Antibiotic cases Flashcards
What is the origin of antibiotics and how are they defined in this context?
Antibiotics are derived from living organisms (e.g., penicillin) and in this context, they will be used to mean antibacterial drugs, including chemotherapeutic agents that were synthesized.
What is the emphasis of the lecture regarding antibiotics?
The emphasis is on drugs for community-acquired infections.
Are drugs for nosocomial infections included in the lecture?
Yes, drugs for nosocomial infections are included for completeness, denoted by an H in a red circle.
Which antibiotics exhibit concentration-dependent killing?
Antibiotics like aminoglycosides and quinolones exhibit concentration-dependent killing.
What determines the effectiveness of concentration-dependent antibiotics?
The effectiveness is directly related to the concentration achieved in the blood or at the site of infection.
What does the Area Under the Curve (AUC)/Minimum Inhibitory Concentration (MIC) ratio indicate?
The AUC/MIC ratio correlates with the efficacy of the antibiotic, with a higher ratio generally indicating better bacterial eradication.
What is the Minimal Inhibitory Concentration (MIC)?
MIC is the lowest concentration of the antibiotic that inhibits visible growth of the bacterium.
Why is it important to achieve concentrations well above the MIC for concentration-dependent antibiotics?
Achieving concentrations well above the MIC is crucial for effective treatment and bacterial killing.
What are the risks of underdosing concentration-dependent antibiotics?
Underdosing can lead to subtherapeutic levels, potentially resulting in treatment failure and the development of resistance.
Which antibiotics exhibit time-dependent killing?
Antibiotics like beta-lactams exhibit time-dependent killing.
What determines the effectiveness of time-dependent antibiotics?
The effectiveness is related to the duration of time that the drug concentration remains above the Minimum Inhibitory Concentration (MIC).
For beta-lactams, what percentage of the dosing interval should drug concentrations remain above the MIC to correlate with clinical cure?
Maintaining drug concentrations above the MIC for 40-60% of the dosing interval correlates with clinical cure.
In certain infections like meningitis, what is the optimal duration for drug levels to be above the MIC?
Optimal bacterial killing occurs when drug levels are above the MIC for 95-100% of the dosing interval in infections like meningitis.
Why is it important for patients to adhere to the prescribed dosing schedule for time-dependent antibiotics?
Adherence ensures that drug concentrations remain above the MIC, reducing the risk of subtherapeutic levels, treatment failure, and resistance.
What are the risks associated with skipping doses of time-dependent antibiotics?
Skipping doses can result in subtherapeutic levels, reducing the effectiveness of the antibiotic and increasing the risk of resistance.
B lactam antibiotics
- Penicillin
- Clavulanic (B lactamase inhibitor)
- Cephalosporin
- Carbapenem (H)
What is the primary target of beta-lactam antibiotics?
Beta-lactams target the synthesis of peptidoglycan, an essential component of the bacterial cell wall.
What role does peptidoglycan play in bacterial cells?
Peptidoglycan provides structural integrity and strength to the bacterial cell wall, helping to maintain its shape and prevent lysis.
How do beta-lactams exert their effect on bacteria?
Beta-lactams bind to and inhibit penicillin-binding proteins (PBPs), which are enzymes involved in the final stages of peptidoglycan synthesis.
What is the function of penicillin-binding proteins (PBPs)?
PBPs catalyze the cross-linking of peptidoglycan chains, a critical step in forming a strong, rigid cell wall.
What reaction is inhibited by beta-lactams, leading to a weakened cell wall?
Beta-lactams inhibit the transpeptidation reaction, which forms cross-links between peptidoglycan chains.
How does the inhibition of cell wall synthesis by beta-lactams lead to bacterial cell death?
The inhibition of cell wall synthesis activates autolytic enzymes within the bacterium, further degrading the cell wall and leading to bacterial cell lysis and death.
Are beta-lactams bactericidal or bacteriostatic?
