What are the antimicrobial drug groups based on
– Chemical Structure
– Mechanism of Action (MoA)
– Spectrum of Activity
β-Lactam antibiotics
β-Lactam antibiotics are one of the most important
groups of antibiotics
– Include Penicillins, Cephalosporins and Carbapenem
Penicillins
– Effective primarily against gram-positive bacteria
– Some synthetic forms are effective against some
gram-negative bacteria
– Target cell wall synthesis
β-lactams: Penicillins
Penicillin G is produced by the fungus Penicillium chrysogenum Targets cell wall synthesis Effective primarily against Gram-positive bacteria Semi-synthetic forms effective also against some Gram-negatives
Resistance to Antimicrobial Drugs
Misuse can increase spread of antibiotic resistance:
• Use of antibiotics for inappropriate conditions such as the common cold
• Failure to complete the full course of antibiotics
• Use of outdated, weakened antibiotics
• Excessive non-medical usage of antibiotics
Bacteria gain acquired resistance in what two ways
- Point mutations in chromosomal genes
* Acquisition of R plasmids via conjugation, transformation or transduction
Mechanisms of antibiotic resistance
- Slow or prevent the entry of drug into the cell
- Produce an enzyme that destroys or deactivates drug
- Pump antimicrobial drug out of the cell before it can act
- Alter target of drug so it binds less effectively
3 Examples of Bacterial Pathogens that are
Multi-Drug Resistant(“Superbugs”)
MRSA: Methicillin-resistant Staphylococcus aureus
VRE: Vancomycin-resistant Enterococci
MDR-TB: Multi-drug resistant Mycobacterium tuberculosis
Antimicrobial Resistance: Global Report on Surveillance, WHO 2014
Antimicrobial resistance (AMR) threatens the
effective prevention and treatment of an ever-
increasing range of infections caused by
bacteria, parasites, viruses and fungi.
Patients with infections caused by drug-
resistant bacteria are generally at increased
risk of worse clinical outcomes and death, and
consume more healthcare resources than
patients infected with the same bacteria that
are not resistant.
Gonorrhoea
The second most common bacterial STI in New Zealand after chlamydia
In New Zealand and other countries, gonorrhoea is treated with antibiotics as follows:
- a single dose of an injection with ceftriaxone
- a single dose of tablet with azithromycin
Treatment of enterococcal infections
Vancomycin is used in combination with an aminoglycoside
to treat enterococcal infections with penicillin MIC > 8 mg/L
Principles of antimicrobial use
The Antimicrobial Creed
M Microbiology guides therapy wherever possible
I Indications should be evidenced-based
N Narrowest spectrum therapy required
D Dosage individualised to the patient and appropriate to the site and type of infection
M Minimise duration of therapy
E Ensure oral therapy is used where clinically appropriate
Antibiotic Therapies
Prophylactic therapy: aims to prevent
infection when there is a significant
clinical risk of infection developing
Empirical therapy: treats an
established infection when the
causative agent has not been
identified
Directed therapy: treats an
established infection when the
pathogen has been identified
Clinical Considerations in Prescribing Antimicrobials
Routes of Administration
– Topical application of drug for external infections
– Oral route requires no needles and is self-administered
– Intramuscular administration delivers drug via needle
into muscle
– Intravenous administration delivers drug directly to
bloodstream
– Must know how antimicrobial agent will be distributed to
infected tissues
Safety and Side Effects
– Toxicity
• Cause of many adverse reactions is poorly
understood
• Drugs may be toxic to kidneys, liver, or nerves
– Allergies
• Allergic reactions are rare but may be life threatening
• Anaphylactic shock
– Disruption of normal microbiota
• May result in secondary infections
• Overgrowth of normal flora, causing superinfections
Tackling Antibiotic Resistance
- Antimicrobial Stewardship
i. e. an organised antimicrobial management program in line with therapeutic guidelines and local incidence of antimicrobial-resistant pathogens - Infection Control
i. e. prevention of the spread of antibiotic resistant organisms particularly in healthcare settings according to national / international standards - Development of New Antibiotics
i. e. discovery of new classes of antibiotics or synthetic derivatives
Multi-Drug Resistant(MDR) TB + treatment
Resistant to both isoniazid AND rifampin
Intensive phase 4 to 6 months
Continuation phase 5 months
In patients with rifampicin-resistant or multidrug-resistant TB, a regimen with at least five effective TB medicines during the intensive phase is recommended, including:
pyrazinamide and four core second-line TB medicines
- one chosen from group A
- one from group B
- and at least two from group C
Controlling Antimicrobial Resistance
- Use antimicrobials conservatively and specifically in therapy
- Use an adequate dose and duration of therapy so as to eliminate the pathogen but also minimize risk of selecting resistant strains
- Select antimicrobials according to susceptibility of the target pathogen
- Use narrow spectrum antibiotics where possible
- Use combinations of antimicrobials where they are known to prevent emergence of resistant mutants
- Use antimicrobials prophylactically only when it is proven to be valuable, and for the shortest possible time so as to reduce chance of resistance evolving
- Use good hygiene to prevent spread of microorganisms
- Isolate patients infected with resistant strains, use protective measures for those that are highly susceptible
- Epidemiologically monitor resistant organisms and apply enhanced control measures if a problem develops
- Avoid environmental contamination with antimicrobials, and restrict the
use of therapeutically valuable antimicrobials for non-medical (e.g. agricultural) purposes
Combating antibiotic resistance requires emphasis on
- Antimicrobial Stewardship
- Infection Control
- Development of New Antibiotics
What is promoting the spread of antimicrobial resistance
Overuse and misuse of antibiotics
Gene causing many bacteria to be resistant to penicillin
The spread of a gene encoding β-lactamase activity, which destroys the β-lactam ring of penicillins, has rendered many bacteria resistant to penicillin.
What do β-lactam antibiotics target
target peptidoglycan synthesis in bacteria
