EARS-Net data on Antimicrobial Resistance in Ireland, Q

EARS-Net data on antimicrobial resistance in Ireland Quarter 1-4 2017 20th June 2018

EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2017
KEY POINTS, 2017 (General) Increasing numbers of invasive infections in recent years due to the following pathogens: K. pneumonaie, P. aeruginosa, S. pneumoniae, E. coli and E. faecium Escherichia coli The proportions of 3rd generation cephalosporin- and gentamicin resistance plus ESBL-positivity have increased to their highest proportions to date Four carbapenemase-producing E. coli were reported Staphylococcus aureus/ MRSA The proportion of MRSA bloodstream infections have increased: this is the first increase in over 10 years Klebsiella pneumoniae 3rd generation cephalosporin-resistance and ESBL-positivity have stabilised Four carbapenemase-producing K. pneumoniae were reported Enterococcus faecium/ VREfm (vancomycin-resistant E. faecium) The proportion of VREfm bloodstream infections has decreased to its lowest level since 2011 One linezolid-resistant isolate was reported (which was also vancomycin-resistant) Enterococcus faecalis One linezolid-resistant isolate was reported, which was confirmed as optrA-positive Acinetobacter spp. One carbapenemase-producing MDR Acinetobacter spp. was reported EARS-Net data on Antimicrobial Resistance in Ireland, Q

KEY POINTS, 2017 (1) Increasing numbers of invasive infections in recent years due to the following pathogens: K. pneumoniae (up 52% since 2014), P. aeruginosa (up 18% in one year and 43% since 2013), S. pneumoniae (up 37% since 2015), E. coli (up 16% since 2013), E. faecium (up 11% since 2014) Escherichia coli The proportion of invasive infections caused by 3rd generation cephalosporin-, fluoroquinolone- and multi-drug (MDR; displaying resistance to three or more antimicrobial classes) resistant E. coli have increased to 12.5%, 26.7% and 15.1%, respectively, the highest proportions to date; the proportion E. coli extended-spectrum beta-lactamase (ESBL)-producing is also at its highest level (11.%) to date Four isolates were found to be carbapenemase-producers (all OXA-48) Staphylococcus aureus/ MRSA The proportion of S. aureus bloodstream infections (BSIs) that were meticillin-resistant (MRSA) increased to16.3% EARS-Net data on Antimicrobial Resistance in Ireland, Q

KEY POINTS, 2017 (2) Klebsiella pneumoniae The proportion of invasive infections caused by fluoroquinolone-, gentamicin-/aminoglycoside- and multi-drug (MDR; displaying resistance to three or more antimicrobial classes) resistant K. pneumoniae have increased to 22.8%, 17.0%/18.3/% and 21.0%, respectively, the highest proportions to date Four isolates were found to be carbapenemase-producers (all OXA-48): the emergence of carbapenemase-producing strains of K. pneumoniae and other enterobacteriaceae (CPE) in recent years is cause for a concern; a national CPE public health emergency was declared in November 2017 Enterococcus faecium/ VREfm (vancomycin-resistant E. faecium) The proportion of E. faecium BSI that are vancomycin-resistant (i.e. VREfm) has decreased to 39.4%, the lowest level since 2011 Ireland had the 2nd highest proportion of VREfm in Europe in 2016 (and before that the highest since 2008) Acinetobacter spp. One carbapenemase-producing (OXA-23/51) MDR isolate was reported EARS-Net data on Antimicrobial Resistance in Ireland, Q

Why do surveillance of antimicrobial resistance?
Surveillance data provides information for action: timely data collection, validation, analysis, feedback and reporting therefore very important Monitor trends over time: Emergence and spread of AMR phenotypes Inform policy makers Effect of interventions, e.g. following introduction of vaccine EARS-Net data on Antimicrobial Resistance in Ireland, Q

