Monitoring of AMR in Russia Surveillance studies conducted by

Institute of Antimicrobial Chemotherapy (IAC) Centre for Monitoring of Antimicrobial Resistance (CMAR)

Prospective surveillance studies on AMR in Russia Ø  Collection of microbial isolates and patient’s data (in CRFs) matching the

defined study criteria and patients’ population

Ø  Repeated cross-sectional studies conducted at intervals of 1-3 years or continuous studies

Ø  Main focuses:

§  Nosocomial infections

§  Community-acquired UTIs

§  Community-acquired LRTI

Ø  Consecutive non-duplicate isolates (one per patient / case of infection)

Ø  Various types of specimens (representative for infection type)

Ø  AST in central laboratory of IAC

Ø  Storage of all isolates (regardless of AMR profile)

Moscow

Participants of IAC / IACMAC surveillance studies on AMR 1994-95: 4 hospitals in 2 cities; 400 isolates

Smolensk

2013-15: 62 hospitals in 50 cities of Russia; ~4000 isolates/year

Krasnodar

Kazan

Novosibirsk

Omsk

Тomsk

Krasnoyarsk

Irkutsk

Voronezh

Stavropol

Tyumen

Yakutsk

Volgograd

Vladivostok

Kaluga

Kemerovo

Lipetsk

Rostov-on-Don

Nizh.Novgorod Orel

Novokuznetsk

Seversk

Nizhnevartovsk

Perm

Chelyabinsk

St.-Petersburg

Tolyatti Ufa

Ryazan

Samara

Yaroslavl

Anadyr

Noyabrsk

Ulan-Ude Barnaul

Khanty-Mansiysk

Surgut Nizhni Tagil

Yekaterinburg

Nab. Chelny Izhevsk

Penza

Rostov

Archangelsk

Petrozavodsk

Murmansk

Vologda Cherepovets

Kislovodsk

+ collaborating sites in 9 cities of Belarus, Kazakhstan, Ukraine and Moldova

Khabarovsk

1994-95 Nosocomial Gram-negative Pathogens Prevalence and Resistance Survey in ICUs (NPRS I) 4 hospitals in 2 cities

1998-99 NPRS II 30 hospitals in 14 cities

2002-04 Antimicrobial resistance in nosocomial bacterial pathogens in Russian ISUs (RESORT) 33 hospitals in 20 cities

2006-08 Antimicrobial resistance in nosocomial bacterial pathogens in wards with intensive use of antibiotics (REVANSH) 36 hospitals in 26 cities

2011-12 Monitoring of prevalence and antimicrobial resistance of nosocomial pathogens and use of antimicrobial agents in tertiary hospitals (MARATHON) 23 hospitals in 19 cities

…

National surveys of AMR in nosocomial pathogens in Russia

New design of AMR surveillance studies in hospitals in Russia

MARATHON-2013: 23 hospitals in 19 cities

MARATHON-2014: 33 hospitals in 22 cities

MARATHON-2015: 23 hospitals in 16 cities (isolates and data submitted by Dec. 2015)

+

APEx (since 2013): carbapenemase-producing Acinetobacter spp., Pseudomonas aeruginosa and Enterobacteriaceae

Ø  Transition from repeated cross-sectional to continuous study design

Ø  Any infections in hospitalised patients: nosocomial or community-acquired (distinguished based on formal ‘48-hour’ criterion and recorded in CRF)

Gram(-) ….............. 72,1% % Escherichia coli 7,8 Klebsiella pneumoniae 17,0

Klebsiella oxytoca 0,4 Enterobacter cloacae 2,6 Enterobacter aerogenes 0,7 Enterobacter asburiae 0,2 Serratia marcescens 1,9 Serratia ureilytica 0,1 Proteus mirabilis 1,7 Proteus vulgaris 0,5 Proteus penneri 0,1 Citrobacter freundii 0,4 Morganella morganii 0,4 Raoultella ornithinolytica 0,1

