Irrational Use of Antibiotics
Author(s): Gaash, B
Vol. 5, No. 1 (2008-03 - 2008-04)
Gaash, B
Dr Bashir Gaash, MD, Phd, DCH, is a public health practitioner
with a particular interest in emergence of resistance to commonly used antibiotics
Contact: Cell: 9419089018
Email: gaashb_10(at)yahoo.co.in
Pharmaco-epidemiology, among other things, monitors trends of antibiotic use and the
emergence of resistance to commonly used antibiotics. In our place, the concept has not
taken up yet and rampant misuse of antibiotics is a rule, with dramatic emergence of
multi-drug resistant typhoid, pneumonia, urinary tract infection, reproductive tract
infection and nosocomial infections. Here we discuss the problem in an international and
Indian perspective.
Introduction
The accidental discovery of the first
antibiotic by Alexander Fleming1 in 1928
revolutionized the therapy of infection, and saved
millions of lives especially during the two World
Wars. The dramatic impact was attributable to lack
of primary resistance among microbes and scarcity
of antibiotics with a high cost which necessitated
extraordinary prudence in their use.
Then came a time when, with
progressively falling costs and increasing
availability of antibiotics, prescribing became less
judicious. The global pharmaceutical industry was
quick to take advantage of the declining costs of
production, expanding world markets especially in
developing countries, and gullibility of the
prescribers. Every week a new antibiotic started to
be pumped into the market leaving no time for
doctors to fully get acquainted with new products
while, at the same time, providing ample chances
to microorganisms to develop different means of
resistance to guarantee their survival.
Global scenario
Currently, antimicrobials are the most
widely used category of drugs in the world. In
2004, the World Health Organization reported the
figure for unwarranted antibiotics prescriptions
standing at roughly 50%. Overuse and misuse of
antibiotics was particularly high (50% to almost
100%) in upper respiratory infections, most of
which are generally viral and self-limited. A WHO
study of antibiotic use in 13 low-, middle- and
high-income countries from 1992 to 1996 revealed
that antibiotics were wrongly prescribed for
approximately 30% of cases of URTI. Studies have
revealed the existence of compulsive antibiotic
prescribing all over the world3.
Developed world: Contrary to expectations,
antibiotic misuse and overuse is common not only in
developing countries but also in the developed
world. A large study in the USA found that 51% of
patients with colds and URTI were receiving
antibiotics and estimated that over 20% of all
antibiotic prescriptions were clinically useless4. In
addition, it was found that only 20-25% of
antibiotic use in USA was based on the results of
culture and sensitivity tests.
A 2003 article by Ronning et al5 reviewed
antibacterial usage in 16 European countries. This
study demonstrated that the antibiotic use was
higher than required, largely irrational and
generally empirical. In Italy, a mere 2% of
antibiotic use was determined by culture and
sensitivity. A European study presented at the 14th
European Congress of Clinical Microbiology and
Infectious Diseases held in Prague in May 20046
reported that 36% of the children with symptoms
reported use of antibiotics within 2 weeks, most
frequently for acute respiratory infections (ARI)
and diarrhoea-like syndromes.
In Australia, it was found that, even with
‘antibiotic guidelines’ in place, less than 50% of
antibiotic treatment in the wards of teaching
hospitals in Melbourne complied with the
recommendations. In far-flung centres in that
country, more than 90% of surgical prophylaxis
was found to be inappropriate7.
The situation of drug overuse or irrational
use in developing world is particularly alarming.
China: A comparative study of antibiotic use in
35 countries showed that the overall rate for the
use of antibiotics for upper respiratory tract
infection in 1997 was as high as 97% in China8
Multicentric studies showed that over
70% of patients were prescribed antibiotics in
Indonesia and Pakistan.
Indonesia: A WHO-World Bank supported study
found an antibiotic overuse of 43% in Indonesia.
While only 46% of the under fives received oral
rehydration salts (ORS) for the treatment of
diarrhea, 73% of them received oral antibiotics.
For patients aged over five years, the respective
figures were 36% and 91%. In terms of mild upper
respiratory infection treatment, 75-86% of patients
received antibiotics.9
Pakistan: In Pakistan, the average number of drugs
per prescription was 3.5, with antibiotics
accounting for 76% of the prescribed drugs.
Almost 75% of antibiotics were given by injection.
Even at the rural health service levels, antibiotics
were prescribed to 78% patients, 74% receiving
them parenterally. The antibiotic prescription
frequency in case of children aged 1-15 was as
high as 84%.10
The over-prescribing of antibiotics and
injections is confirmed by the breakdown of
prescribing for the 10 most frequently diagnosed
diseases (Fig 1), which also reveals gross
irrationality in antibiotic prescribing.
Fig 1: Most frequent indications for antibiotic use in Pakistan16

Nepal: In Nepal, over 50% of antibiotics
prescribed in 1996 were found to be unnecessary.
Studies performed between 1997 and 199911, 12
reported a prevalence of 61% antimicrobial use in
intensive care units. Results of studies performed
in 2004-0513 were no different. Analysis of
prescriptions showed that 50.2% of the patients
received an antimicrobial, and that 84.5% of the
antimicrobials were used without obtaining
bacteriological evidence of infection. Combination
therapy was not uncommon: the prescribing
frequency of combination antimicrobials was
14.6%, of which 84.4% of the combination
prescriptions were for ampicillin + cloxacillin.
Almost 62% of the antimicrobials were prescribed
by the parenteral route. Almost 30% of the
antibiotics prescribed were for lower respiratory
tract infections, mainly for COPD followed by
pneumonia.
Approximately 71% of the patients
receiving an antimicrobial were from the medical
side while 29.5% were surgical patients.
Antimicrobials were used for prophylaxis in 30.9%
and for non-bacteriologically proven infection in
51%. The most commonly prescribed
antimicrobials were metronidazole, ampicillin,
combination of ampicillin and cloxacillin and
gentamicin. This profile closely resembled that
used in Pakistan.
Studies on prophylaxis showed
metronidazole, ampicillin+cloxicillin, gentamicin,
ampicillin and cefotaxime, in that order, to be the
most frequently prescribed antibiotics. It is
noteworthy that prophylactic use of antimicrobials
has a very high potential of easy abuse and overuse
with consequent costly and dangerous
implications.
Retrospective analysis of case records
showed that, in 26.2% cases, the use of the
antimicrobials was irrational. Common examples
of illogical prescribing were prescription of a third
generation cephalosporin where a cheaper
antimicrobial would have been satisfactory, use of
a cocktail of antimicrobials with overlapping
spectrums for abdominal infections, and use of
antimicrobials in cases of cerebrovascular
accidents, acute confusional states, etc. Costly
antimicrobial combinations and newer
antimicrobials were used where an older
antimicrobial would have worked satisfactorily.
A study of antibiotic practices in 35
countries of the world14, 15 presented at the 1st
International Conference for Improving the Use of
Medicines (ICIUM) in Thailand held in 1997
showed that, on an average, 45% of patients were
prescribed antibiotics (Half of them parenterally).
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 antibiotics.
In Eritrea, 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.
Fig 2: Results of a 35-country study – Percentage of patients receiving antibiotics

Oman: Study of sub-speciality prescribing at
hospital facilities in Oman (Muscat and Dhofar)
revealed that 14-29% of patients were prescribed
antibiotics. Suburban PHCs revealed a frequency
of 21-23% and urban PHCs 25%. The highest
antibiotic prescribing was seen in medical and ENT
sub-specialities. The methodology used a large
sample size of 600 prescriptions per facility.
Antibiotic utilization studies in Sudan and
Jordan showed that the respective percentage of
prescriptions involving antibiotics was as high as
63% and 60.9%. The comparative figures for
Nigeria (48%), Zimbabwe (29%), Lebanon
(17.5%) and Yemen (46%) were lower.17-21
Uzbekistan: Studies in Uzbekistan222 found that at
least 21% of prescriptions contained an antibiotic.
