Clinical Aspects of
Antimicrobial
Therapy
CONTENTS OF LECTURE
Empiric Antibiotic Guidelines
 Antibiotic Policy, Audit, Surveillance
 Summary of commonly used antibiotics
 For this session a copy of the Empiric
Antibiotics guidelines for SJH should be
used by each student for clinical
scenarios
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ANTIBIOTICS
May be:
 Bacteriostatic – inhibits growth of
Bacteria, so acts by preventing bacteria
from multiplying and then hosts
defences deal with the small number of
bacteria left
 Bactericidial – kills Bacteria, so
eliminates bacteria
Available www.ndsc.ie
SARI REPORT APRIL 2001
RECOMMENDED STRATEGIES
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Recommended
Infrastructure
Surveillance of
Antimicrobial
Resistance
National
Reference
Laboratories
Monitoring Supply
and Use of
Antimicrobials
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Development of
Guidance for
Appropriate Use of
Antibiotics
Education in relation
to appropriate use of
Antibiotics
Development of
Principles in relation
to Infection Control
Future Research in the
Area
On www.ndsc.ie
St.James`s Hospital Empiric
Antibiotic Guidelines-June
2005
St.James`s Hospital Empiric
Antibiotic Guidelines-June 2005
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These guidelines are developed on a
yearly basis by the Antimicrobial SubCommittee of the Pharmacy and
Therapeutics Committee. Printed in the
Prescriber`s guide, distributed
throughout the hospital ( all doctors,
pharmacists, wards etc) and available
on the St.James`s intranet
Objectives- to understand :
Principles of Antibiotic Guidelines
 Therapeutic Drug Monitoring(
Glycopeptides, Aminoglycosides)
 Guidelines for Empiric Treatment of
common infections
 Principles of Surgical Prophylaxis
 Empiric guidelines for Surgical
Prophylaxis
 Guidelines for the prevention of
Endocarditis

Principles of Antibiotic Guidelines
Guide to the empiric use of antibiotics.
 Empiric treatment is the choice of
antibiotic prior to sensitivity results
being available
 Avoid unnecessary use .If clinically
feasible await results of
microscopy/culture/susceptibility data
for directed therapy

Principles of Antibiotic Guidelines
Specimens for microbiology should be taken
prior to commencement of empiric treatemnt.
In an emergency , at a minimum a set of
blood cultures should be taken e.g meningitis.
 Ensure any history of allergy is documented
on the cover of notes and drug kardex prior
to commencing antibiotics
 Prescribing Practice
-Document reason for starting agent or any
change
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Principles of Antibiotic Guidelines
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Empiric antibiotics should be reviewed
once Gram satin/
mcroscopy/culture/sensitivity or
PCR available.Empiric therapy
should be changed to directed
therapy as soon as possible.
Directed therapy should be the
narrowest spectrum antibiotic to
adequately cover the pathogens
Principles of Antibiotic Guidelines
Pharmacokinetics and Pharmacodynamics
issues may necessitate dose adjustments( e.g
renal impairment etc). Doses of antibiotics
should take into account creatinine clearance
and review regularly. Consider co prescribed
interacting drugs
 Refer to BNF, hospital pharmacist,
Microbiologist or Infectious disease physician
if advice about dose is required
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Definitions
Pharmacokinetics
 Mathematical
study of the rate
process involved
in absorption,
distribution,
metabolism and
excretion
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Pharmacodynamics
Time course of drug
effects and other
interactions between
antimicrobials and
the bacterium(MIC,
Post Antibiotic Effect
and interactions
between the immune
system and the
agent)
Principles of Antibiotic Guidelines
All antibiotic prescriptions should be reviewed
after 48 hours
 Consider i/v to oral switch
 In general avoid topical antibiotic use. When
topical antibiotics are used do not use
antibiotic used systemically
 Consultations from Clinical Microbiology
ext.2039 or Infectious Diseases Bleep 192 or
ext. 2507/2402 are encouraged
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General Principles of Therapy
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Avoid unnecessary use- e.g clinical well
patient and CSU colonization, leg ulcers
colonization, post-operative atelectasis
 Choice of suitable drug
 Toxicity e;g allergy, enhancement of toxicity,
change of flora etc
 Combined therapy
 Prescribing Practice
-Document reason for starting agent or any
change
General Principles of Therapy
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Generic names to be used
Specify dose, number of doses or period of
time , review at 48 hours with results of
investigations and clinical status
If no improvement within 36-48 hours check
(1) Adequate dose and /or level of drug
(2) Host defences e.g drain abscess, removal
of foreign material etc
(3) Is the drug active against fastidious or
difficult organisms to isolate, consult with
microbiologist
General Principles of Therapy
Do regular antibiotic rounds/review use to
avoid unnecessary prolonged courses
