应发生率为17.78%,差异无统计学意义。结论 雷贝拉唑、阿莫西林联合甲硝唑对幽门螺旋杆菌的临床治疗效果较好,能够有效改善患者的临床症状,具有积极的临床意义。     

Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis

Background: The systemic use of combined amoxicillin and metronidazole (AMX/MET) as an adjunctive treatment to full‐mouth scaling and root planing (FMSRP) has been proposed for the treatment of generalized aggressive periodontitis; however, its effectiveness and clinical safety remain to be defined. The purpose of the present meta‐analysis is to assess the effectiveness of FMSRP + AMX/MET compared to FMSRP alone. Methods: An electronic search of eight databases and a hand‐search of 10 international dental journals were conducted through September 11, 2011. Gain in clinical attachment level (CAL), reduction in probing depth (PD), secondary outcomes, and adverse events were analyzed. A random‐effect model was used to pool the extracted data. The weighted mean difference (MD) with 95% confidence interval (CI) was calculated for continuous outcomes, whereas risk difference (RD) with 95% CI was used for dichotomous data; heterogeneity was assessed with the χ²‐based Cochran Q test and I² statistic. The level of significance was set at P <0.05. Results: After the selection process, six randomized clinical trials were included. Results of the meta‐analysis showed significant CAL gain (MD, 0.42; 95% CI, 0.23 to 0.61; P <0.05) and PD reduction (MD, 0.58; 95% CI, 0.39 to 0.77; P <0.05) in favor of FMSRP + AMX/MET; moreover, no significant RD was found in the occurrence of adverse events (RD, 0.01; 95% CI, ?0.02 to 0.04; P >0.05). Conclusion: The findings of the meta‐analysis seem to support the effectiveness and the clinical safety of FMSRP + AMX/MET; however, future studies are needed to confirm these results.     

Doxycycline hydrochloride-metronidazole solid lipid microparticles gels for treatment of periodontitis: development,in-vitro and in-vivo clinical evaluation

Objective: To formulate solid lipid microparticles (SLMs) encapsulating doxycycline hydrochloride (DH) and metronidazole (MT) for the treatment of periodontal diseases.

Methods: SLMs were prepared applying hot homogenization method, using different types of lipids and stabilized with various types and concentrations of surfactants. The optimized formula was subjected to freeze-drying followed by incorporation into poloxamer gel. Microbiological and clinical evaluation of the selected SLMs on patients suffering from periodontal diseases was performed.

Results: SLMs could entrap high percentage of both drugs (81.14% and 68.75 % for doxycycline hydrochloride and metronidazole respectively). Transmission electron microscopy images of SLMs showed nearly spherical particles. Freeze-dried SLMs showed satisfactory stability for three months. Combined drugs were molecularly dispersed in SLMs. Incorporation of the freeze-dried SLMs powder in poloxamer gel could control the drugs release for 72 h. In-vivo study revealed effective and safe use of SLMs gel for periodontitis treatment. Significant improvement in both microbiological and clinical parameters was observed as compared to scaling and root planing alone.

Conclusion: The formulated SLMs gel offers an applicable dosage form that can be injected directly into the periodontal pocket as adjunctive to scaling and root planing.     

Sustained Simultaneous Delivery of Metronidazole and Doxycycline From Polycaprolactone Matrices Designed for Intravaginal Treatment of Pelvic Inflammatory Disease

Poly(?-caprolactone) (PCL) intravaginal matrices were produced for local delivery of a combination of antibacterials, by rapidly cooling a mixture of drug powders dispersed in PCL solution. Matrices loaded with different combinations of metronidazole (10%, 15%, and 20% w/w) and doxycycline (10% w/w) were evaluated in vitro for release behavior and antibacterial activity. Rapid “burst release” of 8%-15% of the doxycycline content and 31%-37% of the metronidazole content occurred within 24 h when matrices were immersed in simulated vaginal fluid at 37°C. The remaining drug was extracted gradually over 14 days to a maximum of 65%-73% for doxycycline and 62%-71% for metronidazole. High levels of antibacterial activity up to 89%-91% against Gardnerella vaginalis and 84%-92% against Neisseria gonorrhoeae were recorded in vitro for release media collected on day 14, compared to “nonformulated” metronidazole and doxycycline solutions. Based on the in vitro data, the minimum levels of doxycycline and metronidazole released from PCL matrices in the form of intravaginal rings into vaginal fluid in vivo were predicted to exceed the minimum inhibitory concentrations for N. gonorrhea (reported range 0.5-4.0 μg/mL) and G. vaginalis (reported range 2-12.8 μg/mL) respectively, which are 2 of the major causative agents for pelvic inflammatory disease.     

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by oral metronidazole

Baboon syndrome is a special form of systemic contact dermatitis to systemic or local administration of contact allergens. Baboon syndrome without known previous cutaneous sensitisation was also described as drug-related baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). The major drugs causing SDRIFE was beta-lactam antibiotic such as amoxicillin and ampicillin. We report a case of 16-year-old woman who developed pruritic eruptions after oral metronidazole treatment for diarrhea. She was diagnosed SDRIFE according to her clinical and histopathological findings. To our knowledge, our patient is the first case who developed SDRIFE due to metronidazole in the literature.     

甲硝唑在胆汁中的浓度动态分布的实验研究

目的研究甲硝唑在家兔胆汁中的浓度动态分布,为预防和治疗肝胆系统厌氧菌感染提供参考和依据。方法家兔行胆总管造瘘术,静脉注射甲硝唑后于不同时间点采集胆汁标本,采用高效液相色谱法（HPLC）测定其在胆汁中的浓度,了解用药后不同时间药物在胆汁中的动态分布。结果家兔静脉注射甲硝唑（40mg／kg）后0．25h胆药浓度即大大超过有效杀菌浓度,胆汁药物达峰时间Tmax为（0．29±0．10）h;峰浓度Cmax为（29．49±10．02）±g／mL,远远超过其对厌氧菌的有效杀菌浓度（0．25-2μg／mL）,给药后4h胆药浓度仍达到最低抑菌浓度。结论甲硝唑可作为预防和治疗胆道厌氧菌感染较好的药物。