Antibiotics & Disinfectants

Introduction

Bactericidal ® Kill bacteria

Penicillins and Cephalosporins
Aminoglycosides
Co-trimoxazole
Isoniazid, Rifampicin & Ethambutol
Vancomycin
Eythromycin (high dose)
Ciprofloxacin

Bacteriostatic ® hinder growth of bacteria

Sulphonamides
Tetracyclines
Chloramphenicol
Erythromycin
PAS
Lincamycin / Clindamycin
Fucidic Acid

Sterilisation

Process where by all living organisms including spores are destroyed

Disinfectants

Substances which kill potentially infectious organisms, and are usually used on surfaces (not the skin)
Destroys only vegetative forms of the organisms

Antiseptics

(Mild disinfectants) Relatively non-toxic non-irritant anti microbial agents ® can be applied topically to the body
Iodine best skin preparation but irritant to raw areas (Betadine) Must remain on surface for 60 sec ® lead to effect
Alcohol pure solution useless as a disinfectant but 50 - 70% solution useful skin antiseptic
Chlorhexidine (phenolic derivative) powerful antiseptic agent against vegetative organisms ® good skin antiseptic with low toxicity

Asepsis

Preventing wound contamination by ensuring that only sterile material makes contact with the wound and that airborne transmission of organisms is minimised

Chemotherapeutic Agents

Chemicals used to kill or inhibit the growth of micro organisms directly established in tissues of the body

Dry Heat

Inefficient method of sterilisation as need 160o for 60 mins which ® melt plastics and damage fabrics. Indicated for only fluids, glassware and powders.

Moist Heat

Is more efficient requiring less heat and time. Steaming under pressure ® increased boiling point ® decreased time required for sterilisation
121o for 15 mins, 126o for 10 mins and 134o for 3 mins ® sterilisation

Other methods

UV light good for surface sterilisation but has no penetration
Radiation used commercially
Filtration for fluid sterilisation
Gas sterilisation (ethylene oxide) slow
Liquid bath (4 - 8% gluteraldehyde)

Antibiotics

Introduction

Nearly all antibiotics penetrate the synovium well in the presence of inflammation ® 60 -90% serum levels
Definitive therapy depends on prolonged administration of the single most effective, least toxic and least costly agent
Oral therapy can be used if
  1. Clinical response to parenteral anti microbial therapy
  2. Isolation of pathogen that is susceptible to orally administered antibiotic
  3. Patient tolerance of the oral agent
  4. Adequate serum activity of the oral agent
  5. Ensurance of patient compliance

Beta Lactam antibiotics (Penicillins & Cephalosporins)

Similar structure and action but different spectra of anti microbial activity
Bind at various sites in the cell membrane ® growth inhibition and alter protein synthesis ®cell lysis ? exact mechanism

Toxicity: (low incidence)

Anaphylaxis and cross reactivity in 5 - 20% therefore use cephalosporins with caution in those with penicillin hypersensitivity
Some varieties ® bleeding disorders due to inhibition of platelet aggregation (methicillin and ampicillin)
Gastrointestinal upset diarrhoea, nausea, vomiting
Pseudo membranous colitis
Methicillin associated rarely with nephrotoxicity 10% of children ® haematuria (microscopic) less than 1% ® renal insufficiency
High dose of penicillin ® seizures

Penicillins

Penicillins: (Penicillin G, Phenoxymethyl penicillin (oral))

Active against
Gram positive cocci except penicillinase producing staph aureus
No gram negative activity
Dose
25,000 - 30,000u/kg IV 4 - 6/24

Amino Penicillins: (Ampicillin, Amoxicillin)

Active against
Gram positive cocci but also activity against a number of gram negative organisms (E coli, haemophillus, salmonella and proteus)
Not active against penicillinase producers
Dose
Children 20 - 40mgkg/day IV 4 - 6/24
Adults 250 - 500mg Oral 6 -8 /24

Isoxoly Penicillins: (Methicillin or Flucloxacillin)

Activity against
penicillinase producing staph aureus with same spectrum as penicillin G
No significant gram negative activity
Dose
Children 100 - 200mg/kg/day IV/Oral 6/24
Neonates 200 - 300mg/kg/day
Adults 2gm 4 - 6/24

Carboxy Penicillins (Carbenicillin)

Active against
Gram positive activity similar to amoxy penicillins but broader gram negative cover ® activity against pseudomonas
Dose
70 mg/kg 4/24

Acylureido penicillins (Piperacillin)

