146 Questions
What was the major challenge in producing penicillium?
Difficulty in purifying
Who discovered streptomycin and in what year?
Waksman, 1944
What was used by ancient Greeks against tapeworms and roundworms?
Chenopodium ambrosioides (wormseed goosefoot)
What was the significance of streptomycin?
First antibiotic against tuberculosis
What was Lister's contribution to treatment of infections?
Use of carbolic acid to treat wound infections
What was the source of streptomycin?
Streptomyces griseus
What is the mechanism of action of bleach as a biocide?
Denaturing proteins
What is the stage of infection targeted by most antibiotics?
Multiplication in host tissue
What is the mechanism of action of beta-lactams?
Inhibition of cell wall formation
What was used to treat syphilis in the early 20th century?
Mercury
What was the limitation of sulfa drugs developed in the 1930s?
Limited spectrum of activity
What is the mechanism of action of sulphonamides?
Inhibition of metabolic pathways
What is the common name for Chenopodium ambrosioides?
All of the above
What is the stage of infection where the host defences are usually able to regain control?
Multiplication in host tissue
What was used to treat leprosy in the past?
Chaulmoogra oil
What is the percentage of IMS (isopropyl alcohol) commonly used as a biocide?
70%
What is the mechanism of action of Vancomycin?
Prevention of transglycosylation
What type of organisms harbor Extended-Spectrum Beta-Lactamases (ESBLs)?
Gram-negative organisms
What is the function of Penicillin-Binding Proteins (PBPs)?
Formation of cross-links between peptidoglycan chains
What is the consequence of beta-lactam antibiotics binding to PBPs?
Cell lysis
What is the mechanism of action of Beta-Lactamase enzyme?
Hydrolysis of beta-lactam ring
What is the consequence of Escherichia coli harboring ESBLs?
Increased resistance to beta-lactam antibiotics
What is the characteristic of Vancomycin-Resistant Enterococci (VRE)?
Resistance to Vancomycin
What is the characteristic of Cephalosporins?
Presence of a dihydrothiazine ring
What is the primary mechanism of action of quinolones?
Binding to gyrase, causing DNA uncoiling
Which of the following macrolides has improved bioavailability and half-life?
Azithromycin
What is the primary function of topoisomerases in bacterial chromosome replication?
Untwisting of supercoiled DNA by nicking one of the strands
What is the limitation of 1st generation quinolones, such as nalidixic acid?
They have a limited antibacterial spectrum of activity
What is the general mechanism of action of inhibitors of nucleic acid synthesis?
Interruption of nucleotide metabolism and synthesis, perturbation of DNA as a template, and inhibition of enzymatic processes
What is the significance of the interaction between gyrase, DNA, and quinolone molecules?
It stimulates the binding of quinolone to DNA
Which of the following quinolones is classified as a 3rd generation quinolone?
Lomefloxacin
How many gene products are involved in bacterial chromosome replication, according to the quinolone mechanism of action?
18
What type of infections is gonorrhoeae linked with?
UTIs, hospital acquired pneumonia, line infections, and sepsis
What is the mechanism of action of beta-lactamase inhibitors?
They inhibit the beta-lactamase enzyme, allowing the antibiotic to work effectively
What is the key difference between beta-lactams and vancomycin?
Beta-lactams bind to transpeptidase, while vancomycin binds to the D-alanyl-D-alanine terminus of the growing peptidoglycan chain
What is the mechanism of action of polymyxins?
They disrupt the inner and outer cell membranes, causing cell lysis
What is the role of autolysins in bacterial cell wall synthesis?
They break down the bacterial cell wall, allowing for the insertion of new peptidoglycan
What is the characteristic of beta-lactamase inhibitors that allows them to be effective?
They are able to bind irreversibly to the beta-lactamase enzyme
What is the result of the inhibition of transpeptidase by beta-lactams?
The cell wall becomes weaker and more prone to lysis
What is the difference between the mechanisms of action of beta-lactams and polymyxins?
Beta-lactams inhibit cell wall synthesis, while polymyxins disrupt the cell membrane
Triclosan is effective against viruses.
