Infections Flashcards
Gentamicin / Amikacin
Aminoglycosides
Bactericidal - bind irreversibly to bacterial ribosomes (30S subunit) and inhibit protein synthesis. Spectrum of action: Gram- aerobic bacteria, staphylococci, mycobacteria. causes slight conformation change to A site, resulting in mis-reading of tRNA and incorrect amino acids added to growing protein chain: produces ‘nonsense’ proteins. This alters function of bacterial membrane with loss of membrane semi-permeability, difficult to repair
Cefalexin / Cefotaxime / Ceftriaxone / Ertapenem
Cephalosporins / Carbapenems
b-lactam ring broad-sprectum antibiotics - inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell walls. This weakens cell walls, preventing them from maintaining an osmotic gradient, resulting in bacterial cell swelling, lysis and death
Clarithromycin / Erythromycin / Azithromycin
Macrolides
Inhibit bacterial protein synthesis by binding to 50S subunit of the ribosome and block translocation (process required for elongation of polypeptide chain) = Bacteriostatic
Relatively broad spectrum activity against Gram+ & Gram-
Resistance can be due to ribosomal mutation preventing macrolide binding
Metronidazole
enters bacterial cells by passive diffusion. In anaerobic bacteria, reduction of metronidazole generates a nitroso free radical.
This binds to DNA, reducing synthesis and causing widespread damage, DNA degradation and cell death
Bacterial resistance to metronidazole is generally low but is increasing in prevalence. Mechanisms include reduced uptake of metronidazole and reduced generation of nitroso free radicals.
Nitrofurantoin
Nitrofurantoin is metabolised (reduced) in bacterial cells by nitrofuran
reductase. Its active metabolite damages bacterial DNA and causes cell death (bactericidal effect). Nitrofurantoin is active against the Gram-negative (e.g. Escherichia coli) and Gram-positive (Staphylococcus saprophyticus) organisms that commonly cause urinary tract infection
Trimethoprim
Bacteria are unable to use external sources of folate, so need to make their own for essential functions including DNA synthesis. Trimethoprim inhibits bacterial folate synthesis, slowing bacterial growth (bacteriostatic). It has a broad spectrum of action against Gram-positive and Gram-negative bacteria, particularly enterobacteria, e.g. Escherichia coli. However, its clinical utility is reduced by widespread bacterial resistance. Mechanisms of resistance include reduced intracellular antibiotic accumulation and reduced sensitivity of target enzymes. Sulfonamides (e.g. sulfamethoxazole) also inhibit bacterial folate synthesis, but at a different step in the pathway to trimethoprim. Together trimethoprim and sulfamethoxazole cause more complete
inhibition of folate synthesis (at least in vitro), making them bactericidal
Penicillins
Penicillins inhibit the enzymes responsible for cross-linking peptidoglycans in bacterial cell walls. This weakens cell walls, preventing them from maintaining an osmotic gradient. Uncontrolled entry of water into bacteria causes cell swelling, lysis and death. Penicillins contain a β-lactam ring, which is responsible for their antimicrobial activity. Side chains attached to the β-lactam ring can be modified to make semi-synthetic penicillins.
Resistance: Bacteria resist the actions of penicillins by making β-lactamase, an
enzyme which breaks the β-lactam ring and prevents antimicrobial
activity. Other mechanisms of resistance include limiting the intracellular
concentration of penicillin (reduced bacterial permeability or increased
extrusion) or changes in the target enzyme to prevent penicillin binding
Ciprofloxacin / Levofloxacin
Quinolones
Quinolones kill bacteria by inhibiting DNA synthesis. They are particularly
active against aerobic Gram-negative bacteria, which explains their utility in
treatment of urinary and gastrointestinal infections
Bacteria rapidly develop resistance to quinolones. Some bacteria
prevent intracellular accumulation of the drug by reducing permeability
and/or increasing efflux. Others develop protective mutations in target
enzymes. Quinolone resistance genes are spread horizontally between
bacteria by plasmids, accelerating acquisition of resistance.
Doxycycline / Lymecycline
Quinolones
inhibit bacterial protein synthesis. They bind to the
ribosomal 30S subunit found specifically in bacteria. This prevents the binding of transfer RNA to messenger RNA, which prevents the addition of new amino acids to growing polypeptide chains. Inhibition of protein synthesis is ‘bacteriostatic’ (stops bacterial growth), which assists the immune system in killing and removing bacteria from the body. Tetracyclines have a relatively broad spectrum of antibacterial activity. Tetracyclines were discovered in 1945 and have been widely used.
Consequently, some bacteria have acquired resistance to these antibiotics. A
common mechanism is through acquisition of an efflux pump, which allows
bacteria to pump out tetracyclines, preventing cytoplasmic accumulation.
Doxycycline / Lymecycline
Quinolones
inhibit bacterial protein synthesis. They bind to the
ribosomal 30S subunit found specifically in bacteria. This prevents the binding of transfer RNA to messenger RNA, which prevents the addition of new amino acids to growing polypeptide chains. Inhibition of protein synthesis is ‘bacteriostatic’ (stops bacterial growth), which assists the immune system in killing and removing bacteria from the body. Tetracyclines have a relatively broad spectrum of antibacterial activity. Tetracyclines were discovered in 1945 and have been widely used.
Consequently, some bacteria have acquired resistance to these antibiotics. A
common mechanism is through acquisition of an efflux pump, which allows
bacteria to pump out tetracyclines, preventing cytoplasmic accumulation.
Vancomycin
Vancomycin inhibits growth and cross-linking of peptidoglycan chains,
inhibiting synthesis of the cell wall of Gram-positive bacteria. It
therefore has specific activity against Gram-positive aerobic and
anaerobic bacteria and is inactive against most Gram-negative bacteria,
which have a different (lipopolysaccharide) cell wall structure. Bacterial
resistance to vancomycin is increasingly reported. One mechanism is
modification of cell wall structure to prevent vancomycin binding.
