Antibiotic Therapy

Oral

15 minutes

Urine or liver and biliary tract

1 hour

True

Cell wall, ribosomes, DNA replication, DNA gyrases, Metabolic pathways, Cell. membrane function

Inhibit cell wall synthesis by preventing cross linking of peptidoglycan - bactericidal

• β lactam
• Very few side effects
• Range from narrow to broad spectrum
• Excreted (rapidly) via kidneys
• Safe in pregnancy

-Patients can be hypersensitive (allergic). -Rapid excretion via the kidneys. This results in frequent dosing -Resistance- Due to a long history of clinical use, many microbes have been exposed to these compounds and some resistant strains have been selected for.

1. Benzylpenicillin- penicillin G, intravenous IV
2. Phenoxymethyl penicillin- penicillin V, oral
3. Benzathine penicillin- long acting, intramuscular (IM)

Penicillin V is effective on a narrow range of largely Gram +ve bacteria. Absorbed through intestine Sensitive to stomach acid (30 mins before meal or 3 hours after) Peak plasma concentration 30-60 minutes after taking 75-90% binds to plasma proteins Serum levels maintained for 30-60 minutes

Amoxicillin is administered via IV or orally. It is a safe, well tolerated antibiotic. It is well-absorbed when given orally. It has a low binding ability to plasma proteins (longer half life) and good tissue distribution. Its effectiveness is challenged by spread of beta-lactamases.

Amoxycillin has a broad spectrum effect across Gram +ve and Gram -ve bacteria. Absorbed through the intestine Stable in the presence of stomach acid Peak plasma concentration 60-120 minutes after taking Wide tissue distribution and it also has the capacity to enter the CSF (cerebrospinal fluid) if meninges are inflamed. 20% binds to plasma proteins Plasma half life is 60 minutes

1. Inhibitory/ bactericidal
2. Time Dependant action (peak plasma concentration)
3. Spectrum (Gram +ve or -ve)/ Anaerobic bacteria
4. Absorption- Peritoneal versus IV, where it gets absorbed, acid sensitivity
5. Distribution- Plasma binding proteins, GI/urinary tract, environment permissive for activity 6)Elimination via liver or kidney

Kills bacteria, selective toxicity, good tissue distribution, long half life, peritoneal absorption, no significant drug interactions.

Cephalosporins inhibit cell wall synthesis and are bactericidal. Modified beta-lactam It has a longer half life in plasma Excreted via kidneys and urine Has a few side effects, reduced allergy Safe in pregnancy Narrow Gram -ve to broad (3rd) and extended spectrum (4th) Relatively resistant to beta lactamases

Cephalosporins are broad spectrum antibiotics, which significantly affect the normal bowel flora. They kill the normal gut bacteria and allow the overgrowth of C. difficile which causes bad gastroenteritis. Their use in Tayside is very restricted.

1)They are not Beta lactic antibiotics. 2)Bactericidal 3)Excreted via the kidneys and urine; toxic levels of vancomycin in the blood can build up in patients who have kidney failure- causes red man syndrome 4) Limited to bacteria with Gram positive cell wall 5) Oral vancomycin can target Gram +ve GI microbes as it builds up in intestines. It doesn't get absorbed too easily and therefore is effective against C. difficile. 6) It has no activity against Gram -ve organisms.

Antibiotics that inhibit protein synthesis do so by attaching to bacterial ribosomes, which are structurally different from mammalian ribosomes.

Usually, protein synthesis can resume when the antibiotic is removed so most of these antibiotics (macrolides, tetracycline) are bacteriostatic. However, in aminoglycosides, the binding of these antibiotics to the ribosomes is lethal. This is what makes it bactericidal.

1. Aminoglycosides e.g. Gentamicin
2. Tetracyclines e.g. Doxycycline/Minocycline
3. Macrolides e.g. Erythromycin

Aminoglycosides are protein synthesis inhibitors which are not absorbed from the gut and therefore must be given in IV.

1. Binds irreversibly to ribosomes inhibiting protein synthesis and thus it is bactericidal.
2. Active mostly against Gram -ve aerobic bacteria. (coliform and Pseudomonas aeruginosa). It is effective in hospital for treating life threatening gram -ve infection.
3. Excreted in urine
4. Excessive levels in the serum would cause damage to kidney and the 8th cranial nerve- need to monitor blood levels of aminoglycosides.