Beta-lactams are typically bactericidal, meaning they kill bacteria rather than merely inhibiting their growth.
What determines the efficacy of beta-lactams?
The efficacy of beta-lactams depends on the duration of time that the drug concentration remains above the Minimum Inhibitory Concentration (MIC) during the dosing interval.
Do all beta-lactams have the same spectrum of activity?
No, different beta-lactams have varying spectra of activity, with some being effective against Gram-positive bacteria, others against Gram-negative bacteria, and some having broad-spectrum activity.
Where do beta-lactam antibiotics exert their action?
Beta-lactam antibiotics act on the bacterial cell wall.
What type of bactericidal action do beta-lactams have?
Beta-lactams have a time-dependent bactericidal action.
What is notable about the therapeutic index of beta-lactams?
Beta-lactams have a wide therapeutic index, but they can cause CNS toxicity at maximal doses
What is the main adverse effect of beta-lactam antibiotics?
The main adverse effect of beta-lactam antibiotics is hypersensitivity.
How are most beta-lactam antibiotics eliminated?
Most beta-lactam antibiotics are eliminated by renal tubular secretion.
What is the most common resistance mechanism against beta-lactam antibiotics?
The most common resistance mechanism is mediated by beta-lactamases.
Can beta-lactamase resistance be overcome by using higher doses of beta-lactams?
No, beta-lactamase resistance cannot be overcome by using higher doses.
What types of bacteria commonly produce beta-lactamases in the community?
In the community, most aerobic Gram negatives, anaerobes, and staphylococci produce beta-lactamases.
Where are extended spectrum beta-lactamases (ESBLs) typically found, and what is their impact?
ESBLs are typically found in aerobic Gram negatives in hospitals, leading to high-level resistance to all penicillins and cephalosporins.
What is the second resistance mechanism to beta-lactam antibiotics, and how can it be overcome?
The second resistance mechanism involves mutations in penicillin-binding proteins (e.g., S. pneumoniae), usually causing low-level resistance that can be overcome by using higher doses.
Against which types of bacteria is penicillin active?
Penicillin is active against Gram positives and spirochaetes.
For which infections is penicillin the drug of choice?
Penicillin is the drug of choice for:
- Streptococci (with few S. pneumoniae being highly resistant)
- Syphilis and other spirochaetes
- Enterococci
- Listeria
- Actinomyces
Is penicillin susceptible to beta-lactamase?
Yes, penicillin is susceptible to beta-lactamase.
What are the different forms of penicillin administration and their uses?
Penicillin G: Intravenous injection (IVI)
Penicillin V: Oral (poorly absorbed, concentrations inadequate for S. pneumoniae)
Benzathine Penicillin: Long-acting injectable (intramuscular injection, IMI) that lasts for 21 days
What are the two types of aminopenicillins and their modes of administration?
Ampicillin: Intravenous (IV) only
Amoxicillin: Oral (well absorbed)
How do aminopenicillins compare with penicillin in terms of bacterial coverage?
Aminopenicillins cover the same bacteria as penicillin plus Haemophilus (except for the +15% that have beta-lactamase).
Why are aminopenicillins recommended for respiratory infections?
Aminopenicillins have excellent activity against S. pneumoniae, making them recommended for respiratory infections.
Which penicillins resist beta-lactamase from Staphylococci?
Cloxacillin and flucloxacillin
Which penicillin has better oral absorption?
Flucloxacillin is better absorbed orally than cloxacillin.
What type of bacteria are cloxacillin and flucloxacillin effective against?
Both are only effective against Gram-positive bacteria.
What are cloxacillin and flucloxacillin widely used for?
They are widely used for skin and soft tissue infections.
What are B-lactamase inhibitors?
B-lactamase inhibitors are compounds that bind irreversibly to B-lactamases, enzymes produced by bacteria that confer resistance to B-lactam antibiotics.
What are irreversible inhibitors of β-lactamases?