 Oral if possible instead of I/V preparations
 Criteria for I/V to Oral switch
-Fever settled
-wcc returning to normal
-Patient clinically stable
-No gastrointestinal upset
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General Principles of Therapy
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Reserve Antibiotics
Use to be discussed with consultant or
microbiologist
Reasons are to preserve usefulness by
avoiding emergence of resistance
Where toxic effects do not justify use in
trivial infections
Expense
General Principles of Therapy
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Antibiotic Tables ( see hospital policies)
for use empirically before results of Culture
and Sensitivity available
Change when this information is available TO
DIRECTED THERAPY
Specimens ( e.g for culture , PCR etc) should
be taken before commencing therapy
exception e.g meningitis)
In serious sepsis Parental route of
Administration to be use
General Principles of Therapy
Pharmacokinetics/ Pharmacodynamic may
require dose/choice adjustment
 Avoid use of topical antibiotics, use those not
used systemically
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Consultations Microbiologists or ID physicians
 Treatment and Prophylaxis clearly defined
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CLASSIFICATION
Concentration dependent bactericidal
activity
-Aminoglycosides
-Quinolones
-Carbapenems
 Time dependent bactericidal activity
-B-lactams
-Glycopeptides
 Bacteriostatic Activity
-Erythromycin
-Tetracycline
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Therapeutic Drug Monitoring
TDM necessary to ensure therapeutic efficacy
of a drug while ensuring toxic and sub
therapeutic doses are avoided.
 TDM is performed on drugs with narrow
therapeutic indices such as glycopeptides (
e.g vancomycin) and aminoglycosides (e,g
gentamicin)
 These drugs may be associated with toxicity
so levels should be regularly monitored
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ANTIBIOTIC ASSAYS
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Assay when an antibiotic has a narrow
therapeutic index e.g Aminoglysocides
Assay when normal route of excretion is
impaired e.g. patient with renal impairment
on vancomycin
Assay in patients receiving prolonged therapy
for serious infection e.g. endocarditis
Assay in Neonates with serious infection
Assay if failure to respond to therapy
Assay to check compliance
Concentration Dependent
Killing
Peak
Example: Aminoglycosides
Conc
Therapeutic Range
Trough1
Time
Time Dependent Killing
Example: Glycopeptides
Conc
MIC
Time
General advice on taking levels
It is important to ensure the levels are
taken at the correct time.
 Frequency: first level see tables, repeat
levels twice weekly for those with stable renal
function, more frequently if renal function
rapidly changing
 When: See tables. In general trough must be
taken immediately before the next due
dose.Peak one hour after administration of
dose.
 Levels done twice Saturday and once sunday
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General advice on taking levels
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Label correctly: if intermittent irregular dosing
label as trough
Random levels are not interpretable
Action to be taken on receipt of levels,
If level is within therapeutic range,
continue current dosing
Putting an antibiotic on hold is not an
appropriate intervention. Modify the
dosing interval and / or dose.
Advice from clinical Microbiology(ext
2985) or ID Pharmacist
In general interpretation of levels
If trough high, dosing interval needs to be
prolonged where appropriate
 If trough is low( subtherpeutic) dosing
interval needs to be shortened and /or dose
will need to be increased where appropriate
 If peak high, dose needs to be reduced
where appropriate
 If peak low the dose may need to be
increased where appropriate
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Example: Vancomycin
Page 134
Order bloods for renal function and calculate
CrCl
 Vancomycin is the first line glycopeptide in
SJH
 Normal dose normal renal function 1 g B.D
 Recommended range
-Trough- 5-12 mg/l
Normally taken before 3rd dose
Toxicity and Efficacy best determined by trough
level
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Creatinine Clearance
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CrCl= (x)(140-age)(IBW)
Serum Creatinine
X= 1.23 males, x= 1.04 for females
Male IBW= 50 KG+ ( 2.3 kg) x (inches over 5 feet)
Female IBW= 45.5KG + ( 2.3 kg) x (inches over 5 feet)
Using Empiric Guidelines
Clinical symptoms/Signs
 Table Format
 Follow general principles covered early
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Example page 136
75 year gent with cough purulent
sputum, pyrexia, confusion, RR 22/min
BP 110/70mmHg,
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COMMUNITY ACQUIRED PNEUMONIA:
WHAT’S CAUSING IT?
Page 136
Common pathogens?
 Adult empiric therapy?
 What tests to be sent
 Then directed therapy
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Using empiric guidelines
Page 137
 20 year presents with celluitis right arm
 No history of therapy
 Empiric therapy?
