North South University Cover Page

Department of Public Health Name: Parth Protim Barmon

ID No: 1020688080

Course name and code: Directed studies in Public Health

PBH 705

Course Taken: Summer 2011

Title of the Research: Impact of Antimicrobial resistance (AMR) in developing countries.

Submitted to: Prof. Tahera Ahmed,

Part-time Faculty NSU.

Length: 5,974 Words

Date of Submission: December 30, 2011

Declaration

I hold a copy of this research paper that I can produce if the original is lost or damaged. I hereby certify

that no part of this research paper or product has been copied from any other student’s work or from any

other source expect where due acknowledgement is made in the research. No part of this research paper /

product has been written / produced for me by any other person where such collaboration has been

authorized by the subject lecture/ tutor concerned.

Signature………………

Note: An examiner or lecturer/ tutor have the right not to mark this assignment if the above declaration

has not been signed.

Title of the study:

Impact of Antimicrobial resistance (AMR) in developing countries.

Back ground of the study:

Antimicrobial resistance (AMR) is resistance of a microorganism to an antimicrobial medicine to

which it was previously sensitive. Resistant organisms (they include bacteria, viruses and some

parasites) are able to withstand attack by antimicrobial medicines, such as antibiotics, antivirals,

and antimalarials, so that standard treatments become ineffective and infections persist and may

spread to others. AMR is a consequence of the use, particularly the misuse, of antimicrobial

medicines and develops when a microorganism mutates or acquires a resistance gene. [10]

Several reports suggest that antimicrobial resistance is an increasing global problem; but like

most pandemics, the greatest toll is in the less developed countries. The dismally low rate of

discovery of antimicrobials compared to the rate of development of antimicrobial resistance

places humanity on a very dangerous precipice. Since antimicrobial resistance is part of an

organism's natural survival instinct, total eradication might be unachievable; however, it can be

reduced to a level that it no longer poses a threat to humanity. While inappropriate antimicrobial

consumption contributes to the development of antimicrobial resistance, other complex political,

social, economic and biomedical factors are equally important. Tackling the hazard therefore

should go beyond the conventional sensitization of members of the public and occasional press

releases to include a multi-sectoral intervention involving the formation of various alliances and

partnerships. Involving civil society organisations like the media could greatly enhance the

success of the interventions.

It is difficult to determine the worldwide prevalence of antimicrobial resistance (AMR); but

several reports suggest that it is an increasing problem of phenomenal proportions, affecting both

rich and poor countries [1-8]

. In 2007, the prevalence of Methicillin-resistant Staphylococcus

aureus (MRSA) ranged from 27.4 to 62.4% and Penicillin-nonsusceptible Streptococcus

pneumoniae from 23.3% to 54.5% in the different census regions of the United States [1]

. In the

UK, enterobacteriacea resistance to cephalosporins is on the increase [2]

, as is the prevalence of

MRSA[3]

in hospital and community settings. The recent report of the European Antimicrobial

Resistance Surveillance System showed a rising prevalence of resistance among the seven

bacterial species (Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli,

Enterococcus faecalis, Enterococcus faecium, Klebsiella pneumoniae and Pseudomonas

aeruginosa) that serve as indicators for the development of antimicrobial resistance in Europe to

many of the mainline antibiotics [4]

. In India, up to 80% of S. aureus strains are resistant to

penicillin and ampicillin[5]

. Of 3362 pneumococcal isolates collected from 69 centres in 25

countries in the PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the

Ketolide Telithromycin) study between 1999 and 2000, resistance to Penicillin G was 53.4% in

Asia (overall prevalence), France 46.2%, Spain 42.1% and North Korea 71.5%; resistance to

erythromycin varied from 4.7% in Sweden to 87.6% in South Korea; while resistance to

fluoroquinolones in Hong Kong was 14.3% [6]

. And in South Africa, macrolide resistance and

penicillin non-susceptibility were 54% and 74% respectively [7]

. Chloroquine is almost useless as

an antimalarial in most malaria endemic countries, while MDR-TB and XDR-TB are now

assuming frightening proportions [9]

. While AMR is a growing global problem, like most

epidemics, the greatest toll is usually in the less developed countries. Unfortunately, the rate at

which antimicrobial resistance is developing far outstrips the rate at which new antimicrobials

are being discovered, placing humanity on a very dangerous precipice.

According to WHO (February 2011):

Infections caused by resistant microorganisms often fail to respond to conventional

treatment, resulting in prolonged illness and greater risk of death.

