Indian tick typhus presenting as Purpura fulminans

Seriously ill patients presenting with purpura fulminans, sepsis and multi-organ failure often require extensive diagnostic workup for proper diagnosis and management. Host of common infections prevalent in the tropics, e.g. malaria, dengue; other septicemic infections e.g. meningococcemia, typhoid, leptospirosis, toxic shock syndrome, scarlet fever, viral exanthems like measles, infectious mononucleosis, collagen vascular diseases (Kawasaki disease, other vasculitis) diseases, and adverse drug reactions are often kept in mind, and the index of suspicion for rickettsial illness is quite low. We present a case of Indian tick typhus presenting with purpura fulminans (retiform purpura all over the body), sepsis and multiorgan failure without lymphadenopathy and eschar, successfully treated with doxycycline and discharged home. Hence, a high index clinical suspicion and prompt administration of a simple therapy has led to successful recovery of the patient.     

Doxycycline‐Loaded β‐Tricalcium Phosphate Release Following EDTA Root Surface Etching Improved the Clinical Outcomes in Chronic Periodontitis: An In Vivo Study

Background: The main objective of the present study is to quantify doxycycline (DOX) release from β‐tricalcium phosphate (β‐TCP) after EDTA root surface treatment. Methods: Thirty systemically healthy patients with ≥1 paired contralateral interproximal intrabony defect ≥4 mm deep along with an interproximal probing depth ≥6 mm and clinical attachment level ≥4 mm were randomized into two groups. Group 1 (G1) consisted of sites treated with open flap debridement followed by placement of DOX blended with β‐TCP (DOX‐β‐TCP), whereas group 2 (G2) sites were treated with flap surgery followed by the placement of DOX blended with β‐TCP after EDTA etching of the exposed root surfaces (DOX‐β‐TCP + EDTA). Samples of gingival crevicular fluid (GCF) were obtained 1, 3, 7, 14, and 21 days after surgery. Quantitative measurements of DOX were taken with high‐performance liquid chromatography. Clinical evaluation and follow‐up for 6 months were performed. Results: At 21 days, the DOX‐β‐TCP + EDTA–treated group showed a 194.7 µg/mL value. The DOX‐β‐TCP + EDTA–treated group retained more DOX during the periods of 3, 7, 10, 14, and 21 days than the DOX‐β‐TCP–treated group. Six months after therapy, DOX‐β‐TCP + EDTA–treated sites showed more significant clinical improvements compared to DOX‐β‐TCP–treated sites (P ≤ 0.05). Conclusions: EDTA root surface etching enhances DOX availability in the GCF following its release from β‐TCP as a drug carrier.     

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.     

Effect of residual doxycycline concentrations on resistance selection and transfer in porcine commensal Escherichia coli

Pig feed may contain various levels of antimicrobial residues due to cross-contamination. A previous study showed that a 3% carry-over level of doxycycline (DOX) in the feed results in porcine faecal concentrations of approximately 4?mg/L.The aim of this study was to determine the effect of residual DOX concentrations (1 and 4?mg/L) in vitro on selection of DOX–resistant porcine commensal Escherichia coli and transfer of their resistance plasmids.Three different DOX–resistant porcine commensal E. coli strains and their plasmids were characterised. These strains were each brought in competition with a susceptible strain in a medium containing 0, 1 and 4?mg/L DOX. Resistant bacteria, susceptible bacteria and transconjugants were enumerated after 24?h and 48?h.The tet(A)–carrying plasmids showed genetic backbones that are also present among human E. coli isolates. Ratios of resistant to susceptible bacteria were significantly higher at 1 and 4?mg/L DOX compared with the blank control, but there was no significant difference between 1 and 4?mg/L. Plasmid transfer frequencies were affected by 1 or 4?mg/L DOX in the medium for only one of the resistance plasmids.In conclusion, DOX concentrations of 1 and 4?mg/L can select for resistant E. coli in vitro. Further research is needed to determine the effect of these concentrations in the complex environment of the porcine intestinal microbiota.     

