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Pathogens Important to Infection Prevention and Control 1. List special pathogens of interest to IP&C, and for each, describe the impact on the IP&C programme 2. Explain how antibiotic-resistant bacteria cause problems in healthcare 3. Outline preventive measures for a given special pathogen December 1, 2013 Learning objectives 2 • 90 minutes December 1, 2013 Time involved 3 • Everyday problem microorganisms for infection prevention and control include: • Mycobacterium tuberculosis • Clostridium difficile • Antibiotic resistant organisms December 1, 2013 Special pathogens • MRSA, VRE • Gram-negative multiply resistant organisms • Enterobacteria (Escherichia coli, Klebsiella pneumoniae) • Pseudomonas aeruginosa • Acinetobacter baumanii 4 • Mycobacterium tuberculosis causes tuberculosis (TB) • TB affects 1/3 of the world’s population • 9.4 million new cases in 2008 • 1.8 million deaths in 2008 • Leading cause of death in people living with human immunodeficiency virus (HIV) December 1, 2013 Mycobacterium tuberculosis 5 • Spread by the airborne route when someone with active disease and positive sputum smear coughs, talks, sneezes, or spits • Bigger droplets spread up to 1 m, smaller spread by air • Bacteria inhaled into lungs December 1, 2013 Transmission and pathogenesis of TB - 1 • In lung tissue and lymph nodes the bacteria grow and reproduce • Can travel to any location in the body 6 • Latent TB – bacteria contained in the body • 10% of people with latent TB will develop active disease • Most commonly affected organ - Lungs • Untreated, a person with active disease can infect 10 to 15 people a year December 1, 2013 Transmission and pathogenesis of TB - 2 7 • Pulmonary TB (active) • Cough with thick cloudy, sometimes bloody sputum • Tiredness • Appetite loss/unexplained weight loss • Night sweats • Fever/chills • Shortness of breath December 1, 2013 Clinical forms • Extra pulmonary TB • Signs and symptoms vary with site of infection • Other common sites include central nervous system, bones, joints, and genitourinary system 8 • Weakened immune system • Contact with someone with active TB • Caring for active TB patients • Living or working in crowded conditions with someone with active TB • e.g., prisons, nursing homes, homeless shelters • Poor access to healthcare • Alcohol or drug abuse • Travel to places where TB is endemic • Being born in a country where TB is endemic • Some medications for rheumatoid arthritis December 1, 2013 Risk Factors 9 • BCG strain of Mycobacterium bovis is used as a vaccine • BCG is given to infants (best soon after birth) • Vaccination against TB does not protect against infection but only against severe forms of disease December 1, 2013 Vaccination • Meningitis • Disseminated TB (miliary) 10 • Chest x-ray • Sputum smear for acid fast bacilli • Tuberculin skin test (TST) December 1, 2013 Diagnosis & Management • Can take up to 3 months for those newly exposed to develop positive test • May be falsely positive because of BCG vaccination • Interferon gamma release assays (IGRA) in vaccinated persons • Culture (can take up to six weeks) and sensitivity test 11 Management of Exposure • Confirmation of positive infection • Medical evaluation to determine follow up December 1, 2013 Management & Treatment Treatment of patients • Treatment for latent or active TB should follow World Health Organization recommendations • Incomplete treatment can cause resistance • Adherence to therapy is critical 12 Engineering controls • Negative pressure rooms • High efficiency particulate air (HEPA) filtration system • Enhanced ventilation • Ultraviolet irradiation (only in empty room) • Sunlight exposure • Open window (last resort if no other options) December 1, 2013 IP&C Measures 13 HEPA filter December 1, 2013 Negative presssure room Air flow Patient with active TB isolated in negative pressure room 14 Administrative Controls • Identify patients with signs and symptoms of TB • Additional precautions for patients suspected to have active TB • Prompt treatment • Vaccination of healthcare personnel • Respiratory etiquette December 1, 2013 IP&C Measures - 1 15 Personal Protective Equipment* • N-95 fit tested masks for healthcare workers • If not available, then surgical masks • Surgical masks for patients leaving their rooms December 1, 2013 IP&C Measures - 2 * Typically used for pulmonary TB if the patient is expectorating or has an open lesion 16 • Despite the high global impact of TB, it is treatable and preventable • Occupation exposures remain a significant risk for healthcare workers • IP&C measures are needed to decrease exposures to patients and healthcare workers December 1, 2013 Conclusion 17 • There is a global increase in Clostridium difficile infections (CDI) and outbreaks over the past 10 years; however the illness is not a problem in all countries • CDI primarily occurs in those patients exposed to antibiotics in healthcare facilities December 1, 2013 Clostridium difficile: Background 18 • A Gram-positive spore forming anaerobic bacillus • Widely distributed in the environment • In its vegetative state December 1, 2013 Pathology - 1 • Produces toxins • Can be killed by antibiotics • Spore form • • • • Dormant No toxin production Resistant to antibiotics and disinfectants Can persist for months in the environment 19 • Produces 2 toxins • Toxin A and Toxin B • Bind to intestinal epithelial cells causing inflammation and diarrhea • Toxins are cytotoxic and enteropathic • Alteration of the gut flora by antibiotics an important risk factor (decrease of normal gut flora) December 1, 2013 Pathology - 2 20 • Mild disease • Non-bloody diarrhoea, often mucoid and foul smelling, cramping, nausea, dehydration, low grade fever, leukocytosis December 1, 2013 Clinical Significance • Severe disease • Colitis, watery diarrhoea, abdominal pain, fever, nausea, abdominal distension, pseudomembranes in the gut, toxic mega colon, death 21 • Increased incidence of B1/NAP1/027 strain • Causes severe disease • More resistant to standard therapy • More likely to relapse • Associated with higher mortality • 16x more toxin A; 23x more toxin B • Related to excessive use of certain drugs/antibiotics December 1, 2013 New Strain 22 • Approximately 3-5% of healthy adults and 20 to 40% of hospitalised patients may be colonised • Colonised patients generally are not symptomatic December 1, 2013 Colonisation • May be a potential reservoir for transmission • Evidence suggest spores on the skin of asymptomatic patients can contaminate the hands of the healthcare worker • No recommendations to treat carriers nor to perform admission screening 23 Patients at Risk Admission Screening Route of Transmission Isolation Precautions Accommodation Documentation (flagging of patients) Environmental Cleaning Discontinuation of Precautions Follow-up of Contacts Point Prevalence Additional Outbreak Measures Previous antibiotic use Severe underlying illness Prolonged hospital stay Advanced age Gastrointestinal surgery/manipulation History of irritable bowel disease Patients on proton pump inhibitors No Contact Yes Single room preferred Separate toileting facilities May be of benefit to implement a system to designate patients known to be colonised or infected for early notification on readmission Routine cleaning with attention to high touch surfaces and use of a sporicidal agent Consider double-cleaning for outbreak situations No diarrhoea for at least 48 hours No No Strict cleaning of multi-use equipment between patients Dedicated patient equipment to positive cases Education of staff, patients and visitors Auditing of outbreak unit/area including hand hygiene, isolation practices and environmental cleaning December 1, 2013 Transmission and Control Measures 24 • Discontinuation of all antibiotics in a symptomatic patient (except for CDI) • Facility-wide antibiotic control policies • Early notification of patients with diarrhoea to the IC team • Not recommended December 1, 2013 Additional Control Measures • Routine identification of carriers • Repeat testing post treatment for clearance 25 December 1, 2013 Antibiotic Resistant Microorganisms 26 December 1, 2013 Methicillin Resistant Staphylococcus aureus (MRSA) 27 • Staphylococcus aureus is a Gram-positive bacteria • 30% of people are permanently colonised • Nose • Pharynx • Perineum • Transient colonisation occurs, mainly on hands • Colonisation although harmless, increases the risk of infection and transmission December 1, 2013 Background 28 • First a problem in 1960s • Globally has reached epidemic proportions • Both community associated (CA) and healthcare associated (HA) strains of MRSA • Rates vary by • Country • Region • Individual healthcare facility December 1, 2013 Clinical Significance of MRSA 29 Patients at Risk Admission Screening Sites Route of Transmission Isolation Precautions Accommodation Documentation (flagging of patients) Environmental Cleaning Discontinuation of Precautions Follow-up of Contacts Point Prevalence Additional Outbreak Measures Previous antibiotic use Severe underlying illness Prolonged hospital stay Previous contact with medical facility Use of invasive procedures Close proximity to a patient colonised or infected with MRSA Yes, based on patient risk factors Nares, rectal, wounds, exit sites Contact (plus droplet for symptomatic patients with pneumonia) Yes Single room preferred December 1, 2013 MRSA Transmission and Control Measures May be of benefit to implement a system to designate patients known to be colonised or infected for early notification on readmission Routine cleaning with attention to high touch surfaces Unresolved issue: Some institutions use the following criteria: Negative results from all colonised/infected body sites- 3 consecutive cultures taken at least one week apart in the absence of antibiotic therapy Note: Re-colonisation is known to occur so on-going monitoring is recommended Consider maintaining isolation precautions in an outbreak setting Two sets of specimens taken on different days with one taken a minimum of 7 days after the last exposure, especially in an outbreak setting In