The document discusses the use of antimicrobial therapy and various classes of antibiotics. It provides details on the mechanisms of action, spectra of activity, indications for use, and side effects of different classes of antibiotics including beta-lactams (penicillins, cephalosporins, carbapenems), glycopeptides, quinolones, sulfonamides/trimethoprim, metronidazole, tetracyclines, chloramphenicol, macrolides, aminoglycosides, streptogramins, and oxazolidinones. It also discusses Clostridium difficile infection as a common gastrointestinal side effect caused by antibiotic use.

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.