Antimicrobial Chemotherapy Flashcards
Define bactericidal
An antimicrobial that kills bacteria (e.g. the penicillin
Define bacteriostatic
An antimicrobial that inhibits growth of bacteria (e.g. erythromycin).
Define a sensitive organism
An organism is considered sensitive if it is inhibited or killed by levels of the antimicrobial that are available at the site of infection
Define a resistant organisms
An organism is considered resistant if it is not killed or inhibited by levels of the antimicrobial that are available at the site of infection.
Define MIC
Minimal inhibitory concentration is de ned as the minimum concentration of antimicrobial needed to inhibit visible growth of a given organism.
Define MBC
Minimal bactericidal concentration is de ned as the minimum concentration of the antimicrobial needed to kill a given organism.
Describe some routes of drug administration
Topical - to surface e.g. king
Systemic - internal, either oral or parenterally
Parenteral - IV, intramuscularly, subcutaneously
What are the three main mechanisms of action of antibiotics?
Inhibit cell wall synthesis e.g. penicillins and cephalosporins, glycopeptides (vancomycin and teicoplanin)
Inhibit nucleic acid synthesis e.g. trimethoprim and ciproflaxacin
Inhibit protein synthesis e.g. gentamicin and erythromycin
Why don’t penicillins and cephalosporins (Beta-lactams) affect human cells?
These antibiotics disrupt peptidoglycan synthesis, and PG is not found in human cells.
Describe the action of penicillins and cephalosporins
Both are beta-lactam antibiotics, which inhibit peptidoglycan synthesis by binding the enzymes responsible for cross-linking carbohydrate chains, the penicillin binding proteins (PBPs). Cells are then killed by autolytic enzymes. Inhibit cell wall synthesis!
What are glycopeptides and what is their antimicrobial action?
Examples include vancomycin and teicoplanin, and this group of drugs inhibit cell wall synthesis. Also inhibit cell wall synthesis, though inhibit a stage earlier than beta-lactam antibiotics. Only act on gram positive organism as they can not penetrate the gram negative cell wall. Given parenterally though they are not absorbed in the GI tract. Vancomycin is toxic, monitor serum levels.
Define the antimicrobial effect of aminoglycosides
Example is gentamicin, which are used to treat serious gram negative infections by injection, and inhibit protein synthesis. Serum levels need to be monitored as gentamicin is highly toxic.
Define the antimicrobial effect of macrolides and tetracyclines?
Macrolides (e.g. erythromycin, clarithromycin) and the tetracyclines both inhibit protein synthesis, and are useful alternatives to penicillin in those with penicillin allergies for the treatment of gram positive infections.
Define the antimicrobial effect of oxazolidinones
Linezolid is the only example of this new class of protein synthesis inhibitors. Has good activity against serious MRSA infections and given orally.
Define the antimicrobial effect of cyclic lipopeptides
Daptomycin is a novel agent used against serious gram positive and MRSA infections, and inhibits protein synthesis.
Which drugs inhibit purine synthesis?
Trimethoprim and sulphamethoxazole
What class of drugs includes trimethoprim and sulphamethoxazole, and what are they used for together?
Inhibit purine synthesis and commonly used in combined form co-trimoxazole to treat chest infections to reduce the risk of subsequent C.difficile infections
What is trimethoprim used for?
On its own for UTIs, and in conjunction with sulphamethoxazole for chest infections
Which bacteria are more susceptible to the action of penicillin and cephalosporins?
Gram positive organisms such as streptococci and staphylococci. Gram negative cell walls are relatively impermeable.
Give some examples of glycopeptides
Vancomycin and teicoplanin. These inhibit the assembly of a peptidoglycan precursors in gram positive organisms.
How are glycopeptides administered?
Parenterally (IV, not absorbed well orally)
What are aminoglycosides?
Inhibit protein synthesis e.g. gentamicin
What is gentamicin used for?
Inhibits protein synthesis, given IV to treat gram negative infections e.g. E.Coli and coliforms. Requires a careful dosing regime as it is highly toxic
Describe the macrolides and tetracyclines
Includes erythromycin and clarithromycin
Prevent protein synthesis
Used to treat gram positive infections in those allergic to penicillin
What drugs are used to treat gram positive infections in those who are allergic to penicillin?
Macrolides (erythromycin and clarithromycin) and tetracyclines
Give an example of an oxazolidinone and their therapeutic action
Linezolid, inhibits protein synthesis. Used to treat serious MRSA orally
What drug is given to treat serious MRSA infections?
Linezolid
Daptomycin
How is Linezolid administered?
Orally
Give an example of a cyclic lipopeptide
Daptomycin
What is daptomycin used for?
Inhibits protein synthesis in gram positive infections, particularly useful in MRSA infections
Give an example of fluoroquinolones
Ciprofloxacin, used to inhibit DNA synthesis to treat gram negative infections
What is ciprofloxacin used for?
Gram negative infections
When is an organisms considered resistant to a drug?
An organism is considered resistant when it is unlikely to respond to attainable levels of that drug in tissues.
What is meant by inherent or intrinsic resistance?
In some cases, all strains of a certain species of a organism are naturally resistant to a drug e.g. inability of cell wall synthesis inhibitors to lyse gram negative bacterium
How can resistance be acquired?
Spontaneous mutations
Genes for resistance spread via transposons or plasmids
What are the two major mechanisms of resistance to beta-lactams?
Beta-lactamase production
Alteration of PBP target sites
What are the two ways you can tackle beta-lactamase production?
Use alongside beta lactase inhibitors e.g. clavulanic acid
Modify antibiotic side chain to reduce actions of beta lactamase
What is co-amoxiclav?
Amoxicillin and cavulanic acid (beta lactamase inhibitor)
What beta-lactam is resistant to the action of beta-lactamases?
Flucloxacillin
Describe Extended Spectrum Beta-lactamases (ESBLs)
Beta lactamases produced by some gram negative organisms which can render organisms resistant to all beta-lactams
Describe Carbapenemase Producing Enterobacteriacae (CPE)
Group of extremely resistant gram negative bacteria which are resistant to carbapenems (very broad class of antibiotics). Sometimes have no antimicrobial options.
Describe the mechanism of glycopeptide resistance
There are some vancomycin resistant gram positive enterococci which have altered the structure of their peptidoglycan precursors so vancomycin cant bind
Give some examples of drugs in the carbapenem class and what they act against
Imipenem, meropenem. Active against most bacteria, including anaerobes.
What drug is effective against both gram positive and gram negative anaerobes?
Metronidazole, used in cases such as intra-abdominal infection or any situation which may involve anaerobic infection
What is metronidazole used for?
Metronidazole is used in cases such as intra-abdominal infection or any situation which may involve anaerobic infection
What drug is useful in staphylococcus infections, particularly in staphylococcus osteomyelitis and pneumonia?
Fusidic acid
What drug is useful in some genital tract (chlamydia) and respiratory tract infections?
Tetracyclines
How is linezolid administered?
Orally
What is one side effect of linezolid acid?
Bone marrow suppression
What two drugs are commonly used in urinary tract infections?
Nalidixic acid
Nitrofurantoin
What is nalidixic acid used to treat?
UTIs caused by gram negative aerobic coliforms
What is nitrofurantoin used for?
UTIs caused by gram negative bacteria and some gram positive bacteria
What drugs are most commonly associated with allergic reactions?
Beta-lactam group
What % of penicillin allergic patients will also be allergic to cephalosporins?
10%
Describe immediate hypersensitivity
Type I - IgE mediated
Occurs within minutes
Itching, urticaria, nausea and vomiting, wheezing, shock
Describe delayed hypersensitivity
Type III - immune complex formation
May take hours or days to develop
Rashes, fever, serum sickness, erythema nodosum
What is Stevens-Johnson syndrome?