Pseudomonas aeruginosa 19,9 Pseudomonas mendocina 0,1 Pseudomonas mosselii 0,1 Pseudomonas stutzeri 0,1

Acinetobacter baumannii 14,0 Acinetobacter pittii 0,4 Acinetobacter calcoaceticus 0,2 Acinetobacter genomosp. 13 0,1 Acinetobacter haemolyticus 0,1

Stenotrophomonas maltophilia 2,8 Alcaligenes faecalis 0,5 Alcaligenes xylosoxidans 0,1 Achromobacter xylosoxidans 0,1 Myroides odoratimimus 0,1

Species distribution of bacterial nosocomial pathogens in Russia

Gram(+) …............. 27,9% % Staphylococcus aureus 16,9

Staphylococcus epidermidis 2,0 Staphylococcus haemolyticus 1,4 Staphylococcus hominis 0,5 Staphylococcus albus 0,1 Staphylococcus saprophyticus 0,1 Staphylococcus simulans 0,1 Staphylococcus warneri 0,1

Enterococcus faecalis 4,2 Enterococcus faecium 2,1

Enterococcus gallinarum 0,1 Enterococcus avium 0,1 Enterococcus raffinosus 0,1

Streptococcus agalactiae 0,1 Streptococcus pneumoniae 0,1 Streptococcus pyogenes 0,1

MARATHON Study

Krasnodar

Moscow

Kazan

Novosibirsk

Omsk Тomsk

Krasnoyarsk

Irkutsk

Voronezh

Stavropol

Tyumen

Yakutsk

Volgograd

Vladivostok

Carbapenem resistance (%I+R) and production of carbapenemases in nosocomial Enterobacteriaceae in Russia 2006-07: CPE 1 isolate (0.1%)

Kaluga

Kemerovo

Lipetsk

Rostov-on-Don

Nizh.Novgorod Orel

Novokuznetsk

Seversk

Nizhnevartovsk Yekaterinburg

Smolensk

Perm

Chelyabinsk

St.-Petersburg

Tolyatti Ufa

Ryazan

2011-12: CPE 19 isolates (3.4%), 3 cities

Samara

Yaroslavl

Khabarovsk

Noyabrsk

• OXA-48 (dominant) • VIM-4 (single)

• NDM-1 (sporadic)

• KPC-2 (local)

Barnaul

2012-15 (all studies): CPE >100 isolates, 11 cities

0.1 0.3

2.8 3.2 3.6 2.1

8.4 6.7

9.8

14.0

0.0 0.0 0.1

3.3

1997-99 (n=1598)

2002-04 (n=1374)

2006-07 (n=1039)

2011-12 (n=572)

MER IPM ETP Ca-se.-pos.

Н Н

Krasnodar

Moscow

Kazan

Novosibirsk

Omsk Тomsk

Krasnoyarsk

Irkutsk

Voronezh

Stavropol

Tyumen

Yakutsk

Volgograd

Vladivostok

2002-04: MBL(+) 47 isolates (4.5%), 3 cities

Kaluga

Kemerovo

Lipetsk

Rostov-on-Don

Nizh.Novgorod Orel

Novokuznetsk

Seversk

Nizhnevartovsk Yekaterinburg

Smolensk

Perm

Chelyabinsk

St.-Petersburg

Tolyatti Ufa

Ryazan

• VIM-2 (dominant) • IMP-30 (local)

2006-07: MBL(+) 160 isolates (20.1%), 12 cities 2011-12: MBL(+) 97 изолятов (28.0%), 13 cities

Samara

Yaroslavl

Khabarovsk

Noyabrsk

19.0

39.0

55.9 58.5 55.4

79.3

66.8

0.0 4.5

20.1 28.3

1997-99 (n=821) 2002-04 (n=1053)

2006-07 (n=787) 2011-12 (n=347)

IPM MER MBL-pos.

