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&
MANAGING PATIENTS WITH
INFECTION
Dr.Partha Pratim DE
Head of Lab Medicine and Consultant Microbiologist
Tan Tock Seng Hospital
Singapore
Microbiology & The Patient
Day 1
68 yo
male, diabetic
vegetable grower
cough for past month,
increasing for last 10 days
increasing shortness of
breath last 3 days
rainy season
Day 1
68 yo
68 yo
U 18 mmol/L
R 35 / min
BP 110/70
Day 1
68 yo
Assess
immunosuppression.
Day 1
68 yo
Conclusion
These data have major implications for diagnostic strategies and
empirical treatment. Narrow-spectrum antibiotics targeting S.
pneumoniae may be inappropriate in many Asian settings, and agents
active against TB may lead to partial response and delayed TB
diagnosis.
Results Different regions have different
As in western studies, Streptococcus pneumoniae, Mycoplasma
pathogens
pneumoniae, Chlamydophila pneumoniae, Legionella spp. and
Haemophilus influenzae were all significant pathogens. However,
compared with western studies, S. pneumoniae was of less relative
Guidelines
importance. Gram-negative from othertuberculosis
bacilli and Mycobacterium countries were
more important, and in northeast
need Thailand
to be Burkholderiato
modified pseudomallei
your needs
was a major pathogen.
Conclusion
You need local data to modify
These data have major implications for diagnostic strategies and
guidelinesantibiotics targeting S.
empirical treatment. Narrow-spectrum
pneumoniae may be inappropriate in many Asian settings, and agents
active against TB may lead to partial response and delayed TB
diagnosis.
What antibiotic therapy would you recommend?
A. Amoxicillin-clavulanate
E. Moxifloxacin
Day 1
68 yo
U 18 mmol/L
Given imipenem and
clarithromycin R 35 / min
BP 110/70
Singapore Antimicrobial Stewardship 2017
Review
Results
Testing
Seven Steps
Review
Results
Testing
Seven Steps
DIAGNOSTIC TESTING
Encompasses:
testing, sample collection, laboratory
CULTURE SEROLOGY
aerobic culture all sorts
anaerobic culture
fungal culture
viral culture MICROSCOPY
mycobacterial culture Gram stain
other culture fungal microscopy
acid-fast stain
Immuno-fluorescence
MOLECULAR TESTING scrapings
PCR other microscopy
Probe testing parasitology
What diagnostic tests could you perform?
Blood cultures
Balance of:
Legionella urine antigen
1.Availability
Streptococcus
pneumoniae urine antigen 2.Clinical utility
Sputum cultures 3.Cost
Silver stain, broncho- 4.Test timing
alveolar lavage fluid
5.Disease severity
Influenza virus culture
Mycoplasma IgG serology
Results turn around time
Non-culture tests Culture
PCR TB culture
1-3 days 10-42 days
The diagnosis and management of CAP has hardly changed for decades.
Postma, Douwe F., Cornelis H. van Werkhoven, and Jan Jelrik Oosterheert. "Community-acquired pneumonia requiring hospitalization: rational decision
making and interpretation of guidelines." Current opinion in pulmonary medicine 23.3 (2017): 204-210.
There
The diagnosis and management arehas
of CAP new diagnostic
hardly tools
changed for decades.
Postma, Douwe F., Cornelis H. van Werkhoven, and Jan Jelrik Oosterheert. "Community-acquired pneumonia requiring hospitalization: rational decision
making and interpretation of guidelines." Current opinion in pulmonary medicine 23.3 (2017): 204-210.
Day 1 Day 2 Day 3
Results
Testing
Seven Steps
REVIEW RESULTS
What does it mean?
What is the diagnosis now?
Step 9: Review results & diagnosis
What is the infecting Escherichia coli?
organism?
Staphylococcus aureus?
Gram-positive cocci?
All three?
Sterile Sites
contamination?
infection?
Blood culture:
contamination? (Coagulase-negative
staphylococci,
diptheroids)
growing organisms that are
not from the intended site Urine culture:
culture Mixed bacterial growth, low
viable counts
Sterile sites:
(Coagulase-negative
staphylococci, diptheroids)
Non-Sterile Sites
contamination?
colonisation?
infection?
diagnosis clinical features pathogen
Interpreting results
colonisation? Superficial swabs:
Gram-negative bacilli,
coagulase-negative staph,
diptheroids
growing organisms that are
unlikely to cause infection Urine culture:
or growing organisms without Bacterial growth from
signs of infection indwelling catheters
Respiratory tract:
(non-invasive)
[ Gram-negative bacilli ]
Day 1 Day 2 Day 3
Patient Microbiology
Pneumonia Sputum:
Community-acquired Escherichia coli
? risk factors MDRO Not likely respiratory
pathogen from SAP
Some chronic disease
Mixed with other bacteria
Day 1 Day 2 Day 3
Patient Microbiology
Pneumonia Urine:
Community-acquired Why urine?
? risk factors MDRO
Some chronic disease Blood cultures:
Streptococcus something…
Day 1 Day 2 Day 3
Escherichia coli
Scanty growth Staphylococcus aureus
Enterococcus species Viable count 10,000
Scanty growth cfu/ml
- Pending
susceptibilities
Step 9: Review the diagnosis (again)
What is the diagnosis? clinical
other investigations
microbiology
progression
time!
Review
Results
Testing
Seven Steps
REVIEW ANTIBIOTICS
Was your empirical antibiotic correct?
