Antibiotics

Judith Coombes, University of Queensland

General Principles

• Establish the need for antibiotic therapy• When not to prescribe

– Viral or minor bacterial disease– Viral diarrhoea– Sore throat– Sinusitis– Common cold

Are self limitingCommon cold needs common sense campaign

Antibiotic treatment can be• Prophylactic antibiotics prevent serious infection in

specific situations (e.g. preventing the spread of meningococcal disease).

• Presumptive antibiotic therapy is indicated in some circumstances (e.g. a human bite to the hand

• Use empirical antibiotic therapy — which is aimed at the likely causative organism — to manage an infection until microbiological culture and susceptibility results are known

• When the cause of an infection is confirmed, directed therapy is aimed at the specific pathogen.

MIND ME

M microbiology guides therapy wherever possibleI indications should be evidence-basedN narrowest spectrum requiredD dosage appropriate to the site and type of

infectionM minimise duration of therapyE ensure monotherapy in most situations

5 Antibiotics• Benzylpenicillin or Amoxycillin

– Streptococcis• Cloxacillin

– Staphylococcis• Vancomycin

– MRSA• Gentamicin

– Pseudomonas• Metronidazole

– anaerobes

Skin and Soft TissueCondition Organism Antibiotic Duration

Wound infections surgical or trauma

Staphylococcus aureas

Cloxcillin 5 days

Cellulitis Streptococcus pyogenes

Cloxacillin 500mg q6h

7-14 days

Diabetic foot ulcer

Anaerobic, mixed g +ve and g-ve

Metronidazole 400mg q2h + Cephalxin 500mg q6h

Depends on response

UTICondition Organism Antibiotic Duration

Cystitis in men + non pregnant women

E coli, ebsiella, Enterococcus faecalis, proteus mirabilis

Trimethoprim 300mg daily or Amoxycillin/clavulanate 875/125 q12h

W 3 days men 14 daysW 5 days men a4 days

Catheter associated infections

Only treat if symptoms, change catheter

Cystitis in pregnant women

As above Cephalexin 500mg q12h

10-14 days

CardiovascularCondition Organism Antibiotic Duration

Endocarditis empiric

Viridans streptococci other streptococciEnterococciStaphylococci

Benzylpenicillin 1.8 g iv q4h + cloxacillin 2g iv q4h plus gentamicin 4-6mg/kg/day iv

Modify as soon as organism and sensitivity is known

RespiratoryCondition Organism Antibiotic Duration

Community acquired pneumoniamild

Strep. PneumoniaHaemophyllis influenzie

Amoxycillin 1g q8h + Roxithramycin 300mg daily

Moderate BenzylPenicillin 1.2g q6h + Roxithramycin 300mg daily

severe Azithromycin 500mg iv + gentamicin 4-6g daily + Benzylpenicillin 1.2g q6h

CNSCondition Organism Antibiotic Duration

Suspected bacterial Meningitis

Neiserria meningitis, Strep. Pneumonia, Haemophilus influenzae

Ceftriaxone 4g iv daily (OR 2g bd)

7-21 days

Prophylaxis if known

Neiserria meningitis, Haemophilus influenzae

Rifampicin 600mg daily

2 days

Sepsis- definition

• In adults and older children, severe sepsis is the systemic response to an infection manifested by organ dysfunction, hypoperfusion or hypotension combined with 2 or more of the following: – fever, – tachycardia, – tachypnoea, – elevated white cell count

SepsisCondition Organism Antibiotic Duration

Sepsis Psuedomonas has high morbidity

Cloxacillin 2g q4-6h + Gentamicin 4-6mg/kg dose 1 then adjust

2 days then add

Neutropenic sepsis

Pseudomonas most dangerous

Gentamicin 4-6mg/kg/dayTicarcillin/Clavulanate 3.1g q6h

Suspect staph- skin wound or at 48 hrs

Vancomycin 1g q12h

At 96 hrs antifungals

Gentamicin Revision

• Gram negative bactericidal agent• Excellent anti-pseudomonal cover• Once daily dosing benefits vs tds or bd:

- high peak level – excellent distribution- post antibiotic effect (>24-36 hours) - reduced monitoring and administration- reduced nephro and ototoxicity- easier monitoring (10-12 hours post dose)

Severe risks of nephrotoxicity and ototoxicity

• Mrs HR• 78 years, wt 57kg• Admitted to outlying hospital acute exacerbation

COPD• Baseline Cr 80mol/L, Urea 8.5 • Charted gentamicin 160mg daily for 5/7 – no

levels requested • Baseline CrCl = 45ml/min

Date Gent Dose Level Cr Urea3/6 0.08 8.55/6 160mg6/6 160mg 0.11 15.57/6 160mg 6.2 0.138/6 160mg 9.0 0.17 21.99/6 160mg10/6 ceased 16.9 0.22 28.311/612/6 7.8 0.36 35.013/6 0.3914/6 0.41 33.615/6 0.5016/6 0.59 38.917/6 0.65 40.6

Patient progress• 15/6 K+ = 6.7, Acidotic to ICU + haemodialysis

• 21/6 Gent level still 1.4!!!!

• 23/6 complaining of dizziness, unsteady feeling, vestibular symptoms, vomiting

• 1/7 Cr 0.21 recovering

• 14/11 Out patient – permanent Ototoxicity

Local Sri Lankan Hospital

• 75 yr old patient post amputation, septic• Gentamicin iv 80mg tds, Co Amoxyclav iv +

metronidazole iv• Day 7 reviewed by anesthetists – pain control• Noted Urea increased from 7.1 – 15.2• Patient not septic - ? Need for antibiotic• Seen Day 12 post operative, Urea = 26 same

dose gentamicin

Aminoglycoside dosing and Monitoring

Case continued…

Day 3:• Mr AD (67yrs) has now developed sever hospital

acquired pneumonia • Ward round decisions

- start gentamicin once a day dose as per levels each night at 20:00 recall patient weighs 70 kg creatinine has improved (now 140 micro mole/l)

- start Co-Amoxiclav 1.2g IV q8h

Creatinine Clearance• Recall Cockcroft-Gault Formula:

CrCl (mL/min) = [140-age (years)] * ideal weight (kg) [0.814 * serum creatinine

(micromol/L)]

{♀ * 0.85 }If patient 70 kg, 67 y.o. with serum

creat~140micromol/L:CrCl ≈ 42 mL/min (140-67 X 70) / (0.814 x

140)

Calculating first dose gent

Gentamicin Dose Adjustment

Day 4: gentamicin level = 2.5

(taken 08:00, 12 hrs post dose)• The initial dose given in emergency department was

280mg (4mg/kg x approx 70kg)

Prescribe new gentamicin dose based on level

2.5

Gentamicin Dose Adjustment

• Level at 12 hours = 2.5 (ideal = < 2)

• New Dose = Level Wanted (mg/L) x Dose Given (mg)

Level Achieved (mg/L)

In this case: (1.5/2.5) x 280 = 168 mg• round down to 160 (nearest multiple of 40 mg)

- amps = 40 mg/mL

Adjusting doses of gentamicin

When NOT to take levels

• Do not take levels if:• Stat dose • Or• Patient has Normal renal function and is

only receiving 1 or 2 doses ie prophylactic

Variable Dose MedicationDrug Level and Time Taken

Dose Time and Actual Time Given

Use in moderate to severe renal function

• Where ever possible withhold other nephrotoxic drugs and ensure no other altenative

• Ie unavoidable use of gentamicin:• Requires extended dose intervals 36, 48

or 96 hours• Effectively daily levels wait til < 1.0mmol/l

then dose again