Substances that bind permanently to β-lactamases, preventing the enzyme from breaking down β-lactam antibiotics.
How do irreversible inhibitors of β-lactamases work?
They bind to the active site of β-lactamase, inhibiting its action and thus protecting the β-lactam antibiotic from degradation.
What is the benefit of combining β-lactam antibiotics with β-lactamase inhibitors?
This combination can reverse bacterial resistance, making the antibiotics effective against bacteria that produce β-lactamase enzymes
Can you name two examples of irreversible β-lactamase inhibitors?
Clavulanate and Tazobactam.
Give an example of a combination of a β-lactam antibiotic and a β-lactamase inhibitor
Amoxicillin-clavulanate.
Piperacillin-tazobactam (H)
What spectrum of activity does Amoxicillin-clavulanate have?
It has a broad spectrum of activity.
What types of infections can Amoxicillin-clavulanate treat?
It can treat community-acquired infections caused by Gram-positive, Gram-negative, and anaerobic bacteria.
Must know penicillin drugs
Penicillin (IV, oral and depot IM)
Cloxacillin/flucloxacillin
Amoxicillin
Amoxicillin-clavulanate
How were cephalosporins developed?
Cephalosporins were developed in successive waves or generations.
What is the spectrum of 1st generation cephalosporins?
The spectrum is largely limited to Streptococci and Staphylococci.
Can you name examples of 1st generation cephalosporins and their routes of administration?
Cefazolin (IV) and Cephalexin (PO).
What additional bacteria does the 2nd generation cephalosporin spectrum cover compared to the 1st generation?
It covers Haemophilus and community-acquired Gram negatives, in addition to Streptococci and Staphylococci.
Can you name examples of 2nd generation cephalosporins and their routes of administration?
Cefuroxime (PO & IV).
What additional bacteria and conditions does the 3rd generation cephalosporin spectrum cover compared to the 2nd generation?
It covers typhoid, spirochetes, and has good CSF penetration.
Can you name examples of 3rd generation cephalosporins?
Cefotaxime, ceftriaxone, and ceftazidime.
What is ceftazidime specifically effective against, and what is it poor for?
It is effective against Pseudomonas and poor for Streptococci, commonly used for hospital-acquired infections
What is the spectrum of 4th generation cephalosporins?
Similar to ceftazidime and cefotaxime.
Can you name an example of a 4th generation cephalosporin?
Cefepime.
What type of infections is cefepime commonly used for?
Hospital-acquired infections.
What is Cefazolin used for at induction?
It is used for surgical prophylaxis.
What type of serious infections is Cefazolin also used for?
Serious staphylococcal infections.
What are the routes of administration for Ceftriaxone?
Intravenous injection (IVI) and intramuscular injection (IMI).
How is Ceftriaxone primarily excreted from the body?
It is excreted mainly through the bile
What is the spectrum of Ceftriaxone?
It covers community-acquired Gram-positive (including most S. pneumoniae, but not ideal for S. aureus) and Gram-negative bacteria.
What is Ceftriaxone’s significance in the treatment of bacterial meningitis?
It has good CSF penetration and is the empiric drug of choice for bacterial meningitis.
For which serious infections is Ceftriaxone the drug of choice?
Typhoid and gonorrhea (IMI).
Why is Ceftriaxone considered a useful broad-spectrum agent?
It is effective for serious community-acquired infections.
What is the spectrum of activity for carbapenems?
Extremely broad spectrum covering most hospital-acquired Gram-positive, Gram-negative, and anaerobes.
What type of infections are carbapenems used for?
Only for nosocomial (hospital-acquired) infections.
Are carbapenems effective against cloxacillin-resistant Staphylococci?
No, they are not active against cloxacillin-resistant Staphylococci.
What is a significant drawback of using carbapenems?
They are very expensive
With which class of antibiotics is the incidence of hypersensitivity reactions highest?
Penicillins, with an incidence of 1 to 6%.
