Pathogens Important to Infection Prevention and Control

Learning objectives

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

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Time involved

• 90 minutes

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Special pathogens

• Everyday problem microorganisms for infection prevention and control include:• Mycobacterium tuberculosis • Clostridium difficile• Antibiotic resistant organisms

• MRSA, VRE• Gram-negative multiply resistant organisms

• Enterobacteria (Escherichia coli, Klebsiella pneumoniae)• Pseudomonas aeruginosa• Acinetobacter baumanii

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Mycobacterium tuberculosis• 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)

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Transmission and pathogenesis of TB - 1

• 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• In lung tissue and lymph nodes the bacteria grow

and reproduce

• Can travel to any location in the body

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Transmission and pathogenesis of TB - 2• 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

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Clinical forms• Pulmonary TB (active)

• Cough with thick cloudy, sometimes bloody sputum

• Tiredness• Appetite loss/unexplained weight loss• Night sweats• Fever/chills• Shortness of breath

• Extra pulmonary TB • Signs and symptoms vary with site of infection• Other common sites include central nervous

system, bones, joints, and genitourinary system

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Risk Factors• 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

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Vaccination

• 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• Meningitis• Disseminated TB (miliary)

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Diagnosis & Management

• Chest x-ray• Sputum smear for acid fast bacilli• Tuberculin skin test (TST)

• 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

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Management & Treatment

Management of Exposure• Confirmation of positive infection• Medical evaluation to determine follow up

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

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IP&C MeasuresEngineering 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)

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Negative presssure room

Air flow

Patient with active TB isolated in negative pressure room

HEPA filter

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IP&C Measures - 1Administrative 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

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IP&C Measures - 2Personal Protective Equipment*

• N-95 fit tested masks for healthcare workers• If not available, then surgical masks

• Surgical masks for patients leaving their rooms Dec

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* Typically used for pulmonary TB if the patient is expectorating or has an open lesion

Conclusion

• 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

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Clostridium difficile: Background

• 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

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Pathology - 1

• A Gram-positive spore forming anaerobic bacillus• Widely distributed in the environment• In its vegetative state

• 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

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Pathology - 2

• 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)

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Clinical Significance

• Mild disease • Non-bloody diarrhoea, often mucoid and foul

smelling, cramping, nausea, dehydration, low grade fever, leukocytosis

• Severe disease • Colitis, watery diarrhoea, abdominal pain,

fever, nausea, abdominal distension, pseudomembranes in the gut, toxic mega colon, death

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New Strain

• 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

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Colonisation

• Approximately 3-5% of healthy adults and 20 to 40% of hospitalised patients may be colonised

• Colonised patients generally are not symptomatic• 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

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Patients at Risk Previous antibiotic useSevere underlying illnessProlonged hospital stayAdvanced ageGastrointestinal surgery/manipulationHistory of irritable bowel diseasePatients on proton pump inhibitors

Admission Screening NoRoute of Transmission ContactIsolation Precautions YesAccommodation Single room preferred

Separate toileting facilitiesDocumentation (flagging of patients) May be of benefit to implement a system to designate patients known to be

colonised or infected for early notification on readmissionEnvironmental Cleaning Routine cleaning with attention to high touch surfaces and use of a sporicidal

agentConsider double-cleaning for outbreak situations

Discontinuation of Precautions No diarrhoea for at least 48 hoursFollow-up of Contacts NoPoint Prevalence NoAdditional Outbreak Measures Strict cleaning of multi-use equipment between patients

Dedicated patient equipment to positive casesEducation of staff, patients and visitorsAuditing of outbreak unit/area including hand hygiene, isolation

practices and environmental cleaning

Transmission and Control Measures

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Additional Control Measures

• 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

• Routine identification of carriers • Repeat testing post treatment for clearance

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Antibiotic Resistant Microorganisms

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Methicillin Resistant Staphylococcus aureus (MRSA)

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Background• 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

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Clinical Significance of MRSA

• 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

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Patients at Risk Previous antibiotic useSevere underlying illnessProlonged hospital stayPrevious contact with medical facilityUse of invasive proceduresClose proximity to a patient colonised or infected with MRSA

Admission Screening Sites Yes, based on patient risk factorsNares, rectal, wounds, exit sites

Route of Transmission Contact (plus droplet for symptomatic patients with pneumonia)

Isolation Precautions 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

Environmental Cleaning Routine cleaning with attention to high touch surfaces

Discontinuation of Precautions 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 therapyNote: Re-colonisation is known to occur so on-going monitoring is recommendedConsider maintaining isolation precautions in an outbreak setting

Follow-up of Contacts 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

Point Prevalence In an outbreak setting:Conduct serial (e.g., weekly) unit specific point prevalence cultures to determine if transmission has decreased or ceasedConsider discharge and/transfer screening of patients until transmission has decreased or ceased

Additional Outbreak Measures Strict cleaning of multi-use equipment between patientsDedicated patient equipment to positive casesEducation of staff, patients and visitorsAuditing of outbreak unit/area including hand hygiene, isolation practices and environmental cleaning