EARS-Net (previously known as EARSS)
Established as European Antimicrobial Resistance Surveillance System (or EARSS) in 1998 by EC DG-SANCO organised by Dutch public health institute (RIVM) = Europe-wide co-ordination HPSC in Ireland Transferred to ECDC in 2010 Name changed to EARS-Net An international network of national surveillance systems with laboratories and hospitals from 29 EU/EEA countries participating in 2016 Aims to collect comparable & reliable antimicrobial resistance (AMR) data for public health action EARS-Net data on Antimicrobial Resistance in Ireland, Q

EARS-Net Objectives Collect comparable, representative and accurate AMR data Analyse temporal and spatial trends of AMR in Europe Provide timely AMR data for policy decisions Encourage the implementation, maintenance and improvement of AMR surveillance programmes Support national systems in their efforts to improve diagnostic accuracy by offering an annual External Quality Assessment (EQA) EARS-Net data on Antimicrobial Resistance in Ireland, Q

EARS-Net case definition
EARS-Net collects antimicrobial resistance data on the first invasive isolate (specimen types indicated below) per patient per quarter for eight key pathogens (arranged in order of frequency reported): Escherichia coli (blood or CSF) Staphylococcus aureus (blood only) Enterococcus faecium (blood only) Klebsiella pneumoniae (blood or CSF) Streptococcus pneumoniae (blood or CSF) Enterococcus faecalis (blood only) Pseudomonas aeruginosa (blood or CSF) Acinetobacter spp. (blood or CSF) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Data collected by EARS-Net
Routinely-generated data from laboratories on key antibiotics for eight pathogens under surveillance Qualitative, i.e. RIS data (interpretations only) Quantitative, i.e. MIC/Etest results in mg/l* *especially important for pneumococci/penicillin and cefotaxime Reference laboratory data Serotypes on pneumococci Confirmation on K. pneumoniae/E. coli isolates that are carbapenemase-producing CRE EARS-Net data on Antimicrobial Resistance in Ireland, Q

Data Management Nationally Data stored in WHONET format (a freeware from WHO, which is versatile for collecting, storing and analysing AMR data) and in an Access database at HPSC Locally WHONET files* LIMS files*, that can be translated to WHONET via BacLink software Excel template* Isolate Record Forms *all electronic files should be encrypted before being sent to HPSC by EARS-Net data on Antimicrobial Resistance in Ireland, Q

Participation in EARS-Net
Between 2007 and 2014, all laboratories (n=39) and acute hospitals (n=58) participated in EARS-Net resulting in 100% coverage of the Irish population Between 2015 and 2017, a number of laboratories suspended their participation due to resource issues: Midland Regional Hospital Portlaoise for two periods: Q2 - Q and Q Q1 2017 Cavan General Hospital from Q onwards Midland Regional Hospital Tullamore between Q2 and Q3 2015 Letterkenny General Hospital between Q3 and Q4 2015 The overall population coverage by EARS-Net was estimated to be ~97% in 2015, ~99% in 2016 and ~99.5% in 2017 Note: estimated population coverage by EARS-Net in other EU/EEA countries varies considerably from <20% to 100% EARS-Net data on Antimicrobial Resistance in Ireland, Q

Data Management EUCAST vs CLSI (situation as of Q4 2017) 35 labs have now adopted EUCAST guidelines = 94% of all isolates 4 labs still using CLSI Data collection (in Q4 2017) WHONET – 24 labs – representing 87% of data* LIMS file – 2 labs – 4% of data* Excel – 3 labs – 4% of data* Paper forms – 11 labs – 4% of data* * Not adding up to 100% due to rounding EARS-Net data on Antimicrobial Resistance in Ireland, Q

