Prevention of Post-Metronidazole Candidosis with Amphotericin B Pessaries*

Total Page:16

File Type:pdf, Size:1020Kb

Prevention of Post-Metronidazole Candidosis with Amphotericin B Pessaries* Br J Vener Dis: first published as 10.1136/sti.45.2.163 on 1 June 1969. Downloaded from Brit. J. vener. Dis. (1969), 45, 163 PREVENTION OF POST-METRONIDAZOLE CANDIDOSIS WITH AMPHOTERICIN B PESSARIES* BY LEONARD Z. OLLER St. Luke's Hospital, Bradford Trichomonas vaginalis and Candida albicans are vagina in about 80 per cent. of cases treated with the two organisms most commonly responsible for one pessary nightly for 14 days. Although similar an excessive irritating vaginal discharge (Danezis results, a cure rate of 78 per cent., were attained and Marsellou, 1960). It has been suggested that in by Csonka (1967), he found Nystatin somewhat the last few years, as a result of the widespread more effective when comparing the effect of one use of antibiotics, Candida infection has become amphotericin B pessary with that of two Nystatin the principal cause of vulvovaginitis (Rohatiner, pessaries inserted nightly for 15 days. 1966; Rohatiner and Grimble, 1967). Metronida- zole has also been incriminated in this way. Vaginal Clinical Material and Methods candidosis developed during treatment in three of copyright. At the Venereal Diseases Clinic, St. Luke's Hospital, 42 women treated with the drug by Moffett and Bradford, during a period of 4 months in 1966 and one McGill (1960), giving rise in two cases to severe or of 5 months in 1967 (with an interval of 7 months during moderately severe symptoms. The number of which the clinic was under reconstruction), 113 women patients with C. albicans demonstrated in the were found at some stage of their attendance to have a vaginal discharge after treatment with metronida- trichomonal infestation. T. vaginalis was identified in zole increased by 24-5 per cent. in 102 cases treated the vaginal secretion by wet smear examined micro- by Keighley (1962), by 19 per cent. in 100 treated scopically by direct light, by culture, or by a Papanicolou- http://sti.bmj.com/ by Beveridge (1962), by 11 per cent. in 101 treated stained smear in those cases in which specimens for by Csonka (1963), and by 4-4 per cent. in 69 treated routine cytological screening were collected at the same time. High vaginal swabs were submitted in non- by Brochin and Buxton (1963). On the other hand nutrient transport medium to the laboratory where the neither Rees (1960) nor Rodin, King, Nicol, and growth medium (Oxoid Trichomonas medium No. 2) Barrow (1960) found any evidence to suggest that was inoculated for both T. vaginalis and C. albicans. the drug favoured or inhibited the growth of Similar methods of identification of the two organisms Candida species. were used at follow-up examinations. on September 27, 2021 by guest. Protected In an attempt to prevent post-metronidazole As soon as the diagnosis of trichomoniasis was candidosis, Beveridge (1964) prescribed a Nystatin established, treatment was started as follows: 58 pessary to be inserted nightly during the week women were given a supply of metronidazole (Flagyl) metronidazole was taken; she succeeded in reducing comprising 21 200-mg. tablets to be taken 8-hourly for the post-treatment incidence of fungus infection one week (first group), and 53, who were seen at one of from 19 to 7 per cent., but considered the result four selected clinical sessions, were given in addition disappointing. seven 50-mg. amphotericin B vaginal pessaries, one to be In this paper the results are reported of a similar inserted each night during that week (second group). attempt, using pessaries containing 50 mg. ampho- Table I (overleaf) shows the duration of the follow-up tericin B, a polyene antifungal antibiotic reported to period. be