False
Arsphenamine is a true antibiotic.
False
Penicillium rubens is the species used for drug production.
False
Antibiotics work by affecting targets found in mammalian eukaryotic cells.
False
Bisphenol is effective against spores.
False
Chlorine denatures lipids.
False
Antimicrobial components were produced in sufficient quantities and purity for clinical use during the 1920s.
False
Salvarsan is a broad-spectrum antibiotic.
False
Streptomycin was discovered from Streptomyces griseus in 1942.
False
Penicillin is typically used to treat tuberculosis.
False
Quinolones target the cell wall/membrane to inhibit bacterial growth.
False
Daptomycin is an antibiotic that targets protein synthesis.
False
Most antibiotics target the attachment of bacteria to the epithelial surface.
False
Sulphonamides are a type of antibiotic that targets the cell wall/membrane.
False
Isoniazid is an antibiotic that targets protein synthesis.
False
Metronidazole is effective against bacterial infections.
False
Glycopeptides bind to the growing peptidoglycan chain and prevent transpeptidation.
False
Vancomycin is often regarded as an antibiotic of first resort.
False
Penicillin-binding proteins (PBPs) are responsible for transglycosylation in the growing cell wall.
False
Cephalosporins have a beta-lactam ring with a dihydrothiazine ring and a pentapeptide.
False
Beta-lactamase enzymes are produced by Gram-positive organisms.
False
ESBLs (Extended-Spectrum Beta-Lactamases) are harbored by Gram-positive organisms.
False
Vancomycin binds to penicillin-binding proteins (PBPs) in the growing cell wall.
False
Resistant organisms modify cell-wall precursors by replacing D-alanine with D-serine.
False
The rate of mcr-1 clinical resistance in E. coli in China was estimated to be 0.7% in 2016.
False
Colistin is effective against Pseudomonas aeruginosa.
False
Tigecycline is effective against all Gram-negative bacteria.
False
The rate of mcr-1 positive faecal E. coli samples from clinical settings was 20% in 2022.
False
Quinupristin-dalfopristin is effective against Gram-negative bacteria.
False
Linezolid is effective against Gram-negative bacteria.
False
Ceftazidime is a type of beta-lactamase inhibitor.
False
Polymyxins are effective against both Gram-positive and Gram-negative bacteria.
False
Transpeptidase enzymes break peptide bonds in bacterial cell wall synthesis.
False
Beta-lactamase inhibitors must bind reversibly to beta-lactamase to be effective.
False
Vancomycin targets the stage of infection where the host defenses are usually able to regain control.
False
Gonorrhoeae is linked with infections such as UTIs and hospital-acquired pneumonia.
True
The mechanism of action of beta-lactams is to disrupt the inner and outer cell membranes.
False
Clavulanate is a type of beta-lactam antibiotic.
False
Which bacterium is commonly associated with catheterisation or instrumentation?
Staphylococcus epidermidis
What is the recommended treatment for uncomplicated lower UTI in adults and children over 3 months old?
Trimethoprim and nitrofurantoin
Why should quinolones be avoided in pregnancy?
They can cause congenital abnormalities
What is a concern in patients with E. coli that produces ESBL enzymes?
Increased risk of resistance to multiple antibiotics
Why is nitrofurantoin avoided at term in pregnancy?
It can cause hemolysis in the newborn
What is the typical treatment route for upper UTI (acute pyelonephritis)?
IV antibiotics initially, followed by oral antibiotics
What is the primary consequence of stepwise proliferation of antimicrobial-tolerant strains?
Development of resistance to antibiotics
What is the characteristic of aminoglycosides in the context of Pseudomonas aeruginosa?
Increasing resistance among members of this group
What is the significance of the sustained presence of antibiotics?
It allows the small population of tolerant cells to replicate
What is the consequence of ineffective treatment against Pseudomonas aeruginosa?
Only a few members of the beta-lactam group are effective
What is the role of specialist anti-pseudomonal antibiotics?
To treat Pseudomonas aeruginosa infections
What is the significance of beta-lactam antibiotics?