an outbreak setting: Conduct serial (e.g., weekly) unit specific point prevalence cultures to determine if transmission has decreased or ceased Consider discharge and/transfer screening of patients until transmission has decreased or ceased Strict cleaning of multi-use equipment between patients Dedicated patient equipment to positive cases Education of staff, patients and visitors Auditing of outbreak unit/area including hand hygiene, isolation practices and environmental cleaning 30 • Vancomycin is drug of choice for treating MRSA infections • Staphylococcus aureus with decreased (intermediate) susceptibility to vancomycin = VISA • Staphylococcus aureus with resistance genes Van A or Van B = VRSA December 1, 2013 VISA and VRSA • So far only few isolates in different parts of the world 31 December 1, 2013 Vancomycin Resistant Enterococcus (VRE) 32 • Enterococci are normal gut bacteria • May also be present in the oropharynx, vagina, or on skin • Causes serious bacterial infections • • • • December 1, 2013 Background Wound infections Urinary tract infections Endocarditis Sepsis • Often resistant to ampicillin (the drug of choice); infections then treated with glycopeptides 33 • VRE is enterococcus that is resistant to the glycopeptide vancomycin • First isolated in the 1980’s • Spread globally causing asymptomatic colonization, infections, and outbreaks • The prevalence of VRE varies worldwide December 1, 2013 VRE Epidemiology 34 • Clinically relevant strains carry Van A or Van B resistance genes • Limited antibiotics to treat VRE infections • Transfer of resistance genes to other microorganisms such as MRSA is a great concern December 1, 2013 Clinical Significance 35 Patients at Risk Admission Screening Sites Route of Transmission Isolation Precautions Accommodation Documentation (flagging of patients) Environmental Cleaning Discontinuation of Precautions Follow-up of Contacts Point Prevalence Additional Outbreak Measures Previous antibiotic use Severe underlying illness Prolonged hospital stay Previous contact with medical facility Use of invasive procedures Close proximity to a patient colonised or infected with VRE Yes, based on patient risk factors. Rectum Contact Yes Single room preferred Separate toileting facilities May be of benefit to implement a system to designate patients known to be colonised or infected for early notification on readmission Routine cleaning with attention to high touch surfaces Consider double cleaning in outbreak situations Unresolved issue: Some institutions use the following criteria: Negative results from all colonised /infected body sites- 3 consecutive cultures taken at least one week apart in the absence of antibiotic therapy Note: Re-colonization is known to occur so on-going monitoring is recommended. Consider maintaining isolation precautions in an outbreak setting Two sets of specimens taken on different days with one taken a minimum of 7 days after the last exposure, especially in an outbreak setting In an outbreak setting: Conduct serial (e.g., weekly) unit specific point prevalence cultures to determine if transmission has decreased or ceased Consider discharge and/transfer screening of patients until transmission has decreased or ceased Strict cleaning of multi-use equipment between patients Dedicated patient equipment to positive cases Education of staff, patients and visitors Auditing of outbreak unit/area including hand hygiene, isolation practices and environmental cleaning December 1, 2013 VRE Transmission and Control Measures 36 December 1, 2013 Multi-Drug Resistant GramNegative Microorganisms (MDRGN) 37 • The “Enterobacteriaceae” family of bacteria are a normal part of the gastrointestinal flora • The most frequent isolates are: December 1, 2013 MDRGN - 1 • Escherichia coli • Klebsiella pneumoniae • Serratia marcescens • Enterobacter species 38 Escherichia coli and Klebsiella pneumoniae can have extended spectrum beta-lactamase (ESBL) enzymes that cause resistance to beta-lactam antibiotics including: December 1, 2013 Mechanisms of Resistance • Penicillins • Cephalosporins • Cephamycins • Monobactams 39 • There are various types of ESBLs including • TEM • SHV • CTX-M December 1, 2013 Epidemiology of ESBL strains • ESBLs were first detected in Europe in 1980s • Surveillance data from several surveillance systems indicate high rates of ESBLs in many parts of the world including USA, Canada, Europe, China, India and Latin America 40 • Carbapenem antibiotics are the treatment of choice for serious infections due to ESBLproducing bacteria • Carbapenem Resistant Enterobacteriaceae (CRE) has also been reported • Carbapenemases of importance include KPC, VIM, OXA and NDM-1 • CREs have been reported in many areas of the world and have also been associated with outbreaks December 1, 2013 Epidemiology of CRE 41 • The following bacteria are present in aquatic environments • Acinetobacter baumannii • Pseudomonas aeruginosa December 1, 2013 MDRGN - 2 • Opportunistic pathogens in humans • A major cause of healthcare-associated infections • Septicemia • Ventilator-associated