Microbiology 3- Hospital Acquired Infection and immunity Flashcards
Describe Prontosil: the first example of a sulphonamide antibiotic
Bacteriostatic.
Synthetic
Examples include sulpha-methoxazole. Sometimes used together with Trimethoprim (co-trimoxazole).
Used to treat UTIs, RTIs, bacteraemia and prophylaxis for HIV+ individuals.
Becoming more common due to resistance to other antimicrobials, despite some host toxicity.
Describe beta-lactams
Interfere with the synthesis of the peptidoglycan component of the bacterial cell wall.
Examples include Penicillin and methicillin.
Bind to penicillin-binding proteins.
PBPs catalyse a number of steps in the synthesis of peptidoglycan.
What type of bacteria is prontosil effective against
Gram-negative
Describe the development of antibiotics and its importance
Prior to the discovery of prontosil & penicillin even minor infections were potentially fatal. Surgery was a major risk.
The potential of prontosil took years to be realised and was never patented to treat infection.
Penicillin was discovered by chance by Sir Alexander Fleming at St. Mary’s Hospital.
However, Fleming realised that an irritating contaminant actually held the key to defeating bacterial infections.
Chain, Florey and Heatly contributed to developing ways to mass produce and administer penicillin.
Fleming, Chain & Florey won the 1945 Nobel prize in Medicine or Physiology.
What is an antibiotic
An antibiotic is an antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms.
Most antibiotics in use today are produced by soil-dwelling fungi (Penicillium and Cephalosporium) or bacteria (Streptomyces and Bacillus).
However, antibiotics commonly used today encompass a range of natural, semi-synthetic and synthetic chemicals with antimicrobial activity.
What is meant by antimicrobial
Antimicrobial – chemical that selectively kills or inhibits microbes (bacteria, fungi, viruses).
What is meant by bactericidal
Kills bacteria
What is meant by bacteriostatic
Stops bacteria growing
What is meant by anti-septic
chemical that kills or inhibits microbes that is usually used topically to prevent infection.
Why has the development of antibiotics slowed
After 1950s no economic incentive to develop more antibiotics
What is meant by the minimal inhibitory concentration
Minimal inhibitory concentration (MIC) = the lowest concentration of AB required to inhibit growth
Describe antibiotic resistance
Low MIC- SENSITIVE
High MIC- RESISTANT
Breakpoint conc is clinically achievable concentration, hence bacteria with MIC higher than breakpoint are resistant.
Explain how resistance may exist before the antibiotic was used
Some strains may be resistant. Some isolates of S. aureus were resistant to penicillin from the start!
Routine use of penicillin provided selective pressure for the acquisition and maintenance of resistance genes.
Describe antibiotic by natural selection
Population contains cells with AB resitance due to mutations/acquired DNA – possibly with a fitness cost e.g. Slow growth
In absence of selection pressure (e.g. ABs) AB resistant strains have no advantage (and may have a disadvantage)
Low prevalence of AB resistant strains in patient population
In presence of selection pressure (e.g. Abs) resistant mutants outcompete WT
High prevalence of AB resistant strains in patient population
Describe the misconceptions at the dawn of the antibiotic era
Resistance against more than one class of antibiotics at the same time would not occur. Horizontal gene transfer would not occur. Resistant organisms would be significantly less ‘fit’ (sometimes true, sometimes not).
Describe the different mechanisms of bacterial genetic variability
Point mutations may occur in a nucleotide base pair, which is referred to as microevolutionary change. These mutations may alter the target site of an antimicrobial agent, interfering with its activity.
Macroevolutionary change results in rearrangement of large segments of DNA as a single event. These rearrangements may include inversions, duplications, insertions, deletions or transposition of large sequences of DNA from location of bacterial chromosome to another.
Acquisition of foreign DNA carried by plasmids, bacteriophages or transposable genetic elements. These foreign elements give the organism the ability to adapt to antimicrobial activity.
Describe the economic costs of antibiotic resistance bacteria
Less effective antibiotics results in increased morbidity, mortality, length of hospital stay and subsequent cost. Requires more antibiotics, which increases the chance for more resistance.
Increased time to effective therapy.
Requirement for additional approaches – e.g. surgery.
Use of expensive therapy (newer drugs).
Use of more toxic drugs e.g. vancomycin.
Use of less effective ‘second choice’ antibiotics.
Why do pharma companies not want to develop antibiotics
Less financial incentive, less profits in developing drugs that only certain people can use.
When does resistance usually emerge
Resistance usually emerges soon after the arrival of a new AB
List the major gram-negative bacteria that are multi-drug AB resistant
Pseudomonas aeruginosa Cystic fibrosis, burn wound infections. Survives on abiotic surfaces. E. Coli (ESBL) GI infect., neonatal meningitis, septicaemia, UTI. E. coli, Klebsiella spp (NDM-1) As above. Salmonella spp. (MDR) GI infect. , typhoid fever. Acinetobacter baumannii (MDRAB) Opportunistic, wounds, UTI, pneumonia (VAP). Survives on abiotic surfaces. Neisseria gonorrhoeae Gonorrhoea.
List the major gram-positive bacteria that are multi-drug AB resistant
Staphylococcus aureus (MRSA, VISA)
Wound and skin infect. pneumonia, septicaemia, infective endocarditis.
Streptococcus pneumoniae
Pneumonia, septicaemia.
Clostridium difficle
Pseudomembranous colitis, antibiotic-associated diarrhoea.
Enterococcus spp (VRE)
UTI, bacteraemia, infective endocarditis.
Mycobacterium tuberculosis (MDRTB, XDRTB) Tuberculosis
Describe aminoglycosides
E.g. Gentamicin, streptomycin.
Bactericidal.
Target protein synthesis (30S ribosomaml subunit), RNA proofreading and cause damage to cell membrane.
Toxicity has limited use, but resistance to other antibiotics has led to increasing use.
In general, aminoglycosides kill aerobic gram-negative enteric organisms (enteric organisms are the bugs that call the G.I tract their home). Most end in -mycin
Aminoglycosides are among the handful drugs that kill Pseudomonas aeruginosa
Why are aminoglycosides often used with penicillin.
Aminoglycosides must diffuse across the cell wall to enter the bacterial cell, so they are often used with penicillin, which breaks down this wall to facilitate diffusion.
List the side effects of aminoglycosides
Eighth cranial nerve toxicity: vertigo, hearing loss
Renal toxicity- removed by Kidney, follow patient BUN and creatine levels which increase with kidney damage
Neuromuscular blockade- unable to move muscle or breathe
Side effects occur if dose is high, the drug level I the blood is checked after steady state levels have been achieved.
