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Multiresistant bacteria

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The document discusses multiresistant bacteria and MRSA, providing definitions and causes of resistance. It notes increasing resistance due to misuse of antibiotics in medicine and agriculture. MRSA infections have increased substantially in German hospitals since the 1990s. Strict isolation procedures and adequate therapy are important for controlling MRSA and other multiresistant bacteria.

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Multiresistant bacteria in conflict between theory and practice 16th September 2011, Düsseldorf Old and new insights into multiresistant bacteria  h  m  i  hygiene  microbiology  infectious diseases Prof. Dr. med. B. Wille Doctor of hygiene and environmental medicine Doctor of microbiology, virology and the epidemiology of infection 16.09.2011 - MRE - Düsseldorf
16.09.2011 - MRE - Düsseldorf Deaths (per 100 000 citizens) due to infection in the U.S.A., 1900-1996 Influenza Pandemic First use of penicillin
1962: “ It‘s time to close the book on infectious diseases“ (Quoted by a senior American health official) 16.09.2011 - MRE - Düsseldorf
Definition of multiresistant bacteria? 16.09.2011 - MRE - Düsseldorf
List of known viruses according to § 23 Abs. 1 S. 1 Types of bacteria: resistance to the following substances has been tested in the framework of clinical-microbiological diagnostics. 1 S. aureus: Vancomycin, Oxacillin , Gentamicin, Quinolone Gr. IV (e.g. Moxifloxacin), Teicoplanin, Quinupristin / Dalfopristin 2 S. pneumoniae: Vancomycin, Penicillin (Oxacillin 1 µg), Cefotaxim, Erythromycin, Quinolone Gr. IV (e.g. Moxifloxacin) 3 E. faecalis / E. faecium: Vancomycin , Gentamicin (“high level”: Gentamicin 500 mg/l; Streptomycin 1000 mg/l (Mikrodil.) or 2000 mg/l (Agardil.), Teicoplanin E. faecium: zusätzlich Quinupristin / Dalfopristin 4 E. coli / Klebsiella spp.: Imipenem / Meropenem, Quinolone Gr. II (e.g. Ciprofloxacin), Amikacin, Ceftazidim, Piperacillin / Tazobactam, Cefotaxim or analogous test substances 5 Enterobacter cloacae / Citrobacter spp. / Serratia marcescens: Imipenem / Meropenem, Chinolon Gr. II (e.g. Ciprofloxacin), Amikacin 6 P. aeruginosa / A. baumannii: : Imipenem / Meropenem, Quinolone Gr. II (e.g. Ciprofloxacin), Amikacin, Ceftazidim, Piperacillin / Tazobactam 7 S. maltophilia: Quinolone Gr. II (e.g. Ciprofloxacin), Amikacin, Ceftazidim, Piperacillin / Tazobactam, Cotrimoxazol 8 Candida spp. * Fluconazol * Only recorded in establishments with haemotological-oncological departments. For the main resistant species the leading resistances are in bold and underlined. Multiresitant bacteria 2010 16.09.2011 - MRE - Düsseldorf
Causes of MRB 1. Misuse of antibiotics in medicine - MRSA: Gyrase inhibitors - ESBL: 3rd generation Cephalosporines - VRE: Vancomycin use 2. Reduced cost of valuable antibiotics 3. Use of antibiotics in veterinary medicine/ intensive farming 16.09.2011 - MRE - Düsseldorf
16.09.2011 - MRE - Düsseldorf Rate of multiresistant bacteria per 1,000 patient days
Increase in resistance through use of antibiotics Increase in Quinolone use of around 1 %  After one month, increase in the incidences of nosocomial ESBL infections reached 4.43 % 16.09.2011 - MRE - Düsseldorf
Increase in resistance through antibiotic use Increase in the use of 3rd Generation Cephalosporins over 12 weeks:  Doubling of ESBL-related nosocomial infections 16.09.2011 - MRE - Düsseldorf
A common wrong interpretation: Out of the 600,000 new incidences per year in Germany “ only“ 5-10 % are due to multiresistant bacteria! 16.09.2011 - MRE - Düsseldorf
16.09.2011 - MRE - Düsseldorf Basic principle of MRB MRB are not different from bacterial infections apart from by their RESISTANCE TO ANTIBIOTICS This means: - They transfer from person to person easily - They are capable of surviving (epidemic MRSA strains)? - Disinfection treatments have limitations *Discussion: Is MRSA connected to increased virulence?