pneumonia • Urinary tract infections 42 • These microorganisms have intrinsically lower susceptibility to antibiotics • Acquiring additional resistance genes (ESBL genes, other genes for resistance to beta lactam antibiotics, resistance genes for aminoglycosides and fluoroquinolones) very often means that they are • susceptible only to carbapenems or • colistin or • resistant to all antibiotics (panresistant) December 1, 2013 MDR P. aeruginosa and MDR A. baumannii 43 • MDRGN (including ESBLs, CREs, MDR PA and MDR AB) pose a significant treatment challenge including December 1, 2013 Clinical Significance • Increased length of stay • Increased mortality • Increased cost • Contributes to the global crisis of antimicrobial resistance • Control requires an aggressive world-wide strategy 44 Patients at Risk Admission Screening Sites Previous antibiotic use Severe underlying illness Prolonged hospital stay Previous contact with medical facility Contact with a facility with known outbreaks with MDRGN organisms Yes, based on local epidemiology and patient risk factors. Rectum Isolation Precautions Contact (plus droplet for symptomatic patients with pneumonia) Yes Accommodation Single room preferred Documentation (flagging of patients) May be of benefit to implement a system to designate patients known to be colonised or infected for early notification on readmission Routine cleaning with attention to high touch surfaces Route of Transmission Environmental Cleaning Discontinuation of Precautions Follow-up of Contacts Point Prevalence Additional Outbreak Measures December 1, 2013 MDRGN Transmission and Control Measures Unresolved issue: Some institutions use the following criteria: Negative results from all colonised /infected body sites- 3 consecutive cultures taken at least one week apart in the absence of antibiotic therapy Note: Re-colonisation is known to occur so on-going monitoring is recommended Consider maintaining isolation precautions in an outbreak setting Based on local epidemiology and patient risk factors In an outbreak setting: Conduct serial (e.g., weekly) unit specific point prevalence cultures to determine if transmission has decreased or ceased Consider discharge and/transfer screening of patients until transmission has decreased or ceased Strict cleaning of multi-use equipment between patients Dedicated patient equipment to positive cases Education of staff, patients and visitors Auditing of outbreak unit/area including hand hygiene, isolation practices and environmental cleaning 45 • IP&C measures vary based on institutional setting and available resources • Hand hygiene should be a routine part of patient care in all settings • Additional precautions may be considered depending on the pathogen, the institutional setting and outbreak circumstances December 1, 2013 Management of Pathogens in Low Resource Countries 46 • Antimicrobial resistance is a world-wide public health problem • Solutions require a multi-faceted approach • Improving behaviours is essential • Global awareness and surveillance is required • Implementation of appropriate IP&C practices and antimicrobial stewardship processes may be beneficial December 1, 2013 Conclusion 47 • Tuberculosis and multi-drug resistant bacteria are important infection prevention and control issues • Many have developed resistance to antimicrobials making them less effective • Control measures vary by organism, setting and resources December 1, 2013 Key Points 48 • Apisarnthanarak A, Fraser VJ. Feasibility and efficacy of infection control interventions to reduce the number of nosocomial infections and drug resistant microorganisms in developing countries: what else do we need? CID 2009;48:22-24 • EARS-Net. http://www.ecdc.europa.eu/en/activities/surveillance/EARS -Net/Pages/index.aspx • WHO 2010. Global tuberculosis control http://www.who.int/mediacentre/factsheets/fs104/en/inde x.html • Special pathogens, in Damani N. Manual of infection prevention and control, 3rd ed. Oxford University Press, Oxford, 2012:183-249. December 1, 2013 Further reading 49 1. When a patient with active tuberculosis has to leave the isolation room for tests, s/he has to wear a N95 mask. T/F? 2. Admission screening for MRSA encompasses the following specimens: a. b. c. d. December 1, 2013 Quiz Nares alone Nares, wounds, exit sites Nares, wounds Nares, exit sites 3. ESBL genes are transmitted by plasmids and are restricted to Enterobacteriaceae. T/F? 50 • IFIC’s mission is to facilitate international networking in order to improve the prevention and control of healthcare associated infections worldwide. It is an umbrella organisation of societies and associations of healthcare professionals in infection control and related fields across the globe . • The goal of IFIC is to minimise the risk of infection within healthcare settings through development of a network of infection control organisations for communication, consensus building, education and sharing expertise. • For more information go to http://theific.org/ December 1, 2013 International Federation of Infection Control 51