MRSA Transmission and Control Measures

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VISA and VRSA• 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• So far only few isolates in different parts of the

world

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Vancomycin Resistant Enterococcus (VRE)

Background• Enterococci are normal gut bacteria• May also be present in the oropharynx, vagina,

or on skin• Causes serious bacterial infections

• Wound infections• Urinary tract infections• Endocarditis • Sepsis

• Often resistant to ampicillin (the drug of choice); infections then treated with glycopeptides

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VRE Epidemiology

• 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

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Clinical Significance

• 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

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Patients at Risk Previous antibiotic useSevere underlying illnessProlonged hospital stayPrevious contact with medical facilityUse of invasive proceduresClose proximity to a patient colonised or infected with VRE

Admission Screening Sites Yes, based on patient risk factors. RectumRoute of Transmission Contact

Isolation Precautions YesAccommodation Single room preferred

Separate toileting facilitiesDocumentation (flagging of patients) May be of benefit to implement a system to designate patients known to be colonised or infected

for early notification on readmissionEnvironmental Cleaning Routine cleaning with attention to high touch surfaces

Consider double cleaning in outbreak situationsDiscontinuation of Precautions 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 therapyNote: Re-colonization is known to occur so on-going monitoring is recommended. Consider maintaining isolation precautions in an outbreak setting

Follow-up of Contacts 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

Point Prevalence In an outbreak setting:Conduct serial (e.g., weekly) unit specific point prevalence cultures to determine if transmission has decreased or ceasedConsider discharge and/transfer screening of patients until transmission has decreased or ceased

Additional Outbreak Measures Strict cleaning of multi-use equipment between patientsDedicated patient equipment to positive casesEducation of staff, patients and visitorsAuditing of outbreak unit/area including hand hygiene, isolation practices and environmental cleaning

VRE Transmission and Control Measures

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Multi-Drug Resistant Gram- Negative Microorganisms

(MDRGN)

MDRGN - 1

• The “Enterobacteriaceae” family of bacteria are a normal part of the gastrointestinal flora

• The most frequent isolates are:• Escherichia coli• Klebsiella pneumoniae• Serratia marcescens• Enterobacter species

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Mechanisms of Resistance

Escherichia coli and Klebsiella pneumoniae can have extended spectrum beta-lactamase (ESBL) enzymes that cause resistance to beta-lactam antibiotics including:

• Penicillins• Cephalosporins• Cephamycins• Monobactams

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Epidemiology of ESBL strains

• There are various types of ESBLs including • TEM• SHV • CTX-M

• 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

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Epidemiology of CRE

• Carbapenem antibiotics are the treatment of choice for serious infections due to ESBL-producing 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

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MDRGN - 2

• The following bacteria are present in aquatic environments• Acinetobacter baumannii• Pseudomonas aeruginosa

• Opportunistic pathogens in humans • A major cause of healthcare-associated

infections• Septicemia• Ventilator-associated pneumonia • Urinary tract infections

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MDR P. aeruginosa and MDR A. baumannii

• 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)

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Clinical Significance

• MDRGN (including ESBLs, CREs, MDR PA and MDR AB) pose a significant treatment challenge including • Increased length of stay• Increased mortality • Increased cost

• Contributes to the global crisis of antimicrobial resistance

• Control requires an aggressive world-wide strategy

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Patients at Risk Previous antibiotic useSevere underlying illnessProlonged hospital stayPrevious contact with medical facilityContact with a facility with known outbreaks with MDRGN organisms

Admission Screening Sites Yes, based on local epidemiology and patient risk factors. Rectum

Route of Transmission Contact (plus droplet for symptomatic patients with pneumonia)

Isolation Precautions 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

Environmental Cleaning Routine cleaning with attention to high touch surfaces

Discontinuation of Precautions 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 therapyNote: Re-colonisation is known to occur so on-going monitoring is recommendedConsider maintaining isolation precautions in an outbreak setting

Follow-up of Contacts Based on local epidemiology and patient risk factors

Point Prevalence In an outbreak setting:Conduct serial (e.g., weekly) unit specific point prevalence cultures to determine if

transmission has decreased or ceasedConsider discharge and/transfer screening of patients until transmission has decreased or

ceased

Additional Outbreak Measures Strict cleaning of multi-use equipment between patientsDedicated patient equipment to positive casesEducation of staff, patients and visitorsAuditing of outbreak unit/area including hand hygiene, isolation

practices and environmental cleaning

MDRGN Transmission and Control Measures

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Management of Pathogens in Low Resource Countries • 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

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Conclusion

• 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

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Key Points

• 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

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Further reading• 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/index.html

• Special pathogens, in Damani N. Manual of infection prevention and control, 3rd ed. Oxford University Press, Oxford, 2012:183-249.

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Quiz

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. Nares aloneb. Nares, wounds, exit sitesc. Nares, woundsd. Nares, exit sites

3. ESBL genes are transmitted by plasmids and are restricted to Enterobacteriaceae. T/F?

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International Federation of Infection Control• 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/

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