1. Antimicrobial therapy
Beta-Lactam Antibiotics
These antibiotics have a B-lactam ring structure and exert a bactericidal action by distrupting cell wall synthesis in rapidly dividing organisms.Generally , they achieve good levels in the lung, kidney , bone , muscle and liver ,and in pleural , synovial , pericardial and peritoneal fluids.They are classified into 8 groups :

2. 1.Natural penicillins:benzylpenicillin,phenoxymethylpenicillin.
2.Penicillinase- resistant penicillins: meticillin, flucloxacillin.
3.Aminopenicillins :ampicillin,amoxicillin.
4.Carboxy-and ureidopenicillins:ticarcillin ,piperacillin.
5.Cephalosporins :1st-4th generation compounds.
6.Monobactams:aztreonam.
7.Carbapenems: imipenem ,meropenem.
8.B-lactamase inhibitors ,e.g. clavulanic acid.

4. Pharmacokinetics *Not inhibited by abscess environment ( low PH ,low O2 , high protein and polymorphonuclear cells). *Poor penetration to monocytes , low CSF levels except in the presence of inflammation. *Generally safe in pregnancy ( except imipenem/cislastatin).

5. Adverse reactions
*Generalized allergy :0.7-10%.
*Anaphylaxis : %
*Infectious mononucleosis :>90% develop a rash if given aminopenicillins.
N.B….established penicillin allergy does not imply allergy to other classes,particularly the cephalosporins.
*The 2nd and 3 rd generations cephalosporins have a low incidence of allergy and an almost negligible rate of anaphylaxis.

6. Adverse effects
*GI upset ,diarrhea ,and a mild irreversible hepatitis.
*Leucopenia , thrombocytopenia and coagulation deficiencies.
*Interstitial nephritis and increased renal damage in combination with aminoglycosides.
*Seizures and encephalopathy particularly with high doses in the presence of renal insufficiency.
N.B…..direct intrathecal injection of a B- lactam is contraindicated.

7. Macrolide and lincosamide antibiotics
Erythromycin:remains the ‘reference’ macrolide antibiotic
Pharmacokinetics:
-Poorly absorbed orally.
-Short half –life(except azithromycin)
-High protein binding.
-Excellent intracellular accumulation, good CSF penetration.

8. Pharmacokinetics of lincosamide:
-Good bioavailability.
-Food has no effect on absorption.
-Limited CSF penetration.
Adverse effects(both macrolides and lincosamides)
*Generally very safe.
*GI upset , especially in young adults.
*Cholestatic jaundice with erythromycin estolate.
*Prolongation of QT interval on ECG ,potential for torsades de pointes.
*Clindamycin-diarrhea in 2-30% linked to Cl.difficile.

9. Aminoglycosides:
*Are very effective anti-Gram negative antibiotics.
*Are particularly useful where B-lactam or quinolones resistance occurs in health care –acquired infections.
Pharmacokinetics:
-Negligible oral absorption.
-Hydrophilic so excellent penetration to body cavities and serosal fluids.

10. -Very poor intracellular penetration( except hair cells in cochlea and renal cortical cells ).
-Negligible CSF and corneal penetration.
-Peak plasma levels 30 minutes after infusion.
-Post-antibiotic effect allows once-daily administration ( except in endocarditis , pregnancy , chronic renal disease and ascites ).
-Monitoring of therapeutic levels required.

11. Adverse reactions
*Renal toxicity ( usually reversible) , worse with concomitant vancomycin , cisplatin , amphotericin B,contrast media.
*Cochlear toxicity( permanent) more likely in order people.
*Neuromuscular blockade after rapid intravenous infusion( increased with calcium channel blockers , myasthenia gravis and hypomagnesaemia).
N.B…..Aminoglycosides are very effective in Gram-negative sepsis and body fluid infection.

12. Quinolones
*Of these synthetic agents, the early quinolones had purely anti-Gram negative activity, fluoroquinolones ( e.g. ciprofloxacin) have times greater activity against Gram-negative organisms , and newer drugs , levo-,moxi-, spar-,gemi- and gatefloxacin, have improved anti –Gram-positive and anti-anaerobic capability.
N.B…..These antibiotics may now be used against respiratory pathogens in an empirical manner.

13. Pharmacokinetics:
*Well absorbed after oral administration but delayed by food , antacids,ferrous sulphate and multivitamins.
*Wide volume of distribution.
*Good intracellular penetration concentrating in phagocytes with high bioavailability.
*Tissue concentration twice that of serum.

