Antimicrobial Chemotherapy Flashcards
What class of drug does daptomycin belong to?
Cyclic Lipopeptide
What is the standard length of an antimicrobial course?
7 days
What are the three ways antibiotics work?
Inhibition of cell wall synthesis Inhibition of Protein synthesis Inhibition of nucleic acid synthesis
How is aciclovir administered?
Orally or intravenously
Where are beta-lactamases common?
In Gram negative Bacilli
What is the activity of daptomycin?
Good activity against gram positive bacteria in general and MRSA in particular
(inhibition of protein synthesis)
What antibiotic is associated with optic nerve damage? (optic neuropathy)
Ethambutol
What are ESBL’s?
Extended spectrum beta lactamses - they are resistant to all beta lactamases
What are CPE’s?
Carbapenemase producing Enterobacteriaceae, they are extremely resistant gram negative organisms - resistant to the carpebenems.
What is Tenofovir used for?
Hepatitis B
What can happen to stop Beta lactams binding to PBP’s?
Mutations in PBP genes, resulting in a modified target site, to which beta lactams will no longer bind
What are the susceptible groups who need extra care when administering antimicrobials?
Extremes of age, pregnant women, patients with renal or liver insufficiency.
What is the spectrum of glycopeptides?
They act against ONLY gram positive organisms - both aerobic and anaerobic
What is the difference between Nalidixic acid and Nitrofurantoin?
Also effective against some gram positive bacteria.
What is the effect of trimethoprim and sulphamethoxazole?
Inhibit different steps in purine synthesis
What drug can be used against the herpes simplex virus and the varicella zoster virus?
Aciclovir
What are the side effects of vanomycin?
Otoxicity, nephrotoxicity and skin rashes
What is the disadvantage of clindamycin?
Common cause of pseudomembranous collitis
What is defined as clinical resistance?
When the organism is unlikely to respond to attainable levels of that drug in the tissues
What is Voriconazole used to treat?
Aspergillosis
What is used to treat chronic hepatitis B and C infections?
Interferon - a
What are the signs of delayed hypersensitivity?
Drug rashes, drug fever, serum sickness and erythema nodosum
What is Nitrofurantoin active against?
Most gram negative organisms with the exception of pseudomonas and proteus
What is cystitis?
Lower urinary tract infections
What is special about the treatment of pseudomonas with ciproflaxin?
It is the only oral therapy available
How do aminoglycosides lyse most gram negative cells?
By inhibiting protein synthesis Staphylococci are also sensitive to aminoglycosides, streptococci are not
Describe the combination therapy used to treat patients with HIV
Combination therapy with at least three drugs. Drugs are active on at least two different stages of the HIV replication. Examples of the actions of these drugs : 1. Analogue nucleoside which inhibits reverse transcriptase 2. Non-nucleoside reverse transcriptase inhibitor 3. Protease inhibitor which inhibits viral protease enzyme.
When is genotypic analysis of a virus useful?
May help choosing rational treatment in selected patients
What is the advantage of Teicoplanin?
Less toxic, single daily dosing advantage
Do all strains of C.diff produce toxins?
NO
What is metronidazole effective against?
It is a miscellaneous Antibiotic - effective against both gram negative and gram positive bacteria Resistance against anaerobes is virtually unknown No useful activity against aerobes
What is ribavarin used for?
Treatment of severe respiratory syncytial virus infections. Used in combination treatment for chronic hepatitis C with Interferon - a
How is treatment of C.Diff achieved?
Metronidazole or oral vanomycin (not absorbed in the GI tract so it is the only circumstance where the oral form is used.
What form of penicillin has a better absorption when taken orally?
Phenoxymethylpenicillin, as well as amoxicillin and ampocillin (these confer better gran negative activity)
How is ribavarin administered?
Inhaled as a fine spray
Give an example of a oxazolidinone
Linezolid - protein synthesis inhibitor
What is the effect of zidovudine?
Nucleoside analogue Interferes with the action of reverse transcriptase. Slows down the replication of the virus but does not kill it. Prolongs survival of AIDS patients
What is a cause of diarrhoea that is associated with antibiotic therapy?
Diarrhoea associated with toxin production by clostridium difficile. It overgrows normal flora during therapy
What can cause an overgrowth in candida albicans?
Broad spectrum penicillins or cephalosporins causing oral and or vaginal candidiasis, also known as thrush
Give examples of cidal drugs
B lactams, aminoglycosides, glycopeptides and quinolones
Which drugs are usually associated with nephrotoxicity and ototoxicity?
Aminoglycoside (gentamicin) or with vanomycin
What is the main cause of CDI in recent years?