New concept for multi-resistent bacteria ESKAPE (bad bugs, no drugs: no ESKAPE) 16.09.2011 - MRE - Düsseldorf
E : Enterococcus faecium S : Staphyloccocus aureus K : Klebsiella pneumoniae A : Acinetobacter baumannii P : Pseudomonas aeruginosa E : Enterobacter species Eskape 16.09.2011 - MRE - Düsseldorf
MRSA-related deaths in Intensive Care Units KISS-Data: 274 ICUs / 505487 Patients 6,888 Pneumonia 1,851 S. aureus 2,357 Primary Septicaemia 378 S. aureus Pneumonia: 105 of 1502 MSSA   (  7 %) 59 of 349 MRSA   (  16.9 %) Primary Septicaemia: 17 of 283 MSSA   (  6 %) 16 of 95 MRSA   (  16.8 %) Gastmeier et al.: Mortality Risk Factors with Nosocimial S. aureus Infections in Intensive Care Units Infection 2005; 33: 50-55 16.09.2011 - MRE - Düsseldorf
ESBL – clinical significance Seoul, Children‘s hospital. Bacteremia with E. coli & K.pneumoniae: Lethality ESBL +: 26,7%; ESBL -: 5,7 % p=0.001 Kim et al. AAC 2002; 46: 1481-91 Los Angeles;  Alter 56y, Bacteremia with E. coli & K. pneumoniae: Failure of initial treatment: ESBL+: 82 %; ESBL -: 20 %; p=0.009 Wong-Beringer et al. CID 2002; 34: 135-46 16.09.2011 - MRE - Düsseldorf
Profile: MRSA / MRSE Omnipotent pyogenic organism MRSA: strong tendency to spread, also among out-patients Outbreaks are falling Large general interest 16.09.2011 - MRE - Düsseldorf
MRSA in Germany (2008) Resistance (in %) against other selected antibiotics 16.09.2011 - MRE - Düsseldorf 2006 2007 2008 Ciprofloxacin 93.8 97.8 91.1 Moxifloxacin - 94.4 89.6 Clindamycin 65.4 72.0 73.4 Gentamycin 13.3 9.8 10.5 Oxytetrazyklin 7.4 6.8 7.8 Rifampicin 2,5 1,1 0.4 Cotrimoxazol 3.1 2.0 10.8 Fosfomycin 3.3 0.6 1.1 Linezolid 0.04 0.11 0.1 Muporizin 2.6 3.3 5.3
MRSA and other multiresistant bacteria Frequency of multiresistant bacteria in German hospitals MRSA: 1990: 1.7 % 1998: 15.2 % 2001: 20.7 % (MRSA proportion of all S. aureus isolates) ICUs: 2003 > 30 % Retirement and care homes: 1-3% of patients (Source PEG, 2003) 16.09.2011 - MRE - Düsseldorf
Breakdown of MRSA ha-MRSA (hospital acquired-MRSA) ca-MRSA: community acquired (community associated MRSA) la-MRSA: lifestock-associated MRSA (presumably low infectivity und pathogenicity from la-MRSA ST 398) 16.09.2011 - MRE - Düsseldorf
Saarland (from 18/10 to 12/12/2010) All registered in-patients during this time period Results: More than 80%, 90% in some hospitals  around 20,000 patients with a total of 405 positive results corresponding prevalence around 0.52 % New data from MRSA screening 16.09.2011 - MRE - Düsseldorf
16.09.2011 - MRE - Düsseldorf Reduction of nosocomial MRSA infections after the introduction of MRSA screening with the LightCycler MRSA advanced test in the Southwest clinical network, Germany (colours correspond with areas within the network), Number of ha-MRSA infections/colonisations New screening implemented
An increased risk for an MRSA colonisation in line with RKI* recommendations exists for: Patients with known MRSA anamnesis Transfers from regions/establishments with a known high MRSA prevalence In-patients who have stayed in hospital for more than 3 days in the last 12 months Patients who have direct (occupational) contact with animals and agricultural animal feed (pigs) In-patients who during their stay have had contact with MRSA carriers (e.g. by staying in the same room) 16.09.2011 - MRE - Düsseldorf * Robert Koch Institute, Germany
An increased risk for an MRSA colonisation in line with RKI recommendations exists for: 6. Patients with two or more of the following risk factors: They are in need of constant care They have had a course of antibiotics in the last 6 months They have a catheter (e.g. bladder catheter, PEG tube) They have dialysis They have skin ulcers/ gangrene/ chronic wounds/ deep infection of soft tissues They have burns 16.09.2011 - MRE - Düsseldorf
The microbiological screening rules include: - A swab of the nose, mouth and - A swab of wounds if necessary 16.09.2011 - MRE - Düsseldorf If the MRSA results are positive (ICD-10: U 80.0): Take hygiene measures (see text) Recommended measures include isolation If the MRSA results are negative: Standard hygiene practices Source: Epi. Bull. 46/2004
Isolation in a single room: 84.5 % Protective overalls: > 90 % Gloves: > 90 % Covered mouth or nose: > 85 % Covered head: 40-50 % (more nurses than doctors) Surface disinfection: daily, almost without exception New MRSA results (Results of a survey from the DGKH* and the BVÖGD**, Autumn 2010) 16.09.2011 - MRE - Düsseldorf *Deutsche Gesellschaft f ür Krankenhaushygiene (German Society for Hospital Hygiene) **Bundesverband der Ärztinnen und Ärzte des Öffentlichen Gesundheitsdienstes (German Federal Association of Doctors in the Public Health Service)
