ANTIBIOTICS-V

Narrow-spectrum Antibiotics
 Effective against only a limited range of
organisms
 Broad-spectrum antibiotics, such as
tetracyclines and chloramphenicol, affect both
gram-positive and some gram-negative
bacteria. An extended-spectrum antibiotic is
one that, as a result of chemical modification,
affects additional types of bacteria, usually
those that are gram-negative.
ANTIMICROBIALS COMBINATION
THERAPY

There is certain rationale behind the simultaneous

use of two or more antibiotics in specific
situations. As the various groups of drugs exert
their different effects on microorganisms, one
drug may have the potential to either inhibit or
enhance the effect of the other drug.
Likewise, the combinations of antibiotics, that
have been expertly selected to treat the
infection, may have additive toxicities. For
example vancomycin exhibits minimal
nephrotoxicity when given alone but when it is
given in combination with tobramycin, the
combination causes marked renal function
impairment.
 CLINICAL INDICATIONS FOR THE USE
OF COMBINATIONS OF ANTIBIOTICS
Following are a few of numerous reasons given
to justify the rational use of antimicrobial
combinations.
1- Treatment of Mixed Bacterial Infection:-
Some infections are caused by two or more than
two microorganisms. These include
intraabdominal, hepatic and brain abscesses and
infections of the genital tract.
 In such scenario, it becomes necessary to use
different drugs with different antimicrobials
spectra to achieve the desired breadth of activity.
2- Combination therapy is most commonly
employed in empirical therapy of those infections
whose causative agent has not been or cannot be
identified. In such situations, the prime objective
of the treatment is to provide the broader
antimicrobial coverage for microorganisms that
are most likely to cause the infection.
Selection of therapy must be based on clinical
judgment of the physician which obviously
reflects the knowledge of signs and symptoms of
the diseases, microbiology of the diseases and
spectrum of available drugs. The continuation of
combination therapy becomes inevitable in cases
when the physician fails to obtain adequate
cultures before initiating empirical therapy.
However, prolonged use of multiple drug therapy
may lead to overuse of toxic and expensive drugs.
3- Enhancement of Antibacterial Activity in the
Treatment of Specific Infections:-
Synergistic effect of expertly selected suitable
combination of drugs is used to treat certain
specific infections. The use of such combinations
is based on documented proof of efficacy. For
example penicillin plus streptomycin produce
synergistic effect against streptococci. Also
sulfonamides with trimethoprim are synergistic in
vitro and the combination is effective against
infections caused by microorganisms that might
be resistant to sulfonamide alone.
4- Prevention of Emergence of Resistant
Microorganisms:-
The use of combination therapy was first proposed
as a tool to prevent the emergence of resistant
mutants during therapy. This approach has been
extensively used in the treatment of tuberculosis
when co-current use of two or more appropriate
drugs markedly reduces the probability of
development of drug resistance in mycobacterium
tuberculosis.
 DISADVANTAGES OF
COMBINATION THERAPY
i- Increased toxicity due to two or more drugs.
ii- Increased cost of treatment.
iii-Antagonism of antibacterial effect if
bacteriostatic and bactericidal agents are given
concomitantly.
 THE PROPHYLAXIS OF INFECTION
WITH ANTIBIOTICS
CHEMOPROPHYLAXIS
A large percentage of antibiotics is used to prevent
the infection rather than treating the established
infection. This practice accounts for some of the
most flagrant misuses of these drugs. Generally, if
a single, effective, nontoxic drug is used to
prevent infection caused by a specific
microorganism or to eradicate infection
immediately or soon after it has become
established, then chemoprophylaxis is frequently
successful.
 On the other hand, if the aim of prophylaxis is to
prevent colonization or infection by any or all
microorganisms present in the environment of a
patient, then prophylaxis often fails. If a person
has been exposed to specific microorganism,
prophylaxis can be used to protect the individual
from contracting the disease caused by that
microorganism. Success has been established in
the following cases:-
1-Penicillin G is used to prevent infection caused by
group-A streptococci (Streptococcus pyogenes).
