Rational use of Microbiology - For comprehensive patient ...bsmedicine.org/congress/2012/Dr._Chris_Parry.pdf · Individual patient microbiology ... •Cefuroxime 500 mg po bid for

Chris Parry

Wellcome Trust Major Overseas Programme in Tropical Medicine Mahidol-Oxford Tropical Medicine Research Unit

Bangkok, Thailand

Chittagong Medical College Hospital, Bangladesh Angkor Hospital for Children, Cambodia

Rational use of Microbiology

What are the problems?

Individual patient microbiology

Public health microbiology and disease surveillance

Does it matter?

Rational use of Microbiology

What are the problems?

Private laboratories

Sample Result Cost?

Private laboratories

Sample Result Quality?

Outside the government network

• Individual patient management

• Microscopy

• Bacterial culture

• Serology

• Molecular methods management

What is the laboratory service for?

Laboratory network

Level 1 – Peripheral Malaria and TB microscopy. HIV testing

Level 2 – District Microscopy, biochemistry, serology, blood transfusion

Level 3 – Regional Culture of blood, CSF, faeces, TB. Molecular tests for influenza

Level 4 – Central TB culture and DST. Centres for QA of malaria and HIV tests.

Viral culture laboratories (Polio network)

Laboratory network






Laboratory network






• 25/M, teacher

• Previously well

• Fever, cough and nausea for 5 days

• Cefuroxime 500 mg po bid for 4 days

• Temperature 1030F

• Slight hepatomegaly

• WBC 6200 (N 78, L 20)

• AST 138; ALT 127

Patient 1

• Cefixime 200 mg IV bd -1 day

• Co-amoxyclav 1.2 g IV tds – 4 days

• No improvement

• Still high fever

Patient 1

Blood culture

Blood culture:

Salmonella enterica serovar Typhi

Resistant to

Chloramphenicol , Ampicillin and Co-trimoxazole

Nalidixic acid

Decreased susceptibility to

Ciprofloxacin

Susceptible to

Ceftriaxone, Azithromycin

Patient 1

• Diagnosis: Typhoid fever

• Ceftriaxone 2 g IV od – 5 days

• Clinical condition was improved

• Discharged home

• Azithromycin 500mg oral od - 7 more days

Patient 1

Patient 2

• 30/M, farmer

• Fever; Abdominal pain; Nausea and vomiting 5 days

• Co-amoxyclav – no improvement

• Unwell; Temp 101.40C;

• Tender L side abdomen

• WBC 14000 (N 90, L 10)

• Urine: Pus cells ++

• Blood culture:

• Enterobacter cloacae

• Resistant:

• Ampicillin, chloramphenicol, co-trimoxazole,

co-amoxyclav, ceftriaxone

Patient 2

Extended spectrum beta lactamase (ESBL)+

• Blood culture:

• Enterobacter cloacae

• Resistant:

• Ampicillin, chloramphenicol, co-trimoxazole,

co-amoxyclav, ceftriaxone

• Suscseptible:

• Imipenem, ciprofloxacin, gentamicin

Patient 2

• Diagnosis:

Enterobacter UTI with bacteraemia

ESBL + strain

• Treatment changed to ciprofloxacin

• Good recovery

Patient 2

Bacterial Culture - Advantages

– Establish the microbiological diagnosis

– Sensitivity/resistance result to guide antimicrobial

choice

Inappropriate antibiotic therapy is a risk factor for mortality among patients in the ICU

Kollef et al. Chest 1999;115:462–474

Hospital mortality (%)

0

20

50

Appropriate therapy

Inappropriate therapy

40

30

10

Infectious disease-related

p<0.001 50% 25% 0%

Bacterial Culture – Further advantages

– Establish the common bacteria causing sepsis in

your location

– Define the resistance patterns of these common infections

– Helps with empiric antimicrobial choices

– Lead to development of an antimicrobial guideline

Bacterial Culture - Disadvantages

– Slow

– Expensive

– Skin contamination

– May be negative because of:

• Prior antibiotic treatment • Volume of blood too small

– Negative blood culture does not exclude infection

• Newborn -Boy

• Full term - prolonged delivery

• Birth trauma - fracture left humerus • Inflamed umbilicus with pus

• Intubated and ventilated • Arm splinted • Ampicillin and gentamicin

Patient 3

• Blood culture: No growth • Umbilical swab: Coagulase negative Staphylococcus

• Persistent umbilical infection • Change to cloxacillin

Patient 3

• Day 8 • Improving • No fever for 3 days

• Extubated • ET aspirate sent for culture

Patient 3

• Culture:

– Klebsiella pneumoniae (ESBL +) +++

• Isolate resistant to cloxacillin

• Isolate susceptible to imipenem

Patient 3 – ET Aspirate

Should we change treatment from cloxacillin to

imipenem?

