LA-MRSA in the Netherlands: the past, presence and future.

LA-MRSA in the Netherlands: the past, presence and future. Prof. Jaap Wagenaar DVM, PhD With input from Prof. Jan Kluytmans MD, PhD Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht - NL Central Veterinary Institute, Lelystad - NL j.wagenaar@uu.nl

Outline MRSA background, the problem in humans LA-MRSA in pigs, veal calves and food products LA-MRSA in humans How do we manage LA-MRSA in the Netherlands? The future and conclusions

When Staphylococcus aureus becomes MRSA classification..

HA-MRSA, CA-MRSA, LA-MRSA HA-MRSA: Hospital acquired emerged in the 60 s (after introduction of methicillin in 1959) multi-resistant antibiotic usage facilitates spread most important control method is prevention of cross-contamination CA-MRSA: Community associated emerged in the 90 s in community no relation health care settings resistance moderate but often toxin (PVL+) LA-MRSA

MRSA in hospitals: a problem?

EARSS report 2013 (invasive MRSA)

MRSA (in general) in the Netherlands (humans) Dutch policy for health care institutions: Restrictive use of antibiotics Very strict infection control MRSA search and destroy policy: Screening of persons at risk for MRSA at admission to a hospital Isolation of colonized patients and decolonization therapy Prevalence of MRSA in the Dutch community < 0.1%

MRSA in animals

First findings in 2005...(1) Publication of 2 Dutch medical doctors: MRSA is present in pigs and there is transmission of MRSA to humans. Strong concerns from medical and public health side (Search and Destroy Policy) Uncertainty about prevalence, capacity to cause disease, antimicrobial resistance, transmission between humans, spread in the food chain...

First findings in 2005...(2) Until then farmers were not identified as risk group. Till 2003 no pig-mrsa (NT-MRSA; LA-MRSA). Many pig farmers, many people in contact with pigs, nurses living on farms

Science (329), 27 August 2010

3000 1500 NT-MRSA MRSA 0 2002 2002 2003 2004 2005 2006 2007 De Neeling

Prevalence MRSA veal farms: 88% People living at veal farms on average 16% Farmers: 33% Family members: 8% Prevalence MRSA on pig farms: >70% People living on pig farms on average 14% Farmers: 49% Family members: 3%

LA-MRSA in Europe (2009)

LA-MRSA in pigs: not limited to CC398 Italy: ST1 China, Malaysia: ST9 Korea (meat): ST72

MRSA in other animals than pigs Poultry: not frequent (although meat...) Cattle: mastitis cases (overflow from pig farming) Calves arriving at veal calf farm: 10-14% positive Dogs: sporadic cases (overflow) Rabbits...

MRSA in horses 16 14 12 10 8 6 4 t011 t064 t2123 2 0 2003 2004 2005 2006 2007 2008 Van Duijkeren et al., 2010 Picture: Gerald van de Top

MRSA in meat (% positive) NL Germany Canada Korea Beef 10 6 1 Calf 17 lamb/sheep 6 Porc 10 10 0,3 Chicken 27 22 3 0,3 Chicken import 1 Turkey 31 50 21% Game 3 50% De Boer at al, 2009; Fessler et al., 2011; Weese et al., 2010; Lim et al., 2010

Four important questions. Where did LA-MRSA come from? What is the burden in animals? Can a country live with LA-MRSA? Is there any intervention possible?

Where did LA-MRSA come from? Emerging and not only by improved detection ST398 MSSA humans => pigs (acquisition of methicillin and tetracycline resistance) ST9 in other geographical areas? Did anything change in husbandry?

Burden in animals (LA-MRSA vs MSSA) No increase of burden in pigs and poultry Increase of burden in cattle, horses and pets (clinical infections)

Can a country live with LA-MRSA?

General findings as basis for the current policy in NL (I) Prevalence in animal sectors: high in pigs and veal calves, less prevalent in poultry, overflow to horses and companion animals. Risk factors for animals/farms: AMU, trade, management. Risk groups: people working with animals. Transmission of ST398 within hospitals is strongly reduced compared to non-st398 MRSA. Capacity to cause disease: missing virulence factors

General findings as basis for the current policy in NL (II) Presence and potential spread through food: widely present but low concentration considered as a minimal risk for spread into the population. 58% of the initial positive farmers test negative after a period of non-exposure to animals. People living in pig, cattle and veal calf dense municipalities have a slightly increased risk for CC398 in comparison to non-cc398.

