2Today we are going to cover… The factors that contribute to nosocomial infectionsExamples of nosocomial infections and the organisms which cause themControl of nosocomial infectionsSurveillance of nosocomial infections
3Nosocomial infections The word derives from the Greek nosokomeian, meaning hospitalThese days the terms hospital acquired – and healthcare associated – are usedA very emotive subject with the public, driven by the pressDo hospitals really deserve to be blamed for all cases of hospital infection?
4Nosocomial 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 stayA significant financial burden on NHS
5Impact of nosocomial infections Possibly up to100,000 infections per year in UKA cause of ~5,000 deaths with nosocomial infections playing a role in ~15,000 othersCosts the NHS £1 billion – 9% of its in-patient budgetCannot be eradicated but it’s thought they could be reduced by up to 30%
6Impact of nosocomial infections Longer stays in hospital – bed occupancyOutbreaks leading to ward closures especially norovirus and C. difficilePain and anxiety for patients and familiesLoss of earnings
9Why are we more likely to get an infection in hospital? Consider 4 important factors…The hostThe microbesThe environmentTreatment
10The host 1 People in hospital are already sick! They may have poor general resistance to infectionLack of immunityExtremes of ageImmunocompromised (eg cancer chemotherapy)
11The host 2 Reduced immunity Poor local resistance Surgery Diabetes, severe burnsPoor local resistancePoor blood supply to tissuesSurgeryWounds, suturesMedical devicesCatheters, prostheses, tubing etc
13The microbes Virtually any infection can be acquired in hospital However a number of “usual suspects” predominateWhat are they, where do they come from and why do they cause nosocomial infection?
14Opportunistic infections Nosocomial infections are often caused by opportunistic pathogens i.e. those which do not normally cause infection in healthy peopleMay be a reflection of reduced defences of host or access to sites not normally colonised by organismsMay be from normal flora or environmentAntibiotic resistance is a problem
15Opportunistic pathogens Pseudomonas aeruginosastaphylococciE. coli and other coliformsstreptococci and enterococciBacteroides fragilisCandida albicansHerpes simplex virusCytomegalovirus
16BiofilmsBiofilms are microbial communities (cities) living attached to a solid support eg catheters/ other medical devicesBiofilms are involved in up to 60% of nosocomial infectionsAntibiotics are less effective at killing bacteria when part of a biofilm
17The EnvironmentThere are many different sources of pathogens when in hospitalOur own normal flora (endogenous infection)Infected patientsMovement of staff and visitorsEnvironment e.g. fungi, LegionellaBlood products (v. rare)Surgical instruments eg vCJD (v. rare)
18ENVIRONMENTAL SOURCES OF PATHOGENS IN THE HEALTHCARE SETTING BacteriaVirusesFungiAirGram-positive cocci (originating from skin)TuberculosisVaricella zoster (chickenpox),InfluenzaAspergillusWater (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)NorovirusesExophiala jeanselmeiFoodSalmonella 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 monocytogenesRotavirusCaliciviruses
19TreatmentThere is continuous usage of antibiotics in hospitals especially in ICUAs a result there will be a natural selection for strains that are antibiotic resistant – infections are getting harder to treatThis has led to problems with multi-resistant bacteria e.g. MRSA, VRE, ESBLsAntibiotic treatment can also lead to alterations in normal flora and allow pathogens cause infection eg C. difficile
21Bloodstream nosocomial infections Coagulase-negative staphylococciEnterococciFungi e.g Candida albicansStaphylococcus aureusE. coli and other coliformsPseudomonas aeruginosaAcinetobacter baumannii with substantial antimicrobial resistance - Reported with increasing frequency
22Urinary Tract Infections E. coli and other coliformsCandida albicansEnterococcusStaphylococcusPseudomonas
23Surgical site infections S. aureusPseudomonas aeruginosaCoagulase-negative staphylococciEnterococcusCandida albicansE. coli
24Causes of death Primary bloodstream infection Pneumonia Infection of surgical site
25Staphylococcus aureus A common coloniser of the skin and mucosa (e.g. the nose) it is a classic opportunistCauses skin and wound infections as well as septicaemia, urinary tract infections and pneumoniaMost strains are sensitive to many antibiotics…some are not…
26MRSA Methicillin (Meticillin) Resistant Staphylococcus aureus S aureus carried by 30% of us (nose/ skin)MRSA is more difficult to treat compared to MSSAResistance due to mecA gene – encodes PBP2a, doesn’t react with PenicillinsEmerging Vancomycin resistance is a concernThe Biomedical Scientist Jan 2008 p39-41
28Epidemic MRSA (EMRSA)Epidemic strains have acquired a selective advantage for transmission in hospital environmentsEMRSA-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 rapdilyApprox 60% of MRSA isolates in hospitals are EMRSA-15, and 35% EMRSA-16
29Rapid MRSA screeningCurrent methods for screening for MRSA are based on culture and take 48 hoursPCR-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 staphylococciPCR developed using primers for SCCmec and orfX on the S. aureus chromosome
32Extended spectrum β-Lactamases ESBLs are enzymes responsible for resistance to 3rd generation Cephalosporin antibiotics such as Ceftazidime and CefotaximeResistance is found in E. coli and other members of the EnterobacteriacaeOften cross-resistance with other antibiotics making treatment difficult – use carbapenems
34Clostridium difficile Causes antibiotic-associated diarrhoea and pseudomembranous colitis – life-threatening illnessesNormally affects only the elderly, especially those on long-term broad-spectrum antibioticsProduces two powerful toxins and is a spore-former– difficult to eradicate, resistant to alcoholReasons for the rapid increase in cases is still not known
36Clostridium difficile Nosocomial disease spread primarily by hands of staff and “outbreaks” are commonPatients 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 recurOnce 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 sporesSome use ppm hypochlorite – highly caustic and damaging to surfaces. There may be rapid re-contamination of environment.