Sanitation of MRSA positive patients: 60% antiseptic washes/showers Mupirocin nose salve: 52 % antiseptic mouthwash: 43 % Entry screening: 38 % refer to the KRINKO* recommendations! New MRSA results (Results of a survey from the DGKH and the BVÖGD, Autumn 2010) 16.09.2011 - MRE - Düsseldorf *Kommision f ür Krankenhaushygiene und Infektionsprävention (The Commission for Hospital Hygiene and Infection Control)
Summary: In 8-12 % of hospitals the MRSA patient recommendations were not satisfactorily applied. 78 % carry out the risk-based screening with at least 50% of the KRINKO recommendations. Source: Hyg. Med. 2011; 36-6, pp. 254-255 New MRSA results (Results of a survey from the DGKH and the BVÖGD, Autumn 2010) 16.09.2011 - MRE - Düsseldorf
MRSA General characteristics of MSSA and MRSA Transfer: Predominately through physical contact (particularly hands!) Aerogens (dust, droplets) Virulence depends on the strain! Contagiousness: depends on the strain and the patient Mode of infection: both endogenous and exogenous 16.09.2011 - MRE - Düsseldorf
MRSA and other multiresistant bacteria Bacteria-related measures for MRSA Strict isolation (including “just“ colonisation cases) Adequate therapy Sanitisation Prevent re-colonisation Avoid postponments in hospital Epidemiological recording/ analysis 16.09.2011 - MRE - Düsseldorf
Psychological aspects of isolation - Measures: Keep isolated patients better informed Show understanding for the unusual situation For longer periods of isolation: a room with a toilet A bathroom for shared rooms Adequate number of staff on wards Daily contact with the ward‘s doctor (very important!) Facilitate flexible visiting hours Aim for individual isolation (thereby protecting personal space) When entering the room, staff should always introduce themselves Always maintain hygiene measures 16.09.2011 - MRE - Düsseldorf C. Hartmann: Wie erleben Patienten die Isolation im Krankenhaus aufgrund einer Infektion o. Kolonisation mit MRSA* Hyg. Med. 30. Jg. 2005 - Issue 7/8, S. 234 - 243 *How patients experience isolation in hospital due to MRSA infection or colonisation
c-MRSA Occurs along with: Deep skin infection (USA, Australia) Invasive infections such as Septicaemia, Endocarditis, Osteomyelitis in prisons, homosexual scenes, sailors It is possibly brought into hospitals USA: Puerperal Mastitis 16.09.2011 - MRE - Düsseldorf
Profile: VRE VR-E. faecalis VR-E. faecium among others No marked virulence Found in the bowels Survival ability: high environmental resistance Not particularly adhesive Immunodeficient patients at risk Nevertheless: outbreaks (oncology) 16.09.2011 - MRE - Düsseldorf
MRSA and other multiresistant bacteria Epidemiology Glycopeptide-Resistant Enterococci (VRE - GRE) USA: from 1989 0.4 % general wards / 0.6 % ICUs 2002 : 76.3 % with E. faecium / 4.5 % with E. faecalis Europe: high rates in England, Italy, Portugal, Greece Germany: E. faecium 5 % maximum E. faecalis < 1 % 16.09.2011 - MRE - Düsseldorf
VRE Strains/ mechanisms of Glycopeptid-Resistence 1 5 strains “ Acquired resistance“: VanA, VanB, VanD, VanE “ Natural resistance“: VanC with 3 subdivisions VanC1 (E. gallinarum) VanC2 VanC3 (E. casselliflavus / E. flavescens) Cross-resistance between VAN and TPL 16.09.2011 - MRE - Düsseldorf
Profile: ESBL ( Extended-Spectrum Beta-Lactamases ) Concerning Enterobacteria (E. coli, Klebsiella spp., among others) but also non-fermenters (P. aeruginosa, Acinetobacter sp., Stenotrophomonas maltophilia, among others) = not a uniform group Resistance: particularly against 3rd and 4th generation cephalosporine Survival ability: love humid environments Bowels, humid biotop Not particularly adhesive (except for P. aeruginosa -> biofilms) 16.09.2011 - MRE - Düsseldorf
MRSA and other multiresistant bacteria ESBL ( Extended-Spectrum Beta-Lactamases ) show resistance to 2nd and 3rd generation Gephalosporins: Germany < 1 -5 % Southern European countries up to 30 % India up to 70 % 20 recorded cases of outbreaks in retirement and care homes No data for: Pseudomonas aeruginosa / Stenotrophomonas maltophilia, Acinetobacter sp. 16.09.2011 - MRE - Düsseldorf
16.09.2011 - MRE - Düsseldorf Development of the rate of 3 rd Generation Cephalosporin resistant E. coli Average ESBL strains make up a growing proportion of E. coli-isolates in German ICUs Month/Year y axis: percent of resistant bacteria
16.09.2011 - MRE - Düsseldorf ESBL – clinical significance Seoul, Children‘s hospital. Bacteremia with E. coli & K.pneumoniae: Lethality ESBL +: 26,7%; ESBL -: 5,7 % p=0.001 Kim et al. AAC 2002; 46: 1481-91 Los Angeles;  Alter 56y, Bacteremia with E. coli & K. pneumoniae: Failure of initial treatment: ESBL+: 82 %; ESBL -: 20 %; p=0.009 Wong-Beringer et al. CID 2002; 34: 135-46
