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Bintari Anindhita

Antimicrobial agents are among the most commonly known drug, not only by the
medical community, but also by the society. Unfortunately, the society know antibiotics in
the wrong way. In fact, antibiotics are the most commonly used and misused of all drugs.

Antibiotic misused is one form of irrational prescribing. Irrational prescribing can be
seen in the form of overprescribing, underprescribing, use of multiple unneeded drugs
(polypharmacy), use of more toxic drug, use antibiotics for viral infection, use injection form
instead of oral form, and many more.

The widespread use of antibiotics has led to at least two undesirable consequences. The
one consequence includes the emergence of antibiotic-resistant pathogens, resulting in an
increasing need for new antibiotics. The other one includes changes in normal microbial flora
which lead to unpleasant and occasionally lethal side effects.

Antibiotics resistance has become a global pandemic and is one of the biggest global
concern. Based on data from RS Dr Kariadi in 2002, show that all of the blood isolate had a
high antibiotics multiresistance level and 45-56% had irrational antibiotics use.

Antibiotics were prescribed in 68% of acute respiratory tract visits and of those, 80%
were unnecessary according to CDC guidelines.

Antibiotic use in hospitalized patients in Indonesia is high and often inappropriate. Two
hospitals in Surabaya and Semarang showed that depending on the type of department
between 67% (Internal Medicine) and 90% (Surgery and Paediatrics) of patients who are
hospitalized for at least 5 days are treated with antibiotics during their stay in hospital. Only
21% of prescriptions were considered appropriate, for 42% there was no indication for
treatment and 15% were inappropriate regarding choice, dosage or duration.

Reducing inappropriate antibiotic use is thought to be the best way to control resistance.
Although awareness of the consequences of antibiotic misuse is increasing, overprescribing
remains widespread, driven largely by patient demand, time pressure on clinicians, and
diagnostic uncertainty. If the gains in the treatment of infectious diseases are to be preserved,
clinicians must be wiser and more selective in the use of antimicrobial agents.

Antibiotics are antibacterial substances produce by various species of microorganisms
(bacteria, fungi, and actinomyecetes) that suppress the growth of other microorganisms.
Common usage often extends the term antibiotics to include synthetic antimicrobial agents
such as sulfonamides and quinolones.
Antibiotics treatment employs substances that injure
bacteria and thereby prevent their further multiplication without harming cells of the host
organism. Specific damage to bacteria is particularly feasible when a substance interferes
with a metabolic process that occurs in bacterial.

Antibiotics have three general uses, empirical therapy, definitive therapy, and
prophylactic or preventive therapy. As empirical or initial therapy the antibiotic shoud cover
all the likely pathogens because the infecting organisms has not yet been defined. However,
once the infecting microorganism is identified, definitve antimicrobial therapy should be
institued with a narrow-spectrum, low-toxicity agent to complete the course of treatment.

The effect of antibacterial drugs observed in vitro are bactericidal effect (bacteria are
killed) and bacteriostatic effect (bacteria survive, but do not multiply).

Antimicrobial agents are classified based on chemical structure and proposed
mechanisms of action, among others are:
a. Agents that inhibit synthesis of bacterial cell walls, including the -lactam class (e.g.,
penicilins, caphalosporines, and carbapenems) and dissimilar agents such as
cycloserine, vancomycin and bacitrasin.
Inhibitors of cell wall synthesis are suitable
antibacterial agents because human cells lack a cell wall. These agents exert a
bactericidal action on growing or multiplying germs.

b. Agents that act directly on the cell membrane of the microorganism, increasing
membrane permeability which lead to leakage of intracellulare compounds, including
polymixin, polyene antifungal angents (e.g., nystatin and amphotericin B) which bind
to cell-wall sterols and the lipopeptide daptomycin.

c. Agents that disrupt the fynction of 30S or 50s ribosomal subunits to reversibly inhibit
protein synthesis, which are bacteriostatic (e.g., chloramphenicol, tetracyclines,
erythromycine, clindamycin, stretogramins, and linezolid).

