DOCSLIB.ORG

Microbiome Manipulation: Antibiotic Effects on Cutaneous Leishmaniasis Presentation and Healing

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Microbiome Manipulation: Antibiotic Effects on Cutaneous Leishmaniasis Presentation and Healing 299 Rayad Barakat Microbiome Manipulation: Antibiotic Effects on Cutaneous Leishmaniasis [email protected] Tel: (301) 295-5895 Presentation and Healing Fax: (301) 301-0680 4301 Jones Bridge Rd Bethesda, MD 20814 R. Barakat1, C. Olsen1, N. Aronson1,2 1F. Edward Hebert School of Medicine, Uniformed Services University, Bethesda, MD 2Walter Reed National Military Medical Center, Bethesda, MD Discussion Results Abstract Clinical Presentation Rationale: Cutaneous ulcers of leishmanial infection are chronic wounds with an Table 1. Demographic Data Figure 1. Study Flow Diagram Somewhat more African-American men with cutaneous leishmaniasis received antibiotic treatment as anaerobe-predominant microbiome, further impacted by the immunomodulatory effects compared to those without antibiotic exposure. The most commonly prescribed antibiotic was amoxicillin- of Leishmania and superinfecting bacteria. Leveraging a policy to give presumptive Abx+ Abx- p-value Enrollment Assessed for eligibility (n=418) clavulanate (n=123 courses in 94 subjects), generally given in one- or two-week courses, and with several pyoderma treatment prior to evaluation for leishmaniasis, we assessed the effect of patients receiving multiple courses or multiple antibiotics. It was usually not possible to determine whether antibiotic therapy upon clinical presentation or treatment outcome among those with Total 195 165 Excluded (n=58) antibiotics were given per command policy to r/o pyoderma or for clinical illness such as superinfected cutaneous leishmaniasis. Methods: Data were obtained from a 418-patient open label Sex 0.13 Received Prior Treatment (n=53) ulcers. Doxycyline was given per command policy for malaria prophylaxis and received by 29 subjects, study of 10 or 20 days of sodium stibogluconate (SSG) therapy conducted at Walter Non-cutaneous leishmaniasis (n=3) Male 189 (97%) 164 (99%) Consent withdrawn (n=2) those individuals receiving it from the start of their time in theater until their return for CL treatment+28 Reed Army Medical Center. Subjects with parasitologically confirmed leishmaniasis days. Female 6 (3%) 1 (1%) were undergoing their first treatment course. We assessed clinical presentation by We observed no significant differences in duration of illness, baseline lesion size, number of CL lesions, Race 0.01 number and aggregate size of lesions, appearance, and lymphatic involvement. We Allocation regional lymphadenopathy, or presence of ulceration compared between those with or without antibiotic evaluated treatment outcome by patient report of healing at 2, 6, 12 months post SSG. Caucasian 133 (68%) 123 (75%) exposure. Patients were divided into those receiving antibiotics prior to treatment, those receiving Asian 3 (2%) 1 (<1%) antibiotics during treatment, and those who had not received any antibiotics. We Allocated to antibiotic group (n=195) Allocated to no-antibiotic group Treatment Outcome Hispanic 16 (8%) 18 (11%) (n=165) evaluated the two pre-treatment populations with Mann-Whitney Tests and Fisher’s Those receiving antibiotics during SSG treatment were assumed to have clinical bacterial infection, in Exact Test and the three posttreatment populations with χ2 and Kruskal-Wallis tests. contrast to those receiving antibiotics prior to SSG treatment (who may have received antibiotics per African-American 38 (19%) 20 (12%) Results/Conclusions: The cohort was 360 mainly young white males, with 4 median Antibiotic received pre-presentation command policy). Although at the 2-month follow-up timepoint non-antibiotic receiving patients appeared to lesions in both groups. The most commonly used antibiotics were doxycycline (n=29 Other 5 (3%) 3 (2%) (n=137) trend to lower cure rates than those with prior antibiotic treatment in both 10-day SSG and 20-day SSG courses), cephalexin (33), and amoxicillin-clavulanate (123). Statistical analysis found Mean Age (yr) (SD) 28.06 (7.5) 27.67 (7.8) 0.49 Antibiotic received post-presentation groups, this difference was not statistically significant, and by the 6-month follow-up any observable no significant difference between the pretreatment groups (antibiotics, no antibiotics) in SSG regimen 0.12 (n=58) differences had disappeared. Healing is generally seen without therapy in L. major infection by 6-12 clinical presentation, and no significant difference between the post-treatment groups in months so the 2 month timepoint would be most illustrative of antibiotic effect. Of note, there was 10 day 59 (30%) 63 (38%) Follow-up treatment outcomes. significant loss to follow up at the 2 month visit as subjects had returned to a combat zone and were 20 day 136 (70%) 102 (62%) Lesion size change lost to follow-up (n=0) Lesion size change lost to follow-up difficult to reach, however most redeployed to the US by the 6 month follow-up visit. Background Median Duration of Illness (n=2) Amoxicillin-clavulanate administration with its’ attendant anaerobic spectrum was not associated with any Days (IQR) 112 (55) 121 (58) 0.49 Analysis statistically significant change in clinical outcome. Strains of Staphylococcus and Streptococcus developed ♦ Cutaneous leishmaniasis (CL) presents a risk to non-immune populations in endemic CO3 Analyzed (n=195) Analyzed (n=163) in the cutaneous dysbiosis associated with leishmanial infection may exhibit resistance to treatment with regions, with notable recent outbreaks associated with conflict. Patients beginning antibiotics (Abx) during treatment are included in the Abx+ group amoxicillin-clavulanate [9]. ♦ Leishmanial infection alters the host immune response, and causes a chronic wound, Amoxicillin-clavulanate and doxycycline were the most commonly reported antibiotics contributing to secondary infection of ulcers [1-3] with indigenous microbiota affecting Figure 2a-d. Clinical presentation used. resistance to healing and susceptibility to leishmanial treatment [4,5]. comparison in antibiotic vs. no Conclusions antibiotic groups ♦ CL itself may restrict lesion microbiota, skewed toward anaerobes or coagulase • Despite the interplay between systemic antibiotic usage, leishmanial infection, local negative Staphylococcus [6], leading to substantial secondary infection and even ) immunomodulation, and the skin microbiome, no significant effects associated with sepsis [7]. 2 188 119 antibiotic use were observed in CL lesion healing outcomes or clinical presentation prior to 664, n=223 702, n=137 4, n=223 ♦ In mouse models, the treatment of secondary bacterial infection in leishmaniasis was specific antileishmanial treatment with SSG in this study. associated with an increased cure rates [7] as well as reduced splenic and hepatic 4, n=137 0.54 >0.99 disease burden [8]. • Prior antibiotic use was considered random, since most given as presumptive initial Percent ♦ Limited diagnostic capability early in Operation Iraqi Freedom (OIF) led to a policy of Percent therapy of chronic skin lesions under a command policy. treating leishmaniasis-like sores with a 5-7 day course of antibiotics for pyoderma, >0.99 35 18 • Limitations of this study included that this was a retrospective ad hoc analysis of clinically 0.81 lesions of Number resulting in patients receiving broad-spectrum antibiotics before transfer to the US for 2d collected data; there was much variability in the antibiotic administered, their dosages, leishmaniasis treatment. Aggregate size/subject (mm 2c duration, some inter-observer differences in lesion measurement and appearance ♦ We sought to determine if any significant differences could be found in clinical 2a 2b descriptions, and challenges with early outcome follow-up due to return to combat zone. presentation and treatment outcome between patients who had received antibiotics Table 2. Median Cure Rates (range) by month of follow up • Future work exploring the effects of antibiotic use on CL and treatment outcomes may before or during their CL treatment and those who had not received antibiotics. benefit from a more systematic approach including serial lesion microbiologic assessment, Figure 3 a,b. Change in lesion size with 10 days SSG 2 mo.(n=63) 6 mo.(n=91) 12 mo.(n=87) Consolidated (n=122) Methods a standardized antibiotic regimen targeted to predominant organisms in secondary SSG treatment compared with and Antibiotic prior 85 (65, 94) 94 (80, 98) 100 (89) • Data were obtained from records of a 418-patient open label study of 10 or 20 days of sodium without antibiotic use 84 (71, 92) infection, and investigation of systemic versus topical antimicrobial use. stibogluconate (SSG) therapy conducted at Walter Reed Army Medical Center among US service Antibiotic during 60 (23, 92) 92 (67, 99) 100 (68) 87 (62, 98) members who had acquired CL in Iraq or Afghanistan (mainly L. major). 