Severe form of delayed hypersensitivity caused by sulphonamides affecting both the skin and mucosal membranes
What causes pseudomembranous colitis?
Antibiotic treatment leading to the overgrowth of C.difficile, causes severe diarrhoea and infection that requires surgical intervention
How is C.difficile infection induced diarrhoea diagnosed?
Detection of toxin in stools by enzyme immunoassay
What drugs are used to treat C. difficile infections?
Metronidazole or oral vancomycin
What are the 4 C’s related to the increase in CDI over the last couple years?
Due to increased use of broad spectrum agents Cephalosporins Ciprofloxacin Clindamycin Co-amoxiclav
What broad spectrum antibiotics are linked to the overgrowth of Candida albicans and thrush development?
Penicillins and cephalosporins
What drugs are known to cause liver toxicity?
Tetracycline
Isoniazid
Rifampicin
Flucloxacillin
What drugs are known to cause renal toxicity?
Aminoglycosides
Vancomycin
What drugs cause ototoxicity (drug related damage to inner ear)?
Aminoglycosides
Vancomycin
What drug causes optic neuropathy?
Ethambutanol (anti-TB drug)
What drugs can lead to encephalopathy and convulsions?
High dose penicillins and cephalosporins
Aciclovir
What drugs can cause peripheral neuropathy?
Metronidazole and nitrofurantoin
Whats the difference between neutropenia and pancytopenia?
Neutropenia - Selective depression of one cell line of BM
Pancytopenia - Unselective depression of all bone marrow elements
What drug is thought to affect growing cartilage so is not used in children?
Ciprofloxacin
Why is combination therapy useful?
Mixed infections
Two drugs can be synergistic
Minimise development of resistant strains
How long is the standard course of antimicrobial treatment?
7 days
How long is IV therapy for Staph Aureus bacteraemia?
14 days
How long is the antimicrobial treatment of osteomyelitis and endocarditis?
Several weeks
How long is the treatment for UTI infections?
3 days
What is the mechanism of action of polyenes?
“Pore forming” - bind to ergosterol in fungal cell wall which results in the increase in their permeability
What two polyenes are in clinical use and what are their indications?
Amphotericin B - IV serious systemic fungal infection
Nyastatin - topical and oral, candidiasis
Why are polyenes toxic?
Can bind to other sterols e.g. cholesterol in mammalian cell membranes
Describe the mechanism of action of azoles
inhibit ergosterol synthesis e.g. ketaconazole, fluconazole, intraconazole etc
What is fluconazole used to treat?
Yeast infections
What azoles are used to treat aspergillosis?
Voriconazole and itraconazole
What is the mechanism of action of allylamines?
Suppress ergosterol synthesis e.g. terbinafine
What is terbinafine used for?
Allylamine used to treat dermatophyte infections of the skin and nails
What are echinocandins used for?
Serious candida and aspergillus infections. Inhibit the synthesis of glucan polysaccharides.
Examples include caspofungin, mycanfungin and anidulafungin
What effect do anti-viral have on viruses?
Virustatic, not virucidal
Name 4 examples of the Herpes virus
Herpes simplex virus
Varicella-Zoster virus
Epstein Barr virus
Cytomegalovirus
Name some anti-herpes virus drugs
Aciclovir
Famiclovir
Valaciclovir
What is ganciclovir used against?
Active against CMV. IV infusion in serious infections of the immunocompromised
Describe the mechanism of action of zidovudine
Nucleoside analogue which interferes with the action of reverse transcriptase. Used for HIV treatment.
What is used to treat chronic hepatitis B and C infections?
Interferon-a
What is used to treat influenza A or B virus?
Zanamivir
Oseltamivir
What is used to treat severe respiratory syncytial virus (RSV) infections?
Ribavarin, inhaled
