AntimicroChemo Flashcards
MIC
- Minimal inhibitory concentration
- Minimum concentration of antimicrobial needed to inhibit visible growth of a given organism
MBC
- Minimal bactericidal concentration
- Minimum concentration of the antimicrobial needed to kill a given organism
Sensitive
Organism inhibited or killed by levels of the antimicrobial that are available at the site of infection
Resistant
- Organism that is not killed or inhibited by levels of the antimicrobial that are available at the site of infection
Bactericidal
An antimicrobial that kills bacteria -> penicillins
Bacteriostatic
Antimicrobial that inhibits growth of bacteria -> erythromycin
Routes of administration
Topical: on surface, skin or mucous membranes
Systemic: Internal, oral or parenteral (IV or IM, occasionally subcutaneously)
Three different areas of metabolic activity to inhibit or kill bacteria
- Inhibition of cell wall synthesis
- Inhibition of protein synthesis
- Inhibition of nucleic acid synthesis
Inhibition of cell wall synthesis and examples
- Human cells don’t have cell walls which means that these antibiotics don’t inhibit their synthesis
- Penicillins and cephalosporins (β-lactams)
- Vancomycin, teicoplanin
Penicillins and cephalosporins mechanism
β-lactams inhibit cell wall synthesis, they disrupt peptidoglycan synthesis by inhibiting enzymes that crosslink C-chains
Vancomycin and teicoplanin
- Act on cell wall synthesis and stage prior to β-lactams. Inhibit assembly of peptidoglycan precursor.
- Can only act on Gram positive since they cannot penetrate Gram negative cell wall
- Given parenterally
- Vancomycin is toxic, needs monitoring
Inhibition of protein synthesis and examples
- Involves translation of mRNA at the ribosome
- Gentamicin (Aminoglycosides)
- Erythromycin, clarithromycin and tetracyclines
- Linezolid
- Daptomycin
Gentamicin
- Gram -ve antimicrobial
- Also, most staphylococci are sensitive to them
- Injectable rather than oral abx
- Toxicity needs to be monitored -> hearing and renal function loss
Erythromycin, clarithromycin and tetracyclines
- E and C are macrolides, a good alternative to penicillin in Gram +ve infections -> allergy to penicillin
- Some resistance: Staph aureus, Strep. Pyogenes and Strep. Pneumoniae
- C has better penetration into tissue -> lower MIC. Good for Haemophilus influenza
Linezolid
- Good against MRSA
- Can be given orally
- Reserved for serious infections
Daptomycin
- Active against Gram positives in general and MRSA especially.
- Serious infections, specialist advice
Inhibition of nucleic acid synthesis and examples
- Inhibit DNA synthesis either directly or indirectly by interrupting the supply of DNA precursors
- Trimethoprim and sulphamethoxazole
- Ciprofloxacin
Trimethoprim and sulphamethoxazole
- Can be used in a combined form called co-trimoxazole as they inhibit different steps in purine sythesis
- Less likely to cause C.diff
- Trimethoprim commonly used in UTIs
Ciprofloxacin
- Particularly effective against Gram negative organisms including Pseudomonas
- Fluoroquinolones
- Inhibits DNA synthesis more directly
- Can be used orally as well as parenterally
- Can’t use on children as it interferes with cartilage growth
Antifungal drugs
- Polyenes
- Azoles
- Allylamines
- Echinocandins
Polyenes
- Bind to ergosterol in fungal cell wall
- Also bind to sterols e.g. cholesterol -> toxicity: renal, cardiac and hepatic toxicity
- Examples: amphotericin B (IV) only given for serious yeast infections, Nystatin (only give topically)
Azoles
- Inhibit ergosterol synthesis
- Examples: fluconazole, used parenterally and orally to treat yeast infections, not all yeasts sensitive to fluconazole.
Voriconazole and itracoazole used to treat filamentous fungi, aspergillosis spp.
Allylamines
- Suppress ergosterol synthesis, act at different stage in pathway from azoles
- Example: Terbinafine is used to treat skin (dermatophytes) and nail (oncycohmycosis) infections either orally or topically
Echinocandins
- Inhibit synthesis of glucan polysaccharides in several types of fungi
- Fungicidal against Candida spp. and several Aspergillus spp. for serious infections on specialist advice
Anti-Viral Drugs and examples of viruses you can treat
- Only virustatic
- Antiherpes
- Anti-HIV
- Chronic Hep B and Hep C
- Viral Respiratory Infections
Antiherpes
- Nucleoside analogue
- Aciclovir, used against VZV and Herpes Simplex
Anti-HIV
- Nucleoside analogue interferes with the action of reverse transcriptase
- Slows replication of virus
- Zidovudine (AZT)
Chronic Hep B and C
- Pegylated interferon-α is manufactured (usually in body as part of host immune response) given as subcutaneous injection
Viral Respiratory Infections
- Treat influenza A and B within 48 hours of the onset of symptoms and post-exposure prophylaxis
- Zanamavir and Oseltamivir
2 basic mechanisms of bacterial resistance
- Inherent resistance
- Acquired resistance
Inherent resistance
- All strains of given species are naturally resistant to an antibiotic. Usually due to inability of the drug to penetrate the bacterial cell wall
Acquired resistance - 2 basic ways resistance is acquired
- Target may have changed. Spontaneous mutation during multiplication of bacterial DNA can result in a change in structure of function which no longer allows the antibiotic to work.
