Clinical Aspects of Antimicrobial Therapy

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Clinical Aspects of Antimicrobial Therapy
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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

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Available www.ndsc.ie
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SARI REPORT APRIL 2001 RECOMMENDED STRATEGIES

• Recommended Infrastructure
• Surveillance of Antimicrobial Resistance
• National Reference Laboratories
• Monitoring Supply and Use of Antimicrobials

• 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

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St.Jamess Hospital Empiric Antibiotic
Guidelines-June 2005
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St.Jamess 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 Prescribers guide, distributed throughout
  the hospital ( all doctors, pharmacists, wards
  etc) and available on the St.Jamess intranet

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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

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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

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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

• 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

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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

• 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)

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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

• Avoid unnecessary use- e.g clinical well patient
  and CSU colonization, leg ulcers colonization,
  post-operative atelectasis
• Choice of suitable drug
• Toxicity eg allergy, enhancement of toxicity,
  change of flora etc
• Combined therapy
• Prescribing Practice
• -Document reason for starting agent or any change

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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

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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

• 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

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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

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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

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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

• 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

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Concentration Dependent Killing
Peak
Example Aminoglycosides
Conc
Therapeutic Range
Trough1
Time
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Time Dependent Killing
Example Glycopeptides
Conc
MIC
Time
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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

• 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

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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

• 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)
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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 WHATS CAUSING IT?
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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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Oslers nodes Tender, s/c nodules
Janeway lesions Nontender Erythematous, Haemorrha
gic, Or pustular Lesions often On palms or
soles
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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

• Patient with prosthetic valve undergoing dental
  extractions under general anaesthetic ( history
  of treatment of RTI 3 weeks earlier with
  co-amoxiclav)?

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Site of Infection Likely Organisms Empirical Tx.
Meningitis S. pneumoniae, N. meningitidis, H. influenzae Cefotaxime 2g 4hourly (/- Vancomycin) rifampicin 600mg bd po/iv
Endocarditis (native valve) Streptococci, S. aureus,(MSSA) Enterococci Benzylpenicillin 2.4G 4 hourly I/v Flucloxacillin 2g 4 hourly I/v I/v Gentamicin1mg/kg tds I.v
Abdominal Sepsis GNBs, Anaerobes, enterococci Amoxicillin-clavulanate ciprofloxacin metronidazole( all I/v)

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Site of Infection Likely Organisms Empirical Tx.
Community Acquired Infection S. pneumoniae, H. influenzae, consider atypicals Amoxicillin-clavulanate /-Clarithromycin(I/v or po)
Cellulitis Group A Streptococcus S. Aureus Benzylpenicillin I/v Flucloxacillin I/v
Osteomyelitis S. Aureus(MSSA) Flucloxacillin I/v Fusidic acid p/o
Simple cystitis (no catheter) E. coli, other GNB, coag neg staph Trimethoprim or Nitrofurantoin
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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

• 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

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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

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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.