1. Antimicrobial therapy
The decision to use antimicrobials should be with knowledge of the likely causative organisms,
antimicrobial sensitivity, site of infection, spectrum of activity of antimicrobials & the risks of
treatment & of untreated infection.
Inhibitors of bacterial cell wall synthesis
The bacterial cell wall is a common target as it differs from that of human cells. The structure is
different in Gram-negative & Gram-positive organisms & in addition, some bacteria such as
Chlamydia , donot possess a bacterial cell wall.
Β-lactum antibiotics : Penicillins, cephalosporins, monobactums& carbapenems are similar
compound containing a β-lactum ring which is back-bone of the cell wall.
1)Penicillins
1. Natural penicillins: penicillin V; Gram-positive bacteria including streptococci, clostridia&
corynbacteria, meningococci & most anaerobes(excluding Bacteroides fragilis).
2. Penicillinase-resistance penicillins, e.g. flucloxacillin: Additional activity aganist penicillin-resistance
staphylococci aureus.
3. Aminopenicillin ; ampicilin & expanded-spectum penicillins(piperacillin): Additional activity
against Gram-negative bacilli including haemophilus & many of enterobacteriaceae.
4. Carbapenems : imipenem; broad-spectum against Gram-positve& Gram- negative bacteria,
including the β-lactamase producing Gram-negative organisms& anaerobic activity including
Bacteroides fragilis(B.fragilis).
5. Monobactums : aztreonam; No Gram-positive but good Gram-negative activity including
pseudomonas.
6. Β-lactamase inhibitors e.g. clavulanic acid: in combination with β-lactam with similar
pharmokinetic properities they have increased activity against anaerobes &
enterobacteriaceae.
Side effect of penicillins
1. The most serious but uncommon side effect is anaphylaxis.
2. Other allergic manifestations include angioneurotic oedema,urticaria, Stevens-Johnson
syndrome, dermatitis, morbiliform eruptions & allergic vasculitis.
3. Reversible neutropenia sometimes occurs with prolonged high-dose penicillin therapy.
4. High-dose therapy in renal failure can precipitate epilepsy if dose adjustments are not made.

2. 5. Diarrhoea including Clostridium difficile infection is more commonly associated with
ampicillin & amoxicillin.
Indications of penicillins
1. Penicillin are used to treat streptococci infections( including pneumococcal meningitis once
penicillin sensitivity is confirmed), meningococcal, penicillin-sensitive gonococcal infections.
2. Aminopenicillins are used to treat upper& lower respiratory infection as they are active
against Haemophilus influenza.
3. Penicillinase-resistance penicillins(flucloxacillin) are used to treat methicillin-sensitive
staphylococcal infections. The majority of staphylococcus aureus are resistance to penicillin
due to the production of penicillinase.
2) Cephalosporins
These compounds are closely related to the penicillins & classified into four main generations. As
Gram-negative acitivity increases Gram-positive activity decrease. There is a low incidence of
anaphylaxis but cross-reactivity in approximately 10% of penicillin-allergic patients& rashes can
occur.
a) First generation cephalosporins such as cefradine are well absorbed orally. The first
generation cephalosporins are more active against methicillin-sensitive S. Aureus &
streptococci.
b) Second generation cephalosporin are usually given intravenously but are available in oral
formulations.
c) The third-generation cephalosporins are injectable agents, cefotaxime& ceftriaxone are able
to cross the blood-brain barrier. Third & fourth generation cephalosporins have increased
Gram-negative activity & some pseudomonas activity(ceftazidime). Third generation
cephalosporin are associated with a higher risk of clostridium difficile diarrhoea(C.difficile).
They do not active against enterococci( Gram-positive cocci live in our intestine, form
commensals to leading causes of drug resistance . Enterococci faecalis, Enterococcus
faecium, Enterococcus durans are common. Enterococcal species can cause a variety of
infection UTI, Bacteremia, endocarditis, meiningitis).
3) Glycopeptides (Vancomycin & teicoplanin)
They only have Gram-positive activity as they are unable to penetrate Gram-negative cell walls.
Resistance is uncommon but increasing, particularly in enterococci. They are larger molecules, they
are not absorbed orally & do not cross the blood-brain barrier. Red man syndrome can occur with
rapid infusions of vancomycin due to release of histamine.
They are used for treatment of1) enterococci infection,2) sepsis due to resistant Gram-positve
infections(MRSA) or3) allergic to penicillins.