The respective frequency of antibiotic prescribing
for upper and lower respiratory infections was as
high as 93.5% and 78.9%, of which 79% and 54.8%
were given by injections. Significantly, 30.2%
diarrhoeal patients were prescribed antibiotics
along with other largely unnecessary drugs.
Peru: In Peru, a study23 conducted jointly by
IHCAR, Karolinski Institute (Sweden), Institute of
Tropical Medicine, Peru University, and University
of Florence (Italy) showed that 71% of 6-72 month
old children receiving antibiotics had their
antibiotics prescribed by a health care professional,
8% had consulted a pharmacist and 19% had selfmedicated
without consulting a health care
supplier. It was surprising to find that children
whose caregivers have consulted a health care
provider were more likely to be treated with
antibiotics than children who had been exclusively
self-medicated by their caregivers. About 28% of
the children with upper ARI-like symptoms were
treated with antibiotics. A higher percentage of the
children with ARI-diarrhoea mixes (38%), lower
ARI (50%) and diarrhoea (44%) received
antibiotics.
India24: Being a populous country with rampant
corruption and lax controls, India is an ideal
country for multinational companies to pump in
their newly developed but poorly researched drugs
including antibiotics.
Utilization studies and prescription audits in
Goa have shown that antibiotics constitute about
39% of drugs prescribed to outdoor patients25; 30%
in indoor perinatal patients26; and 22% in rural
hospitals27.
Medical activists in India have been
raising their fingers at the rampant misuse of
antibiotics for quite sometime now28. Overprescribing
of antibiotics has been widely
reported29,30 The use of single injection of
tetracycline to a febrile child has been highlighted
even in the press.31
A recent survey in Goa revealed that
polypharmacy was the norm, with 80% of
prescriptions having more than one medicine,
(many patients receiving 5 or more preparations
simultaneously). Antibiotics (with analgesics) were
included in almost a quarter of prescriptions32. The
average frequency of antibiotic prescribing in the
neighbouring Pune was found to be 43%33.
In a north Indian study of 2400
prescriptions, antibiotics were found to be widely
and inappropriately used by practitioners34. A
study of 2953 prescriptions from PHCs in south
India revealed that patients received an average of
2.71 drugs and that antibiotics (with analgesics and
antihistamines) were the most commonly used
drugs accounting for more than 80% of the drugs
prescribed29.
In Andhra Pradesh, 60% of drugs
(particularly antibiotics and vitamins) prescribed in
rural areas and 47% of them in urban areas, were
non-essential, compared to 47% in urban areas35.
Studies also revealed that in the majority
of cases antibiotic prescribing was empirically
directed at the putative site of infection. Since the
meager culture facilities are available in a very
small number of hospitals in India, empirical
antibiotic use is rampant36. The distressing fact is
that where these are available, they are
infrequently requested and when advised, often the
results are not considered for decision making.
Although antibiotic use is rampant in
medical outpatients and wards, surgeons don’t lag
behind. In spite of several available guidelines for
the appropriate use of antimicrobials in perioperative
patients, the fear of high morbidity and
mortality associated with intra-abdominal
infections and surgical site infections has led to
misuse of antimicrobials in the perioperative
period. Studies37 show that the third/fourth
generation cephalosporin plus an anti-anaerobic
agent were preferred (84% cases) for treating intraabdominal
infections. Approximately 55% of the
surgeons prescribed a single antibiotic for clean
surgeries. A combination of two or three
antimicrobial agents was preferred in clean
contaminated (42.3%) and dirty (46.9%) surgeries
respectively. Third generation cephalosporins
(particularly ceftriaxone and cefotaxime) were the
commonly prescribed antibiotics (80%) for all
surgeries. However, in majority of cases antibiotics
were prescribed for durations longer than
recommended in standard guidelines.
A recent (2007) study at the Jawahar Lal Nehru Medical
College, AMU, revealed that the most commonly
prescribed drugs by general surgeons were antibiotics
(93%) – mostly ceftriaxone and amikacin. (Salman MT et
al. Drug Prescribing Pattern in Surgical wards of a
Teaching Hospital in North India. Ind J Pract Doctor
2008;IV(5):5+
Unnecessary medication: Globally, the figure for
unwarranted antibiotics prescriptions stands at
roughly 50%. According to figures gathered by
surveys presented to WHO in 2000, about 60% of
antibiotics in Nigeria were prescribed
unnecessarily. In Nepal, over 50% of antibiotics
prescribed in 1996 were not needed and 40% of
medicine expenditure in the same year was wasted
due to inappropriate prescriptions. Retrospective
analysis of case records in Nepal in 2003 showed
that, in 26.2% cases, the use of the antimicrobials
was irrational
The World Health Organization pointed out
that nearly 2 out of every 3 antidiarrhoeal
preparations sold in 12 countries in Latin America
in 1990 contained an antibiotic. Similarly, a survey
carried out in 1989 showed that nearly one out of
two antidiarrhoeal products in Third World
countries contained an unnecessary antibiotic.
The conclusions drawn at the consultative
group discussion23 in Peru were that the results
suggested ever increasing potential of irrational
use of antibiotics for children, including short
courses, over-prescribing, and self medication.
In a north Indian study of 2400
prescriptions, antibiotics were found to be widely
and inappropriately used by practitioners.34
Study of emergency room prescriptions in
private hospitals in Manila showed that over 90%
of patients who received antibiotics did not really
need them.
Side effects: Antibiotics can potentially do the
same to the host what they do to the bacterium. For
example, trimethoprim can depress folic acid in
both the microorganism and the host. Many
antibiotics can lead to adverse effects through
multiple means: chloramphenicol depresses bone
marrow in all the recipients but may drastically do
so in a person with idiosyncrasy. A State Food and
Drug Administration (SFDA; China’s drug
watchdog) survey revealed that nearly 50% of the
total side-effect reports from drugs were for
prescribed antibiotics. Experts there believe that
many of the 20 million people with hearing
disabilities in China might be suffering because of
the irrational use of antibiotics8. In the 1960s and
1970s, nationwide abuse of acheomycin is said to
have resulted in damage to the teeth of a
generation of Chinese people.8
Recently, fluoroquinolones are being
blamed for multiple adverse effects which may be
long lasting. The sufferers have hosted their web
sites to denounce what they call ‘floxing’.
In addition to development of resistance,
superinfection may result from overuse or
prolonged administration of broad spectrum
antibiotics. Many wide spectrum antibiotics are
recognized to cause death of the normal intestinal
and vaginal flora. Fungal infections are linked to
overuse of such expensive antibiotiocs as
cephalosporins37a.
Problem of Resistance: Irrational use (overuse,
misuse, prolonged use) of antimicrobials are
contributing to growing resistance to treatment for
the very diseases that contribute most to the burden
of illness in low-income countries. The irrational
use of pharmaceutical drugs, contributing to
increasing resistance was particularly discussed at
the 9-day long World Health Assembly in May
200538. The World Health Organisation says that
anti-microbial resistance is one of the world’s most
serious public health problems; a major cause
being the wrong use of medicines.
The World Health Assembly in May 2005
warned that the anti-microbial resistance was
rapidly increasing, with resistance of up to 70-90%
to original first-line antibiotics for dysentery
(shigella), pneumonia (pneumococcal),
gonorrhoea, and hospital infections (staph.
Aureus).
Global antimicrobial resistance prevalence rates:
- Malaria (chloroquine resistance in 81 out of 92 countries);
- Tuberculosis (0-17% primary multi-drug resistance);
- HIV/AIDS (0-25% primary resistance to at least one antiretroviral drug);
- Gonorrhoea (5-98% penicillin resistance);
- Pneumonia and bacterial meningitis (0-70% penicillin resistance in streptococcus pneumonia); diarrhoea:
shigellosis (10-90% ampicillin resistance, 5-95% cotrimoxazole resistance);
- Hospital infections (0-70% resistance of staphylococcus aureus to all penicillins and cephalosporins).
