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 limiting

Common 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 possible

I indications should be evidence-based

N narrowest spectrum required

D dosage appropriate to the site and type of infection

M minimise duration of therapy

E ensure monotherapy in most situations

5 Antibiotics

• Benzylpenicillin or Amoxycillin– Streptococcis

• Cloxacillin– Staphylococcis

• Vancomycin– MRSA

• Gentamicin– Pseudomonas

• Metronidazole– anaerobes

Skin and Soft Tissue

Condition 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

UTI

Condition 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 days

W 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

Cardiovascular

Condition Organism Antibiotic Duration

Endocarditis empiric

Viridans streptococci other streptococci

Enterococci

Staphylococci

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

Respiratory

Condition Organism Antibiotic Duration

Community acquired pneumonia

mild

Strep. Pneumonia

Haemophyllis 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

CNS

Condition 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

Sepsis

Condition 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/day

Ticarcillin/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 Medication

Drug 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