Nosocomial Infections Patrick Kimmitt

Today we are going to cover… The factors that contribute to nosocomial infections Examples of nosocomial infections and the organisms which cause them Control of nosocomial infections Surveillance of nosocomial infections

Nosocomial infections The word derives from the Greek nosokomeian, meaning hospital These days the terms hospital acquired – and healthcare associated – are used A very emotive subject with the public, driven by the press Do hospitals really deserve to be blamed for all cases of hospital infection?

Nosocomial infections are… Infections that are acquired in hospital (48 hours or more after admission) Approx 7% of patients will suffer from an infection whilst in hospital – the risk increases with length of stay A significant financial burden on NHS

Impact of nosocomial infections Possibly up to100,000 infections per year in UK A cause of ~5,000 deaths with nosocomial infections playing a role in ~15,000 others Costs the NHS £1 billion – 9% of its in-patient budget Cannot be eradicated but it’s thought they could be reduced by up to 30%

Impact of nosocomial infections Longer stays in hospital – bed occupancy Outbreaks leading to ward closures especially norovirus and C. difficile Pain and anxiety for patients and families Loss of earnings

Where is the money spent?

Best to be proactive rather than reactive!!

Why are we more likely to get an infection in hospital? Consider 4 important factors… The host The microbes The environment Treatment

The host 1 People in hospital are already sick! They may have poor general resistance to infection Lack of immunity Extremes of age Immunocompromised (eg cancer chemotherapy)

The host 2 Reduced immunity Poor local resistance Surgery Diabetes, severe burns Poor local resistance Poor blood supply to tissues Surgery Wounds, sutures Medical devices Catheters, prostheses, tubing etc

The microbes Virtually any infection can be acquired in hospital However a number of “usual suspects” predominate What are they, where do they come from and why do they cause nosocomial infection?

Opportunistic infections Nosocomial infections are often caused by opportunistic pathogens i.e. those which do not normally cause infection in healthy people May be a reflection of reduced defences of host or access to sites not normally colonised by organisms May be from normal flora or environment Antibiotic resistance is a problem

Opportunistic pathogens Pseudomonas aeruginosa staphylococci E. coli and other coliforms streptococci and enterococci Bacteroides fragilis Candida albicans Herpes simplex virus Cytomegalovirus

Biofilms Biofilms are microbial communities (cities) living attached to a solid support eg catheters/ other medical devices Biofilms are involved in up to 60% of nosocomial infections Antibiotics are less effective at killing bacteria when part of a biofilm

The Environment There are many different sources of pathogens when in hospital Our own normal flora (endogenous infection) Infected patients Movement of staff and visitors Environment e.g. fungi, Legionella Blood products (v. rare) Surgical instruments eg vCJD (v. rare)

ENVIRONMENTAL SOURCES OF PATHOGENS IN THE HEALTHCARE SETTING Bacteria Viruses Fungi Air Gram-positive cocci (originating from skin) Tuberculosis Varicella zoster (chickenpox), Influenza Aspergillus Water (tap and bath) Gram-negative bacteria (Pseudomonas aeruginosa, Aeromonas hydrophilia, Burkholderia cepacia, Stenotrophomonas maltophilia, Serratia marcescens, Flavobacterium meningosepticum, Acinetobacter calcoaceticus, and Legionella pneumophila) Mycobacteria (Mycobacterium xenopi, Mycobacterium chelonae, or Mycobacterium avium-intracellularae) Molluscum contagiosum Human papillomavirus (bath water) Noroviruses Exophiala jeanselmei Food Salmonella species, Staphylococcus aureus, Clostridium perfringens, Clostridium botulinum, Bacilluscereus and other aerobic spore-forming bacilli Escherichia coli Campylobacter jejuni ,Yersinia enterocolitica, Vibrio parahaemolyticus, Vibrio cholerae, Aeromonas hydrophilia, Streptococcus species Listeria monocytogenes Rotavirus Caliciviruses

Treatment There is continuous usage of antibiotics in hospitals especially in ICU As a result there will be a natural selection for strains that are antibiotic resistant – infections are getting harder to treat This has led to problems with multi-resistant bacteria e.g. MRSA, VRE, ESBLs Antibiotic treatment can also lead to alterations in normal flora and allow pathogens cause infection eg C. difficile

Sites of HAIs

Bloodstream nosocomial infections Coagulase-negative staphylococci Enterococci Fungi e.g Candida albicans Staphylococcus aureus E. coli and other coliforms Pseudomonas aeruginosa Acinetobacter baumannii with substantial antimicrobial resistance - Reported with increasing frequency

Urinary Tract Infections E. coli and other coliforms Candida albicans Enterococcus Staphylococcus Pseudomonas