What is the most common hypersensitivity reaction to β-lactam antibiotics?
Maculopapular rash.
When does a maculopapular rash typically appear after β-lactam administration?
After 72 hours.
Which β-lactam antibiotic is usually associated with maculopapular rash?
Amoxicillin
How soon can anaphylaxis occur after β-lactam administration?
Within 1 hour.
What is the incidence rate of anaphylaxis due to β-lactam antibiotics?
Rare, 0.01 to 0.05%.
Through which route is anaphylaxis most commonly triggered?
Mostly through parenteral (injection) administration.
What immunoglobulin is associated with anaphylaxis?
IgE
When can angioedema, urticaria, or bronchospasm occur after β-lactam administration?
Within 72 hours.
What immunoglobulin is associated with angioedema, urticaria, or bronchospasm?
IgE.
What is the incidence of cross reactions between cephalosporins and penicillins?
Less than 5%.
What is the incidence of cross reactions between 3rd generation cephalosporins and penicillins?
Less than 1%.
Is it safe to use cephalosporins in patients with a penicillin allergy?
It is OK to use if the hypersensitivity reaction was not IgE mediated.
What should be done if the penicillin allergy was IgE-mediated?
Avoid the entire class of β-lactam antibiotics.
What can be done in exceptional cases for patients with IgE-mediated reactions?
Desensitization may be considered.
How common are cross reactions between carbapenems and other β-lactam antibiotics?
Cross reactions with carbapenems are rare.
What type of infections are glycopeptides primarily used for?
Hospital-acquired infections.
How do glycopeptides work?
They are active against cell walls
What type of killing do glycopeptides exhibit?
Time-dependent killing.
Are glycopeptides absorbed orally?
No, they are not absorbed orally.
What is the spectrum of activity for glycopeptides?
They cover only Gram-positive bacteria.
Which type of resistant bacteria are glycopeptides especially effective against?
Cloxacillin-resistant Staphylococci.
Can you name an example of a glycopeptide?
Vancomycin.
What is essential when administering Vancomycin?
A slow IV infusion to prevent red man syndrome.
What are the potential toxicities of glycopeptides?
They are mildly nephrotoxic and ototoxic.
When should the concentration of glycopeptides be measured?
In cases of renal failure and for selected organisms.
What type of bacteria are aminoglycosides particularly potent against?
Aerobic Gram-negative bacilli.
How do aminoglycosides work?
They are bactericidal inhibitors of protein synthesis.
What type of killing do aminoglycosides exhibit?
Concentration-dependent killing.
Do aminoglycosides require synergy with other antibiotics?
Synergy with β-lactams is seldom necessary.
What is a characteristic of aminoglycosides in terms of tissue penetration?
They are polar compounds with poor tissue penetration.
How are aminoglycosides typically administered?
They must be given parenterally.
Where are aminoglycosides concentrated in the body?
They are concentrated in the urine.
What is the recommended dosing schedule for aminoglycosides?
Single daily dosing is best, due to the post-antibiotic effect.
When should aminoglycoside concentrations be measured?
If treatment is longer than 3 days or in cases of renal failure.
Examples of aminoglycosides
- Gentamicin
- Amikacin
What types of infections is Gentamicin used for?
Serious community infections, including pyelonephritis
When is Gentamicin combined with β-lactams?
For polymicrobial infections or for synergy, such as in enterococci and streptococcal endocarditis.
What type of infections is Amikacin used for?
Hospital-acquired infections.
What is aminoglycoside toxicity related to?
Prolonged elevated trough concentrations.
What are the two types of ototoxicity caused by aminoglycosides?
Cochlear ototoxicity (high tone deafness initially) and vestibular ototoxicity.
Is aminoglycoside-induced ototoxicity reversible?
It is irreversible in many cases.
What type of nephrotoxicity is caused by aminoglycosides?
Tubular toxin.
Is aminoglycoside-induced nephrotoxicity reversible?