WHO country data 2002-03
On a global scale resistance to penicillin
treatment was estimated to be between 5% and
98% for gonorrhoea and between 12% and 55% for
pneumonia and bacterial meningitis39,40
In Bangladesh41, resistance to ampicillin in
the treatment of shigellosis diarrhoea is estimated
to be over 90%. In addition, resistance to treatment
with nalidixic acid increased from less than 10% in
1987 to over 90% in 1992.
Overuse of chloroquine for the treatment
of malaria led to widespread resistance which is
now established in 81 of the 92 countries where the
disease is endemic – substantially raising the costs
of treatment with second- and third-line
antimalarial medicines42. This was a matter of
great concern at the 2nd International Conference
on Improving Use of Medicine (Chang Mai),
sponsored by WHO, the Thai Network for Rational
Use of Drugs (ThaiNRUD), Management Sciences
for Health, the Centre for International Health,
Boston University School of Public Health;
Harvard Medical School and the International
Network for the Rational Use of Drugs.
Economics of Antibiotic Overuse:
Currently, antimicrobials are the most
widely used category of drugs in the world,
accounting for over one-quarter of hospital drug
costs2.
Studies found in Indonesia that, in terms of
cost, antibiotics ranked highest, followed by cough
and cold medicines, and analgesics. Drugs for the
treatment of diarrheal diseases and respiratory
conditions accounted for 68% of all under-five
health centre drug costs and 38% of all over-five
drug costs.43 The observed treatment cost was Rp.
512 per case (4 times the expected cost).
Antibiotics accounted for 60-63% of URI
treatment costs.
About 40% of medicine expenditure in
Nepal in 1996 was wasted due to inappropriate
antibiotic prescriptions. Such avoidable wastage
has great implications for an economically weak,
resource-poor country with a high burden of
infectious diseases.
Drugs in the present day world have come
to mean money for the manufacturer as well as
prescriber and retailer. According to the WHO, the
global sales of prescription drugs in 2000 were
$282.5 billion. This has to be borne in mind that all
this money has to come from the pocket of a
patient, who is often poor and financially drained,
or from the resource-less governments of poor
countries, antibiotics and other essential drugs
have to be procured at the cost of food, child
education and family welfare.
A joint 1992 study by the National
University of Malaysia and the Health Ministry
conducted at six government hospitals found that,
alhough the WHO Essential Drug List
recommends only 20 antibiotics, yet there are over
200 antibiotic preparations sold in Malaysia. Thus,
it does not surprise to learn that the 1993 imports
of antibiotics cost the country over RM85 million
(up 100% since 1982) – with penicillins taking up
28% of the total. Antibiotics made up 14% of all
medicinal and pharmaceutical products produced
or imported into that country.
In Australia, drug companies spend A$200
million every year just to market their products.
The sum represents almost A$10,000 a year spent
on attempting to win each of Australia’s 21,000
GPs. This is 50% more than allowed by law in the
UK for marketing.
In Japan, there are an estimated 43,000 drug
salesmen and almost as many wholesaler
representatives. An average Japanese doctor
receives 450 sales calls a year. Returns for drug
companies are enormous: In 1988, Japan’s market
for injectable antibiotics amounted to about £1.7
billion; cephalosporins accounting for 71% of the
total compared to about 24-55% in the US and
Europe.
In Britain the pharmaceutical industry also
realises the importance of bringing new products to
the attention of GPs. As a result, about two million
visits are paid by sales representatives, with the
average GP receiving some 62 visits a year.
To top them all, drug promotion costs in
the US were $15.7 billion in 2000. This far
exceeded the entire WHO budget in that year to
discourage aggressive drug promotion.
The aggressive campaigning by
pharmaceutical companies has paid off. Data on
trends in medicine use show that globally the
average number of drugs used increased from 1990
to 2003 from 2.2 to 2.7 per patient between 1990
and 2003. Only 40-50% of patients were treated in
compliance with standard treatment guidelines; in
other words 50-60% of antibiotic use in the world
is either because of our innocence or the drug
companies’ shrewdness.
Quinolones (fluoroquinolones) which are
among the latest antibiotics to be developed in the
1980s, accounted for 15% of the world antibiotic
market in 1990. Americans spend US$700,000 a
day on just one type, ciprofloxacin. In 1989,
ciprofloxacin was the 4th most commonly
prescribed antibiotic in the US – with over 5
million prescriptions at a cost of US$248 million.
The sales soared only because of heavy promotion.
In the first half of 1988, ciprofloxacin was the 2nd
most advertised product.
A WHO Expert Committee has suggested
that a reserve list of fewer antibiotics like the thirdgeneration
cephalosporins, quinolones and
vancomycin be set aside for specific indications
such as infections caused by organisms resistant to
standard drugs and not be available for unrestricted
use. However, the former two products are widely
used as first-line antibiotics by doctors including
specialists in private practice.
The cost of excessive promotion is met by
huge profit margins of life-saving drugs like
antibiotics. According to WHO, profit margins for
expensive drugs like cephalosporins make up a
large part of a hospital’s income in developed
countries. The value of this discount scheme is
estimated at £7 billion each year!
The promotion for medicine, especially
antibiotics, according to the Research Institute for
Tropical Medicine, Manila, is heaviest in
developing countries44. This, on the one hand,
increases the cost of drugs, particularly antibiotics,
and on the other hand, puts the prescriber under
social or economic pressure to unnecessary use of
the adverstised antibiotics.
According to the Working Group on Health
and Development (WEMOS) in Amsterdam, 75
products (including many antibiotics) which had
been pulled out or banned in one or more European
countries were identified in the Third World in
1991. This proves that multinational companies
forced to withdraw certain products considered to
be dangerous, ineffective or unnecessary turn to
the developing world for profiteering. They resort
to aggressive campaigning to make up for their
loss of business in the developed world.
Though WHO has come out with an
Essential Drug List (EDL) of 250 preparations, in
India alone the drug market has 70,000
preparations. Most of these drugs comprise of
antibiotics, vitamins and anti-inflammatory
analgesics.
Jammu and Kashmir State is a considered a
huge consumer of drugs, required or not. One
guess puts the number of drug companies
operating in the State at a whopping 9000!. People
of Kashmir Valley are particularly fond of
medicines, and have been made habitually tolerant
to polypharmacy.
An average prescription has 4-5 different
drugs. Antibiotics are prescribed freely, and in
absence of Drugs and Cosmetic Act, can be
purchased from any pharmacy at will. Majority of
children still receive one or two antibiotics for
diarrhea, though ORS use has not been more than
38%45. All cases of ARI are managed by giving
the latest antibiotics. Doctors compete with each
other in prescribing the most recently introduced,
albeit very costly, antibiotics. Often the freshly
introduced antibiotic is prescribed within the first
10 minutes of introduction. Salesmen (called
medical representatives) try all means to fulfill
their sale targets, and more often than not the
doctor may not even get a chance to go through the
company leaflet describing the prescribed drug.
The doses are often substandard and durations
shorter or much longer than those recommended.
The consequences have been the rapidly increasing
resistance among commonly found organisms. One
study46 conducted by us found that majority of the
uropathogens had already developed resistance to
most commonly used drugs including norfloxacin,
co-trimoxazoile, and ampicillin. Multi-drug
resistant community-acquired pneumonia and
typhoid are common in the Valley.
Drug prescribing in Kashmir has taken
shape of a racket where every stake holder, except
the patient, is benefitted. Promotion is vehemently
aggressive, and the nexus between pharmaceutical
companies and the prescribers is keeping the
environment favourable for flourishing
substandard drug (called here Number 2) trade.
