Antibioottiresistenssi eilen, tänään ja huomenna Martti Vaara 27.8.212 Therapia Fennica -68 % Miten MRSA yleistyi USA:ssa 4 3 Hospital size 3 2 <2 beds 2 1 2- beds 1 > beds 197 1979 1983 1987 1991 199 Emergence of antibiotic resistance follows typically a sigmoidal curve. This figure shows the share (%) of multiresistant MRSA strains amongst all isolated Staphylococcus aureus strains in U.S. hospitals (NNIS). 1
2
Infectious Diseases Society of America (IDSA) 24: Bad bugs, no drugs www.idsociety. org HUSRES Annual Report 211 Martti Vaara www.huslab.fi www.intra.hus.fi The basis of this HUSRES 211 report is the HUSLAB/Whonet database 211, which contains susceptibility data on more than 199. bacteria isolated and studied in 211 by HUSLAB. The susceptibility interpretations are according to EUCAST 211. The isolates originate from patients in Helsinki University Central Hospital, other hospitals in Helsinki - Uusimaa region, as well as outpatient health centers. HUSRES 211 report contains data on 31 clinically most important bacterial species/groups. Previous annual reports from 2 are also located at www.huslab.fi Streptococcus pneumoniae FINRES 21 www.finres.fi EARS NET 21 EACAST www.eucast.org M. Vaara 3
11VV2696 XXXXXXXXXX, Emma 1V xxxxxxxxxx JOPPLT:9-4718 284 THU 1.6.211 4:4 veri (AER/THU) #J32226# 11.6.211 viggosta TTI: 79-11-9934 4. B -BaktJVi-vastaus 14.6.211 -PJT-varsinainen 1. löydös STREP.PNEUMONIAE kiekot ja micitt-11187 1 72 Kasvaa aerobipullossa 2 1 Pneumokokkikannan penisilliiniherkkyys alentunut 3 1263 Penisilliini I-tuloksen tulkinta: pneumoniaa aikuisannoksella 2.4gx6 hoidettaessa tulkitaan S. Meningiittiä hoidettaessa tulkinta R. kiekko MIC kiekko MIC Ampisill D.64=S Levoflok 2=S Erytromy Meropene 6=R.64=S Imipenem 3=S Moksiflo 23=S Keftriax.64=S Penisill.94=I Kefuroks.19=S Rifampis 29=S Klindamy 6=R Telitrom 2=S Kloramfe 27=S Vankomys S=S Multiresistant pneumococci* 26 211 (HUSLAB) Multiresistant pneumococci* 211 (HUSLAB) MIC distribution for penicillin G and ceftriaxone (n = 2) % 8 7 6 Proportion (%) 4 3 2 1 26 27 28 29 21 211 * Pen MIC >.64 g/ml and non-susceptibility to Ery, Cli, Dox and SxT. One isolate per patient. * Pen MIC >.64 g/ml and non-susceptibility to Ery, Cli, Dox and SxT. Pneumokokin ja A-ryhmän streptokokin erytromysiiniresistenssi 1997 28 Suomessa EryR+I pneumokokki 21 3 2 Resistenssi (%) 2 1 1 StrA 1997 1998 1999 2 21 22 23 24 2 26 27 28 PNC FiRe aineisto EARS 4
MRSA 29 St. aureus EARS Numbers of MRSA bacteraemias in England by 6 month periods from 21 to 28 (bars, left axis) and rates of bacteraemia per 1 bed days (line, right axis) MRSA 21 Livermore, D. M. J. Antimicrob. Chemother. 29 64:i29-36i; doi:1.193/jac/dkp2 Copyright restrictions may apply. EARS MRSA cases in Finland 199 211 Pink columns: Helsinki and Uusimaa District, blue columns: other parts of Finland Tapausten lukumäärä 18 17 16 1 14 13 12 11 84 1416 1 9 93 92 131 8 128 97 978 7 6 82 4 49 3 634 2 267 447 36 62 36 61 83 111 77 77 12 231 29 363 16 1 184 29 321 336 1 27 72 9 199 1996 1997 1998 1999 2 21 22 23 24 2 26 27 28 29 21 211 Vankomysiiniresistentti enterokokki (VRE) Helsingin ja Uudenmaan shp Muu Suomi Source: National Institute for Health and Welfare