Use of broad spectrum antibiotics
Is C.diff killed by alcohol hand rub?
NO
When do patients require several weeks of antimicrobial therapy?
Patients with osteomyelitis, endocarditis
What can linezolid be used to treat?
MRSA
What is the only polyene available for intravenous polyene use?
Amphoterecin B Treats serious systemic fungal infection Extremely toxic Renal, Hepatic and cardiac toxicity
Describe the activity of cephalosporins against gram negative and gram positive bacteria as the generation number increases
Gram negative activity increases - even effective against Pseudomonas Gram positive activity decreases
What is the most common and cheapest aminoglycoside?
Gentamicin
What is the effect of the liver on the antimicrobials?
Metabolised by the liver and excreted in bile
What is the function of Allylamines?
Suppress ergosterol synthesis, but act on a different stage of the synthetic pathway from Azoles.
What are penicillin binding proteins?
Enzymes responsible for peptidoglycan synthesis
What is the other polyene in clinical use?
Nystatin - available for topical use only (fungal skin infections in pessaries for vaginal candida infections) and in oral suspension (for oral and oesophageal candidiasis)
What determines the choice between Vanomycin and teicoplanin?
The two glycopeptides have the same spectrum of activity, the choice is however dependant on cost
What drugs are associated with hepatotoxicity?
Tetracyline, isoniazid and rifampicin (anti tuberculosis drugs), flucloxacilin
What are examples of Echinocandins?
Caspofungin, Mycafungin and anidulafungin
Describe the problems associated with Fluconazole and resistance
Resistance among some candida species is emerging Majority of Candida albicans (commonest species of yeast associated clinical infection) with strains remain sensitive but resistance can emerge during treatment,
Why has cephalosporin use decreased over recent years?
They appear to encourage clostridium difficile infections
What drugs are both licensed for the treatment of influenza and what are there limitations?
Zanamavir and Oseltamavir Used to treat A or B within 48 hours of symptoms and also for post-exposure prophylaxis.
Describe the resistance of bacteria with modified PBP’s against beta lactams
Resistant to all beta lactam agents
Describe the action of fluconazole
Used for oral and parenteral treatment of yeast infections (no activity against filamentous fungi-aspergillus)
What is the first choice treatment against staphylococcal infections (which are gram positive btw)? And Why?
Flucloxacillin - resistant to the actions of staphylococcal beta lactamase.
What can linezolid cause?
Bone marrow suppression
What are the different forms of fungi?
Yeasts and filamentous fungi (moulds)
Give examples of static drugs
Macrolides, tetracyline, trimethoprim
Is treatment against staphylococcal infections be possible with ciproflaxin?
Yes although it would not be first choice
What is the effect of beta lactam antibiotics?
Inhibits carbohydrate cross chain linkage - disrupting peptidoglycan synthesis
What can cause peripheral neuropathy?
Metronidazole and nitrofuratonin may produce reversible peripheral neuropathy Isoniazid too
What is a benefit of co-trimoxazole to other broad spectrum antibiotics like cephalosporins? (in the treatment of chest infections)
Less likely to cause clostridium difficile infections
What is the efffect of Macrolides and Tetracylines?
Treat gram positive infections, useful if the patient is allergic to penicillin, act on protein synthesis
Why is staphylococcus aureus resistant to benzyl penicillin?
Produces beta-lactamse
When is an antimicrobial agent useless even though the serum concentration is within the therapeutic range?
When it is unable to penetrate the site of infection
What does linezolid have activity against?
MRSA
How are glycopeptides administered?
They are administered parenterally, they are not absorbed from the GI tract
What is lamivudine used for?
HIV treatment
What is Nalidixic acid used against?
Gram negative aerobes (coliform) organisms
What are the applications of tetracylines?
Broad spectrum agents that inhibit protein synthesis Useful for some genital tract (chlamydia) infections and respiratory infections They should not be prescribed to children under 12 or pregnant as they are deposited in teeth and bone
Why are 20-30 percent of coliform agents now resistant to amoxicillin and ampocillin?
beta lactamse production
What are the two ways to combat a bacteria which can produce beta lactamase?
Introduce a beta lactamase inhibitor OR Modify the R1 side chain to produce an antibiotic which is resistant to the effects of beta lactamase
Why aren’t Fluoroquinolones (ciphroplaxins) given to children?
Due to the danger of interference with cartilage growth
What is the drug terbinafine primarily used against?
Dermatophyte infections of the nails and skin
What is the only allaylamine in common use?
Terbinafine
What are the pathologies associated with c. diff toxins?