Costs due to multiresistant gram-negative bacteria vs. MRSA F. Dachsböck, Medizinische Universität Wien (Medical University Vienna) Hyg. Med. 31. Jahrgang 2006 – Issue 6, pp. 284-285 n/MRGRN: 99 n/MRSA: 74 Length of stay in both groups: + 6 days compared with normal patients Cost per patient with MRGN:  12,429 EUR Cost per patient with MRSA:  4,545 EUR 16.09.2011 - MRE - Düsseldorf
ESBL Principles ESBL is considerably less persistent on surfaces, appliances, hands and protective clothing than MRSA and VRE. The airborne transmission of ESBL plays a secondary role as it does for nosocomial infection bacteria generally. 16.09.2011 - MRE - Düsseldorf
3rd generation Cephalosporin-resistant Enterobacteria (CRE) Quinolone and 3rd generation Cephalosporin-resistant Enterobacteria (Chin-CRE) Carbapenem-resistant Enterobacteria (Carb-CRE) Consensus recommendation, Baden-Württemberg: Umgang mit Patienten mit hochresistenten Enterobakterien inkl. ESBL-Bildnern*, Hyg.-Med. 2010; 35 (1/2), pp. 40-45 Management of antibiotic resistant Enterobacteria 16.09.2011 - MRE - Düsseldorf *Dealing with patients with high resistant Enterobacteria including ESBL-producers
Infected patients Stool Urine Anogenital region Respiratory tract (rarer) Colonisation of the bowels of staff of healthcare establishments Sources of infection for CRE: 16.09.2011 - MRE - Düsseldorf
Longer patient stays, particularly in ICUs Stays in long-term care facilities Antibiotic use (3rd generation Cephalosporins, SXT, Ciprofloxacin) Transurethral catheter, intubation, tracheotomy, gastrostomy Decubital ulcers Heavy need for care Risks from CRE: 16.09.2011 - MRE - Düsseldorf
Dependent on details about antibiotic resistance Dependent on the type of ward First requirement: a series of Chin-CRE und Carb-CRE negative swabs Carb-CRE: always placed in single room Chin-CRE: room isolation if necessary (Consensus recommendations, Baden-Württemberg) Proposed measures for CRE 16.09.2011 - MRE - Düsseldorf
MBL-producers = Metallo-Beta-Lactamase-producers For infections with ESBL-producers regular therapy with Carbapenems is recommended: Imipenem Meropenem Doripenem Ertapenem Start educating about Carbapenemases and Metallo-Beta-Lactamases 16.09.2011 - MRE - Düsseldorf
MBL 16.09.2011 - MRE - Düsseldorf Carbapenemase-producers discovered so far The phenomenon of Carbapenem resistance is not new; 4 different resistance mechanisms are currently known Italy Turkey India
MBL Cabapenemase/ Metallo-Beta-Lactamase Development VIM, 1999 Italy KPC, 2001 USA OXA 48, 2004 Turkey NDM-1, 2008, India Affected bacteria: Klebsiellen, A. baumannii, E. coli, E. cloacae, P. aeruginosa u.a. Actual data from Germany: NRZ* 1/1/11 to 28/2/11 66 strains nationwide, particularly Berlin, North Rhine-Westphalia, Baden-W ürttermberg - At the time, no recommendations made regarding screening or specific measures 16.09.2011 - MRE - Düsseldorf * Nationales Referenzzentrum für Surveillance von nosokomialen Infektionen (National Reference Centre for the Surveillance of Nosocomial Infections)
ESBL / MBL Applicable antibiotics: Tigecycline Colistin Fosfomycin Combinations Pharmacokinetics and side effects! Pan-resistance possible (Tigecycline: higher mortality rate) 16.09.2011 - MRE - Düsseldorf
Hygiene measures for patients with MBL colonisation/infection Generally the same as ESBL: Gloves/overalls Hygenic disinfection of hands Basic hygiene measures! Individual treatment only if high risk of pathogens spreading (diarrhoea, large open wounds, tracheotomy etc.) 16.09.2011 - MRE - Düsseldorf
Measures for ESBL Isolation Customised solution for every house In unproblematic cases no isolation Screening Use not yet established, possibly to be considered for selected situations (Eich, 2006) 16.09.2011 - MRE - Düsseldorf
Measures for ESBL Decolonisation: No sustained success documented Problems: Quinolone resistance General development of resistance Other areas with colonisation (Nasopharynx: Iodopovidone: J Hosp Infect 2001; 48: 207-213.) 16.09.2011 - MRE - Düsseldorf
Aspects of hospital hygiene for outbreaks of multiresistant bacteria Measures to avoid MRB 1. General antibiotic therapy 2. Antibiotic therapy for patients with MRE in accordance with regulations 3. Quick sanitisation (Example: MRSA) 4. Discharge patients quickly if possible 5. BASIC HYGIENE!!! 16.09.2011 - MRE - Düsseldorf
Increase in the use of alcoholic hand disinfectants of around 1 %  after 4 months Reduction in incidences of infection by around 7 % Basic hygiene/ Disinfection of hands 16.09.2011 - MRE - Düsseldorf
MRSA Measures Sanitisation Skin: Most important principle: Wash when possible! Varied handwashes ( no antiseptics!) Reduces skin irritation Complete body wash Alternative: “wash“ without water with wipes impregnated with active agents. 16.09.2011 - MRE - Düsseldorf
