Presentation on theme: "Pathogens Important to Infection Prevention and Control"— Presentation transcript:
1Pathogens Important to Infection Prevention and Control
2Learning objectivesList special pathogens of interest to IP&C, and for each, describe the impact on the IP&C programmeExplain how antibiotic-resistant bacteria cause problems in healthcareOutline preventive measures for a given special pathogenDecember 1, 2013
4Special pathogensEveryday problem microorganisms for infection prevention and control include:Mycobacterium tuberculosisClostridium difficileAntibiotic resistant organismsMRSA, VREGram-negative multiply resistant organismsEnterobacteria (Escherichia coli, Klebsiella pneumoniae)Pseudomonas aeruginosaAcinetobacter baumaniiDecember 1, 2013
5Mycobacterium tuberculosis Mycobacterium tuberculosis causes tuberculosis (TB)TB affects 1/3 of the world’s population9.4 million new cases in 20081.8 million deaths in 2008Leading cause of death in people living with human immunodeficiency virus (HIV)December 1, 2013Mycobacterium tuberculosis is one of the most resistant pathogens to different environmental conditions. It is resistant to desiccation and low temperatures and can survive in a dark environment for a long time. Therefore, bacilli can live in desiccated droplets and can spread by air through long distances.M.tuberculosis is very sensitive to UV radiation (sunlight) and high temperatures. It is acid fast and this characteristic is very important in rapid diagnosis of sputum smear positivity.Acid-fastness is a physical property of certain bacteria, specifically their resistance to de-colorisation by acids during staining procedures. Acid-fast bacteria are difficult to characterise using standard microbiological techniques (e.g., Gram stain - if you gram stained an acid-fast bacillus (AFB) the result would be an abnormal Gram positive organism, which would indicate further testing), though they can be stained using concentrated dyes, particularly when the staining process is combined with heat. Once stained, these organisms resist the dilute acid and/or ethanol-based de-colorisation procedures common in many staining protocols—hence the name acid-fast.
6Transmission and pathogenesis of TB - 1 December 1, 2013Spread by the airborne route when someone with active disease and positive sputum smear coughs, talks, sneezes, or spitsBigger droplets spread up to 1 m, smaller spread by airBacteria inhaled into lungsIn lung tissue and lymph nodes the bacteria grow and reproduceCan travel to any location in the bodyOnly a small proportion of persons exposed to TB develop clinical symptoms (about 5-10%). Nevertheless, M. tuberculosis can remain in their body in a latent form and later in their life cause clinical infection.A positive sputum smear means that there is at least 1000 M. tuberculosis/ml of sputum. If the number is lower, transmission usually does not occur easily. If the M. tuberculosis is a fully sensitive strain, strict isolation measures can be stopped when the sputum smear is no longer positive. For extensively drug-resistant tuberculosis (XDRG) strains, three sputum smears should be negative before stopping strict isolation measures.
7Transmission and pathogenesis of TB - 2 Latent TB – bacteria contained in the body10% of people with latent TB will develop active diseaseMost commonly affected organ - LungsUntreated, a person with active disease can infect 10 to 15 people a yearDecember 1, 2013After initial contact, so-called primary TB can develop; later on, if the immune system of a person with latent TB weakens, reactivation TB develops. Most frequently lungs are involved in both primary and reactivation TB, but other organs can be involved too (then called extrapulmonary TB).Latent TB InfectionTB bacteria can live in the body without making the person sick. This is called latent TB infection. In most people who breathe in TB bacteria and become infected, the body is able to fight the bacteria to stop them from growing. People with latent TB infection do not feel sick and do not have any symptoms. People with latent TB infection are not infectious and cannot spread TB bacteria to others. However, if TB bacteria become active in the body and multiply, the person will go from having latent TB infection to being sick with TB disease.Active TBTB bacteria become active if the immune system can't stop them from growing. When TB bacteria are active (multiplying in the body), this is called TB disease. People with TB disease are sick. They may also be able to spread the bacteria to people they spend time with every day.Many people who have latent TB infection never develop TB disease. Some people develop TB disease soon after becoming infected (within weeks) before their immune system can fight the TB bacteria. Other people may get sick years later when their immune system becomes weak for another reason.ReactivationReactivation TB may occur if an individual's immune system becomes weakened and is no longer able to contain the dormant bacteria. The bacteria then become active and make the person sick with TB. This is called TB disease.
