Antimicrobial chemotherapy is the use of drugs to control microorganisms for the prevention and treatment of disease. The most successful drugs
interfere with vital processes that differ between the pathogen and host,
thereby seriously damaging the target microorganism while harming its host as
little as possible.
Ideally,
chemotherapeutic agents used to treat infectious disease destroy pathogenic
microorganisms or inhibit their growth at concentrations low enough to
avoid undesirable damage to the host. Most of these agents are antibiotics [Greek
anti, against, and bios, life], microbial products or their derivatives
that can kill susceptible microorganisms or inhibit their growth. Drugs such as
the sulfonamides are examples of synthetic chemotherapeutic agents and are not
microbially synthesized.
Chemotherapy
Paul Ehrlich is
considered the father of the modern era of chemotherapy. Ehrlich was fascinated
with dyes that specifically bind to and stain microbial cells-that would
selectively destroy pathogens without harming human cells—a “magic bullet.” By
1904 Ehrlich found the dye trypan red active against the trypanosome that causes
African sleeping sickness and arsphenamine (commercially, Salvarsan) active
against the syphilis spirochete. In 1927, Gerhard Domagk discovered Prontosil
Red, (the source of sulfonamides, or sulfa drugs) against pathogenic Streptococci
and Staphylococci. Domagk received the 1939 Nobel Prize in Physiology or
Medicine for his discovery of sulfonamides, or sulfa drugs. In the 1920s,
Alexander Fleming, a Scottish physician, found that human tears contained a
naturally occurring antibacterial substance that he termed “lysozyme.” The
first true antibiotic Penicillin was later discovered by Fleming.
In 1896, by a
21-year-old French medical student named Ernest Duchesne had actually
discovered penicillin but it was Fleming’s discovery which made it famous.
Penicillium
mold colony secretes penicillin that kills Staphylococcus aureus
Fleming, Florey, and
Chain received the Nobel Prize in 1945 for the discovery
and production of penicillin. The discovery of penicillin stimulated the search
for other antibiotics.
Selman Waksman
announced in 1944 and his associates found a new antibiotic, streptomycin,
produced by the actinomycete Streptomyces griseus. Streptomycin was the
first drug that could successfully treat tuberculosis. Waksman received the Nobel
Prize in 1952
Search for other
antibiotic-producing soil microorganisms led to the isolation of
chloramphenicol, neomycin and tetracycline by 1953. The discovery of
chemotherapeutic agents and the development of newer, more powerful drugs have
transformed modern medicine and greatly alleviated human suffering.
Characteristics of
Antimicrobial Drugs
To be successful a
chemotherapeutic agent must have selective toxicity: it must kill or
inhibit the microbial pathogen while damaging the host as little as possible.
The degree of selective
toxicity is expressed as
(1) the therapeutic
dose, the drug level required for clinical treatment of a particular
infection
(2) the toxic dose,
the drug level at which the agent becomes too toxic for the host.
The therapeutic
index is the ratio of the toxic dose to the therapeutic dose. The larger
the therapeutic index, the better the chemotherapeutic agent (all other things
being equal).
A drug that disrupts a
microbial function not found in eucaryotic animal cells often has a greater
selective toxicity and a higher therapeutic index. For example, penicillin
inhibits bacterial cell wall peptidoglycan synthesis but has little effect on
host cells because they lack cell walls; therefore penicillin’s therapeutic
index is high. A drug which inhibits the same process in host cells or
damages the host in other ways may have a low therapeutic index. The
undesirable effects on the host, or side effects, are of many kinds and may
involve almost any organ system. Because side effects can be severe,
chemotherapeutic agents should be administered with great care.
Some bacteria and
fungi are able to naturally produce many of the commonly employed
antibiotics. In contrast, several important chemotherapeutic agents, such as
sulfonamides, trimethoprim, chloramephenicol, ciprofloxacin, isoniazid, and
dapsone, are synthetic—that is, manufactured by chemical procedures. Semisynthetic
antibiotics are natural antibiotics that have been structurally modified by
the addition of chemical groups which make them less susceptible to
inactivation by pathogens (e.g., ampicillin, carbenicillin, and methicillin). Many
semisynthetic drugs have a broader spectrum of antibiotic activity than their
parent molecule. e.g., ampicillin, amoxycillin
Microbial
Sources of Some Antibiotics
|
Microorganism
|
Antibiotic
|
|
Actinomyces
|
|
|
Streptomyces
spp.