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Using Empiric guidelines page
138
60 year gent admitted with abdominal
pain 12 hours duration , generalised
guarding, boardlike rigidity
 Air under diaphragm on CXR
 Empiric therapy?
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Using guidelines page 141
20 year old presenting with severe
headache, neck stiffness, non-blanching
rash
 Empiric treatment?
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Using Empiric Guidelines
Patient 48 age female presents with
malaise, anorexia, fever for 3 weeks
 New heart murmur heard
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Osler`s nodes
Tender, s/c
nodules
Janeway lesion
Nontender
Erythematous,
Haemorrhagic,
Or pustular
Lesions often
On palms or
soles
Using Empiric guidelines page
145
Common pathogens
 Therapy?
 Tests to be sent?
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Surgical Prophylaxis
Page 149
 For ERCP?
 For femoral-popliteal bypass?
 For Compound fracture?
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Guidelines for prevention of
Endocarditis PAGE 151
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Patient with prosthetic valve undergoing
dental extractions under general
anaesthetic ( history of treatment of
RTI 3 weeks earlier with co-amoxiclav)?
Site of
Infection
Likely
Organisms
Empirical Tx.
Meningitis
S. pneumoniae, N.
meningitidis, H.
influenzae
Cefotaxime 2g
4hourly
(+/- Vancomycin) +
rifampicin 600mg bd
po/iv
Benzylpenicillin
2.4G 4 hourly I/v+
Flucloxacillin 2g 4
hourly I/v+ I/v
Gentamicin1mg/kg
tds I.v
Endocarditis Streptococci,
(native valve) S. aureus,(MSSA)
Enterococci
Abdominal
Sepsis
GNBs, Anaerobes,
enterococci
Amoxicillinclavulanate +
ciprofloxacin
Site of
Infection
Likely
Empirical Tx.
Organisms
Community
Acquired
Infection
S. pneumoniae,
H. influenzae,
consider
atypicals
Group A
Streptococcus
S. Aureus
Amoxicillinclavulanate +/Clarithromycin(I/v
or po)
E. coli, other
Trimethoprim or
Nitrofurantoin
Cellulitis
Osteomyelitis
Simple cystitis
(no catheter)
Benzylpenicillin I/v
+
Flucloxacillin I/v
S. Aureus(MSSA) Flucloxacillin I/v +
Fusidic acid p/o
GNB, coag neg
staph
Spectrum of Activity
Benzyl penicillin: mainly active against
Gram Positive organisms e.g. Streptococci
and Staphylococci
 Ureidopenicillins: active against certain
gram positive and gram negative organisms
 Anti-pseudomonal Penicillins active
against gram positive organisms(s) and gram
negatives and pseudomonads
 Cephalosporins: Broad spectrum of activity
gram negative and positive organisms,
different generations have different spectra of
activity.
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Carbapenems
Imipenem, meropenem: have a very broad
spectrum activity against gram-negative
bacteria, anaerobes, streps
 Now used to treat gram negative infections
due to so called ESBL producing organisms
eg, E coli, Klebsiella
 Ertapenem is a new member of the group but
its not active against Pseudomonas
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Cephalosporins: main uses
Cefuroxime: surgical prophylaxis
 Cefotaxime/ceftriaxone: meningitis
nosocomial infections excluding
Pseudomonal,
 Ceftazidime: nosocomial infections
including Pseudomonal
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Other major antibiotic groups:
aminoglycosides
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Gentamicin, amikacin (tobramycin,
streptomycin)
Mainly active against gram negative bacteria
Mainly used to treat nosocomial infections:
pneumonia in ITU, septicaemia
Limiting factors are nephrotoxicity (and
ototoxicity) and resistance
Also used in combination
Current major antibiotic
resistance problems: community
infections
Respiratory tract: penicillin resistance in
pneumococcus increasing
 Gastrointestinal: quinolone resistance in
Campylobacter
 Sexually transmitted: penicillin, quinolone
resistance in gonococcus
 Urinary tract: beta lactam resistance in Esch
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coli
MRSA and MDRTB
 Tropical: multidrug resistance in Salmonella
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typhi, Shigella spp, malaria
Current major resistance
problems: hospital infections
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MRSA: current strains are often multiplyantibiotic resistant
VISA/GISA: intermediate resistance to
glycopeptides (thickened cell wall)
VRSA/GRSA: highly resistant (transferable on
plasmids) from enterococci
VRE: enterococci (multiply resistant)
Broad spectrum beta lactam resistant (ESBL)
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Multiply antibiotic resistant enterobacteria:
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Esch coli, Klebsiella spp.
Acinetobacter, Stenotrophomonas, Serratia
spp.