more active in vitro against Candida species than Eighteen women did not return after treatment, leaving Nystatin (Ewing, 1967). In clinical trials ampho- for assessment 51 in the first group and 42 in the second. tericin B (Fungilin) was reported by Ewing (1967) Irrespective of the length of the follow-up period, to be successful in eliminating Candida from the 30 patients attended only once from 7 to 32 days after completing treatment, 29 had two follow-up examina- *Received for publication September 2, 1968. tions, twenty had three, and fourteen had four or more. 163 Br J Vener Dis: first published as 10.1136/sti.45.2.163 on 1 June 1969. Downloaded from 164 BRITISH3OURNAL OF VENEREAL DISEASES TABLE I TABLE III LENGTH OF FOLLOW-UP AFTER TREATMENT LABORATORY FINDINGS BEFORE AND AFTER TREATMENT Number of Patients Treated Follow-up Metronidazole + Metronidazole + Initial Metronidazole Amphotericin B Metronidazole Amphotericin B Laboratory Findings No. of No. of No further attendance 7 11 Swabs Percentage Swabs Percentage Up to 2 wks 13 3 T. vaginalis only 31 60-8 22 52-4 T. vaginalis + 2 wks to 1 mth 21 10 Gonococci 15 29-4 11 26-2 T.vaginalis + 1 mth to 2 mths 13 10 Candidaalbicans 5 9*8 8 19.0 T. vaginalis + 3 m:hs 4 19 Gonococci + 2 Candida albicans - 0 1 2*4 Total assessable 51 42 Total 51 100 0 42 100 0 Candida before The age groups and marital status of the 93 patients Therapy 5 9*8 9 21*4 are shown in Table II. Two women, one in each group, Candida after were taking oral contraceptives. Eight women in the Therapy 15 29-4 6 14-2 first group and six in the second were pregnant. There Effect of Therapy on Candida 10 19-6 3 7-2 were no cases of glycosuria. Increase Decrease TABLE II AVERAGE AGE AND MARITAL STATUS OF PATIENTS (per cent.) three of those with pre-treatment evidence of the fungus. Three women had symptoms and clinical Metronidazole + Metronidazole Amphotericin B evidence of Candida infection (pruritus vulvae and Treatment.. inflammation of the vulva and vagina with profuse No. in Average No. in Average copyright. Group Age Group Age cheesy vaginal discharge); in only one of them, a Under 20 14 17-9 11 17-8 pregnant woman, was the fungus detected before 28 24-3 18 23-9 treatment, but one other had been treated for Age 30-3920-29 7 33*3 11 34-1 Group 40-49 2 44*5 2 44*0 vaginal candidosis 4 months previously. These (yrs) Total 51 24-5 42 25*6 three women required treatment and were success- fully treated with amphotericin B pessaries inserted Single 30 58-8 21 50 Married 13 11 26-2 nightly for 15 days. 25*5 http://sti.bmj.com/ Marital Divorced treated with metronidazole in Status Separatede 8 15*7 10 23-8 In the group Widowed J conjunction with pessaries, Candida was detected Total 51 100-0 42 100-0 before treatment in nine women and after treatment in six women, three of them pregnant. The fungus was found both before and after treatment in only Fifty-one patients had a gonococcal infection and in one case. None of the women in this group 26 cases (15 in the first group and 11 in the second) the showed clinical evidence of Candida infection. diagnosis of gonorrhoea was established on the same on September 27, 2021 by guest. Protected occasion as that of trichomoniasis; these 26 patients Seven of the 21 patients with post-treatment received anti-gonorrhoeal treatment during the period occurrence of Candida had been treated for gonorr- metronidazole was taken. Eight (in 1966) were given hoea initially, six with penicillin and one with one dose and thirteen (in 1967) two doses on successive cephaloridine, which was more or less in proportion days of 1-2 mega-units aqueous procaine penicillin (the to the total number under study. In the woman in routine clinic treatment for women with gonorrhoea in the first group who was taking the contraceptive the