ANTIBIOTICS

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 suppressionfatal 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

Common choices for specific organisms

Staph. aureus flucloxacillin

MRSA teicoplanin, vancomycin, linezolid
Strep. pneumoniae cefuroxime, benzylpenicillin
N. meningitidis ceftriaxone, cefotaxime, benzylpenicillin
H. influenzae cefuroxime, cefotaxime
E. coli ampicillin, ceftazidime, ciprofloxacin, gentamicin,
ciprofloxacin, gentamicin, imipenem, meropenem
Klebsiella spp. ceftazidime, ciprofloxacin, gentamicin, imipenem,
meropenem
Ps. aeruginosa ceftazidime, ciprofloxacin, gentamicin, imipenem,
meropenem, Piptazobactam

Side-effects

 Hypersensitivity reactions (all)

 Seizures (high dose penicillins, high dose metronidazole, ciprofloxacin)
 Gastrointestinal disturbance (cephalosporins, erythromycin, clindamycin, teicoplanin, vancomycin,co-
trimoxazole, rifampicin, metronidazole, ciprofloxacin, amphotericin, flucytosine)
 Vestibular damage (aminoglycosides)
 Renal failure (aminoglycosides, teicoplanin, vancomycin, ciprofloxacin, rifampicin, amphotericin, aciclovir)
 Erythema multiforme (co-trimoxazole)
 Leucopenia (co-trimoxazole, metronidazole, teicoplanin, ciprofloxacin, flucytosine, aciclovir)
 Thrombocytopenia (linezolid)
 Peripheral neuropathy (metronidazole)