2- Penicillin G is used to prevent syphilis (G +ive)
and gonorrhea in persons after having a contact
with infected individual.
3- The intermittent use of septran is effective in
preventing reoccurrence of urinary tract infection
caused by E-coli.
4- Chemoprophylaxis is recommended to prevent
endocarditis in patients with valvular or other
structural lesions of heart who are undergoing
dental, surgical or other procedure that produces
high risk of bacteremia (presence of bacteria in
blood).
 Any procedure that injures mucous membrane
where there are large number of bacteria will
produce bacteremia. Streptococci from mouth,
enterococci from GIT and genitourinary tract and
staplylococci from skin have great propensity to
cause endocarditis. Thus chemoprophylaxis is
recommended for these microbes.
5- The most extensive use of chemoprophylaxis is
to prevent wound infection after various surgical
procedures. For this purpose, antibiotics should be
administered within two hours of making the
initial surgical incision and may need to be
 re-administered to maintain consistent plasma
levels of the drug during the procedure. A single
preoperative antibiotic dose is usually sufficient
prophylaxis for most surgical procedures.
Exceptions include infected cases, surgery of long
duration and placement of prosthetic material.
Several factors are important for rational and
effective use of antibiotics in such conditions.
i- Antibiotic must be present at the wound site at the
time of closure. This demands that drug should be
 given immediately preoperatively and if necessary
intraoperatively.
ii- The antibiotic must be effective or active against
the most likely infecting microorganisms. This
prompted the use of first generation
cephalosporins.
iii- There is mounting evidence that the continued
use of the drug after surgical procedure is
unwarranted and potentially harmful. The use of
antibiotics beyond 24-hrs is not only unnecessary
but also results in the development of more
resistant flora and there are more chances of super
infections by antibiotic resistant strains. The risk
of toxicity and undue cost of therapy are
additional disadvantages. Chemoprophylaxis is
only justified in dirty and contaminated surgical
procedures (e.g. resection of colon). Also it is
indicated when the surgical procedure involves
insertion of prosthetic implant. It is very
important to always keep in mind that systemic
use of antibiotics prophylactically does not
reduce the need for absolute sterile and skilled
surgical techniques.
Superinfections:-
Superinfection may be defined as the emergence
of bacteriological and clinical evidence of a new
infection during chemotherapy of a primary one.
This phenomenon is very common and potentially
very dangerous because the eradication of
microorganisms responsible for superinfection is
very difficult with the available antimicrobials.
Among the various side-effects of the antibiotics,
alterations in the normal microbial population of
skin,
 A superinfection is a second infection
superimposed on an earlier one, especially by
a different microbial agent of exogenous or
endogenous origin, that is resistant to the
treatment being used against the first infection.
 upper respiratory tract, intestinal tract and
genitourinary tract is of special importance
because it leads to the development of
superinfection. The normal flora play a vital role
in the maintenance of health and causation of
disease by the following ways.
i- The normal flora can cause disease, especially in
immunocompromised and debilitated individuals.
Although these organisms are non-pathogens in
their usual anatomic location, they can be
pathogens in other ports of the body.
ii- They constitute a protective host defense
mechanism.
 The non-pathogenic bacteria occupy ecologic
niches, and so pathogens have difficulty in
multiplying efficiently. If the normal flora is
suppressed, pathogens may grow and cause
disease.
iii- They may serve a nutritional function. The
intestinal flora produce several B vitamins and
vitamin k. Poorly nourished people may suffer
vitamin deficiency when being treated with
antibiotics due to reduction in normal flora.
iv- Many members of the normal flora appear to
produce antibacterial substances (bacteriocins)
and they also compete with pathogens for
essential nutrients. Thus broader the effect of an
antibiotic against microorganisms, greater the
alteration in normal flora and greater the
possibility that a single microorganisms will
become predominant, invade the host, and
produce infection. The incidence of
superinfection is the lowest with penicillin G and
higher with chloramphenicol, tetracyclines and
highest with combinations of broad spectrum
antibiotics and expanded-spectrum third
generation cephalosporins. The prolonged use
increases the incidences of superinfection. Infact,
the after-effects (harmful) of therapeutic or
prophylactic use of antimicrobials must never
deter the physician from their administration in
the situation where they are definitely needed.
