Mongolia September 2012
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1 MICROBIOLOGY: bacterial resistance Roßburg / MVZ DORTMUND - Dr.Eberhard u. Partner - MICROBIOLOGY bacterial resistance control, role of the laboratory MIKROBIOLOGY / mikro@labmed.de Mongolia September 22 accreditation since april 23 (DIN EN ISO 589; DACH)
2 MICROBIOLOGY: bacterial resistance Roßburg / Multi-Drug-Resistent bacteria - a challenge clinical/epidemiological relevant bacteria (e.g. wound) Staphylococcus aureus Enteroccus sp. (CAVE: MRSA!) (CAVE: VRE!) increasing: drug resistant Gram-Negative bacteria (GN) - Escherichia coli (CAVE: ESBL-pos.) - Klebsiella sp. (CAVE: ESBL-pos.) - Pseudomonas aeruginosa (CAVE: MDR) - Proteus sp. - Enterobacter cloacae etc. anaerobes (Clostridium perfringens, Bacteroides sp.) 2
3 MICROBIOLOGY: bacterial resistance Roßburg / mechanisms of drug resistance loss of porines/ changes in permeability ß-laktamase/ enzyme efflux-pump change in bonding site 3
4 MICROBIOLOGY: bacterial resistance Roßburg / No ESKAPE...? problematic bacteria... IDSA (USA) E nterococcus faecium S taphyloc. aureus K lebsiella pneumoniae A cinetob. baumannii P seudom. aeruginosa E nterobacter cloacae VRE MRSA ESBL Carbapenemases, MDR Carbapenemases, MDR ESBL+AmpC, MDR IDSA: Bad bugs No drugs 4
5 MICROBIOLOGY: bacterial resistance Roßburg / MRSA development (patients) - region of Dortmund (revised statistic: [n] = patients with St. aureus ; 2 total 3.5 MRSA-patients!) Staphylococcus aureus: resistent [%] hospitals / physicians:..2 bis n = patients! H n P n H n P n H n P n H n P n H n P n Penicillin Oxacillin Vancomycin/ Teicoplanin (.. until 3.2.2): H: Kliniken: 34 % MRSA (n=734) P: Praxen : 5 % MRSA (n=434) 5
6 MICROBIOLOGY: bacterial resistance Roßburg / reaction by the Ministry of Health: a new law - Act on the Prevention and Control of Infectious Diseases in Man (Protection against Infection Act / IfSG since 2) -... ultimate ambition: PREVENTION!... to prevent communicable human diseases, to detect infections early and to avoid spreading the disease..." list of bacteria - data should be documented by hospital ( 23 Abs.S.): spezies Staphylococcus aureus Enteroc. faecalis/faecium Escherichia coli Klebsiella spp. Enterobacter cloacae etc. Pseudomonas aeruginosa* Acinetobacter baumannii confirmed resistance Vancomycin, Oxacillin, Gentamicin, Chinolon Gr.IV (z.b. Moxifloxacin), Teicoplanin, Quinupristin/Dalfopristin Vancomycin, Gentamicin ( high level ); Teicoplanin Imipenem/Meropenem, Chinolon Gr.II (z.b.ciprofloxacin), Amikacin, Ceftazidim, Piperacillin/Tazobactam, Cefotaxim Imipenem/Meropenem, Chinolon Gr.II (z.b. Ciprofloxacin), Amikacin Imipenem/Meropenem, Chinolon Gr.II (z.b. Ciprofloxacin), Amikacin, Ceftazidim, Piperacillin/Tazobactam 6
7 MICROBIOLOGY: bacterial resistance Roßburg / monitoring klinical/epidemiological relevant bacteria (statistics for hospitals every six months... or on demand) list of all cases (Patients) with relevant bacteria (special drug resistance) including patients name, date of detection, clinic, ward etc. 7
8 MICROBIOLOGY: bacterial resistance Roßburg / sensitive antibiotics for important bacteria / in parenthesis number of isolates; revised > same bacteria, same patient and same specimen > counted only once 8