8Clinical forms Pulmonary TB (active) Extra pulmonary TB Cough with thick cloudy, sometimes bloody sputumTirednessAppetite loss/unexplained weight lossNight sweatsFever/chillsShortness of breathExtra pulmonary TBSigns and symptoms vary with site of infectionOther common sites include central nervous system, bones, joints, and genitourinary systemDecember 1, 2013While active pulmonary TB is highly contagious, extra-pulmonary TB is not contagious.TB meningitis tends to be more severe than other forms of meningitis. Although % of those affected will survive, up to one quarter of those may have long-term after effects. This is mainly because it is so difficult to recognise the disease at an early stage. By the time treatment begins, there may be damage to brain tissue as well as nerves and blood vessels in the area around the brain.
9Risk Factors Weakened immune system Contact with someone with active TBCaring for active TB patientsLiving or working in crowded conditions with someone with active TBe.g., prisons, nursing homes, homeless sheltersPoor access to healthcareAlcohol or drug abuseTravel to places where TB is endemicBeing born in a country where TB is endemicSome medications for rheumatoid arthritisDecember 1, 2013These risk factors are important for both primary and reactivation TB. An impaired immune system is the most important risk factor in cancer patients and HIV-positive persons. Age is also a very important risk factor: very young and very old persons have a naturally weaker immune system.
10Vaccination 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 diseaseMeningitisDisseminated TB (miliary)December 1, 2013The BCG strain (Bacillus Calmete-Guerin) is an attenuated strain of M. bovis that shares antigens with M.tuberculosis and is not virulent. Vaccination against TB is not universally used. In some countries it is mandatory and given to newborns, in other countries it is available, however it is not mandatory.The World Health Organization recommends BCG be given to all children born in countries highly endemic for TB because it protects against miliary TB and TB meningitis.
11Diagnosis & Management Chest x-raySputum smear for acid fast bacilliTuberculin skin test (TST)Can take up to 3 months for those newly exposed to develop positive testMay be falsely positive because of BCG vaccinationInterferon gamma release assays (IGRA) in vaccinated personsCulture (can take up to six weeks) and sensitivity testDecember 1, 2013Tuberculin skin test (TST) is used when there is clinical suspicion of TB, after performing a chest X-ray and sputum smear for acid fast bacilli (if negative) to determine previous contact with TB.As tuberculin is not highly specific for TB, TST will be positive in persons who were vaccinated. An IGRA test is performed with protein antigens specific for M.tuberculosis. It has no cross reactivity with the BCG strain or most atypical mycobacteria.TST and IGRA tests cannot distinguish between active and latent TB.
12Management & Treatment Management of ExposureConfirmation of positive infectionMedical evaluation to determine follow upTreatment of patientsTreatment for latent or active TB should follow World Health Organization recommendationsIncomplete treatment can cause resistanceAdherence to therapy is criticalDecember 1, 2013As healthcare workers are in risk of acquiring TB during their work, it is usefull to test them for TB before beginning work, and then periodically during employment in healthcare.WHO Treatment of tuberculosis: guidelines for national programmes -
13IP&C Measures Engineering controls Negative pressure rooms High efficiency particulate air (HEPA) filtration systemEnhanced ventilationUltraviolet irradiation (only in empty room)Sunlight exposureOpen window (last resort if no other options)December 1, 2013Various engineering controls are available depending on the facility’s resources.Negative pressure rooms are relatively expensive to build; not all hospitals have them. They are necessary for patients with X-MDR TB, together with HEPA filters. If this is not possible, the patient is to be placed in single room with doors closed at all times.Enhanced ventilation will dilute the bacteria and decrease the chance of transmission. UV irradiation is possible only as terminal disinfection of the air, when a patient is discharged and the room is empty. Very often the only possible measures are exposure of the room to sunlight and opening windows to dilute airborne bacteria.