• Clinically improving • Extubated • No fever • No clinical signs of pneumonia • WCC: 10.8 • CRP: 1.0

• Conclusion: • Oropharyngeal colonisation not infection • No change in treatment

Patient 3

• Remained well until…

• Day 20 • Worse again • Lung crackles and fever

• WCC: 17.0 (Neutrophils 8.4) • CRP: 2.3

Patient 3

• Clinical diagnosis of pneumonia • CXR new L sided density

• Health care associated

• Empiric treatment?

• Imipenem

Patient 3

• Blood culture and ET Aspirate • Pseudomonas aeruginosa

• Isolates sensitive to imipenem

• Recovered

Patient 3

• Diagnosis of infection is clinical

• The microbiology result does not tell you whether

there is infection

• Particularly with cultures from sites with a normal bacterial flora

How can the microbiology laboratory help you?

• Diagnosis of infection is clinical

• The microbiology result does not tell you whether

there is infection

• Particularly with cultures from sites with a normal bacterial flora

• If there is evidence of clinical infection

• The microbiology result tells you what is the likely infecting pathogen

How can the microbiology laboratory help you?

• Malaria • HIV • Leishmaniasis • Dengue • Hepatitis • Syphilis

Why don’t we use rapid diagnostic tests (RDT)?

• Advantages

• ‘Point of care’ • Kit based • Easy to perform

• Disadvantages

• Expense • User variability • Poor sensitivity and specificity

Why don’t we use rapid diagnostic tests (RDT)?

Pastoor Diag Microbiol Infect Dis 2008

RDT for typhoid fever Sensitivity 60% Specificity 98% compared with clinical diagnosis of enteric fever

What if we use this RDT in all patients with fever 3 days?

• 100 patients 4 true Typhoid Fever cases

• RDT Sensitivity 60%; Specificity 98%

• 4 true TF 2 RDT + 2 RDT - • 96 not TF 2 RDT + 94 RDT –

What if we use this RDT in all patients with fever 3 days?




• 4 RDT positive

• 2 (50%) true positive • 2 (50%) false positive

• Positive Predictive Value 50%

What if we use this RDT only in patients with a fever 1 week and features of enteric fever




What if we use this RDT only in patients with a fever 1 week and features of enteric fever




• 20 RDT positive

• 18 (90%) true positive • 2 (10%) false positive

• Positive Predictive Value 90%

Molecular methods

GeneXpert MTB/Rif Cost

Easy Quick Sensitive Specific

Laboratory network






Public Health Microbiology

To investigate community

outbreaks of infection

Food, water and environmental

monitoring

Surveillance of communicable diseases

in the community

Surveillance of new and emerging pathogens

Avian influenza Nipah virus MDR and XDR TB NDM carbapenameses in Enterobacteriacae

H5N1 Avian influenza

Misdiagnosis

Inadequate treatment

Increased mortality

Increased expenditure Increased rates of resistance

Absent, unreliable and inaccurate diagnostics

Does it matter?

Learning points

• Microbiology can be helpful for clinicians

– For individual patient management

– To provide local epidemiological data

– Inform antimicrobial guidelines

Learning points

• Careful clinical interpretation of results

– Isolates from sterile sites

– Isolates from sites with a normal flora

– Serology result interpretation

– Be aware of the limitations of microbiology

Learning points

• Public health microbiology

• Important function distinct from routine diagnostic microbiology

• Linked to disease epidemiology and surveillance

Learning points

• Countries need a laboratory network

• Trained staff

• Relevant panel of standardised investigations at each level

• Quality Assurance of results !!

• Public - private collaboration ?

Thank you

Documents

Rational use of Microbiology - For comprehensive patient ...bsmedicine.org/congress/2012/Dr._Chris_Parry.pdf · Individual patient microbiology ... •Cefuroxime 500 mg po bid for