9 MICROBIOLOGY: bacterial resistance Roßburg / methods: identification / resistance culture identification resistance streaking manual or VITEK 2/XL (biochem.) or agar-diffusion or Innova (automated) MALDI-TOF (massspectrom.) VITEK 2/XL (MIC) 9
10 MICROBIOLOGY: bacterial resistance Roßburg / resistance determination (e.g. important pathogens) common annotations: - important: pure monoculture (!) - otherwise no reliable results - statistical data (hospitals/physicians): (data / situation can vary by different hospitals / regions) - revised: same patient, same specimen, same bacteria > case - green: important antibiotics... should be tested - ineffective antibiotics tested? to provide reliability for identification! - agardiffusion: measuring the diameter - ONE standard! (NCCLS?) - VITEK 2/XL panels used: gram (+) usually AST-N8 MDR AST-N gram (-) Staphylocossus AST-P58 Enterococcus AST-P586
11 MICROBIOLOGY: bacterial resistance Roßburg / Methicillin-resistant Staphylococcus aureus/mrsa 3 groups of MRSA: detected via PCR Healthcareassociated MRSA (HA-MRSA) Community acquired MRSA (CA-MRSA) Livestock associated MRSA (LA-MRSA) where? health care community community, associated with animal keeping elder patients even younger patients even younger patients molecularbiological meca-gene meca-gene and PVL-gene meca-gene and ST 398 resistance all ß-Laktames, Fluorchinolones, Macrolides all ß-Laktames, Fusidinacid all ß-Laktames, Tetracycline
12 MICROBIOLOGY: bacterial resistance Roßburg / Vancomycin-resistant-Enterococcus/VRE Enterococcus species usually show drug resistance against: Penicillin, Cephalosporines, Clindamycin, Co-Trimoxazol, Tetracycline and are sensitive against: Glycopeptides (Vancomycin / Teicoplanin) and Linezolid! - if you start VRE-Screening (ICU: specimen from anal region):... you will find them! 2
13 MICROBIOLOGY: bacterial resistance Roßburg / extended-beta-lactamase/esbl-positive extended impact on ß-lactame-antibiotics (Cephalosporines and Penicillines)... amount of detected variants is increasing at this time 9 different groups are known: TEM, SHV, CTX-M, PER, VEB, GES, TLA, BES, OXA; new: NDM- (New Dehli-Metallo-ß-Lactamase) only Colistin and Tigecyclin sensitive! exchange of genes (plasmids: several resistances can be coded) between different species is possible! 3
14 MICROBIOLOGY: bacterial resistance Roßburg / carbapenemase/3mrgn or 4MRGN Pseudomonas aeruginosa, Acinetobacter baumannii and others... own a lot of natural resistance mechanisms:... if additionally Ciprofloxacine / Levofloxacine is resistant: no more sensitive oral antibiotics available!... resistance against Imipenem / Meropenem possible: Pan-resistance! this even concerns to: Klebsiella pneumoniae... ESBL + Carbapenemases Enterobacter, Serratia, Citrobacter... natural resistance + ESBL + Carbapenemase... Germany: categories of relevance were defined to support hygiene management! 4
15 MICROBIOLOGY: bacterial resistance Roßburg / MDR gramnegatives - 3MRGN and 4 MRGN: new classification (by RKI in september 2 / Germany) 5
