Non-Susceptibility of Bacterial Pathogens Causing Hospital-Onset Pneumonia UK and Ireland,

Transcription

1 Non-Susceptibility of Bacterial Pathogens Causing Hospital-Onset Pneumonia UK and Ireland, Alicia Russell Federation of Infection Societies conference 14 th November 2018 alisia_russell

2 BSAC Respiratory Resistance Surveillance The BSAC Respiratory RSP collects susceptibility data for microorganisms associated with community- and hospital-onset pneumonia: 2

3 BSAC Respiratory Resistance Surveillance The BSAC Respiratory RSP collects susceptibility data for microorganisms associated with community- and hospital-onset pneumonia: Hospital-acquired pneumonia (HAP) Acquired >48 hours after hospital admission Significant cause of morbidity Most common HCAI leading to death 3

4 BSAC Respiratory Resistance Surveillance The BSAC Respiratory RSP collects susceptibility data for microorganisms associated with community- and hospital-onset pneumonia: Staphylococcus aureus Pseudomonas species Acinetobacter species Enterobacterales* *Previously Enterobacteriaceae 4

5 WHO priority antibiotic-resistant pathogens CRAB CRPA CRE MRSA, VISA, VRSA 5 Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics, World Health Organisation

6 Isolate collection Samples collected from LRT of patients with clinically significant hospital-onset pneumonia Isolates re-identified at the Central Testing Laboratory Species identification using MALDI-TOF (from 2012/13) 6

7 Isolate collection Year* Number of collecting labs Central testing laboratory Target isolate collection per lab S. aureus, Pseudomonas spp., Acinetobacter spp. Enterobacterales 2008/09 23 LGC /10 23 LGC /11 40 LGC /12 40 LGC /13 40 LGC / PHE / PHE /16 24 PHE *Period of isolate collection: 1 st October 30 th September

8 Number of isolates collected Isolates collected between Acinetobacter spp. 600 Pseudomonas spp. Staphylococcus aureus Enterobacterales / / / / / / / /16 Year

9 Isolates collected between Bacterial group Total isolates Sex (%) Modal age group Male Female Sputum Major source of isolate (%) Tracheal/ endotracheal secretions Bronchoalveolar lavage Acinetobacter spp S. aureus Pseudomonas spp Enterobacterales

10 2008/ / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / /16 Susceptibility testing Antibiotic 10 Panel of antimicrobials including sponsor agents BSAC agar dilution method EUCAST breakpoints Isolates defined as susceptible or non-susceptible (resistant or intermediate) to each drug Acinetobacter species Staphylococcus aureus Pseudomonas species Enterobacterales Amikacin* Amoxiciilin Azithromycin Carbenicillin Cefotaxime Cefoxitin Ceftaroline* Ceftazidime Ceftobiprole* Ceftolozane-tazobcatam* Cefuroxime Ciprofloxacin Clindamycin Co-amoxiclav Colistin Ertapenem Erythromycin* Fusidic acid Gentamicin Imipenem* Imipenem-relebactam* Lefamulin* Linezolid Meropenem Minocycline Moxifloxcin Mupirocin Oxacillin Penicillin Piperacillin-tazobactam Razupenem Rifampicin Solithromycin Tedizolid* Teicoplanin Telavancin Telithromycin Tetracycline Tigecycline Tobramycin Trimethoprim Vancomycin

11 Multi-drug resistance (MDR) Isolates classed as MDR based on definition by Magiorakos et al, 2012 If non-susceptible to at least one antimicrobial in at least three antimicrobial classes= MDR 11

12 Surveillance data Staphylococcus aureus Acinetobacter spp Pseudomonas spp Enterobacterales/Enterobacteriaceae 12

13 Number of isolates collected Staphylococcus aureus Isolate collection 250 MSSA (75%) 1296 isolates MRSA (25%) 424 isolates MSSA MRSA 50 Defined by presence/absence of meca gene 0 13 Year

14 Percentage of isolates non-susceptible Percentage of isolates non-susceptible Staphylococcus aureus Non-susceptibility trends MRSA MSSA Year 100% susceptibility to amikacin, tedizolid, ceftobiprole, vancomycin, teicoplanin and telavancin Year

15 Percentage of isolates non-susceptible Percentage of isolates non-susceptible Staphylococcus aureus Non-susceptibility trends MRSA MSSA Year 100% susceptibility to amikacin, tedizolid, ceftobiprole, vancomycin, teicoplanin and telavancin Year