Only a few members of this group are effective against Pseudomonas aeruginosa
What is the term for bacteria having a higher-than-expected minimum inhibitory concentration (MIC)?
Tolerance
What is the purpose of determining the minimum inhibitory concentration (MIC)?
To determine the susceptibility of bacteria to antibiotics
What is the principle behind the disc-diffusion method of measuring antibiotic susceptibility?
Antibiotics diffuse into the agar, creating a radial concentration gradient
What is the significance of antibiotic breakpoints?
They interpret the results of antibiotic susceptibility tests
What is the advantage of molecular methods for ascertaining resistance?
They can identify specific resistance genes
What is the consequence of selective pressure on bacterial populations?
Increased resistance to antibiotics
What is the primary reason for preserving and conserving penicillin despite Staphylococcus aureus resistance?
It is still important for treating Streptococcal infections, Syphilis, and Listeriosis.
What is the current recommended treatment for Gonococcal disease?
Ceftriaxone and Azithromycin
What is the most common cause of urinary tract infections?
E. coli
What is the consequence of untreated urinary tract infections?
All of the above
Why are steroids preferably administered before the first antibiotic dose in Meningococcal disease treatment?
To reduce the risk of shock
What is the primary mechanism of action of antibiotics used to treat Meningococcal disease?
Inhibition of cell wall synthesis
What is the significance of benzyl penicillin and amoxicillin in the treatment of Meningococcal disease?
They are used to treat Meningococcal disease and have a low risk of resistance
What is the primary role of vasoactive treatments in Meningococcal disease?
To reduce the risk of shock
What is a consequence of antimicrobial resistance according to the WHO?
Longer hospital stays
What is the projected total global antibiotic consumption from 2000 to 2030?
Billions of DDDs
What is a major challenge posed by antimicrobial resistance?
Compromised organ transplants
What is the estimated number of surgical admissions in the UK per year?
4.5 million
What is the percentage of the UK population that has diabetes?
6%
What is the title of the review on antimicrobial resistance?
Antimicrobial Resistance: Tackling a Crisis
What is the estimated number of new cancer cases per year?
350,000
What is the estimated number of transplants per year?
5,000
Pseudomonas aeruginosa is often associated with catheterisation or instrumentation.
False
Nitrofurantoin is avoided during pregnancy.
False
E. coli with ESBL enzymes are sensitive to nitrofurantoin.
True
Upper UTI treatment usually involves oral antibiotics.
False
Staphylococcus epidermidis is usually associated with sexually active people.
False
Trimethoprim is avoided in patients with renal impairment.
False
Staph.aureus resistance to penicillin makes it an ineffective treatment for meningitis.
False
Neisseria gonorrhoea is susceptible to all antibiotics introduced for its treatment.
False
Cefixime is a first-line treatment for Meningococcal disease.
False
E.coli is a rare causative organism of urinary tract infection.
False
Klebsiella / Proteus spp. are rare causative organisms of urinary tract infection.
False
Penicillin is the primary treatment for Syphilis.
True
Only a few members of the aminoglycoside group are effective against Pseudomonas aeruginosa.
False
Benzyl penicillin is a second-line treatment for Meningococcal disease.
False
The presence of an antibiotic leads to the immediate elimination of all bacterial mutants.
False
Specialist anti-pseudomonal antibiotics are rarely used to treat Pseudomonas aeruginosa.
False
Steroids are used as a maintenance therapy for shock in Meningococcal disease.
True
The stepwise proliferation of antimicrobial-tolerant strains can lead to increased sensitivity to antibiotics.
False
Beta-lactam antibiotics are effective against Pseudomonas aeruginosa due to its lack of resistance to this group.
False
The sustained presence of antibiotics can lead to the elimination of all tolerant cells.
False
A broth dilution test measures the minimum bactericidal concentration of an antibiotic.
False
Tolerance to antibiotics is the same as resistance to antibiotics.
False
Antibiotic breakpoints are based on the MIC of an antibiotic.
False
Molecular methods for ascertaining resistance require phenotypic methods to identify the MIC.
False
The disc-diffusion test measures the MIC of an antibiotic.
