L16 - antimicrobial chemotherapy Flashcards
Centor criteria definition
gives an indication of the likelihood of a sore throat being due to bacterial infection
Centor criteria
tender anterior neck glands, fever over 38 degrees, absence of cough
IF 3/4 cantor criteria are met…
positive predictive value is 40-60%
Absence of 3/4 cantor criteria…
fairly high negative predictive value of 80%
Antiviral
a small molecule that works by blocking nucleic acid synthesis or binding a target site on a receptor or enzyme
can prevent through many different areas of virus lifecycle
Antiviral usually used in…
treatment for humans in influenza A and B, and RSV
Flu antiviral
neuraminidase inhibitors, competitive inhibitors of flus neuraminidase enzyme
binds to enzyme to prevent vision release therefore halted viral replication
Flu antiviral effectiveness
shortens symptoms by half a day in adults compared to placebo, no reliable evidence for reducing risk being admitted to hospital or developing other conditions
Flu antiviral NICE indication
used for people in at-risk groups, need to start treatment within 48 hours of first symptoms, or 36 within children
Ribavirin
Nucleoside inhibitor, analogue of guanosine, stops viral RNA synthesis, good in vitro activity against RSV and studies show inconsistent results
reserved for immunocompromised children with severe RSV infection
Ribavirin results
possible shorter duration, less need for ventilator or oxygen BUT TERATOGENIC
early use of inhaled ribavirin has been shown to reduce morbidity and mortality in adult bone marrow cell transplant recipients
Antibiotic
molecules that work by binding a target site on a bacteria
target points of biochemical reactions crucial to bacteria survival
crucial binding site varies with antibiotic class
S. Pneumoniae
gram positive cocci, alpha haemolytic, optocochia sensitive with over 90 serotypes. any age, can be severely ill with respiratory failure or sepsis
invasive pneumococcal disease
S. Pneumonia treatment
B-lactam antibiotics i.e. amoxicillin, cefuroxime, cefotaxime
macrolides, clarithromycin, fluoroqinolines and ciproflaxacin
H. Influenzae
Gram negative cocobacilli, originally thought to be influenza cause, encapsulated or un-encapsulated
H. Influenza treatment
amoxicillin and calvulanic acid (co-amoxiclave)
tetracyclines - deoxycyclone
but not macrolides
Staph. Aureus
may complicate recent influenza, ventilator-associated pneumonia
Staph. Aureus treatment
Flucloxacillin, cerfuroxime, vancomycin, linezolid
Klebsiella pneumoniae
fram-negative bacilli, enterobacteriacane
normal flora of mouth and intestines
effects mainly homeless, alcoholics and hospital-associated
klebsiella pneumoniae treatment
Co-amoxiclav and cephalosporins
Atypical pathogens
difficult to detect as they are intracellular, don’t grow on agar easily and need serology, need special antibiotics
Atypical pathogen treatment
need special antibiotics as not susceptible to B-lactam and penicillin
macrolides, fluorquinolones and tetracyclines
Hospital-acquired pneumonia early onset
under 5 days in hospital
organisms similar to CAP and anaerobes
Metronidazole or use a B-lactam with inhibitor of B-lacatamase i.e. co-amoxiclav or piperacillin-tazobactam
Hospital-acquired pneumonia late onset
over 5 days
Staph. Aureus including methicillin-resistant
Pseudomonas aeruginosa
Acinetobcteria baumanii and klebsiella pneumoniae
Pulmonary tuberculosis
curable, treat with at least 4 drugs for 6 months
TB UK treatment
Rifampicin and isoniazid for 6 months or 12 if in CNS
Directly observed therapy for TB
give meds in supervised fashion 3 or more a week
Rifampicin
Enters bacilli in a conc-dependent manner, achieving steady-state conc. within 15 mins
Drug binds to B-syunit of DNA-dependent RNA polymerase to form a stable drug-enzyme complex, suppressing chain formation in RNA synthesis
Pyrazinamide
Activated to pyrazinoic acid under acidic conditions that likely prevail at edges of necrotic TB cavities where inflammatory cells produce lactic acid
inhibition of fatty acid synthase type I leading to interference with mycelia acid synthesis
binding to ribosomal protein S1 and inhibition of trans-translation
reduction of intracellular pH disruption of membrane transport by HPOA
Isonazid
enters bacilli by passive diffusion
Drug is not directly toxic to bacillus but must be activated to its toxic form within the bacillus by KatG
activated drug forms adducts with bacillary NAD+ and NADP+ that inhibit essential steps in mycelia acid synthesis and nucleic acid synthesis
KatG
multifunctional catalase peroxidase
Mycolic acid
part of cell wall
Change of antibiotic target
bacteria changes the molecular configuration of antibiotic binding or masks it
Destruction of antibitoi
destroyed or inactivated in susceptible host, inactivation through hydrolysis
Prevent antibiotic access
modify the bacterial membrane porin channel size, numbers and selectivity
Remove antibiotic from bacteria
Proteins in bacterial membranes act as an export or efflux protein - so level of antibiotic reduced
How does resistance develop?
Bacterium which was previously susceptible obtains ability to resist activity of a particular antibiotic
only certain strains of species will be reisstane
can occur through spontaneous gene mutation
Conjugation horizontal gene transfer
sharing of extra-chromosomal DNA plasmids i.e. MRSA
Transduction horizontal gene transfer
insertion of DNA by bacteriophages
Transformation horizontal gene transfer
picking up naked DNA
TB resistance
drug unable to penetrate cell wall
low pH renders drug inactive
drug exported from cell before it reaches target
anaerobic conditions lead to dormancy
mutations in DNA repair genes
Alteration of target protein structure prevents drug recognition
alteration fo enzyme prevents conversion of pro-drug to active form
Clostridium difficile 5Cs
Ciprofloxacin, Clindomucin, Cephalosporins, Co-amoxiclav, Carbapenems
