The use of Antibiotics

Professor Elhadi Eltayeb abbas

• Antibiotics constitute one of the most
important therapeutic agents.
• They had a lot of impact on life threatening
infections.
• Most prescribing especially in the community
is empirical and even in hospital practice.
Prescribing antibiotics requires:
Understanding the pharmacokinetics of drugs.
Their mode of action.
Their spectrum of activity against infecting
organisms.
Clinical skills to diagnose the body system
affected.
Diagnose most likely organism.
 Bactericidal Versus Bacteriostatic
Bactericidal drugs used in bacterial
endocarditis and where host defence
mechanisms are compromized.
Combinations of antibiotics are sometimes
necessary to avoid resistance and to achieve
synergism.
Effective Antimicrobial therapy is :
Dynamic process which must account for
developing resistance and changing
pathogenisty in infecting agents.
 Dose and Duration of Therapy
This will vary according to the nature, severity
and response to therapy:
Prolonged treatment is necessary in certain
conditions.
In most improvement occurs in 2-3 days.
Oral route should be used for most.
Short duration for some asymptomatic
infections like bacteruria.
 Renal and hepatic insuffiency
• Many drugs require dose reduction in renal
insuffiency.
• Some will require dose reduction and caution
in hepatic insuffiency.
 Antimicrobial Resistence
Causes:
 Inappropriate prescription for non-specific
febrile illness or common viral infections.
Inadequate dosage or treatment length.
Poor compliance/adherence to regimens by
patients.
Use of broad spectrum antimicrobials.
Over the counter availability of antibiotics.
Use in food industry and veterenary.
Failure to reach the target site.
Enzyme inactivation.
Alteration of the target site (e.g. single point
mutation in E. coli or a penicillin-binding
protein.)
Mechanism of action of antibiotics
Antibiotics act on different sites of the
bacterium.
Penicillins, cephalosporins and vancomycin act
on the cell wall.
Erythromycin and aminoglycosides affect
protein synthesis.
Rifampicin affect RNA synthesis.
Quinolones and metronidazole affect DNA
synthesis.
 Science of antimicrobial therapy
MIC : Minimum inhibitory concentration
defined as: Lowest concentration of antibiotic
required to inhibit 90% of colonies of a
particular organism.
Plasma half life (t ½):
Lipophilic and hydrophilic drugs.
 Empirical Antibiotic Choice
Identify system involved and likely pathogen.
Take appropriate lab samples.
Choose the most appropriate antibiotics
according to experience or policy of the
institutions.
In severe infections bactericidal rather than
bacteriostatic.
 Route of Administration
 Some antibiotics are only available
parenterally e.g. aminoglycosides.
 Parenteral route should be reserved for
patients who are severely ill or those who can
not take orally.
 Switch to oral therapy should be made as soon
as possible.
 Most authorities accept 48 hours free of fever
as switch time.
 Monitoring of Antibiotic therapy
When potentially toxic drugs are used drug
levels should be monitered trough and peak.
This practice ensures:
 Prevention of accumlation of drug.
Check if required levels are reached i.e. MIC.
 Chemoprophylaxis
 Rheumatic fever.
 Infective endocarditis.
 Splenectomy/ spleen malfunction.
 Meningitis: Meningococi and H influenzae.
 Tuberculosis.
 Beta-Lactum Antibiotics
 They all have a common ring structure.
 Acts on the cell wall.
 Penicillins, cephalosporins, Monobactums,
Carbapenems, B lactamase inhibitors and
cephamycins.
 Achieve good levels in lung, kidney, bone,
muscle, liver, and pleural, synovial, pericardial
and peritoneal fluids.
 Cephalosporins
• Advantage over penicillin is their resistance to
staphlococal pencillinase.
• Broader spectrum with activity including both
gm –ve and +ve.
• Used in serious systemic infections.
• Toxicity simillar to penicillin
• Different generations of cephalosporins.
 Monobactums
• Known one is aztreonam.
• Acts by inhibiting bacterial cell wall synthesis.
• Limited activity to aerobic gm –ve organisms.
 Carbapenems
Semisynthetic B-lactums.
Currently most broad spectrum antibiotics
active against majority of gm +ve and –ves as
well as anaerobes.
Rather expensive.
Used in serious nosocomial infections or
mixed infections.
Toxicity includes: nausea, vomitting and
diarrhoea. Imipenem may cause seizors.
 Macrolides
• Erythromycin was the drug and now others:
clarithromycin, azithromycin, roxithromycin.
• Have simillar but not identical antibacterial
activity like penicillin.
• Clarithromycin used in triple therapy against
helicobactor pylori.
• Toxicity: diarrhoea, vomitting and abdominal
pain. May rarely produce cholestatic jaundice,
prolonged QT interval.
 Ketolides
 Developed in view of the rapid development
of resistance to penicillins and macrolides.
 It is said to overcome most of the common
forms of macrolide resistance and a
theoretical possibility of lower resistance
development.
 Telithromycin is the first to reach the market.
 Aminoglycosides
Streptomycin used only in tuberculosis.
Neomycin is only topical.
Gentamycin and topramycin are parenteral.
Netilmycin and amikacin are more resistant to
the aminoglycoside inactivating enzymes.
.
Interactions: enhanced nephrotoxicity with
other drugs, enhanced ototoxicity with
diuretics and neuromuscular blockade with
curariform drugs.
Toxicity: Dose related. Nephrotoxic and
ototoxic (vestibular and auditory) particularly
in the elderly. Therapeutic drug monitoring
could be necessary.
 Quinolones
o Anti-Gram negative mainly.
o Newer ones have as well anti-Gram positive
and anti-anaerobic activities.
o Well absorbed from the GIT.
o Delayed by food, antiacids and ferous sulphate
and multivitamins.
o Wide volume of distribution.
o Tissue concentration twice that of serum.
• Very few side effects.
• Photosensitivity.
• GIT symptoms.
• Tremors, dizziness and occasional seizurs.
• Bone and joint disease in animal studies limit
use in children.
• CNS side effects especially in the elderly.
 Tetracyclines
o Bacteriostatic drugs.
o Tetracycline, oxytetracycline, demeclocycline,
doxycycline and minocycline.
o Indicated: against gm+ve bacteria with limited
use. Acnae, rosacea. V cholerae, mycoplasma,
rickettsia, chlamydia.
o Efficacy reduced by antiacids and oral iron.
o Enhance or establish renal failure, brown
discolouration of growing teeth. Photosensivity
can occur.
 Chloramphenicol
 Bacteriostatic generally but bacterocidal to H
influenzae, Strep. Pneumoniae and Nisseria
meningitidis.
Broad spectrum against aerobics and
anaerobic organisms, spirochaetes, ricketsiae,
Chlamydia and mycoplasma.
Dose dependent grey baby syndrome,
reversible bone marrow depression, severe
aplastic anaemia
 Cyclopeptides
o Vancomycin and Teicoplanin.
o Effective against gm +ve organisms.
o Use of vancomycin should be limited to the
treatment of clostridium difficile infections.
o Teicoplanin more lipophilic than Vancomycin.
o Red man anaphylactoid reaction.
o Nephrotoxicity.
 Folate Antagonists
Combination of sulphonamide and either
trimethoprim or pyrimethamine.
Absorbed orally and well tolerated.
Used in UTI.
Displace bilirubin from albumin and so can
cause kernicterous in neonates.
 Nitroimidazoles
 Metronidazole and , tinidazole.
Main clinical use in anaerobic infections.
Have significant antiprotozoal activity and can
are used against amoeba and giardia.
Used as radiosensitizing in certain solid
tumours.