Can you modify your empirical antibiotic?
What antibiotic therapy would you recommend?
A. Why change?
EMPIRICAL
Microbiology
data
Clinical data
ANTIBIOTIC SUSCEPTIBILITY TESTING
Susceptibility testing
Qualitative Quantitative
Susceptible Susceptible
How susceptible?
Intermediate
Resistant
Resistant How resistant?
Method
Phenotypic
Disc testing
Minimum inhibitory concentration (MIC)
Special tests
Genotypic
Standardised methods
important to ensure results are
consistent
reproducible
reliable
variables:
inoculum, testing media, methodology,
interpretation, breakpoints, quality control
Advantages
cheap
flexible
widely available
easily understood
reliable (if done properly)
Disadvantages
Source: http://www.cdc.gov/
not automated
technique dependant
quality control important
needs training to read and interpret
qualitative results
Source: http://www.cdc.gov/
Disk Diffusion
Minimum inhibitory concentration
compares efficacy of different
antibiotics against a particular
organism
MIC methods
Advantages
quantitative results
may assist antibiotic dosing
Disadvantages
expensive
less flexibility
quality control important
time consuming
limited availability
MIC methods
in-vivo
isolates are not inhibited by the usually achievable
concentrations of the agent with normal dosage
resistant schedules and/or demonstrate MICs/zone diameters
that fall in the range where specific microbial
resistance mechanisms (e.g., β-lactamases) are likely
and that clinical efficacy against the isolate has not
been shown reliably in treatment studies
Streptococcus pneumoniae
Antibiotic
susceptibilities to
follow
What antibiotic therapy would you recommend?
Results
Testing
Seven Steps
REVIEW ANTIBIOTICS
Was your empirical antibiotic correct?
Can you modify your empirical antibiotic?
Step 10: Review the antibiotics
Continue same antibiotic
Change antibiotics
resistant organism
different body site
susceptible organism
Stop antibiotics
48-72hr 3-5 days
review review
EMPIRICAL DIRECTED
Microbiology Pathogen
data directed?
Clinical data IV-PO?
Duration?
Microbiology &
Infectious Diseases
SUSCEPTIBILITY DATA
Antibiogram
annual summary
of susceptibility
rates
“cumulative
antibiogram
report”
trimethoprim/sulfamethoxazole
Number of isolates (2011)
amoxycillin / clavulanate
piperacillin/tazobactam
ampicillin/sulbactam
GRAM NEGATIVE
ciprofloxacin
meropenem
minocycline
ceftazidime
ceftriaxone
ertapenem
gentamicin
aztreonam
cephalexin
tigecycline
imipenem
cefepime
amikacin
Gram-negative
Acinetobacter baumannii 225 45 34 21 25 21 40 22 23 34 37 susceptibility > 80%
Enterobacter spp. 200 97 51 82 51 51 71 80 74 97 100 61 68
Escherichia coli 2050 98 75 75 37 74 74 74 57 99 83 100 100 95 97 58 susceptibility 50-79%
Klebsiella spp. 1050 96 68 69 60 71 70 69 69 92 79 100 99 77 93 61
Pseudomonas aeruginosa 750 93 76 88 86 85 86 91 91 92 susceptibility < 50%
Proteus spp. 280 94 85 86 71 87 87 87 63 99 70 95 100 99 50
not applicable
trimethoprim/sulfamethoxazole
Number of isolates (2011)
GRAM POSITIVE
erythromycin
ciprofloxacin
moxifloxacin
daptomycin
vancomycin
clindamycin
tetracycline
fusidic acid
cloxacillin
ampicillin
penicillin
linezolid
90%
% imipenem resistant 1.20
incidence per 1,000-inpatient days
80%
+2SD
1.00
70%
60%
50%
0.60
40%
30%
0.40
0% 0.00
Q2-05 Q3-05 Q4-05 Q1-06 Q2-06 Q3-06 Q4-06 Q1-07 Q2-07 Q3-07 Q4-07 Q1-08 Q2-08 Q3-08 Q4-08 Q1-09 Q2-09 Q3-09 Q4-09 Q1-10 Q2-10 Q3-10 Q4-10 Q1-11 Q2-11 Q3-11 Q4-11 Q1-12
linked to disease
real-time
predictive
EPIDEMIOLOGY OF DISEASE
local pathogens
local risk factors
availability of
local patient tests
types
GUIDE PATIENT MANAGEMENT
Antibiotic Patient Antibiogram
Prescribing has an infection
what is the likeliest
organism?
The way it should be
based on risk factors,
severity of infection, etc
antibiotic prescribed
GOOD MICROBIOLOGY
appropriate testing
appropriate testing Specimen quality
urine culture (epithelial cells)
sputum culture (epithelial cells)
tissues v.s. swabs
tips of superficial drains
Specimen transport
conditions, transport, viability
appropriate reporting
appropriate testing Guidelines for reporting organisms
appropriate reporting
rapid diagnosis
appropriate testing 24 hour microbiology laboratories
“direct” susceptibility testing
appropriate reporting
rapid identification technologies
rapid diagnosis Vitek automated systems
MALDI-TOF
fluorescent hybridisation
PCR identification
improved workflows
rapid diagnostics
appropriate testing
Blood cultures
N&T swab
Day 1
Blood cultures
+ Anti-TB therapy?
+ Influenza therapy?
Day 1 Day 2
Blood cultures
+ Anti-TB therapy?
Day 1 Day 2
Ceftriaxone?
Penicillin?
PATIENT