3a References NA20 • Subjects with parasitologically confirmed leishmaniasis were included in this analysis if this was No antibiotic 58 (41, 73) 85 (74, 92) 92 (80, 97) 79 (68, 88) 1. Belkaid Y, Segre JA. Dialogue Between Skin Microbiota and Immunity. Science. 2014;346(6212):954-959. their first CL treatment course. 0.89 doi:10.1126/science.1260144. p 0.09 0.43 0.18 0.72 2. Naik S, Bouladoux N, Wilhelm C, et al. Compartmentalized Control of Skin Immunity by Resident Commensals. Science. • We assessed clinical presentation using number of and aggregate size of lesions, appearance, 20 days SSG 2 mo.(n=129) 6 mo.(n=189) 12 mo.(n=179) Consolidated (n=238) 2012;337(6098):1115-1119. doi:10.1126/science.1225152. and lymphatic involvement. Lesions were described and measured on presentation and upon 3. Gimblet C, Loesche MA, Carvalho L, et al. IL-22 Protects Against Tissue Damage During Cutaneous Leishmaniasis. Stäger S, ed. completion of therapy. Antibiotic prior 81 (69, 89) 93 (85, 97) 100 (95) PLOS ONE. 2015;10(8):e0134698. doi:10.1371/journal.pone.0134698. • Outcome status was ascertained by phone, email, or letter at 2, 6, and 12 months after treatment. 88 (80, 93) 4. Lopes MEM, Carneiro MBH, dos Santos LM, Vieira LQ. Indigenous Microbiota and Leishmaniasis. Parasite Immunology. • Patients who received antibiotics after beginning their course of SSG treatment were categorized Change Percent Antibiotic during 56 (33, 76) 91 (76, 96) 97 (84, 100) 81 (67, 90) 2016;38(1):37-44.
Load more

Recommended publications
  • Review Article Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions
    SAGE-Hindawi Access to Research Molecular Biology International Volume 2011, Article ID 571242, 23 pages doi:10.4061/2011/571242 Review Article Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions Arun Kumar Haldar,1 Pradip Sen,2 and Syamal Roy1 1 Division of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4 Raja S. C. Mullick Road, Kolkata West Bengal 700032, India 2 Division of Cell Biology and Immunology, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh 160036, India Correspondence should be addressed to Syamal Roy, [email protected] Received 18 January 2011; Accepted 5 March 2011 Academic Editor: Hemanta K. Majumder Copyright © 2011 Arun Kumar Haldar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V) in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistant Leishmania donovani isolates in murine model.
    [Show full text]
  • Drugs for Amebiais, Giardiasis, Trichomoniasis & Leishmaniasis
    Antiprotozoal drugs Drugs for amebiasis, giardiasis, trichomoniasis & leishmaniasis Edited by: H. Mirkhani, Pharm D, Ph D Dept. Pharmacology Shiraz University of Medical Sciences Contents Amebiasis, giardiasis and trichomoniasis ........................................................................................................... 2 Metronidazole ..................................................................................................................................................... 2 Iodoquinol ........................................................................................................................................................... 2 Paromomycin ...................................................................................................................................................... 3 Mechanism of Action ...................................................................................................................................... 3 Antimicrobial effects; therapeutics uses ......................................................................................................... 3 Leishmaniasis ...................................................................................................................................................... 4 Antimonial agents ............................................................................................................................................... 5 Mechanism of action and drug resistance ......................................................................................................