Vankores. E. faecium 21 VRE cases in Finland 1992-211 Green columns: Helsinki and Uusimaa District; blue columns: other parts of Finland 16 14 12 1 8 6 4 2 1992 1993 1994 199 1996 Tapausten lukumäärä 1997 1998 1999 2 21 22 23 24 2 26 27 28 29 21 211 Pääkaupunkiseutu muu Suomi EARS Source: National Institute for Health and Welfare Pseudomonas aeruginosa Acinetobacter baumannii Ps. aeruginosa, MDR strains 21-211* *Nonsusceptibility to 1) meropenem and 2) tobramycin as well as 3) ceftazidime and/or piperacillintazobactam. HUSLAB material from Helsinki and Uusimaa District. 16 14 12 Number of patients 1 8 6 All sources Other sources Meilahti Hosp 4 Panresistant Pseudomonas aeruginosa Foto: M. Vaara 2 21 22 23 24 2 26 27 28 29 21 211 6
Acinetobacter spp., MDR strains* *Nonsusceptibility to meropenem, tobramycin and piperacillin-tazobactam HUSLAB material from Helsinki and Uusimaa District. Bacterial Invaders, Acinetobacter is Iraqibacter U.S. military men and women gravely wounded in Iraq and Afghanistan face another threat A. baumannii infection affects hospitalized patients at their most vulnerable. Now, antibiotics that once could overcome the dangerous bacteria have lost nearly all effect. 6 Number of patients 4 3 2 All sources Other sources Toolo Hosp 1 21 22 23 24 2 26 27 28 29 21 211 Salmonella typhi 2-211, susceptibility to ciprofloxacin HUSLAB material from Helsinki and Uusimaa Districts. One isolate per patient (the first isolate), n = 22 Salmonellat EUCAST 211 Salmonella - there is clinical evidence for ciprofloxacin to indicate a poor response in systemic infections caused by Salmonella spp with low-level fluoroquinolone resistance (MIC>.64 mg/l). The available data relate mainly to S. typhi but there are also case reports of poor response with other Salmonella species. Salmonella spp 2-211, susceptibility to ciprofloxacin HUSLAB material from Helsinki and Uusimaa Districts. One isolate per patient (the first isolate), n = 278 EUCAST 211 Salmonella - there is clinical evidence for ciprofloxacin to indicate a poor response in systemic infections caused by Salmonella spp with low-level fluoroquinolone resistance (MIC>.64 mg/l). The available data relate mainly to S. typhi but there are also case reports of poor response with other Salmonella species. 11VV328 XXXXXXX, Markku B 18V xxxxx-xxxxx MEPPKL:471 76164 21.1.211 19:4 veri (AA/PÄAA) #M183739# 3. B -BaktVi-vastaus 2.1.211 -PQ- varsinainen 1. löydös SALMON. TYPHI kiekot ja micitt-19264 1 74 Kasvaa molemmissa pulloissa. 2 21 Löydöksestä on lääkärillä ilmoitusvelvollisuus. 3 1116 Huom.kannan siprofloksasiini MIC=.12 tai suurempi voi viitata kliinisen tehon alentumiseen. kiekko MIC Amox+kla S Ampisill S Kefotaks S Keftriax.94=S Levoflok S Meropene S Pip+tazo S Siproflo.2=S Trim/sul S 7
Neisseria gonorrhoeae, resistance to ciprofloxacin 21-211 HUSLAB material from Helsinki and Uusimaa Districts (211, n = 88) 9 8 7 Gonokokki % R+I 6 4 3 2 1 21 22 23 24 2 26 27 28 29 21 211 THL:n valtakunnallien raportti (-21) koostuu liki kokonaan HUSLABin materiaalista Neisseria gonorrhoeae, MIC of ceftriaxone 211 HUSLAB material from Helsinki and Uusimaa Districts (n = 88) Keftriaksonin MIC gonokokeille, HUSLABin materiaali 21-211 (n=72) % 4 4 3 3 2 2 1 1 <.2.4.8.16.32.64.12.2. 1 MIC (mg/l) 21-23 24-26 27-29 21-211 Neisseria gonorrhoeae, MIC of azithromycin 211 HUSLAB material from Helsinki and Uusimaa Districts (n = 88) E. coli, K. pneumoniae ESBL = extended spectrum betalactamase puree rikki kaikki betalaktaamit (paitsi karbapeneemit) 8
