ndm - 1 role of diagnostic microbiology

8/7/2019 NDM - 1 Role of Diagnostic Microbiology

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Dr.T.V.Rao MD 1

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The Lancet

Opens the Pandora box Gram-negative

Enterobacteriaceae withresistance to carbapenems

conferred by New Delhimetallo--lactamase 1(NDM-1) are potentially amajor global health problem.

We investigated theprevalence of NDM-1, inmultidrug-resistantEnterobacteriaceae inIndia, Pakistan, and theUK.

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Travel makes patients

venerable The superbug called

New Delhi metallo-beta-lactamase, or

NDM-1, was identifiedin 50 people whotraveled to India orPakistan for surgeryand then returned to

the United Kingdom,British scientistsreported in the journalLancet InfectiousDiseases

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Naming the strain as New Delhi

creates controversy

The gene was named after New Delhi, the capitalcity of India, as it was first described by Yong et al. in2009 in a Swedish national who fell ill with an antibiotic-resistant bacterial infection that he acquired in India . Theinfection was unsuccessfully treated in a New Delhihospital and after the patient's repatriation to Sweden, acarbapenem-resistantKlebsiella pneumoniaestrain

bearing the novel gene was identified. The presentingauthors concluded that the new resistance mechanism"clearly arose in India, but there are few data arising fromIndia to suggest how widespread it is."

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Bugs becomes Superbugs

Antibiotic resistancedevelops through geneaction or plasmid

exchange betweenbacteria of the samespecies. If a bacteriumcarries severalresistance genes, it is

called multiresistantor, informally, asuperbug.

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CDC Reports

Three Enterobacteriaceae isolatescarrying a newly describedresistance mechanism, the New

Delhi metallo-beta-lactamase(NDM-1) , were identified from

three U.S. states at the CDCantimicrobial susceptibilitylaboratory. This is the first

report of NDM-1 in the UnitedStates, and the first report ofmetallo-beta-lactamase carriageamong Enterobacteriaceae in theUnited States

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Mark Toleman of Britain's Cardiff UniversitySchool of Medicine, creates concerns ?

The inhabitants of NewDelhi are continuallybeing exposed to

multidrug-resistant andNDM 1-positivebacteria," said MarkToleman of Britain'sCardiff University

School of Medicine,who published thefindings in a study onThursday.

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Tolemans Study a Concern

to India Tolemans study, carried out

with Cardiff UniversitysTimothy Walsh and

published in The LancetInfectious Diseases journal,investigated how commonNDM 1-producing bacteriaare in community waste

seepage such as waterpools or rivulets in streets and tap water in urban NewDelhi.

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In September and October 2010, Walshs research

team collected 50 samples from public drinkingwater taps in New Delhi and 171 samples from

seepage, standing water that had pooled nearpublic areas, both of which are used by residents fordrinking, washing and/or other householdfunctions. The scientists found bacterial strains withthe NDM-1 mutation in two of the drinking water

samples and in 51 of the seepage samples. Forcomparison, they collected 70 samples from Cardiffswater supply and found no evidence of bacteria withNDM-1 mutations.

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Facts Reported on the Present

Study


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Facts on NDM-1 are Concern to

the National Health

Speech is silver

Silence is Gold

Ignoring the

facts isDangerous

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Why Microbiologists are Important

in the Changing ScenarioAdequate clinical

management ofinfectious diseases

relies primarily on theaccurate identificationof the causal micro-organism and theproduction of reliable

information on itsantimicrobialsusceptibility

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Now Clinicians Need Faster

Diagnostic Information Traditional diagnostic

methods inmicrobiology have lim-

ited the ability oflaboratories to providedoctors with timely andclinically relevantinformation, but recent

technology providesresults in minutes orhours rather than daysor weeks.

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Safety of the Laboratory Personal

A Top Priority The protection of personnel

and the immediatelaboratory environment

from exposure to infectiousagents is provided by bothgood microbiologicaltechnique and the use ofappropriate safety

equipment. The use ofvaccines may provide anincreased level of personalprotection.

