MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 MVZ DORTMUND - Dr.Eberhard u. Partner - MICROBIOLOGY bacterial resistance control, role of the laboratory MIKROBIOLOGY www.labmed.de / mikro@labmed.de Mongolia September 22 accreditation since april 23 (DIN EN ISO 589; DACH)
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 mechanisms of drug resistance loss of porines/ changes in permeability ß-laktamase/ enzyme efflux-pump change in bonding site 3
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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 3.2.29 n = patients! 2 22 23 24 29 H n P n H n P n H n P n H n P n H n P n Penicillin 8 427 77 2835 88 43 79 2796 85 475 83 2756 86 475 87 342 79 5866 73 3896 Oxacillin 6 498 2 279 422 3 2733 4 464 6 2736 6 4742 7 33 3 588 4 3996 Vancomycin/ Teicoplanin 893 389 46 4746 5848 2 (.. until 3.2.2): H: Kliniken: 34 % MRSA (n=734) P: Praxen : 5 % MRSA (n=434) 5
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 sensitive antibiotics for important bacteria / in parenthesis number of isolates; revised > same bacteria, same patient and same specimen > counted only once 8
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 resistance determination (e.g. important pathogens) common annotations: - important: pure monoculture (!) - otherwise no reliable results - statistical data (hospitals/physicians):..22-3.6.22 (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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 MDR gramnegatives - 3MRGN and 4 MRGN: new classification (by RKI in september 2 / Germany) 5
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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. 33 2 65 2 clin. relevant isloates: not efficiant Cefaclor 4 3 83 86 clin. relevant isloates: not efficiant Gentamicin/Tobramycin 92 8 44 Ciprofloxacin/Levofloxacin 84 3 3 256 effective; even ambulant patients Cotrimoxazol 89 244 e.g. urinary-tract infections Tetracyclin 86 2 2 254 oral; Imipenem/Meropenem 9 9 52 i.v. at serious infections Ceftazidim 55 4 3 38 i.v. at serious infections Ampic.+ Sulbactam 52 47 8 like Amoxic.+Clavulana. - but i.v. Piperac.+ Tazobactam 65 6 9 5 i.v. at serious infections Cefixim/Cefpodoxim 4 3 83 77 3.gen.-cephalosp.: oral Cefotaxim/ Ceftriaxon 4 3 83 5 3.gen.-cephalosp.: i.v. Cefuroxim 9 3 88 2 clin. relevant isloates: not efficiant Levofloxacin 84 4 2 256 6
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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 [%] 6 6 87 5 I [%] 4 R [%] 94 94 99 3 95 86 isolates [n] 362 362 35 35 362 356 352 362 27 65 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 Escherichia coli resistance varies from "polysensitive" to "MDR" substance Ampic./ Amoxic. Amoxic.+ Clavulans. S [%] 48 62 I [%] 7 R [%] 5 2 isolates [n] 676 6753 treatment depends on susceptibility testing and seriousness of desease Mezlocillin/Piperacillin Cefaclor Gentamicin/Tobramycin Ciprofloxacin/Levofloxacin Cotrimoxazol 47 9 94 78 67 53 9 6 22 33 389 267 3932 676 6758 CAVE: increasing resistance! Nitrofurantoin 9 7 2 2678 only urinary-tract-infections Tetracyclin 64 36 6757 Imipenem 45... if not carbapenem-resistent... Ceftazidim 87 3 393 Piperac.+ Tazobactam 6 9 2 3873 Cefixim 9 9 79 Cefotaxim/ Ceftriaxon 83 7 437 here: 7 % ESBL Meropenem 3966 Cefpodoxim 9 9 2799 Cefuroxim/ C.-Axetil 8 5 4 398 i.v./oral Fosfomycin 99 2348 urinary-tract inf. (not complicated) Moxifloxacin 75 25 286 Trimethoprim 65 35 252 8