There is an urgent need to enforce the
Essential Drug List of the WHO in public as well
as private medical practice. The Government must
take the lead by purchasing generic drugs for
hospitals and peripheral health outlets. Private
medical setup will either follow or can be made to
fall in line through legislation and legal
enforcement.
References:
- Kendall F. Haven, Marvels of Science (Libraries
Unlimited, 1994); p182
- Smith AJ, Aronson JK, Thomas M. Antibiotic
policies in the developing world. Euro J Clinical
Pharmacol. 1991, 41:85-87.
- Swindell, P.J., Reevs,
D.S., Bullock, D.W., Davies, A.J. and Spence, C.E.
Audit of antibiotic prescribing in a Bristol hospital.
British Medical Journal.1983, 286:118-122.
- Gonzales R, Steiner JF, Sande MA. Antibiotic
prescribing for adults with colds, upper respiratory tract
infections, and bronchitis by ambulatory care
physicians. Jam Med Assoc, 1997, 278(11):901-4.
- Ronning M, et al. Problems in collecting comparable
national drug use data in Europe: the example of
antibacterials. Berlin, Springer-Verlag. 2003.
- Kristiansson C. Social and financial factors influencing
rational use of antibiotics. 14th European Congress of
Clinical Microbiology and Infectious Diseases Prague /
Czech Republic, May 1–4, 2004 (Abstract no. 902-
p1162)
- Harvey, Ken. Therapeutic guidelines – the way ahead.
Essential Drug Monitor (WHO).1995, No19:10-11.
- Hui L, Li X, Zeng X, Dai Y, et al. Patterns and
determinants of use of antibiotics for acute respiratory
tract infection in children in China. Paed. Infect Dis J,
1997, 16(6):560-564.
- Arustiyono. Promoting rational use of drugs at the
community health centres in Indonesia, 1999, WHOWorld
Bank Health Project IV.
(http://dcc2.bumc.bu.edu/prdu/ Other_Documents/
ARUS_INDONESIA_PRDU.htm).
- Memon K. Use of drugs in Sind Province Pakistan
primary health care facilities.
(http://dcc2.bumc.bu.edu/prdu/Other_Documents/Khalil
_Concentration_Paper.htm).
- Burke JP, Pestotnik SL. Antibiotic use and
microbial resistance in intensive care units: impact of
computer-assisted decision support. J Chemother
1999;11(6):530-5.
- Bergmans DC, Bonten MJ, Gaillard CA, van Tiel
FH, van der Geest S, de Leuw PW, Stobberingh EE.
Indications for antibiotic use in ICU patients: a one-year
prospective surveillance. J Antimicrob Chemother
1997;39(4):527-35.
- Shankar R, Partha P, Shenoy N, Brahmadathan
KN,Ravi Shankar P. Investigation of antimicrobial use
pattern in the intensive treatment unit of a teaching
hospital in western Nepal. 2005, Clinical Medicine and
Health Research.
- Pavin M, et al. Prescribing practices of rural primary
health care physicians in Uzbekistan. Trop Med. and Int.
Health, 2003;8 (2):182-190.]
- Chorliet S, Gulija M, Andreeva V. Drug use survey
in Macedonia 2000. http://dcc2.bumc.bu.edu/richardl/IH820/Resource_materials/Drug_use_survey_in_Macedonia1.doc).
- Memon K. Use of drugs in Sind Province Pakistan
primary health care facilities.
(http://dcc2.bumc.bu.edu/prdu/Other_Documents/Khalil
_Concentration_Paper.htm).
- WHO Action Programme on Essential Drugs and
Vaccines. How to investigate drug use in health
facilities: selected drug use indicators. Geneva, World
Health Organization, 1993
- Desta Z et al. Assessment of rational drug use and
prescribing in primary health care facilities in north
west Ethiopia. East African Med jJ, 1997, 74:758–63.
- Tomson G, Diwan V, Angunawela I. Paediatric
prescribing in out-patient care. An example from Sri
Lanka. Euro J Clinical Pharmacol, 1990, 39:469–73.
- Krause G et al. Rationality of drug prescriptions in
rural health centers in Burkina Faso. Health Policy and
Planning, 1999, 14:291–8
- Hamadeh GN et al. Common prescriptions in
ambulatory care in Lebanon. Annals of
pharmacotherapy, 2001, 35: 636–40
- Pavin M, et al. Prescribing practices of rural primary
health care physicians in Uzbekistan. Trop Med. and Int.
Health, 2003;8 (2):182-190.
- Kristiansson C, Larsson M, Thorson A, Gotuzzo E,
et al. Toward Improving Rational Use of Antibiotics in
Peru. http://mednet3.who.int/icium/icium2004/resources/ppt/CH011.ppt
- Patel V ; Vaidya R ; Naik D ; Borker P. Irrational
drug use in India: A prescription survey from Goa. J
Postgrad Med, 2005; 51:9-12
- Thawani, V.R., Motghare, V.M., Dani, A.D. and
Shelgaonkar, S.D. Therapeutic audit of dermatological
prescriptions. Ind J Dermatol. 1995; 40 (1):13-18
- Motghare, V.M., Thawani, V.R., Purwar, M.B. and
Pagare, A. Perinatal prescribing to indoor patients in
Govt. Medical College Hospital, Nagpur. J Obstet
Gynaecol Fmly Welf.1996, 7(2):4-8.
- Thawani, V.R., Motghare, V.M., Pagare, A. and
Gharpure, K.J. Antimicrobial drug utilization in rural
hospitals. The Antiseptic. 1996, 93(4):144-45
- Jaju, Ulhas. Misuse of antibiotics and
antimicrobials. in Under the Lense : Health and
medicine. Jayarao KS and Patel AJ (Eds) Voluntary
Health Association of India, New Delhi.1986,139-147
- Bapna, J.S., Tekur, U., Gitanjali, B., Shashindran,
C.H., Pradhan, S.C., Thulasimani, M. and Tomson, G.
Drug Utilization at primary health care level in Southern
India. Eur J Clin Pharmacol 1992; 43:413-5.
- Thawani, Vijay, and Gharpure, K.J., The rationale
of drug rationing. Bull Drug and Hlth Inform.1996,
3(2):39-40,43.
- Ruckmani, A. Rational drug use : A remote
possibility ? Bull Drug Hlth Inform 1995, 2(1):20.
- Patel V, Vaidya R, Naik D, Borker P. Irrational drug
use in India: A prescription survey from Goa. J
Postgrad Med 2005;51:9-12(SEARO)
- Kshirsagar MJ et al. Prescribing patterns among
medical practitioners in Pune, India. Bulletin of the
World Health Organization, 1998, 76:271–5.
- Greenhalgh T. Drug prescription and selfmedication
in India: An exploratory survey. Soc Sci
Med 1987;25:307-18.
- Dineshkumar B, Raghuram TC, Radhaiah G,
Krishnaswamy K. Profile of drug use in urban and rural
India. Pharmacoeconomics 1995;7:332-46.
- Rattan, A. and Kumar, A. Antibiotics – use and
misuse. Journal of Academy of Hospital Administration.
1995, 7(1):19-22.
- Kulkarni RA, Kochhar PH, Dargude VA,
Rajadhyakshya SS, Thatte UM. Patterns of
antimicrobial use by surgeons in India. Ind J Surg
2005;67:308-15
37a. WHO Increasing the relevance of education for
health professional-Report of a WHO study group on
problem solving education for the health professions
Technical Report Series 838, WHO,Geneva 1993,P15.
- Khor, M. Report on Proceedings of the World
Health Assembly (May 2005). South-North
Development Monitor (SUNS), 27 May 2005.
- Tapsall J. Antimicrobial resistance in Neisseria
gonorrhoea. Geneva, World Health Organization, 2001.