Isolates received in the Dutch national MRSA surveillance - MRSA isolated from humans received in the time period 01-01-2008 31-08-2015. The number of isolates are based on one isolate per person per year: the first received and typed MRSA isolate. - Livestock LA-MRSA is defined as MRSA with MLVA-types belonging to MLVA-complex MC0398 (ST398) all other isolates are defined as non-la-mrsa. Source: Leo Schouls and Thijs Bosch National Institute for Public Health and the Environment (RIVM). Infectious Diseases Research, Diagnostics and Screening, dept. Bacterial Surveillance and Response, Bilthoven, Netherlands

Disease (burden) in humans

at present the impact of MRSA in general and LA-MRSA in particular on bacteraemias for the Dutch population appears to be very limited..

Clinical cases in the Netherlands (16 million inh) Fatal (all) MRSA cases ~ 4 per year, ~ 1-2 LA-MRSA (estimated). First isolates submitted as carriage or clinical. Carriers have increased risk for Skin and Soft Tissue infections, no further increased disease risk.

Current approach in health care (I) (thanks to Jan Kluytmans and Marc Bonten) People in contact with production animals are at risk and kept in quarantaine (testing takes 1 hour). Positives (irrespective their type of MRSA) are kept in quarantaine without immediate decontamination. Treatment with mupirocine is common for surgery patients (both MRSA and MSSA). LA-MRSA positives are not decontaminated before going home if they are farmer.

Current approach in health care (II) Unintended LA-MRSA positives in a normal ward are not very prone to transmit the strain to other patients. Outpatients are screened (depending on the hospital) but contacts are considered to be too limited for transmission. No specific measures for nurses living on farms. The burden to the public health system is considered to be limited.

Costs of MRSA control (Search and Destroy) 8 M annually (Van Rijen et al.; Wassenberg et al.) Total budget of care is 92,000,000,000... Strongly dependent on the region (pig dense: 80% of MRSA = LA-MRSA; Utrecht <10%, Amsterdam < 5%; average 40%)

Ongoing concerns about LA-MRSA 20 % of the LA-MRSA positive cases have an unexplained origin (Van Rijen et al., 2014; Lekkerkerk et al., 2015). How unexplained is unexplained... Any change in transmission or disease capacity may increase the burden considerably. When and who will identify this? Some clinical microbiologists are more concerned than others depending on their individual risk-assessment and risk-perception.

Control strategies

MRSA control in humans Use of antimicrobials facilitates colonization and spread Most important control measure: prevent cross contamination! search and destroy strategy

Control options Risk factors Pigs Antimicrobial usage Hygiene Obtaining animals from a positive holding Veal Antimicrobial usage Cleaning and disinfection

Actions on LA-MRSA in animal production Specific actions of farmers (Erik van de Heuvel) PIP effect? Application of bacteriophages (research project), not very promising until now Management changes Reduction in the use of antimicrobials Reduction of the shedding and environmental contamination

Future

Exposure of the general public.. Newspapers, television,.

Chain of action in the Netherlands... Findings/facts (LA-MRSA; ESBLs; Q-fever) Professional discussions Translation towards general public Questions in the parliament (Party for animal rights) Minister of Agriculture set tresholds Action by animal sectors, veterinarians supported by ministry

Effect on sales of antibiotics for animals - NL ~ 65% reduction (2007-2014) Fluoroquinolones and 3rd/4th-gen cefalosporines usage reduced to a minimum

Effect of reductions on the occurrence of antimicrobial resistance in commensal E. coli (MARAN 2015)

Effect of reductions on the occurrence of antimicrobial resistance in commensal E. coli (MARAN 2015)

Conclusions and future LA-MRSA is not the biggest concern More attention towards E. coli (and other Gram-negatives) Overall and specific reduction of AMU: vaccination, biosecurity, improved diagnostics Attention for environmental contamination Preparedness for carbapenemase producing bacteria Very good collaboration between meds and vets