Antibiotics & Homeopathic Antidotes. – Dr. Sayeed Ahmad

Index

Antibiotics
& Homeopathic Antidotes.
Dr. Sayeed Ahmad D.
I. Hom. (London)

I.

–
INTRODUCTION

Antibiotics (Greek
anti,”against;”bios,”life”) are chemical compounds
used to kill or inhibit the growth of infectious organisms. Originally
the term antibiotic referred only to organic compounds, produced by
bacteria or molds, that are toxic to other microorganisms. The term is
now used loosely to include synthetic and semisynthetic organic
compounds. Antibiotic refers generally to antibacterials; however,
because the term is loosely defined, it is preferable to specify
compounds as being antimalarials, antivirals, or antiprotozoals. All
antibiotics share the property of selective toxicity: They are more
toxic to an invading organism than they are to an animal or human host.
Penicillin is the most well-known antibiotic and has been used to fight
many infectious diseases, including syphilis, gonorrhea, tetanus, and
scarlet fever. Another antibiotic, streptomycin, has been used to combat
tuberculosis.

II.

–
HISTORY

Although the mechanisms of antibiotic action were not
scientifically understood until the late 20th century, the principle of
using organic compounds to fight infection has been known since ancient
times. Crude plant extracts were used medicinally for centuries, and
there is anecdotal evidence for the use of cheese molds for topical
treatment of infection. The first observation of what would now be
called an antibiotic effect was made in the 19th century by French
chemist Louis Pasteur, who discovered that certain saprophytic bacteria
can kill anthrax bacilli. In the first decade of the 20th century,
German physician and chemist Paul Ehrlich began experimenting with the
synthesis of organic compounds that would selectively attack an
infecting organism without harming the host organism. His experiments
led to the development, in 1909, of salvarsan, a synthetic compound
containing arsenic, which exhibited selective action against
spirochetes, the bacteria that cause syphilis. Salvarsan remained the
only effective treatment for syphilis until the purification of
penicillin in the 1940s. In the 1920s British bacteriologist Sir
Alexander Fleming, who later discovered penicillin, found a substance
called lysozyme in many bodily secretions, such as tears and sweat, and
in certain other plant and animal substances. Lysozyme has some
antimicrobial activity, but it is not clinically useful.

Penicillin, the archetype of antibiotics, is a
derivative of the mold Penicillium notatum. Penicillin was discovered
accidentally in 1928 by Fleming, who showed its effectiveness in
laboratory cultures against many disease-producing bacteria. This
discovery marked the beginning of the development of antibacterial
compounds produced by living organisms. Penicillin in its original form
could not be given by mouth because it was destroyed in the digestive
tract and the preparations had too many impurities for injection. No
progress was made until the outbreak of World War II stimulated renewed
research and the Australian pathologist Sir Howard Florey and
German-British biochemist Ernst Chain purified enough of the drug to
show that it would protect mice from infection. Florey and Chain then
used the purified penicillin on a human patient who had staphylococcal
and streptococcal septicemia with multiple abscesses and osteomyelitis.
The patient, gravely ill and near death, was given intravenous
injections of a partly purified preparation of penicillin every three
hours. Because so little was available, the patient’s urine was
collected each day, the penicillin was extracted from the urine and used
again. After five days the patient’s condition improved vastly. However,
with each passage through the body, some penicillin was lost. Eventually
the supply ran out and the patient died.

The first antibiotic to be used successfully in the
treatment of human disease was tyrothricin, isolated from certain soil
bacteria by American bacteriologist Rene Dubos in 1939. This substance
is too toxic for general use, but it is employed in the external
treatment of certain infections. Other antibiotics produced by a group
of soil bacteria called actinomycetes have proved more successful. One
of these, streptomycin, discovered in 1944 by American biologist Selman
Waksman and his associates, was, in its time, the major treatment for
tuberculosis.

