Antibiotics MOA Flashcards
Define Infection
invasion & multiplication of pathogenic microbes
Define Antibiotic
= anti-bacterial medication (not including disinfectants)
Define anti-bacterial
kills or inhibits growth of bacteria
Define broad spectrum
active against many bacteria (may kill normal flora)
Define narrow spectrum
active against few bacteria (may not kill all pathogens
Define Bactericidal
kills bacteria (by affecting bacterial cell wall)
Define bacteriostatic
inhibits growth of bacteria (by affecting RNA & DNA)
What is MINIMUM BACTERICIDAL CONCENTRATION (MBC)
lowest concentration that kills 99.9% of a population
what is Minimum inhibitory concentration (MIC)
lowest concentration which inhibits visible growth of bacteria
what is Breakpoint
MIC cut-off which separates strains where there is a high likelihood of treatment succeeding from those where treatment is more likely to fail
Describe Bacteria
size?
DNA?
metabolism?
cell wall?
Bacteria : 1 – 10 μm in size
DNA as a single chromosome (prokaryotes)
Independent metabolism & no organelles
Cell wall (different from cell membranes of host organism)
Peptidoglycan cell wall = Gram stain +ve
Lipopolysaccharide cell wall = Gram stain -ve
How are bacteria classified?
Bacteria are classified based on Gram staining & shape
- Gram = positive or negative
- Shape = coccus or bacillus/rod
Name examples of Gram positive cocci
Staphylococcus species, Streptococcus species
Name examples of Gram positive bacilli
Bacillus anthracis, Lactobacilli species
Name examples of gram negative cocci
Neisseria meningitidis, Haemophilus influenzae
name examples of Gram negative bacilli
Escherichia coli, Salmonella species
What are the potential targets of antibiotics?
- Bacterial cell wall
- Bacterial RNA & protein synthesis
- Bacterial DNA structure & function
- Folic acid synthesis
Which type of antibiotics target the bacterial cell wall?
usually bactericidal
Beta-lactams (penicillins, cephalosporins & carbapenems)
Glycopeptides
Which type of antibiotic targets Bacterial RNA & protein synthesis?
usually bacteriostatic
Macrolides
Lincosamides
Tetracyclines
Aminoglycosides
Which type of antibiotic targets Bacterial DNA structure & function
bactericidal if high dose
Quinolones
Nitroimidazoles
Nitrofurantoin
Which type of antbiotic targets Folic acid synthesis (required for DNA synthesis)
usually bacteriostatic
Trimethoprim
Sulphonamides
Describe Beta-Lactams (Penicilins)
What is their target?
Penicillins :
Target : bacterial cell wall (bactericidal) - cell lysis by blocking cell wall synthesis
Penicillin (original & sometimes still the best) eg. tonsillitis
Amoxicillin (enhanced uptake by bacteria) eg. LRTI
Flucloxacillin (penicillinase-resistant) eg. SSTI
Co-amoxiclav (beta-lactamase inhibitor) eg. mixed infections
Benzylpenicillin
Piperacillin-tazobactam (anti-pseudomonal) eg. complex LRTI
Describe Beta-Lactams (Cephalosporins)
What is their target?
Target = Bacterial cell wall (bactericidal)
Ceftriaxone = 4th generation
Later generations have ↑ spectrum of activity
but also kill more natural flora (& ↓ efficacy against Gram +ves)
Used in bacterial meningitis & orthopaedic infections (ceftriaxone)
What is the target of Beta-Lactams - Carbapenems
Target : bacterial cell wall (bactericidal)
Examples : meropenem, ertapenem
Uses : infections in ITUs, complex & multi-drug resistant UTIs
What is the target of macrolides?
Target : RNA & bacterial protein synthesis (bacteriostatic)
Examples : erythromycin, clarithromycin, azithromycin
Uses : URTI, LRTI, SSTI (in place of penicillins)
Atypical LRTIs (intracellular organisms)
What is the target of Lincosamides?
Target : RNA & bacterial protein synthesis (bacteriostatic)
Example : clindamycin
Uses : SSTI (in place of penicillins or when IV access is limited)
Note : excellent bioavailability & tissue penetration when taken orally
What is the target for Tetracyclines?
Target : RNA & bacterial protein synthesis (bacteriostatic)
Example : doxycycline, Tetracycline
Uses : “atypical” bacteria that lack usual cell wall eg. Chlamydia, Mycoplasma
Rickettsia infections eg. typhus
What is the target of Aminoglycosides?
Target : RNA & bacterial protein synthesis (bactericidal if high dose)
Example : gentamicin
Uses : severe Gram –ve infections
synergistic treatment for endocarditis
Note : renal toxicity & need for therapeutic drug monitoring limits use
What is the target for Quinolones?
Examples?
Uses?
Target : bacterial DNA structure & function (bactericidal if high dose)
Examples : ciprofloxacin, levofloxacin
Uses : Gram –ve infections (excluding anerobes)
MRSA infections
LRTIs (levofloxacin only)
Note : also associated with CDAD
What is the target for Nitroimidazoles?
Example?
Uses?
Target : bacterial DNA structure & function (bactericidal if high dose)
Example : metronidazole
Uses : anaerobic infections (abscesses)
What is the target for Ntrofurantoin?
Uses?
Target : bacterial DNA synthesis (bactericidal if high dose)
Uses : uncomplicated UTIs
Note : poor bioavailability, but is concentrated in urine
What is the target for anti-folates?
Example?
Uses?
Target : folic acid synthesis & so DNA synthesis (bacteriostatic)
Examples : trimethoprim, sulphonamides
Uses : uncomplicated UTIs (but not in pregnant women)
What do you need to consider when choosing an antibiotic?
- Sepsis & supportive treatments
- Use the diagnostic process
- Microbiology tests
- Consider antibiotic guidelines
What is the Sepsis 6 care bundle?
- Give high-flow oxygen
- Take blood cultures
- Give empirical IV antibiotics
- Measure FBC & serum lactate
- Start IV fluid resuscitation
- Start accurate urine output measurements
Briefly outline the diagnostic process?
History = PC, HPC, PMH, ADT, FH, SH, ROS
↓
Examination = General, CVS, RS, ABDO, NS, LMS etc.
↓
Differential Diagnosis
↓
Investigations = (bedside), body fluids, imaging, physiology, histopathology
↓
Diagnosis
↓
Treatment
What microiology samples would you request?
Samples : Swabs = pus, skin, nose, throat, urethra, vagina etc.
Body fluids = pus, urine, faeces, blood, CSF etc.
Body tissues = biopsies (rarely)
What microbiology investigations would you request?
Can be divided into direct & indirect techniques …
Direct :
- Microscopy, culture & sensitivity (usually refers to bacteria or fungi)
- Antigen detection tests (eg. malaria, Legionella, C. difficile toxin)
- PCR tests (eg. Mycobacteria, 16S Ribosomal DNA)
Indirect :
• Serology tests (eg. rare or neglected tropical infections)
Name some factors affecting antiobiotic choice relating to the organism
- Known organism +/- sensitivities & resistance profile
- Or the most likely organisms and their sensitivities/resistance
Name some factors affecting antiobiotic choice relating to the patient
- Allergy/Intolerance
- Renal & liver function
- Severity of infection/Is patient immunocompromised?
- Risk of antibiotic-associated infection
- Route of administration
- Interactions with other medication
- age/ethnic group
- Pregnant, breast feeding or taking oral contraception
Why do we need antibiotic guidelines?
- To produce effective and efficient treatment
- To reduce over-pescribing and use of broad spectrum antibiotics which can lead to antibiotic resistance and other complicatons