14Patient with active TB isolated in negative pressure room Negative presssureroomDecember 1, 2013HEPA filterAir flowIt is important that staff always wear masks when entering this room even though the air flow is directed to a filter unit.Patient with active TB isolated in negative pressure room
15IP&C Measures - 1 Administrative Controls Identify patients with signs and symptoms of TBAdditional precautions for patients suspected to have active TBPrompt treatmentVaccination of healthcare personnelRespiratory etiquetteDecember 1, 2013Identification of patients with active TB is not often easy to do. We have to educate patients to perform respiratory etiquette: every patient who coughs or sneezes should wear mask when coming to the doctor. It is very practical to have a box of surgical masks together with a poster about the use of these masks in a waiting room for emergency admissions, or in a waiting room of a doctor’s office.Additional precautions to prevent spread are placement in an isolation room and use of personal protective equipment. It is not necessary for the patient to have marked crockery (special dishes or silverware), and no special precautions are needed for bed linen, books, or other personal items.
16IP&C Measures - 2 Personal Protective Equipment* N-95 fit tested masks for healthcare workersIf not available, then surgical masksSurgical masks for patients leaving their roomsDecember 1, 2013* Typically used for pulmonary TB if the patient is expectorating or has an open lesionN-95 fit tested masks- A mask or respirator that blocks out 95 percent of airborne particles larger than 0.3 microns. FFP3 masks could also be used.These medical masks are a type of disposable respirator that may be used in a medical setting. They function by filtering out particulates in the air before they reach the respiratory system. Both the USA’s Food and Drug Administration and the National Institute for Occupational Safety and Health approve the use of N95 respirator masks to protect against tuberculosis transmission.
17ConclusionDespite the high global impact of TB, it is treatable and preventableOccupation exposures remain a significant risk for healthcare workersIP&C measures are needed to decrease exposures to patients and healthcare workersDecember 1, 2013One could also say that despite known measures of prevention and treatment, TB is still a large global problem. The main reasons might be an unavailabilty of health care and antituberculous drugs in many areas of the world, low compliance to treatment that is protracted and consists of multiple drug regimens (3 or 4 drugs for 6 to 24 months), and unavailability of negative pressure isolation rooms.
18Clostridium 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 countriesCDI primarily occurs in those patients exposed to antibiotics in healthcare facilitiesDecember 1, 2013Clostridium difficile was first recognized as a cause of antibiotic-associated colitis (pseudomembranous colitis) and antibiotic-associated diarrhoea in hospitalised patients receiving clindamycin and other antibiotics. Nowadays it is well known that chemotherapeutic drugs can also cause CDI. In addition, CDI can develop in outpatients not receiving any drugs. CDI is now more common than MRSA infections in some countries.The clinical forms range from uncomplicated self-limiting diarrhoea to pseudomembranous colitis, ileus or toxic megacolon and death. CDI is often a recurrent disease.C. difficile is more common is some countries than in others.
19Pathology - 1 A Gram-positive spore forming anaerobic bacillus Widely distributed in the environmentIn its vegetative stateProduces toxinsCan be killed by antibioticsSpore formDormantNo toxin productionResistant to antibiotics and disinfectantsCan persist for months in the environmentDecember 1, 2013C. difficile is a fastidious anaerobic microorganism that cannot easily survive in the human gut as long as normal flora is preserved. If normal flora is destroyed by antibiotics (especially antibiotics that are active against Gram-negative anaerobic flora), C. difficile has the space and the food for unhampered growth. If the strain produces toxins, disease can develop.Antibiotics that kill C. difficile are vancomycin and metronidazole
20Pathology - 2 Produces 2 toxins Toxin A and Toxin BBind to intestinal epithelial cells causing inflammation and diarrheaToxins are cytotoxic and enteropathicAlteration of the gut flora by antibiotics an important risk factor (decrease of normal gut flora)December 1, 2013Toxin B is necessary for disease development. This is important for diagnostic methods that have to identify existence of toxin B.The two major toxins, A and B, have been studied intensively since their initial recognition as major C. difficile virulence factors. In addition to their contribution to disease, A and B are the primary markers for diagnosis of C. difficile disease and are detected in the stools of patients by antibody-based and cytoxicity assays.Most pathogenic strains of C. difficile produce both toxin A and B. Strains that are A-B+ are fully pathogenic and capable of producing the full spectrum of disease.
21Clinical Significance Mild diseaseNon-bloody diarrhoea, often mucoid and foul smelling, cramping, nausea, dehydration, low grade fever, leukocytosisSevere diseaseColitis, watery diarrhoea, abdominal pain, fever, nausea, abdominal distension, pseudomembranes in the gut, toxic mega colon, deathDecember 1, 2013Severe disease is important for transmission of C. difficile. In severe disease, the patient is often incontinent and bacteria are dispersed widely to the patient’s environment.