False
Quantitative methods for measuring antibiotic susceptibility and resistance are only used for research purposes.
False
Around 6% of the UK population have diabetes.
True
The predicted total global antibiotic consumption from 2000 to 2030 is in millions of DDDs.
False
The book 'Microbiology – An introduction' by Tortora, GJ is the main textbook for the module.
True
The Review on Antimicrobial Resistance was chaired by Eili Y. Klein.
False
Around 5000 organ transplants are performed every year.
True
The book 'Antibiotics and Chemotherapy: anti-infective agents and their use in therapy' by Finch et al. is available on Bibliu.
False
Antimicrobial resistance is predicted to cause more deaths than cancer chemotherapy by 2030.
True
The ISBN of the book 'Antimicrobial Chemotherapy' by Greenwood et al. is 0443071292.
False
Study Notes
A Brief History of Antimicrobial Chemotherapy
- Early treatments against infectious diseases:
- Oils and crude plant extracts as anti-helminths (e.g. Chenopodium ambrosioides for tapeworms and roundworms)
- Quinine for malaria
- Mercury for syphilis
- Chaulmoogra oil for leprosy
- Lister used carbolic acid to treat wound infections, but it had low efficacy and was damaging to healthy tissue
- In the 1900s, arsenicals were used as antiprotozoal agents and for schistosomiasis and syphilis
- Sulfa drugs were introduced in the 1930s, but had a limited spectrum of activity
Biocides: Disinfectants and Antiseptics
- 70% IMS/isopropyl alcohol/rubbing alcohol: denatures proteins and has a broad spectrum of activity
- Bleach: difficult to purify and produce in clinically useful amounts
Mechanisms of Action and Resistance
- Nucleic acid synthesis inhibitors:
- Quinolones bind to unpaired DNA bases and have a complex interaction with gyrase, DNA, and quinolone molecules
- Inhibit topoisomerases, which untwist supercoiled DNA by 'nicking' one of the strands
- Cell wall/membrane inhibitors:
- Beta-lactams (e.g. penicillin) bind to penicillin-binding proteins (PBPs) in the growing cell wall, inhibiting cross-links between peptidoglycan chains and leading to cell lysis
- Vancomycin binds to the growing peptidoglycan chain and prevents transglycosylation
- Protein synthesis inhibitors:
- Anti-metabolites (e.g. sulphonamides, trimethoprim) inhibit enzyme activity
- Glycopeptides (e.g. vancomycin) bind to the growing peptidoglycan chain and prevent transglycosylation
Beta-Lactam Antibiotics
- Mechanism of action:
- Bind to penicillin-binding proteins (PBPs) in the growing cell wall
- Inhibit cross-links between peptidoglycan chains, leading to cell lysis
- Different classes of beta-lactams:
- Penicillins (e.g. penicillin G, ampicillin)
- Cephalosporins (e.g. cephalosporin C, cephalexin)
- Extended-spectrum beta-lactams (ESBLs)
- Beta-lactamase inhibitors:
- Clavulanate: binds to beta-lactamase and inhibits its activity
- Tazobactam: binds to beta-lactamase and inhibits its activity
Inhibitors of Cell Membrane Function and Synthesis
- Polymyxins:
- Disrupt inner and outer cell membranes, causing cell lysis
- Act only on Gram-negative bacteria
Inhibitors of Nucleic Acid Synthesis
- Quinolones:
- Bind to unpaired DNA bases and have a complex interaction with gyrase, DNA, and quinolone molecules
- Inhibit topoisomerases, which untwist supercoiled DNA by 'nicking' one of the strands
- Have a broad spectrum of activity, with 1st, 2nd, 3rd, and 4th generation quinolones having increasing potency
Antimicrobial Agents
- Triclosan dissolves lipids and is ineffective against spores and some viruses.
- Chlorine denatures proteins, affecting multiple targets in the membrane and cytoplasm.
- Bisphenol is found in dentifrices and incorporated into plastic and fabrics.
Principles of Selective Toxicity
- Antibiotics work by targeting bacterial cells, not mammalian eukaryotic cells.