WHO/ CDS/CSR/DRS/2001.3.
- Schrag S, Beall B, Dowell SF. Resistant
pneumococcal infections: the burden of disease and
challenges in monitoring and controlling antimicrobial
resistance. Geneva, World Health Organization, 2001.
WHO/CDS/CSR/DRS/ 2001.6.]
- Sack DA, et al. Antimicrobial resistance in
shigellosis, cholera and campylabcater. Geneva, World
Health Organization, 2001,
WHO/CDS/CSR/DRS/2001.8.
- The 2nd International Conference on Improving Use
of Medicine, Chiang Mai, Thailand (30 March- 2 April,
2005).
- Ministry of Health, Republic of Indonesia. Final Report
on Pre-Post Controlled Trial of Drug Use, Jakarta, 1994
- Saniel, M. New Straits Times (Malaysia), 6
February 1996).
Gaash, B
Dr Bashir Gaash, MD, Phd, DCH, is a public health practitioner
with a particular interest in emergence of resistance to commonly used antibiotics
Contact: Cell: 9419089018
Email: gaashb_10(at)yahoo.co.in
Pharmaco-epidemiology, among other things, monitors trends of antibiotic use and the emergence of resistance to commonly used antibiotics. In our place, the concept has not taken up yet and rampant misuse of antibiotics is a rule, with dramatic emergence of multi-drug resistant typhoid, pneumonia, urinary tract infection, reproductive tract infection and nosocomial infections. Here we discuss the problem in an international and Indian perspective.
Introduction
The accidental discovery of the first antibiotic by Alexander Fleming1 in 1928 revolutionized the therapy of infection, and saved millions of lives especially during the two World Wars. The dramatic impact was attributable to lack of primary resistance among microbes and scarcity of antibiotics with a high cost which necessitated extraordinary prudence in their use.
Then came a time when, with progressively falling costs and increasing availability of antibiotics, prescribing became less judicious. The global pharmaceutical industry was quick to take advantage of the declining costs of production, expanding world markets especially in developing countries, and gullibility of the prescribers. Every week a new antibiotic started to be pumped into the market leaving no time for doctors to fully get acquainted with new products while, at the same time, providing ample chances to microorganisms to develop different means of resistance to guarantee their survival.
Global scenario
Currently, antimicrobials are the most widely used category of drugs in the world. In 2004, the World Health Organization reported the figure for unwarranted antibiotics prescriptions standing at roughly 50%. Overuse and misuse of antibiotics was particularly high (50% to almost 100%) in upper respiratory infections, most of which are generally viral and self-limited. A WHO study of antibiotic use in 13 low-, middle- and high-income countries from 1992 to 1996 revealed that antibiotics were wrongly prescribed for approximately 30% of cases of URTI. Studies have revealed the existence of compulsive antibiotic prescribing all over the world3.
Developed world: Contrary to expectations, antibiotic misuse and overuse is common not only in developing countries but also in the developed world. A large study in the USA found that 51% of patients with colds and URTI were receiving antibiotics and estimated that over 20% of all antibiotic prescriptions were clinically useless4. In addition, it was found that only 20-25% of antibiotic use in USA was based on the results of culture and sensitivity tests.
A 2003 article by Ronning et al5 reviewed antibacterial usage in 16 European countries. This study demonstrated that the antibiotic use was higher than required, largely irrational and generally empirical. In Italy, a mere 2% of antibiotic use was determined by culture and sensitivity. A European study presented at the 14th European Congress of Clinical Microbiology and Infectious Diseases held in Prague in May 20046 reported that 36% of the children with symptoms reported use of antibiotics within 2 weeks, most frequently for acute respiratory infections (ARI) and diarrhoea-like syndromes.
In Australia, it was found that, even with ‘antibiotic guidelines’ in place, less than 50% of antibiotic treatment in the wards of teaching hospitals in Melbourne complied with the recommendations. In far-flung centres in that country, more than 90% of surgical prophylaxis was found to be inappropriate7.
The situation of drug overuse or irrational use in developing world is particularly alarming.
China: A comparative study of antibiotic use in 35 countries showed that the overall rate for the use of antibiotics for upper respiratory tract infection in 1997 was as high as 97% in China8 Multicentric studies showed that over 70% of patients were prescribed antibiotics in Indonesia and Pakistan.
Indonesia: A WHO-World Bank supported study found an antibiotic overuse of 43% in Indonesia. While only 46% of the under fives received oral rehydration salts (ORS) for the treatment of diarrhea, 73% of them received oral antibiotics. For patients aged over five years, the respective figures were 36% and 91%. In terms of mild upper respiratory infection treatment, 75-86% of patients received antibiotics.9
Pakistan: In Pakistan, the average number of drugs per prescription was 3.5, with antibiotics accounting for 76% of the prescribed drugs. Almost 75% of antibiotics were given by injection. Even at the rural health service levels, antibiotics were prescribed to 78% patients, 74% receiving them parenterally. The antibiotic prescription frequency in case of children aged 1-15 was as high as 84%.10
The over-prescribing of antibiotics and injections is confirmed by the breakdown of prescribing for the 10 most frequently diagnosed diseases (Fig 1), which also reveals gross irrationality in antibiotic prescribing.
Fig 1: Most frequent indications for antibiotic use in Pakistan16
Nepal: In Nepal, over 50% of antibiotics prescribed in 1996 were found to be unnecessary. Studies performed between 1997 and 199911, 12 reported a prevalence of 61% antimicrobial use in intensive care units. Results of studies performed in 2004-0513 were no different. Analysis of prescriptions showed that 50.2% of the patients received an antimicrobial, and that 84.5% of the antimicrobials were used without obtaining bacteriological evidence of infection. Combination therapy was not uncommon: the prescribing frequency of combination antimicrobials was 14.6%, of which 84.4% of the combination prescriptions were for ampicillin + cloxacillin. Almost 62% of the antimicrobials were prescribed by the parenteral route. Almost 30% of the antibiotics prescribed were for lower respiratory tract infections, mainly for COPD followed by pneumonia.
Approximately 71% of the patients receiving an antimicrobial were from the medical side while 29.5% were surgical patients.
Antimicrobials were used for prophylaxis in 30.9% and for non-bacteriologically proven infection in 51%. The most commonly prescribed antimicrobials were metronidazole, ampicillin, combination of ampicillin and cloxacillin and gentamicin. This profile closely resembled that used in Pakistan.
Studies on prophylaxis showed metronidazole, ampicillin+cloxicillin, gentamicin, ampicillin and cefotaxime, in that order, to be the most frequently prescribed antibiotics. It is noteworthy that prophylactic use of antimicrobials has a very high potential of easy abuse and overuse with consequent costly and dangerous implications.
Retrospective analysis of case records showed that, in 26.2% cases, the use of the antimicrobials was irrational. Common examples of illogical prescribing were prescription of a third generation cephalosporin where a cheaper antimicrobial would have been satisfactory, use of a cocktail of antimicrobials with overlapping spectrums for abdominal infections, and use of antimicrobials in cases of cerebrovascular accidents, acute confusional states, etc. Costly antimicrobial combinations and newer antimicrobials were used where an older antimicrobial would have worked satisfactorily.
A study of antibiotic practices in 35 countries of the world14, 15 presented at the 1st International Conference for Improving the Use of Medicines (ICIUM) in Thailand held in 1997 showed that, on an average, 45% of patients were prescribed antibiotics (Half of them parenterally). 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 antibiotics.
In Eritrea, 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.