respective years); four were treated with single pill, Candida was found after but not before treat- injections of 2 g. cephaloridine and one with an injection ment; in the woman on oral contraceptives in the of 2 g. kanamycin. second group, Candida was absent throughout. Results The initial laboratory findings and the incidence Discussion of Candida in the vaginal secretions before and Winner (1966) defines Candida as yeast-like after treatment are shown in Table III. fungi which frequently inhabit the human body In the group treated with metronidazole alone, without causing disease, which occasionally cause Candida was detected before treatment in five cases; mild disease, and which rarely cause serious disease. after treatment it was found in fifteen, including The reported frequency of occurrence of Candida Br J Vener Dis: first published as 10.1136/sti.45.2.163 on 1 June 1969. Downloaded from PREVENTION OF CANDIDOSIS 165 in the vagina varies widely. Pickhardt and Breen in addition to metronidazole 200 mg. 8-hourly for (1957) compiled reports from eleven investigators the same period. For comparison, 58 women with which gave the incidence of vaginal candidosis with trichomoniasis were treated with metronidazole and without symptoms as ranging from 0-08 to alone. 42 of those receiving the combined treatment 61-7 per cent. in non-pregnant women and from and 51 of those receiving metronidazole alone were 0 74 to 66-7 per cent. in pregnant women; the available for assessment. average was 17-6 per cent. in a total of 13,450 non- The percentage of vaginal swabs from which C. pregnant and 30 2 per cent. in a total of 5,305 albicans was cultured decreased by seven after pregnant women. These figures are somewhat combined treatment and increased by nineteen higher than the 16 and 25 per cent. in non-pregnant after treatment with metronidazole alone.
Recommended publications
  • Tetracycline and Sulfonamide Antibiotics in Soils: Presence, Fate and Environmental Risks
    processes Review Tetracycline and Sulfonamide Antibiotics in Soils: Presence, Fate and Environmental Risks Manuel Conde-Cid 1, Avelino Núñez-Delgado 2 , María José Fernández-Sanjurjo 2 , Esperanza Álvarez-Rodríguez 2, David Fernández-Calviño 1,* and Manuel Arias-Estévez 1 1 Soil Science and Agricultural Chemistry, Faculty Sciences, University Vigo, 32004 Ourense, Spain; [email protected] (M.C.-C.); [email protected] (M.A.-E.) 2 Department Soil Science and Agricultural Chemistry, Engineering Polytechnic School, University Santiago de Compostela, 27002 Lugo, Spain; [email protected] (A.N.-D.); [email protected] (M.J.F.-S.); [email protected] (E.Á.-R.) * Correspondence: [email protected] Received: 30 October 2020; Accepted: 13 November 2020; Published: 17 November 2020 Abstract: Veterinary antibiotics are widely used worldwide to treat and prevent infectious diseases, as well as (in countries where allowed) to promote growth and improve feeding efficiency of food-producing animals in livestock activities. Among the different antibiotic classes, tetracyclines and sulfonamides are two of the most used for veterinary proposals. Due to the fact that these compounds are poorly absorbed in the gut of animals, a significant proportion (up to ~90%) of them are excreted unchanged, thus reaching the environment mainly through the application of manures and slurries as fertilizers in agricultural fields. Once in the soil, antibiotics are subjected to a series of physicochemical and biological processes, which depend both on the antibiotic nature and soil characteristics. Adsorption/desorption to soil particles and degradation are the main processes that will affect the persistence, bioavailability, and environmental fate of these pollutants, thus determining their potential impacts and risks on human and ecological health.