Association between tetracycline or doxycycline and hepatotoxicity: a population based case-control study

BACKGROUND AND OBJECTIVE: An FDA Working Group, along with representatives of PhRMA and the American Association for the Study of Liver Diseases, as well as the Institute of Medicine Report 'To Err is Human: Building a Safer Health Care System' have suggested that post-marketing drug surveillance is a important method to decrease adverse drug events. While tetracyclines are known to cause hepatotoxicity, no post-marketing drug surveillance studies have examined the risk of developing hepatotoxicity with tetracyclines. Therefore, the objective of this study is to determine the difference in risk of hepatotoxicity in patients receiving doxycycline or tetracycline using California Medicaid claims. METHODS: This study used a retrospective, matched case-control study using California Medicaid claims data. The cases were defined as recipients who had at least one diagnosis of hepatotoxicity any time from 1 July 1999 to 31 December 2001. One control was identified for each case, matched on age, gender and race. Logistic regression was used to determine the adjusted odds ratio (OR) and 95% confidence intervals for current users and past users of tetracycline and doxycycline. Covariates controlled for in the analysis were age, use of other hepatotoxic drugs, renal dysfunction, pregnancy, and alcohol or illicit drug use. RESULTS: A total of 3377 cases of hepatotoxicity were identified. Current users and past users of tetracycline had a statistically significant increased risk of developing hepatotoxicity (current use OR 3.70, 95% CI 1.19-11.45; past use OR 2.72, 95% CI 1.26-5.85). Current users or past users of doxycycline did not have an increased risk of developing hepatotoxicity (current use OR 1.49, 95% CI 0.61-3.62; past use OR 1.74, 95% CI 0.99-3.06). Tetracycline was commonly used for acne, acute bronchitis and upper respiratory infections. Doxycycline was commonly used for acute bronchitis, vaginitis and acne. DISCUSSION AND CONCLUSION: Doxycycline was potentially less hepatotoxic than tetracycline. Doxycycline could potentially be a safe substitute for tetracycline, when appropriate.     

Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline

Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the matrix degradation cascade associated with Achilles tendon rupture and disease. The goal of this study was to examine the effects of daily administration of doxycycline (Doxy) through oral gavage on MMP activity and on the repair quality of Achilles tendons in vivo. Our findings indicate that Achilles tendon transection resulted in increasing MMP‐8 activity from 2 to 6 weeks post‐injury, with peak increases in activity occurring at 4 weeks post‐injury. Doxy adiministration at clinically relevant serum concentrations was found to significantly inhibit MMP activity after continuous treatment for 4 weeks, but not for continuous administration for shorter durations (96 h or 2 weeks). Extended doxy administration was also associated with improved collagen fibril organization, and enhanced biomechanical properties (stiffness, ultimate tensile strength, maximum load to failure, and elastic toughness). Our findings indicate that a temporal delay exists between Achilles tendon transection and associated increases in MMP‐8 activity in situ. Our findings suggest that inhibition of MMP‐8 at its peak activity levels ameliorates fibrosis development and improves biomechanical properties of the Achilles tendon. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:500–506, 2014.     

复方多西环素缓释凝胶的体内释放度测定

目的：观察复方多西环素缓释凝胶的体内缓释性能。方法将11名患者的26颗患牙随机分为实验组和对照组,于基础治疗1周后,分别在牙周袋内置入复方多西环素缓释凝胶和复方多西环素凝胶,并于置药后每天定时用滤纸条法采集龈沟液样本,高效液相色谱法测定龈沟液内多西环素的浓度。结果复方多西环素凝胶在用药后第3天,龈沟液内多西环素浓度已降至6．82μg/ml;复方多西环素缓释凝胶在用药7 d后龈沟液内多西环素浓度仍可达到60．46μg/ml。结论复方多西环素缓释凝胶在牙周袋内可缓慢释放,较长时间维持有效浓度。     

复方多西环素缓释凝胶对实验性牙周炎龈沟液IL-4和 TNF-α的影响

目的：研究复方多西环素缓释凝胶对实验性牙周炎大鼠牙龈指数（ GI）、牙周袋深度（ PD）、附着丧失程度（AL）及龈沟液中白介素-4（IL-4）和肿瘤坏死因子-α（TNF-α）水平的影响。方法选用Wister大鼠42只,随机分为3组：正常对照组（N组）,阳性对照组（C组）和实验组（T组）,每组14只。 C组和T组建立牙周炎模型后,C组给米诺环素软膏治疗,T组给复方多西环素缓释凝胶治疗,均为每周上药1次共4次,并分别在治疗前和治疗后记录GI、PD、AL及龈沟液中IL-4和TNF-α水平。结果治疗后,C组和T组GI、PD、AL均较治疗前显著下降（ P ＜08．05）。牙周炎大鼠龈沟液中IL-4水平显著低于正常组（ P ＜0．05）,治疗后显著增高（ P ＜0．05）,且T组明显高于C组（ P ＜0．05）;牙周炎大鼠龈沟液中TNF-α水平显著高于正常组（ P ＜0．05）,治疗后显著降低（ P ＜0．05）,T组和C组治疗后差异无统计学意义（ P ＞0．05）。结论复方多西环素缓释凝胶能明显改善牙周炎临床症状,显著降低龈沟液中TNF-α水平,提高龈沟液中IL-4水平。