d. Agents that bind to the 30s ribosomal subunits (e.g., aminoglycosides)

e. Agents that affect bacterial nuclei acid metabolism, such as rifamycins (e.g., rifampin
and rifambutin) which inhibit RNA polymerase, and the quinolones, which inhibit

f. Antimetabolites agent, including trimethroprim and the sulfonamides which block
essential enzymes of folate metabolism.
Tetrahydofolic acid (THF) is a coenzyme in
the synthesis of purine bases and thymidine. These are constituents of DNA and RNA
and are required for cell growth and replication. Lack of THF leads to inhibition of cell

Figure 1. Antibiotics Mechanisms of Action (7)

The emergence of antibiotic resistance is a very serious development that threatens the
end of the antibiotic era. More than 70% of the bacteria associated with hospital-acquired
infections in the United States are resistant to one or more of the drugs previously used to
treat them.

When bacterial growth remains unaffected by an antibacterial drug, bacterial
resistance is present. This may occur due to certain metabolic characteristics that confer a
natural insensitivity to the drug on a particular strain of bacteria (natural resistances).
example of natural resistance is Pseudomonas aeruginosa, whose low membrane
permeability is likely to be main reason for its innate resistance to many antimicrobials.

When a random genetic alteration (mutation) occur, naturally susceptible bacterial
strains can be transformed under the influences of antibacterial drugs into resistant ones
(acquaired resistance). Resistances in bacteria may be acquired by a mutation and passed
vertically by seletion to daughter cells, and more commonly by horizontal transfer of
resistance genes between strains and species. Exchanges of genes is possible by
transformation, transduction or conjugation.

Under the influence of the drug, the susceptible bacteria die off, whereas the mutant
multiplies unimpeded. The more frequently a given drug is applied, the more probable the
emergence of resistant strains.

Antibiotic must reach its target in active form, bind to the target and interfere with its
function to be effective. Bacterial resistance to an antimicrobial agent is attributable to three
general mechanisms, which are the drug dose not reach its target, the drug is not active, and
the target is altered.

Bacteria have efflux pumps that export drugs out of the cell and keep its intracellular
concentrations at low levels. Efflux pump mechanism is thought to play a role in multidrug
resistance to tetracycline, chloramphenicol, fluoroquinolones, macrolides, and -lactam
antibiotics because these antibiotics inhibit different aspects of protein and DNA

Drug inactivation is the second general mechanism of drug resistance. The
mechanisms within the category of antibiotic inactivation include the production of
enzymes that degrade or modify the drug itself through hydrolysis, group transfer, and
redox mechanisms.

The third major resistance mechanism is the modificarion of the antibiotic target site
which lead to the antibiotic is unable to bind properly.This may be due to mutation of the
natural target (e.g., fluoroquinolone resistance), target modification (e.g., ribosomal
protection type of resistance to macrolides and tetracyclines), or acquisition of a resistant
form of the native, susceptible target (e.g., staphylococcal methicillin resistance caused by
production of a low-affinity penicillin-binding protein).

It is thought that self medication is the key determinant of improper antimicrobial use.
Self medication is practised widely and by far antimicrobials were the group of medicines
that were most often used in self medication.

One of the form of antibiotic misuses is in infections that have been proved by
experimental and clinical observation to be nonresponsive to treatment with antimicrobial
agents. Among of these are disease caused by viruses such as measles, mumps, 90%
infection of the upper respiratory tract and many GI infections.

Fever of undetermined cause are frequently and inappropriately treated with empirical
antimicrobial agents. Whereas, fever of short duration in the absence of localizing signs
probably is associated with undefined viral infections.

Most of the causes of antibiotic use by doctors is the concerns of not recognize
bacterial infection so that all patients with fever was given antibiotics. Doctors feel better
mistakenly prescribing antibiotics for viral diseases instead of mistakenly not giving
antibiotics for bacterial diseases, without considering the side effect which is the emergence
of antibiotic resistance.