    [Show full text]
  • 204684Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 204684Orig1s000 SUMMARY REVIEW Division Director Review NDA 204684, Impavido (miltefosine)Capsules 1. Introduction NDA 204684 is submitted by Paladin Therapeutics, Inc., for the use of miltefosine for the treatment of visceral, cutaneous, and mucosal leishmaniasis in patients ≥12 years of age. The proposed dosing regimen is one 50 mg capsule twice daily with food for patients weighing 30- 44 kg (66-97 lbs.) and one 50 mg capsule three times daily with food for patients weighing ≥ 45 kg (≥ 99 lbs.). Leishmaniasis is caused by obligate intracellular protozoa of the genus Leishmania. The clinical manifestations are divided into three syndromes of visceral leishmaniasis, cutaneous leishmaniasis, and mucosal leishmaniasis. A single species of Leishmania can produce more than one clinical syndrome and each of the syndromes can be caused by more than species of Leishmania. Human infection is caused by about 21 of 30 species that infect mammals. These include the L. donovani complex with 2 species (L. donovani, L. infantum [also known as L. chagasi in the New World]); the L. mexicana complex with 3 main species (L. mexicana, L. amazonensis, and L. venezuelensis); L. tropica; L. major; L. aethiopica; and the subgenus Viannia with 4 main species (L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and L. (V.) peruviana). Leishmaniasis is transmitted by the bite of infected female phlebotomine sandflies. The promastigotes injected by the sandflies during blood meals are phagocytized by macrophages and other types of mononuclear phagocytic cells and transform into amastigotes. The amastigotes multiply by simple binary fission and lead to rupture of the infected cell and invasion of other reticuloendothelial cells.1 Miltefosine is an alkyl phospholipid analog with in vitro activity against the promastigote and amastigote stages of Leishmania species.
    [Show full text]
  • Guidelines for Diagnosis, Treatment and Prevention of Visceral Leishmaniasis in South Sudan
    Guidelines for diagnosis, treatment and prevention of visceral leishmaniasis in South Sudan Acromyns DAT Direct agglutination test FDA Freeze – dried antigen IM Intramuscular IV Intravenous KA Kala–azar ME Mercaptoethanol ORS Oral rehydration salt PKDL Post kala–azar dermal leishmaniasis RBC Red blood cells RDT Rapid diagnostic test RR Respiratory rate SSG Sodium stibogluconate TFC Therapeutic feeding centre TOC Test of cure VL Visceral leishmaniasis WBC White blood cells WHO World Health Organization Table of contents Acronyms ...................................................................................................................................... 2 Acknowledgements ....................................................................................................................... 4 Foreword ...................................................................................................................................... 5 1. Introduction ........................................................................................................................... 7 1.1 Background information ............................................................................................... 7 1.2 Lifecycle and transmission patterns ............................................................................. 7 1.3 Human infection and disease ....................................................................................... 8 2. Diagnosis ..............................................................................................................................
    [Show full text]
  • Public Health Goal for ANTIMONY in Drinking Water
    Public Health Goal for ANTIMONY in Drinking Water Prepared by Pesticide and Environmental Toxicology Section Office of Environmental Health Hazard Assessment California Environmental Protection Agency December 1997 LIST OF CONTRIBUTORS PHG PROJECT MANAGEMENT REPORT PREPARATION SUPPORT Project Officer Author Administrative Support Anna Fan, Ph.D. Lubow Jowa, Ph.D. Edna Hernandez Coordinator Chemical Prioritization Primary Reviewer Laurie Bliss Report Outline Robert Brodberg, Ph.D. Sharon Davis Joseph Brown, Ph.D. Kathy Elliott Coordinator Secondary Reviewer Vickie Grayson David Morry, Ph.D. Michael DiBartolomeis, Ph.D. Michelle Johnson Yi Wang, Ph.D. Juliet Rafol Final Reviewers Genevieve Shafer Document Development Anna Fan, Ph.D. Tonya Turner Michael DiBartolomeis, Ph.D. William Vance, Ph.D. Coordinator Library Support George Alexeeff, Ph.D. Editor Mary Ann Mahoney Hanafi Russell, M.S. Michael DiBartolomeis, Ph.D. Valerie Walter Yi Wang, Ph.D. Website Posting Public Workshop Robert Brodberg, Ph.D. Michael DiBartolomeis, Ph.D. Edna Hernandez Coordinator Laurie Monserrat, M.S. Judy Polakoff, M.S. Judy Polakoff, M.S. Organizer Hanafi Russell, M.S. Methodology/Approaches/ Review Comments Joseph Brown, Ph.D. Robert Howd, Ph.D. Coordinators Lubow Jowa, Ph.D. David Morry, Ph.D. Rajpal Tomar, Ph.D. Yi Wang, Ph.D. We thank the U.S. EPA’s Office of Water, Office of Pollution Prevention and Toxic Substances, and National Center for Environmental Assessment for their peer review of the PHG documents, and the comments received from all interested parties. ANTIMONY in Drinking Water ii December 1997 California Public Health Goal (PHG) PREFACE Drinking Water Public Health Goal of the Office of Environmental Health Hazard Assessment This Public Health Goal (PHG) technical support document provides information on health effects from contaminants in drinking water.