    [Show full text]
  • Sexually Transmitted Diseases Treatment Options
    Sexually transmitted disease (STD) treatment options PREFERRED & ALTERNATIVE OPTIONS Many clinical partners are operating in a limited capacity during the COVID-19 pandemic. Below are preferred (in clinic or other location where injections can be given) and alternative (when only oral medicines are available 1) treatments for STDs. Syndrome Preferred Treatments Alternative Treatments Follow-up Male urethritis syndrome Ceftriaxone 250mg intramuscular (IM) x 1 PLUS Men who have sex with men (MSM) and transgender women2: Patients should be counseled to azithromycin 1g PO x 1 Cefixime 800 mg PO x 1 PLUS doxycycline 100 mg PO BID x 7 days be tested for STDs once clinical Presumptively treating: care is resumed in the local If azithromycin is not available: doxycycline 100 Men who have sex with women only: gonorrhea clinics. Clients who have been mg PO BID for 7 days (except in pregnancy3) Cefixime 800mg PO x 1 PLUS azithromycin 1g PO x 1 referred for oral treatment If cephalosporin allergy5 is reported, gentamicin If cefixime is unavailable, substitute cefpodoxime 400mg PO q12h should return for 240mg IM x 1 PLUS azithromycin 2g PO x 1 x 2 for cefixime in above regimens4 comprehensive testing and screening and linked to services If oral cephalosporin not available or history of cephalosporin at that time. allergy5: azithromycin 2g PO x 1 If azithromycin is not available: doxycycline 100 mg PO BID for 7 days (except in pregnancy3) Patients should be advised to abstain from sex for 7 days Treatment typically guided by examination and For presumptive therapy when examination and laboratory following completion of Vaginal discharge syndrome treatment.
    [Show full text]
  • The Nitroimidazole Family of Drugs
    Br J Vener Dis: first published as 10.1136/sti.54.2.69 on 1 April 1978. Downloaded from British Journal of Venereal Diseases, 1978, 54, 69-71 Editorial The nitroimidazole family of drugs In 1955 an antibiotic complex isolated from a operative infection caused by susceptible anaerobes, strain of Streptomyces on the island of Reunion particularly in gynaecological surgery, appendi- was found by research workers of Rhone-Poulenc in cectomy, and colonic surgery. Paris to contain a trichomonacidal antibiotic- Real innovations in chemotherapy, such as azomycin. It had previously been isolated in Japan metronidazole, always attract attention from other (Maeda et al., 1953) and identified as 2-nitroimi- research groups. Although interest was slow to dazole (Ia see Table) (Nakamura, 1955). At the develop, research workers have sought analogous, time, and for some years after, this remarkably structurally-modified compounds which might afford simple compound defied synthesis, but it stimulated some advantage in clinical use-for example, the workers at Rhone-Poulenc to prepare and test greater potency, better tolerance and freedom from the activity of the more readily accessible isomeric side effects, a broader spectrum of action, a longer 5-nitroimidazoles (II). It was their good fortune in duration of action, or in some other characteristic. 1957 to find that these isomers were more active This effort has been concerned with important antiprotozoal agents than the natural product veterinary uses of 5-nitroimidazoles as well as the (Cosar and Julou, 1959). In a series of 150 related applications in human medicine. compounds, the one with a P-hydroxyethyl group Metronidazole has been a difficult target to in the 1-position gave the best compromise between improve upon, but several other drugs of this activity and toxicity and this brand of metroni- chemical family have been introduced to clinical dazole was introduced as Flagyl.
    [Show full text]
  • Common Oral Antibiotics for Horses Antibiotics Are Commonly Used In
    Common Oral Antibiotics for Horses Antibiotics are commonly used in horses for a variety of conditions. In order to determine which antibiotic is appropriate for a specific condition, a culture of the affected area needs to be performed. The culture is sent to a lab where the bacteria are grown and identified. A sensitivity test is then performed to find out which antibiotics will be effective. Some of the more common oral antibiotics in horses include trimethoprim sulfa, metronidazole, enrofloxacin, and chloramphenicol. Trimethoprim sulfa (SMZ, TMS, sulfa tabs) is an antibiotic which has a broad spectrum of activity against a variety of bacteria. It is broken down by the liver and excreted in the urine. Side effects of this drug include diarrhea, allergic reactions, and effects on the blood, including decreased number of red blood cells (anemia), decreased number of platelets (thrombocytopenia), and decreased number of white blood cells (leucopenia). Trimethoprim sulfa commonly comes in 960mg tablets. The dose range for horses is 15-30 mg/kg. Generally, 10 tablets administered orally for a 1000lb horse is effective. This medication is given twice a day (every 12 hours) and is best absorbed if given without food. Trimethoprim sulfa may be prescribed by your veterinarian for simple wounds, such as those on the face or legs. Metronidazole is an antibiotic commonly used for anaerobic (bacteria which can grow in the absence of oxygen) infections. For example, deep puncture wounds, respiratory infections, peritonitis, soft tissue infections, and abscesses are infections that often involve anaerobic bacteria.. It is broken down by the liver and excreted in the urine and in the feces.