Since antibiotics came into general use in the 1950s,
they have transformed the patterns of disease and death. Many diseases
that once headed the mortality tables—such as tuberculosis, pneumonia,
and septicemia—now hold lower positions. Surgical procedures, too,
have been improved enormously, because lengthy and complex operations
can now be carried out without a prohibitively high risk of infection.
Chemotherapy has also been used in the treatment or prevention of
protozoal and fungal diseases, especially malaria, a major killer in
economically developing nations. Slow progress is being made in the
chemotherapeutic treatment of viral diseases. New drugs have been
developed and used to treat shingles and chicken pox. There is also a
continuing effort to find a cure for acquired immunodeficiency syndrome
(AIDS), caused by the human immunodeficiency virus (HIV).

III.

–
CLASSIFICATION

Antibiotics can be classified in several ways. The
most common method classifies them according to their action against the
infecting organism. Some antibiotics attack the cell wall; some disrupt
the cell membrane; and the majority inhibit the synthesis of nucleic
acids and proteins, the polymers that make up the bacterial cell.
Another method classifies antibiotics according to which bacterial
strains they affect: staphylococcus, streptococcus, or Escherichia coli,
for example. Antibiotics are also classified on the basis of chemical
structure, as penicillins, cephalosporins, aminoglycosides,
tetracyclines, macrolides, or sulfonamides, among others.

A. Mechanisms of Action

Most antibiotics act by selectively interfering with
the synthesis of one of the large-molecule constituents of the cell—the
cell wall or proteins or nucleic acids. Some, however, act by disrupting
the cell membrane (see Cell Death and Growth Suppression below). Some
important and clinically useful drugs interfere with the synthesis of
peptidoglycan, the most important component of the cell wall. These
drugs include the Â-lactam antibiotics, which are classified according
to chemical structure into penicillins, cephalosporins, and carbapenems.
All these antibiotics contain a Â-lactam ring as a critical part of
their chemical structure, and they inhibit synthesis of peptidoglycan,
an essential part of the cell wall. They do not interfere with the
synthesis of other intracellular components. The continuing buildup of
materials inside the cell exerts ever greater pressure on the membrane,
which is no longer properly supported by peptidoglycan. The membrane
gives way, the cell contents leak out, and the bacterium dies. These
antibiotics do not affect human cells because human cells do not have
cell walls.

Many antibiotics operate by inhibiting the synthesis
of various intracellular bacterial molecules, including DNA, RNA,
ribosomes, and proteins. The synthetic sulfonamides are among the
antibiotics that indirectly interfere with nucleic acid synthesis.
Nucleic-acid synthesis can also be stopped by antibiotics that inhibit
the enzymes that assemble these polymers—for example, DNA polymerase
or RNA polymerase. Examples of such antibiotics are actinomycin,
rifamicin, and rifampicin, the last two being particularly valuable in
the treatment of tuberculosis. The quinolone antibiotics inhibit
synthesis of an enzyme responsible for the coiling and uncoiling of the
chromosome, a process necessary for DNA replication and for
transcription to messenger RNA. Some antibacterials affect the assembly
of messenger RNA, thus causing its genetic message to be garbled. When
these faulty messages are translated, the protein products are
nonfunctional. There are also other mechanisms: The tetracyclines
compete with incoming transfer-RNA molecules; the aminoglycosides cause
the genetic message to be misread and a defective protein to be
produced; chloramphenicol prevents the linking of amino acids to the
growing protein; and puromycin causes the protein chain to terminate
prematurely, releasing an incomplete protein.

B. Range of Effectiveness

In some species of bacteria the cell wall consists
primarily of a thick layer of peptidoglycan. Other species have a much
thinner layer of peptidoglycan and an outer as well as an inner
membrane. When bacteria are subjected to Gram’s stain, these differences
in structure affect the differential staining of the bacteria with a dye
called gentian violet. The differences in staining coloration
(gram-positive bacteria appear purple and gram-negative bacteria appear
colorless or reddish, depending on the process used) are the basis of
the classification of bacteria into gram-positive (those with thick
peptidoglycan) and gram-negative (those with thin peptidoglycan and an
outer membrane), because the staining properties correlate with many
other bacterial properties. Antibacterials can be further subdivided
into narrow-spectrum and broad-spectrum agents. The narrow-spectrum
penicillins act against many gram-positive bacteria. Aminoglycosides,
also narrow-spectrum, act against many gram-negative as well as some
gram-positive bacteria. The tetracyclines and chloramphenicols are both
broad-spectrum drugs because they are effective against both
gram-positive and gram-negative bacteria.