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 Klebsiella pneumoniae natural resistance (always R): - Ampi-/Amoxicillin - Mezlo-/Piperacillin; substance Ampic./ Amoxic. Amoxic.+ Clavulans. Cefaclor S [%] 78 54 I [%] 3 34 R [%] 8 2 isolates [n] 887 887 85 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 93 86 84 24 8 86 47 5 6 4 6 3 6 4 566 887 886 244 886 62 573 no carbapenem-resistence (3/4MRGN) Imipenem - R: carbapenemresistance!! (3MRGN/4MRGN?) Ampic.+ Sulbactam Piperac.+ Tazobactam Cefotaxim/ Ceftriaxon Meropenem 78 8 8 4 3 8 7 2 569 567 6 585...2 % ESBL! here: not found Cefpodoxim Cefuroxim/ C.-Axetil 86 82 2 3 5 32 569 i.v./oral Fosfomycin 82 8 97 Trimethoprim 82 8 74 9
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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] 292 283 Imipenem - R: NO (!) carbapenemase but "poor target" for Proteus spp. Mezlocillin/Piperacillin Cefaclor Gentamicin/Tobramycin Ciprofloxacin 7 89 89 83 29 7 776 249 849 289 Cotrimoxazol 66 34 29 Nitrofurantoin 327 always R (natural resistance) Tetracyclin 292 always R (natural resistance) Imipenem 4 86 763 not suitable! "poor target" Ceftazidim 98 2 787 Ampic.+ Sulbactam 9 5 4 788 Piperac.+ Tazobactam 92 5 3 782 Cefotaxim/ Ceftriaxon 98 2 789...only 2 % ESBL Meropenem 794 no carbapenem-resistence (3/4MRGN) Cefpodoxim 98 2 5 Cefuroxim/C.Axetil 86 3 79 i.v./oral Fosfomycin 82 8 254 urinary-tract inf. (not complicated) Levofloxacin 83 6 29 2
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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 [%] 3 76 87 93 72 I [%] 24 4 6 2 R [%] 73 7 7 6 isolates [n] 32 26 87 9 823 37 32 36 32 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 88 9 77 5 4 5 8 7 9 259 27 8 83 5 3b.gen.-cephalosp.: i.v.; serious inf. always R (natural resistance) like Piperacillin many side-effects! lokal application?! Fosfomycin 4 86 2 as a combi partner Levofloxacin 7 27 38 2
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 Staphylococcus aureus (koagulase-pos) first choice: basic cephalosporines (Cefazolin, Cefuroxim), and Oxacillin substance Ampic./ Amoxic. Mezlocillin/Piperacillin Amoxic.+ Clavulans. S [%] 23 7 7 I [%] R [%] 77 83 29 isolates [n] 667 396 662 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 55 79 97 45 2 3 398 268 4292 for children in the case of MRSA: Vancomycin/Teicoplanin (in combination with Rifampicin if necessary) or Linezolid Tobramycin Ciprofloxacin/Levofloxacin Cotrimoxazol Tetracyclin Penicillin Erythromycin 87 66 99 96 23 69 3 34 4 77 3 3866 658 65 659 665 5693 77 % penicillinase-bilding; rarely S Clindamycin 7 3 5647 Oxacillin 7 29 648 29 % MRSA; most in hospitals Vancomycin/Teicoplanin 393 Imipenem/Meropenem 55 45 395 Cefotaxim/ Ceftriaxon 55 45 398 Cefazolin/Cefuroxim 56 44 3857 same resistance like Oxacillin Rifampicin 369 combi with Vanco/Teico: endocarditis Chloramphenicol 82 Fusidinsäure 98 835 Fosfomycin 99 388 combi with Vanco/Teico: endocarditis Mupirocin 687 nasal ointment Cefuroxim- Axetil Linezolid 79 2 2724 75 oral - ambulant patients 22
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22 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
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22... according to all medical issues it is useful to act as qualified, effective and innovative PARTNERS...... working hand in hand, and... 24
MICROBIOLOGY: bacterial resistance Roßburg / 9.9.22... remembering hand disinfection! (... the most important vehicle for microorganisms!) Please support your hygiene-management! Thanks for your attention! 25