CDAF (c.diff associated diarrhoea), CDI (infection) or a life threatening condition called pseudomembranous collitis
Are the antiviral drugs available virucidal or virustatic?
Virustatic
What is itraconazole used to treat?
Yeast and filamentous fungi including aspergillus and dermatophytes
What is the effect of echinocandins?
Inhibits the synthesis of glucan polysaccharide in several types of fungi. They are fungicidal against candida species and inhibit the growth of several aspergillus species.
What are newer quinolones such as ciproflaxin effective against?
Nearly all gram negative organisms including pseudomonas
What is the best known example of a beta lactamase inhibitor?
Co-amoxiclav - consists of amoxicillin (antibiotic) and Clavulanic acid (beta lactamase inhibitor)
What are the possible side effects of antibiotics on the liver?
Possible elevation of enzymes to severe hepatitis
What is the combined form of trimethoprim and sulphamethoxazole?
Co-trimoxazole
What are allergic reactions most commonly associated with?
Beta lactam groups of drugs
Why is Fusidic acid always given with another anti- staphylococcal drug such as flucloxacillin?
Staph aureus can easily develop resistance to this drug
What is usually the cause of an organism to be naturally resistant to an antibiotic?
Drug can not penetrate the cell wall
What is the function of glycopeptides?
They act on cell wall synthesis at a stage prior to beta lactams, and inhibit the assembly of a peptidoglycan precursor
How do polyenes work?
Binds to ergesterol which is present in the fungal cell wall but not the bacterial cell wall - increase in the permeability of the cell wall
What are the two ways resistance is normally acquired?
Aspontaneous mutation during multiplication of bacterial DNA - antibiotics target may have now changed Gene coding for resistance spreads from one organism to another - or even one species to another. The vector of genes are plasmids or transposons.
What is the advantage of clindamycin?
Good tissue penetration, e.g into the bone and it can be taken orally
What organisms causes atypical pneumonia?
Chlamydia psittacci, Coxiella burnetti, Mycoplasma pneumonia and Leigonella Pneumophilia
What is the route of administration for Glycopeptides and Aminoglycosides?
Parenteral use only
What are the features of carbapenems?
They exhibit the widest spectrum of all and are active against most bacteria including anaerobes
What is the effect of one cidal drug and one static drug?
May result in atnagonism
What are the different routes of administration of antimicrobial chemotherapy?
Topical Systemic Parenteral
Why is there limited use of interferon - a
Low response rate, serious side effects and high cost
Give a name to a newer azole (triazole)
Fluconazole
What is the second largest group of beta lactam antibiotics?
Cephalosporins
What two significant species is piperacillin effective against?
pseudomonas species and Enterococcus faecalis
What is the spectrum of Aminoglycosides?
Acts against gram negative organisms including pseudomonas - relatively little resistance seen in the UK recently (Gram Positive) Staphylococci are sensitive, streptococci are not Gentamicin
What are polyenes active against?
Both Yeasts and filamentous fungi (moulds)
When does prophylaxis of antimicrobials happen?
When the patient has been exposed to other patients with highly communicable disease OR Surgical procedures associated with high post-operative infection rates.
How is toxin production diagnosed?
Detection of toxin in the stool by an enzyme immunoassay.
What are the strains that are resistant to Macrolides and tetracylines?
Staph aureus (Coagulase positive), strep pyogenes (Beta haemolytic group A)
Why are some gram negative bacteria resistant to benzyl penicillin?
Because of the relative impermeability of the cell wall.
What type of bacteria do Fluoroquinolones (ciphroplaxins )act against?
Gram negative
Give an example of an antibiotic with a modified side chain - making it resistant to the effects of beta-lactamase
The antistaphylococcal drug - Flucloxacillin, which is a modified form of penicillin
What is the effect of two cidal or static drugs?
Additive or synergistic
What is a possible side effect of gentamicin?
Ototoxicity, nephrotoxicity
What is the function of Fluoroquinolones (ciphroplaxins)?
Inhibit DNA synthesis
Why are some antimicrobials contraindicated in pregnancy?
Because they are thought to be mutagenic (include mutation in foetal chromosomes), teratogenic (associated with congenital abnormalities) Or because their effect on the unborn foetus is unknown
What is piperacillin commonly used in combination with?
Betalactamase inhibitor tazocin, (commonly called Pip/Taz)
Define transposons
Packets of DNA that insert themselves into the chromosome
Which type of bacteria have recently started expressing resistance to vanomycin?
Enterococci
When is it appropriate to use a combination instead of monotherapy?
