Infectious disease formulatory teaching Flashcards
Empirical definition
Best guess
Based on predicted pathogens
Broad spectrum definition
Active against a wide range of pathogens
De-escalation definition
Refining antibiotic treatment based on microbiological results to narrowest spectrum possible
Absorption
The uptake of drugs by the tissues of the body from the site of administration
Generally refers to absorption from the gastro-intestinal tract
Distribution
The distribution of drugs to various parts of the body including site of action
Metabolism
The breakdown of drugs by the body
Excretion
The removal of waste products of metabolism or unchanged drug from the body
Concentration dependent antibiotics
Bacterial effect related to peak concentration at site of infection
Continue to kill the bacteria until next dose given
e.g. aminoglycosides, quinolones
Time dependent antibiotics
Bacterial effect dependent upon maintaining blood concentration above the minimum inhibitory concentration
Little or no post-antibacterial effect
e.g. penicillins, macrolides, glycopeptides
Antibiotic targets in bacteria
Cell wall synthesis
DNA synthesis
RNA synthesis
Protein synthesis
Folic acid synthesis
Antibiotics targeting cell wall synthesis
Penicillins
Cephalosporins
Carbapenems
Daptomycin
Glycopeptides
Antibiotics targeting DNA synthesis
Fluoroquinolones
Antibiotics targeting RNA synthesis
Rifampin
Antibiotics targeting protein synthesis
Macrolides
Chloramphenicol
Tetracycline
Aminoglycosides
Oxazolidonones
Antibiotics targeting folic acid synthesis
Sulfonamides
Trimethoprim
Infection factors
Likely pathogen
- emprical vs targeted therapy
Resistance
- MRSA
- local resistance patterns
Site of infection
Severity
- local/ systemic
- septic shock
- toxin production
Patient factors
Penicillin allergy
Pregnancy and breast feeding
IV or oral
Medication history
Renal/ hepatic function
Age
Obesity
PMH
Severity of disease
Drug factors
Activity against likely pathogen
- mechanism of action
- resistance
Good penetration to site of infection
Dose
Monotherapy vs combination
Broad spectrum
Cellulitis
Diffuse, spreading, superficial infection of skin
Without underlying suppurative foci in muscle or fascia
Without associated necrosis
Involves deeper dermis and subcutaneous fat
Treatment always required
Characteristics of cellulitis
Heat, erythema, induration, localised tenderness, orange skin appearance
Blisters or bullae
Not raised and without a well demarcated edge
May have systemic inflammatory response and regional lymphadenopathy
Causes of cellulitis
Infection following minor breach of skin
- insect bite
- tinea pedis
Increased risk of cellulitis infection in
Immunocompromised
Following trauma/ surgery
Diabetes mellitus/ lymphoedema
Morbidly obese
Bacteria to cause cellulitis
Group A streptococcus (strep pyogenes)
Staphylococcal aureus (MSSA and MRSA)
Other beta haemolytic streptococci
Dog/ cat bite (paseurella multicoda, capnocytophaga carnimorsus, human bite corridens)
Salt water exposure vibrio vulnificus
Beta lactamase sensitive penicillins
Benzylpenicillin (IV)
Phenoxymethylpenicillin (PO)
Broad spectrum penicillins
Amoxicillin
Co-amoziclav
Beta-lactamase resistant penicillins
Flucloxicillin
Anti-pseudomonal penicllins
Piperacillin
Tazobactam
Indications for penicillins
Streptococcal infections
Exacerbations of COPD
Pneumonia
Cellulitis
Endocarditis
Otitis media
Abdominal sepsis
UTIs
Penicillin mode of action
Bactericidal
Beta-lactam ring integrity crucial for antimicrobial activity
Activity against bacteria with PGN cell walls
Inhibit cell wall peptidoglycan synthesis
Penicillin activity
Gram +ve, -ve, aerobes, anaerobes
Not chlamydia, mycoplasma
IgE mediated pencillin allergy
Type 1 reaction
Sudden, life threatening, occurs up to 24 hours post exposure
Antigen and pre-formed IgE antibody cause histamine release
- anaphylaxis
- urticaria
- puritic rash
- laryngeal oedema
- angioedema
- bronchospasm
Cross- sensitivity: cephalosporins
0.5-6.5% penicillin allergic patients also allergic to cephalosporins
Patients with IgE mediated reactions should not be given cephalosporins
Cross- sensitivity: other beta lactam antibiotics
Namely carbapenems
e.g. meropenem
IV -> oral switch
After 48 hours IV teicoplanin, patient is apyrexial, haemodynamically stable, cellulitis receeding, inflammaotry markers improving
Decision to discharge on oral antibiotics
Aminoglycosides
e.g. gentamicin, amikacin, tobramycin, streptomycin
Not absorbed in the GI tract
- given IV/ IM
Polycations, highly polar
- do not cross blood brain barrier
- cross the placenta (avoid in pregnancy)
- concerns about lung tissue concentrations of gentamicin
Excretion of aminoglycosides
Virtually entirely via kidenys
Consider alternative in renal impairment/ renal replacement
Monitoring serum levels
Dose related nephrotoxicity and ototoxicity
High risk antibiotic
Glycopeptides
e.g. vancomycin, teicoplanin
Not absorbed from gut
- given IV
Excretion almost entirely via glomerular filtration into urine
