ANTIBIOTICS

ROLE OF ANTIBIOTICS
• Therapeutic : to treat existing infection
• Prophylactic: reduces risk of wound infection
AMINOGLYCOSIDES
• Most infections on the surgical ward are due to one or
more gram negative rods acting on either sole pathogens
or a principal component in microbial flora.

• 4 classes of aminoglycosides:
Amikacin
Gentamicin
Neomycin
tobramycin
MOA
• Displays a concentration dependent bactericidal activity
against most G-ve aerobic and facultative anaerobic
bacilli apart from some bacilli and methicillin resistant
staphylococci
• Inhibition of protein synthesis- mediated through
aminoglycoside energy dependent
INDICATIONS
• Infections involving: aerobic G-ve bacteria
• Some mycobacteria including the bacteria that causes T.B
are susceptible to aminoglycosides
• Role of aminoglycosides such as streptomycin and
amikacin has been outdone except for multiple drug
resistant strains
USES
• Most frequent :
Empiric therapy for serious infection eg septicaemia
Complicated intra abdominal infections
Complicated UTI
nosocomial respiratory tract infections
ROUTE OF ADMINISTRATION
• Are administered IV and IM
• Some used in topical preparation for wound
• Oral medication used for gut decontamination
• Tobramycin – admitted in nebulizer form
CONTRAINDICATION AND SIDE EFFECTS
• aminoglycoside can exacerbate weakness in patients

• SIDE EFFECTS :
• Ototoxicity
• nephrotoxicity
streptomycin
• Bactericidal antibiotic
RESISITANCE:
Streptomycin can be used clinically to treat tuberculosis in
combination with other medications and susceptible strains
which cause bacterial endocarditis.
USES OF STREPTOMYCIN
• Treatment of diseases:
1. Infective endocarditis
2. Tuberculosis
3. Plague
Streptomycin is traditionally given as IM, but the drug may
also be administered as IV
- To minimize the development of drug resistant bacteria
and remain maintenance of streptomycin, it should only be
used to treat and prevent infections caused by bacteria
• SIDE EFFECCTS:
Fever
 rashes
 The Vestibular portion of cranial nerve VIII (the
vestibulocochlear nerve) can be affected
NEOMYCIN
• Aminoglycoside antibiotic found in many topical
medications such as creams, ointments, and eye drops
• Due to oto and nephrotoxicity of these substances:
systemic uses has declined as safer alternatives become
available
USES:
• Not absorbed from GIT and has been used on a
preventative measure- hepatic encephalopathy and
hypercholesterolemia
• MOLECULAR BIOLOGY:
• Resistance is conferred by either one of 2 aminoglycoside
phosphotransferase genes
• Neo genes is commonly included in DNA plasmids used in
molecular biology to establish stable mammalian cell lines
expressing cloned protein in culture
SPECTRUM
• Has excellent activity against G-ve bacteria and has
partial activity against G+ve bacteria
• Relatively toxic to humans and many people have allergic
reactions
• SIDE EFFECTS
• May cause permanent hearing loss, nerve damage and
severe kidney damage
• Also cause severe muscle relaxation progressing to
paralysis and breathing problems
• INDICATION:
• Suppression of intestinal bacteria of bowel before colonic
surgery
• PRECAUTIONS
• Gastrointestinal, renal, hepatic
CARBAPENEMS
• Class of B lactam antibiotics with broad spectrum
• Last resort for many bacterial infection e.g. E.coli and
Klebseilla , pneumonia