22New Strain Increased incidence of B1/NAP1/027 strain Causes severe diseaseMore resistant to standard therapyMore likely to relapseAssociated with higher mortality16x more toxin A; 23x more toxin BRelated to excessive use of certain drugs/antibioticsDecember 1, 2013B1/NAP1/027 is called a hypervirulent strain as the toxin production is greatly enhanced due to a gene mutation. Besides hypervirulence, this strain also has enhanced epidemiological potential.This strain causes more severe disease and increased mortality. The epidemic strain produces a third toxin, binary toxin; its role in human disease is not yet defined, but it is suggested that it may contribute to the pathogenesis of CDI. This strain has increased antimicrobial resistance, notably to clindamycin and fluoroquinolones [gatifloxin and moxifloxacin]. Research shows that the epidemic strain produces toxins A and B and common antigen (glutamate dehydrogenase) and reacts in commercial C. difficile tests specific for the toxins or for antigen.
23ColonisationApproximately 3-5% of healthy adults and 20 to 40% of hospitalised patients may be colonisedColonised patients generally are not symptomaticMay be a potential reservoir for transmissionEvidence suggest spores on the skin of asymptomatic patients can contaminate the hands of the healthcare workerNo recommendations to treat carriers nor to perform admission screeningDecember 1, 2013Patients can be infected not only by the hands of staff but also by their own hands, if they are mobile, and touch different areas in the room that may be contaminated. This is important to keep in mind as this is the reason why there is a high percentage of colonised patients in hospitals. Therefore it is important to teach patients about hand hygiene.C. difficile is transmitted from person to person by the faecal-oral route.
24Transmission and Control Measures Patients at RiskPrevious antibiotic useSevere underlying illnessProlonged hospital stayAdvanced ageGastrointestinal surgery/manipulationHistory of irritable bowel diseasePatients on proton pump inhibitorsAdmission ScreeningNoRoute of TransmissionContactIsolation PrecautionsYesAccommodationSingle room preferredSeparate 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 CleaningRoutine cleaning with attention to high touch surfaces and use of a sporicidal agentConsider double-cleaning for outbreak situationsDiscontinuation of PrecautionsNo diarrhoea for at least 48 hoursFollow-up of ContactsPoint PrevalenceAdditional Outbreak MeasuresStrict 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 cleaningDecember 1, 2013The most important measure to decrease transmission of C. difficile is hand hygiene as hands of staff and of patients are the most important means of transmission. Alcohol hand rub will kill vegetative forms, however it will not kill spores. Therefore hands should be washed with soap and water before and after every contact with a patient and/or the patient’s environment.Non-sterile (clean) gloves should be used for patient care. After removing gloves, hand washing with soap and water should be performed.
25Additional Control Measures Discontinuation of all antibiotics in a symptomatic patient (except for CDI)Facility-wide antibiotic control policiesEarly notification of patients with diarrhoea to the IC teamNot recommendedRoutine identification of carriersRepeat testing post treatment for clearanceDecember 1, 2013The hypervirulent strain is resistant to fluoroquinolones; in an outbreak situation, fluoroquiolones should not be widely used. If possible, patients with healthcare-associated diarrhoea should be immediately placed in single room.There is a CDI prevention bundle*:Antibiotic prescribing (stop antibiotic or go to a narrow spectrum)Early diagnosisPrompt isolationImplementation of infection prevention & control precautionsClean and disinfect environmentDecontaminate/sterilise patient care items/equipment*Clostridium difficile infection: How to deal with the problem, Health Protection Agency, Department of Health, and High Impact Intervention Care bundle to reduce the risk from Clostridium difficile -
26Antibiotic Resistant Microorganisms December 1, 2013The second part of the presentation deals with antibiotic resistant microorganisms. Some of these organisms are already well known and widespread, while others are newly developed and often first a local problem, which then becomes widespread. These are:methicillin-resistant Staphylococus aureus (MRSA)vancomycin-resistant Enterococci (VRE)extended spectrum beta lactamase producing Enterobacteriacae (ESBL)carbapenamase producing Klebsiella ( a carbapenem resistant Enterobacteriacae or CRE)multidrug resistant Pseudomonas aeruginosa (MDR PA) andmultidrug resistant Acinetobacter baumannii (MDR AB).