16 MICROBIOLOGY: bacterial resistance Roßburg / Acinetobacter spp. owns a lot of natural resistances substance Ampic./ Amoxic. S [%] 6 I [%] 2 R [%] 8 isolates [n] 244 clin. relevant isloates: not efficiant Amoxic.+ Clavulana clin. relevant isloates: not efficiant Cefaclor clin. relevant isloates: not efficiant Gentamicin/Tobramycin Ciprofloxacin/Levofloxacin effective; even ambulant patients Cotrimoxazol e.g. urinary-tract infections Tetracyclin oral; Imipenem/Meropenem i.v. at serious infections Ceftazidim i.v. at serious infections Ampic.+ Sulbactam like Amoxic.+Clavulana. - but i.v. Piperac.+ Tazobactam i.v. at serious infections Cefixim/Cefpodoxim gen.-cephalosp.: oral Cefotaxim/ Ceftriaxon gen.-cephalosp.: i.v. Cefuroxim clin. relevant isloates: not efficiant Levofloxacin
17 MICROBIOLOGY: bacterial resistance Roßburg / Enterococcus faecium natural resistance (always R): - nearly all ß-lactamantibiotics: cephalosporines/ penicillines! (even combinations with ß-lactamaseinhibitors!) suitable: - Vancomycin/Teicopl. and Linezolid Tigecycline: treatment only at soft tissue infection - NOT at blood-steaminfections substance Ampic./ Amoxic. Amoxic.+ Clavulans. Cefotaxim/ Ceftriaxon Gentamicin/Tobramycin Ciprofloxacin/Cotrimoxazol Vancomycin/Teicoplanin Imipenem Levofloxacin Linezolid Tigecyclin S [%] I [%] 4 R [%] isolates [n] not suitable! not suitable! not suitable! only combi (endocarditis: +Van/Tei) not suitable! important substance: initial therapy not suitable! not suitable! important substance: initial therapy CAVE: usually within this species we can find VRE! (3 %!) 7
18 MICROBIOLOGY: bacterial resistance Roßburg / Escherichia coli resistance varies from "polysensitive" to "MDR" substance Ampic./ Amoxic. Amoxic.+ Clavulans. S [%] I [%] 7 R [%] 5 2 isolates [n] treatment depends on susceptibility testing and seriousness of desease Mezlocillin/Piperacillin Cefaclor Gentamicin/Tobramycin Ciprofloxacin/Levofloxacin Cotrimoxazol CAVE: increasing resistance! Nitrofurantoin only urinary-tract-infections Tetracyclin Imipenem if not carbapenem-resistent... Ceftazidim Piperac.+ Tazobactam Cefixim Cefotaxim/ Ceftriaxon here: 7 % ESBL Meropenem 3966 Cefpodoxim Cefuroxim/ C.-Axetil i.v./oral Fosfomycin urinary-tract inf. (not complicated) Moxifloxacin Trimethoprim
19 MICROBIOLOGY: bacterial resistance Roßburg / Klebsiella pneumoniae natural resistance (always R): - Ampi-/Amoxicillin - Mezlo-/Piperacillin; substance Ampic./ Amoxic. Amoxic.+ Clavulans. Cefaclor S [%] I [%] 3 34 R [%] 8 2 isolates [n] always R (natural resistance) suitable see above - in combination with ß-lactam-inhibitor CAVE: - ESBL: more isolates found here than in K. oxytoca Gentamicin/Tobramycin Ciprofloxacin/Levofloxacin Cotrimoxazol Nitrofurantoin Tetracyclin Imipenem Ceftazidim no carbapenem-resistence (3/4MRGN) Imipenem - R: carbapenemresistance!! (3MRGN/4MRGN?) Ampic.+ Sulbactam Piperac.+ Tazobactam Cefotaxim/ Ceftriaxon Meropenem % ESBL! here: not found Cefpodoxim Cefuroxim/ C.-Axetil i.v./oral Fosfomycin Trimethoprim