- Antibiotics become concentrated in bacterial cells, not host cells.
Types of Antibiotics
- Bactericidal antibiotics kill bacteria, while bacteriostatic antibiotics inhibit bacterial growth.
- Antibiotics vary in their ability to fulfill the criteria of selective toxicity.
Discovery of Clinically Useful Antibiotics
- Paul Ehrlich developed arsphenamine (Neosalvarsan) in 1912, which has limited activity against spirochaetes.
- Penicillium chrysogenum is used for drug production, not Penicillium rubens, which was discovered by Flemming.
- Mary Hunt discovered antimicrobial components in the 1930s.
- Selman Waksman discovered streptomycin, the first drug to treat tuberculosis, in 1944.
Mechanisms of Action
- Nucleic acid inhibitors: quinolones, metronidazole
- Cell wall/membrane inhibitors: beta-lactams, vancomycin
- Protein synthesis inhibitors: sulphonamides, trimethoprim
- Anti-metabolites: isoniazid
Beta-Lactam Antibiotics
- Bind to penicillin-binding proteins (PBPs) in growing cell walls
- Inhibit cross-links between peptidoglycan chains, causing cell lysis
- Cephalosporins have a beta-lactam ring with a dihydrothiazine ring
- Different classes of beta-lactams: penicillinases, extended-spectrum beta-lactamases (ESBLs), metallo-beta-lactamases, cephalosporinases
Beta-Lactamase Inhibitors
- Have a lactam ring, but are weak antibiotics
- Must have higher affinity for inhibitor than drug
- Inhibitor must bind irreversibly to beta-lactamase
- Examples: clavulanate, sulbactam
Difference between Beta-Lactams and Vancomycin
- Beta-lactams bind to transpeptidase, while vancomycin binds to the growing peptidoglycan chain
- Autolysins break peptide bonds, but no further bonds are created with vancomycin
Polymyxins
- Disrupt inner and outer cell membranes, causing cell lysis
- Act only on Gram-negatives
- Examples: polymyxin B, polymyxin E (colistin)
Impact of Colistin Resistance
- First clinical infection caused by a colistin-resistant strain in the US in 2016
- Estimated 1.4% of E. coli and 0.7% of Klebsiella pneumoniae isolates in China are resistant
- Newer molecular measures are more reliable in detecting resistance
Importance of Preserving Antibiotics
- Despite Staphylococcus aureus resistance, penicillin remains important for treating:
- Listeriosis
- Meningitis
- Streptococcal infections
- Syphilis
Treatment of Meningococcal and Gonococcal Diseases
- Meningococcal disease:
- Treated with IV antibiotics (benzyl penicillin or amoxicillin)
- Rare occurrence of drug resistance
- Maintenance therapy for shock (fluids, etc.)
- Vasoactive treatments (IV adrenaline and steroids)
- Experimental therapies (anti-cytokine and anti-endotoxin) have been investigated
- Gonococcal disease:
- Developed resistance to all antibiotics introduced for treatment
- 3rd generation cephalosporins (e.g. cefixime or ceftriaxone) are first-line treatments
- Dual treatments (e.g. ceftriaxone and azithromycin) are now recommended due to the emergence of "superbugs" resistant to ceftriaxone
Urinary Tract Infections (UTIs)
- Can cause fever, loin pain, and ascending infection
- Secondary spread can lead to:
- Renal abscess
- Bacteremia
- Pyelonephritis
- Cystitis (exacerbated by urinary stasis)
- Prostatitis
- Urethritis
- Epididymitis
- Contamination from faecal/perineal flora is a common cause of UTIs
- Aetiological agents of UTIs include:
- E. coli (very common)
- Klebsiella/Proteus spp. (less common)
- Pseudomonas aeruginosa (hospital-associated)
- Staphylococcus epidermidis (associated with catheterization or instrumentation)
- Enterococcus faecalis
- Chlamydia trachomatis (in sexually active people)
- Neisseria gonorrhoea
Treatment Guidelines and Precautions for UTIs
- Uncomplicated lower UTI:
- Trimethoprim and nitrofurantoin are recommended (concentrated in urine and remain active in the bladder)
- Variations in dose for different patient groups