|
Amphotericin
B
Chloramphenicol
(also synthetic)
Kanamycin
Neomycin
Nystatin
Rifampin
Streptomycin
Tetracyclines
Vancomycin
|
|
Bacteria
|
|
|
Micromonospora
spp.
|
Gentamicin
|
|
Bacillus
spp.
|
Bacitracin
Polymyxins
|
|
Fungi
|
|
|
Penicillium
spp.
|
Griseofulvin
Penicillin
|
|
Cephalosporium
spp.
|
Cephalosporins
|
Drugs have different
range of effectiveness. Many are narrow-spectrum drugs— effective only
against a limited variety of pathogens. Broad-spectrum drugs act against
many different kinds of pathogens.
Drugs may also be
classified based on the general microbial group they act against: antibacterial,
antifungal, antiprotozoan, and antiviral. Some agents can be used against
more than one group; for example, sulfonamides are active against bacteria and
some protozoa.
Chemotherapeutic
agents, like disinfectants, can be either cidal or static. Static agents
reversibly inhibit growth; if the agent is removed, the microorganisms will
recover and grow again. A cidal agent kills the target pathogen. The effect of
an agent also varies with the target species: an agent may be cidal for one
species and static for another. A static agent may not be effective if the
host’s resistance is too low.
The minimal inhibition
concentration (MIC) is the lowest concentration of a drug that prevents
growth of a particular pathogen. The minimal lethal concentration (MLC)
is the lowest drug concentration that kills the pathogen. A cidal drug
generally kills pathogens at levels only two to four times the MIC, whereas a
static agent kills at much higher concentrations.
ANTIBACTERIAL DRUGS
Antibiotics damage
pathogens in several ways. Examples of antibiotics with the process inhibited,
are the following: chloramphenicol (bacterial protein synthesis), cycloserine
(peptidoglycan synthesis), nalidixic acid and novobiocin (bacterial DNA
synthesis), rifampin (bacterial RNA synthesis), cycloheximide (eucaryotic
protein synthesis), polyoxin D (fungal cell wall chitin synthesis), and
cerulenin (fatty acid synthesis.
A few antibacterial drugs
are described here, with emphasis on their mechanisms of action.
- Inhibitors
of Cell Wall Synthesis
- Inhibitors
of Protein Synthesis
- Inhibitors
of Nucleic acid Synthesis
- Antimetabolites
Inhibitors of Cell Wall
Synthesis
The most selective antibiotics are those that
interfere with bacterial cell wall synthesis. Drugs like penicillins,
cephalosporins, vancomycin, and bacitracin have a high therapeutic index
because they target structures not found in eukaryotic cells.
Penicillins
Most penicillins (e.g.,
penicillin G or benzylpenicillin) are derivatives of 6-aminopenicillanic acid
and differ from one another with respect to the side chain attached to its
amino group. β-lactam ring, is essential for bioactivity. Many
penicillin-resistant bacteria produce penicillinase (β -lactamase), an enzyme
that inactivates the antibiotic by hydrolyzing a bond in the β lactam ring.
Penicillin structure resemble the terminal D-alanyl-D-alanine found on the peptide side chain of the peptidoglycan subunit. This structural similarity blocks the enzyme catalyzing the transpeptidation reaction that forms the peptidoglycan cross-links. Thus formation of a complete cell wall is blocked, leading to osmotic lysis. Hence, penicillins act only on growing bacteria that are synthesizing new peptidoglycan.
Penicillins also bind to several periplasmic proteins (penicillin-binding proteins, or PBPs) and may also destroy bacteria by activating their own autolytic enzymes. Penicillin may stimulate special proteins called bacterial holins to form holes or lesions in the plasma membrane, leading directly to membrane leakage and death.
The two naturally occurring penicillins, penicillin G and penicillin V, are narrow-spectrum drugs. Penicillin G is effective against gonococci, meningococci, and several gram-positive pathogens such as streptococci and staphylococci. However, it is destroyed by stomach acid and it must be administered by injection (parenterally). Penicillin V is similar to penicillin G in spectrum of activity, but can be given orally because it is more resistant to acid.
The semisynthetic penicillins, have a broader spectrum of activity. Ampicillin can be administered orally and is effective against gram-negative bacteria such as Haemophilus, Salmonella, and Shigella. Carbenicillin and Ticarcillin are potent against Pseudomonas and Proteus.