20 MICROBIOLOGY: bacterial resistance Roßburg / Proteus spp. treatment depending on localisation and seriousness of desease substance Ampic./ Amoxic. Amoxic.+ Clavulans. S [%] 6 9 I [%] 4 R [%] 39 4 isolates [n] Imipenem - R: NO (!) carbapenemase but "poor target" for Proteus spp. Mezlocillin/Piperacillin Cefaclor Gentamicin/Tobramycin Ciprofloxacin Cotrimoxazol Nitrofurantoin 327 always R (natural resistance) Tetracyclin 292 always R (natural resistance) Imipenem not suitable! "poor target" Ceftazidim Ampic.+ Sulbactam Piperac.+ Tazobactam Cefotaxim/ Ceftriaxon only 2 % ESBL Meropenem 794 no carbapenem-resistence (3/4MRGN) Cefpodoxim Cefuroxim/C.Axetil i.v./oral Fosfomycin urinary-tract inf. (not complicated) Levofloxacin
21 MICROBIOLOGY: bacterial resistance Roßburg / Pseudomonas aeruginosa natural resistance (always R): - Ampic./Amoxicillin (incl. +ß-lactam.-inhib.) - most Cephalosporines (e.g. Cefaclor,Cefazolin, Cefotaxim/Ceftriaxon) - Cotrimoxazol - Nitrofurantoin - Tetracyclin - Moxifloxacin - Trimethoprim - Tigecyclin substance Ampic./ Amoxic. Mezlocillin Piperacillin Gentamicin Tobramycin Ciprofloxacin Cotrimoxazol Nitrofurantoin Tetracyclin S [%] I [%] R [%] isolates [n] always R (natural resistance) not suitable! like Piperacillin+ß-lactamase-inhib. as a combi-partner as a combi-partner the only oral substance Imipenem-R: carbapenem-resistence!! (3MRGN/4MRGN) here: found!!! Imipenem/Meropenem Ceftazidim Ampic.+ Sulbactam Piperac.+ Tazobactam Colistin b.gen.-cephalosp.: i.v.; serious inf. always R (natural resistance) like Piperacillin many side-effects! lokal application?! Fosfomycin as a combi partner Levofloxacin
22 MICROBIOLOGY: bacterial resistance Roßburg / Staphylococcus aureus (koagulase-pos) first choice: basic cephalosporines (Cefazolin, Cefuroxim), and Oxacillin substance Ampic./ Amoxic. Mezlocillin/Piperacillin Amoxic.+ Clavulans. S [%] I [%] R [%] isolates [n] same resistence like Penicillin same resistence like Penicillin Oxacillin - R (MRSA): all ß-lactam-substances and carbapenems are R! Amp.+ Sulb./Pip.+Taz. Cefaclor Gentamicin for children in the case of MRSA: Vancomycin/Teicoplanin (in combination with Rifampicin if necessary) or Linezolid Tobramycin Ciprofloxacin/Levofloxacin Cotrimoxazol Tetracyclin Penicillin Erythromycin % penicillinase-bilding; rarely S Clindamycin Oxacillin % MRSA; most in hospitals Vancomycin/Teicoplanin 393 Imipenem/Meropenem Cefotaxim/ Ceftriaxon Cefazolin/Cefuroxim same resistance like Oxacillin Rifampicin 369 combi with Vanco/Teico: endocarditis Chloramphenicol 82 Fusidinsäure Fosfomycin combi with Vanco/Teico: endocarditis Mupirocin 687 nasal ointment Cefuroxim- Axetil Linezolid oral - ambulant patients 22
23 MICROBIOLOGY: bacterial resistance Roßburg / conclusion: effective cooperation of all participants is necessary! - fast (!), effective diagnostic - fast (!), effective treatment - Paul Ehrlich (854-95): "Frapper fort et frapper vite" "Hit hard and fast" (Address to the 7th International Congress of Medicine, 93) 23
24 MICROBIOLOGY: bacterial resistance Roßburg / according to all medical issues it is useful to act as qualified, effective and innovative PARTNERS working hand in hand, and... 24
25 MICROBIOLOGY: bacterial resistance Roßburg / remembering hand disinfection! (... the most important vehicle for microorganisms!) Please support your hygiene-management! Thanks for your attention! 25
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