14. Adverse reactions
*Very rare side-effects.
*Rare skin reactions ( phototoxicity).
*GI side effects in 1-5% , tremor , dizziness and occasional seizures in 5-12%.
*Coadministration with xanthines and theophylines reduces clearance of these drugs so may produce insomnia and increases seizure potential.
*CNS effects such as confusion and seizures occur potentially in elderly.

15. Glycopeptides(vancomycin and teicoplanin)
*Vancomycin is effective against Gram-positive organisms and, with teicoplanin, remains useful against MRSA and enterococci.
*The inappropriate use of vancomycin should be limited , particularly in the management of Cl. Difficle infections , to prevent further resistance development.

16. Pharmacokinetics of vancomycin:
-Must be given by slow intravenous infusion with good tissue distribution and has a short half-life.
-Only enters CSF in the presence of inflammation.
Pharmacokinetics of teicoplanin:
-Longer half-life allows once-daily dosing.
-More lipophilic than vancomycin, with good tissue penetration.

18. Averse effects of vancomycin:
*Histamine release due to rapid infusion produces the ‘ red- man’ anaphylactoid reaction.
*Nephrotoxicity enhanced by concomitant aminoglycosides.
*Requires therapeutic monitoring.
Adverse effects of teicoplanin:
*Rash , bronchospasm , eosinophilia and anaphylaxis.
*Markedly less toxic than vancomycin ; only requires monitoring in renal impairment.

19. Folate antagonists
-Interfere with the prokaryotic cell metabolism of para-aminobenzoic acid to folic acid.
-A combination of two antibiotics ( a sulphonamide and either trimethoprim or pyrimethamine) is most commonly used.
N.B…..Co-trimoxazole in high doses ( 120 mg/kg) is the first- line drug for Pneumocystis pneumoniae infection in HIV disease.

20. Pharmacokinetics:
*Well absorbed orally with good bioavailability.
*Displace bilirubin from albumin so predispose to kernicterus in infants.
*Sulphonamides are hydrophilic , distributing well to the extracellular fluid.
*Trimethoprim is lipophilic with high tissue concentrations.

21. Adverse reactions:
*Most are dose- and time- related( therapy for UTI should be no more than 3 days),
*Fatal marrow dysplasia and hemolysis in G6PD more common in the elderly.
*Skin and mucocutaneous reactions especially common and related to sulphonamide component.
*All reactions more common in high- dose therapy in HIV disease.

22. Tetracyclines
*Of this mainly bacteriostatic class , the newer drugs doxycycline and minocycline show better absorption and disribution than older ones.
*Are mostly used against Mycoplasma ,Chlamydia and Rickettsia , plus Borrelia and other spirochaetes.

23. Pharmacokinetics:
*Best oral absorption in the fasting state( doxycycline 100% absorbed unless gastric PH rises).
*CSF levels increased in chronic inflammation( useful in Lyme disease).

24. Adverse reactions:
*All tetracyclines except doxycycline are contraindicated in renal failure.
*Marked effect on bowel flora , causing side-effects of nausea and diarrhoea.
*Bind to metallic ions in bones and teeth , causing discoloration(avoid in children and pregnancy).
*Phototoxic skin reactions.
*Hypernatraemia ( used therapeutically in hyponatraemia)

25. Chloramphenicol
*This potentially toxic antibiotic is bacteriostatic to most organisms but apparentlly bactericidal to H.influenzae ,Strep. Peumoniae ,and Neisseria meningitidis.
*It has a very broad spectrum of activity against aerobic and anaerobic organisms, spirochaetes,Rickettsia , Chlamydia and Mycoplasma.
*It has quite useful clinical activity against anaerobes such as Bacteroides fragilis.

26. Pharmacokinetics:
*Well absorbed after i.v. or oral dose ( not i.m.).Good tissue distribution and levels.
*Good CSF levels.
*Crosses placenta and reaches breast milk.
*Competes for binding site with macrolides and lincosamides.

27. Adverse reactions:
*Dose- dependent ‘ grey-baby’ syndrome in infants( cyanosis and circulatory collapse due to inability to conjucate drug and excrete active form in urine).
*Reversible dose- dependent bone marrow depression( adults) if >4 g per day administered or cuulative dose>25 g.
*Severe idiopathic aplastic anaemia in 1: treatment regimens ( unrelated to dose , duration of therapy or route of administration)