Many bacteria have
become resistant to natural penicillins and many of the semisynthetic analogs. Specific
semisynthetic penicillins that are not destroyed by β -lactamases such as, methicillin,
nafcillin, and oxacillin are used to combat antibiotic-resistant pathogens such
as methicillin-resistant bacteria.
Although penicillins
are the least toxic of the antibiotics, about 1 to 5% of the adults may be
allergic to them. Occasionally, a person will die of a violent allergic
response; therefore, patients should be questioned about penicillin allergies before
treatment is begun.
Cephalosporins
Cephalosporins are a
family of antibiotics originally isolated in 1948 from the fungus Cephalosporium acremonium.
They contain a β -lactam structure that is very similar to that of the
penicillins. Cephalosporins also inhibit the transpeptidation reaction during
peptidoglycan synthesis.
They are broad-spectrum drugs frequently given to
patients with penicillin allergies (although about 10% of patients allergic to
penicillin are also allergic to cephalosporins).
Cephalosporins are
broadly categorized into generations (groups of drugs that are
sequentially developed) based on their spectrum of activity.
First generation
cephalosporins are more effective against Gram-positive organisms, such as staphylococci and streptococci, and minimal coverage against Gram-negative bacteria. Examples include cefazolin, cephalothin, cephradine, cefadroxil, and cephalexin.
Second-generation drugs,
developed after the first generation, have improved effects on gram negative
bacteria with some anaerobe coverage. These cephalosporins are more effective against Gram-negative bacteria, but less effective against Gram-positive bacteria. Has better cell penetration. Increased resistance to beta lactamases. Examples include cefuroxime and cefprozil.
Third-generation drugs are effective against gram-negative pathogens, and some reach the
central nervous system. This is important because many antimicrobial agents do
not cross the blood-brain barrier. Examples include cefotaxime, ceftazidime, cefdinir, ceftriaxone, cefoperazone, and cefixime.
Fourth-generation cephalosporins
are broad spectrum with excellent gram-positive and gram-negative coverage and,
like their third-generation predecessors, inhibit the growth of the difficult
opportunistic pathogen Pseudomonas aeruginosa. These cephalosporins have an improved gram-positive spectrum while retaining the expanded gram-negative activity of the third generation. Wider spectrum of activity and improved resistance to beta lactamases. Examples include cefepime and cefpirome.
Fifth generation These cephalosporins
include ceftaroline and ceftobiprole. These are approved for treating critical
infections, such as hospital-acquired pneumonia.
Vancomycin
Vancomycin is a glycopeptide antibiotic
produced by Streptomyces oreintalis. It is a cup-shaped molecule
composed of a peptide linked to a disaccharide.
Vancomycin’s peptide portion
blocks the transpeptidation reaction by binding specifically to the
D alanine-D-alanine terminal sequence on the pentapeptide portion of peptidoglycan.
The antibiotic is bactericidal for Staphylococcus and some members of the
genera Clostridium, Bacillus, Streptococcus, and Enterococcus.
It is given both
orally and intravenously and is important in the treatment of antibiotic resistant
staphylococcal and enterococcal infections.
Vancomycin has been
considered the “drug of last resort” in cases of antibiotic resistant S.
aureus. However, vancomycin-resistant strains of Enterococcus and resistant
Staphylococcus aureus (VRSA) are prevalent now
Teicoplanin
Teicoplanin is a glycopeptide antibiotic from the actinomycete Actinoplanes
teichomyceticus that is similar in structure and mechanism of action to
vancomycin, but has fewer side effects. It is active against Staphylococci,
Enterococci, Streptococci, Clostridia, Listeria, and many other gram-positive
pathogens.
Protein Synthesis Inhibitors
Many antibiotics inhibit
protein synthesis by binding with the prokaryotic ribosome. Because these drugs
discriminate between prokaryotic and eucaryotic ribosomes, their therapeutic index
is fairly high, but not as high as that of cell wall inhibitors. Some drugs
bind to the 30S (small) ribosomal subunit, while others attach to the 50S
(large) subunit.
Several different steps in protein synthesis can be affected:
aminoacyl-tRNA binding, peptide bond formation, mRNAreading, and translocation.