Surgical site infections S. aureus Pseudomonas aeruginosa Coagulase-negative staphylococci Enterococcus Candida albicans E. coli

Causes of death Primary bloodstream infection Pneumonia Infection of surgical site

Staphylococcus aureus A common coloniser of the skin and mucosa (e.g. the nose) it is a classic opportunist Causes skin and wound infections as well as septicaemia, urinary tract infections and pneumonia Most strains are sensitive to many antibiotics…some are not…

MRSA Methicillin (Meticillin) Resistant Staphylococcus aureus S aureus carried by 30% of us (nose/ skin) MRSA is more difficult to treat compared to MSSA Resistance due to mecA gene – encodes PBP2a, doesn’t react with Penicillins Emerging Vancomycin resistance is a concern The Biomedical Scientist Jan 2008 p39-41

MRSA bacteraemia

Epidemic MRSA (EMRSA) Epidemic strains have acquired a selective advantage for transmission in hospital environments EMRSA-1 was identified in S.E. England in 1984. Subsequent surveys showed further 13 multi-hospital MRSA (EMRSA-2 to -14) Mid-1990s: EMRSA-15 and -16 emerged and spread rapdily Approx 60% of MRSA isolates in hospitals are EMRSA-15, and 35% EMRSA-16

Rapid MRSA screening Current methods for screening for MRSA are based on culture and take 48 hours PCR-based screening can generate a result in 2 hours! mecA is carried on a transferable gene cassette called SCCmec – but also found in coagulase-negative staphylococci PCR developed using primers for SCCmec and orfX on the S. aureus chromosome

Use of SCCmec/orfX PCR MRSA MSSA MR CN-Staph PCR product mecA SCC 3` end orfX MRSA No PCR product MSSA orfX No PCR product MR CN-Staph mecA SCC 3` end Cuny & Witte Clin Microbiol Infect (2005) 11:834-837

Vancomycin Resistant Enterococci

Extended spectrum β-Lactamases ESBLs are enzymes responsible for resistance to 3rd generation Cephalosporin antibiotics such as Ceftazidime and Cefotaxime Resistance is found in E. coli and other members of the Enterobacteriacae Often cross-resistance with other antibiotics making treatment difficult – use carbapenems

Clostridium difficile Causes antibiotic-associated diarrhoea and pseudomembranous colitis – life-threatening illnesses Normally affects only the elderly, especially those on long-term broad-spectrum antibiotics Produces two powerful toxins and is a spore-former– difficult to eradicate, resistant to alcohol Reasons for the rapid increase in cases is still not known

Clostridium difficile Nosocomial disease spread primarily by hands of staff and “outbreaks” are common Patients generally respond to discontinuation of the inciting agent or therapy with metronidazole or vancomycin. Response is rapid but Mtz and Vanc may also alter normal flora and may allow disease to recur Once the colon is injured it is more susceptible to re-infection. “Relapse” rates are up to approx 20% Almost impossible, at present, to rid the environment of C. difficile spores Some use 1000-10000ppm hypochlorite – highly caustic and damaging to surfaces. There may be rapid re-contamination of environment.

Nosocomial transmission of C. difficile Contamination rates after contact with CDAD patients: Physicians & medical Students 75% of the time Dialysis Technicians 66% of the time Nurses 56% of the time Physiotherapists 50% of the time Underside of fingernails 43% Fingertips and Palms 37% Underside of Rings 20% C difficile spores remain in environment in 34-58% of sites after “detergent” cleaning CDC 2005

Success story Scunthorpe and Goole NHS trust looked at changing their antibiotic prescribing policy to reduce the incidence of C. difficile disease Cost £12,000 extra to implement Saved £280,000 in staffing, bed occupancy, treatment, use of isolation rooms and of course lives

Infection Control Infections may derive from endogenous (auto-infection) or exogenous sources (cross-infection) We need to consider the chain of infection and the transmission of an infectious agent

Transmission Contact – most common Airborne Transmission Direct (physical contact) Indirect (via contaminated objects) Airborne Transmission Droplet respiratory secretions on surfaces Inhalation of infectious particles Blood-borne transmission (v. rare) Food-borne (rare)

The Cycle of Contagion Susceptible person Infection or colonisation Transmission Pathogen

X The Cycle of Contagion Immunisation or prophylaxis Individual treatment Infection control hygiene Susceptible person Infection or colonisation Transmission Pathogen X

Role of infection control teams Education and training Development and dissemination of infection control policy Monitoring and audit of hygiene Clinical audit

Isolation & barrier precautions Decontamination of equipment Prudent use of antibiotics Hand washing Decontamination of environment

The 5 pillars of infection control Isolation & barrier precautions Decontamination of equipment Prudent use of antibiotics Hand washing Decontamination of environment

Cleanyourhands campaign An initiative that was rolled out in 2004 Increased procurement of alcohol rub in wards Poster campaign Evaluation of this published in BMJ May 3 2012

Tabloid sensationalism?