About 440 000 new cases of multidrug-resistant tuberculosis (MDR-TB) emerge

annually, causing at least 150 000 deaths.

Resistance to earlier generation antimalarial medicines such as chloroquine and

sulfadoxine-pyrimethamine is widespread in most malaria-endemic countries.

A high percentage of hospital-acquired infections are caused by highly resistant bacteria

such as methicillin-resistant Staphylococcus aureus (MRSA).

Inappropriate and irrational use of antimicrobial medicines provides favourable

conditions for resistant microorganisms to emerge, spread and persist.

Antimicrobial resistance is a global concern because:

AMR kills

Infections caused by resistant microorganisms often fail to respond to the standard treatment,

resulting in prolonged illness and greater risk of death.

AMR hampers the control of infectious diseases

AMR reduces the effectiveness of treatment because patients remain infectious for longer, thus

potentially spreading resistant microorganisms to others.

AMR threatens a return to the pre-antibiotic era

Many infectious diseases risk becoming uncontrollable and could derail the progress made

towards reaching the targets of the health-related United Nations Millennium Development

Goals set for 2015.

AMR increases the costs of health care

When infections become resistant to first-line medicines, more expensive therapies must be used.

The longer duration of illness and treatment, often in hospitals, increases health-care costs and

the financial burden to families and societies.

AMR jeopardizes health-care gains to society

The achievements of modern medicine are put at risk by AMR. Without effective antimicrobials

for care and prevention of infections, the success of treatments such as organ transplantation,

cancer chemotherapy and major surgery would be compromised.

AMR threatens health security, and damages trade and economies

The growth of global trade and travel allows resistant microorganisms to be spread rapidly to

distant countries and continents. [10]

Inappropriate and irrational use of medicines provides favorable conditions for resistant

microorganisms to emerge and spread. For example, when patients do not take the full course of

a prescribed antimicrobial or when poor quality antimicrobials are used, resistant

microorganisms can emerge and spread.

Underlying factors that drive AMR include:

inadequate national commitment to a comprehensive and coordinated response, ill-

defined accountability and insufficient engagement of communities;

weak or absent surveillance and monitoring systems;

inadequate systems to ensure quality and uninterrupted supply of medicines

inappropriate and irrational use of medicines, including in animal husbandry:

poor infection prevention and control practices;

Depleted arsenals of diagnostics, medicines and vaccines as well as insufficient research

and development on new products. [10]

Research question:

What are the risk factors for Antimicrobial resistance (AMR) in developing countries?

The research will look into the following to arrive at a sound conclusion:

What are the socio- demographic factors associated with higher Antimicrobial resistance

(AMR) in developing countries?

Why developing countries are vulnerable for Antimicrobial resistance?

The role of poverty in antimicrobial resistance

Burden of Antimicrobial Resistance.

.

Literature review:

Antimicrobial resistance (AMR) is an important public health concern shared by developed and

developing countries. In developing countries the burden of infectious diseases is greater and

exacerbated by limited access to, and availability and affordability of, antimicrobials required

treating infections caused by AMR organisms. With drugs not listed on the essential drugs list

(EDL), problems of increased morbidity, costs of extended hospitalization and mortality are

extremely serious. The problem of susceptibility to and spread of infections caused by multidrug-

resistant (MDR) infectious agents is fuelled by factors such as limited access to clean water and

sanitation to ensure personal hygiene, malnutrition, and the HIV/TB epidemic. [12]

In 1990, an estimated 78% of the world's total population lived in the developing world. Of the

39.5 million deaths in the developing world, 9.2 million were estimated to have been caused by

infectious and parasitic diseases. 98% of child mortality occurs in the developing world, due

mainly to infections. Based upon information gathered through searches of the Medline and Bath

Information and Data Services computerized databases, discussions with colleagues, and

personal experiences, the authors consider the progress and impact of bacterial resistance to

antimicrobial drugs in the developing world. While antibiotics are important in developing

countries, they are often scarce commodities which are affordable and therefore available to only

the comparatively wealthy. Because the use of antibiotics is unregulated in many developing

countries, antibiotics are often misused and overused. Such use has provoked the development of

infectious agents which are resistant to antimicrobial drugs, such as strains of pneumococcal

meningitis, tuberculosis, and typhoid fever. Levels of morbidity and mortality are increasing as a

result. Better access to diagnostic laboratories is needed, as well as improved surveillance of the

emergence of resistance, better regulation of antibiotics' use, and better education of the public,

physicians, and veterinarians in the appropriate use of drugs. [11]

According to WHO facts on antimicrobial resistance (February 2011):

About 440 000 new cases of multidrug-resistant tuberculosis (MDR-TB) emerge annually,

causing at least 150 000 deaths. Extensively drug-resistant tuberculosis (XDR-TB) has been

reported in 64 countries to date.