Wrong frequency of administration or the use of either an excessive or a
subtherapeutic dose are common misused of antibiotics. Excessive amount can result in
significant toxicities including seizures (e.g.,penicillin), vestibular damage (e.g.,
aminoglycosides) and renal failure (aminoglycosides). On the contrary, too low a dose may
result in treatment failure and is most likely giving rise to microbial resistance.

Prudent use of antibiotics means as use of antibiotics with right indication, right
patient, right drugs, right doses, wary of the antibiotics side effects, provide clear
information and evaluation.

Prudent use of antibiotics has 3 components, rational use, adherence to local
guidelines and policies, and avoidance or reversal of upward demographic trends in antibiotic

WHO recommendation in 2001 stating that to limit antibiotic resistance, improvement
in the quality use of antibiotics should be the main key. The biggest problem in the use of
antibiotics was not the error in determining the dose, duration or types of antibiotics but
whether there is any indication of giving antibiotics.

The right excuse to use antibiotics in patient with fever is whether there is a high risk
of bacterial infection, focal infection (e.g., meningitis, otitis media, pneumonia, bacterial
gastroenteritis, urinary tract infection, skin infection) and age less than three months. By
applying this algorithm, turns out the use of antibiotics can be reduced significantly without
increasing the morbidity and mortality of patients.

The first consideration in selecting an antimicrobial agent is wheter it is even
indicated. Obtaining an accurate infectious disease diagnosis is important in selecting an
antimicrobial agent. An infectious disease diagnosis is reached by determining the site of
infection, defining the host, and establishing when possible, a microbiological diagnosis. In
the absence of a clear indication, antibiotics often may be used if disease is severe and if it
seems likely that withholding therapy will result in failure to manage a potentially serious or
life-threatening infection.

The timing of initial therapy should be guided by the urgency of the situation. In
critically ill patients, such as those in septic shock, febrile neutropenic patients, and patients
with bacterial meningitis, empiric therapy should be initiated immediately after or
concurrently with collection of diagnostic specimens. In more stable clinical circumstances,
antimicrobial therapy should be deliberately withheld until appropriate specimens have been
collected and submitted to the microbiology laboratory.

Selection of an antibiotic regimen should rely on the clinical presentation, which may
suggest the specific microorganism, and knowledge of the microorganisms most likely to
cause specific infections in a given host. In addition, information about the antimicrobial
susceptibility of the infecting microorganism is important for appropriate drug selection
because bacterial strains, even from the same species, may vary widely in sensitivity to

Initial therapy for infection is often empiric and guided by the clinical presentation
because microbiological results do not become available for 24 to 72 hours. It has been
shown that inadequate therapy for infections in critically ill, hospitalized patients is
associated with poor outcomes, including greater morbidity and mortality as well as
increased length of stay. Therefore, a common approach is to use broad-spectrum
antimicrobial agents as initial empiric therapy with the intent to cover multiple possible
pathogens commonly associated with the specific clinical syndrome.

In selecting empiric antimicrobial therapy for such infections, clinicians should
consider the following:
The site of infection and the organisms most likely to be colonizing that site (eg,
intravascular catheter associated bacteremia is frequently a result of colonization and
infection caused by staphylococci present on the skin);
Prior knowledge of bacteria known to colonize a given patient (eg, a screening nasal
swab may indicate that the patient is colonized with MRSA);
The local bacterial resistance patterns or antibiograms that are available for important
pathogens at most hospitals.

Once microbiology results have helped to identify the etiologic pathogen and/or
antimicrobial susceptibility data are available, every attempt should be made to narrow the
antibiotic spectrum. This is a critically important component of antibiotic therapy because it
can reduce cost and toxicity and prevent the emergence of antimicrobial resistance in the

The emergence and spread of resistance bacteria is a threat to patient safety in hospitals
because infections with antibiotic-resistant bacteria result in increased patient morbidity and
mortality as well as increased hospital length of stay. Antibiotics resistance frequently leads
to a delay in appropriate antibiotic therapy. The current new antibiotics is limited and if the
resistance continues to grow, there will be no effective antibiotics for treatment. Therefore,
prudent use of antibiotics is thought to be the best way to control resistance.


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