- Genes that code for resistance can spread from organism to organism or species to species. Commonest
2 mechanisms of resistance to β-lactam antibiotics
- β-lactamase production
2. Alteration of penicillin binding protein (PBP)
β-lactamase production
- Cleaves β-lactam ring of the antibiotic. Inactivated
- Resistant to penicillins or cephalosporins
- Most strains of Staph. aureus produve β-lactamase
- Common in Gram negative bacilli
Combating β-lactamase
- Introduce second component to the antibiotic that protects enzyme degradation. E.g. co-amoxiclav has β-lactamase inhibitor clavulanic acid
- Modify antibiotic side chain to produce an antibiotic resistant to actions of β-lactamase e.g. flucloxacillin
Alteration of penicillin binding protein
- β-lactams can no longer bind as PBP genes have mutated
- These are resistant to all β-lactams
- Example: Staph aureus, MRSA strain
Glycopeptide resistance
- Vancomycin and teicoplanin resistance, unusual in Gram positive organisms
- Vancomycin resistant enterococci is a new one: peptidoglycan precursor has altered structure, vancomycin can’t bind
2 Factors that affect side effects
- Dose
- Length of treatment.
Too much of one of these and you can get a side effect
Side effects
- Immediate hypersensitivity
- Delayed hypersensitivity
- Gastro intestinal
- Thrush
- Liver toxicity
- Renal toxicity
- Neurological toxicity
- Haematological toxicity
Immediate hypersensitivity
- Anaphlactic
- IgE mediated and occurs within minutes of administration
- Itching, urticaria, nausea, vomiting ,wheezing and shock
- Laryngeal oedema may prove fatal
Delayed hypersensitivity
- Hours or days
- Immune complex or cell mediated mechanism
- Drug rashes are most common manifestation
- Drug fever - serum sickness and erythema nodosum may also occur
Gastro Intestinal side effects
- Nausea and vomiting are common
- Diarrhoea can come from toxin production by C. diff -> anaerobic gram positive bacillus carried asymptomatically in GI tract -> appears to overgrow -> CDAD, associated diarrhoea or CDI, infection -> pseudomembranous colitis
- This is why broad spectrum antibiotics are restricted
Thrush
- Broad spectrum antimicrobials also suppress normal flora and there can be overgrowth of resistant organisms
Liver toxicity
- Transient elevation of enzymes or severe hepatitis can occur
- More common in people with pre-existing liver disease and in pregnancy
- Associated drugs: tetracycline, anti-TB drugs and rifampicin, flucloxacillin
Renal toxicity
- Kidney is most important route of drug excretion
- Nephrotoxicity is more common in patients with pre-existing renal disease
- Most commonly seen with aminoglycosides or vancomycin
Neurological toxicity
- Ototoxicity -> aminoglycoside or vancomycin
- Optic neuropathy -> ethambutol (anti-TB drug) with dose related optic nerve damage
- Encephalopathy and convulsions -> may result from high dose β-lactams or aciclovir, needs to be reduced in the presence of renal impairment
- Peripheral neuropathy -> metronidazole and nitrofurantoin can cause this. Anti-TB drug, isoniazid can also induce neuropathy
Haematological toxicity
- Toxic effect -> selective depression of one cell line or unselective depression of all bone marrow elements
Prevention of adverse reactions
- Antimicrobials should be used only when indicated
- Minimum dose
- Minimum duration necessary to achieve efficacy
- Be aware of who could be affected by adverse effects from kidney and liver
- Never underestimate side effects of antibiotics, always report any side effects
Prophylaxis
- Prevent future infection
- If patient has been exposed to other patients with highly communicable disease
- Following surgical procedure associated with high post-operative infection rate
Monotherapy vs combination
- Additive 1+1=2
- or antagonistic 1+1=0
- or synergistic 1+1=4
- 2 cidal and 2 static drugs are additive or synergistic
- 1 static and 1 cidal are antagonistic
Penetration to site of infection
Antimicrobial needs to reach site of infection
Role of lab
- Monitoring efficacy: can measure that therapeutic levels have been achieved, make sure they’ve not gone toxic. Measure with serum
- Susceptibility: automated (computers), E test (simple, measure one antibiotic against one organism)