To cover mixed infections caused by more than one organism Some antimicrobials have an enhanced effect together (synergy) To minimise the development of resistant strains to any one agent
What happens after the cell wall is destroyed?
Autolytic enzymes kill the organism
What is trimethoprim commonly used in the treatment of?
Urinary tract infections
What is Daptomycin used to treat?
Gram positive infections and may be useful in the treatment of serious MRSA infections
Vanomycin resistance is usually uncommon amongst which type of bacteria?
Gram positive organisms
When is empirical antimicrobial chemotherapy initiated?
When the cause of the infection is unknown and urgent treatment is required
What is a low therapeutic index and what antimicrobials are examples?
The different between a therapeutic dose and a toxic does is small Gentamicin and vanomycin - serum levels should be monitored
What is the best choice for intravenous treatment against serious pneumococcal, meningococcal and strep pyogenes?
Benzyl penicillin
What are the HIV combination therapy drugs also used for?
Prophylaxis following exposure to HIV positive body fluids Decrease the transmission of HIV from mothers to unborn children.
What is the only lincosamide antibiotic in common use with good gram positive activity against staph and strep, also good activity against anaerobes.
Clindamycin
What does benzyl penicillin act against?
Gram positive organisms, meningococci is an exception
Give two examples of glycopeptides
Vanomycin and Teicoplanin
How do Azoles work?
They inhibit ergosterol synthesis
What is the best known example of an altered PBP?
Staph aureus, strains are known as meticillin resistant Staph Aureus (MRSA)
Why are narrow spectrum antibiotics used?
Less likely to encourage resistance or Clostridium difficile
What is an E test?
Paper strip has a gradient of antibiotic concentration absorbed into it MIC determined at the point where organism growth intersects the strip
What are the three possible outcomes of the combination of antimicrobials?
Their effects are additive They are antagonistic, their collective effect are less than the sum of their individual effects They are synergistic - their collective effect are greater than the sum of their individual effects (penicillin and gentamicin - breaks down cell wall then gentamicin accesses the ribosome)
What is common amongst circumstances of immediate hypersensitivity?
Usually as a result of parenteral administration
What drug is a broad spectrum penicillin? Offers extended gram negative cover
Piperacillin
What is the reason for polyenes toxicity?
They bind to other sterols like cholesterol in mammalian cell membranes
Where can you find out the appropriate dosage schedules for various antimicrobials?
British national formulary Grampian formulary
Give an example of a macrolide that is often used instead of Penicillin for patients with penicillin hypersensitivity?
Clarithromycin and erythromycin
How is susceptibility testing achieved
Automated methodology involving computer controlled hardware. Growth of the bacteria is measured using a mixture of antimicrobials with a mixture of different concentrations. The MIC of the antibiotic is calculated for that organism The test gives a PREDICTION to wether the infection is likely to be cured by the antibiotic in question. In practice the outcome depends on route of administration, dosing schedule, penetration of antibiotic to the target site and interactions with other drugs
What is the effect of some antimicrobials on bone marrow?
toxic effect, Selective depression of one cell line (neutropenia), or unselective depression of all bone marrow elements (pancytopenia)
How is the environment contaminated by C.diff?
It is contaminated by spores
What antibiotic is useful against staphylococcal osteomylitis and pneumonia and why?
Fusidic acid - Diffuses well into bone and tissue
Activity of quinolones against streptococci is usually quite poor, however, what is the new quinolone levoflaxin active against?
Pneumococci, Organisms causing atypical pneumonia
What type of bacteria do glycopeptides act on?
Gram positive because they can not pass through the gram negative cell wall
Give examples of carbapenems
Imepenem, meropenem
What are the two types of resistance to Beta lactam antibiotics?
Production of beta-lactamse OR Changing the structure of their Penicillin Boinding Protein
What is the spectrum of Clarithromycin and Erythromycin?
Active against gram positive organisms Macrolides are also effective against organisms causing atypical pneumonia
How is vancomysin normally measured?
By measuring a trough level immediately before a dose is given to make sure the dose is not too high
Why is piperacillin a good choice of antibiotic against serious intra-abdominal infection?
Has good anti-anaerobic activity
What is the new macrocyclic antibiotic Fidaxomicin bacteriacidal against?
C. diff
What are the common gastrointestinal side effects?
Vomiting, nausea
What antibiotics are associated with encephalopathy and convulsion?
Penicillin, cephalosporin and aciclovir
Describe the structure of many antiviral drugs
They are anologues of nucleosides - interfere with nucleic acid synthesis
What length of course is recommended for patients with staph aureus bacteraemia?
14 days of intravenous therapy