    [Show full text]
  • Antibiotics and Antibiotic Resistance
    This is a free sample of content from Antibiotics and Antibiotic Resistance. Click here for more information on how to buy the book. Index A Antifolates. See also specific drugs AAC(60)-Ib-cr, 185 novel compounds, 378–379 ACHN-975 overview, 373–374 clinical studies, 163–164 resistance mechanisms medicinal chemistry, 166 sulfamethoxazole, 378 structure, 162 trimethoprim, 374–378 AcrAB-TolC, 180 Apramycin, structure, 230 AcrD, 236 Arbekacin, 237–238 AdeRS, 257 Avibactam, structure, 38 AFN-1252 Azithromycin mechanism of action, 148, 153 resistance, 291, 295 resistance, 153 structure, 272 structure, 149 Aztreonam, structure, 36 AIM-1, 74 Amicoumacin A, 222 Amikacin B indications, 240 BaeSR, 257 structure, 230 BAL30072, 36 synthesis, 4 BB-78495, 162 Aminoglycosides. See also specific drugs BC-3205, 341, 344 historical perspective, 229–230 BC-7013, 341, 344 indications, 239–241 b-Lactamase. See also specific enzymes mechanism of action, 232 classification novel drugs, 237 class A, 67–71 pharmacodynamics, 238–239 class B, 69–74 pharmacokinetics, 238–239 class C, 69, 74 resistance mechanisms class D, 70, 74–77 aminoglycoside-modifying enzymes evolution of antibiotic resistance, 4 acetyltransferases, 233–235 historical perspective, 67 nucleotidyltransferases, 235 inhibitors phosphotransferases, 235 overview, 37–39 efflux-mediated resistance, 236 structures, 38 molecular epidemiology, 236–237 nomenclature, 67 overview, 17, 233 b-Lactams. See also specific classes and antibiotics ribosomal RNA modifications, 235–236 Enterococcus faecium–resistancemechanisms,
    [Show full text]
  • The Role of Nitroreductases in Resistance to Nitroimidazoles
    biology Review The Role of Nitroreductases in Resistance to Nitroimidazoles Carol Thomas 1 and Christopher D. Gwenin 2,* 1 School of Natural Sciences, Bangor University, Bangor LL57 2UW, UK; [email protected] 2 Department of Chemistry, Xi’an Jiaotong-Liverpool University, 111 Ren’ai Road, Suzhou Industrial Park, Suzhou 215123, China * Correspondence: [email protected]; Tel.: +86-(0)512-81888710 Simple Summary: Antimicrobial resistance continues to be a major global health threat. It is estimated by the WHO that 700,000 people die each year because of drug resistance, and this is predicted to rise to 10 million by 2050. As well as the increased cost, which is forecast to exceed $100 trillion, as more expensive drugs have to be deployed, illnesses often last longer and require hospital treatment. This, in turn, increases the strain on often-inadequate healthcare systems. As resistances continue to grow, finding alternatives is crucial. This review showed that nitroreductases play a role in drug activation but are also associated with resistance mechanisms. These mechanisms require further investigation to fully understand them before they can be utilised against multidrug- resistant organisms. This will depend on committed collaborations between the private and public sector to translate academic research into the clinic. Abstract: Antimicrobial resistance is a major challenge facing modern medicine, with an estimated 700,000 people dying annually and a global cost in excess of $100 trillion. This has led to an increased need to develop new, effective treatments. This review focuses on nitroimidazoles, which have seen a resurgence in interest due to their broad spectrum of activity against anaerobic Gram-negative and Gram-positive bacteria.
