PRICIPLES OF CHEMOTHERAPY
Definitions
Antimicrobial agents
antibiotics + synthetic chemotherapeutics
Antibiotics
classical definition - chemical substances produced by various microorganisms that suppress
the growth of others microorganisms and may actually destroy them
Common used definition of antibiotics - antibiotics + synthetic antimicrobial agents
Selection of an antibiotic – what is important?
Type of therapy: empiric or definitive
Empiric therapy - no microbiological confirmation. What has to be considered?
Site of infection, clinical characteristics and origin of infection
Site of infection
Microbes
Nose and oral cavity
Teeth
Skin
Genitourinary tract
Intestine
Staph, Strep, diphteroids, Neisseria, Haemophilus
Strep., anerobes (Bacteroides, Fusobacterium), Actinomyces
Staph, diphteroids, Strep, Pseudomonas, anaerobes, Candida Pithyrosporum
Gram-negative rods (E.coli, proteus, Serratia), Staph., Strep.
Anaerobes (Bacteroides, Fusobacterium, Clostridia), Gram-negative-rods (E.
coli, Salmonella), Stap., Strep., (Strep. Faecalis), Pseudomonas,
Lactobacillus
Infection origin: community – acquired infection and hospital – acquired infection.
Definitive therapy - microbiological identification/confirmation is necessary
The effect of antibacterial drugs observed in vitro: bactericidal or bacteriostatic
Types of antibiotic resistance among bacteria: primary or secondary (due to mutation - onestep, multi-step or to migration of genetic material – most frequent)
Pharmacokinetics and antimicrobial effect
Concentration-dependent effect – aminoglycosides, fluorochinolones
Dose-dependent effect – azithromycin, flourochinolones
Time-dependent effect – beta-lactams
Antibiotic selection – what should be considered?
a)route of administration and site of infection: vancomycin - orally – pseudomembranous
colitis, i.v. – pneumonia; polimyxines - topically – intrabronchially – pneumonia, i.v. –
urosepsis; aminoglicosides - orally – prevention against hepatic encephalopathy, i.v. – acute
pyelonephritis
1
b) absorption
Agent
Disease
Bioavailability
Amoxicillin

Celiac disease
Erythromycin Leśniowski-Crohn disease 
Trimetoprim Celiac disease

Vankomycin Ulcerative colitis

Metronidazole Ulcerative colitis

Clindamycin Leśniowski-Crohn disease 
c)distribution - proteins in plasma: hipoalbuminemia (hepatic failure, nephrotic syndrome) –
Sulfonamides? Aminoglycosides? Leukocytosis (leukemia), anemia – Aminoglycosides?
CNS infection - Penicillins? Metronidazole? Aminoglycosides? Bones infection.
Clindamycin? Aminoglycosides? Prostatitis. Norfloxacin? Aminopenicillins? Biliary tract
infection. Ampicillin? Natural penicillins?
d) topical factors - hematoma, abscessus, urine pH, gastic acid pH, synthetic valves, vascular
prostheses, catheters
e)time of therapy - urethitis – 1-3 days, endocardistis – 30 days, pneumonia 7-21 days
f) adverse effects
Kidneys dysfunction – avoid: aminoglycosides, vancomycin, polipeptides, amphotericin B.
Liver dysfunction - avoid: doxycyclin, clindamycin, erythromycin, ketokonazole, isoniasid
Neurologic diseases. Attention: high doses of natural penicillins, nitrofurantoin, quinolones
Hypersensitivity. Attention: beta-lactams, sulfonamides, macrolides
Genetic problems. Sulfonamides, nitrofurantoin – glucose-6-phosphate dehydrogenase
deficiency
Neutropenia. Attention: metronidazole, aminopenicillins, cefalosporins
Anemia. Attention: zidovudine, amphotericin B
g) patient status - proteins in plasma
• Organs function : GI tract, liver, kidneys
• Age: neonates and infants – tetracyclines, quinolones, sulfonamides!!!
Older persons: attention: tetracyclines, aminoglycosides, vancomycin, quinolones
 Pregnancy and lactation: acceptable –natural penicillins, aminopenicillins, 1st
generation cephalosporins, erythromycin
Contraindicated: quinolones, tetracyclines, sulfonamides
• diabetic foot – angiopathy
• immunosupression - neutropenia, limfopenia
2
Indications for the clinical use of antibiotics combinations
• treatment of mixed infections
• empiric therapy
• achievement of synergism
• doses reduction
• resistance prevention
Combination of:
• ..cidal+..cidal - synergism or indifference (additive result), never antagonism
• ..static+..static - additive effect, never synergism or antagonism
• ..cidal+..static- indifference or antagonism when bacteria is high susceptible to ..cidal
or synergism when bacteria is low susceptible to ..cidal
The prophylaxis of infection with antibiotics
• to protect healthy persons from acquisition of or invasion by specific microorganism
to which they are exposed
• to prevent secondary bacterial infections in patients who are ill with other diseases
• to prevent endocarditis in patients with valvular or other structural lesions of the heart
who are undergoing dental, surgical or other procedures that produce a high incidence
of bacteriemia
• to prevent wound infections after various surgical procedures
Superinfections
The appearance of bacteriological and clinical evidence of a new infection during
chemotherapy of a primary one.
• changes in the normal microbial population of the intestinal, upper respiratory and
genitourinary tract
• when broad-spectrum agents are used
3