37Nosocomial transmission of C. difficile Contamination rates after contact with CDAD patients:Physicians & medical Students % of the timeDialysis Technicians % of the timeNurses % of the timePhysiotherapists % of the timeUnderside of fingernails %Fingertips and Palms %Underside of Rings %C difficile spores remain in environment in 34-58% of sites after “detergent” cleaningCDC 2005
38Success storyScunthorpe and Goole NHS trust looked at changing their antibiotic prescribing policy to reduce the incidence of C. difficile diseaseCost £12,000 extra to implementSaved £280,000 in staffing, bed occupancy, treatment, use of isolation rooms and of course lives
39Infection ControlInfections 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
40Transmission Contact – most common Airborne Transmission Direct (physical contact)Indirect (via contaminated objects)Airborne TransmissionDroplet respiratory secretions on surfacesInhalation of infectious particlesBlood-borne transmission (v. rare)Food-borne (rare)
41The Cycle of Contagion Susceptible person Infection or colonisation TransmissionPathogen
42X The Cycle of Contagion Immunisation or prophylaxis Individual treatmentInfection control hygieneSusceptible personInfection or colonisationTransmissionPathogenX
43Role of infection control teams Education and trainingDevelopment and dissemination of infection control policyMonitoring and audit of hygieneClinical audit
44Isolation & barrier precautions Decontamination of equipmentPrudent use of antibioticsHand washingDecontamination of environment
45The 5 pillars of infection control Isolation & barrier precautionsDecontamination of equipmentPrudent use of antibioticsHand washingDecontamination of environment
46Cleanyourhands campaign An initiative that was rolled out in 2004Increased procurement of alcohol rub in wardsPoster campaignEvaluation of this published in BMJ May
48Government 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.
49Government 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 waterInclude soap as well as alcohol rub on wards
50Some progressIn recent years there has been a steady decline in cases and deaths caused by both MRSA and C. difficleIs our infection control policy paying off?
56Resistant 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 cephalosporinsCRE – Carbapenem Resistant Enterobacteriacae e.g. NDM-1 - very few treatment options here (colistin)
57SurveillanceContinuous monitoring of the frequency and distribution of infectious diseasesDetermines the most important causes of infectious diseases and identifies at risk groups
58Uses of surveillance Used to identify new “problems” Used to identify where resources are most neededUsed to determine the burden of diseaseUsed for strategic planning and policiesUse surveillance for measuring outcomes of intervention strategies
59EpidemiologySurveillance is also used to detect epidemics and outbreaksEpidemiologists at Centre for Infections analyse data sent from laboratories throughout the country
60Surveillance reports published in CDR weekly http://www. hpa. org But how do Biomedical Scientists help with this work?Isolating and identifying the pathogens - hospitalsTyping – specialist laboratories
61Typing of pathogensThere 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 speciesThis is called typing: there are a number of methods availableThose based on phenotype (traditional)Those based on genotype (recent)
62Typing methodsTyping is usually performed at specialised Reference Laboratories such as those at HPA Centre for InfectionsDifferent methods are used for different pathogens – use the one which gives best discriminationPathogens of the same type may be part of an outbreak, if they are of a different type an outbreak can be ruled out
63Phage TypingPhage (bacteriophage) is a virus that infects and kills bacteriaDifferent strains are susceptible to different phagesGives a fingerprint that can discriminate between strainsUsed in the typing of S. aureus and Salmonella
64SerotypingUsed to detect variations in certain antigens present on the pathogenUse 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
65BiotypingBiotyping explores the metabolism of an organism eg a particular enzyme activity or ability to ferment a particular sugarEg. coagulase-negative staphylococci
66GenotypingThere are a number of methods available – most rely on sequence variation in non-coding (intergenic) DNAThis variation is characteristic of a particular strain (or type)Strains from an outbreak will be the same typeSimilar to DNA fingerprinting used in CSI and paternity disputes
67Restriction Fragment Length Polymorphism (RFLP) DNA extracted from bacterial isolates is digested (cut) with a restriction enzyme eg EcoR IProduces DNA fragments of varying size – gel electrophoresisPattern of bands is strain-specific
68Pulsed Field Gel Electrophoresis Used to separate large DNA fragments >10 kbChromosomal DNA digested with restriction enzyme and fragments separated by PFGEBanding pattern is strain specific – used e.g in MRSA typing
69Repetitive DNAMuch of the bacterial genome consists of short repeating DNA sequences – micro or minisatellitesBy comparing the number of repeats present at specific loci the relationship between strains can be investigatedOften known as VNTR typing
70Summary 1Can 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?
71Summary 25. 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?