- Pregnancy:
- Avoid quinolones and trimethoprim
- Nitrofurantoin: avoid at term, use amoxicillin or cephalosporin instead
- E. coli with ESBL enzymes:
- Increasing prevalence
- Nitrofurantoin remains sensitive
- Renal impairment:
- Caution when using antibiotics in this patient group
- Upper UTI (acute pyelonephritis):
- Antibiotics are initially administered via IV route due to septicaemia risk
- Cephalosporin, quinolone, and gentamicin are used
- Pseudomonas aeruginosa has intrinsic resistance
Antibiotic Resistance and Consequences
- Antimicrobial resistance (AMR) compromises:
- Organ transplant
- Cancer chemotherapy
- Diabetes management
- Routine surgery (e.g. hip replacements, caesarians)
- Other impacts of AMR:
- Longer hospital stays
- Longer time intubated
- Longer duration of antibiotic treatment
- Greater financial costs
- Predicted deaths attributable to AMR are expected to surpass deaths from other causes by 2050
Importance of Preserving Antibiotics
- Despite Staphylococcus aureus resistance, penicillin remains important for treating:
- Listeriosis
- Meningitis
- Streptococcal infections
- Syphilis
Treatment of Meningococcal and Gonococcal Diseases
- Meningococcal disease:
- Treated with IV antibiotics (benzyl penicillin or amoxicillin)
- Rare occurrence of drug resistance
- Maintenance therapy for shock (fluids, etc.)
- Vasoactive treatments (IV adrenaline and steroids)
- Experimental therapies (anti-cytokine and anti-endotoxin) have been investigated
- Gonococcal disease:
- Developed resistance to all antibiotics introduced for treatment
- 3rd generation cephalosporins (e.g. cefixime or ceftriaxone) are first-line treatments
- Dual treatments (e.g. ceftriaxone and azithromycin) are now recommended due to the emergence of "superbugs" resistant to ceftriaxone
Urinary Tract Infections (UTIs)
- Can cause fever, loin pain, and ascending infection
- Secondary spread can lead to:
- Renal abscess
- Bacteremia
- Pyelonephritis
- Cystitis (exacerbated by urinary stasis)
- Prostatitis
- Urethritis
- Epididymitis
- Contamination from faecal/perineal flora is a common cause of UTIs
- Aetiological agents of UTIs include:
- E. coli (very common)
- Klebsiella/Proteus spp. (less common)
- Pseudomonas aeruginosa (hospital-associated)
- Staphylococcus epidermidis (associated with catheterization or instrumentation)
- Enterococcus faecalis
- Chlamydia trachomatis (in sexually active people)
- Neisseria gonorrhoea
Treatment Guidelines and Precautions for UTIs
- Uncomplicated lower UTI:
- Trimethoprim and nitrofurantoin are recommended (concentrated in urine and remain active in the bladder)
- Variations in dose for different patient groups
- Pregnancy:
- Avoid quinolones and trimethoprim
- Nitrofurantoin: avoid at term, use amoxicillin or cephalosporin instead
- E. coli with ESBL enzymes:
- Increasing prevalence
- Nitrofurantoin remains sensitive
- Renal impairment:
- Caution when using antibiotics in this patient group
- Upper UTI (acute pyelonephritis):
- Antibiotics are initially administered via IV route due to septicaemia risk
- Cephalosporin, quinolone, and gentamicin are used
- Pseudomonas aeruginosa has intrinsic resistance
Antibiotic Resistance and Consequences
- Antimicrobial resistance (AMR) compromises:
- Organ transplant
- Cancer chemotherapy
- Diabetes management
- Routine surgery (e.g. hip replacements, caesarians)
- Other impacts of AMR:
- Longer hospital stays
- Longer time intubated
- Longer duration of antibiotic treatment
- Greater financial costs
- Predicted deaths attributable to AMR are expected to surpass deaths from other causes by 2050
Learn about the history of antimicrobial chemotherapy, antibiotic drug classes, mechanisms of action and resistance, and understand recent trends in antimicrobial consumption.
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