Resistance to earlier generation antimalarial medicines such as chloroquine and sulfadoxine-

pyrimethamine is widespread in most malaria-endemic countries. Falciparum malaria parasites

resistant to artemisinins are emerging in South-East Asia; infections show delayed clearance

after the start of treatment (indicating resistance).

A high percentage of hospital-acquired infections are caused by highly resistant bacteria such as

methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci.

Resistance is an emerging concern for treatment of HIV infection, following the rapid expansion

in access to antiretroviral medicines in recent years; national surveys are underway to detect and

monitor resistance.

Ciprofloxacin is the only antibiotic currently recommended by WHO for the management of

bloody diarrhoea due to Shigella organisms, now that widespread resistance has developed to

other previously effective antibiotics. But rapidly increasing prevalence of resistance to

ciprofloxacin is reducing the options for safe and efficacious treatment of shigellosis, particularly

for children. New antibiotics suitable for oral use are badly needed.

AMR has become a serious problem for treatment of gonorrhoea (caused by Neisseria

gonorrhoeae), involving even "last-line" oral cephalosporins, and is increasing in prevalence

worldwide. Untreatable gonococcal infections would result in increased rates of illness and

death, thus reversing the gains made in the control of this sexually transmitted infection.

New resistance mechanisms, such as the beta-lactamase NDM-1, have emerged among several

gram-negative bacilli. This can render powerful antibiotics, which are often the last defence

against multi-resistant strains of bacteria, ineffective. [10]

Figure. A simplified ARCS diagram showing the close relationship between antimicrobial

resistance containment, disease control and antimicrobial resistance surveillance. [48]

Global Situation of AMR

Pathogens causing TB, malaria, sexually transmitted infections, typhoid, bacterial

dysentery, and pneumonia are now resistant or multidrug-resistant (MDR).

Up to 17% of TB is MDR. And, extensively drug-resistant (XDR) TB is now being

recorded in countries worldwide.

In 81 of 92 malaria-prevalent countries, chloroquine is no longer effective. [13]

Salmonella typhi

Multidrug resistance emerged as a public health problem in Asia.

Shigella

Resistance to ampicillin, tetracycline, co-trimoxazole, and chloramphenicol is

widespread in Africa.

Up to 90% resistance to ampicillin and co-trimoxazole has been found in parts of

Asia.

Resistance is emerging to fluoroquinolones, the only available option to left for

treatment.

Vibrio cholera

Up to 90% of isolates are resistant to at least one antibiotic. [15]

Streptococcus pneumonia

Penicillin and erythromycin resistance is an emerging problem in community

acquired pneumonia in Asia, Mexico, Argentina, Brazil, Kenya, and Uganda.

MDR (penicillin + two other classes) in Africa is 25%; in the Far East, 63%; in

the Middle East, 18%; in Latin America, 20%; in eastern Europe, 12%; in western

Europe, 18%; and in the United States, 26%. [15]

Widespread resistance to penicillin and tetracycline resulted in replacement with more

expensive first-line medicine. Penicillin resistance ranges from 9 to 90% across Asia and

is over 35% in sub-Saharan Africa and the Caribbean.

Replacement medicines also developed resistant problems, azithromycin resistance was

found in 16%–72% in the Caribbean and South America and quinolone resistance is

commonly reported in Asia and Africa.

The only option remaining may be a very expensive third-generation cephalosporin. [14]

The Burden of Resistance

For most diseases, the burden of the illness consists entirely of treatment costs, morbidity and

mortality among the ill, and the costs of public prevention efforts. Infectious diseases are

different. Because they often are communicable, fear of contagion may induce even uninfected

individuals (and their physicians) to alter their behavior [31]

. The financial and psychological

costs associated with these behavioral changes add to the burden of infectious diseases. Philipson

and Posner [32

] argue that in the case of AIDS, for example, some individuals living in areas with

a high prevalence of infection will avoid risky sexual activities

Use of an antibiotic in a disease outbreak or in an individual infection is often commenced

before the diagnosis is confirmed and almost always before the susceptibility pattern to the

pathogen can be fully ascertained. To choose an antibiotic, the important consideration is the

level of resistance to that antibiotic.[41]