Aminoglycosides
Aminoglycoside
antibiotics contain a cyclohexane ring and amino sugars. Streptomycin,
kanamycin, neomycin, and tobramycin are synthesized by different Streptomyces
species, whereas gentamicin comes from another actinomycete, Micromonospora
purpurea.
Aminoglycosides bind to the 30S (small) ribosomal subunit and interfere
with protein synthesis by directly inhibiting the synthesis process and also by
causing misreading of the mRNA.
These antibiotics are bactericidal and are most
effective against gram-negative pathogens. Streptomycin is effective in treating
tuberculosis and but widespread drug resistance is a problem. Gentamicin
is used to treat Proteus, Escherichia, Klebsiella, and Seratia infections.
Aminoglycosides can be quite toxic, however, and can cause deafness, renal damage,
loss of balance, nausea, and allergic responses.
Tetracyclines
The tetracyclines are a
family of antibiotics with a common four ring structure to which a variety of
side chains are attached. Oxytetracycline and chlortetracycline are produced
naturally by Streptomyces species while others are semisynthetic drugs.
These
antibiotics are similar to the aminoglycosides and combine with the 30S (small)
subunit of the ribosome. This inhibits the binding of aminoacyl-tRNA molecules
to the A site of the ribosome.
Because their action is only bacteriostatic,
the effectiveness of treatment depends on active host immune system.
Tetracyclines are broad-spectrum antibiotics that are active against
gram-negative, as well as gram-positive bacteria, Rickettsias, Chlamydiae, and
Mycoplasmas. High doses may result in nausea, diarrhea, yellowing of teeth in
children, and damage to the liver and kidneys.
Macrolides
The macrolide
antibiotics contain 12- to 22-carbon lactone rings linked to one or more sugars.
Erythromycin is usually bacteriostatic and binds to the 23S rRNA of the
50S (large) ribosomal subunit to inhibit peptide chain elongation during
protein synthesis. Erythromycin is a relatively broad-spectrum antibiotic
effective against gram-positive bacteria, mycoplasmas, and a few gram-negative
bacteria. It is used with patients who are allergic to penicillins and in the
treatment of whooping cough, diphtheria, diarrhea caused by Campylobacter, and
pneumonia from Legionella or Mycoplasma infections.
Clindamycin is
effective against a variety of bacteria including staphylococci, and anaerobes
such as Bacteroides. Azithromycin, is particularly effective against
Chlamydia trachomatis.
Chloramphenicol
Chloramphenicol was
first produced from cultures of Streptomyces venezuelae but is now
synthesized chemically. Like erythromycin, this antibiotic binds to 23S rRNA on
the 50S ribosomal subunit to inhibit the peptidyl transferase reaction. It has
a very broad spectrum of activity but, is quite toxic. Allergic responses or
neurotoxic reactions may be seen. The most common side effect is depression of
bone marrow function, leading to aplastic anemia and a decreased number of
white blood cells. So, this antibiotic is used only in life-threatening
situations when no other drug is adequate.
Metabolic Antagonists
Several drugs
act as antimetabolites—they antagonize, or block, the functioning of
metabolic pathways by competitively inhibiting the use of metabolites by key
enzymes. These drugs can act as structural analogs, molecules that are
structurally similar to naturally occurring metabolic intermediates. These
analogs compete with intermediates in metabolic processes because of their
similarity, and prevent normal cellular
metabolism. They are bacteriostatic and broad spectrum.
Sulfonamides or Sulfa
Drugs
The first antimetabolites to be used successfully
as chemotherapeutic agents were the sulfonamides, discovered by G. Domagk.
Sulfonamides, or sulfa drugs, are structurally related to sulfanilamide,
an analog of p-aminobenzoic acid, or PABA.
PABA is used in the
synthesis of the cofactor folic acid (folate). When sulfanilamide or another
sulfonamide enters a bacterial cell, it competes with PABA for the active site
of Dihydropteroate synthase, an enzyme involved in folic acid synthesis, causing a decline in folate
concentration. Folic acid is a precursor of purines and pyrimidines, the bases
used in the construction of DNA, RNA, and other important cell constituents so
this decline is harmful to the bacterium. The resulting inhibition of purine
and pyrimidine synthesis leads to inhibition of protein synthesis and DNA
replication, thus the pathogen dies.
Sulfonamides thus have a high therapeutic index. Sulfonamides are
selectively toxic for many pathogens because these bacteria manufacture their
own fo late and cannot effectively take up this cofactor, whereas humans do not
synthesize folate (we must obtain it in our diet).