3. Inhibitors of bacterial nucleic acid synthesis
1. Quinolone : Gram-negative ,anaerobic, pseudomonal acitivity & Gram-positive activity due
to additions of a fluorine atom. There is good oral absorption & wide tissue distribution
except for the CSF. Adverse effects are include epileptic seizures & photosensitivity.
Interaction with other drugs such as theophylline.
2. Sulphonamides & trimethoprim: they have Gram-positive, Gram-negative activity & activity
against pneumocystis carnii. Resistance in enterobacteriaceae has increased. Sulphonamide
are associated with severe allergic rashes,including Steven-Johnson syndrome.
Trimethoprim is used in isolation for simple urinary & respiratory tract infections.
3. Metronidazole : the spectrum of activity is aganist anaerobic bacteria & protozoa such as
Giardia species. Metronidazole is well absorbed orally& crosses the blood-brain barrier.
Peripheral neuropathy & encephalopathy can occur with long-term treatment.
Inhibitors of bacterial protein synthesis
1. Tetracyclines : they bind to the 30s ribosomal subunit of bacteria. They are effective against
the atypical bacteria, such as Chlamydia, mycoplasmas, rickettsias & spirochaetes. They have
Gram-positive including staphylococcus aureus& some of Gram-negative organisms such as
H. Influenza & gonococci & some anaerobic activity.
2. Chloramphenical : they bind with 50s ribosomal subunit of bacteria. Widely tissue
distribution & cross the blood brain barrier. Acitivity like tetracycline.Gram-positive, Gram-negative,
anaerobic, mycoplasma, rickettsiae, spirochaetes.
3. Macrolide (erythromycin, clarithromycin, azithromycin): they bind with 50s ribosomal
subunit of bacteria. Azithromycin concentrates intracellularly & intravenous administration
causes thrombophlebitis. Alternative treatment for respiratory tract infections if atypical
organisms or penicillins allergy.
4. Aminoglycoside :they bind to ribosomal subunit of bacteria. They are active against gram-negative
acitivity but no anaerobic activity. They are not absorbed orally. Ototoxicity ,
nephotoxicity,neuromuscular paralysis are important side effect.
5. Streptogramins : they binds to50s ribosomal subunit of bacteria. Gram-positive infection
including enterococci(multiresistant enterococci).
6. Oxazolidinones (Linezolid). They bind with ribosomal subunit of bacteria. They are indicated
MRSA & vancomycin-resistance enterococci (VRE)
Note all anaerobes are treated with penicillins or metronidazole except Bacteroides fragilis(B.fragilis)
are treated with imipenem. All Gram-positive bacteria are treated with penicillin except penicillinase
producing(B-lactamase) treated with flucloxacillin. They are usually methicillin-sensitive
staphylococcus. But MRSA(methicillin resistant staphylococcus aureus) are treated with linezolid. All

4. enterococci infection are treated with vancomycin but vancomycin-resistant enterococci(VRE) are
treated with linezolid or streptogramins.
Gastrointestinal side effects of antibiotics
Diarrhoea can be caused by alteration of the colonic microflora & overgrowth of toxin producing
C.difficile. C. Difficile infection can result in a spectrum of disease from asymptomatic carriage or
mild diarrhoea through to severe diarrhoea with pseudomembranous colitis. Although most
antibiotic have been associated with a predisposition to C.difficile infection. The most commonly
implicated agents have been clindamycin,cephalosporins& ampicillins & most recently quinolones.