    [Show full text]
  • 204684Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 204684Orig1s000 MEDICAL REVIEW(S) Clinical Investigator Financial Disclosure Review Template Application Number: 204684 Submission Date(s): September 27, 2012 and April 19, 2013 Applicant: Paladin Therapeutics, Inc. Product: IMPAVIDO (miltefosine) Reviewer: Hala Shamsuddin, M.D. Date of Review: February 24, 2014 Covered Clinical Study (Name and/or Number): Study 3154 Study 3168 Study Z020a and b Study SOTO Study Z022 Dutch PK study Was a list of clinical investigators provided: Yes X No (Request list from applicant) Total number of investigators identified: Six (6) Number of investigators who are sponsor employees (including both full-time and part-time employees): None Number of investigators with disclosable financial interests/arrangements (Form FDA 3455): Six (6) If there are investigators with disclosable financial interests/arrangements, identify the number of investigators with interests/arrangements in each category (as defined in 21 CFR 54.2(a), (b), (c) and (f)): Compensation to the investigator for conducting the study where the value could be influenced by the outcome of the study: None Significant payments of other sorts: None Proprietary interest in the product tested held by investigator: None Significant equity interest held by investigator in sponsor of covered study: None Is an attachment provided with details Yes X No (Request details from of the disclosable financial applicant) interests/arrangements: Is a description of the steps taken to Yes X No (Request information minimize potential bias provided: from applicant) Number of investigators with certification of due diligence (Form FDA 3454, box 3) None Is an attachment provided with the NA No (Request explanation Reference ID: 3464181 reason: from applicant) Discuss whether the applicant has adequately disclosed financial interests/arrangements with clinical investigators as recommended in the guidance for industry Financial Disclosure by Clinical Investigators.
    [Show full text]
  • Tapeworm Infection1.Qxd
    Page 1 of 2 TAPEWORM infection Drug Adult dosage Pediatric dosage — Adult (intestinal stage) Diphyllobothrium latum (fish), Taenia saginata (beef), Taenia solium (pork), Dipylidium caninum (dog) Drug of choice: Praziquantel1,2 5-10 mg/kg PO once 5-10 mg/kg PO once Alternative: Niclosamide3* 2 g PO once 50 mg/kg PO once Hymenolepis nana (dwarf tapeworm) Drug of choice: Praziquantel1,2 25 mg/kg PO once 25 mg/kg PO once Alternative: Nitazoxanide1,4 500 mg PO once/d or bid x 3d5 1-3yrs: 100 mg PO bid x 3d5 4-11yrs: 200 mg PO bid x 3d5 — Larval (tissue stage) Echinococcus granulosus (hydatid cyst) Drug of choice:6 Albendazole7 400 mg PO bid x 1-6mos 15 mg/kg/d (max. 800 mg) x 1-6mos Echinococcus multilocularis Treatment of choice: See footnote 8 Taenia solium (Cysticercosis) Treatment of choice: See footnote 9 Alternative: Albendazole7 400 mg PO bid x 8-30d; can be 15 mg/kg/d (max. 800 mg) PO in repeated as necessary 2 doses x 8-30d; can be repeated as necessary OR Praziquantel1,2 100 mg/kg/d PO in 3 doses x 100 mg/kg/d PO in 3 doses x 1 day then 50 mg/kg/d in 1 day then 50 mg/kg/d in 3 doses x 29 days 3 doses x 29 days * Availability problems. See table below. 1. Not FDA-approved for this indication. 2. Praziquantel should be taken with liquids during a meal. 3. Niclosamide must be chewed thoroughly before swallowing and washed down with water.
