Infectious disease formulatory teaching Flashcards by Holly O'Flanagan

Empirical definition

Best guess

Based on predicted pathogens

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Broad spectrum definition

Active against a wide range of pathogens

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De-escalation definition

Refining antibiotic treatment based on microbiological results to narrowest spectrum possible

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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

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Distribution

The distribution of drugs to various parts of the body including site of action

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Metabolism

The breakdown of drugs by the body

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Excretion

The removal of waste products of metabolism or unchanged drug from the body

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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

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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

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Antibiotic targets in bacteria

Cell wall synthesis

DNA synthesis

RNA synthesis

Protein synthesis

Folic acid synthesis

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Antibiotics targeting cell wall synthesis

Penicillins

Cephalosporins

Carbapenems

Daptomycin

Glycopeptides

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Antibiotics targeting DNA synthesis

Fluoroquinolones

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Antibiotics targeting RNA synthesis

Rifampin

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Antibiotics targeting protein synthesis

Macrolides

Chloramphenicol

Tetracycline

Aminoglycosides

Oxazolidonones

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Antibiotics targeting folic acid synthesis

Sulfonamides

Trimethoprim

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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