Antimicrobial treatments with a minimum risk of resistance

Transcription

1 Antimicrobial treatments with a minimum risk of resistance - and Critical Important Antimicrobials Jenny Dahl Knudsen Senior Hospital Physician, M.D., D.M.Sc. Department of Clinical microbiology Copenhagen University Hospital Hvidovre Hospital Jenny.dahl.knudsen@hvh.regionh.dk

2 Antimicrobial agents, statements Antimicrobials are drugs that provide causal treatments against infectious diseases Antimicrobials are developed for short-time treatments Effect on the whole body and its microbiota, not only the infective microorganisms

3 In the ideal world The antimicrobial therapy only harms/kills the invasive microorganisms Antimicrobial therapy is only used when a patient will gain from it Antimicrobial therapy is only given for the time necessary to cure the patient Antimicrobial resistance is not a seen

4 CIA critical important antimicrobials Antimicrobials that are second or third line choices for treatments, - or used for critically ill patients (septic shock, necrotizing fasciitis, etc) Fluoroquinolones Cephalosporins Carbapenems.. Piperacillin-tazobactam Linezolid Vancomycin Colistin/polymycin

5 The world is not ideal! Due to increasing resistance, the CIA s become first-line drugs Only unfavourable drugs are left Sometimes there is no treatment possible With resistance, there is increasing morbidity, mortality, and need for resources

6 % isolates % of isolates Cephalosporin resistant E. coli in Europe Fluoroquinolone resistant E. coli in Europe Austria Belgium Bulgaria Cyprus Czech Republic Denmark Estonia Finland France Germany Greece Hungaria Iceland Ireland Italy Latvia Lituania Luxenburg Malta The Netherlands Norway Poland Portugal Romania Slovakia Sweden Spain Slovenia 2 United Kingdom Austria Latvia 29 21

7 Blood-culture isolates, EARS data % MRSA MRSA in Europe Austria Belgium Bulgaria Cyprus Czech Republic Denmark Estonia Finland France Greece Germany Hungaria Iceland Ireland Italy Latvia Lituania Luxenburg Malta The Netherlands Norway Poland Portugal Romania Slovakia Sweden Spain Slovenia United Kingdom

8 % of isolates % of isolates % of isolates MRSA in Europe low Iceland The Netherlands Norway MRSA in Europe Sweden medium Finland Denmark Austria Slovenia Bulgaria France Latvia Poland MRSA in Europe high Ireland Romania United Kingdom Cyprus Greece Spain Belgium Italy Estonia Germany Lituania Luxenburg Slovakia Czech Republic Hungaria Portugal Malta

9 Impact of consumption Community use is 1 x the hospital use, and therefore an enormous impact on resistance Consumptions of antimicrobials in the European countries are very different Rates of resistance in the European countries are very different Resistance and consumption are related

10 Total outpatient consumption in 29 Adriaenssens N et al. JAC 211

11 Number of treatments in 29 Adriaenssens N et al. JAC 211

12 quinolones cephalosporins Adriaenssens N et al. JAC 211 Versporten A et al. JAC 211

13 Hospital consumption CIA!

14 Nursing home usage

15 Amtimicrobials in nursing homes Antimicrobial usage Indication SSI Prophylaxis Empiric Documented RTI UTI Bacteremia Other Latour K, et al, Pharmacoepidemiology and Drug Safety, 212

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17 Problems in hospitals right now Gram positive resistance Vancomycin resistant Enterococci MRSA, Methicillin resistant Staphylococcus aureus Penicillin-resistant Pneumococci Gram negative resistance Fluoroquinolone resistant Enterobacteriaceae (E. coli, etc) ESBL/AmpC producing Enterobacteriaceae Carbapenem resistant Enterobacteriaceae Carpapenem resistant Pseudomonas Multiresistant Acinetobacter spp.

18 Risk factors for acquiring (multi)- resistant microbe Prior admittance to a hospital Prior antimicrobial therapy especially fluoroquinolones and cephalosporins Surgery and transplantations Artificial nutrition, high age, diabetes, alcoholisms, other co-morbidities Travels to Asia Schwaber: CID 211, JAC 27, AAC 26; Cassier: CMI 211; Rodrigues-Banõ: CID 21; Demirdag: J Infect Dev Ctries 21.