28Background Staphylococcus aureus is a Gram-positive bacteria 30% of people are permanently colonisedNosePharynxPerineumTransient colonisation occurs, mainly on handsColonisation although harmless, increases the risk of infection and transmissionDecember 1, 2013S. aureus is the most frequent bacterial pathogen of humans (along with Escherichia coli). S.aureus causes an array of infections – from self-limited skin infections to severe sepsis, pneumonia and osteomyelitis.
29Clinical Significance of MRSA First a problem in 1960sGlobally has reached epidemic proportionsBoth community associated (CA) and healthcare associated (HA) strains of MRSARates vary byCountryRegionIndividual healthcare facilityDecember 1, 2013MRSA strains are resistant not only to all beta lactam antibiotics (although nowadays we have a new antistaphylococcal cefalosporins) but very often to most antistaphylococcal antibiotcs except glycopeptodes (vancomycin, teicoplanin) and linezolid.CA MRSA are very important problem in the USA; it is not so pronounced in other parts of the world.
30MRSA Transmission and Control Measures Patients at RiskPrevious antibiotic useSevere underlying illnessProlonged hospital stayPrevious contact with medical facilityUse of invasive proceduresClose proximity to a patient colonised or infected with MRSAAdmission Screening SitesYes, based on patient risk factorsNares, rectal, wounds, exit sitesRoute of TransmissionContact (plus droplet for symptomatic patients with pneumonia)Isolation PrecautionsYesAccommodationSingle room preferredDocumentation (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 CleaningRoutine cleaning with attention to high touch surfacesDiscontinuation of PrecautionsUnresolved 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 settingFollow-up of ContactsTwo sets of specimens taken on different days with one taken a minimum of 7 days after the last exposure, especially in an outbreak settingPoint PrevalenceIn 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 ceasedAdditional Outbreak MeasuresStrict 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 cleaningDecember 1, 2013
31VISA and VRSAVancomycin is drug of choice for treating MRSA infectionsStaphylococcus aureus with decreased (intermediate) susceptibility to vancomycin = VISAStaphylococcus aureus with resistance genes Van A or Van B = VRSASo far only few isolates in different parts of the worldDecember 1, 2013VISA strains first appeared in Japan in 1996, now they have been found in different parts of the world (United Kingdom, Asia, Brazil, United States, France, Croatia. True VRSA with the enterococcal Van A or Van B genes is so far very rare and mostly sporadic cases are reported from different parts of the world.
32Vancomycin Resistant Enterococcus (VRE) December 1, 2013Vancomycin Resistant Enterococcus (VRE)
33Background Enterococci are normal gut bacteria May also be present in the oropharynx, vagina, or on skinCauses serious bacterial infectionsWound infectionsUrinary tract infectionsEndocarditisSepsisOften resistant to ampicillin (the drug of choice); infections then treated with glycopeptidesDecember 1, 2013The most serious infections caused by VRE are endocarditis and sepsis in immunocompromised hosts. These infections are always treated with combination therapy using ampicillin or vancomycin plus gentamicin.
34VRE EpidemiologyVRE is enterococcus that is resistant to the glycopeptide vancomycinFirst isolated in the 1980’sSpread globally causing asymptomatic colonization, infections, and outbreaksThe prevalence of VRE varies worldwideDecember 1, 2013The prevalence of VRE is highest in the USA, especially in intensive care units. It is identified much less in Europe and other parts of the world.
35Clinical Significance Clinically relevant strains carry Van A or Van B resistance genesLimited antibiotics to treat VRE infectionsTransfer of resistance genes to other microorganisms such as MRSA is a great concernDecember 1, 2013People with colonised VRE (bacteria are present, but have no symptoms of an infection) do not need treatment. Most VRE infections can be treated with antibiotics other than vancomycin. Laboratory testing of the VRE can determine which antibiotics will work. For people who get VRE infections in their bladder and have urinary catheters, removal of the catheter when it is no longer needed can also help get rid of the infection.