On the contrary, irrational prescribing, dispensing

and consumption of medicines remain widespread, especially in the private sectors, despite

having so many efforts. Such irrational use can also be a major source of impoverishment

for poor populations as well as a hazard to health. It is particularly a serious public

health problem in developing countries (like Bangladesh) where between 50-90% of drug

purchases are made in the private sector without any prescription. Therefore, selling of

antibiotics has become an unauthorized right of the druggists that has been silently creating

devastating nature of bacterial drug resistance. [42]

Bangladesh. Pattern of resistance in E. coli was as follows: resistance towards ampicillin,

cephradine, nalidixic acid, co-trimoxazole, ciprofloxacin and ceftriaxone were 84.6%, 64.1%,

62.6%, 51.5%, 37.8% and 19.6% respectively. Whereas, 69.9% and 66.6% of strains were

sensitive to gentamicin and nitrofurantoin, respectively. Though resistance to ceftriaxone

was the lowest (19.6%) but 36.4% trains were intermediate. In addition, over 50% strains

appeared to be resistant towards combination of at least 2antibiotics.[43]

In another report from the same settings, it was found that above 85% and 23% isolates of

S. aureus showed resistance to penicillin and oxacillin, respectively indicating existence of

methicillin-resistant S. aureus (MRSA).5 More than 32% isolates appeared as intermediate

towards erythromycin. Ciprofloxacin resistance was noticed in 15% isolates, whereas >75%

isolates were sensitive to gentamicin. Another study reported of having quite high percentage

of Pseudomonas strains sensitive towards ceftazidime (>71%), but over 30% strains

showed intermediate sensitive pattern against ceftriaxone and resistance to ciprofloxacin.

Sensitivity value towards gentamicin was good (>60%). [43]

The Role of Poverty in Antimicrobial Resistance

Antimicrobial resistance is a worldwide problem that has deleterious long-term effects as the

development of drug resistance outpaces the development of new drugs. Poverty has been cited

by the World Health Organization as a major force driving the development of antimicrobial

resistance. In developing countries, factors such as inadequate access to effective drugs,

unregulated dispensing and manufacture of antimicrobials, and truncated antimicrobial therapy

because of cost are contributing to the development of multidrug-resistant organisms. [16]

More than any other issue, poverty and inadequate access to drugs continue to be a major force

in the development of resistance. In many developing nations drugs are freely available – but

only to those who can afford them. This means that most patients are forced to resort to poor

quality counterfeit, or truncated treatment courses that invariably lead to more rapid selection of

resistant organisms. A patient infected with a resistant strain may endure prolonged illness (often

resulting in death) and hospital stays which in turn result in lost wages, lost productivity, family

hardship and increased infectiousness. Treatment with second and third-line drugs is costly, more

often toxic to the patient, and increasingly ineffective owing to the speed with which mutant

organisms develop resistance. In India, the past five years has seen 20% of typhoid isolates

become resistant to ciprofloxacin, a relatively recent and expensive third-line drug.[40]

In developing countries with high mortality, infectious diseases remain the main cause of

death.[20]

In 1990, an estimated 78% of the world's population lived in developing countries. In

those countries, 23% of deaths were attributable to infectious and parasitic disease.[21]

Resistant bacteria have emerged in these developing countries. In 1996, in Bangladesh, over 95%

of Shigella dysenteriae isolates were resistant to ampicillin, co-trimoxazole, and nalidixic acid,

and up to 40% were resistant to mecillinam.[22]

In Quetta, Pakistan, 69% of Salmonella typhi

isolated from blood were multidrug resistant.[23]

In tropical countries, there has been an

emergence of Streptococcus pneumoniae that is resistant to penicillin, cefotaxime, and

chloramphenicol.[24]

Neisseria gonorrhoeae has developed strains resistant to penicillin,

sulfonamides, tetracyclines, and fluoroquinolones.[25]

This problem of multidrug-resistant organisms in developing countries can also directly affect

and threaten more developed countries (such as the United States) because international travel,

driven by globalized trade, allows for easier dissemination of these strains. For example,

penicillin-resistant and multidrug-resistant pneumococci, like the serotype 23F clone, have been

found not only in Mexico, South Africa, South Korea, and Croatia, but also in Portugal, France,

and the United States.[26]

Reasons for multidrug-resistant organisms in developing countries are numerous, but the

inadequate access to effective drugs, the unregulated manufacture and dispensation of

antimicrobials, and the lack of money available to pay for appropriate, high-quality medications

are some of the major poverty-driven factors contributing to antimicrobial resistance.[17-19]