    [Show full text]
  • Antimicrobial Resistance in Bacteria
    Cent. Eur. J. Med. • 4(2) • 2009 • 141-155 DOI: 10.2478/s11536-008-0088-9 Central European Journal of Medicine Antimicrobial resistance in bacteria Review Article Katrijn Bockstael*, Arthur Van Aerschot** Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium Received 9 July 2008; Accepted 17 November 2008 Abstract: The development of antimicrobial resistance by bacteria is inevitable and is considered as a major problem in the treatment of bacterial infections in the hospital and in the community. Despite efforts to develop new therapeutics that interact with new targets, resistance has been reported even to these agents. In this review, an overview is given of the many therapeutic possibilities that exist for treatment of bacterial infections and how bacteria become resistant to these therapeutics. Keywords: Antimicrobial agents • Resistance development • Efflux • Alteration of drug target • Antibacterials © Versita Warsaw and Springer-Verlag Berlin Heidelberg. 1. Introduction 2. Different mechanisms of resistance to antimicrobials The history of humankind can be regarded from a medical point of view as a struggle against infectious 2.1. Intrinsic resistance diseases. Infections were the leading cause of death Bacteria may be inherently resistant to an antimicrobial. th worldwide at the beginning of the 20 century. Since This passive resistance is a consequence of general the discovery of penicillin by Alexander Fleming in adaptive processes that are not necessary linked to a 1929 and the first introduction of the sulpha drugs by given class of antimicrobials. An example of natural Domagk in 1932, the number of new antimicrobials resistance is Pseudomonas aeruginosa, whose low available has increased tremendously between 1940 membrane permeability is likely to be a main reason for and 1960.
    [Show full text]
  • Challenges of Antibacterial Discovery Lynn L
    CLINICAL MICROBIOLOGY REVIEWS, Jan. 2011, p. 71–109 Vol. 24, No. 1 0893-8512/11/$12.00 doi:10.1128/CMR.00030-10 Copyright © 2011, American Society for Microbiology. All Rights Reserved. Challenges of Antibacterial Discovery Lynn L. Silver* LL Silver Consulting, LLC, 955 S. Springfield Ave., Unit C403, Springfield, New Jersey 07081 INTRODUCTION .........................................................................................................................................................72 The Discovery Void...................................................................................................................................................72 Class Modifications versus Novel Classes.............................................................................................................72 BACKGROUND............................................................................................................................................................72 Early Screening—a Brief and Biased Philosophical History .............................................................................72 The Rate-Limiting Steps of Antibacterial Discovery ...........................................................................................74 The Multitarget Hypothesis ....................................................................................................................................74 ANTIBACTERIAL RESISTANCE ..............................................................................................................................75
    [Show full text]
  • Rifaximin Preserves Intestinal Microbiota Balance in Patients Undergoing Allogeneic Stem Cell Transplantation
    Bone Marrow Transplantation (2016) 51, 1087–1092 © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0268-3369/16 www.nature.com/bmt ORIGINAL ARTICLE Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation D Weber1, PJ Oefner2, K Dettmer2, A Hiergeist3, J Koestler3, A Gessner3, M Weber4, F Stämmler5, J Hahn1, D Wolff1, W Herr1 and E Holler1 Intestinal dysbiosis has been associated with acute gastrointestinal GvHD and poor outcome following allogeneic stem cell transplantation (ASCT). To assess the effect of a switch in 2012 from ciprofloxacin/metronidazole to rifaximin for gut decontamination on intestinal microbiota composition and ASCT outcome, we retrospectively analyzed 394 patients receiving ASCT from September 2008 through June 2015. In 131 and 90 patients, respectively, urinary 3-indoxyl sulfate levels and intestinal enterococcal load were measured before conditioning and weekly within the first 28 days after ASCT. The use of rifaximin correlated with lower enterococcal positivity (6.9 vs 21.9%, P=0.05) and higher urinary 3-indoxyl sulfate concentrations (10.5 vs 4.6 μmoL/mmoL crea, Po0.001) after ASCT. Patients on rifaximin showed lower 1-year transplant-related mortality (P=0.04) and higher overall survival (P=0.008). Treatment of infectious complications with systemic antibiotics did not abrogate the beneficial effects of rifaximin on intestinal microbiota composition in the early course of ASCT and outcome. The data underscore the importance of