Escherichia coli EARS-Net data on Antimicrobial Resistance in Ireland, Q

Escherichia coli invasive infections
AMP, Ampicillin; 3GC, 3rd-generation cephalosporins; FQ, fluoroquinolones; GEN, gentamicin; AG, aminoglycosides; MDR, multi-drug resistance Key messages: The numbers of invasive E. coli infections have increased by 26% over the past 5 years 3rd generation cephalosporin- and gentamicin resistance have increased in 2017 to their highest proportions to date ESBL-positive E. coli has also increased in 2017 to its highest proportion to date EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in E. coli invasive infections showing percentage resistance to fluoroquinolones, aminoglycosides and 3rd-generation cephalosporins FQREC, fluoroquinolone (e.g. ciprofloxacin)-resistant E. coli; GEN, gentamicin, TOB, tobramycin; AMK, amikacin (GEN, TOB and AMK are aminoglycosides); 3GC, 3rd-generation cephalosporins (e.g. cefotaxime, ceftazidime) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in E. coli invasive infections showing percentage 3GC-resistance and ESBL-positivity 3GC, 3rd-generation cephalosporins (e.g. cefotaxime, ceftazidime); ESBL, extended-spectrum beta-lactamase EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of 3rd-generation cephalosporin resistant E
Distribution of 3rd-generation cephalosporin resistant E. coli in EARS-Net countries in 2016 IE rank: 18/30 (12.2%) EU/EEA: 12.4% (population-weighted mean) 2016 trends 11 countries 1 country Map downloaded from ECDC’s TESSy database on 20/10/2017:

Trends in E. coli invasive infections with percentage multi-drug resistance MDR, multidrug resistance (defined as resistance to 3 or more classes of antibiotics OR a confirmed carbapenemase producer) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Carbapenase-producing carbapenem- resistant enterobacteriaceae (CRE)
CBP, carbapenem; CPE, carbapenemase-producing enterobacteriaceae Key messages: 4 confirmed carbapenemase-producing E. coli isolates from invasive infections reported in 2017: all OXA-48 8 confirmed carbapenemase-producing invasive E. coli isolates reported to date: NDM (one each in 2014, 2015 and 2016) and 5 OXA-48 (one in 2015 and 4 in 2017) EARS-Net data on Antimicrobial Resistance in Ireland, Q

EARS-Net data on Antimicrobial Resistance in Ireland, Q3 2015
Resistance to 3 or more antimicrobial groups: Ireland ranks 16th of 30 countries Ireland has one of the lowest proportions of isolates that are fully susceptible to all 5 antimicrobial groups EARS-Net data on Antimicrobial Resistance in Ireland, Q3 2015

Distribution of multi-drug resistant (MDR) E
Distribution of multi-drug resistant (MDR) E. coli in EARS-Net countries in 2016 IE rank: 16/30 (5.3%) EU/EEA: 4.8% (population-weighted mean) Note: MDR defined as combined resistance to 3GCs, fluoroquinolones and aminoglycosides 2016 trends 7 countries 2 countries Map downloaded from ECDC’s TESSy database on 20/10/2017:

Staphylococcus aureus
EARS-Net data on Antimicrobial Resistance in Ireland, Q

Staphylococcus aureus bloodstream infections
Key messages: The proportion of S. aureus bloodstream infections that was meticillin-resistant (i.e. %MRSA) increased to 16.3% in 2017: this is the first increase in over 10 years The %MRSA (14.7%) in 2016 was the lowest proportion to date EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in S. aureus bloodstream infections showing %MRSA

Distribution of MRSA in EARS-Net countries in 2016
IE rank: 12/30 (14.3%) EU/EEA: 13.7% (population-weighted mean) 2016 trends 1 country 11 countries Map downloaded from ECDC’s TESSy database on 20/10/2017: EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of MRSA in EARS-Net countries in 2016

Trends in S. aureus bloodstream infections (rates)
Key message: In 2017, the %MRSA and MRSA rate increased compared to 2016, while the MSSA rate decreased EARS-Net data on Antimicrobial Resistance in Ireland, Q

For S. aureus/MRSA data by acute hospital in Ireland, please click here EARS-Net data on Antimicrobial Resistance in Ireland, Q