16 Staphylococcus aureus MDR prevalence 20% of all S. aureus isolates collected defined as multi-drug resistant 74% of MRSA isolates, 2% of MSSA isolates Isolate Aminoglycoside Ansamycin Beta-lactam Fluoroqunolone Fucidane Glycopepties Glycylcycline Lincosamide Macrolide Oxazolidinone Tetracycline GEN RIF OXA CIP FUS TEC VAN TLV TGC CLI ERY LZD MIN TET MIC values MRSA > <= >128 > MRSA > <= >128 > MRSA > <= >128 > MRSA > <= >128 > MRSA > <= >128 > MRSA > <= >128 > MRSA > >128 > MRSA > MSSA > MSSA 32 >2 0.5 > >128 >128 2 >2 64 MSSA > Key: Nonsusceptible Susceptible

17 Surveillance data Staphylococcus aureus Acinetobacter spp Pseudomonas spp Enterobacterales/Enterobacteriaceae 17

18 Number of isolates collected Acinetobacter spp. Isolate collection 80 A. baumannii (69%) 322 isolates Other Acinetobacter species* (31%) 141 isolates Other species A. baumannii 18 *Includes A. johnsonii, A. calcoaceticus, A. lwoffii, A. haemolyticus, A. junii, A. ursingii, A. pittii, A. guillouiae, A. nosocomialis, A. beijerinckii, A. radioresistens, A. bayli, A. virianii 10 0 Year

19 Percentage of isolates non-susceptible Percentage of isolates non-susceptible Acinetobacter spp. Non-susceptibility trends A. baumannii Ciprofloxacin Imipenem Gentamicin Tobramycin Amikacin Meropenem Colistin Non- A. baumannii Year Year

20 Acinetobacter spp. MDR prevalence 21% of all Acinetobacter isolates collected defined as multi-drug resistant 30% of A. baumannii isolates Isolate Carbapenem Ciprofloxacin Aminoglycoside Polymixin IPM MEM CIP GEN AMK TOB CST MIC values Resistance mechanism A. baumannii > >256 1 OXA-23 & OXA-51 A. baumannii >256 >512 >256 1 OXA-23 & OXA-51 A. baumannii > OXA-51 & OXA-58 A. baumannii >256 >256 >512 >256 8 OXA-23 & OXA-51 A. baumannii >256 >256 >512 > OXA-23 & OXA-51 A. baumannii OXA-23 & OXA-51 & OXA-58 A. baumannii > >256 1 OXA-23 & OXA-51 A. baumannii >256 >512 >256 1 OXA-23 & OXA-51 A. baumannii > OXA-51 & OXA-58 A. baumannii >256 >512 >256 1 OXA-23 & OXA Key: Nonsusceptible Susceptible

21 Acinetobacter spp. Resistance mechanisms OXAs: class D beta-lactamases OXA-23 & OXA-51 prevalent in A. baumannii A. baumannii (113 isolates tested) Mechanism Positive isolates OXA (23%) OXA (98%) OXA-58 3 (3%) OXA-23 & 51 8 (7%) OXA-51 & 58 2 (2%) OXA-23 & 51 & 58 1 (1%) None 2 (2%) Non-A. baumannii (88 isolates tested) Mechanism Positive isolates OXA-23 1 (1 %) OXA-51 0 OXA-58 2 (2%) OXA OXA OXA None 85 (97%) 21

22 Surveillance data Staphylococcus aureus Acinetobacter spp Pseudomonas spp Enterobacterales/Enterobacteriaceae 22

23 Number of isolates collected Pseudomonas spp. Isolate collection 250 P. aeruginosa (99.1%) 1712 isolates Other Pseudomonas species* (0.9%) 16 isolates Other species P. aeruginosa *Includes P. fluorescens, P. mendocina, P. putida, P. rhodesiae, P. stutzeri, P. koreensis 0 Year

24 Percentage of isolates non-susceptible Pseudomonas spp. Non-susceptibility trends 100 Beta-lactams Meropenem Imipenem Piperacillin-tazobactam Ceftazidime Ceftolozane-tazobactam 24 Year

25 Percentage of isolates non-susceptible Pseudomonas spp. Non-susceptibility trends 100 Beta-lactams Meropenem Imipenem Piperacillin-tazobactam Ceftazidime Ceftolozane-tazobactam Year

26 Percentage of isolates non-susceptible Percentage of isolates non-susceptible Pseudomonas spp. Non-susceptibility trends 100 Beta-lactams 100 Non-beta-lactams Meropenem Imipenem Piperacillin-tazobactam Ceftazidime Ceftolozane-tazobactam Ciprofloxacin Gentamicin Colistin Amikacin Tobramycin Year Year