Active against
Expansion of activity of carboxy penicillins ® more anti pseudomonal activity and also klebsiella
Axlocillin ® narrow spectrum with major activity against pseudomonas
Dose
Children & Infants 200 - 300mg/kg/day
Adults 6 - 16gm/day (max 24gm)

Cephalosporins

1st Generation: (Cephalothin, Cephalexin (oral), Cefazolin)

Active against
Staph aureus, streptococcus
Non hospital acquired E coli, klebsiella and proteus
Clostridia
Meningococcus
Not active against
MRSA, haemophillus, pseudomonas
Serratia (indole positive proteus)
Dose
Cephalothin 25 - 30mg/kg IV 6/24
Cephalexin 25 - 50mg/kg/day Oral 6/24
Adults 1 - 4gm/day (divided)
Fluclox better for staph if broad spectrum not required
Don't use when haemophillus or proteus potential pathogens
Has poor penetration of CSF

2nd Generation: (Cephamandole, Cefoxitin, Cefaclor (oral))

Active against
Enhanced activity against gram negative organisms and many E coli and klebsiella resistant to the 1st generation cephalosporins
Less gram positive activity
Dose
Cephamandole 50 - 100mg/kg/day IV 6/24
Cefaclor 20 - 40mg/kg/day 8/24

3rd Generation: (Cefotaxime, Ceftriaxone)

Active against
Further increased gram negative activity being active against haemophillus and pseudomonas
Only 1/10 to 1/40 activity against staph aureus
Not active against pseudomonas
Dose
Cefotaxime 100 - 200mg/kg/day IV 8/24
(Usually 100 - 150mg/kg/day)
1st generation agents should always be used for sensitive organisms
2nd and 3rd generation agents should be used only for organisms resistant to 1st generation cephalosporins as they are preferable to the more toxic aminoglycosides
Duration of administration 5/7 to 6/52 IV and 4/52 to 6/12 oral

Vancomycin

Natural product of streptomyces orientalis
Action
Like beta- lactam antibiotics inhibits cell membrane synthesis ® altered cell membrane permeability and inhibition of RNA synthesis
Toxicity
Skin rash
Drug fever and nausea have been observed
Flushing, pruritus, rash and hypertension follows rapid administration in some individuals ® IV administration should be slow over 30 - 60 mins
Active against
Mainly gram positive aerobic and anaerobic organisms
Useful in patients with a penicillin allergy
Also useful against methicillin resistant staph aureus
Dose
30 - 40mg/kg/day IV 6/24

Aminoglycosides

Gentamycin, tobramycin and amikacin
Action
Inhibit bacterial protein synthesis at the 30s ribosomal sub unit and inhibit protein synthesis
Toxicity
Nephrotoxicity and oto-toxicity usually permanent and dose related ® monitor levels
Neuromuscular blockade may follows surgery and use of muscle relaxants or may potentiate weakness in myasthenia gravis or botulism
Active against
Enteric gram negative bacilli and strains of pseudomonas
Often used in combination with a b lactam antibiotic ® act synergstically
Dose
Gentamycin / Tobramycin 7.5mg/kg/day IV / IM 8/24
Amikacin 15 - 20mg/kg/day IV /IM 8/24

Ciprofloxacin

Action
Interferes with DNA gyrase ® bactericidal action
Toxicity
Nausea, diarrhoea, vomiting, rashes, restlessness, termor, headache, dizziness, pruritus, vaginitis
Mild side effects often not requiring cessation of treatment
May ® joint erosions in pre-pubertal children therefore not recommended for use in children
Active against
Wide range of both aerobic and anaerobic gram positive and gram negative organisms with good bio availability from oral preparation
Active against staph aureus (methicillin resistant and sensitive strains) strep epidermidus and streptococcus
Also active against E coli, salmonella pseudomonas, haemophillus, and neiseria
Dose
(bone & joint infection) 750mg 12/24
Increase dose in gram negative infection

Sulphonamides

Inhibit formation of folic acid necessary for cell growth, a step which is not required in human cells therefore not toxic
Limited susceptible organisms
Blockage is via competitive inhibition

Other antibiotics

Antibiotics affecting protein synthesis include chloramphinicol, streptomycin, neomycin, tetracyclines and erythromycin
Streptomycin and neomycin act via the 30s component of the ribosome and chloramphenicol and erythromycin the 50s segment
Tetracyclines interfere with the binding of mRNA to the ribosome

Clostridia Dificile

Pseudo membranous colitis
Results from alteration in the bacterial flora of the gut during administration of broad spectrum antibiotics

Investigation

Blood and stool sample for culture and fluorescent antibody test

Treatment

Vancomycin is the drug of choice to eliminate the organism