Tetracyclines are protein synthesis inhibitors that are bacteriostatic in nature.

1. Broad spectrum- useful against intracellular bacteria and atypical bacteria like chlamydia
2. Resistance- increasing as more is being used
3. Adverse effects- Destruction of normal intestinal flora resulting in increased secondary infections. Staining and impairment of the structure of bone and teeth, restricted use in infants, children and pregnancy.

Tetracyclines are actively transported into the cell. It binds to 30S subunit and prevents attachment of tRNA to acceptor sites. It stops the chain elongation. Doxycycline and Minocycline provide more efficient absorption- lower concentrations in gut, less disturbance, higher concentration in serum.

Macrolides are

1. bacteriostatic
2. commonly prescribed for Penicillin allergy and intracellular pathogens.
3. This group of antibiotics is excreted via the liver, biliary tract and into the gut. They are not excreted in the urine.
4. Lipophilic antibiotics pass through cell membranes easily.
5. Useful in treating infections where intracellular bacteria hide from host's immune system 6)Safe in pregnancy

Erythromycin, Clarythromycin (Gram -ve) and Azithromycin (Gram +ve)

It binds to the 50S subunit and blocks translocation- therefore no release of peptides.

Fluoroquinolones (for Gram -ve and Gram +ve) Metronidazole (for Anaerobes and protozoa) Trimethoprim (for primary use in urinary tract infection)

1. Bactericidal
2. Good intracellular activity
3. Activity on infection of bones, UTIs, community acquired pneumonia
4. Effective on gram -ve bacteria mostly

Binds to the A subunit of DNA gyros (topoisomerase) and prevent supercoiling of DNA. It directly inhibits DNA synthesis.

Use of broad spectrum antibiotics is now severely restricted to reduce the risk of C. difficile GI infection, especially in elderly patients.

Ciprofloxacin, moxiflocin, levofloxacin

1)It has good activity against anaerobe bacteria and parasites/ protozoa. 2) Administered via Oral or IV methods 3) Resistance is rare 4) Adverse reactions with alcohol- furred tongue etc.

The drug is activated by reduction in strict anaerobes and it forms a toxic intermediate that induced DNA strand breakage.

1. Active against some Gram -ve and Gram -ve bacteria
2. Common for acute UTI e.g. E. coli
3. Excreted via the urine
4. Administered orally (on its own) or Administered in a combination with a sulphomethoxazole (a sulphonamide) in oral and IV form.

It inhibits Folic acid synthesis as it is a key intermediate metabolism. Folic acid vitamin is required for synthesis of key cellular components like thymidine, purines etc.

hypersensitivity/skin reactions

cholestatic jaundice

C. difficile colitis

GI disturbances, hepatitis, Q-T interval

Q-T interval, convulsions, tendonitis

nephrotoxicity/ototoxicity

‘red man’ syndrome

hepatotoxicity, staining teeth, photosensitivity, dysphagia

peripheral neuropathy, pulmonary fibrosis

aplastic anaemia, grey baby

blood dyscrasias, MAOI, optic neuropathy

hepatotoxicity

Stevens-Johnson syndrome, blood dyscrasias

blood dyscrasias

Enzyme inhibitors interact with erythromycin, clarithromycin, isoniazid, metronidazole, ciprofloxacin.

Rifampicin is affected by enzyme inducers.

Antacids/calcium can reduce the absorption of tetracyclines and quinolones.

Entero-hepatic cycling can lead to contraceptive failure when taken with broad-spectrum antimicrobials and oral contraceptives.

Taking broad-spectrum antimicrobials with warfarin leads to increased INR.

Metronidazole can cause a disulfiram-like interaction with alcohol.

Quinolones can interact with steroids, leading to tendonitis, and with NSAIDs, leading to convulsions.

Macrolides and Quinolones can interact with Q-T prolonging drugs.

Aminoglycosides/glycopeptides/colistin with loop diuretics or ciclosporin or tacrolimus - nephrotoxicity