Government response… Hospital superbug must be halved Bloodstream infections with the hospital superbug MRSA must be halved in three years, the government has said. Health Secretary John Reid tasked NHS hospitals with achieving a year on year reduction up to and beyond March 2008.

Government meddling?? By forcing targets on NHS trusts for reduction of MRSA numbers, has this led to an increase in infections with other “superbugs”? Hand washing with alcohol-based antiseptics is fine for decontamination of MRSA but have no effect on spores of C. difficile - need to wash with soap and water Include soap as well as alcohol rub on wards

Some progress In recent years there has been a steady decline in cases and deaths caused by both MRSA and C. difficle Is our infection control policy paying off?

Resistant Gram negative bacteria The emphasis is switching to multi-resistant Gram negative pathogens e.g. CTX-M ESBL producers, seen in E. coli and other Enterobacteriacae providing resistance to 3rd generation cephalosporins CRE – Carbapenem Resistant Enterobacteriacae e.g. NDM-1 - very few treatment options here (colistin)

Surveillance Continuous monitoring of the frequency and distribution of infectious diseases Determines the most important causes of infectious diseases and identifies at risk groups

Uses of surveillance Used to identify new “problems” Used to identify where resources are most needed Used to determine the burden of disease Used for strategic planning and policies Use surveillance for measuring outcomes of intervention strategies

Epidemiology Surveillance is also used to detect epidemics and outbreaks Epidemiologists at Centre for Infections analyse data sent from laboratories throughout the country

Surveillance reports published in CDR weekly http://www. hpa. org But how do Biomedical Scientists help with this work? Isolating and identifying the pathogens - hospitals Typing – specialist laboratories

Typing of pathogens There are many different strains of a bacterial/ fungal/ viral species so in order to identify a possible outbreak and identify the source we need to discriminate between organisms of the same species This is called typing: there are a number of methods available Those based on phenotype (traditional) Those based on genotype (recent)

Typing methods Typing is usually performed at specialised Reference Laboratories such as those at HPA Centre for Infections Different methods are used for different pathogens – use the one which gives best discrimination Pathogens of the same type may be part of an outbreak, if they are of a different type an outbreak can be ruled out

Phage Typing Phage (bacteriophage) is a virus that infects and kills bacteria Different strains are susceptible to different phages Gives a fingerprint that can discriminate between strains Used in the typing of S. aureus and Salmonella

Serotyping Used to detect variations in certain antigens present on the pathogen Use specific antisera and observe a Antibody-Antigen reaction (usually a precipitation or agglutination reaction) Eg Streptococcus pyogenes M-protein typing – M1 type is important in invasive infections (flesh eating etc) H and N typing of influenza eg H5N1, H1N1 etc

Biotyping Biotyping explores the metabolism of an organism eg a particular enzyme activity or ability to ferment a particular sugar Eg. coagulase-negative staphylococci

Genotyping There are a number of methods available – most rely on sequence variation in non-coding (intergenic) DNA This variation is characteristic of a particular strain (or type) Strains from an outbreak will be the same type Similar to DNA fingerprinting used in CSI and paternity disputes

Restriction Fragment Length Polymorphism (RFLP) DNA extracted from bacterial isolates is digested (cut) with a restriction enzyme eg EcoR I Produces DNA fragments of varying size – gel electrophoresis Pattern of bands is strain-specific

Pulsed Field Gel Electrophoresis Used to separate large DNA fragments >10 kb Chromosomal DNA digested with restriction enzyme and fragments separated by PFGE Banding pattern is strain specific – used e.g in MRSA typing

Repetitive DNA Much of the bacterial genome consists of short repeating DNA sequences – micro or minisatellites By comparing the number of repeats present at specific loci the relationship between strains can be investigated Often known as VNTR typing

Summary 1 Can you explain in detail why patients in hospital are more prone to infection? Can you define a primary and an opportunistic pathogen? Can you give examples of nosocomial infections, with predisposing factors and examples of the pathogens which cause them? Can you discuss infections due to MRSA and C. difficile in detail?

Summary 2 5. Can you discuss the transmission of infection in hospitals, uses of infection control and the role of infection control teams? Why is surveillance of nosocomial infections important? What is the role of the laboratory in the diagnosis and surveillance of nosocomial infections? Can you give examples of the methods used in the laboratory for diagnosis and surveillance of nosocomial infections?