27 Pseudomonas spp. MDR prevalence 6% of all P. aeruginosa isolates collected defined as MDR Isolate Aminoglycoside Carbapenem Cephalosporin Fluoroquinolone Beta-lactam Polymyxin GEN AMK TOB MEM CAZ CIP TZP CST C_T MIC values Resistance mechanism P. aeruginosa >256 > VIM P. aeruginosa >256 >32 > >256 NDM P. aeruginosa > >256 VEB P. aeruginosa > P. aeruginosa P. aeruginosa PER P. aeruginosa OprD loss + efflux + AmpC P. aeruginosa VIM P. aeruginosa VIM P. aeruginosa > > VIM 27 Key: Nonsusceptible Susceptible

28 Pseudomonas spp. Resistance mechanisms P. aeruginosa Mechanism Positive isolates NDM 1 VIM 4 VEB 1 PER 1 AmpC 1 28

29 Surveillance data Staphylococcus aureus Acinetobacter spp Pseudomonas spp Enterobacterales/Enterobacteriaceae 29

30 Number of isolates collected Enterobacterales* Isolate collection E. coli (35%) Klebsiella spp. (30%) K. aerogenes, K. oxytoca, K. pneumoniae, K. variicola Enterobacter spp. (17%) E. clocae, E. amnigenus, E. asburiae, E. cloacae, E. gergoviae, E. hermanii, E. kobei, E. ludwigii, E. sakazakii Other (18%) Includes Citrobacter spp., Raoultella spp., Serratia spp., Pantoea spp., Proteus spp., Providencia spp., Hafnia alvei, Escherichia hermannii, Ewingella americana, Morganella morganii E. coli Klebsiella Enterobacter Other 30 *Previously Enterobacteriaceae Year

31 Percentage of isolates non-susceptible Percentage of isolates non-susceptible E. coli Non-susceptibility trends Beta-lactams Non-beta lactams Amoxicillin Co-amoxiclav Cefotaxime Piperacillin-tazobactam Ceftazidime Ciprofloxacin Amikacin Gentamicin Tobramycin Colistin 40 Ceftobiprole Ceftolozane-tazobactam Imipenem Meropenem Year Year

32 Percentage of isolates non-susceptible Klebsiella spp. Non-susceptibility trends Beta-lactams Co-amoxiclav Cefotaxime Piperacillin-tazobactam Ceftazidime Ceftobiprole Ceftolozane-tazobactam Imipenem Meropenem 32 Year

33 Percentage of isolates non-susceptible Percentage of isolates non-susceptible Klebsiella spp. Non-susceptibility trends Beta-lactams Co-amoxiclav Cefotaxime Piperacillin-tazobactam Ceftazidime Ceftobiprole Ceftolozane-tazobactam Non-beta-lactams Ciprofloxacin Amikacin Gentamicin Tobramycin Colistin Imipenem Meropenem Year Year

34 Percentage of isolates non-susceptible Percentage of isolates non-susceptible Enterobacter spp. Non-susceptibility trends Beta-lactams Cefotaxime Piperacillin-tazobactam Ceftazidime Ceftobiprole Ceftolozane-tazobactam Imipenem Meropenem Non-beta-lactams Ciprofloxacin Amikacin Gentamicin Tobramycin Colistin Year Year

35 Enterobacterales MDR prevalence 14% of all Enterobacterales collected defined as multi-drug resistant 15% of E. coli isolates, 11% of Klebsiella isolates, 22% of Enterobacter isolates Isolate Aminoglycoside Carbapenem Cephalosporin ES Cephalosporin Fluoroquinolone Tetracycline Beta-lactam Polymyxin Resistance mechanism AMK GEN TOB IPM MEM ETP CXM CTX CAZ CIP TGC AMC CST E. coli >64 1 CTX-M 1 E. coli > E. coli > K. pneumoniae >256 >256 > >256 >256 >256 >256 >64 32 MBL NDM K. pneumoniae >256 >256 >512 >256 >256 >256 >256 >256 >256 >64 64 MBL NDM K. pneumoniae >128 >64 2 KPC E. cloacae > >64 1 ESBL + AmpC E. cloacae > OXA-48 + CTX-M E. asburiae > >32 S. marcescens > >64 >32 P. mirabilis > >64 AmpC R. terrigena > P. mirabilis Key: Nonsusceptible Susceptible

36 Enterobacterales Resistance mechanisms Organism ESBL CTX-M CTX-M 1 CTX-M 2 CTX-M 8 CTX-M 9 AmpC K1 KPC NDM OXA-48 E. coli 254 (12%) 197 (9.5%) (1.2%) 1 Klebsiella 48 (10%) 91 (5.2%) (0.2%) Enterobacter 177 (5%) 27 (2.7%) (7.8%) Other 8 (0.7) 5 (0.5%) (6%) 36

