Antibiotics Flashcards
Name anaerobic antibiotics
Metronidazole
Orala or IV or Gel
Indications of using metronidazole
1) C.Diff (gram +ve) - this is 1st line
2) Oral infections - due to gram -ve in the mouth
3) Aspiration pneumonia
4) Surgical and gynae infections due to gram -ve anaerbobes from the colon
5) Protozoal infections e.g. trichomonal vaginosis, dysentry, giardasis
Mechanisms of metronidazole
Passively diffuses into anaerobic bacterial cells
Reduced to generate a nitroso free radical
Binds to DNA
Reduces syntheses causing widespread damage - DNA degradation and cell death
Why doesnt metronidazole work on aerobic bacteria
As they dont reduce it to a nitrosos free radical
Is there resistance to metronidazole
Generally low resistance
But can be resistanct due to decreased uptake and decreased generation of nitroso free radicals
ADverse effects of metronidazole
1) GI Upset
2) Hypersensitivity
3) Neuro effects –> if at high doses or prolonged courses e.g. peripheral and optic neuropathy, seizures and encephalopathy
Warnings of metronidazole
Metabolised by hepatic CP450 ensymes –> reduce dose in hepatic impairment
Inhibits acetalderhyde dehydrogenase enzye –> this clears intermediate alcohol metabolite –> hence if you drink a disulfram-like reaction occurs –> flushing, headach, nausea and vomiting
What cant you do whilst taking metronidazole
Drink alcohol
Interactions of metronidazole
1) inhibitory effect on CP450 en`ymes
2) Excitory effect on CP450 inducers
3) Increased risk of lithium toxicity
What do we measure if we treat longer than 10 days on metronidazole
Measure FBC and LFTs
Indications of nitrofurantoin
1) Uncomplicated lower UTI - 1st line
Reaches therapeutic concentration in the urine through renal excretion
Action of nitrofurantoin
Metabolised in bacterial cells by nitrofuran reuctase
Its active metabolite damages bacterial DNA causing cell death
what organisms is nitrofurantoin active against
Gram +ve (staph. saprophyticus) and gram -ve (E. Coli) that cause UTIs commonly
What bacteria are resistant to nitrofurantoin
Bacteria with reduced nitrofuran reductase activity
Also less common causes of UTIs e.g. Klebsiella, Proteus have intrinsic resistant
Relatively rare for E. Coli to develop resistance
Adverse effects of nitrofurantoin
1) GI upset
2) Hypersensitivity
3) Chronic pulmonary reactions - pneumonitis, fibrosis
4) Hepatitis and peripheral neuropathy
5) haemolytic aneamia in neonates –> as immature RBCs are unable to mop up nitrofurantoin stimulated superoxides which damages RBCs
6) can turn urine dark yellow or brown
Patiet whousl warn if any unexplained symtpoms e.g.breathlessness
Contrainidcatinos of nitrofurantoin
1) Pregnancy towards term
2) Under 3 months old
3) Renal impairment - as impaired excretion increases its toxicity and decreases its efficacy
Caution of using nitrofurantoin in who
Long term UTI prevention –> high risk of adverse effects
Interactions of nitrofurantoin
No significant interactions
How can we minimise GI upset in nitrofurantoin
Take with food or mulk
Why shouldn’t we prescribe nitrofurantoin for pyelonephritis
As tissue concentrations are low
Use co-amoxiclav or gentamicin instead
What does co-trimoxazole contain
Trimethoprim and sulfamethoxazole
Indications of trimethprim
1) UTI - 1st line for uncomplicated
2) Pneuocytis Pneumonia - use co-trimoxazole
Action of trimethoprim
Inhibits bacterial folate synthesis by inhibiting dihydrofolate reductase
Bacteria are unable to use external folate for DNA synthesis –> therefore inhibiting it is bacteriostatic
What organisms is trimethoprim effective against
Broad spectrum against gram -ve and gram +ve - Particularly E. Coli
BUT widespread bacterial resistance
How do sulfonamide antibiotics work
Inhibits bacterial folate syntheisis - but inhibits dihydropteroate syhnthetase as structual analoge of PABA
Why do we combine trimethoprim and sulfomethoxazole?
As both are bacteriostatic and in combination they cause more inhibition making it bacteriacidial