36VRE Transmission and Control Measures Patients at RiskPrevious antibiotic useSevere underlying illnessProlonged hospital stayPrevious contact with medical facilityUse of invasive proceduresClose proximity to a patient colonised or infected with VREAdmission Screening SitesYes, based on patient risk factors. RectumRoute of TransmissionContactIsolation PrecautionsYesAccommodationSingle room preferredSeparate 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 CleaningRoutine cleaning with attention to high touch surfacesConsider double cleaning in outbreak situationsDiscontinuation of PrecautionsUnresolved 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 settingFollow-up of ContactsTwo sets of specimens taken on different days with one taken a minimum of 7 days after the last exposure, especially in an outbreak settingPoint PrevalenceIn 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 ceasedAdditional Outbreak MeasuresStrict 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 cleaningDecember 1, 2013Admission screening is is not usefull in low prevalence areas.
38MDRGN - 1The “Enterobacteriaceae” family of bacteria are a normal part of the gastrointestinal floraThe most frequent isolates are:Escherichia coliKlebsiella pneumoniaeSerratia marcescensEnterobacter speciesDecember 1, 2013While E.coli is most often susceptible to various antibiotics, and only occasionally (less than 5% of strains) is multidrug resistant, K.pneumoniae, Serratia marcescens and Enterobacter spp are very often highly resistant to antibiotics.In general, E.coli is the most frequent cause of infections in outpatients and inpatients; K.pneumoniae, Serratia spp and Enterobacter spp cause mostly infections of inpatients.
39Mechanisms of Resistance Escherichia coli and Klebsiella pneumoniae can have extended spectrum beta-lactamase (ESBL) enzymes that cause resistance to beta-lactam antibiotics including:PenicillinsCephalosporinsCephamycinsMonobactamsDecember 1, 2013ESBL production is coded by genes on plasmids, so this gene spreads very easily among different Gram-negative bacteria. On the same plasmid there are genes that confer resistance to many other antibiotics, including aminoglycosides and fluoroquinolones. Therefore, ESBL strains are often susceptible to only carbapenems.
40Epidemiology of ESBL strains There are various types of ESBLs includingTEMSHVCTX-MESBLs were first detected in Europe in 1980sSurveillance data from several surveillance systems indicate high rates of ESBLs in many parts of the world including USA, Canada, Europe, China, India and Latin AmericaDecember 1, 2013ESBL - Extended-spectrum beta-lactamases – enzymes produced by some bacteria. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam. TEM-1 is the most commonly encountered beta-lactamase in Gram-negative bacteria. Up to 90% of ampicillin resistance in E. coli is due to the production of TEM-1. SHV-1 shares 68 percent of its amino acids with TEM-1 and has a similar overall structure. The SHV-1 beta-lactamase is most commonly found in K. pneumoniae and is responsible for up to 20% of the plasmid-mediated ampicillin resistance in this species. CTX-M enzymes are not very closely related to TEM or SHV beta-lactamases in that they show only approximately 40% identity with these two commonly isolated beta-lactamases.The most comprehensive surveillance systems are SENTRY and SMART surveillance systems that are industry sponsored systems for surveillance of resistance among Gram-negative bacteria.SENTRY -SMART -
41Epidemiology of CRECarbapenem antibiotics are the treatment of choice for serious infections due to ESBL-producing bacteriaCarbapenem Resistant Enterobacteriaceae (CRE) has also been reportedCarbapenemases of importance include KPC, VIM, OXA and NDM-1CREs have been reported in many areas of the world and have also been associated with outbreaksDecember 1, 2013Carbapenem resistant Enterobacteriaceae are relatively new strains of E.coli and K.pneumoniae that are spreading very successfully throughout the world. The origin of some of them appears to be Asia; tourists bring it to Europe and the USA. However, some of these resistance mechanisms originated in developed countries as well.Carbapenemases are a diverse group of β-lactamases that are active not only against the oxyimino-cephalosporins and cephamycins but also against the carbapenems. The VIM family, was reported from Italy in 1999 and now includes 10 members, which have a wide geographic distribution in Europe, South America, and the Far East and have been found in the United States. The OXA group of β-lactamases occur mainly in Acinetobacter species and are divided into two clusters. OXA carbapenemases hydrolyse carbapenems very slowly in vitro, and the high MICs seen for some Acinetobacter hosts (>64 mg/L) may reflect secondary mechanisms. A few class A enzymes, most noted the plasmid-mediated KPC enzymes, are effective carbapenemases as well.NDM-1 (New Delhi metallo-β-lactamase) - Originally described from New Delhi in 2009, this gene is now widespread in Escherichia coli and Klebsiella pneumoniae from India and Pakistan.K. pneumoniae carbapenemase (KPC) is particularly important in Greece, the USA and Israel.A CRE prevention toolkit is atWHO information at andCase study at
42MDRGN - 2 The following bacteria are present in aquatic environments Acinetobacter baumanniiPseudomonas aeruginosaOpportunistic pathogens in humansA major cause of healthcare-associated infectionsSepticemiaVentilator-associated pneumoniaUrinary tract infectionsDecember 1, 2013Pseudomonas aeruginosa is a major causative agent of ventilator-associated pneumonia in Iintensive care unit patients. It also causes severe sepsis and skin/soft tissue infections in immunocompromised patients, as welll as urinary tract infections in urologic patients. P. aeruginosa is very sensitive to drying; it lives in every humid part of the facility. It can also colonise the mouth, gut and other areas of patients.Acinetobacter baumannii can also be found in aquatic environments; however it often colonises the skin of humans. A. baumannii is very resistant to desiccation and can survive very long in dust. Infections are usually not so severe as infections caused by P. aeruginosa, but can be severe in immunocompromised patients.