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Let our Policy to start with

Containment The term "containment" is

used in describing safemethods for managinginfectious materials in the

laboratory environmentwhere they are beinghandled or maintained.The purpose ofcontainment is to reduce oreliminate exposure of

laboratory workers, otherpersons, and the outsideenvironment to potentiallyhazardous agents.

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Implementing Biosaftey at Medical

Establishments in India It is time to educate on

Biosafety issues.Document the

Information regardingthe Biosafteyequipment available inthe Hospital, Colleges,if not, to do at the

earliest, and concernsof the Health of theLaboratory personalshould be mademandatory.


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Continues to be Most Neglected part ofDiagnostic Microbiology

Can be Improved

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Endocervical swabs for GC

Per nasal swabs for pertussis

whole EMU for TB

Sputum , not saliva

Blood culture bottles, not clotted blood

Correctly timed Gentamicin assays

Pus, not swabs

Major value of the Diagnostic Microbiology islost in unscientific methods, left casually to illtrained staff

Collecting the correct specimen most neglectedpart of Diagnostic Microbiology

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Getting the specimen to the

laboratory Problems in delay or inappropriate storage delay in

diagnosis & treatment pathogens die

contaminants overgrow

Blood cultures directly into incubator not refrigerator!

CSF straight to lab Don't put an entire surgical specimen into formalin!

Send a portion to microbiology in a sterilecontainer

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Collecting the specimen correctly

Take an mid-stream urine avoids contamination with perineal flora

CSF Avoid contamination

Avoid bloody tap

Throat swab

Make the patient gag! Blood cultures Avoid contamination with skin organisms

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Labelling Specimens &

Infection Control Please be considerate to

lab staff!!

Label hazardousspecimens

Don't send specimensto the lab without

proper packing Leaking or blood-

stained specimens arenot acceptable!!!

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Factors limiting usefulness of bacteriologicalinvestigations

What is going WrongWrong sample e.g. saliva instead of sputum

Delay in transport / inappropriate storage e.g. CSF

Overgrowth by contaminants e.g. blood cultures

Insufficient sample / sampling error e.g.in mycobacterial disease

Patient has received antibiotics

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The major control on use , misuse ofAntibiotics can be controlled with Good

Practices

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The role of antimicrobial susceptibility tests to guideempirical therapy, to refine therapy once pathogens

have been isolated and identified, and to detect newtypes of antimicrobial resistance is well established.Other roles of antimicrobial susceptibility testing forpatient care, such as development of cumulativeAntibiograms, creation of antimicrobial formularies,and detection of new antimicrobial resistance strainsor trends, are also well established.

ANTIMICROBIAL

SUSCEPTIBILITY TESTING

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Quality Control on Antimicrobialtesting is crucial

Generating accurateand reproducible

antimicrobialsusceptibility test datarequires perhaps themost extensive QCprogram used in

clinical laboratoriestoday

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The CLSI publishes guidelines for the QC of

antimicrobial susceptibility tests . These guidelinesare extensive and require rigorous adherence to each

step of testing for results to be accurate andreproducible. Specific guidelines have beendeveloped not only for different categories ofbacteria and fungi (e.g., members of theEnterobacteriaceae family) but also for individual

species. Perhaps the most important guidelinespublished by CLSI are that antimicrobial agentsshould be tested against different microbialpathogens

Adherence to CLSI Guidelines ..

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The information used to develop these guidelines is based

on clinical, pharmacologic, and microbiologic data. It isstrongly recommended that clinical microbiologylaboratories and providers both adhere to theseguidelines; testing antimicrobial agentpathogencombinations that are not recommended may generateantimicrobial susceptibility test results that either aremisleading or cannot be interpreted.

In general, it is also strongly recommended that newantimicrobial agents should not be tested in clinicallaboratories until there are sufficient data for CLSIguidelines to be developed and published

Why All DiagnosticLaboratories should adhere to

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Reporting newer pattern ofResistance needs reference Methods

Detection of new types orpatterns of antimicrobialresistance may be

fortuitous or the result ofactive surveillance. Theformer should not beused to guide patient careuntil the data areconfirmed by a reference

method; publishedreports of new types orpatterns of resistancetypically reflect extensiveconfirmatory testing.