Klebsiella pneumoniae

Klebsiella pneumoniae invasive infections
Key messages: The number of invasive K. pneumoniae infections have increased by 52% over the past 5 years 3GC-resistance and ESBL-positivity have stabilised over the past 3 years Fluoroquinolone-, gentamicin-/aminoglycoside- and multi-drug resistance have fluctuated widely over the past 5 years Carbapenem-resistance among K. pneumoniae, particularly as a result of carbapenemase production (see later slide), is an emerging problem EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in K. pneumoniae invasive infections showing percentage resistance to fluoroquinolones, aminoglycosides and 3rd-generation cephalosporins 3GC, 3rd-generation cephalosporins (e.g. cefotaxime, ceftazidime); CIP, ciprofloxacin; OFX, ofloxacin (CIP and OFX are fluoroquinolones); GEN, gentamicin, TOB, tobramycin; AMK, amikacin (GEN, TOB and AMK are aminoglycosides) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in K. pneumoniae invasive infections with percentage 3GC-resistance and ESBL-positivity EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of 3rd-generation cephalosporin resistant K. pneumoniae in EARS-Net countries in 2016 IE rank: 21/30 (15.7%) Median = 31.1% 2016 trends 6 countries 4 countries Map downloaded from ECDC’s TESSy database on 20/10/2017: EARS-Net data on Antimicrobial Resistance in Ireland, Q

Carbapenemase-producing K. pneumoniae
CBP, carbapenem; CPE, carbapenemase-producing enterobacteriaceae * An additional carbapenemase-producing isolate (also OXA-48) was reported that was carbapenem-susceptible Key messages: A national public health emergency for carbapenemase-producing enterobacteriaceae (CPE) was declared in November 2017 In 2017, there were 4confirmed carbapenemase-producing K. pneumoniae from invasive infections compared to 4 in 2016, 7 in 2015 and 2 each in 2014 and 2013 Of 23 confirmed carbapenemases to date, 17 were OXA-48 and 6 were KPC EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in carbapenemase-producing K. pneumoniae
CBP, carbapenem EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in K. pneumoniae invasive infections with percentage 3GC- and carbapenem-resistance CBP, carbapenem EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of carbapenem-resistant K
Distribution of carbapenem-resistant K. pneumoniae in EARS-Net countries in 2016 IE rank: 13/30 (0.7%) EU/EEA: 6.1% (population-weighted mean) 2016 trends 2 countries 3 countries Map downloaded from ECDC’s TESSy database on 20/10/2017:

Trends in K. pneumoniae invasive infections with percentage multi-drug resistance (MDR) MDR, multi-drug resistance (defined as resistance to 3 or more of the 5 antibiotic classes EARS-Net data on Antimicrobial Resistance in Ireland, Q

2008 data downloaded from TESSy, 31/03/2016
Distribution of multi-drug resistant (MDR) K. pneumoniae in EARS-Net countries in 2016 2008 data downloaded from TESSy, 31/03/2016 IE rank: 21/30 (5.8%) EU/EEA: 15.8% (population-weighted mean) Note: MDR defined as combined resistance to 3GCs, fluoroquinolones and aminoglycosides 2016 trends 4 countries 3 countries Map downloaded from ECDC’s TESSy database on 20/10/2017:

EARS-Net data on Antimicrobial Resistance in Ireland, Q3 2015
Resistance to 4 or more antimicrobial groups: Ireland ranks 21st of 30 countries Ireland has one of the lowest proportions of invasive K. pneumoniae isolates that are MDR EARS-Net data on Antimicrobial Resistance in Ireland, Q3 2015

Enterococcus faecium EARS-Net data on Antimicrobial Resistance in Ireland, Q

Enterococcus faecium bloodstream infections
VAN, vancomycin; VREfm, vancomycin-resistant E. faecium Key messages: The number of invasive E. faecium infections have increased by 11% over the past 4 years Ireland had the 2nd highest proportion (%) of VREfm in Europe after Cyprus in 2016 (and the highest for the previous 8 successive years) In 2017, the %VREfm bloodstream infections decreased to its lowest level since 2011 One linezolid-resistant isolate (also vancomycin-resistant) was reported in 2017 EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in E. faecium bloodstream infections showing %VRE
VAN, vancomycin; VRE, vancomycin-resistant enterococcus; VREfm, vancomycin-resistant E. faecium EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of vancomycin-resistant E
Distribution of vancomycin-resistant E. faecium (VREfm) in EARS-Net countries in 2016 IE rank: 2/30 (44.1%) EU/EEA: 11.8% (population-weighted mean) 2016 trends 7 countries 2 countries Map downloaded from ECDC’s TESSy database on 20/10/2017:

Pseudomonas aeruginosa

P. aeruginosa invasive infections
MDR, Multi-drug resistant [defined as resistance to three or more of the 5 required antibiotics/antibiotic classes: piperacillin-tazobactam (TZP); ceftazidime (CAZ); carbapenems (IMP/MEM); fluoroquinolones (FQ); aminoglycosides (AG)] Key message: The numbers of invasive P. aeruginosa infections have increased by 18% over the past year and by 43% over the past 5 years EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in P. aeruginosa invasive infections showing percentage resistance to mandatory antibiotics/ antibiotic classes (according to EARS-Net protocol) PIP, piperacillin; TZP, piperacillin/tazobactam; CAZ, ceftazidime; IPM, imipenem; MEM, meropenem (IPM and MEM are carbapenems); CIP, ciprofloxacin; OFX, ofloxacin (CIP and OFX are fluoroquinolones); GEN, gentamicin; TOB, tobramycin and AMK, amikacin (GEN, TOB and AMK are aminoglycosides) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in P. aeruginosa invasive infections with percentage multi-drug resistance (MDR) MDR, multi-drug resistance defined as resistance to three or more of the 5 required antibiotics/antibiotic classes (piperacillin-tazobactam; ceftazidime; carbapenems; fluoroquinolones; aminoglycosides) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Streptococcus pneumoniae

Invasive Streptococcus pneumoniae infections
PSSP, penicillin-susceptible S. pneumoniae; PNSP, penicillin-non-susceptible S. pneumoniae; I, intermediate-level resistance; R, high-level resistance; NS, non-susceptible; ND, not determined Key messages: In 2016, the numbers of invasive S. pneumoniae infections increased by 37% since 2015 to the highest level since 2008 when PCV7 was introduced to the vaccination schedule The proportion of invasive infections due to PNSP decreased to its lowest level since 2006 Four isolates from bloodstream infections were determined to be HLR, all belonged to serotype 19A EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in S. pneumoniae bloodstream infections showing %PNSP
PCV7 introduced Sept ‘08 PCV13 introduced Dec ‘10 PNSP, penicillin-non-susceptible S. pneumoniae; I, intermediate; HLR, high-level resistant EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of penicillin-non-susceptible S
Distribution of penicillin-non-susceptible S. pneumoniae (PNSP) in EARS-Net countries in 2016 IE rank: 8/29 (16.5%) BUT issues re: comparability of EU data as not all data are interpreted in a standard way (see next slide) Map downloaded from ECDC’s TESSy database on 20/10/2017:

Penicillin MIC distribution: Latest CLSI non-meningitis breakpoints
Effect of different interpretive criteria to categorise penicillin susceptibility results in pneumococci Penicillin MIC distribution: Latest CLSI meningitis breakpoints (same as EUCAST meningitis bps) Penicillin MIC distribution: Latest CLSI non-meningitis breakpoints A B S, ≤2mg/L; I, 4mg/L; R, ≥8mg/L S, ≤0.06mg/L; R, ≥0.12mg/L Penicillin MIC distribution: Latest CLSI oral (=old) breakpoints (similar to EUCAST non-meningitis bps) C Our current strategy (in line with most European countries) CLSI: S, ≤0.06mg/L; I, mg/L; R, ≥2mg/L (EUCAST: S, ≤0.06mg/L; I, mg/L; R, ≥4mg/L)

Monitoring pneumococcal serotypes: serotype replacement
Data from the Irish Pneumococcal Reference Laboratory Effects of vaccination with PCV13: Decreases among most PCV13 serotypes expected; Increases among a few serotypes due to poor immunogenicity of these serotypes in the vaccine PCV13 serotypes (selected) Non-PCV13 serotypes (selected) Increases among certain non-PCV13 serotypes = serotype replacement EARS-Net data on Antimicrobial Resistance in Ireland, Q