In some developing countries, regulation of the manufacture of antibiotics may not exist to any

extent that would assure the quality and potency of the medications. A 500-mg capsule of

ciprofloxacin that was acquired locally in Vietnam was analyzed and found to contain the

equivalent of only 20 mg of ciprofloxacin.[18]

Studies conducted in several other developing

countries have also demonstrated counterfeit drugs with few or no active ingredients.[19]

Many developing countries allow the dispensation of antibiotics without a prescription; this can

lead to self-medication and dispensation of drugs by untrained people. In one survey from the

Rajbari district of Bangladesh, 100,000 doses of antibiotics had been dispensed without a

prescription in 1 month.[27]

In another study from Bangladesh, 92% of medications dispensed by

pharmacies were dispensed without a prescription.[28]

In Manila, Philippines, a survey of

drugstores showed that 66% of antibiotic purchases were made without a prescription.[29]

The

ease of obtaining an antibiotic without a prescription was directly experienced by this author,

who was able to purchase antimicrobials without a prescription from local pharmacies in both

Lahore, Pakistan and Iquitos, Peru.

Comparison of resistance pattern of E. coli in different years shows gradual increase in

resistance against almost all the antibiotics except imipenem (2% in 2001 and 1% in

2003) and pefloxacin (40% in 2001 and 17% in 2003). Mentionable increase was noted against

ceftazidime (47% in 2001 and 77% in 2003) and ceftriaxone (43% in 2001 and 71% in

2003). (Table I) [44]

.

Data are collected from Aerobic culture and sensitivity tests were done in the department of

Microbiology, Mymensingh Medical College (MMC) including specimens sent from

outpatient (OPD) and inpatient department (IPD) of the same Medical College Hospital, during

the period from April' 2001 to December' 2003.

Comparison of resistance pattern of S. aureus in different years shows gradual increase in

resistance against almost all the antibiotics except co-trimoxazole, where it was found to be

55% in 2001 and 57% in 2003. Mentionable increase was noted against ciprofloxacin (17% in

2001 and 43% in 2003) and ceftriaxone (28% in 2001 and 83% in 2003). Although,

oxacillin resistance increased from 22% in 2001 to 42% in 2003, but no resistance against

vancomycin was noted in any year. (Table II)

Resistance pattern of Pseudomonas species in different years shows gradual increase against

almost all the antibiotics except carbenicillin (92% in 2001 to 50% in 2003). Resistance

of mentionable increased from 2001 to 2003 as noted against ciprofloxacin (47% to 71%),

ceftriaxone (50% to 74%) and ceftazidime (39% to 58%). None of the strains showed

resistance against imipenem. (Table III)

[44]

Poverty-stricken patients may forgo the cost of a physician consultation and self-medicate.[19]

They may be more likely to purchase the least expensive (and possibly least potent drug) under

the assumption that they were all bioequivalent. Furthermore, these people may only complete a

truncated course of therapy because of their inability to pay for the full course of medications.[29]

Such inappropriate use of antibiotics for inadequate periods of time can exert strong selective

pressures on bacterial populations and can contribute to resistance.

A cross-sectional survey was conducted between Mayto July 2007 to identify commonly used

antimicrobials especially cefuroxime sensitivity and/or resistance in respiratory tract pathogens

in Bangladesh.

RESULTS

As shown in Table IV, a total of 384 clinically suspected cases of upper respiratory tract

infections, among them only 383 throat swab samples were considered for final analysis. Mean

age of the patients was 23 years and half of them were children and others were teenagers and

adults. Among all the samples, one among every four cases showed growth of any pathogenic

bacteria in culture and sensitivity test.

Table IV: Distribution of bacterial growth among all participants. Cross sectional study, Dhaka,

Bangladesh

According to the report of culture and sensitivity test, the isolated pathogens in the aggregates

were β hemolytic streptococci (28.7%), Klebsiella pneumoniae (28.7%), Staphylococci (25.7%),

Pseudomonas (4%), E. coli (2%), Pneumococcus (2%) (Table V).

Among the commonly used antimicrobials in URTI, sensitivity profiles were observed with

amoxycillin (7.9%), penicillin (33.7%), ampicillin (36.6%), co-trimoxazole (46.5%),

azithromycin (53.5%), erythromycin (57.4%), cephalexin (69.3%), gentamycin (78.2%),

ciprofloxacin (80.2%), cephradine (81.2%), levofloxacin (86.2%), ceftazidime (93.1%),

ceftriaxone (93.1%). Sensitivity to cefuroxime was reported in 93.1% cases. However,

antimicrobial resistance was observed most against amoxycillin (90.1%). Resistance to others

was as follows, penicillin (61.4%), ampicillin (64.1%), co-trimoxazole (43.6%), erythromycin

(39.6%), and azithromycin (34.7%) (Table VI).