37 37 Guidelines for HAP treatment

38 Guidelines for HAP treatment National guidelines: UK (BSAC) USA (IDSA) Canada (AMMI) Sweden India South Africa Portugal Europe (ERS, ESICM, ESCMID, ALAT) 38

39 Guidelines for HAP treatment 39 National guidelines: UK (BSAC) USA (IDSA) Canada (AMMI) Sweden India South Africa Portugal Europe (ERS, ESICM, ESCMID, ALAT) Antibiotic Mild HAP Moderate HAP Severe HAP Amikacin 1 3 Aztreonam 2 2 Cefepime Cefoperazone-sulbactam 1 1 Cefotaxime 4 2 Cefpriome 1 1 Ceftazidime Ceftriaxone 3 2 Cefuroxime 1 Ciprofloxacin Co-amoxiclav 2 Colistin 2 Gentamicin 1 3 Imipenem Imipenem-cilastatin 1 Levofloxacin Linezolid 3 2 Meropenem Moxifloxacin 1 1 Piperacillin-tazobactam Teicoplanin 1 1 Ticarcillin-clavulanate 1 1 Tobramycin 1 3 Vancomycin 3 4

40 Guidelines for HAP- UK UK NHS guidelines: 260 NHS Trusts across England, Scotland, Wales and Northern Ireland We analysed 46 antibiotic prescribing policy guidelines for HAP 40

41 41 Guidelines for HAP- UK UK NHS guidelines: 260 NHS Trusts across England, Scotland, Wales and Northern Ireland We analysed 46 antibiotic prescribing policy guidelines for HAP Summarised most commonly recommended abx for: 1 st -line mild and severe HAP 2 nd -line mild and severe HAP MRSA risk Antibiotic 1st line Penicillin allergy MRSA risk Mild HAP Severe HAP Mild HAP Severe HAP Amoxicillin + doxycycline 3 1 Amoxicillin + gentamicin 1 1 Amoxicillin + linezolid 1 Amoxicillin + metronidazole 1 Amoxicillin + teicoplanin 1 Amoxicillin 3 Aztreonam 1 2 Cefotaxime 1 Ceftriaxone 1 1 Cefuroxime 1 1 Cefuroxime then doxycycline 1 Chloramphenicol 3 Ciprofloxacin 1 1 Ciprofloxacin + linezolid 2 Clarithromycin 1 3 Co-amoxiclav + clarithromycin 1 1 Co-amoxiclav 6 5 Co-amoxiclav + gentamicin 2 Co-amoxiclav + teicoplanin 2 Co-amoxiclav + vancomycin 2 Co-trimoxazole Doxycycline Doxycycline then rifampicin + gentamicin 1 Doxycycline then trimethoprim 1 1 Levofloxacin Levofloxacin + linezolid 2 Levofloxacin + vancomycin 1 1 Linezolid 1 Meropenem Meropenem + teicoplanin 1 Penicillin + ciprofloxacin 1 Piperacillin-tazobactam 2 11 Piperacillin-tazobactam + gentamicin 1 Piperacillin-tazobactam + teicoplanin 3 Piperacillin-tazobactam + vancomycin 1 Teicoplanin + aztreonam 2 Teicoplanin + ciprofloxacin 1 1 Teicoplanin + gentamicin 1 2 Vancomycin 2 Vancomycin + ciprofloxacin 1

42 Guidelines for HAP- UK UK NHS guidelines: 260 NHS Trusts across England, Scotland, Wales and Northern Ireland We analysed 46 antibiotic prescribing policy guidelines for HAP Most commonly recommended abx: Co-amoxiclav, doxycycline, levofloxacin, meropenem, pip-taz Antibiotic 1st line Penicillin allergy MRSA risk Mild HAP Severe HAP Mild HAP Severe HAP Co-amoxiclav 6 5 Doxycycline Levofloxacin Meropenem Piperacillin-tazobactam

43 Doxy for HAP: where is the evidence? Doxycycline is inappropriate for largely Gram-negative aetiology of HAP Why does doxy appear in these guidelines? Clinical studies support use of doxy in CAP, no such evidence for HAP Are these guidelines followed? What is a better alternative? Is HAP over-diagnosed? 43

44 Acknowledgements Dr. Carolyne Horner Prof. David Livermore Prof. Alasdair McGowan BSAC Resistance Surveillance standing committee PHE team in central testing laboratory RSP sponsors Tracey Guise Team at BSAC HQ 44

45 45