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Follow current practices as per

CLSI guidelines Most microbiology

laboratories usecommercial systems forantimicrobial

susceptibility testing,which may or may not yethave the capability ofdetecting newer forms ofresistance, reliable meansof detecting new types or

patterns of antimicrobialresistance often lagbehind publishedinformation.

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Implementation ofWHONET CANHELP TO MONITOR RESISTANCE

Legacy computersystems, qualityimprovement teams,and strategies foroptimizing antibioticuse have the potentialto stabilize resistanceand reduce costs by

encouragingheterogeneousprescribing patternsand use of local

susceptibility patternsto inform em iric


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World Antibiotic ResistanceNetwork

WHO has alsostarted another

program, WARN (theWorld AntibioticResistance Network),to help gather and

analyse the datagenerated by thepeople who use

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Are We Using It How much we use them ?

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Automated and semi automated systems

have been available for some years but

without full realization of their potential forrapid diagnosis. They fall into two maingroups: identification and susceptibilitytesting instruments and blood culture

systems. Whereas some identification andsusceptibility testing instruments take as longas traditional methods, others provide resultswithin a single working day.

Up gradation to Automation inCritical samples

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Blood culture systems have had considerable impact

on the ability to detect bacteremia. Growth isdetected through generation of a radiometric signalor a fluorescent or colorimetric indicator. Most truepositive results are detected within 24 to 36 hours.Identification and susceptibility results may beobtained in many blood culture isolates within the

same time when a blood culture system is combinedwith an automated identification or susceptibilitytesting instrument

Automation in Blood Culturingreduces mortality and Morbidity

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Blood culture systems have been adapted for the

automated or semi automated culture of

Mycobacterium tuberculosis and other mycobacteria.These commercial systems reduce the traditionaldependence on bio chemical reactions to identifyorganisms; avoid the and mycobacteria amongothers. Nucleic acid amplification systems are

available for the direct detection in clinicalspecimens of hepatitis C virus, HIV,M tuberculosis, C trachomatis, andN gonorrhea since morethan a decade.

Several Life threating conditionscan the treated Promptly

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Molecular techniques

Molecular biologicaltechniques have increasedthe speed and sensitivity of

detection methods, as wellas allowing laboratories toidentify organisms that donot grow or grow slowly inculture. These techniquesalso allow microbiologists toidentify genes that result inresistance to antibiotics andto fingerprint individualisolates for epidemiologicaltracking.

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New technologies enable to

New technologies

enable microbiology

results to beavailable in minutesor hours rather thandays.

Early diagnosisbetter prognosis andlesser costs intreatments

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Molecular biological methods

Nucleic acid probehybridization, thepolymerase chainreaction, the ligase chain

reaction, transcriptionmediated amplification,other evolvingamplification methods,and nucleic acidsequencing form the basis

of detecting andcharacterizing an everincreasing range ofviruses, bacteria, fungi,and protozoa

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Immunoassays have benefits

Immunoassays havebenefits of technical

simplicity, rapidity,specificity, and costeffectiveness butoften have poorsensitivity and lownegative predictivevalue

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Molecular Methods helps in

New trends in Recognition of newly

emerging infectiousdiseases and control ofantibiotic resistance in

Streptococcuspneumoniae,Haemophilus influenzaMoraxella catarrhalis,Staphylococcus aureus,

and Common Gramnegative bacilli will relyheavily on these newtechnologies.

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Limitations of Molecular Methods

The introduction ofmolecular diagnosticmethods in themicrobiologic diagnostic

laboratory is subject to anumber of practical andfinancial constraintsrequiring the elaboration ofa sound strategy. Validation

of the tests may require theuse of an expanded goldstandard or the applicationof novel statistical methodssuch as latent class analysis.

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The procedures should be constantly evaluated for false

positive an false negative results. The introduction ofmolecular methods will not only depend on their

performance for each individual microorganism, but also onthe clinical relevance of the diagnostic question asked,the prevalence of the clinical problem and whether the newmethods are added to the procedures in use or will replace

them. Therefore no general rules can be proposed,strategies have to be elaborated for each infectious agent orclinical syndrome

Limitations of Molecular Methods ?