Table V: Bacterial isolates in culture

Table VI: Commonly used antimicrobial sensitivity and resistance status in URTI. Cross

sectional study, Dhaka, Bangladesh

Among 383 reports, 101 (26.3%) were growth positive, while 282 (73.4%) did not show any

growth of pathogenic bacteria. Of the respondents, about 93.1% cases reported sensitivity to

cefuroxime (Figure 1). [19]

Mal. J. Microbiol. Vol 5(2) 2009, pp. 109-112

Scenario in Africa and Asia

Antibiotic resistance is particularly important in developing countries

There are similarities and differences in developing countries

Similarities:

High serious infectious disease burden

Erratic access to effective antibiotics

No local guidelines for antibiotic use (or not followed)

Weak antibiotics policies

Differences:

The major barrier in recognition of antibiotic resistance as a serious global public health threat

sub-Saharan Africa and Southeast Asia continents is…

The lack of comprehensive burden data that illustrates not only the true prevalence of

resistant infections and their impact on health outcomes, but also the associated economic

costs.[46]

The WHO has identified antibiotic resistance as one of the major emerging public health

problems and established monitoring system in different countries. The figure and tables that

given bellow will represent the fats about antimicrobial resistance. This tables and figures are

collected from different journals research papers.

Figure 2. Patterns of antimicro-bial resistance in Shigella species atthe rural diarrhea treatment

center in Matlab, Bangladesh, 1987-1992.Antimicrobials (ampicillin = I; tri-methoprim

sulfamethoxazole = ;nalidixic acid = q; and pivmecilli-nam = M) were tested by the disk

diffusion method.[47]

Figure 3: Patterns of antimicrobial resistance in Shigella dysenter-iae type 1 at rural (Matlab; ■)

and urban (Dhaka; q) diarrhea treatment centers in Bangladesh during 1993. The differences in

pivmecil-linam susceptibilities were statistically significant (P < .001). TMP-SMZ =

trimethoprim sulfamethoxazole. [47]

Figure 4. Patterns of antimicrobial resistance in Shigella flexneriat rural (Matlab; MI) and urban

(Dhaka; q) diarrhea treatment centers in Bangladesh during 1993.TMP-SMZ = trimethoprim-

sulfamethox-azole. [47]

Table VII. HIV Resistance to any Antiretroviral by Region [49]

Figure 5. The median percentage of clinical failure rates of chloroquine for several East, Central,

and Southern Africa Region countries (represents the median of the rates indicated by different

studies.[50]

Figure 6. Trends in Resistance of H. influenzae to Several Antibiotics at a Hospital in Kilifi,

Kenya. [51]

Table VIII. Global AMR Rates for Diseases of Major Public Health Importance. [52]

Table IX: Antimicrobial resistance in Vibrio cholerae isolated at the ICDDR,B laboratory in

Dhaka, Bangladesh, 1991-1993.[47]

Findings:

In many developing countries the use of antimicrobial drugs for treating people and animals is

unregulated; antibiotics can be purchased in pharmacies, general stores, and even market stalls.

In the Rajbari district of Bangladesh, a survey of rural medical practitioners (barefoot doctors)

with an average of 11 years' experience showed that they each saw on average 380 patients per

month and prescribed antibiotics to 60% of these patients on the basis of symptoms alone.[30]

In

one month 14 950 patients were prescribed antibiotics—a total of 291 500 doses. Only 109 500

doses had been dispensed by pharmacies, and a further 100 000 doses had been dispensed

without a prescription.[30]

Thus there is widespread and uncontrolled use of antibiotics, and patients often do not take a full

course of treatment if they are unable to afford it. Another problem in developing countries is the

quality and potency of antimicrobial drugs. In some countries many different antimicrobial drugs

are produced locally. In India, for example, there are over 80 different brands of the

fluoroquinolone ciprofloxacin. In Vietnam a locally acquired 500 mg capsule of ciprofloxacin

costs 400 dong (about 2 pence). The average weight of the capsules is 405 mg with a potency

equivalent to 20 mg of pure ciprofloxacin (J Wain, personal communication)

Inappropriate and irrational use of medicines provides favorable conditions for resistant

microorganisms to emerge and spread. For example, when patients do not take the full course of

a prescribed antimicrobial or when poor quality antimicrobials are used, resistant

microorganisms can emerge and spread.