MRSA Measures Sanitisation Mouth: Various solutions (Polyhexanide/ PVP-I/ Octenidine/ others) 16.09.2011 - MRE - Düsseldorf
MRSA Measures Preventing recontamination in the area Change clothing/ underwear daily Change beds daily Electric tootbrushes/ razers (wet) Disinfect dentures Disinfect personal belongings and everyday items 16.09.2011 - MRE - Düsseldorf
MRSA Measures Take action on failures in hygiene Most recontamination in same areas! Switch to other agents? Second attempt is worth it but have a more stringent course of action 16.09.2011 - MRE - Düsseldorf
Not enough staff: more deaths ICUs with high staff numbers: 17 % patient deaths ICUs with low staff numbers:  45 % patient deaths Increase in staff numbers monitored over 4 years:  Number of patient deaths dropped from 34 to 18 % Tarnoff-Mordi WO, How C, Warden A, Shearer AJ: Hospital mortality in relation to staff work load: 4-year-study in adult intensive-care unit Lancet 2000; 356: 185-189 Prospects and limitations of hygiene 16.09.2011 - MRE - Düsseldorf
Louis Pasteur 1895: “ The microbes always have the last word!“ 16.09.2011 - MRE - Düsseldorf

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Multiresistant bacteria

  • 1. Multiresistant bacteria in conflict between theory and practice 16th September 2011, Düsseldorf Old and new insights into multiresistant bacteria  h  m  i  hygiene  microbiology  infectious diseases Prof. Dr. med. B. Wille Doctor of hygiene and environmental medicine Doctor of microbiology, virology and the epidemiology of infection 16.09.2011 - MRE - Düsseldorf
  • 2. 16.09.2011 - MRE - Düsseldorf Deaths (per 100 000 citizens) due to infection in the U.S.A., 1900-1996 Influenza Pandemic First use of penicillin
  • 3. 1962: “ It‘s time to close the book on infectious diseases“ (Quoted by a senior American health official) 16.09.2011 - MRE - Düsseldorf
  • 4. Definition of multiresistant bacteria? 16.09.2011 - MRE - Düsseldorf
  • 5. List of known viruses according to § 23 Abs. 1 S. 1 Types of bacteria: resistance to the following substances has been tested in the framework of clinical-microbiological diagnostics. 1 S. aureus: Vancomycin, Oxacillin , Gentamicin, Quinolone Gr. IV (e.g. Moxifloxacin), Teicoplanin, Quinupristin / Dalfopristin 2 S. pneumoniae: Vancomycin, Penicillin (Oxacillin 1 µg), Cefotaxim, Erythromycin, Quinolone Gr. IV (e.g. Moxifloxacin) 3 E. faecalis / E. faecium: Vancomycin , Gentamicin (“high level”: Gentamicin 500 mg/l; Streptomycin 1000 mg/l (Mikrodil.) or 2000 mg/l (Agardil.), Teicoplanin E. faecium: zusätzlich Quinupristin / Dalfopristin 4 E. coli / Klebsiella spp.: Imipenem / Meropenem, Quinolone Gr. II (e.g. Ciprofloxacin), Amikacin, Ceftazidim, Piperacillin / Tazobactam, Cefotaxim or analogous test substances 5 Enterobacter cloacae / Citrobacter spp. / Serratia marcescens: Imipenem / Meropenem, Chinolon Gr. II (e.g. Ciprofloxacin), Amikacin 6 P. aeruginosa / A. baumannii: : Imipenem / Meropenem, Quinolone Gr. II (e.g. Ciprofloxacin), Amikacin, Ceftazidim, Piperacillin / Tazobactam 7 S. maltophilia: Quinolone Gr. II (e.g. Ciprofloxacin), Amikacin, Ceftazidim, Piperacillin / Tazobactam, Cotrimoxazol 8 Candida spp. * Fluconazol * Only recorded in establishments with haemotological-oncological departments. For the main resistant species the leading resistances are in bold and underlined. Multiresitant bacteria 2010 16.09.2011 - MRE - Düsseldorf
  • 6. Causes of MRB 1. Misuse of antibiotics in medicine - MRSA: Gyrase inhibitors - ESBL: 3rd generation Cephalosporines - VRE: Vancomycin use 2. Reduced cost of valuable antibiotics 3. Use of antibiotics in veterinary medicine/ intensive farming 16.09.2011 - MRE - Düsseldorf
  • 7. 16.09.2011 - MRE - Düsseldorf Rate of multiresistant bacteria per 1,000 patient days
  • 8. Increase in resistance through use of antibiotics Increase in Quinolone use of around 1 %  After one month, increase in the incidences of nosocomial ESBL infections reached 4.43 % 16.09.2011 - MRE - Düsseldorf
  • 9. Increase in resistance through antibiotic use Increase in the use of 3rd Generation Cephalosporins over 12 weeks:  Doubling of ESBL-related nosocomial infections 16.09.2011 - MRE - Düsseldorf
  • 10. A common wrong interpretation: Out of the 600,000 new incidences per year in Germany “ only“ 5-10 % are due to multiresistant bacteria! 16.09.2011 - MRE - Düsseldorf
  • 11. 16.09.2011 - MRE - Düsseldorf Basic principle of MRB MRB are not different from bacterial infections apart from by their RESISTANCE TO ANTIBIOTICS This means: - They transfer from person to person easily - They are capable of surviving (epidemic MRSA strains)? - Disinfection treatments have limitations *Discussion: Is MRSA connected to increased virulence?