    [Show full text]
  • Stability of Resistance and Extended Potential of Targeting the Folate Synthesis
    Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 45 Microbial Responses to Antibiotics – Stability of Resistance and Extended Potential of Targeting the Folate Synthesis MARIA JÖNSSON ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 UPPSALA ISBN 91-554-6268-5 2005 urn:nbn:se:uu:diva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ist of Papers This thesis is based on the following papers, which will be referred to in the text by their roman numerals. I Clarithromycin treatment selects for persistent macrolide-
    [Show full text]
  • Drug Repositioning in the Treatment of Malaria and TB
    REVIEW SPECIAL FOCUS: NEGLECTED DISEASES For reprint orders, please contact [email protected] Drug repositioning in the treatment of malaria and TB The emergence and spread of drug resistance in the malaria parasite Plasmodium falciparum as well as multi- and extremely drug-resistant forms of Mycobacterium tuberculosis, the causative agent of TB, could hamper the control of these diseases. For instance, there are indications that the malaria parasite is becoming resistant to artemisinin derivatives, drugs that form the backbone of antimalarial combination therapy. Likewise, Mycobacterium tuberculosis strains that are multidrug-resistant or extremely drug-resistant to first- and second-line drugs have been associated with increased mortality. Thus, more than ever, new antimalarials and anti-TB drugs are needed. One of the strategies to discover new drugs is to reposition or repurpose existing drugs, thus reducing the cost and time of drug development. In this review, we discuss how this concept has been used in the past to discover antimalarial and anti-TB drugs, and summarize strategies that can lead to the discovery and development of new drugs. Malaria and TB are the two leading causes of been proposed as an alternative. However, the Alexis Nzila1†, Zhenkun Ma2 mortally worldwide, killing approximately two paucity of available antimalarials limits this & Kelly Chibale1 million people annually [1]. Strategies to control strategy. More than ever, new antimalarials are 1University of Cape Town, and manage these two diseases rest primarily on urgently needed. Departments of Chemistry and Clinical Pharmacology and Institute of the use of effective drugs. The combination of isoniazid, rifampicin, Infectious Disease and Molecular In the case of malaria, the WHO has rec- pyrazinamide and ethambutol has been the cor- Medicine, University of Cape Town, Rondebosch 7701, South Africa ommended the use of artemisinin combina- nerstone of first-line TB treatment.
    [Show full text]
  • Rifaximin New Medicine Assessment Approved
    New Medicine Assessment Rifaximin as second line antibacterial treatment for the treatment of Small Intestinal Bacterial Overgrowth Recommendation: RED Medicine is supplied by the hospital for the duration of the treatment course. Primary care initiation or continuation of treatment is not recommended unless exceptional circumstances such as specialist GP. Red medicines are those where primary care prescribing is not recommended. These treatments should be initiated by specialists only and prescribing retained within secondary care. They require specialist knowledge, intensive monitoring, specific dose adjustments or further evaluation in use. If however, a primary care prescriber has particular specialist knowledge or experience of prescribing a particular drug for a particular patient it would not always be appropriate for them to expect to transfer that prescribing responsibility back to secondary care. There should be a specific reason and a specific risk agreement, protocol and service set up to support this Primary care prescribers may prescribe RED medicines in exceptional circumstances to patients to ensure continuity of supply while arrangements are made to obtain on going supplies from secondary care. Summary of supporting evidence: • The studies show that rifaximin is well tolerated and has a degree of efficacy in treating patients with Small Intestinal Bacterial Overgrowth (SIBO) as indicated by the normalisation of breath tests and relief of symptoms associated with SIBO. • One study showed that rifaximin was not effective
    [Show full text]