The increasing
resistance of many bacteria to sulfa drugs limits their effectiveness. 5% of the patients receiving sulfa drugs experience
adverse side effects, chiefly allergic responses such as fever, hives, and
rashes.
Trimethoprim
Trimethoprim is a
synthetic antibiotic that also interferes with the production of folic acid. It binds to dihydrofolate reductase (DHFR), the enzyme responsible
for converting dihydrofolic acid to tetrahydrofolic acid, competing against the
dihydrofolic acid substrate
It is a broad-spectrum
antibiotic often used to treat respiratory and middle ear infections, urinary
tract infections, and traveler’s diarrhea.
It can be combined with sulfa drugs
to increase efficacy of treatment by blocking two key steps in the folic acid
pathway.
The inhibition of two
successive steps in a single biochemical pthway means that less of each drug
is needed in combination than when used alone. This is termed a synergistic
drug interaction.
The most common side
effects associated with trimethoprim are abdominal pain, abnormal taste,
diarrhea, loss of appetite, nausea, swelling of the tongue, and vomiting.
Taking trimethoprim with food may reduce some of these side effects. Some
patients are allergic to trimethoprim, exhibiting rash and itching. Some
patients develop photosensitivity reactions (i.e., rashes due to sun exposure).
Nucleic Acid Synthesis
Inhibition
The antibacterial drugs that inhibit nucleic acid
synthesis function by inhibiting DNA polymerase and DNA helicase or RNA polymerase,
thus blocking processes of replication or transcription, respectively. These
drugs are not as selectively toxic as other antibiotics because procaryotes and
eucaryotes do not differ greatly with respect to nucleic acid synthesis.
Quinolones
The quinolones are
synthetic drugs that contain the 4-quinolone ring. The quinolones are important
antimicrobial agents that inhibit nucleic acid synthesis. The first quinolone,
nalidixic acid, was synthesized in 1962. Since that time, generations of
fluoroquinolones have been produced. Three of these— ciprofloxacin,
norfloxacin, and ofloxacin—are currently used, and more fluoroquinolones are
being synthesized and tested.
Quinolones
act by inhibiting the bacterial DNA gyrase and topoisomerase II. DNA gyrase
introduces negative twist in DNA and helps separate its strands. Inhibition of
DNA gyrase disrupts DNA replication and repair, bacterial chromosome separation
during division, and other cell processes involving DNA. Fluoroquinolones
also inhibit topoisomerase II, another enzyme that untangles DNA during
replication.
Quinolones are
bactericidal. The quinolones are broad-spectrum antibiotics. They are highly
effective against enteric bacteria such as E. coli and Klebsiella
pneumoniae. They can be used with Haemophilus, Neiserria, P. aeruginosa,
and other gram-negative pathogens. The quinolones also are active against
gram-positive bacteria such as S. aureus, Streptococcus pyogenes,
and Mycobacterium tuberculosis.
They are used in treating urinary tract
infections, sexually transmitted diseases caused by Neisseria and Chlamydia,
gastrointestinal infections, respiratory infections, skin infections, and
osteomyelitis (bone infection).
Quinolones are
effective when administered orally but can sometimes cause diverse side
effects, particularly gastrointestinal upset.
Properties of Some
Common Antibacterial Drugs
|
Antibiotic Group
|
Primary Effect
|
Mechanism of Action
|
Members
|
Spectrum
|
Common Side Effects
|
|
Cell Wall Synthesis
Inhibition
|
|
Penicillins
|
Cidal
|
Inhibit
transpeptidation enzymes involved in the cross-linking polysaccharide
chains of the bacterial cell wall peptidoglycan.
