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Abstrak
Tujuan pedoman penggunaan antibiotik adalah untuk membinbing penggunaannya secara rasional, sehingga antibiotik
digunakan secara efektifdan efisien dengan efek satnping sekecil-kecilnya bagi penderita dan nasyarakat. Tindakan inijuga berdatnpak
mengurangi biaya tanpa mengorbankan penderita,hnasyarakat terhadap penilihan antibiotikyang salah. Pedotnan ini harus mernenuhi
persyaratan tertentu agar dapat diterima oleh pemakainya dan berlaku bagi sebagian besar (kira-kira 9O%) kclotnpok penderita.
Antibiotik terpilih yang diusulkan harus efektif tanpa adanya hasil antibiogratn. Pedoman ini harus berdasarkan pengetahuan
mikrobiologi, fannakologi dan klinik. Paratneter farnakologi yang akan dibahas antara lain adalah fannakodinatnik, fannakokinetik,
efekbksik dan efek samping, hasil uji klinik, percobaan epidemiologi obat sertafarnakolctgi perbandingan antibiotik. Strategi petnilihan
teruta,na berdasarkan penerapan rasio nanfaat-risiko serta biaya; nanfaat antibiotik yang diperkirakan untuk indikasi tertentu harus
lebih besar dari kemungkinan risiko yang dapat ditimbulkannya. Prinsip "Priuutn non nocere" haruslah merupakan pertùnbangan
utana. Antibiotik sering menimbulkan efek satnping dan karena penberiannya perlu bertujuan jelas. Menganggap bahwa "bila tidak
berefek tentunya tidak berbahaya" tidaklah benar. Pedontan bukanlah suutu aturan yang kaku; pertimbangan iltniah harus selalu
merupakan petunjuk akhir, terutatna pada keadaan klinik yang konpleks. Pedonan pemilihan antibiotik perlu diperbaharui terus
,nenerus bilatnana ada infonnasi yang baru. LaTitnnya tidak perlu ada sanksi terhadap penyinpangan kecil dari pedotnan yang ada,
namun penyitnpangan jauh dari suatu pedoman menerlukan dasar ilniah yang jelas.
Abstract
The aim of antibiotic guidelines is to provide guidance on the rational use of antibiotics, so that they serve effectively and eficiently
with the least adverse effects on patients and co,n,tturtity. Tlrc iupact of such strategy nny also be seen in the containtnent of cost without
ieopardizing the patient to un-successful atteupts of antibiotic treatnent. Guidelines have to satisfy certain requiretnents in order to be
accepted by its users. It should workfor the majority (approx.go%) of patient groups and the antibiotic selectiorx suggested should be
effective without or before the results ofantibiograns. Antibiotic guidelines nust be based on nicrobiological, phannacological and
clinical knowledge. Among phannacological paranteters of the antibiotic that will be discussed are pharmacodynanics, phar-
macokinetics, toxicity and adverse effects, results of clinical trials and drug-epideniological studies, and the conparative phannacology
of antibiotics. The main strategy for selection is based on benefit-risk-cost csscssrlent; the presu,ned benefit that the antibiotic could
offer for a certain indication should be greater that the possible risks it conld give rise to. The principle of treatnent: "Pritnum non
nocere" should always be a prior consideration. In this respect the great potential of antibiotics to cause adversity is very often
overlooked, causing the erroneous attitude of "if it does not work, it does not harn either". Guidelines.are neyeruneant to be rigid rules;
scientific judgetnent should always be the final guide, especially in complicated clinical conditions. Renewal of choices of antibiotics
should be instituted whenever recent infonnation is available and updating of an antibiotic guideline is nandatory every year or two.
Usually there are no sanctions for violating good advice, but najor deviations frotn guidelines nust be scientifically justifiable.
tions on the best antibiotic choice (s) available for the of competence of the health service and prescriber for
treatment and prophylaxis of bacterial, fungal and which it is meant; while gentamicin is a good antibiotic
parasitic infections.r to be used in a hospital setting where the close obser-
Guidelines have to satisfy certain requirements in vation of the patient is needed and where monitoring
order to be accepted by its users. It should work for the of antibiotic blood levels may be determined, in a
majority of patient population and the antibiotic selec- primary health setting it may be dangerous.
tions suggested should be effective without of before
the results of sensitivity testings. The majority of in- PHARMACODYNAMIC PARAMETERS
fections in fact may be treated without the necessity of
doing any culture of an infected biological specimen. Antibiotics
are usually chemicals with no or little phar-
Therefore antibiotic guidelines must be based on the macodynamic properties; they do not exert significant
integration of microbiological, pharmacological and actions on the organs of the host. This is a good
clinical knowledge; the results of clinical trials and characteristic of an antibiotic, because they preferably
epidemiological studies especially should determine should only have killing properties on the invading
the validity of the selections made. Not to be underes- microorganisms without doing harm by stimulating or
timated is the value of a correct diagnosis before inhibiting other receptors of the host. Some antibiotics
prescribing an antibiotic in order to distinguish the real however, may have actions on intact human organs or
needs for eradicating or preventing an infection. Fur- give rise to effects that are adverse in nature, and as
thermore, guidelines should be updated or renewed such may limit the use or dose of an antibiotic. Ex-
whenever new knowledge becomes available. amples of such antibiotics are the aminoglycosides that
inhibit neuromuscular conductions when administered
in high doses. This curariform-like effect is seen with
GENERAL CONSIDERATIONS streptomycin, kanamycin, gentamicin, neomycin, and
Among pharmacological parameters that are important probably other aminoglycosides in high doses. When
to be considered are : pharmacodynamics, pharmaco- used with other muscle relaxants this effect will even
kinetics, toxicity and adverse effects of the antibiotic be enhanced. Circumoral paresthesia is also well-
under scrutiny, site ofinfection, special effects on high known with drugs like streptomycin; and vestibular
risk patient group in relation to the antibiotic being dysfunction occurs with relatively high therapeutic
considered, results of clinical trials, drug-epidemio- doses.
logical studies, and above all, the comparative phar- Other reactions may be seen with antibiotics, such
macology of all antibiotics, especially of those belong- as bone-marrow depression with chloramphenicol or
ing to the same class. cephalosporins, hypoprothrombinaemia with moxa-
lactam, etc. These may not be regarded as pharmaco-
The main strategy for selection of a treatment is
dynamic because they occur seldom and are only seen
based on benefit-risk-cost assessment; the presumed or
calculated benefit that an antibiotic could offer for a
with very high doses or are a result of idiosyncratic
reactions and are therefore unpredictable for any given
certain indication should be greater that the possible
patient. Phenotyping and genotyping of the way in-
risks it could give rise to. The principle of treatment :
dividuals do metabolize certain drugs may in the future
"Primum non nocere", which broadly means "do not
determine which patient would be prone to the above
harm when treating patients", should always be a prior
mentioned adverse eflects.a')
consideration. Cost should only be decided after all
scientific judgements have been made and treatment- The pharmacodynamic effects on the micro-or-
ganisms are reflected in the eradicating properties of
cost should be put before drug-unit-cost. When two or
the antibiotic itself; the may be bactericidal or bac-
more antibiotic selections can be made with more or
teriostatic. The degree of eradicating abilities may be
less similar predicted outcome, then cost should be the
expressed by the minimum inhibitory concentrations
determining factors,
(MICs) of the antibiotic. While this simple in vitro test
As for each guideline, it never should be con- is an important parameter, it mty not be used as the
sidered as rigid rules; sound scientific judgement and
single determinant to select an antibiotic for
a scientifically based selection for using antibiotics therapeutic or prophylactic purposes, because in vivo
should always be the final guide. But, major deviations
conditions do not always produce the same results. The
from guidelines must be scientifically justifiable, be- clinical evaluation of the patients must always be taken
cause good guidelines should apply for the majority of
into account.
subjects for whom the guidelines are developed, An important point for consideration is the
Guidelines also should take into consideration the level
destructive specificity for each antibiotic class; they
htl .1, No I, Jtutuurt Marclt 1994 Antibiotic Guidelines
widely promoted in the Australian Antibiotic Guide- to a guideline may sometimes be erroneous when one
lines' as the drug of choice against staphylococcal is confronted by a complex situation or ramification
infections. The resultant steep increase of its use has which necessitates one to deviate from a guideline. It
caused a drastic rise of flucloxacillin associated may however not be assumed that a guideline can be
hepatitis which in turn might not justify the benefit-risk violated any time for invalid reasons. One may
equation for using flucloxacillin routinely any more. reasonably speculate that a guideline works for the
The indication for flucloxaccillin use has recently been majority (907o or more) of cases, but if one departs
limited to include only severe staphylococcal infec- substantially from it there must be valid reasons to
tions, and caution was mandated when presribing the justify one's choice. In a court case where drugs might
drug for older people or when the drug is used for more have caused injury or death to a patient, there will
than 14 days. usually be one or more experts who will testify whether
the treatment had caused the injury. But even then it is
not easy to establish causality as it was exemplified by
RESULTS OF CLINICAL TRIALS
the "Bendectin case" recently in an American Court-
The results of clinical trials are the ultimate "proof of roo..ll Bendectin is an antihistaminic used againts
the pudding", that the antibiotic is efficacious for a vomiting in early pregnancy that was on the American
specific indication. However, the accessability of the market from 1956 until 1983, when it was banned
results on several clinical trials to make an informed because of accusations that it may have caused
judgement on the profile of an antibiotic is usually phocomelia in 2 cases. The Court accepted only peer
scarce. The information is scattered in many journals reviewed journals as "good science" and in 1991 a
and contradictory results are difficult to unify, not the California appeals court rejected the parent's suit. This
least because of the industry's promotional activities was challenged by other scientists and the Supreme
in the form of seminars and literature. Evaluated Court will reopen the case at the time of this writing.
textbooks should give an objective view on the prob- The problem becomes more entangled because of the
lem. The American Medical Association's Drug ihvolvement of the notorious American lawsuit on
Evaluationse is an annual which is an objective guide health related matters and not the least, the statement
for selecting drugs including antibiotics; it describes made that " 'experts' will testify to anything, for a
.
drug classes and individual drugs. Another book en- pnce ,, tl
titled Therapeutic Drugslo i, rnonogruph that has been
published recently; each monograph deals, among
others, with "Major outcome trials" which describes in QUICK REFERENCE FOR ANTIBIOTIC IN-
a nutshell the results of important clinical studies. The DICATIONS
generalizability or external validity of such trials, how-
ever, are sometimes difficult to assess. Therefore an- It may be useful to design a quick reference in a
tibiotic guidelines would be very useful in the every- table-form in which diseases are matched with the
day application of these potent drugs. Studios, involv- appropriate antibiotics. Table I depicts such a
ing larger populations, such as in drug epidemiological guidance; a first and subsequent choice is provided to
research are also valid to supplement the smaller scale accomodate for situations in which the first one cannot
clinical trials. be used. This gives a first impression on what to use
routinely before going into the details of the clinical
condition. It will serve the reader with a useful an-
LEGAL ASPECTS OF AN ANTIBIOTIC GUIDE. tibiotic to start with, which is correct according to the
LINE authors' view at the time of this publication. It must be
emphasized however that in making the final judge-
The status of a scientific guideline should necessarily ment, many of the above mentioned parameters should
deal with scientific issues. Some may have the idea that be taken into consideration, This guideline should be
a guideline of this sort should also be the standard of used in conjunction with other (authoritative) literature
measure when one is confronted with legal implica- so that nuances caused by individual conditions ofthe
tions when deviations from it become a matter of patient can be accomodated.