Fig 2: Results of a 35-country study – Percentage of patients receiving antibiotics
Oman: Study of sub-speciality prescribing at hospital facilities in Oman (Muscat and Dhofar) revealed that 14-29% of patients were prescribed antibiotics. Suburban PHCs revealed a frequency of 21-23% and urban PHCs 25%. The highest antibiotic prescribing was seen in medical and ENT sub-specialities. The methodology used a large sample size of 600 prescriptions per facility. Antibiotic utilization studies in Sudan and Jordan showed that the respective percentage of prescriptions involving antibiotics was as high as 63% and 60.9%. The comparative figures for Nigeria (48%), Zimbabwe (29%), Lebanon (17.5%) and Yemen (46%) were lower.17-21
Uzbekistan: Studies in Uzbekistan222 found that at least 21% of prescriptions contained an antibiotic. The respective frequency of antibiotic prescribing for upper and lower respiratory infections was as high as 93.5% and 78.9%, of which 79% and 54.8% were given by injections. Significantly, 30.2% diarrhoeal patients were prescribed antibiotics along with other largely unnecessary drugs.
Peru: In Peru, a study23 conducted jointly by IHCAR, Karolinski Institute (Sweden), Institute of Tropical Medicine, Peru University, and University of Florence (Italy) showed that 71% of 6-72 month old children receiving antibiotics had their antibiotics prescribed by a health care professional, 8% had consulted a pharmacist and 19% had selfmedicated without consulting a health care supplier. It was surprising to find that children whose caregivers have consulted a health care provider were more likely to be treated with antibiotics than children who had been exclusively self-medicated by their caregivers. About 28% of the children with upper ARI-like symptoms were treated with antibiotics. A higher percentage of the children with ARI-diarrhoea mixes (38%), lower ARI (50%) and diarrhoea (44%) received antibiotics.
India24: Being a populous country with rampant corruption and lax controls, India is an ideal country for multinational companies to pump in their newly developed but poorly researched drugs including antibiotics.
Utilization studies and prescription audits in Goa have shown that antibiotics constitute about 39% of drugs prescribed to outdoor patients25; 30% in indoor perinatal patients26; and 22% in rural hospitals27.
Medical activists in India have been raising their fingers at the rampant misuse of antibiotics for quite sometime now28. Overprescribing of antibiotics has been widely reported29,30 The use of single injection of tetracycline to a febrile child has been highlighted even in the press.31
A recent survey in Goa revealed that polypharmacy was the norm, with 80% of prescriptions having more than one medicine, (many patients receiving 5 or more preparations simultaneously). Antibiotics (with analgesics) were included in almost a quarter of prescriptions32. The average frequency of antibiotic prescribing in the neighbouring Pune was found to be 43%33.
In a north Indian study of 2400 prescriptions, antibiotics were found to be widely and inappropriately used by practitioners34. A study of 2953 prescriptions from PHCs in south India revealed that patients received an average of 2.71 drugs and that antibiotics (with analgesics and antihistamines) were the most commonly used drugs accounting for more than 80% of the drugs prescribed29.
In Andhra Pradesh, 60% of drugs (particularly antibiotics and vitamins) prescribed in rural areas and 47% of them in urban areas, were non-essential, compared to 47% in urban areas35.
Studies also revealed that in the majority of cases antibiotic prescribing was empirically directed at the putative site of infection. Since the meager culture facilities are available in a very small number of hospitals in India, empirical antibiotic use is rampant36. The distressing fact is that where these are available, they are infrequently requested and when advised, often the results are not considered for decision making.
Although antibiotic use is rampant in medical outpatients and wards, surgeons don’t lag behind. In spite of several available guidelines for the appropriate use of antimicrobials in perioperative patients, the fear of high morbidity and mortality associated with intra-abdominal infections and surgical site infections has led to misuse of antimicrobials in the perioperative period. Studies37 show that the third/fourth generation cephalosporin plus an anti-anaerobic agent were preferred (84% cases) for treating intraabdominal infections. Approximately 55% of the surgeons prescribed a single antibiotic for clean surgeries. A combination of two or three antimicrobial agents was preferred in clean contaminated (42.3%) and dirty (46.9%) surgeries respectively. Third generation cephalosporins (particularly ceftriaxone and cefotaxime) were the commonly prescribed antibiotics (80%) for all surgeries. However, in majority of cases antibiotics were prescribed for durations longer than recommended in standard guidelines.
A recent (2007) study at the Jawahar Lal Nehru Medical College, AMU, revealed that the most commonly prescribed drugs by general surgeons were antibiotics (93%) – mostly ceftriaxone and amikacin. (Salman MT et al. Drug Prescribing Pattern in Surgical wards of a Teaching Hospital in North India. Ind J Pract Doctor 2008;IV(5):5+
Unnecessary medication: Globally, the figure for unwarranted antibiotics prescriptions stands at roughly 50%. According to figures gathered by surveys presented to WHO in 2000, about 60% of antibiotics in Nigeria were prescribed unnecessarily. In Nepal, over 50% of antibiotics prescribed in 1996 were not needed and 40% of medicine expenditure in the same year was wasted due to inappropriate prescriptions. Retrospective analysis of case records in Nepal in 2003 showed that, in 26.2% cases, the use of the antimicrobials was irrational
The World Health Organization pointed out that nearly 2 out of every 3 antidiarrhoeal preparations sold in 12 countries in Latin America in 1990 contained an antibiotic. Similarly, a survey carried out in 1989 showed that nearly one out of two antidiarrhoeal products in Third World countries contained an unnecessary antibiotic.
The conclusions drawn at the consultative group discussion23 in Peru were that the results suggested ever increasing potential of irrational use of antibiotics for children, including short courses, over-prescribing, and self medication.
In a north Indian study of 2400 prescriptions, antibiotics were found to be widely and inappropriately used by practitioners.34
Study of emergency room prescriptions in private hospitals in Manila showed that over 90% of patients who received antibiotics did not really need them.
Side effects: Antibiotics can potentially do the same to the host what they do to the bacterium. For example, trimethoprim can depress folic acid in both the microorganism and the host. Many antibiotics can lead to adverse effects through multiple means: chloramphenicol depresses bone marrow in all the recipients but may drastically do so in a person with idiosyncrasy. A State Food and Drug Administration (SFDA; China’s drug watchdog) survey revealed that nearly 50% of the total side-effect reports from drugs were for prescribed antibiotics. Experts there believe that many of the 20 million people with hearing disabilities in China might be suffering because of the irrational use of antibiotics8. In the 1960s and 1970s, nationwide abuse of acheomycin is said to have resulted in damage to the teeth of a generation of Chinese people.8
Recently, fluoroquinolones are being blamed for multiple adverse effects which may be long lasting. The sufferers have hosted their web sites to denounce what they call ‘floxing’.
In addition to development of resistance, superinfection may result from overuse or prolonged administration of broad spectrum antibiotics. Many wide spectrum antibiotics are recognized to cause death of the normal intestinal and vaginal flora. Fungal infections are linked to overuse of such expensive antibiotiocs as cephalosporins37a.
Problem of Resistance: Irrational use (overuse, misuse, prolonged use) of antimicrobials are contributing to growing resistance to treatment for the very diseases that contribute most to the burden of illness in low-income countries. The irrational use of pharmaceutical drugs, contributing to increasing resistance was particularly discussed at the 9-day long World Health Assembly in May 200538. The World Health Organisation says that anti-microbial resistance is one of the world’s most serious public health problems; a major cause being the wrong use of medicines.
The World Health Assembly in May 2005 warned that the anti-microbial resistance was rapidly increasing, with resistance of up to 70-90% to original first-line antibiotics for dysentery (shigella), pneumonia (pneumococcal), gonorrhoea, and hospital infections (staph. Aureus).
Global antimicrobial resistance prevalence rates:
- Malaria (chloroquine resistance in 81 out of 92 countries);
- Tuberculosis (0-17% primary multi-drug resistance);
- HIV/AIDS (0-25% primary resistance to at least one antiretroviral drug);
- Gonorrhoea (5-98% penicillin resistance);
- Pneumonia and bacterial meningitis (0-70% penicillin resistance in streptococcus pneumonia); diarrhoea: shigellosis (10-90% ampicillin resistance, 5-95% cotrimoxazole resistance);
- Hospital infections (0-70% resistance of staphylococcus aureus to all penicillins and cephalosporins).
WHO country data 2002-03
On a global scale resistance to penicillin treatment was estimated to be between 5% and 98% for gonorrhoea and between 12% and 55% for pneumonia and bacterial meningitis39,40
In Bangladesh41, resistance to ampicillin in the treatment of shigellosis diarrhoea is estimated to be over 90%. In addition, resistance to treatment with nalidixic acid increased from less than 10% in 1987 to over 90% in 1992.
Overuse of chloroquine for the treatment of malaria led to widespread resistance which is now established in 81 of the 92 countries where the disease is endemic – substantially raising the costs of treatment with second- and third-line antimalarial medicines42. This was a matter of great concern at the 2nd International Conference on Improving Use of Medicine (Chang Mai), sponsored by WHO, the Thai Network for Rational Use of Drugs (ThaiNRUD), Management Sciences for Health, the Centre for International Health, Boston University School of Public Health; Harvard Medical School and the International Network for the Rational Use of Drugs.
Economics of Antibiotic Overuse:
Currently, antimicrobials are the most widely used category of drugs in the world, accounting for over one-quarter of hospital drug costs2.
Studies found in Indonesia that, in terms of cost, antibiotics ranked highest, followed by cough and cold medicines, and analgesics. Drugs for the treatment of diarrheal diseases and respiratory conditions accounted for 68% of all under-five health centre drug costs and 38% of all over-five drug costs.43 The observed treatment cost was Rp. 512 per case (4 times the expected cost). Antibiotics accounted for 60-63% of URI treatment costs.
About 40% of medicine expenditure in Nepal in 1996 was wasted due to inappropriate antibiotic prescriptions. Such avoidable wastage has great implications for an economically weak, resource-poor country with a high burden of infectious diseases.
Drugs in the present day world have come to mean money for the manufacturer as well as prescriber and retailer. According to the WHO, the global sales of prescription drugs in 2000 were $282.5 billion. This has to be borne in mind that all this money has to come from the pocket of a patient, who is often poor and financially drained, or from the resource-less governments of poor countries, antibiotics and other essential drugs have to be procured at the cost of food, child education and family welfare.
A joint 1992 study by the National University of Malaysia and the Health Ministry conducted at six government hospitals found that, alhough the WHO Essential Drug List recommends only 20 antibiotics, yet there are over 200 antibiotic preparations sold in Malaysia. Thus, it does not surprise to learn that the 1993 imports of antibiotics cost the country over RM85 million (up 100% since 1982) – with penicillins taking up 28% of the total. Antibiotics made up 14% of all medicinal and pharmaceutical products produced or imported into that country.
In Australia, drug companies spend A$200 million every year just to market their products. The sum represents almost A$10,000 a year spent on attempting to win each of Australia’s 21,000 GPs. This is 50% more than allowed by law in the UK for marketing.
In Japan, there are an estimated 43,000 drug salesmen and almost as many wholesaler representatives. An average Japanese doctor receives 450 sales calls a year. Returns for drug companies are enormous: In 1988, Japan’s market for injectable antibiotics amounted to about £1.7 billion; cephalosporins accounting for 71% of the total compared to about 24-55% in the US and Europe.
In Britain the pharmaceutical industry also realises the importance of bringing new products to the attention of GPs. As a result, about two million visits are paid by sales representatives, with the average GP receiving some 62 visits a year.
To top them all, drug promotion costs in the US were $15.7 billion in 2000. This far exceeded the entire WHO budget in that year to discourage aggressive drug promotion.
The aggressive campaigning by pharmaceutical companies has paid off. Data on trends in medicine use show that globally the average number of drugs used increased from 1990 to 2003 from 2.2 to 2.7 per patient between 1990 and 2003. Only 40-50% of patients were treated in compliance with standard treatment guidelines; in other words 50-60% of antibiotic use in the world is either because of our innocence or the drug companies’ shrewdness.
Quinolones (fluoroquinolones) which are among the latest antibiotics to be developed in the 1980s, accounted for 15% of the world antibiotic market in 1990. Americans spend US$700,000 a day on just one type, ciprofloxacin. In 1989, ciprofloxacin was the 4th most commonly prescribed antibiotic in the US – with over 5 million prescriptions at a cost of US$248 million. The sales soared only because of heavy promotion. In the first half of 1988, ciprofloxacin was the 2nd most advertised product.
A WHO Expert Committee has suggested that a reserve list of fewer antibiotics like the thirdgeneration cephalosporins, quinolones and vancomycin be set aside for specific indications such as infections caused by organisms resistant to standard drugs and not be available for unrestricted use. However, the former two products are widely used as first-line antibiotics by doctors including specialists in private practice.
The cost of excessive promotion is met by huge profit margins of life-saving drugs like antibiotics. According to WHO, profit margins for expensive drugs like cephalosporins make up a large part of a hospital’s income in developed countries. The value of this discount scheme is estimated at £7 billion each year!
The promotion for medicine, especially antibiotics, according to the Research Institute for Tropical Medicine, Manila, is heaviest in developing countries44. This, on the one hand, increases the cost of drugs, particularly antibiotics, and on the other hand, puts the prescriber under social or economic pressure to unnecessary use of the adverstised antibiotics.
According to the Working Group on Health and Development (WEMOS) in Amsterdam, 75 products (including many antibiotics) which had been pulled out or banned in one or more European countries were identified in the Third World in 1991. This proves that multinational companies forced to withdraw certain products considered to be dangerous, ineffective or unnecessary turn to the developing world for profiteering. They resort to aggressive campaigning to make up for their loss of business in the developed world.
Though WHO has come out with an Essential Drug List (EDL) of 250 preparations, in India alone the drug market has 70,000 preparations. Most of these drugs comprise of antibiotics, vitamins and anti-inflammatory analgesics.
Jammu and Kashmir State is a considered a huge consumer of drugs, required or not. One guess puts the number of drug companies operating in the State at a whopping 9000!. People of Kashmir Valley are particularly fond of medicines, and have been made habitually tolerant to polypharmacy.
An average prescription has 4-5 different drugs. Antibiotics are prescribed freely, and in absence of Drugs and Cosmetic Act, can be purchased from any pharmacy at will. Majority of children still receive one or two antibiotics for diarrhea, though ORS use has not been more than 38%45. All cases of ARI are managed by giving the latest antibiotics. Doctors compete with each other in prescribing the most recently introduced, albeit very costly, antibiotics. Often the freshly introduced antibiotic is prescribed within the first 10 minutes of introduction. Salesmen (called medical representatives) try all means to fulfill their sale targets, and more often than not the doctor may not even get a chance to go through the company leaflet describing the prescribed drug.
The doses are often substandard and durations shorter or much longer than those recommended. The consequences have been the rapidly increasing resistance among commonly found organisms. One study46 conducted by us found that majority of the uropathogens had already developed resistance to most commonly used drugs including norfloxacin, co-trimoxazoile, and ampicillin. Multi-drug resistant community-acquired pneumonia and typhoid are common in the Valley.
Drug prescribing in Kashmir has taken shape of a racket where every stake holder, except the patient, is benefitted. Promotion is vehemently aggressive, and the nexus between pharmaceutical companies and the prescribers is keeping the environment favourable for flourishing substandard drug (called here Number 2) trade.
There is an urgent need to enforce the Essential Drug List of the WHO in public as well as private medical practice. The Government must take the lead by purchasing generic drugs for hospitals and peripheral health outlets. Private medical setup will either follow or can be made to fall in line through legislation and legal enforcement.