  • 12. New concept for multi-resistent bacteria ESKAPE (bad bugs, no drugs: no ESKAPE) 16.09.2011 - MRE - Düsseldorf
  • 13. E : Enterococcus faecium S : Staphyloccocus aureus K : Klebsiella pneumoniae A : Acinetobacter baumannii P : Pseudomonas aeruginosa E : Enterobacter species Eskape 16.09.2011 - MRE - Düsseldorf
  • 14. MRSA-related deaths in Intensive Care Units KISS-Data: 274 ICUs / 505487 Patients 6,888 Pneumonia 1,851 S. aureus 2,357 Primary Septicaemia 378 S. aureus Pneumonia: 105 of 1502 MSSA   (  7 %) 59 of 349 MRSA   (  16.9 %) Primary Septicaemia: 17 of 283 MSSA   (  6 %) 16 of 95 MRSA   (  16.8 %) Gastmeier et al.: Mortality Risk Factors with Nosocimial S. aureus Infections in Intensive Care Units Infection 2005; 33: 50-55 16.09.2011 - MRE - Düsseldorf
  • 15. ESBL – clinical significance Seoul, Children‘s hospital. Bacteremia with E. coli & K.pneumoniae: Lethality ESBL +: 26,7%; ESBL -: 5,7 % p=0.001 Kim et al. AAC 2002; 46: 1481-91 Los Angeles;  Alter 56y, Bacteremia with E. coli & K. pneumoniae: Failure of initial treatment: ESBL+: 82 %; ESBL -: 20 %; p=0.009 Wong-Beringer et al. CID 2002; 34: 135-46 16.09.2011 - MRE - Düsseldorf
  • 16. Profile: MRSA / MRSE Omnipotent pyogenic organism MRSA: strong tendency to spread, also among out-patients Outbreaks are falling Large general interest 16.09.2011 - MRE - Düsseldorf
  • 17. MRSA in Germany (2008) Resistance (in %) against other selected antibiotics 16.09.2011 - MRE - Düsseldorf 2006 2007 2008 Ciprofloxacin 93.8 97.8 91.1 Moxifloxacin - 94.4 89.6 Clindamycin 65.4 72.0 73.4 Gentamycin 13.3 9.8 10.5 Oxytetrazyklin 7.4 6.8 7.8 Rifampicin 2,5 1,1 0.4 Cotrimoxazol 3.1 2.0 10.8 Fosfomycin 3.3 0.6 1.1 Linezolid 0.04 0.11 0.1 Muporizin 2.6 3.3 5.3
  • 18. MRSA and other multiresistant bacteria Frequency of multiresistant bacteria in German hospitals MRSA: 1990: 1.7 % 1998: 15.2 % 2001: 20.7 % (MRSA proportion of all S. aureus isolates) ICUs: 2003 > 30 % Retirement and care homes: 1-3% of patients (Source PEG, 2003) 16.09.2011 - MRE - Düsseldorf
  • 19. Breakdown of MRSA ha-MRSA (hospital acquired-MRSA) ca-MRSA: community acquired (community associated MRSA) la-MRSA: lifestock-associated MRSA (presumably low infectivity und pathogenicity from la-MRSA ST 398) 16.09.2011 - MRE - Düsseldorf
  • 20. Saarland (from 18/10 to 12/12/2010) All registered in-patients during this time period Results: More than 80%, 90% in some hospitals  around 20,000 patients with a total of 405 positive results corresponding prevalence around 0.52 % New data from MRSA screening 16.09.2011 - MRE - Düsseldorf
  • 21. 16.09.2011 - MRE - Düsseldorf Reduction of nosocomial MRSA infections after the introduction of MRSA screening with the LightCycler MRSA advanced test in the Southwest clinical network, Germany (colours correspond with areas within the network), Number of ha-MRSA infections/colonisations New screening implemented
  • 22. An increased risk for an MRSA colonisation in line with RKI* recommendations exists for: Patients with known MRSA anamnesis Transfers from regions/establishments with a known high MRSA prevalence In-patients who have stayed in hospital for more than 3 days in the last 12 months Patients who have direct (occupational) contact with animals and agricultural animal feed (pigs) In-patients who during their stay have had contact with MRSA carriers (e.g. by staying in the same room) 16.09.2011 - MRE - Düsseldorf * Robert Koch Institute, Germany
  • 23. An increased risk for an MRSA colonisation in line with RKI recommendations exists for: 6. Patients with two or more of the following risk factors: They are in need of constant care They have had a course of antibiotics in the last 6 months They have a catheter (e.g. bladder catheter, PEG tube) They have dialysis They have skin ulcers/ gangrene/ chronic wounds/ deep infection of soft tissues They have burns 16.09.2011 - MRE - Düsseldorf
  • 24. The microbiological screening rules include: - A swab of the nose, mouth and - A swab of wounds if necessary 16.09.2011 - MRE - Düsseldorf If the MRSA results are positive (ICD-10: U 80.0): Take hygiene measures (see text) Recommended measures include isolation If the MRSA results are negative: Standard hygiene practices Source: Epi. Bull. 46/2004
  • 25. Isolation in a single room: 84.5 % Protective overalls: > 90 % Gloves: > 90 % Covered mouth or nose: > 85 % Covered head: 40-50 % (more nurses than doctors) Surface disinfection: daily, almost without exception New MRSA results (Results of a survey from the DGKH* and the BVÖGD**, Autumn 2010) 16.09.2011 - MRE - Düsseldorf *Deutsche Gesellschaft f ür Krankenhaushygiene (German Society for Hospital Hygiene) **Bundesverband der Ärztinnen und Ärzte des Öffentlichen Gesundheitsdienstes (German Federal Association of Doctors in the Public Health Service)
  • 26. Sanitation of MRSA positive patients: 60% antiseptic washes/showers Mupirocin nose salve: 52 % antiseptic mouthwash: 43 % Entry screening: 38 % refer to the KRINKO* recommendations! New MRSA results (Results of a survey from the DGKH and the BVÖGD, Autumn 2010) 16.09.2011 - MRE - Düsseldorf *Kommision f ür Krankenhaushygiene und Infektionsprävention (The Commission for Hospital Hygiene and Infection Control)
