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I

INTRODUCTION

Antibiotics are the most important weapons for the treatment of many infectious

diseases caused by bacteria. 1 Antibiotics are substances that destroy the bacterial

without harming the host, human. Antibiotics are either natural substances that are

produced in nature by microorganisms or synthetic substances, which have been prepared in

the laboratory. To be considered a clinically effective antibiotic and therefore useful in

medicine, the destruction or growth inhibition of the microorganism is achieved in the

respective concentrations of the antibiotic in the body. To date, at least 4,000 antibiotics have

been isolated from cultures of microbes and 30,000 have been prepared semisynthetic.1

Antibiotics may be wide spectrum and narrow spectrum. Wide spectrum kill many

types of bacteria e.g. penicillin.The broad spectrum antibiotics are active against

many types of microbes such as bacteria, rickettsia, mycoplasmas, protozoa, and spirochetes.

Narrow spectrum which kill certain types of bacteria e.g. isoniazid and should be used

where possible to reduce the risk of colonization and super infection with resistant bacteria.1

If used irrationally, it will be increased treatment cost, interference with patient’s

normal flora, selection of drug resistant organisms, increased of untoward side effects. 2,3 In

children with bacteria, antibiotic therapy must be started immediately. Inappropriate antibiotic

treatment may lead to greater expense, toxic side effects, antibiotic resistance, and

superinfections that are difficult to treat. Irrational use of antibiotics significantly increased

morbidity and mortality in children with bacterial infections,. 2,3

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Antibiotics are one of the most commonly used group of d rugs. In USA, 23 million

kg used annually, 50% for medical reasons.4 Studies worldwide has shown a high incidence

of innaproriate use. 4

II

LITERATURE REVIEW

A. Definition and Epidemiology

The conference of experts on the rational use of drugs, convened by WHO in

Nairobi 1985defined that rational use of drugs requires that patient receive medications

appropriately to their clinical needs, in dose that meet their own individual requirements
1,2
for an adequate period of time, at the lowest cost to them and their community. The

rational use of antibiotics is therefore, like any other therapeutic intervention in daily

practice and it should not be random. It requires reflection and thought and should be

based on rules. If used irrationally, it will be increased treatment cost, interference with

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patient’s normal flora, selection of drug resistant organisms, increased of untoward side

effects. 1,2

Although medicines are one of our most cost- effective health-care interventions

and antibiotics are one of our most effective therapeutic classes of medicine, few low-

and middle- income countries are monitoring how they are used. 3,4 Data on medicines

use is conspicuously absent in many health management information systems. By

contrast, developed rich regions, such as Europe, are now monitoring antibiotic

use and taking action to combat irrational antibiotic use.3,4

This tabel shows data from the same countries on antibiotic prescribing .5 Overall

about 45% of the patients were prescribed antibiotics. However, in Indonesia (1990),

Pakistan (1998) and West Bengal, India, (1999) rates in excess of 70% were observed.

Analysis of data from Uzbekistan, Pakistan, Indonesia and Eritrea revealed that 75%-

99% of patients diagnosed with an upper respiratory tract infection (URTI) received

anti-biotics. In E ritrea, for example, it was confirmed that 75% of the adults and

children diagnosed with URTI were prescribed antibiotics even though the cause of the

infection may have been viral. Results from Indonesia demonstrated that 46% of patients

aged under five years received oral rehydration salts (ORS) for the treatment of diarrhrea

while 73% of these same patients received oral antibiotics. Among patients aged over

five years, 36% received ORS, 91% received oral antibiotics, and 25% of patients

received an antibiotic injection.5,6

Table 2.1 Percentage of patients receiving antibiotics

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Reference: Essentials Medicines and Health Products Information Portals . Rational use of

medicines. WHO 2014;10:1-12

Six countries reported information on the percentage of drugs in stock. On

average, 66.5% of the countries had drugs available. At the top end of the scale, Nepal

reported having up to 90% of its drugs currently in stock, while at the bottom end, Ecuador

had only 38% of its drugs in stock.5,6

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Reference: Essentials Medicines and Health Products Information Portals . Rational use of

medicines. WHO 2014;10:1-12

B. The Use of Antibiotics

From 2008, at European level, the 18th November was established as

Awareness Day for Rational Use of Antibiotics, and efforts are made using

campaigns aimed at rationalizing and reducing the over-consumption of

antimicrobial agents. Recipients of these messages are the general public to

raise awareness and to reduce the consumption of antimicrobials, but above all,

for health professionals at all levels of care.1,5

The rational use of antibiotics is therefore, like any other therapeutic

intervention in daily practice and it should not be random. It requires reflection

and thought and should be based on rules. The correct diagnosis, the patient's

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condition, the location of the infection, the severity of the microbial cause

sensitivities antibiotics, the pharmacokinetics and pharmacodynamics of

antimicrobials, the side effects and cost are the main elements which must be

supported in every decision for their use.1,5

In children with bacteria, antibiotic therapy must be started immediately.

Inappropriate antibiotic treatment may lead to greater expense, toxic side effects,

antibiotic resistance, and superinfections that are difficult to treat.6 Irrational use

of antibiotics significantly increased morbidity and mortality in children with

bacterial infections. 6

Children receive a lot of primary healthcare services and, as such,

receive a disproportionately high number of antibiotics compared with middle

aged populations.7 Children are also key drivers of infection within communities

and can contribute to the spread of bacteria from person to person. Despite this,

little research has been published describing the prevalence of bacterial

resistance in children or the risk factors of importance in this group. Urinary

tract infections are one of the most common bacterial infections seen in primary

care.7

For example, in children with a suspected urinary tract infection, the

most common management strategy is to treat empirically with an antibiotic

while results of culture and sensitivity testing are awaited. Young children are

more vulnerable to immediate and long term complications, including renal

scarring and renal failure, and therefore require prompt appropriate

treatment. Escherichia coli is responsible for over 80% of all urinary tract

infections and is also the most common cause of bacteraemia and foodborne

infections and a cause of meningitis in neonates. 7

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C. Antibiotics Resistance

The successful use of any therapeutic agent is always followed by the

potential development of resistance tothat agent from the time it is first employed.

Alexander Fleming, who won a Nobel Prize for his discovery of Penicillin, had

warned about the perils of antibiotic resistance.8 True to this prediction,

resistance began toarise within 10 years of the large scale introduction of

Penicillin.8

Some research conducted a systematic review to investigate the prevalence of

resistance in community acquired E coli urinary tract infection to the most commonly

prescribed antibiotics given to children in primary care and to quantify the relation

between previous exposure to antibiotics in primary care and bacterial resistance. 7,8

They stratified results by OECD (Organisation for Economic Co-operation and

Development) status of the study countries as antibiotics tend to be used differently

in these groups. In the more developed OECD countries antibiotics are obtained

mostly only by prescription, whereas in “developing” non-OECD countries many

antibiotics, including those commonly used to treat urinary tract infection, can be

obtained over the counter, without the need for a prescription.7,8

The most frequently isolated microorganism was E. coli, found in 129 (82%)

children in the first period and in 77 (77%) in the second period. The resistance rate

of E. coli to several antibiotics during these two periods is described in Table 2.4.
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There was no significant change in antimicrobial resistance rate between the two

periods, Aminoglicosides and 3rd generation cephalosporins were the most efficient

antimicrobials against E. coli. 9

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Table 2.4 Bacterial resistance of E.colli tested in two studies in Sao Paulo, Brazil

Reference: Guidoni E et al. Antibiotic resistance patterns of pediatric community-acquired

urinary infections. Braz J Infect Dis 2018;12:1-4

Figure 2.1 summarises the 25 studies included from non-OECD studies that

reported bacterial resistance in 4408 E coli isolates from the same number of

children. All were observational; 10 were retrospective, 11 prospective, one case-

control, and three cross sectional. All 25 non-OECD studies reported information on

prevalence of resistance in urinary E coli. No non-OECD studies reported

information on previous antibiotic exposure. 7,9

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Figure 2.1 Geographical distribution of urinary E coli resistance

prevalence to ampicillin (%) by OECD and non-OECD countries,15

with number of included studies per country in parentheses)

Reference: Bryce A, Hay A D, Lane I F, Thornton H V, Wootton M, Global prevalence of

antibiotic resistance in paediatric urinary tract infections caused by Escherichia

coli and association with routine use of antibiotics in primary care: systematic review

and meta-analysis. BMJ 2016;352:1-17

Tabel 2.5 shows resistance of Salmonella species isolated from children

with diarrhea in Zliten (2001) to antibiotics.7,9

Table 2.5 resistance of Salmonella species isolated from children with

diarrhea in Zliten (2001) to antibiotics.

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No. (%) resistant:

Antibiotics (n= 23)

Ampicillin 22 (100)
Amoxicillin 23 (95,7)
Cefoxitin 20 (87)
Gentamicin 18 (78,3)
Doxycycline 21 (91,3)
Cholaramphenicol 22 (95,3)
Nalidixic acid 1 (4,3)
Norfloxacin 0 (0)
Trimethropim – sulphamehtoxazole 1(4,3)

Reference: Guidoni E et al. Antibiotic resistance patterns of pediatric community-acquired

urinary infections. Braz J Infect Dis 2018;12:1-4

Drug resistance is a concern in the treatment of several organisms.

Treatment is on an inpatient basis. 1,10 Selection of empirical therapy depends on

the most prevalent organisms for each age group as well as on local resistance

patterns. General recommendations often include a third-generation

cephalosporin, such as ceftriaxone or cefotaxime. Ampicillin or penicillin G

may be used against susceptible organisms. Pediatric dosing recommendations

for selected antibiotics are summarized in table 2.6 . 1,10

Tabel 2.6 Pediatric dosing recommendations for selected antibiotics

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Reference: Pick A, Sweet D C, Begley K J. A review of pediatric bacterial meningitis. US

Pharm 2016;41:41-45

These factors, therefore, help resistance and are summarized as 1,10

1. Unnecessary antibiotics.

2. Improper use of antibiotics:

 Smaller dose

 Less treatment time

 Incorrect dosage intervals

3. Extending the life of existing antibiotics based on the rational use, to

work as little as possible in the selection pressure resistance, and in general

all rational use of antibiotics.

 Administration of antibiotics, only for documented infection

and not the common cold, for example.

 If an antibiotic is administered, it must be completed and not

interrupted prematurely. Small doses of antibiotics are easily

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resistant. 1,10

III

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CONCLUSION

Antibiotics are an essential tool of medical use in common medical

procedures, such as bacterial infection, transplantation and chemotherapy.

However, over the years, bacteria have acquired resistance to antibiotics.

Resistant bacteria can be transmitted from animals to humans through the food

chain or by direct contact. Many bacterial infections are becoming resistant to

the treatments most commonly prescribed antibiotics.

The resistance of pathogenic microorganisms to antibiotics not only a

problem for the patient, but also for the environment as the members of the

household are populated by the same pathogen and are more likely to become ill

due to this. So doctors and other professionals should prescribe antibiotics only

when necessary, based on existing guidelines.

Further research is needed to identify markers for rational and irrational


use of antibiotics in children.

REFERENCES

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1. Kourkouta L, Kotsiftopoulos CH, Papageorgiou ,M.Iliadis, CH. Monios, A. The

rational use of antibiotics medicine. iMedPub Jounals 2017;2:1-4

2. Amer FA. Rational use of antibiotics in hospital and community acquired nfections.

ArAPUA 2012.;32:244-59

3. Yusuf Yusuf, Murni I, Setyati A. Irrational use of antibiotics and clinical outcomes in

children. Paediatr Indones 2017;57:1-3

4. Shailaja, K. The rational use of antibiotics [dissertation]. Mysore: SRM College of

Pharmacy, 2014.

5. Holloway, K A.Promoting te rational use of antibiotics.. Reg Heal Forum

2011;15:122-30.

6. Essentials Medicines and Health Products Information Portals . Rational use of

medicines. WHO 2014;10:1-12 [Cited 2018 March 15] Available from:

http://apps.who.int/medicinedocs/en/d/Js6160e/10.html

7. Bryce A, Hay A D, Lane I F, Thornton H V, Wootton M, Global prevalence of

antibiotic resistance in paediatric urinary tract infections caused by Escherichia

coli and association with routine use of antibiotics in primary care: systematic review

and meta-analysis. BMJ 2016;352:1-17 [Cited 2018 March 13] Available from:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793155/

8. De With K, Allerberger F, Amann S, Meyer E. Reuter S. Strategies to enhance

rational use of antibiotics in hospital: a guideline by German society for infectious

diseases. DGI 106; 10: 110-30

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9. Guidoni E et al. Antibiotic resistance patterns of pediatric community-

acquired urinary infections. Braz J Infect Dis 2018;12:1-4 [Cited 2018 March 11]

Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-

86702008000400013

10. Pick A, Sweet D C, Begley K J. A review of pediatric bacterial meningitis. US Pharm

2016;41:41-45

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