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Microbiologists must plan

and Execute for changeWith increase in

availability of costeffective commercial

systems, laboratorieswill be able to capitalizeon the extremespecificity, high

sensitivity, and rapidityof these molecularapproaches.

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Better Diagnosis in Emerging

and Reemerging InfectionAn ever increasing

range of viruses,

bacteria fungi, andprotozoa can bedetected andcharacterized bymolecular biologicalmethods

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Studies prove that misuse of antibiotics may causepatients to become colonized or infected with

antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and highly-resistant Gram-negative bacilli.13-14

Misuse of antibiotics is also associated with anincreased incidence of Clostridium difficileinfections.15-17

Misuse of Antibiotics Drives

Antibiotic Resistance

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Spread of Antibiotic Resistance

Indiscrimate use ofAntibiotics in Animals andMedical practice

R plasmids spread amongco-inhabiting Bacterialflora in Animals ( in gut )

R plasmids may be mainlyevolved in Animals spreadto Human commensal, -Escherichia coli followedby spread to moreimportant humanpathogens Eg Shigella spp.

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Misuse of antibiotics can include any of the following

When antibiotics are prescribed unnecessarily;When antibiotic administration is delayed in critically ill

patients;When broad-spectrum antibiotics are used too generously, or

when narrow-spectrum antibiotics are used incorrectly;When the dose of antibiotics is lower or higher than

appropriate for the specific patient;When the duration of antibiotic treatment is too short or toolong;

When antibiotic treatment is not streamlined according tomicrobiological culture data results.

What is Misuse of

Antibiotics?

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Aim of Antibiotic

PolicyReduce the Antimicrobial resistanceInitiate best efforts in the hospital area as many

resistance Bacteria are generated in Hospitalareas and in particular critical care areas.Initiate good hygienic practices so these bacteria

do not spread to othersPractice best efforts, these resistance strains do

not spill into critically ill patients in the HospitalTo prevent spill into Society, as they present as

community associated infections..

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Objectives of Antibiotic Policy.

Antibiotics should not be used casuallyPolicy emphasizes, avoiding the use of

powerful Antibiotics in the Initial treatments.We should create awareness that we are

sparing the powerful Broad spectrum Drugsfor later treatment

Patient saves MoneyDoctors save Lives.

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Policy Deals on Broad

BasisClinicians /

Microbiologists /Pharmacists and

Nurses do take part. Policies are framed on

demands of the Clinicalareas, depending onrecent Infection

surveillance datacontributed fromMicrobiologyDepartments.

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Education On Antibiotic policy

Acton plan for Education to all concernedclinical staff on Antibiotic prescriptions.

Evaluate the feed back of success andfailures of the policy.Create Infection surveillance DataDeveloping facilities in Microbiology

departments for auditing data and

guidanceRestrictions in prescribing and Antibioticavailability.

A continuous education to Junior Doctors

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Staff Education on AntibioticPolicy

Staff education is most Important principle insuccess

Draw your own plans according to nature ofpatients, your past experiences

Induction training for new staffContinuing Medical Education to both Junior

and Senior DoctorsInclude nursing staff, pharmacists for the

success of the Programme

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Make your conclusions andcontribute to Antibiotic Policy

It is true to say that there is no absolute proofof causative association between antibiotic

use and resistance, But many authoritiesbelieve the association to be virtually certain.It is pragmatic and essential approach to

control of antibiotic resistance with controlof antibiotic use.

Make every one a partner in prevention ofAntibiotic resistance, and success will follow.

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Implementing better training anddevelopment opportunities for all staff andimproved recruitment and improve qualitystandards to produce Centres of Excellencefor Microbiology, with an increased pool ofconsultant expertise across sites

More efficient utilisation of facilities andequipment

Reasons for Forming a NetworkTo improve quality, efficiency and effectiveness

of the service leading to better patient care.

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Modernising Strategy

Managed Microbiology networks providing a wider strategiccontext for planning Microbiology services.Modernisation strategies to support service development.