• Ertapenem
• Imipenem
• Meropenem
• 1: broad spectrum Carbapenems, limited activity against
non fermentive –ve bacilli
• 2: broad spectrum Carbapenems
• 3: includes Carbapenems with clinical activity methicillin
resistant SA
• Most widely used carbapenems includes: meropenem,
imipenem + cilastin
SPECTRUM OF USES
• Broadest spectrum compared to other cephalosporin and
penicillins
• Carbapenems circumvent B lactamase by binding it with
high affinity and acyclating the enzyme rendering it
ineffective
• Are active against G+ve and G –ve bacteria and
anaerobes with exception of intracellular bacteria e.g.
chlamydia
• MOA: inhibits bacterial cell wall synthesis, usually
bactericidal
• STRUCTURE:
• ADVERSE EFFECTS:
Nausea, vomiting , diarrhoea
Local injection site reactions
ADMINISTRATION
• Due to broadest spectrum to avoid generation of resistant
and the fact that in general they have poor bioavailability
so IV is administered
CEPHALOSPORINS
• Worldwide, cephalosporin are the most widely used
antibiotics for surgical prophylaxis
• B lactam originally derived from fungus Acremonium
which was previously known as ‘cephalosporium’
MEDICAL USES
• Prophylaxis
• Treatment of infections caused by bacteria susceptible to
this particular form of antibiotic
• 1st generation active more against G+ve bacteria
• Successive generation has increased inactivity against G-
ve bacteria
MOA
• Are bactericidal
• Same MOA as other B lactam antibiotics, less susceptible
to B lactamases
• Disrupts synthesis of peptidoglycan layer – bacterial cell
wall
ADVERSE EFFECTS
Diarrhoea
Nausea
Rash
Electrolyte disturbances
Pain and inflammation on injection site
CLASSIFICATION
• Cephalosporin nucleus can be modified to gain different
properties. It is sometimes grouped into ‘generations’ by
their antimicrobial properties
• Newer generations has significantly more G-ve
antimicrobial properties than the preceding generation
• LAME
• Classification:
 1st generation- cefalotin, cephalexin, cephazolin
 2nd generation- cefoxitin, cefuroxime
 3rd generation- cefotaxime, ceftazidime, ceftriaxone
 Fourth-generation cephalosporin were considered to be "a
class of highly potent antibiotics that are among
medicine's last defences against several serious human
infections
CEFTRIAXONE
• Antibiotic useful for the treatment of a number of bacterial
infections.
• Broad spectrum activity against G+ve bacteria and
expanded G-ve coverage compared to 2nd generation
agents
INDICATION
• Empirical treatment of severe pneumonia
• Tx of orbital cellulitis
• Bacterial meningitis
• Gonococcal infections
• MEDICAL USE:
• Serious infections caused by organism that are resistant
to most other antibiotics
• Often used with macrolide/aminoglycoside for the tx of
community acquired mild/moderate health care associate
pneumonia
• Bacterial meningitis
• Others: tx of skin and skin infections, bone and joint
infections, gonorrhea, intra abdominal and UTI, pelvic
inflammatory disease
• ADVERSE EFFECTS:
• Precipitate in bile causing biliary sludge, biliary
pseudolithiasis and gallstones specially in children
• Allergic reactions similar to penicillin
SPECTRUM
• Ceftriaxone is active against citrobacter and B lactamase
producing strains of haemophilus and Neisseria
• MOA:
• Inhibits cell wall synthesis by means of binding to the
penicillin binding proteins.
• It is bactericidal and exhibits time dependent killing
GLYCOPEPTIDES
• Is a class of drugs of microbial origin that are composed
of glycosylated cyclic or polycyclic nonribosomal peptides
• Further divided: vancomycin and teicoplanin
MOA
• Inhibits the synthesis of cell walls in susceptible microbes
by inhibiting peptidoglycan synthesis
• Binds to amino acids within cell wall preventing the
addition of new units to the peptidoglycan
USES
• Due to their toxicity, use of glycopeptide is restricted to
patient’s who are critically ill, who have a demonstrated
hypersensitivity to the B lactams
• Antibiotics are primarily effective against G+ve cocci
• Exhibits a narrow spectrum of action
ADVERSE EFFECTS
• Oral vancomycin usually causes only GI adverse effects
unless significant serum concentrations occur
• Most common symptom is phlebitis
• Red mans syndrome
ADMINISTRATION
• Vancomycin usually given IV, can cause tissue necrosis
and phlebitis at the injection site if given too rapidly
• One side effect is red man’s syndrome. It has an
idiosyncratic reaction to bolus caused by histamine
release
Red man syndrome
• Vancomycin Is recommended to be administered in a
dilute solution slowly, over atleast 60minutes due to high
incidence of pain, and thrombophlebitis and to avoid an
infusion reaction
• Characteristics:
 Flushing and rashes affecting face, neck and upper torso
 Due to mast cells degranulation and are not an IgE
related allergic reaction
• Other side effects: nephrotoxicity
• 90% dose excreted in urine
• Oral preparation of vancomycin is available , however the
are not absorbed from the lumen of the gut, so are of no
use in treating systemic infections
VANCOMYCIN
• Naturally occurring antibiotic made from soil bacterium
• Clinically used to treat infection caused by penicillin
resistant staphylococcus Aureus
• MEDICAL USES:
 Infections by G+ve bacteria unresponsive to other
antibiotics
 Not be used to treat methicillin sensitive staphylococcus
aureus
• Tx of pseudomembranous colitis
• Tx of infections caused by G+ve microorganism in
patients with serious allergies to B lactam antimicrobials
• Antibacterial prophylaxis to endocarditis
• Surgical prophylaxis
IV .VS. ORAL ADMINISTRATION
• Must be given IV for systemic therapy since it is not
absorbed from the intestine
• Only approved indication of oral vancomycin therapy is in
the tx of pseudomembranous colitis, must be given orally
to each site of infection of the colon
• SPECTRUM:
• Last resort medication to tx of septicemia and lower
respiratory tract infections caused by G+ve bacteria
MOA
• Acts by binding proper cell wall synthesis in G+ve
bacteria. Due to the different mechanism by which G-ve
bacteria produce their cell walls and various factors
related to entering the outer membrane of G –ve
organisms
• RESISTANCE:
2 types: intrinsic and acquired
• Intrinsic- most G-ve bacteria are intrinsically resistant to
vancomycin because of their outer membrane which is
permeable to large glycopeptide molecules
• Acquired- with newer vancomycin existence, the
widespread use of vancomycin makes resistance to the
drug a significant problem, specially for individual patients
if resistant infections are not quickly identified and the
patient continues ineffective treatment
1. true or false? Vancomycin is used for MRSA
2. give the 3 drugs under carbapenems
3. Vancomycin is effective against which form of bacteria?
4. In what form is tobramycin used in?
5. Give 2 common side effects of aminoglycosides
6.Red man’s syndrome is a common side effect of
________
7. Vancomycin belongs to which class of drugs?
8. 2 main uses of streptomycin
9. Aminoglycosides are effective against which bacterial
strain?
10. Common medical use of cephalosporin
11. In all the classes of drugs discussed above, what is the
most common ROA?
12. What generation does ceftriaxone belong to?
13. The pneumonic “LAME” is used in which class of drug?
14. What are the 2 roles of antibiotics?
15. What form of administration is suitable for
pseudomembranous colitis?
A. IV
B. Oral
C. IM
16. Why is carbapenems preferably given in IV form?\
17. Which of the following are widely used for prophylaxis
of surgery?
A. Carbapenems
B. Cephalosporin
C. Glycopeptides
D. Aminoglycosides
18. Which of the following drugs is being investigated for
prevention of relapse of cocaine addiction?
A. Streptomycin
B. Vancomycin
C. Ceftriaxone
D. imipenem
19. True or false: Red man’s syndrome is an IgE related
allergic reaction?