    [Show full text]
  • The Selection and Use of Essential Medicines
    WHO Technical Report Series 958 THE SELECTION AND USE OF ESSENTIAL MEDICINES This report presents the recommendations of the WHO Expert THE SELECTION AND USE Committee responsible for updating the WHO Model List of Essential Medicines. The fi rst part contains a review of the OF ESSENTIAL MEDICINES report of the meeting of the Expert Subcommittee on the Selection and Use of Essential Medicines, held in October 2008. It also provides details of new applications for paediatric medicines and summarizes the Committee’s considerations and justifi cations for additions and changes to the Model List, including its recommendations. Part Two of the publication is the report of the second meeting of the Subcommittee of the Expert Committee on the Selection and Use of Essential Medicines. Annexes include the revised version of the WHO Model List of Essential Medicines (the 16th) and the revised version of the WHO Model List of Report of the WHO Expert Committee, 2009 Essential Medicines for Children (the 2nd). In addition there is a list of all the items on the Model List sorted according to their (including the 16th WHO Model List of Essential Medicines Anatomical Therapeutic Chemical (ATC) classifi cation codes. and the 2nd WHO Model List of Essential Medicines for Children) WHO Technical Report Series — 958 WHO Technical ISBN 978-92-4-120958-8 Geneva TTRS958cover.inddRS958cover.indd 1 110.06.100.06.10 008:328:32 The World Health Organization was established in 1948 as a specialized agency of the United Nations serving as the directing and coordinating authority for SELECTED WHO PUBLICATIONS OF RELATED INTEREST international health matters and public health.
    [Show full text]
  • The Medical Letter
    Page 1 of 2 TOXOPLASMOSIS (Toxoplasma gondii) Drug Adult dosage Pediatric dosage Drug of choice:1 Pyrimethamine2 25-100 mg/d PO x 3-4 wks 2 mg/kg/d PO x 2d, then 1 mg/kg/d plus (max. 25 mg/d) x 4 wks3 sulfadiazine4 1-1.5 g PO qid x 3-4 wks 100-200 mg/kg/d PO x 3-4 wks 1. To treat CNS toxoplasmosis in HIV-infected patients, some clinicians have used pyrimethamine 50-100 mg/d (after a loading dose of 200 mg) with sulfadiazine and, when sulfonamide sensitivity developed, have given clindamycin 1.8-2.4 g/d in divided doses instead of the sulfonamide. Treatment is usually given for at least 4-6 weeks. Atovaquone (1500 mg PO bid) plus pyrimethamine (200 mg loading dose, followed by 75 mg/d PO) for 6 weeks appears to be an effective alternative in sulfa-intolerant patients (K Chirgwin et al, Clin Infect Dis 2002; 34:1243). Atovaquone must be taken with a meal to enhance absorption. Treatment is followed by chronic suppression with lower dosage regimens of the same drugs. For primary prophylaxis in HIV patients with <100 x 106/L CD4 cells, either trimethoprim-sulfamethoxazole, pyrimethamine with dapsone, or atovaquone with or without pyrimethamine can be used. Primary or secondary prophylaxis may be discontinued when the CD4 count increases to >200 x 106/L for >3mos (MMWR Morb Mortal Wkly Rep 2004; 53 [RR15]:1). In ocular toxoplasmosis with macular involvement, corticosteroids are recommended in addi- tion to antiparasitic therapy for an anti-inflammatory effect.