Poor prescribing practices by Health Professionals

Unnecessary prescription of antibiotics has been documented in many developing countries and

in Bangladesh as well. This is due to poor clinical judgment, lack of updated standard treatment

guidelines or in-service training. In the end, scarce essential antibiotics are wasted on wrong

patients thereby misusing the meager resources and facilitating development of AMR.

Use of antimicrobials in growth promotion

In some communities, poultry farmers use antimicrobials (even antiretroviral drugs) to enhance

chicken growth (verbal information). Resistant bacteria of animal origin have been detected in

humans, making treatment difficult.

Poor quality antimicrobials

Developing countries is threatened with the influx of poor quality antimicrobials which contain

little or none of the active ingredients needed for treatment. Lack of appropriate laboratory

facilities to test the quality and quantity of drugs, limited financial resources to procure good

quality antimicrobials from reputable firms, poor pharmaceutical procurement practices and

weak regulation of drug production, imports and sales have contributed to the massive presence

of substandard antimicrobials. The move made by Pharmacy, Medicine and Poisons Board in

developing countries on drug donation policy and importation will assist in reducing influx and

flushing out poor quality drugs.

Poor Infection Control Practices

Improper practices and non compliance to infection control are commonly seen in most health

facilities in Malawi. This result in spread of resistant microbes among patients and to health

professionals. Promotion and compliance to simple practices such as hand washing, contact

control, disinfection of surface, and isolation of infectious patients are essential in controlling

resistant microbes.

Poor Laboratory Infrastructure

Lack of well established laboratory facilities in developing countries and skilled trained

technicians have led to development of experimental, problem-oriented management strategies

for administering antimicrobials. This has contributed to over prescribing of antimicrobials for

prophylaxis which has contributed to the emergence of AMR Proper lab infrastructure is critical

in diagnosis and treatment of common microbial infections.

Lack of Research activities and Surveillance of AMR

Surveillance is necessary to detect, monitor and document emergence of any AMR in any

locality. This will help in putting in place measures for containment. Findings from studies on

AMR would go a long way to improve care and contain further spread of resistant microbes. [39]

Conclusion

At present, and as a closing example, of the $60 billion (US) spent worldwide annually on health

research by both the public and private sectors, only approximately 10% is devoted to issues that

represent 90% of the world’s health problems. This so-called 10-90 gap has direct consequences

in the poorer populations, where antimicrobial resistance may become a more severe problem. [53]

It has been seen from the study that developing countries are vulnerable for resistant to

antibiotics. Many bacteria (for example, Chlamydia trachoma is and Streptococcus pyogenes)

remain predictably sensitive to routinely available antimicrobial drugs. AMR is of global

concern and some of the issues and solutions that we mention may be significance for

developing countries. But the fact is that, developing countries are suffering most about the bad

impact of antimicrobial resistance because of lack of knowledge, education and overall lack of

proper guidelines of government and non government organizations. Developing countries

should develop protocols like- restriction of dispensing antimicrobials; promote community-wide

education about the responsible use of antibiotics to minimize the risk of antimicrobial

resistance. So maintaining the useful life of antibiotics is relevant in all countries and for all

peoples.

References

1. Denys GA, Koch KM, Dowzicky MJ: Distribution of resistant gram-positive organisms

across the census regions of the United States and in vitro activity of tigecycline, a new

glycylcycline antimicrobial. Am J Infect Control 2007, 35(8):521-526. PubMed Abstract

| Publisher Full Text

2. Potz NA, Hope R, Warner M, Johnson AP, Livermore DM: Prevalence and mechanisms

of cephalosporin resistance in Enterobacteriaceae in London and South-East England. J

Antimicrob Chemother 2006, 58(2):320-326. PubMed Abstract | Publisher Full Text

3. Johnson AP, Pearson A, Duckworth G: Surveillance and epidemiology of MRSA

bacteraemia in the UK. J Antimicrob Chemother 2005, 56(3):455-462. PubMed Abstract

| Publisher Full Text

4. de Kraker M, Sande-Bruinsma N: Trends in antimicrobial resistance in Europe: update

of EARSS results. Euro Surveill 2007, 12(3):E070315-070313. PubMed Abstract

5. Sharma R, Sharma CL, Kapoor B: Antibacterial resistance: current problems and

possible solutions. Indian J Med Sci 2005, 59(3):120-129. PubMed Abstract |

Publisher Full Text

6. Felmingham D, Reinert RR, Hirakata Y, Rodloff A: Increasing prevalence of

antimicrobial resistance among isolates of Streptococcus pneumoniae from the

PROTEKT surveillance study, and compatative in vitro activity of the ketolide,

telithromycin. J Antimicrob Chemother 2002, 50(Suppl S1):25-37. PubMed Abstract |