  • 27. Summary: In 8-12 % of hospitals the MRSA patient recommendations were not satisfactorily applied. 78 % carry out the risk-based screening with at least 50% of the KRINKO recommendations. Source: Hyg. Med. 2011; 36-6, pp. 254-255 New MRSA results (Results of a survey from the DGKH and the BVÖGD, Autumn 2010) 16.09.2011 - MRE - Düsseldorf
  • 28. MRSA General characteristics of MSSA and MRSA Transfer: Predominately through physical contact (particularly hands!) Aerogens (dust, droplets) Virulence depends on the strain! Contagiousness: depends on the strain and the patient Mode of infection: both endogenous and exogenous 16.09.2011 - MRE - Düsseldorf
  • 29. MRSA and other multiresistant bacteria Bacteria-related measures for MRSA Strict isolation (including “just“ colonisation cases) Adequate therapy Sanitisation Prevent re-colonisation Avoid postponments in hospital Epidemiological recording/ analysis 16.09.2011 - MRE - Düsseldorf
  • 30. Psychological aspects of isolation - Measures: Keep isolated patients better informed Show understanding for the unusual situation For longer periods of isolation: a room with a toilet A bathroom for shared rooms Adequate number of staff on wards Daily contact with the ward‘s doctor (very important!) Facilitate flexible visiting hours Aim for individual isolation (thereby protecting personal space) When entering the room, staff should always introduce themselves Always maintain hygiene measures 16.09.2011 - MRE - Düsseldorf C. Hartmann: Wie erleben Patienten die Isolation im Krankenhaus aufgrund einer Infektion o. Kolonisation mit MRSA* Hyg. Med. 30. Jg. 2005 - Issue 7/8, S. 234 - 243 *How patients experience isolation in hospital due to MRSA infection or colonisation
  • 31. c-MRSA Occurs along with: Deep skin infection (USA, Australia) Invasive infections such as Septicaemia, Endocarditis, Osteomyelitis in prisons, homosexual scenes, sailors It is possibly brought into hospitals USA: Puerperal Mastitis 16.09.2011 - MRE - Düsseldorf
  • 32. Profile: VRE VR-E. faecalis VR-E. faecium among others No marked virulence Found in the bowels Survival ability: high environmental resistance Not particularly adhesive Immunodeficient patients at risk Nevertheless: outbreaks (oncology) 16.09.2011 - MRE - Düsseldorf
  • 33. MRSA and other multiresistant bacteria Epidemiology Glycopeptide-Resistant Enterococci (VRE - GRE) USA: from 1989 0.4 % general wards / 0.6 % ICUs 2002 : 76.3 % with E. faecium / 4.5 % with E. faecalis Europe: high rates in England, Italy, Portugal, Greece Germany: E. faecium 5 % maximum E. faecalis < 1 % 16.09.2011 - MRE - Düsseldorf
  • 34. VRE Strains/ mechanisms of Glycopeptid-Resistence 1 5 strains “ Acquired resistance“: VanA, VanB, VanD, VanE “ Natural resistance“: VanC with 3 subdivisions VanC1 (E. gallinarum) VanC2 VanC3 (E. casselliflavus / E. flavescens) Cross-resistance between VAN and TPL 16.09.2011 - MRE - Düsseldorf
  • 35. Profile: ESBL ( Extended-Spectrum Beta-Lactamases ) Concerning Enterobacteria (E. coli, Klebsiella spp., among others) but also non-fermenters (P. aeruginosa, Acinetobacter sp., Stenotrophomonas maltophilia, among others) = not a uniform group Resistance: particularly against 3rd and 4th generation cephalosporine Survival ability: love humid environments Bowels, humid biotop Not particularly adhesive (except for P. aeruginosa -> biofilms) 16.09.2011 - MRE - Düsseldorf
  • 36. MRSA and other multiresistant bacteria ESBL ( Extended-Spectrum Beta-Lactamases ) show resistance to 2nd and 3rd generation Gephalosporins: Germany < 1 -5 % Southern European countries up to 30 % India up to 70 % 20 recorded cases of outbreaks in retirement and care homes No data for: Pseudomonas aeruginosa / Stenotrophomonas maltophilia, Acinetobacter sp. 16.09.2011 - MRE - Düsseldorf
  • 37. 16.09.2011 - MRE - Düsseldorf Development of the rate of 3 rd Generation Cephalosporin resistant E. coli Average ESBL strains make up a growing proportion of E. coli-isolates in German ICUs Month/Year y axis: percent of resistant bacteria
  • 38. 16.09.2011 - MRE - Düsseldorf ESBL – clinical significance Seoul, Children‘s hospital. Bacteremia with E. coli & K.pneumoniae: Lethality ESBL +: 26,7%; ESBL -: 5,7 % p=0.001 Kim et al. AAC 2002; 46: 1481-91 Los Angeles;  Alter 56y, Bacteremia with E. coli & K. pneumoniae: Failure of initial treatment: ESBL+: 82 %; ESBL -: 20 %; p=0.009 Wong-Beringer et al. CID 2002; 34: 135-46
  • 39. Costs due to multiresistant gram-negative bacteria vs. MRSA F. Dachsböck, Medizinische Universität Wien (Medical University Vienna) Hyg. Med. 31. Jahrgang 2006 – Issue 6, pp. 284-285 n/MRGRN: 99 n/MRSA: 74 Length of stay in both groups: + 6 days compared with normal patients Cost per patient with MRGN:  12,429 EUR Cost per patient with MRSA:  4,545 EUR 16.09.2011 - MRE - Düsseldorf
  • 40. ESBL Principles ESBL is considerably less persistent on surfaces, appliances, hands and protective clothing than MRSA and VRE. The airborne transmission of ESBL plays a secondary role as it does for nosocomial infection bacteria generally. 16.09.2011 - MRE - Düsseldorf