43MDR P. aeruginosa and MDR A. baumannii These microorganisms have intrinsically lower susceptibility to antibioticsAcquiring additional resistance genes (ESBL genes, other genes for resistance to beta lactam antibiotics, resistance genes for aminoglycosides and fluoroquinolones) very often means that they aresusceptible only to carbapenems orcolistin orresistant to all antibiotics (panresistant)December 1, 2013
44Clinical Significance MDRGN (including ESBLs, CREs, MDR PA and MDR AB) pose a significant treatment challenge includingIncreased length of stayIncreased mortalityIncreased costContributes to the global crisis of antimicrobial resistanceControl requires an aggressive world-wide strategyDecember 1, 2013
45MDRGN Transmission and Control Measures Patients at RiskPrevious antibiotic useSevere underlying illnessProlonged hospital stayPrevious contact with medical facilityContact with a facility with known outbreaks with MDRGN organismsAdmission Screening SitesYes, based on local epidemiology and patient risk factors. RectumRoute of TransmissionContact(plus droplet for symptomatic patients with pneumonia)Isolation PrecautionsYesAccommodationSingle room preferredDocumentation (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 CleaningRoutine cleaning with attention to high touch surfacesDiscontinuation of PrecautionsUnresolved 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 settingFollow-up of ContactsBased on local epidemiology and patient risk factorsPoint PrevalenceIn 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 ceasedAdditional Outbreak MeasuresStrict 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 cleaningDecember 1, 2013
46Management of Pathogens in Low Resource Countries December 1, 2013IP&C measures vary based on institutional setting and available resourcesHand hygiene should be a routine part of patient care in all settingsAdditional precautions may be considered depending on the pathogen, the institutional setting and outbreak circumstancesHand hygiene is absolutely crucial in prevention of transmission of antibiotic resistant pathogens. The appropriate use of antibiotics is also of utmost importance. So it is very important to combine hand hygiene, isolation precautions, and antimicrobial stewardship in the control of multidrug resistant pathogens.
47ConclusionAntimicrobial resistance is a world-wide public health problemSolutions require a multi-faceted approachImproving behaviours is essentialGlobal awareness and surveillance is requiredImplementation of appropriate IP&C practices and antimicrobial stewardship processes may be beneficialDecember 1, 2013
48Key PointsTuberculosis and multi-drug resistant bacteria are important infection prevention and control issuesMany have developed resistance to antimicrobials making them less effectiveControl measures vary by organism, setting and resourcesDecember 1, 2013
49Further readingApisarnthanarak 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;48:22-24EARS-Net.WHO Global tuberculosis controlSpecial pathogens, in Damani N. Manual of infection prevention and control, 3rd ed. Oxford University Press, Oxford, 2012:December 1, 2013
50QuizWhen a patient with active tuberculosis has to leave the isolation room for tests, s/he has to wear a N95 mask. T/F?Admission screening for MRSA encompasses the following specimens:Nares aloneNares, wounds, exit sitesNares, woundsNares, exit sitesESBL genes are transmitted by plasmids and are restricted to Enterobacteriaceae. T/F?December 1, 2013FalseB
51International 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 toDecember 1, 2013