19 Eurosurveillance, Volume 17, Issue 7, 16 February 212 Table of Contents (Some of the contents) Isolation of NDM-1-producing Klebsiella pnemoniae in Ireland, July 211 by H McDermott, D Morris, E McArdle, G O'Mahony, S Kelly, M Cormican, R Cunney NDM-1 producing Acinetobacter baumannii isolated from a patient repatriated to the Czech Republic from Egypt, July 211 by J Hrabák, M Štolbová, V Študentová, M Fridrichová, E Chudáčková, H Zemlickova Microbiological and molecular characteristics of carbapenemase-producing Klebsiella pneumoniae endemic in a tertiary Greek hospital during by A Zagorianou, E Sianou, E Iosifidis, V Dimou, E Protonotariou, S Miyakis, E Roilides, D Sofianou Emergence and outbreak of carbapenemase-producing KPC-3 Klebsiella pneumoniae in Spain, September 29 to February 21: control measures by A Robustillo Rodela, C Díaz-Agero Pérez, T Sanchez Sagrado, P Ruiz-Garbajosa, MJ Pita López, V Monge

20 A local story

21 ESBL-project / General focus on Bispebjerg Hospital ESBL-steering committee Janne Elsborg, Steen Werner Hansen, Annette Søndergaard, Stig Ejdrup Andersen, Jenny Dahl Knudsen ESBL-coordinationsgroup Marie Stangerup, Jeannette Havstreym, Dorrit Langsted Olsen, Annette Søndergaard, Karin Brems, Mette Christensen, Vibeke Thygesen, Thomas Graeser Kramp, Charlotte Kjærgaard Stig Ejdrup Andersen, Jenny Dahl Knudsen antimicrobials Department of Clinical Microbiology, Hvidovre Hospital, All doctors Hospital Quality council Quality group

22 Antal ptt Antal ptt % af isolater % af isolater Antal ptt Antal ptt % af isolater % af isolater Antal ptt Antal ptt Antal ptt Antal ptt The intervention over time Procent resistente bakterier Bispebjerg Hospital Incidente patienter med ESBL-producerende E. coli Bispebjerg Hospital januar-marts januar februar marts Incidente patienter med ESBL-producerende E. coli Bispebjerg Hospital juli-september 28 juli august september 2 Resistens overvågning, Klinisk mikrobiologisk afdeling, Hvidovre Hospital. Afd I Afd L Afd K Afd M Afd Y AMA Afd S Afd N 28 Afd H Procent resistente bakterier Amager Hospital Afd Z Afd E Afd D Afd G Incidente patienter med ESBL-producerende 35 E. coli Bispebjerg Hospital april-juni april maj juni Incidente patienter med ESBL-producerende K. pneumoniae Bispebjerg Hospital januar-marts 28 5 Project 4 strategy Hvidovre Hospital Project januar februar plan marts AMA Afd S Prevalence studies Afd N Afd H Afd Z Afd E Afd D Incidente patienter med ESBL-producerende K. pneumoniae Carrier Bispebjerg studies Hospital juli-september Incidente patienter med ESBL-producerende K. pneumoniae Bispebjerg Hospital april-juni 28 april maj juni Incidente patienter med ESBL-producerende K. pneumoniae Bispebjerg Hospital oktober-december Pneumokokker-Penicillin I Afdeling M, total 28 Teaching of all doctors juli august september oktober november december Pneumokokker-Penicillin R Methicillin Resistent S. aureus Konvertering til Enterobacteriaceae-Gentamicin R Enterobacteriacea-Ciprofloxacin R Procent resistente bakterier E. coli-cefuroxim Incidente Rpatienter med ESBL-producerende E. coli Frederiksberg Hospital and head nurses Produkt Døgn dosering Pris pr. døgn Antal beh.døgn i 28 Pris i alt, 28 Cefuroxim Ertapenem 1g x 1 Pip+tazo 4g x 4 Klebsielle spc.-cefuroxim Bispebjerg Hospital R oktober-december 28 Pseudomonas-Gentamicin R 4 Cefuroxim break-seal 15 mg x 3 kr 123, kr ,8 Pseudomonas-Ciprofloxacin R Cefuroxim "Farma Plus", pulver t. inj. 15 mg x 3 kr 3, 57 kr 15.21, 35 kr ,3 kr , kr ,13 Guidelines rewritten Cefuroxim break-seal 75 mg x 3 kr 96,6 817 kr ,2 3 Cefuroxim "Farma Plus" pulver t. inj. 75 mg x 3 kr 15,72 84 kr 1.32,48 25 Ceftriaxon 1g x 2 kr 17,9 kr, oktober november december Procent resistente bakterier Ceftriaxon 2g x 2 kr 27,61 kr, Afd I Afd L Afd K Afd M Afd Y Afd G January 28 Chloric cleaning January 29 Summer Ertapenem, i.v. 1g x 1 kr 372, Pip+tazo "Stragen", i.v. 4g x 3 kr 141,71 Intervention January 21 project Cefur til Pip+tazo Ceftriaxon til Erta Ceftriaxon til Pip+tazo Behandlingsregime Cefur til Erta Difference, kr. pr. år kr ,7 kr , Difference, 26 kr. 27 pr. 6 mdr. 28 kr 66.89,35 kr ,92 JDK Note: Break-seal er inkl. 1 ml NaCl og overføringskanyle, der skal ikke manipuleres yderligere med produktet inden indgift. Ertapenem, i.v., eksklusiv NaCl og overføringskanyle, og skal tilberedes af sygeplejersker. Tazocin, i.v., eksklusiv NaCl og overføringskanyle, og skal tilberedes af sygeplejersker. 29