  • 41. 3rd generation Cephalosporin-resistant Enterobacteria (CRE) Quinolone and 3rd generation Cephalosporin-resistant Enterobacteria (Chin-CRE) Carbapenem-resistant Enterobacteria (Carb-CRE) Consensus recommendation, Baden-Württemberg: Umgang mit Patienten mit hochresistenten Enterobakterien inkl. ESBL-Bildnern*, Hyg.-Med. 2010; 35 (1/2), pp. 40-45 Management of antibiotic resistant Enterobacteria 16.09.2011 - MRE - Düsseldorf *Dealing with patients with high resistant Enterobacteria including ESBL-producers
  • 42. Infected patients Stool Urine Anogenital region Respiratory tract (rarer) Colonisation of the bowels of staff of healthcare establishments Sources of infection for CRE: 16.09.2011 - MRE - Düsseldorf
  • 43. Longer patient stays, particularly in ICUs Stays in long-term care facilities Antibiotic use (3rd generation Cephalosporins, SXT, Ciprofloxacin) Transurethral catheter, intubation, tracheotomy, gastrostomy Decubital ulcers Heavy need for care Risks from CRE: 16.09.2011 - MRE - Düsseldorf
  • 44. Dependent on details about antibiotic resistance Dependent on the type of ward First requirement: a series of Chin-CRE und Carb-CRE negative swabs Carb-CRE: always placed in single room Chin-CRE: room isolation if necessary (Consensus recommendations, Baden-Württemberg) Proposed measures for CRE 16.09.2011 - MRE - Düsseldorf
  • 45. MBL-producers = Metallo-Beta-Lactamase-producers For infections with ESBL-producers regular therapy with Carbapenems is recommended: Imipenem Meropenem Doripenem Ertapenem Start educating about Carbapenemases and Metallo-Beta-Lactamases 16.09.2011 - MRE - Düsseldorf
  • 46. MBL 16.09.2011 - MRE - Düsseldorf Carbapenemase-producers discovered so far The phenomenon of Carbapenem resistance is not new; 4 different resistance mechanisms are currently known Italy Turkey India
  • 47. MBL Cabapenemase/ Metallo-Beta-Lactamase Development VIM, 1999 Italy KPC, 2001 USA OXA 48, 2004 Turkey NDM-1, 2008, India Affected bacteria: Klebsiellen, A. baumannii, E. coli, E. cloacae, P. aeruginosa u.a. Actual data from Germany: NRZ* 1/1/11 to 28/2/11 66 strains nationwide, particularly Berlin, North Rhine-Westphalia, Baden-W ürttermberg - At the time, no recommendations made regarding screening or specific measures 16.09.2011 - MRE - Düsseldorf * Nationales Referenzzentrum für Surveillance von nosokomialen Infektionen (National Reference Centre for the Surveillance of Nosocomial Infections)
  • 48. ESBL / MBL Applicable antibiotics: Tigecycline Colistin Fosfomycin Combinations Pharmacokinetics and side effects! Pan-resistance possible (Tigecycline: higher mortality rate) 16.09.2011 - MRE - Düsseldorf
  • 49. Hygiene measures for patients with MBL colonisation/infection Generally the same as ESBL: Gloves/overalls Hygenic disinfection of hands Basic hygiene measures! Individual treatment only if high risk of pathogens spreading (diarrhoea, large open wounds, tracheotomy etc.) 16.09.2011 - MRE - Düsseldorf
  • 50. Measures for ESBL Isolation Customised solution for every house In unproblematic cases no isolation Screening Use not yet established, possibly to be considered for selected situations (Eich, 2006) 16.09.2011 - MRE - Düsseldorf
  • 51. Measures for ESBL Decolonisation: No sustained success documented Problems: Quinolone resistance General development of resistance Other areas with colonisation (Nasopharynx: Iodopovidone: J Hosp Infect 2001; 48: 207-213.) 16.09.2011 - MRE - Düsseldorf
  • 52. Aspects of hospital hygiene for outbreaks of multiresistant bacteria Measures to avoid MRB 1. General antibiotic therapy 2. Antibiotic therapy for patients with MRE in accordance with regulations 3. Quick sanitisation (Example: MRSA) 4. Discharge patients quickly if possible 5. BASIC HYGIENE!!! 16.09.2011 - MRE - Düsseldorf
  • 53. Increase in the use of alcoholic hand disinfectants of around 1 %  after 4 months Reduction in incidences of infection by around 7 % Basic hygiene/ Disinfection of hands 16.09.2011 - MRE - Düsseldorf
  • 54. MRSA Measures Sanitisation Skin: Most important principle: Wash when possible! Varied handwashes ( no antiseptics!) Reduces skin irritation Complete body wash Alternative: “wash“ without water with wipes impregnated with active agents. 16.09.2011 - MRE - Düsseldorf
  • 55. MRSA Measures Sanitisation Mouth: Various solutions (Polyhexanide/ PVP-I/ Octenidine/ others) 16.09.2011 - MRE - Düsseldorf
  • 56. MRSA Measures Preventing recontamination in the area Change clothing/ underwear daily Change beds daily Electric tootbrushes/ razers (wet) Disinfect dentures Disinfect personal belongings and everyday items 16.09.2011 - MRE - Düsseldorf
  • 57. MRSA Measures Take action on failures in hygiene Most recontamination in same areas! Switch to other agents? Second attempt is worth it but have a more stringent course of action 16.09.2011 - MRE - Düsseldorf
  • 58. Not enough staff: more deaths ICUs with high staff numbers: 17 % patient deaths ICUs with low staff numbers:  45 % patient deaths Increase in staff numbers monitored over 4 years:  Number of patient deaths dropped from 34 to 18 % Tarnoff-Mordi WO, How C, Warden A, Shearer AJ: Hospital mortality in relation to staff work load: 4-year-study in adult intensive-care unit Lancet 2000; 356: 185-189 Prospects and limitations of hygiene 16.09.2011 - MRE - Düsseldorf
  • 59. Louis Pasteur 1895: “ The microbes always have the last word!“ 16.09.2011 - MRE - Düsseldorf