E. coli and Klebsiella pneumoniae are the clinically most important Gram-negative bacteria that cause serious infections Näin ESBL valloitti maailman Proportion (%) from all Gram-negative bacteremias that are Community- Health care acquired -associated E. coli & K. pneumoniae 7-87 62-64 P. aeruginosa 2-3 9 Acinetobacter spp. 1 1 Calculated from the data in: J. Kollef et al. 211, J Infect 62:13 Al-Hasan et al. 211, Eur J Clin Microbiol Infect Dis DOI 1.17/s196-11-1424-6) Nov ember 2, 211 Conquistadores E. coli ESBL 21 K. pneum. ESBL 21 EARS Proportion of E. coli ESBL from all E. coli blood isolates. HUSLAB material 21-211 E. coli ESBL 24 211, number of new cases by age categories in Huslab material 6 3 2 Proportion (%) 4 3 2 Number of new cases 2 1 1 24 2 26 27 28 29 21 211 1 21 22 23 24 2 26 27 28 29 21 211-2 21-4 41-6 61-8 81-1 Age group One isolate per patient. 9
ESBL strains, resistance to non-betalactams and carbapenems 211 % R+I in blood, pus, and urine isolates. HUSLAB material from Helsinki and Uusimaa districts. One isolate per patient (the most resistant isolate). E. coli Ciprofloxacin 68 Levofloxacin 78 Tobramycin 46 Sulphatrimetoprim 62 Trimetoprim 6 Nitrofurantoin 6 Meropenem,1 Ertapenem 2,6 n 143 ESBL ulostekantajuus ulkomailta palaavilla ripulipotilailla Ruotsissa 27-28 E. coli ESBL Matkakohde % n Mikä tahansa Euroopan ulkopuolella 36 % /138 Intia 79 % 11/14 Lähi-Itä 67 % 4/6 Egypti % 19/38 Kaakkois-Aasia 38 % /13 Thaimaa 22 % 8/36 9% kannoista CTX-M. CTX-M-1: 68%, CTX-M-9: 24% Tham et al. 21, SJID 42:27 ESBL ulkomaanmatkan jälkeen ruotsalaisilla 27-29 Vapaaehtoisia, jotka eivät kantaneet ESBL:ää matkalle lähtiessään E. coli ESBL Matkakohde % n Intia 88 % 7/8 Muu Aasia 32 % 1/31 Lähi-Itä 29 % 4/14 Etelä-Eurooppa 13 % 2/16 Afrikka 4 % 4/2 Väli- ja Etelä-Amerikka % /7 24 % (/21) kantoi ESBL:ää vielä 6 kk:n jälkeen CTX-M-1/1 8% CTX-M-14 21% CTX-M-9 13% CTX-M-27 8% Tängden et al. 21, AAC 4:364 Tänään ESBL, huomenna CPE 1
Klebsiella pneumoniae, karbapeneemiherkkyydeltään alentuneet kannat 21 NDM-kannat NDM-1:n esiintymisfrekvenssejä Intian niemimaalta 21 Resistenttejä kaikille bakteerilääkkeille paitsi kolistiinille (ja tigesykliinille) Esiintyy jo monissa bakteerilajeissa, mm. E. coli, Klebsiella, Acinetobacter, Ps. aeruginosa, Salmonella, Shigella, V. cholerae bla NDM-1 usein pienessä, helposti siirtyvässä plasmidissa Erityisesti Intian niemimaalla, myös Britanniassa, Balkanilla pesäke Mumbain jätevedessä ja vesijohtovedessä Euroopassa kuvattu ensimmäinen tapaus avohoitopotilaalla, jolla ei mitään matkustusanamneesia. Materiaali Kaupunki Frekv. Enterobakteerikannat sairaala- ja avohoitopotilaista Varanasi, Intia 6,9 % Enterobakteerikannat sairaalapotilaista Bumbai, Intia -8 % Ulostekantajuus sotilassairaalassa ja sen avohoidossa Rawalpindi, Pakistan 18, % Nordmann 211, TIM 19:88 Karbapenemaaseja muodostavat Gram-negatiiviset enterobakteerikannat Suomessa 28 211 1 9 8 7 6 4 3 2 1 28 29 21 211 NMC-A OXA-181 NDM VIM OXA-48 KPC IMI HUSLAB ja THL 11
Gram-negatiivinen panresistenssi on todellinen uhka MISSÄ LÄÄKKEET? VÄHISSÄ USA:ssa hyväksytyt uudet bakteerilääkkeet 1983-211 (lukumäärä) 3 3 2 2 1 1 1983-1992 1993-22 23-211 Bourcher et al. IDSA 211, LB-27 Number (by April 211) of i.v. antibacterial drugs in clinical development with focus on Gram-negative and Gram-positive bacteria. New drugs are those against new bacterial targets or new mode of action. Old drugs are analogs of known scaffolds. Theuretzbacher 211, Curr Opin Pharmacol 11:433 12
13