CHEMOTHERAPY
(General Principles)
OBJECTIVES:
General principles of chemotherapy for other
drugs govern antimicrobial chemotherapy also.
However, there are principles that are more
pertinent to the use of antimicrobial agents as a
group. Particular attentions should be directed to
the following:
1. Mechanisms of actions of different groups of
antibiotics.
2. Mechanisms by which pathogens acquire and
express
resistance to antibiotics.
3. Combination therapy (use of two or more
drugs
concomitantly).
4. Host determinants that influence the selection
and efficacy of antibiotics.
INTRODUCTION TO ANTIMICROBIAL
CHEMOTHERAPY
(General Principles)
PR0TOTYPES
Penicillin G
Rifampin
Polymyxin
Ciprofloxacin
Choramphenicol
Sulfamethoxazole
Streptomycin
CONJUGATION
1.
2.
3.
4.
2.
3.
1.
2.
3.
Cephalosporins:
1.
2.
3.
Production of -LACTAMASE
2.
3.
4.
Semisynthetic Penicillins
1.
2.
3.
4.
(b)
Major Determinants: Benzylpenicilloyl-polylysine (penicilloylpolylysine, PPL or pre-pen), available commercially. Patients showing
positive tests to major determinants are likely to react to therapeutic
doses of -lactams and more likely to manifest slow onset type
reactions.
Minor Determinants: Penicillin G and some of its hydrolyzates. Usually
penicillin G is used for skin test. Positive tests indicate a high-risk for
an immediate, anaphylactic reaction.
**Even negative tests to either or both determinants do not exclude the possibility
of serious, immediate type reactions.
**The major and minor refer to the frequency of reaction and not the seriousness
of reaction (i.e. patients having positive reaction to minor determinants are likely
to have more serious reactions)
before the
A.
B.
-LACTAMASE Inhibitors:
Clavulanic acid; Sulbactam:
by inactivating the enzyme these compounds enhance
the antibacterial activity when used in combination with
other -lactam antibiotics.
OBJECTIVES:
This chapter describes 4 different groups of
chemotherapeutic agents. These groups are discussed
together mainly because these drugs are frequently used for
the same types of infectionsmainly urinary tract infections.
Particular attentions should be directed to the following.
Sulfonamides and quinolones
1. Mechanisms of actions
2. Pharmacological properties of prototypes that
represent different groups
3. Currently important therapeutic uses of specific drugs
4. Significant untoward effects
Trimethoprim-sulfamethoxazole
1.
Mechanism of action
(advantages of the
combination)
2.
Currently important therapeutic
uses
3.
Significant untoward effects
Urinary tract antiseptics and related agents
1.
Definition
2.
Nomenclatures of common
prototype
(sulfonamide, etc)
PROTOTYPES:
SULFONAMIDES: sulfadiazine; silver sulfadiazine;
sulfacetamide;
sulfisoxazole; sulfasalazine; sulfadoxine.
TRIMETHOPRIM-SULFAMETHOXAZOLE:
QUINOLONES: nalidixic acid; ciprofloxacin; ofloxacin;
sparfloxacin
URINARY TRACT ANTISEPTIC: methenamine
URINARY TRACT ANTISEPTIC RELATED AGENT: phenazopyridine
(a)
Sulfacetamide: sodium salt is water-soluble
and is used in eye-drops.
(b)
Silversulfadiazine: for management of burn
wounds.
Patient acceptance is better than
mafenide.
(c)
Sulfasalazine: very useful for treating
ulcerative colitis
(d)
Sulfadoxine: extra long acting sulfonamide.
Useful for
prophylaxis of chloroquine resistant P.
falciparum
malaria.
2.
3.
4.
Therapeutic uses
1.
2.
Some
(a)
(b)
(c)
(d)
(e)
and
(f)
1.
2.
Pharmacokinetics of quinolones
1.
MISCELLANEOUS ANTIBIOTICS
OBJECTIVES:
Antibiotics discussed in this chapter are considered preferred
agents in limited types of infection. Some of these agents are
exquisitely effective for the respective limited purposes. Particular
attentions should be directed to the following with respect to the
prototypes that represent different groups:
1.
2.
3.
4.
Mechanism of action
Pharmokinetics pertinent to therapeutic uses
Therapeutic uses
Significant untoward effects
Prototypes:
Macrolides:
Clindamycin
Spectinomycin
Vancomycin
Polymyxin
Bacitracin
(erythromycin; azithromycin;
clarithromycin)
Therapeutic Use
Erythromycin
Azithromycin*
Clarithromycin*
Clindamycin
Spectinomycin
Vancomycin
Therapeutic Use
Polymyxin*
Bacitracin*
Act. Mech.
Erythromycin
Azithromycin)
Clarithromycin
50s Ribosm
Clindamycin
50s Ribosm
Spectinomycin
30s Ribosm
Minor neuropathy
Vancomycin
Act. Mech.
Polymyxin
Cell
membrane
function
Extreme nephrotoxicity
Bacitracin
Cell wall
1.
Vancomycin
2.
Trimethoprim-sulfamethoxazole
3.
4.
Rifampin, Rifabutin
Amikacin*; doxycycline*
MECHANISM OF ACTION:
1.
2.
3.
UNTOWARD EFFECTS
ISONIAZID:
ETHAMBUTOL:
RIFAMPIN:
PYRAZINAMIDE:
CLOFAZIMINE: