In September 1928, Sir Alexander Fleming returned to his laboratory
after a month away with his family, and noticed that a culture of
Staphylococcus aureus he had left out had become contaminated with a
mold (later identified as Penicillium notatum). He also
discovered that the colonies of staphylococci surrounding this mold had
been destroyed. He later said of the incident: "When I woke up just
after dawn on September 28, 1928, I certainly didn’t plan to
revolutionize all medicine by discovering the world’s first antibiotic,
or bacteria killer. But I suppose that was exactly what I did." He at
first called the substance mold juice, and then named it penicillin,
after the mold that produced it.
As we are celebrating the Rational Antibiotic Day on
28th September and a week thereafter, here is a mnemonic RATIONALE
to fit in some aspects of rational prescribing practices:
R - Reasoning for prescription, Right dose,
route, duration;
A - Academically updated decisions;
T - Training of mind, residents, parents,
pharmacists;
I - Instructions to parents;
O - Organism search;
N - Noting down the diagnosis;
A - Antibiotic Policy;
L - Local sensitivity pattern; and
E - Ethical considerations, Economic condition of
the patient
R – Reasoning behind our prescription.
Prescribing an antibiotic is a three step process. (i) Is the
fever because of infection or of non-infectious origin; (ii) If
because of infection, is it viral or bacterial (or protozoal); and (iii)
If bacterial, what is the likely organism. R also stands for Right
dose, frequency, route and duration. A Pediatrician can refer to a handy
guidebook of antimicrobial therapy for the exact dose and use a
calculator rather than giving a blanket dosing of 1 tsp tid! The
prescription should be in legible handwriting so that the pharmacist
doesn’t dispense cephalexin for cefixime! R also stands for
adverse Reaction to a particular antibiotic. This should be
clearly mentioned at the top of the letterhead.
A – Academically updated decisions. The
pediatrician must be aware of the IAP guidelines for the management of
infectious diseases. The routine use of Beta Lactam-Beta Lactamase
inhibitor (BL-BLI) combinations should be avoided as they are more
expensive, are likely to have more adverse effects, and may cause
accidental under-dosing of the ceftriaxone component. Ceftriaxone is the
drug of choice for the treatment of enteric fever, and there is no
benefit of using ceftriaxone–tazobactam/cefotaxime- sulbactam (the
tam-tam antibiotics!) upfront as salmonella has rarely been shown to
produce resistance through betal-lactamases. Many ‘obsessed’ tricians
feel that every caesarian delivery is an indication for antibiotics!
Some of them are AGOs (Ampi-Genta-Obstetricians) while some are CMOs (Cefotaxime–Mikacin-Obstetricians)!
While treating neonates with sepsis, use of third generation
cephalosporins should be avoided as it potentiates development of
extended-spectrum beta-lactamases. The addition of ampicillin/
amoxicillin does not improve the anti-staphylococcal activity of
cloxacillin, and in fact may worsen diarrhea. Fixed dose combinations of
anti-amebic medicines (like Metronidazole/Tinidazole) with antibiotics
(like Norfloxacin or Ciprofloxacin) are irrational. There are very few
situations where combinations are rational, as in life-threatening
infections with unknown organisms, antibiotics used for synergistic
actions, and anti-tubercular therapy. For treating infections in
immunocompromised children, antibiotics used should be bactericidal and
not bacteristatic.
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BOX 1 Process of Training the Mind
for Choosing an Antibiotic
1. Make a precise clinical diagnosis from the
symptoms, signs and investigations. In a case of pyogenic
meningitis, symptoms could be fever, irritability, altered
sensorium, refusal of feeds, vomiting and convulsions; signs
could be those of raised intracranial tension and meningeal
irritation; and investigations will be CSF examination, blood
counts and blood culture.
2. Consider possible etiologic agents:- S.
pneumoniae, H. influenzae and N. meningitidis. Target
the most likely ones after consideration of age, past history of
trauma, etc.