Activate cell wall
lytic enzymes
|
Penicillin G, Penicillin
V, Methicillin
Ampicillin, Carbenicillin
|
Narrow
(gram-positive)
Broad (gram-positive,
some gram-negative)
|
Allergic responses
(diarrhea, anemia, hives, nausea, renal toxicity
|
|
Cephalosporins
|
Cidal
|
Same as above
|
Cephalothin,
cefoxitin, cefaperazone, ceftriaxone
|
Broad (gram-positive,
gram-negative)
|
Allergic responses,
thrombophlebitis, renal injury
|
|
Vancomycin
|
Cidal
|
Prevents
transpeptidation of peptidoglycan subunits by binding to D-Ala-D-Ala amino
acids at the end of peptide cross-bridges. Thus it has a different binding
site than that of the Penicillins
|
Vancomycin
|
Narrow
(gram-positive)
|
Ototoxic (tinnitus
and deafness), nephrotoxic, allergic reactions
|
|
Protein Synthesis
Inhibition
|
|
Aminoglycosides
|
Cidal
|
Bind to small
ribosomal subunit (30S) and interfere with protein synthesis directly
inhibiting synthesis and causing misreading of mRNA
|
Neomycin, kanamycin,
gentamicin,
Streptomycin
|
Broad (gram-negative,
mycobacteria
Narrow (aerobic, gram-negative)
|
Deafness, renal
damage, loss of balance, nausea, by allergic responses
Same as above
|
|
Tetracyclines
|
Static
|
Same as above
|
Oxytetracycline,
chlortetracyclin
|
Broad (gram-positive
and Gram-negative, rickettsia, chlamydia)
|
Gastrointestinal
upset, teeth and discoloration, renal, hepatic injury
|
|
Macrolides
|
Static
|
Bind to 23S rRNA of
large ribosomal subunit (50S) to inhibit peptide chain elongation during
protein synthesis
|
Erythromycin,
clindamycin
|
Broad (aerobic and
anaerobic gram-positive, Some gram-negative)
|
Gastrointestinal
upset, hepatic injury, anemia, allergic responses
|
|
Chloramphenicol
|
Static
|
Same as above
|
Chloramphenicol
|
Broad (gram-positive
and negative, rickettsia and chlamydia)
|
Depressed bone marrow
function, allergic reactions
|
|
Nucleic Acid
Synthesis Inhibition
|
|
Quinolones and Fluoroquinolones
|
Cidal
|
Inhibit DNA gyrase
topoisomerase IV, thereby blocking DNA replication and transcription
|
Norfloxacin,
ciprofloxacin, Levofloxacin
|
Narrow
(gram-negatives better than gram-positives) Broad spectrum
|
Tendonitis, headache,
lightheadedness, convulsions, allergic reactions
|
|
Rifampin
|
Cidal
|
Inhibits bacterial DNA-
dependent RNA polymerase
|
R-Cin, rifacilin,
rifamycin, rimactane, rimpin, siticox
|
Mycobacterium
infections and some gram-negative such as Neisseria meningitidis and Haemophilus
influenzae
|
Nausea, vomiting,
diarrhea, fatigue, anemia, drowsiness, headache, mouth ulceration, and liver
damage
|
|
Cell Membrane
Disruption
|
|
Polymyxin B
|
Cidal
|
Binds to plasma
membrane and disrupts its structure and permeability properties
|
Polymyxin B, polymyxin
topical ointment
|
Narrow—gram-negatives
only
|
Can cause severe
kidney damage, drowsiness, dizziness
|
|
Antimetabolites
|
|
Sulfonamides
|
Static
|
Inhibits folic acid
synthesis by competing with ρ-aminobenzoic acid (PABA)
|
Silver sulfadiazin,
sodium sulfacetamide, and sulfamethoxazole,
sulfanilamide, sulfasalazine, sulfisoxazole
|
Broad spectrum
|
Nausea, vomiting, diarrhea;
hypersensitivity reactions such as rashes, photosensitivity
|
|
Trimethoprim
|
Static
|
Blocks folic acid
synthesis by inhibiting the enzyme tetrahydrofolate reductase
|
Trimethoprim (in
combination with sulfamethoxazole [1:5])
|
Broad spectrum
|
Same as sulfonamides,
but less frequent
|
|
Dapsone
|
Static
|
Thought to interfere
with folic acid synthesis
|
Dapsone
|
Narrow-mycobacterial infections,
principally leprosy
|
Back, leg, or stomach
pains; discolored fingernails, lips, or skin; breathing difficulties fever,
loss of appetite, skin rash, fatigue
|
|
Isoniazid
|
Cidal if, bacteria are
actively growing, static if bacteria are dormant
|
Exact mechanism is
unclear but it is thought to inhibit lipid synthesis(especially mycolic
acid); putative enoyl-reductase inhibitor
|
Isoniazid
|
Narrow—mycobacterial infections,
principally tuberculosis
|
Nausea, vomiting,
liver damage, seizures, “pins and needles” in extremities (peripheral
neuropathy)
|