Update from the Irish Pneumococcal Reference Laboratory
The Irish Pneumococcal Reference Laboratory in collaboration with Temple Street, Beaumont, RCSI and HPSC would like to thank all the laboratory scientists and consultant microbiologists in Irish hospitals for referring invasive pneumococcal isolates. We would also like to thank all the staff in the Departments of Public Health involved in the surveillance of pneumococcal disease in Ireland. We recently published a paper describing the typing data associated with IPD in older adults in Ireland. Please find the details below: The epidemiology of invasive pneumococcal disease in older adults in the post-PCV era. Has there been a herd effect? Epidemiology and Infection. 2017;145(11): Link: Laboratories are kindly requested to use the Irish Meningitis & Sepsis Reference Laboratory’s (IMSRL) Isolate Referral Forms when referring any isolates (including S. pneumoniae and iGAS) available on our website: EARS-Net data on Antimicrobial Resistance in Ireland, Q

Other pathogens EARS-Net data on Antimicrobial Resistance in Ireland, Q

Enterococcus faecalis (2017; 345 isolates) 2 isolates (0.6%) were reported with resistance to vancomycin One isolate was linezolid-resistant and this was confirmed as optrA gene-positive; in addition, 2 isolates (from one patient, in different quarters) were reported with intermediate-level resistance to linezolid Acinetobacter spp. (2017; 73 isolates) One isolate was MDR, defined as resistant to fluoroquinolones, aminoglycosides and carbapenems: this isolate was also found to be a carbapenemase-producer (OXA-23/51) MDR Acinetobacter is a major problem in Eastern and Southern European countries including: Poland (2016, 60%) Italy (2016, 75%) Greece (2016, 84%) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Candidaemia in Ireland, 2017
Case definition: First isolate of each Candida spp. from blood per patient per year 22 laboratories reported 147 cases from 139 patients in 28 acute hospitals and one non-acute facility (note: 8 patients each had 2 different Candida spp.) No C. auris reported in 2017 No data on candidaemia were received from 17 laboratories Breakdown of Candida spp. isolated from blood in patients in Irish hospitals, 2017 Median age = 68 years Age range = 2 days – 95 years % males = 63% Majority (85, 58%) of cases were from tertiary hospitals Majority of cases (76%) occurred on day 3 or later after admission* *where admission date provided EARS-Net data on Antimicrobial Resistance in Ireland, Q

Acknowledgements All microbiology laboratories for their continued support for EARS-Net and for providing data for this report EARS-Net Steering Group Microbiology team at HPSC Irish Pneumococcal Reference Laboratory National Carbapenemase-Producing Enterobacteriaceae Reference Laboratory Service (CPEaRLS) EARS-Net at ECDC, Stockholm, Sweden for providing the European data and maps EARS-Net data on Antimicrobial Resistance in Ireland, Q

Additional slides EARS-Net data on Antimicrobial Resistance in Ireland, Q

Summary of resistance trends (selected drug/bug combinations)

Monitoring trends over time: changing epidemiology (1)

Monitoring trends over time: changing epidemiology (2)

Breakdown of EARS-Net pathogens by age and sex in 2016

S. aureus BSI, 2016: age and sex breakdown
64% of all S. aureus BSIs were in males (also 67% of MRSA and 64% of MSSA BSIs): males were 1.8-times more likely to get a S. aureus BSI than females Frequency of S. aureus BSIs increased with age, with the majority of infections occurring in adults aged over 60 years (60%; 73% for MRSA and 57% for MSSA BSIs) Median age for MRSA infection was 72 years (95%CI, 69-75) and for MSSA infection was 64 years (95%CI, 63-65)

E. faecium BSI isolates, 2014-2016
45% of E. faecium (EFM) isolates from bloodstream infections (BSIs) in Ireland (IE) are VRE 79% of EFM BSI isolates come from IE’s 9 tertiary hospitals 52% of EFM BSI isolates from tertiary hospitals are VRE compared with 30% from non-tertiary hospitals/facilities

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