23 Pamphlet: new guidelines for antimicrobial therapy Pip-tazo in break-seal Numerous groups working App. June 21: Yellow MRSA/ESBL-stickers for patients charts Yellow triangles for beds Pamphlet for patients and relatives about ESBL s When ordering investigations (Xrays, blood sampling, training, biochemistry, etc,) electronic marks for patients in isolations precaution Start January 18, 21 Project prolonged Daily visit of infection control nurses to department with patients in isolation precautions

24 Photo: Marie Stangerup & Anne-Mette Mud

25 Guidelines in principal Empiric regimes were in principal as narrow spectred as possible, and change from empiric to final therapy was encouraged Change from cephalosporins to penicillins (The former used cefuroxim (1.5 g x 3, i.v.) was replaced with piperacillintazobactam (4 g x 3, i.v.), for penicillin-allergic patients ertapenem or meropenem) Avoid fluoroquinolones when possible (Macrolides for Mycoplasma, Legionella, Chlamydiaphila) All surgical prophylaxes were unchanged cephalosporins (one dose/one day (ortopedic patients))

26 DDD/1 OBD DDD/1 OBD Cefuroxime 4 Cefuroxime: 35 Stable 75% reduction BBH FH Ciprofloxacin Month Ciprofloxacin: Only 25% reduction 2 15 BBH FH Month Graphs from Stig Ejdrup Andersen

27 ESBL/AmpC rates

28 ESBL/AmpC incidences

29 ESBL/AmpC carriers

30 Number totally Number ESBL/AmpC Need for isolation precautions (= resourses) Number of isolation precuations per month 8 6 totally ESBL/AmpC jan 9 feb mar apr maj jun jul aug sep okt nov dec jan 1 feb mar apr maj jun jul aug sep okt nov dec jan 11 feb mar apr maj jun

31 % af isolater % af isolater % af isolater % af isolater Procent resistente bakterier Bispebjerg Hospital Procent resistente bakterier Hvidovre Hospital Pneumokokker-Penicillin I Pneumokokker-Penicillin R Methicillin Resistent S. aureus Enterobacteriaceae-Gentamicin R Enterobacteriacea-Ciprofloxacin R E. coli-cefuroxim R Klebsielle spc.-cefuroxim R Pseudomonas-Gentamicin R Pseudomonas-Ciprofloxacin R Procent resistente bakterier Amager Hospital Procent resistente bakterier Frederiksberg Hospital Rate of resistance

32 %ESBL % ESBL October country prevalence Klebsiella pneumoniae K.p. fra blood culture CPH K.p. fra blood culture DK K.p. urine hospitals CPH K.p. urine hospitals DK 1 K.p. urine out-patients CPH K.p. urine out-patients DK October country prevalence Escherichia coli E.c. fra blood culture CPH E.c. fra blood culture DK E.c. urine hospitals CPH E.c. urine hospitals DK 5 E.c. urine out-patients CPH E.c. urine out-patients DK

33 Similar experience from Sweden ESBL-producing Klebsiella pneumoniae Tängden T el al. JAC 211

34 Is there anything to do? Yes we can - We can stop facilitate spreading resistance - We can be aware if resistance occurs - We can reverse the trends in epidemiology If we don t do anything - More cases with untreatable infections - Treatment expenses increase - More use of the more expensive drugs - More isolation precautions needed

35 Prudent use of antimicrobials Empiric coverage due to local resistance rates Use diagnostic tests All prescription of antimicrobials should be time limited (stop/evaluation date) The reason for the prescription should be given Change to narrow spectred when possible Avoid fluoroquinolones unless proven needed by diagnostics or the patient status Choose penicillins when possible

36 Organization 1. Surveillance of resistance, 2. Infection control and 3. Antimicrobial guidelines should be combined in one organisation!! For hospitals: - With close connection to the hospital managements For general practices: - Governmental, economic reimbursements Clinical microbiologists, infectious disease specialists, epidemiologists, etc.

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38 Effects of antimicrobials The good: kill/inhibit the microorganisms The bad: the side effect for the patients Minor: rash, nausea, headache, etc. Major: liver-failure, agranulocytosis, etc The ugly: the ecological effect The patients treated, - super-infections! In nature (hospitals, institutions, home, etc)

39 Antimicrobial agents, statements If used against a resistant organism you only see the bad and ugly effects If used for too long, you will see more bad and ugly effects If used too broad-spectred you will see more bad and ugly effects

40 There is nothing as pure nature Cool party! Borrowed from WulffMorgenthaler