References:
- Kendall F. Haven, Marvels of Science (Libraries Unlimited, 1994); p182
- Smith AJ, Aronson JK, Thomas M. Antibiotic policies in the developing world. Euro J Clinical Pharmacol. 1991, 41:85-87.
- Swindell, P.J., Reevs, D.S., Bullock, D.W., Davies, A.J. and Spence, C.E. Audit of antibiotic prescribing in a Bristol hospital. British Medical Journal.1983, 286:118-122.
- Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. Jam Med Assoc, 1997, 278(11):901-4.
- Ronning M, et al. Problems in collecting comparable national drug use data in Europe: the example of antibacterials. Berlin, Springer-Verlag. 2003.
- Kristiansson C. Social and financial factors influencing rational use of antibiotics. 14th European Congress of Clinical Microbiology and Infectious Diseases Prague / Czech Republic, May 1–4, 2004 (Abstract no. 902- p1162)
- Harvey, Ken. Therapeutic guidelines – the way ahead. Essential Drug Monitor (WHO).1995, No19:10-11.
- Hui L, Li X, Zeng X, Dai Y, et al. Patterns and determinants of use of antibiotics for acute respiratory tract infection in children in China. Paed. Infect Dis J, 1997, 16(6):560-564.
- Arustiyono. Promoting rational use of drugs at the community health centres in Indonesia, 1999, WHOWorld Bank Health Project IV. (http://dcc2.bumc.bu.edu/prdu/ Other_Documents/ ARUS_INDONESIA_PRDU.htm).
- Memon K. Use of drugs in Sind Province Pakistan primary health care facilities. (http://dcc2.bumc.bu.edu/prdu/Other_Documents/Khalil _Concentration_Paper.htm).
- Burke JP, Pestotnik SL. Antibiotic use and microbial resistance in intensive care units: impact of computer-assisted decision support. J Chemother 1999;11(6):530-5.
- Bergmans DC, Bonten MJ, Gaillard CA, van Tiel FH, van der Geest S, de Leuw PW, Stobberingh EE. Indications for antibiotic use in ICU patients: a one-year prospective surveillance. J Antimicrob Chemother 1997;39(4):527-35.
- Shankar R, Partha P, Shenoy N, Brahmadathan KN,Ravi Shankar P. Investigation of antimicrobial use pattern in the intensive treatment unit of a teaching hospital in western Nepal. 2005, Clinical Medicine and Health Research.
- Pavin M, et al. Prescribing practices of rural primary health care physicians in Uzbekistan. Trop Med. and Int. Health, 2003;8 (2):182-190.]
- Chorliet S, Gulija M, Andreeva V. Drug use survey in Macedonia 2000. http://dcc2.bumc.bu.edu/richardl/IH820/Resource_materials/Drug_use_survey_in_Macedonia1.doc).
- Memon K. Use of drugs in Sind Province Pakistan primary health care facilities. (http://dcc2.bumc.bu.edu/prdu/Other_Documents/Khalil _Concentration_Paper.htm).
- WHO Action Programme on Essential Drugs and Vaccines. How to investigate drug use in health facilities: selected drug use indicators. Geneva, World Health Organization, 1993
- Desta Z et al. Assessment of rational drug use and prescribing in primary health care facilities in north west Ethiopia. East African Med jJ, 1997, 74:758–63.
- Tomson G, Diwan V, Angunawela I. Paediatric prescribing in out-patient care. An example from Sri Lanka. Euro J Clinical Pharmacol, 1990, 39:469–73.
- Krause G et al. Rationality of drug prescriptions in rural health centers in Burkina Faso. Health Policy and Planning, 1999, 14:291–8
- Hamadeh GN et al. Common prescriptions in ambulatory care in Lebanon. Annals of pharmacotherapy, 2001, 35: 636–40
- Pavin M, et al. Prescribing practices of rural primary health care physicians in Uzbekistan. Trop Med. and Int. Health, 2003;8 (2):182-190.
- Kristiansson C, Larsson M, Thorson A, Gotuzzo E, et al. Toward Improving Rational Use of Antibiotics in Peru. http://mednet3.who.int/icium/icium2004/resources/ppt/CH011.ppt
- Patel V ; Vaidya R ; Naik D ; Borker P. Irrational drug use in India: A prescription survey from Goa. J Postgrad Med, 2005; 51:9-12
- Thawani, V.R., Motghare, V.M., Dani, A.D. and Shelgaonkar, S.D. Therapeutic audit of dermatological prescriptions. Ind J Dermatol. 1995; 40 (1):13-18
- Motghare, V.M., Thawani, V.R., Purwar, M.B. and Pagare, A. Perinatal prescribing to indoor patients in Govt. Medical College Hospital, Nagpur. J Obstet Gynaecol Fmly Welf.1996, 7(2):4-8.
- Thawani, V.R., Motghare, V.M., Pagare, A. and Gharpure, K.J. Antimicrobial drug utilization in rural hospitals. The Antiseptic. 1996, 93(4):144-45
- Jaju, Ulhas. Misuse of antibiotics and antimicrobials. in Under the Lense : Health and medicine. Jayarao KS and Patel AJ (Eds) Voluntary Health Association of India, New Delhi.1986,139-147
- Bapna, J.S., Tekur, U., Gitanjali, B., Shashindran, C.H., Pradhan, S.C., Thulasimani, M. and Tomson, G. Drug Utilization at primary health care level in Southern India. Eur J Clin Pharmacol 1992; 43:413-5.
- Thawani, Vijay, and Gharpure, K.J., The rationale of drug rationing. Bull Drug and Hlth Inform.1996, 3(2):39-40,43.
- Ruckmani, A. Rational drug use : A remote possibility ? Bull Drug Hlth Inform 1995, 2(1):20.
- Patel V, Vaidya R, Naik D, Borker P. Irrational drug use in India: A prescription survey from Goa. J Postgrad Med 2005;51:9-12(SEARO)
- Kshirsagar MJ et al. Prescribing patterns among medical practitioners in Pune, India. Bulletin of the World Health Organization, 1998, 76:271–5.
- Greenhalgh T. Drug prescription and selfmedication in India: An exploratory survey. Soc Sci Med 1987;25:307-18.
- Dineshkumar B, Raghuram TC, Radhaiah G, Krishnaswamy K. Profile of drug use in urban and rural India. Pharmacoeconomics 1995;7:332-46.
- Rattan, A. and Kumar, A. Antibiotics – use and misuse. Journal of Academy of Hospital Administration. 1995, 7(1):19-22.
- Kulkarni RA, Kochhar PH, Dargude VA,
Rajadhyakshya SS, Thatte UM. Patterns of
antimicrobial use by surgeons in India. Ind J Surg
2005;67:308-15
37a. WHO Increasing the relevance of education for health professional-Report of a WHO study group on problem solving education for the health professions Technical Report Series 838, WHO,Geneva 1993,P15. - Khor, M. Report on Proceedings of the World Health Assembly (May 2005). South-North Development Monitor (SUNS), 27 May 2005.
- Tapsall J. Antimicrobial resistance in Neisseria gonorrhoea. Geneva, World Health Organization, 2001. WHO/ CDS/CSR/DRS/2001.3.
- Schrag S, Beall B, Dowell SF. Resistant pneumococcal infections: the burden of disease and challenges in monitoring and controlling antimicrobial resistance. Geneva, World Health Organization, 2001. WHO/CDS/CSR/DRS/ 2001.6.]
- Sack DA, et al. Antimicrobial resistance in shigellosis, cholera and campylabcater. Geneva, World Health Organization, 2001, WHO/CDS/CSR/DRS/2001.8.
- The 2nd International Conference on Improving Use of Medicine, Chiang Mai, Thailand (30 March- 2 April, 2005).
- Ministry of Health, Republic of Indonesia. Final Report on Pre-Post Controlled Trial of Drug Use, Jakarta, 1994
- Saniel, M. New Straits Times (Malaysia), 6 February 1996).