3. Specify the therapeutic objectives, such
as sterilization of CSF at the earliest by use of bactericidal
drugs, clinical cure, prevention of relapse, and prevention of
early and late complications.
4. Make an inventory of effective group of
drugs. Choose the most appropriate and effective group based on
the criteria of efficacy, safety, suitability and cost.
5. Choose an appropriate antibiotic from the
chosen group.
6. Decide route of administration, dosage
schedule and standard prescribed duration.
7. Write a legible prescription with name,
age, sex, weight, diagnosis, drug’s generic name, dose, route,
frequency and duration of treatment with other supportive drugs
and treatment measures with signature and date.
8. Give relevant information, instructions
and warnings.
9. Monitor and review the therapeutic
response, and choose an alternative in case of intolerance,
allergy or other adverse drug reactions or poor in vivo
response (midcourse correction).
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T – Training. First is the Training
of mind about 3 ‘O’s; the Organ involved, the causative Organism and the
available therapeutic Option. In reality, very few of us train our minds
to follow the Standard Operating Procedure for prescribing an
antibiotic. The process of training the mind for choosing proper
antibiotics is described in Box 1. These steps may
appear cumbersome for a busy practitioner but they are essential in the
beginning of practice or whenever a new drug comes in the market or when
there is significant antibiotic resistance. Next is the Training
of subordinates and resident doctors about rational antibiotic
practices. Training the parents is also important, who sometimes
pressurize the doctor to prescribe antibiotics for rapid relief. They
should be explained about irrationality of antibiotics in viral
infections, and when antibiotics are necessary, why it is important to
follow all directions and finish the entire prescription even when child
starts to feel better. Pharmacists should be trained to refrain from
selling without valid prescription
I – Instructions. It is expected that a
pediatrician gives time and speaks up about irrationality of antibiotics
in viral infections, and when antibiotics are necessary, why it is
important to follow all directions and finish the entire prescription
even when child starts to feel better. More the written instructions,
lesser the space available for writing medicines!
O – efforts to search the Organism, by
developing a culture of sending cultures. One should remember
that in vitro sensitivities do not always result in clinical
cure; e.g., aminoglycosides cannot cure enteric fever even though the
report always shows sensitivity of salmonella to all of them. Sometimes
an injectable antibiotic is marketed for oral use by simply adding the
suffix O. One should know that the spectrum of these antibiotic
preparations may differ.
N – Noting down a working diagnosis.
Clinical differentiation between bacterial and viral infection, although
difficult is still possible with reasonable certainty most of the times
[1]. Children with viral infections usually have fever, runny nose, red
eyes, red throat, hoarse voice, loose stools or rash. Fever in viral
infections may be high at onset and tends to reduce by the third or the
fourth day. The child is comfortable and not sick in the inter-febrile
period. If you clinically diagnose and write provisional diagnosis as
viral infection, your hands should shake while writing an antibiotic.
These ‘shake hand situations’ include acute watery diarrhea (which is
mostly viral) and bronchiolitis.
A – Antibiotic policy. Box
2 enlists the steps to be followed for any patient who requires
antibiotics. Findings of the audits will drive improvement in antibiotic
use. Even practicing pediatricians can have monthly meetings and have
prescription audits of the colleagues’ prescriptions (without disclosing
the names!). A also stands for Avoiding double standards
i.e. writing one in private clinic, using a different one in a
general hospital, and speaking totally different in conferences!
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BOX 2 Clinical Pathway for
Antibiotic Use
1. Does the patient need an antibiotic?
2. Document the site of infection and possible
microorganism.
3. Send appropriate cultures
4. Choose the antibiotic from the antibiotic
policy after checking for allergy risks.
5. Some antibiotics should be prescribed after
getting an infectious disease consult. These include carbapenems,
colistin, linezolid, teicoplanin, vancomycin, voriconazole,
amphotericin B
6. Follow the clinical response and de-escalate
antibiotics.
7. Infection control team should fill antibiotic audit form and
conduct regular department-wise audits.