Integrating Microbiology into wider service developments

Redesigning systems

Making effective use of IT and new technologies Medical

Informatics

Improving information management

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Modernisation Principles for

MicrobiologyPatient-centred

Appropriate

Develops staff

Integrated

Effective

Efficient

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Our changing Role Microbiologists can and

should play an importantrole in assuring thequality of results that are

generated by clinicalmicrobiologylaboratories. Their mostimportant role is to helpcorrelate clinical,laboratory, and

radiographic data, todetermine the clinicalrelevance, if any, ofmicrobiology test results

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Use of automation to improve and


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Use of automation to improve anddevelop services

Opportunity to develop new HR Strategy Reduced staff where employment difficult

Better use of qualified staff

Multidisciplinary use of staff

Improved Terms and Conditions

Develop services Point of Care Testing Molecular Biology

Diagnostic technicians

Greater efficiency Shift systems

Extended role for non-professional staff Better access times

More efficient and effective service Laboratory Ward

Community

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NDM 1 superbugs found in


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NDM-1 superbugs found inseepage, tap water

Gram-negative bacterialstrains with NDM-1 (NewDelhi Metallo-beta-lactamase-1) gene, alsocalled the superbug, havenow been detected indrinking water andseepage water samplescollected from severalsites in New Delhi.Seepage samples werecollected from waterpools found in streets orrivulets.

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Our Role Has changed withNDM-1 ?

Our role relates to thetimely reporting ofaccurate test results,which depends on thepractice of rigorous QC.There is no compellingreason to deviate fromthis practice, particularlybecause any test resultsthat would be generatedare likely to be clinicallyirrelevant, misleading, oreven dangerous topatients.

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Core Functions of Microbiology


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Core Functions of MicrobiologyLaboratories

1. Communicable disease surveillance, preventionand control2. Outbreak and emergency response to

communicable diseases3. Environmental health and food safety

4. Reference testing, specialized screening anddiagnostic testing5. Biosafety, containment, and biohazard response6. Integrated communicable disease data

management

7. Public health policy development and evaluation8. Laboratory Quality Assurance9. Training and education of health care workers10. Public health related research and development

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Systematic data collection &

interpretation of clinical and lab

informationMultidisciplinary team approach

Labs in community, hospitals, public

health all report to local public healthPublic health analyses and responds

Surveillance & OutbreakResponse Core Function

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Surveillance & OutbreakResponse Core Function

Why?

Ongoing watchfulness

Microbes impact quickly and widely

Microbes know no borders, changequickly

New patterns, novel pathogens, new tests

Alert for early diagnosis, interventionand prevention

NDM -1 should be approached withmultidisciplinary approach

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Research & TrainingCore Function

Faculty and staff carry out publichealth research and training

New knowledge about communicable

diseases (CDs) When novel pathogens appear, critical

skills (capacity)

Need to keep abreast of rapidlyadvancing technologies Many educational/training activities

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Best way to keep the matters

in OrderEvery Hospital should have a policy which is

practicable to their circumstances.

Rigid guidelines without coordination willlead to greater failures

The only way to keep Antimicrobial agentsuseful is to use them appropriately and

Judiciously(Burke A.Cunha, MD,MACP Antimicrobial Therapy. Medical

Clinics of North America NOV 2006)

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India is a country of 1.21 Billion population with complex

problems and unequal Medical Care. However we have aresponsibility to bring the concerns of Antibiotic misuse

both to the Professionals and Common man. Let us strengthen the Diagnostic Microbiology

Laboratories A good direction from Professionals on Antibiotic policy.

Net working and faster Education to all Health care workers. Better working conditions for Laboratory personal, frequent

training on quality of services Above all Technicians need better standard of Living to

improve the Laboratory services.

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How to Overcome NDM-1


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CDC & HHS Select Agents List

http://www.cdc.gov/od/sap/docs/salist.pdf

ABSA Risk Group Classification http://www.absa.org/resriskgroup.html

References

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http://www.cdc.gov/od/sap/docs/salist.pdfhttp://www.absa.org/resriskgroup.htmlhttp://www.absa.org/resriskgroup.htmlhttp://www.cdc.gov/od/sap/docs/salist.pdf


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Created by Dr.T.V.Rao MDon emerging concerns onNDM-1 Email

[email protected]

ndm - 1 role of diagnostic microbiology

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