Utmost care should be taken in employing the
antimicrobials for their right use otherwise
irrational use may convert a simple, benign and
self-limited disease into a serious or even fatal.
 MISUSE OF ANTIBIOTICS
i- Treatment of Untreatable Infections:-
The majority of viral diseases are self-limiting and
do not respond to presently available
antimicrobials. Thus antimicrobial therapy of
measles, mumps and at least 90% of infections of
upper respiratory tract is ineffective and useless.
ii- Therapy of Pyrexia of Unknown Origin:-
Fever of undetermined cause may be of two types:
i- Short Duration Fever (a few days to weak).
ii- Prolonged or Extended Duration Fever.
Both of these conditions are frequently treated
with antimicrobials. In the absence of localizing
signs, fever of short duration, is in majority of
cases, due to undefined viral infections and does
not respond to antibiotics. In the vast majority of
such cases defervescence occurs spontaneously
within a weak or less. The cause of prolonged
fever are i- tuberculosis ii- hidden pyogenic
intrabdominal abscess iii- endocarditis iv- various
types of neoplasma
v- hepatitis vi- atypical rhematiod arthritis vii-
asymptomatic regional enteritis and many other
non infections disorders.
It is worth to be remembered that antibiotics are
not antipyretic and the patient should not be
exposed unnecessarily to chemotherapy with the
hope that if one antibiotic is ineffective, the other
or combination of antibiotics may work. Instead
cause of the fever be probed and treatment should
be given accordingly.
Improper Dosage:-
Erroneous antimicrobial dosage may be of two
types
i- Excessive quantity of drug
ii- Suboptimal quantity of drug.
Overdoses of antimicrobials might cause severe
toxicity in patients with renal or hepatic
dysfunction. Thus it becomes mandatory to use
the proper dose by taking into account all the
factors that might effect the effectiveness of the
therapy.
 However, using the drugs at sub therapeutic levels
because of fear of toxicity may result into clinical
failure and emergence of resistant organisms.
iv- Inappropriate reliance of chemotherapy alone:-
In some cases, cure of an infection is not possible
with the use of anti-infective agent (s) alone. The
conditions in which such problem arises are those
with considerable quantities of purulent exudates
or necrotic or avascular infected tissues.
For example the patient with pneumonia and
empyema cannot be cured with the use of large
doses of effective drug unless drainage of the
involved area is established. Secondly a patient
with renal lithiasis cannot be cured even with the
effective antimicrobials for a number of this
without the removal of stones. Thus as a general
rule, when an appreciable amount of pus, necrotic
tissue or foreign body is present, the most
effective therapy is a combination of antimicrobial
agents and proper surgical procedure.
v- Lack of adequate bacteriological information:-
In Pakistan, over 90% of the hospitalized patients
receive antimicrobial therapy without the support
from microbiological laboratory, this is purely
based on so-called clinical judgment only.
Another major contributor to the misuse of the
antibiotics is chemophylaxis. Bacterial cultures
and Gram stains of infected material are obtained
after trying single or combined antibacterial
therapies. If the bacteriological diagnosis is
available, it is often disregarded in the
selection of antimicrobial combinations with
broadest spectra is a cover for diagnostic
imprecision. The agents are selected and
prescribed by physicians depending upon the
unethical convincing by the sale-promoters of
pharmaceutical manufacturers. This irrational use
of drugs is not only hazardous to the patient health
it also adds to the sufferings of the patient because
of high cost of the therapy. The antimicrobial
therapy must be individualized on the basis of
clinical situation, microbiological information and
pharmacological considerations available.
Empyema- the collection of pus in a cavity in the
body, especially in the pleural
cavity.
Defervescence -the abatement of a fever as indicated
by a decrease in bodily temperature.
An Ecological Niche is the role and position a species
has in its environment; how it meets its needs for
food and shelter, how it survives, and how it
reproduces. A species' nicheincludes all of its
interactions with the biotic and abiotic factors of
its environment.