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L – knowledge of Local sensitivity pattern
through ongoing research. The research need not be in the institutes
alone; it could be a part of Pediatric Research in Office Setting . L
also stands for Learning to increase our Minimum Intelligence
Concentration (MIC!).
E – Empiric antibiotic therapy. On many
occasions, it is difficult to identify the organism, and hence selection
of an antibiotic is an ‘educated guess’ which should depend on the
system involved and the prevalent behavior of the organism (drug
sensitivity and disease epidemiology). There are some classical
presentations of bacterial infection in office practice, and a short
course of an antibiotic is rational without attempt at bacterial
isolation. Some examples are acute tonsillitis, acute otitis media with
bulging eardrum in infant, acute bacillary dysentery, acute suppurative
lymphadenitis and pyoderma. Patient with acute onset of fever and
no localizing signs prove to be a challenge for need for empiric
antibiotic therapy. Pediatricians must train themselves to decide about
the safety of waiting for natural progress to arrive at definite
diagnosis. Close observation and daily follow-up may be necessary to
ensure this [1]. E also stands for giving consideration to
the Economic condition of the patient. If efficacy and safety are
equal, one can use the cheaper alternative. More expensive does not mean
better. Cloxacillin is still better than vancomycin for methicillin-sensitive
S. aureus. E also stands for Ethical
considerations. Doctors are so busy with the work that they hardly find
time to search for the accurate information regarding efficacy, safety,
suitability and cost of drugs, and they often resort to ‘Academic Gurus’
in the form of medical representatives. They focus the brighter side and
conceal the negative points. The pediatrician starts using the new
antibiotic just for the sake of novelty. This tendency results in rapid
emergence of resistance to the newly introduced antibiotic. It also
unnecessarily taxes parents to pay for a new drug. The safety profile of
many of these drugs is known only in the long run.
It is our bounden duty to use antibiotics with
precision after great thought and clear rationale. One must not forget
that the three most important principles in medicine are diagnosis,
diagnosis and diagnosis [2]. We should respect the antibiotics. We
should think before we ink. Pediatricians have a great responsibility to
use antibiotics properly. Misuse of antibiotics can have disastrous
consequences, not only for the patient in question, but by promoting
bacterial resistance can pose a threat to the entire community [3].
Potential risks, cost and community effects of empirical antibiotic
therapy should always be weighed against probable benefits. We have to
be rational as a group, not in isolation. Busy pediatricians are likely
to become members of one of two societies. The first is the ‘No Guilt’
society. As there is no punishment for their unnecessary use, the
members of this society use antibiotics without any remorse. The second
is the ‘No Shame’ society. Trainee pediatricians who have not been
sufficiently guided against the hazards of the unjustifiable use of
antibiotics have no feelings of shame while penning them down. Though a
challenge, we have to vacate the halls where these two societies hold
their meetings and form a new one, based on sound scientific principles
and rigid moral standards – A Rational Antibiotic Society.
Let me end with a story of a person who was very
proud that he could hit exactly in the center of a circle with an arrow.
While on travel in the countryside, he came across many circles on a
wall with an arrow hit in the center. Curious to meet the competitor, he
found out the person with this extraordinary talent and asked for the
secret of this art. The talented archer told him, "My dear, I shoot the
arrow first and then draw the circle around it!" Dear friends, we should
not hit antibiotics first and then keep rationalizing the use. We should
HIT following the proper sequence of History, Investigations
and Treatment. Let us ensure that we do not get infected with the
Human Irrationality Virus (HIV) out of Habit, Ignorance
and Varying factors like pressure from pharma, our ego and
callous disconcern about antibiotic resistance. Until recently,
recognition of new resistant clones was balanced by the promise of newer
and more potent antibiotics. Today fewer new classes of antibiotics are
under development, and clinicians are facing limitations in their
ability to treat some serious bacterial infections. Let us be rational
every day and enjoy REM sleep daily by developing a Rational
Ethical Mindset.