    [Show full text]
  • Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: a Systematic Review
    Clin Pharmacokinet DOI 10.1007/s40262-016-0467-3 SYSTEMATIC REVIEW Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review 1 1,2 Luka Verrest • Thomas P. C. Dorlo Ó The Author(s) 2016. This article is published with open access at Springerlink.com Abstract Methods PubMed was systematically searched for all Introduction Neglected tropical diseases (NTDs) affect clinical trials and case reports until the end of 2015 that more than one billion people, mainly living in developing described the pharmacokinetics of a drug in the context of countries. For most of these NTDs, treatment is subopti- treating any of the NTDs in patients or healthy volunteers. mal. To optimize treatment regimens, clinical pharma- Results Eighty-two pharmacokinetic studies were identi- cokinetic studies are required where they have not been fied. Most studies included small patient numbers (only previously conducted to enable the use of pharmacometric five studies included [50 subjects) and only nine (11 %) modeling and simulation techniques in their application, studies included pediatric patients. A large part of the which can provide substantial advantages. studies was not very recent; 56 % of studies were published Objectives Our aim was to provide a systematic overview before 2000. Most studies applied non-compartmental and summary of all clinical pharmacokinetic studies in analysis methods for pharmacokinetic analysis (62 %). NTDs and to assess the use of pharmacometrics in these Twelve studies used population-based compartmental studies, as well as to identify which of the NTDs or which analysis (15 %) and eight (10 %) additionally performed treatments have not been sufficiently studied.
    [Show full text]
  • Comparative Efficacy of Intra-Lesional Sodium Stibogluconate
    Original Article COMPARATIVE EFFICACY OF INTRA LESIONAL SODIUM STIBOGLUCONATE AND INTRA LESIONAL CHLOROQUIN IN THE TREATMENT OF CUTANEOUS LEISHMANIASIS IN A TERTIARY CARE TEACHING HOSPITAL: A RANDOMIZED CONTROLLED TRIAL Malik Muhammad Hanif,1 Ghulam Mustafa,2 Nasir Mehmood,1 Khizra Akram1 ABSTRACT Background: Pentavalent antimonials are the agents recommended for treatment of cutaneous leishmaniasis (CL). Its use is problematic, because it is expensive, not easily available and because of the potential for drug-associated adverse effects during a lengthy and painful treatment course. Objective: The objective of this study was to compare the effect of intra-lesional chloroquine with intra-lesional sodium stibogluconate in the treatment of cutaneous leishmaniasis. Material and Methods: In this randomized controlled trial, we tested and compared the efficacy of Intralesional Chloroquine with that of intralesional sodium stibogluconate (SSG) for the treatment of CL. We enrolled 50 patients of CL with a single to multiple lesions of various sizes, divided them in group A and B and randomly administered chloroquine or sodium stibogluconate (SSG), intralesional twice weekly (total number of injections and duration of treatment depending on the size and number of lesions). Duration of Study: This study was conducted from1st March, 2010 to 31st September, 2010. Results: Cure occurred in 100 % patients in both groups towards end of the treatment. Mean cost of the treatment per patient in the present study was found to be very high for SSG group (Rs. 5664± 186), as compared to chloroquine group (Rs. 68.4±9) with a p value of <0.000. Mean number of inj. given in SSG group was 14±4.6 as compared to13.6±5.5 in chloroquine group.
    [Show full text]
  • Common Study Protocol for Observational Database Studies WP5 – Analytic Database Studies
    Arrhythmogenic potential of drugs FP7-HEALTH-241679 http://www.aritmo-project.org/ Common Study Protocol for Observational Database Studies WP5 – Analytic Database Studies V 1.3 Draft Lead beneficiary: EMC Date: 03/01/2010 Nature: Report Dissemination level: D5.2 Report on Common Study Protocol for Observational Database Studies WP5: Conduct of Additional Observational Security: Studies. Author(s): Gianluca Trifiro’ (EMC), Giampiero Version: v1.1– 2/85 Mazzaglia (F-SIMG) Draft TABLE OF CONTENTS DOCUMENT INFOOMATION AND HISTORY ...........................................................................4 DEFINITIONS .................................................... ERRORE. IL SEGNALIBRO NON È DEFINITO. ABBREVIATIONS ......................................................................................................................6 1. BACKGROUND .................................................................................................................7 2. STUDY OBJECTIVES................................ ERRORE. IL SEGNALIBRO NON È DEFINITO. 3. METHODS ..........................................................................................................................8 3.1.STUDY DESIGN ....................................................................................................................8 3.2.DATA SOURCES ..................................................................................................................9 3.2.1. IPCI Database .....................................................................................................9
    [Show full text]