dispute in a litigation case. There are certain general principles that are incor-
'We
must emphasize that the legality for such porated into this model guideline, some of them are :
purpose cannot be fully attributed to an antibiotic a. Vy'hen antibiotic treatment has been initiated before
guideline or any other treatment guidelines. Treatment an antibiogram is made and clinical improvement
modalities are a complex subject and adhering simply has been demonstrated clearly, it would be avisable
Vt;l 3, No l, Jurtuury Murch 1994 Antibiotic Guidelines
Endocarditis,
bacterial; acute Staph., strep, enterococci pen.G + clox,+ gentamicin vancomycin + gentamicin
subacute Striviridans, enterococci pen.G + gentamisin idem
Cystitis E.coli, proteus, staphylææci contrimoxazole, ampicillin nitrofurantion, fl uoroquinolone
Pyelonephritis coliform bact. contrimoxazole, ampicilli n fluoroquinolone
Gonorrhoea N.gononhoeae pen.G, ampicillin, ceftriaxone etithromycin, doxycycline, fl uoroquinolone
Urethritis, nonspec. Chlamydia tetracycline/doxycycl ine erithromycin
Lymphogranuloma ven. Chlamydia tetracycline/doxycycl i ne sulfonamide, eritfuomycin
Infi ltrate/furunculosis Str.pyogenes, staphylococci pen.G,erythromycin, (tlu) cloxacil lin spiramycin, clindamycin
Erysipelas Str.pyogenes pen.G. erithromycin, clindamycin
Impetigo Str.progenes, Staph. aureus pen.G, pen.V. erithromycin, spiramycin, flucloxacillin
Infection.mouth/teeth Aerob + anaerobic mictrnrg. pen V, pen G, erythro, macrolide + metronidazol (chronic infection)
Candidiasis, oral Candida mycostalin lozenges/susJnnsion amphotericin lozenges
Tonsillitis, acute Strept(rcoccuspen.G, pen.V, erythromycin spiramycin, clindamycin
Pharyngitis, acute Virus (> 9O%), Str.pyogenes without antibiotic , cin
Common cold, flu Virus without antihiotic r , doxycycline**
Measles Virus without antibiotic r , doxycycline*.
Chicken pox Virus without antibiotic-bath rcgularly r , doxycycline
Parotitis, epidemic Virus no antibiotic-chew on chcwing gum is most effective
Pneumonia : adult Stt.pneumoniae pen.C, erythromycin chloramphenicol, clindamycin + aminoglyc
child H.influenzae amoxycillin chloramphenicol, cotrimoxazole
Otitis media H.infl uenzae- streptococci ampicillin crithromycin, contrimoxazole
Septicemia. Anything possible cephalosporin G3 1+ arn1n,rt;t"., clindamycin + aminoglyc
intra-aMominal Coliform, Bacteroides aminoglyc. + çrenicillin + metrinid. clindamycin + cephalosporin G3
Tetanus CI.tetani pcn.G clindamycin, chloramphenicol + metionid
Gas gangrene CLpcrfringens pen.G cl indamycin, chloramphenicol
Diphteria C.diphteriae pen.G erithromycin
Dianhea, nonspecific Virus, ftxxl, or bacteria (rare) without antibiotic - bismust salt tettacycline (when bacterial [V.choletael])
Typhoid fever S.typhi, S.paratyphi chloramphcnicol, ampicillin cotrimoxazole, fl uoroquinolone
Adapted from Katzung B, ed. Basic and Clinical Pharmacology,4th etl., 1989:619-21, Gllman AG, Gu.xlman LS, Rall TW, Muracl F, ed.
ThePharmacologicalBasisofTherapeutics,8thed., 1990, l}24-33,and AnlibioricGui<ielines,6therllggg-gl,HealrhDepartmentofVictoria,
Australla.
not to change the antibiotic initially used for e Different macrolides may be used interchangebly
another that was more sensitive according to the for the indication cited in the table. Although
antibiogram results. These results may be used later erythromycin is the prototype and is the most
when the first treatment fails. studied, it may cause unbearable gastric irritation
b. The local experience based on scientific judgement for some patents. Other macrolides may be more
and the local sensitivity pattern of pathogens tested tolerated by the stomach. It should always be given
must be taken into account when making antibiotic ll2 an hour before meals to guarantee adequate
selections. When recent sensitivity patterns are absorption.
lacking, Table I may be used as a guide. f. Cotrimoxazole may be substituted by trimetoprim
c. Ampicillin may be interchanged with amoxycillin, alone, especially in urinary tract infections. The
while cloxacillin with flucloxacillin, without caus- sulfa component in cotrimoxazole gives rise to
ing significant clinical outcome. frequent and sometimes serious adverse reactions,
d. Although penicillin G dan penicillin V have almost while the efficacy of trimetoprim alone is not dif-
the same antibiotic spectrum, penicillin V should ferent.
never be used for serious infections. Its action is too û When mycostatin lozenges are not available, it may
weak and aborption of the drug is limited, so that a be substituted by drops or syrup or even tablets
high concentration in the blood cannot be attained. dissolved in a little water. This may be used as a
Dannansjah and Nelwan Med J Univ Indon