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
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
 Recommended  Development of
Infrastructure Guidance for
Appropriate Use of
 Surveillance of Antibiotics
Antimicrobial  Education in relation
Resistance to appropriate use of
 National Antibiotics
Reference  Development of
Laboratories Principles in relation
to Infection Control
 Monitoring Supply  Future Research in the
and Use of Area
Antimicrobials  On www.ndsc.ie
St.James`s Hospital Empiric
Antibiotic Guidelines-June
2005
St.James`s Hospital Empiric
Antibiotic Guidelines-June 2005
 These guidelines are developed on a
yearly basis by the Antimicrobial Sub-
Committee 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
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
Principles of Antibiotic Guidelines
 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
Definitions
 Pharmacokinetics  Pharmacodynamics
 Time course of drug
 Mathematical effects and other
study of the rate interactions between
process involved antimicrobials and
the bacterium(MIC,
in absorption, Post Antibiotic Effect
distribution, and interactions
metabolism and between the immune
excretion 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
General Principles of Therapy
 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
 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
General Principles of Therapy
 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
 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

 Consultations Microbiologists or ID physicians

 Treatment and Prophylaxis clearly defined
CLASSIFICATION
 Concentration dependent bactericidal
activity
-Aminoglycosides
-Quinolones
-Carbapenems
 Time dependent bactericidal activity
-B-lactams
-Glycopeptides
 Bacteriostatic Activity
-Erythromycin
-Tetracycline
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
ANTIBIOTIC ASSAYS
 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
General advice on taking levels
 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
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
Creatinine Clearance

 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
Example page 136
75 year gent with cough purulent
sputum, pyrexia, confusion, RR 22/min
BP 110/70mmHg,
COMMUNITY ACQUIRED PNEUMONIA:
WHAT’S CAUSING IT?
Page 136
 Common pathogens?
 Adult empiric therapy?
 What tests to be sent
 Then directed therapy
Using empiric guidelines
 Page 137
 20 year presents with celluitis right arm
 No history of therapy
 Empiric therapy?
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?
Using guidelines page 141
 20 year old presenting with severe
headache, neck stiffness, non-blanching
rash
 Empiric treatment?
Using Empiric Guidelines
 Patient 48 age female presents with
malaise, anorexia, fever for 3 weeks
 New heart murmur heard
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?
Surgical Prophylaxis
 Page 149
 For ERCP?
 For femoral-popliteal bypass?
 For Compound fracture?
Guidelines for prevention of
Endocarditis PAGE 151
 Patient with prosthetic valve undergoing
dental extractions under general
anaesthetic ( history of treatment of
RTI 3 weeks earlier with co-amoxiclav)?
Site of Likely Empirical Tx.
Infection Organisms
Meningitis S. pneumoniae, N. Cefotaxime 2g
meningitidis, H. 4hourly
influenzae (+/- Vancomycin) +
rifampicin 600mg bd
po/iv
Endocarditis Streptococci, Benzylpenicillin
(native valve) S. aureus,(MSSA) 2.4G 4 hourly I/v+
Enterococci Flucloxacillin 2g 4
hourly I/v+ I/v
Gentamicin1mg/kg
tds I.v
Abdominal GNBs, Anaerobes, Amoxicillin-
Sepsis enterococci clavulanate +
ciprofloxacin
Site of Likely Empirical Tx.
Infection Organisms
Community S. pneumoniae, Amoxicillin-
Acquired H. influenzae, clavulanate +/-
consider Clarithromycin(I/v
Infection
atypicals or po)
Cellulitis Group A Benzylpenicillin I/v
Streptococcus +
S. Aureus Flucloxacillin I/v
Osteomyelitis S. Aureus(MSSA) Flucloxacillin I/v +
Fusidic acid p/o
Simple cystitis E. coli, other Trimethoprim or
(no catheter) GNB, coag neg Nitrofurantoin
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.
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
Cephalosporins: main uses
 Cefuroxime: surgical prophylaxis
 Cefotaxime/ceftriaxone: meningitis
nosocomial infections excluding
Pseudomonal,
 Ceftazidime: nosocomial infections
including Pseudomonal
Other major antibiotic groups:
aminoglycosides
 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
coli
 MRSA and MDRTB
 Tropical: multidrug resistance in Salmonella
typhi, Shigella spp, malaria
Current major resistance
problems: hospital infections
 MRSA: current strains are often multiply-
antibiotic 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)
Esch coli, Klebsiella spp.
 Multiply antibiotic resistant enterobacteria:
Acinetobacter, Stenotrophomonas, Serratia
spp.