Yes, it is reversible.
In which patient populations should aminoglycosides be avoided?
In the elderly and those with chronic kidney disease (CKD).
What enzymes do quinolones target?
DNA gyrase and topoisomerase IV.
What type of killing do quinolones exhibit?
Concentration-dependent killing.
How well are older (first generation) quinolones absorbed?
They are poorly absorbed
What is the spectrum of first generation quinolones?
Limited to Gram-negative aerobes.
What is an example of a first generation quinolone?
Nalidixic acid.
How readily does resistance arise with first generation quinolones?
Resistance arises readily.
How well are second generation fluoroquinolones absorbed?
They are well absorbed
What is the spectrum of second generation fluoroquinolones?
Includes Gram-negative aerobes (including Pseudomonas), but poor for Gram-positive bacteria.
How well are third generation fluoroquinolones absorbed?
They are well absorbed.
What is the spectrum of third generation fluoroquinolones?
Includes both Gram-positive bacteria (especially Streptococci) and Gram-negative bacteria (except Pseudomonas).
What are the common toxicities associated with quinolones?
Rashes, CNS effects (headache, dizziness, excitation, seizures), and tendonitis.
Why is the use of quinolones in children limited?
Due to animal toxicity, but they are OK for restricted indications.
How does resistance to quinolones generally develop?
By mutations in the target genes.
Due to recent toxicity concerns, for what type of infections are quinolones recommended?
Only for serious infections.
What is the drug of choice for bacterial dysentery, pyelonephritis, and prostatitis?
Ciprofloxacin (a second generation fluoroquinolone).
When can ciprofloxacin be used as an alternative to aminoglycosides?
For serious infections where aminoglycosides are typically used.
What is a notable use of ciprofloxacin for systemic infections?
Typhoid, although resistance is increasing.
What is moxifloxacin (a third generation fluoroquinolone) used for in the context of tuberculosis?
It is used for multi-drug resistant tuberculosis (MDR TB).
When can moxifloxacin be used as an alternative for respiratory tract infections?
Only if there is a severe beta-lactam allergy, and it covers atypical pneumonia agents as well as conventional bacterial causes of community-acquired pneumonia.
What is the mechanism of action of macrolides?
They inhibit protein synthesis by binding to the 50S ribosome subunit.
Are macrolides bacteriostatic or bactericidal?
Bacteriostatic.
What type of bacteria are macrolides primarily active against?
Gram-positive bacteria.
What is a concern with the use of macrolides against S. pneumoniae?
There is increasing resistance to macrolides in S. pneumoniae.
How is the bioavailability of erythromycin?
Erythromycin has fair bioavailability.
Example of a macrolides
Erythromycin
clarithromycin
azithromycin
How do newer macrolides like clarithromycin and azithromycin compare to erythromycin in terms of absorption and half-life?
Newer agents are better absorbed and have a longer half-life.
What are common gastrointestinal toxicities associated with macrolides?
Nausea, vomiting, and diarrhea.
Do macrolides inhibit CYP450 metabolism?
Yes, macrolides inhibit CYP450 metabolism, except azithromycin.
For which type of infections can macrolides be used as an alternative to penicillin in allergic patients?
For mild streptococcal and staphylococcal infections.
What atypical pneumonia agents are macrolides active against?
Legionella, Mycoplasma, and Chlamydophila.
Which macrolides are drugs of choice for H. pylori infection?
Clarithromycin and azithromycin.
Which macrolide is used as a single-dose treatment for Chlamydia urethritis and cervicitis?
Azithromycin.
Are macrolides used in the treatment of pertussis?
Yes, macrolides are drugs of choice for pertussis.
Can macrolides be used to treat chancroid?
Yes, macrolides are used in the treatment of chancroid.
Which macrolides are used to treat M. avium complex infections in AIDS patients?
Clarithromycin and azithromycin.
What is the mechanism of action of tetracyclines?