Н

Carbapenem resistance (%I+R) and production of MBLs in nosocomial Pseudomonas aeruginosa in Russia

2006-15 (all studies): MBL(+) >800 isolates, 24 cities

Epidemic spread of P. aeruginosa ST235 VIM-2 in Belarus, Kazakhstan and Russia

Ø  Rise of MBL prevalence in nosocomial P. aeruginosa in Russia from 4.5% to 28.7% between 2002 and 2010

Ø  96.5% of MBL producers belong to the epidemic clone ST235 VIM-2

251 MBL-pos. isolates, 2003-2012

ST111 (VIM, IMP): 29.9% ST235 (VIM, IMP): 20.7% ST357 (VIM): 12.0% ST233 (VIM): 10.4% ST654 (VIM, IMP, NDM): 7.6% ST773 (VIM): 5.2% Other (VIM, IMP, NDM): 14.3%

Krasnodar

Moscow

Kazan

Novosibirsk

Omsk ТOmsk

Krasnoyarsk

Irkutsk

Voronezh

Stavropol

Tyumen

Yakutsk

Volgograd

Vladivostok

2002-04: Ca-se.(+) 11 isolates (2.4%), 3 cities

Kaluga

Kemerovo

Lipetsk Rostov-on-Don

Nizh.Novgorod Orel

Novokuznetsk

Seversk

Noyabrsk

Yekaterinburg

Smolensk

Perm

Chelyabinsk

St.-Petersburg

Tolyatti Ufa

Ryazan

• OXA-23-like

2006-07: Ca-se.(+) 9 isolates (2.7%), 3 cities

2011-12: Ca-se.(+) 111 isolates (44.0%), 13 cities

Samara

Yaroslavl

Khabarovsk

1997-99: Ca-se.(+) 1 isolate (0.5%)

Murmansk

• OXA-24/40-like (dominant)

• OXA-58-like

­ NDM-1

Ижевск

Сургут

2011-15 (all studies): Ca-se.(+) >700 isolates, 20 cities

3.0 6.0 5.1

48.0

11.8

38.6

67.5

0.5 2.4 2.7

44.0

1997-99 (n=202)

2002-04 (n=466)

2006-07 (n=332)

2011-12 (n=252)

IPM MER Ca-se.-pos.

Н

Carbapenem resistance (%I+R) and production of carbapenemases in nosocomial Acinetobacter spp. in Russia

Dominance of international high-risk clones among Russian nosocomial A. baumannii and ‘allodemic’ pattern of carbapenemase-producing strains

SNP typing and MLST of 103 isolates from 54 hospitals, 32 cities

Nosocomial infections due to carbapenemase-producing Gram-negative pathogens in Russia MARATHON Study (2011-12), 26 hospitals, 19 cities

~13% Ca-se.-positive, (most XDR)

~1% PDR K. pneumoniae17,0%

OXA-48, NDM-1: 1,1%

P. aeruginosa19,9%

A. baumannii14.0%

E. coli7,8%

S. aureus16,9%

Другиебактерии

24,4%

VIM-2: 5,6%

OXA-40/-23/-58: 6,2%

Prospective surveillance studies: Pros and Cons

+  Standardised AST in central lab (MIC data)

+  Storage of collected isolates

but…

–  Low coverage of hospitals and patient population

–  Long time to results!

Future development of AMR surveillance in Russia

Ø  Establishing a network of laboratories to collect reliable AST data as part of the CAESAR (Central Asian and Eastern European Surveillance of Antimicrobial Resistance) project

Ø  Collecting AST data in “real time”

Ø  Development of a web-based resource “Map of Antimicrobial Resistance” (supported by the Ministry of Health of Russian Federation”

§  Distributed access system for coordinating centre, participating centres, and “general users”

§  Interactive trends, charts, geographic maps

§  Basic and advanced statistics and BI tools

§  Comparison of local and national AMR data: “my hospital” vs. city / region / country”