C. Cell Death and Growth Suppression

Antibiotics may also be classed as bactericidal
(killing bacteria) or bacteriostatic (stopping bacterial growth and
multiplication). Bacteriostatic drugs are nonetheless effective because
bacteria that are prevented from growing will die off after a time or be
killed by the defense mechanisms of the host. The tetracyclines and the
sulfonamides are among the bacteriostatic antiobiotics. Antibiotics that
damage the cell membrane cause the cell’s metabolites to leak out, thus
killing the organism. Such compounds, including penicillins and
cephalosporins, are therefore classed as bactericidal.

IV

–
TYPES OF ANTIBIOTICS

Following is a list of some of the more common
antibiotics and examples of some of their clinical uses. This section
does not include all antibiotics nor all of their clinical applications.

A. Penicillins

Penicillins are bactericidal, inhibiting formation of
the cell wall. There are four types of penicillins: the narrow-spectrum
penicillin-G types, ampicillin and its relatives, the
penicillinase-resistants, and the extended spectrum penicillins that are
active against pseudomonas. Penicillin-G types are effective against
gram-positive strains of streptococci, staphylococci, and some
gram-negative bacteria such as meningococcus. Penicillin-G is used to
treat such diseases as syphilis, gonorrhea, meningitis, anthrax, and
yaws. The related penicillin V has a similar range of action but is less
effective. Ampicillin and amoxicillin have a range of effectiveness
similar to that of penicillin-G, with a slightly broader spectrum,
including some gram-negative bacteria. The penicillinase-resistants are
penicillins that combat bacteria that have developed resistance to
penicillin-G. The antipseudomonal penicillins are used against
infections caused by gram-negative Pseudomonas bacteria, a particular
problem in hospitals. They may be administered as a prophylactic in
patients with compromised immune systems, who are at risk from
gram-negative infections.

Side effects of the penicillins, while relatively
rare, can include immediate and delayed allergic reactions—specifically,
skin rashes, fever, and anaphylactic shock, which can be fatal.

B. Cephalosporin

Like the penicillins, cephalosporins have a Â-lactam
ring structure that interferes with synthesis of the bacterial cell wall
and so are bactericidal. Cephalosporins are more effective than
penicillin against gram-negative bacilli and equally effective against
gram-positive cocci. Cephalosporins may be used to treat strains of
meningitis and as a prophylactic for orthopedic, abdominal, and pelvic
surgery. Rare hypersensitive reactions from the cephalosporins include
skin rash and, less frequently, anaphylactic shock.

C. Aminoglycosides

Streptomycin is the oldest of the aminoglycosides.
The aminoglycosides inhibit bacterial protein synthesis in many
gram-negative and some gram-positive organisms. They are sometimes used
in combination with penicillin. The members of this group tend to be
more toxic than other antibiotics. Rare adverse effects associated with
prolonged use of aminoglycosides include damage to the vestibular region
of the ear, hearing loss, and kidney damage.

D. Tetracyclines

Tetracyclines are bacteriostatic, inhibiting
bacterial protein synthesis. They are broad-spectrum antibiotics
effective against strains of streptococci, gram-negative bacilli,
rickettsia (the bacteria that causes typhoid fever), and spirochetes
(the bacteria that causes syphilis). They are also used to treat
urinary-tract infections and bronchitis. Because of their wide range of
effectiveness, tetracyclines can sometimes upset the balance of resident
bacteria that are normally held in check by the body’s immune system,
leading to secondary infections in the gastrointestinal tract and
vagina, for example. Tetracycline use is now limited because of the
increase of resistant bacterial strains.

