Basic principles:
Choice of initial therapy:
o Empirical therapy should be directed against the most likely pathogens and possess
the narrowest spectrum that covers these.
o Therapy should be altered in accordance with patient’s course and culture results.
Timing of therapy:
o Acute:
If unstable - Empirical therapy started after cultures obtained.
If stable – Delay empiric treatment to allow for specific antimicrobials based
on initial tests.
o Urgent therapy is indicated in febrile patients who are neutropaenic or asplenic.
o Sepsis, meningitis and rapidly progressive anaerobic or nocrotizing infections should
be treated urgently.
Route of administration:
o IV – Patients with serious infections
o IM or PO – less urgent circumstances. Oral therapy is acceptable when it is tolerated
and can achieve adequate drug concentrations at the site of infection.
1. CELL WALL SYNTHESIS INHIBITORS (BACTERIOCIDAL)
a. Penicillins
Inhibit transpeptidase required for cross-linking peptidoglycan chains by binding to penicillin-binding
proteins PBPs. Inhibition of PBPs enables activity of autolytic bacterial enzymes.
i. Narrow spectrum (β-lactamase sensitive)
Active against gram-positive bacteria
Examples: Benzylpenicillin, Phenoxymethylpenicillin
ii. Narrow spectrum (β-lactamase resistant)
Active against gram-positive bacteria
Mostly used for staphylococcus aureus
Examples: Methicillin, Flucloxacillin
iii. Broad spectrum (β-lactamase sensitive)
Active against gram positive and gram negative bacteria
Active against enterobacteria
Examples: Amoxicillin, Ampicillin
iv. Extended-spectrum (β-lactamase sensitive – Carboxypenicillins)
Active against gram positive and negative bacteria
Active against pseudomonas aeruginosa, Klebsiella
Examples: Pipercillin, Ticarcillin, Carbenicillin
Side effects:Diarrhoea (broad-spectrum), Encephalopathy (excess dose or renal failure) Rarely
Hypersensitivity reactions
b. Cephalosporins
Work by the same mechanism as penicillins. ↑generation ↑activity against gram negative bacteria
and anaerobes, resistance to β-lactamases, ↑ability to reach CSF.
i. 1st generation (β-lactamase sensitive)
Active against gram positive bacteria
Examples: Cefazolin, Cephalexin
ii. 2nd generation (β-lactamase sensitive)
Active against gram positive bacteria and some activity against gram negative
bacteria
Examples: Cefaclor, Cefamandole, Cefuroxime
iii. 3rd generation (mostly β-lactamase resistant)
Active against gram positive and gram negative bacteria
Active against pseudomonas aeruginosa, enterobacteria, gonococcus
Penetrate the CNS used for meningitis
Examples: Cefotaxime, Ceftriaxone
iv. 4th generation (mostly β-lactamase resistant)
Broadest antimicrobial spectrum of any drug
Used for MDR bacteria and mixed infections
Examples: Cefepime, Cefpirome
Side effects: Similar to penicillins. 5-10% of patients with hypersensitivity to penicillin have cross-
reactivity.
c. Carbapenems
d. Monobactams
e. Vancomycin
Only effective against gram positive bacteria
For methicillin-resistant staphylococci
Side effects: Ototoxicity (tinnitus, high-tone deafness)
2. PROTEIN SYNTHESIS INHIBITORS
a. Aminoglycosides
Broad spectrum bacteriocidal antibiotics (NOT anaerobes)
Paraenteral administration
Examples: Gentamicin, Amikacin, Neomycin, Streptomycin, Tobramycin
Side effects: Ototoxicity (destroys outer hair cells in organ of Corti); Nephrotoxicity
(kills proximal tubular cells); Neuromuscular toxicity (respiratory suppression)
b. Tetracyclins
Broad spectrum bacteriostatic antibiotics
Useful for treating rickettsial diseases (Rocky mountain spotted fever),
Spirochetes (Lyme disease), Mycoplasma (Pneumonia)
Oral absorption impaired by food
Examples: Tetracycline, Oxytetracycline, Minocycline, Doxycycline (used to treat
rosacea and prevent rhinophyma)
Side effects: Incorporation in to teeth and bones (staining of the teeth and
retardation of bone growth), Photosensitivity, Abdominal cramps
c. Macrolides
Narrow spectrum antibiotics similar to penicillin (bacteriostatic or bacteriocidal)
Good alternative for patients with penicillin allergy
Good for treating mycoplasma (pneumonia) and Legionella (Legionnaire’s disease)
Examples: Erythromycin, Clarithromycin (H.Pylori), Azithromycin
Side effects: GI disturbances, temporary auditory impairment
d. Chloramphenicol
Very broad spectrum (almost all bacteria except pseudomonas aeruginosa)
Reserved for life threatening, otherwise treatment resistant infections
Side effects: Bone marrow suppressionfatal aplastic anaemia
e. Clindamycin
Medium broad spectrum (Gram-positive organisms, anaerobes)
Used for treatment of penicilin-resistant cocci
Side effects: Collitis (triggered by toxin from clindamycin-resistant C.Difficile
combine with vancomycin to kill C.Difficile)
3. FOLATE ANTAGONISTS
Bacteria synthesize folic acid from p-amino-benzoic acid (PABA). Folate antagonists block folate
synthesis inhibiting nucleotide synthesis bacteriostatic effect. BUT inactive in the presence of pus or
necrotic tissue.
a. Sulfonamides
Structural analogue of PABA so competes for dihydropteroate-synthase.
Used for infected burns, STDs, toxoplasmosis
Examples: Sulfadiazine, Sulfadimidine, Sulfamethoxazole
b. Trimethoprim
Competes with folates for dihydrofolate reductase
Use similar to sulfonamides
Combined with sulfomethoxazole = Co-trimoxazole (used for UTI)
4. QUINOLONES + FLUOROQUINOLONES
Synthetic inhibitors of Topoisomerase II inhibition of DNA synthesis and
transcription
Very broad spectrum, bacteriocidal
Al and Mg interfere with absorption (antacids)
Examples: Ciprofloxacin (very broad spectrum, used in emergencies)
Side effects: Nausea, vomiting, diarrhoea, Rarely: convulsions, CNS effects
Side-effects