They inhibit protein synthesis by binding to the 30S ribosome subunit.
Are tetracyclines bacteriostatic or bactericidal?
Bacteriostatic
How can bacteria develop resistance to tetracyclines?
Through efflux pumps or enzymatic breakdown.
How does the absorption of tetracyclines vary, and which tetracycline has excellent absorption?
Absorption varies among tetracyclines, and doxycycline has excellent absorption.
What impairs the absorption of tetracyclines?
Divalent cations impair the absorption of tetracyclines.
Do tetracyclines have good intracellular penetration?
Yes, tetracyclines have good intracellular penetration.
What gastrointestinal toxicity is associated with tetracyclines?
Nausea and vomiting.
What skin-related toxicity is associated with tetracyclines?
Photosensitivity.
Why should tetracyclines be avoided in children under 8 years old and during pregnancy?
They can cause teeth discolouration.
Which bacterial infection is treated with tetracyclines as the drug of choice?
Rickettsia
Is tetracycline the drug of choice for brucellosis?
Yes, tetracycline is used for brucellosis
For what dermatological condition are low doses of tetracycline used?
Acne
Can tetracycline be used for prophylaxis of falciparum malaria?
Yes, it is used for prophylaxis of falciparum malaria.
Which sexually transmitted infection (STI) can be treated with tetracyclines, although now often superseded by azithromycin?
Chlamydia, including urethritis and pelvic inflammatory disease (PID).
Why is the usefulness of tetracyclines limited as a single agent for respiratory infections?
Because Streptococcus pneumoniae is often resistant.
How does cotrimoxazole work?
It blocks successive steps in the bacterial folate pathway, preventing nucleic acid synthesis
What are the two components of cotrimoxazole?
Sulfamethoxazole (a sulphonamide) and trimethoprim.
How is cotrimoxazole absorbed?
It is well absorbed orally.
What is the main side effect of cotrimoxazole?
Sulphonamide hypersensitivity, which can cause skin rashes.
What severe skin reactions can cotrimoxazole cause?
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.
Why is cotrimoxazole of minimal value outside of HIV?
Due to its toxicity and high prevalence of resistance in community-acquired Gram negatives and Streptococcus pneumoniae.
In HIV infection, what is cotrimoxazole the drug of choice for treating?
- Pneumocystis jirovecii pneumonia
- Toxoplasmosis
- Cystoisospora belli diarrhoea
What role does cotrimoxazole play in primary prophylaxis for HIV patients?
It prevents Pneumocystis jirovecii pneumonia, toxoplasmosis, and Cystoisospora belli diarrhoea, and reduces bacterial infections.
Why do HIV+ patients have a much higher frequency of rash with cotrimoxazole?
Especially with higher doses, HIV+ patients are more prone to rashes.
Is rechallenge or dose reduction often successful for cotrimoxazole-induced rashes in HIV+ patients?
Yes, rechallenge or dose reduction is often successful unless the reaction was severe
How does metronidazole exert its toxic effect on bacteria?
It is toxic to DNA, forming a highly reactive nitro radical with anaerobic metabolism Fe: S proteins.
How is metronidazole absorbed when taken orally?
It has good oral absorption
Besides oral, in what other forms is metronidazole available?
It is also available as PR (rectal) and IVI (intravenous).
How well is metronidazole tolerated in short courses?
It is well tolerated in short courses.
What common side effect does metronidazole cause that affects taste?
It causes a metallic taste.
What should be avoided when taking metronidazole due to a disulfiram-like effect?
Alcohol should be avoided.
What are the potential long-term toxic effects of metronidazole?
Neurotoxicity and neutropenia.
What types of anaerobic organisms is metronidazole effective against?
Cocci, Gram-negative bacilli, and Gram-positive spore-forming bacilli.
Which protozoan infections, lacking mitochondria, can be treated with metronidazole?
Entamoeba histolytica, Trichomonas vaginalis, and Giardia lamblia.