E. Macrolides

The macrolides are bacteriostatic, binding with
bacterial ribosomes to inhibit protein synthesis. Erythromycin, one of
the macrolides, is effective against gram-positive cocci and is often
used as a substitute for penicillin against streptococcal and
pneumococcal infections. Other uses for macrolides include diphtheria
and bacteremia. Side effects may include nausea, vomiting, and diarrhea;
infrequently, there may be temporary auditory impairment.

F. Sulfonamides

The sulfonamides are synthetic bacteriostatic,
broad-spectrum antibiotics, effective against most gram-positive and
many gram-negative bacteria. However, because many gram-negative
bacteria have developed resistance to the sulfonamides, these
antibiotics are now used only in very specific situations, including
treatment of urinary-tract infection, against meningococcal strains, and
as a prophylactic for rheumatic fever. Side effects may include
disruption of the gastrointestinal tract and hypersensitivity.

V.

–
PRODUCTION

The production of a new antibiotic is lengthy and
costly. First, the organism that makes the antibiotic must be identified
and the antibiotic tested against a wide variety of bacterial species.
Then the organism must be grown on a scale large enough to allow the
purification and chemical analysis of the antibiotic and to demonstrate
that it is unique. This is a complex procedure because there are several
thousand compounds with antibiotic activity that have already been
discovered, and these compounds are repeatedly rediscovered. After the
antibiotic has been shown to be useful in the treatment of infections in
animals, larger-scale preparation can be undertaken.

Commercial development requires a high yield and an
economic method of purification. Extensive research may be needed to
increase the yield by selecting improved strains of the organism or by
changing the growth medium. The organism is then grown in large steel
vats, in submerged cultures with forced aeration. The naturally
fermented product may be modified chemically to produce a semisynthetic
antibiotic. After purification, the effect of the antibiotic on the
normal function of host tissues and organs (its pharmacology), as well
as its possible toxic actions (toxicology), must be tested on a large
number of animals of several species. In addition, the effective forms
of administration must be determined. Antibiotics may be topical,
applied to the surface of the skin, eye, or ear in the form of ointments
or creams. They may be oral, or given by mouth, and either allowed to
dissolve in the mouth or swallowed, in which case they are absorbed into
the bloodstream through the intestines. Antibiotics may also be
parenteral, or injected intramuscularly, intravenously, or
subcutaneously; antibiotics are administered parenterally when fast
absorption is required.

In the United States, once these steps have been
completed, the manufacturer may file an Investigational New Drug
Application with the Food and Drug Administration (FDA). If approved,
the antibiotic can be tested on volunteers for toxicity, tolerance,
absorption, and excretion. If subsequent tests on small numbers of
patients are successful, the drug can be used on a larger group, usually
in the hundreds. Finally a New Drug Application can be filed with the
FDA, and, if this application is approved, the drug can be used
generally in clinical medicine. These procedures, from the time the
antibiotic is discovered in the laboratory until it undergoes clinical
trial, usually extend over several years.

VI.

–
RISKS AND LIMITATIONS

The use of antibiotics is limited because bacteria
have evolved defenses against certain antibiotics. One of the main
mechanisms of defense is inactivation of the antibiotic. This is the
usual defense against penicillins and chloramphenicol, among others.
Another form of defense involves a mutation that changes the bacterial
enzyme affected by the drug in such a way that the antibiotic can no
longer inhibit it. This is the main mechanism of resistance to the
compounds that inhibit protein synthesis, such as the tetracyclines.

All these forms of resistance are transmitted
genetically by the bacterium to its progeny. Genes that carry resistance
can also be transmitted from one bacterium to another by means of
plasmids, chromosomal fragments that contain only a few genes, including
the resistance gene. Some bacteria conjugate with others of the same
species, forming temporary links during which the plasmids are passed
from one to another. If two plasmids carrying resistance genes to
different antibiotics are transferred to the same bacterium, their
resistance genes can be assembled onto a single plasmid. The combined
resistances can then be transmitted to another bacterium, where they may
be combined with yet another type of resistance. In this way, plasmids
are generated that carry resistance to several different classes of
antibiotic. In addition, plasmids have evolved that can be transmitted
from one species of bacteria to another, and these can transfer multiple
antibiotic resistance between very dissimilar species of bacteria.

The problem of resistance has been exacerbated by the
use of antibiotics as prophylactics, intended to prevent infection
before it occurs. Indiscriminate and inappropriate use of antibiotics
for the treatment of the common cold and other common viral infections,
against which they have no effect, removes antibiotic-sensitive bacteria
and allows the development of antibiotic-resistant bacteria. Similarly,
the use of antibiotics in poultry and livestock feed has promoted the
spread of drug resistance and has led to the widespread contamination of
meat and poultry by drug-resistant bacteria such as Salmonella.

In the 1970s, tuberculosis seemed to have been nearly
eradicated in the developed countries, although it was still prevalent
in developing countries. Now its incidence is increasing, partly due to
resistance of the tubercle bacillus to antibiotics. Some bacteria,
particularly strains of staphylococci, are resistant to so many classes
of antibiotics that the infections they cause are almost untreatable.
When such a strain invades a surgical ward in a hospital, it is
sometimes necessary to close the ward altogether for a time. Similarly,
plasmodia, the causative organisms of malaria, have developed resistance
to antibiotics, while, at the same time, the mosquitoes that carry
plasmodia have become resistant to the insecticides that were once used
to control them. Consequently, although malaria had been almost entirely
eliminated, it is now again rampant in Africa, the Middle East,
Southeast Asia, and parts of Latin America. Furthermore, the discovery
of new antibiotics is now much less common than in the past.

ANTIBIOTICS AND HOMŒOPATHIC ANTIDOTES

Adverse Effects of Penicillin

Fever with cold feet. Bell., Cupr-ac.

Wheezing and Pseudoasthmatic attack. Aspidosperma
(Quebracho)

When skin eruptions are simultaneouslypresent. Grind.

Anorexia (with Mycin group of drugs likeAureomycin).
Abrot.

Peripheral Neuritis. Ant-t.

Brachiaglia Nocturna (with the pronounced symptoms of
pins and needles). Sec., Act-s.

Pruritus. Apis and Grind. 10 drops mixed in a cup of
milk andapplied locally.

Skin lesions from Penicillin. Agar., Sulph.

Chronic cough after Penicillin. Penicillin 3x or 30,
Seneg. 30 or 200.

In cases when Srepto Peniciliin had been used.
Streptococcin 30 or Staphelococcin 30 (as an intercurrent remedy.

Heart depressing effects of Penicillin. Ars-a.

Harmful effects of Penicillin. Ars-a., Thuj., Nux-v.,
Sil.

Specific to counteract the effects of Penicillin.
Ars-a.

Diarrhœa from Antibiotics (especially Mycins).
Nit-ac.

Allergic reactions to Antibiotics. Sulph.,
Penicillin, Streptomycin.

Headache due to Streptomycin. Bell.

#. Effects of Chloromycetin: cases of typhoid (where
Chloromycetin was given). —– Chloromycetin 30, 200 or 1M (according
to patient’s Constitution). With Placebo for a week. In second week
Typhoidinum 200 or 1M (with Placebo for a fortnight).

Intestinal effects of Aureomycin. Aureomycin leaves a
very weak liver and severe troublewith the bowels. In this case, a pure
constitutional treatment with careful observation of idiosyncrasies is
most effective.

#.

Effects of
Allergy (in general). Ill effects of Penicillin. —– Carb-v.
(Dilutions used: 2x, 3x, 6x, 12x).

References:

1. Contributed by Dr. M. Maureen Dale and Dr. Joel
Mandelstam (MS Encarta Encylopædia 2002).

2. Homœopathy and Adverse Reactions of Allopathic
Drugs by Dr. Sayeed Ahmad.

Copyright © Dr. Sayeed Ahmad
2004

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