Publisher Full Text

7. Felmingham D, Canton R, Jenkins SG: Regional trends in beta-lactam, macrolide,

fluoroquinolone and telithromycin resistance among Streptococcus pneumoniae isolates

2001-2004. J Infect 2007, 55(2):111-118. PubMed Abstract | Publisher Full Text

8. Zhang R, Eggleston K, Rotimi V, Zeckhauser RJ: Antibiotic resistance as a global

threat: evidence from China, Kuwait and the United States. Global Health 2006, 2:6.

PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text

9. Andrews JR, Shah NS, Gandhi N, Moll T, Friedland G: Multidrug-resistant and

extensively drug-resistant tuberculosis: implications for the HIV epidemic and

antiretroviral therapy rollout in South Africa. J Infect Dis 2007, 196(Suppl 3):S482-490.

10. http://www.who.int/mediacentre/factsheets/fs194/en/

11. Hart CA, Kariuki S.Source: Department Medical Microbiology and Genitourinary

Medicine, University of Liverpool, Liverpool L69 3GA. cahmm@liv.ac.uk

12. SAMJ: South African Medical Journal Print version ISSN 0256-9574SAMJ, S. Afr.

med. j. vol.101 no.8 Cape Town Aug. 2011

13. Source: WHO. 2004. Country Data 2000–03, Containing Antimicrobial Resistance,

Policy Perspectives on Medicine, Nov 20. Geneva: WHO.

14. Sources: Okeke, I.N., et al. 2005. Antimicrobial Resistance in Developing Countries.

Part I: Recent Trends and Current Status. Lancet Infectious Diseases 5(8):481–93.

WHO. 2004. Country Data 2000–03.

15. Source: Okeke, I.N., et al. 2005. Antimicrobial Resistance in Developing Countries. Part

I: Recent Trends and Current Status. Lancet Infectious Diseases 5(8):481–93.

16. The Journal of the American Board of Family Medicine doi:

10.3122/jabfm.2007.06.070019 J Am Board Fam Med November-December 2007 vol.

20 no. 6 533-539

17. World Health Organization. Overcoming antimicrobial resistance. World Health

Organization report on infectious diseases. World Health Organization; 2000.

18. Hart CA, Kariuki S. Antimicrobial resistance in developing countries. BMJ. 1998; 317:

647–50.

19. Okeke IN, Lamikanra A, Edelman R. Socioeconomic and behavioral factors leading to

acquired bacterial resistance to antibiotics in developing countries. Emerg Infect Dis.

1999; 5: 18–27.

20. World Health Organization. World health report. Changing history. World Health

Organization; 2004.

21. Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: global

burden of disease study. Lancet. 1997; 349: 1269–76.

22. Hossain MA, Rahman M, Ahmed QS, Malek MA, Sack RB, Albert MJ. Increasing

frequency of mecillinam-resistant shigella isolates in urban Dhaka and rural Matlab,

Bangladesh: a 6-year observation. J Antimicrob Chemother. 1998; 42: 99–102.

23. Mirza SH, Beeching NJ, Hart CA. Multi-drug resistant typhoid: a global problem. J Med

Microbiol. 1996; 44: 317–9.

24. Klugman KP. Management of antibiotic-resistant pneumococcal infections. J

Antimicrob Chemother. 1994; 34: 191–4.

25. Ross JDC. Fluoroquinolone resistance in gonorrhoea: how, where and so what. Int J

STD AIDS. 1998; 9: 318–22.

26. Munoz R, Coffey TJ, Daniels M, et al. Intercontinental spread of a multi-resistant clone

of serotype-23F Streptococcus pneumoniae. J Infect Dis. 1991; 164: 302–6.

27. Mamun KZ. Prevalence and genetics of resistance to commonly used antimicrobial

agents in faecal enterobacteriaceae from children in Bangladesh [PhD thesis]. University

of Liverpool; 1991.

28. Hossain MM, Glass RI, Khan MR. Antibiotic use in a rural community in Bangladesh.

Int J Epidemiol. 1982; 11: 402–5.

29. Lansang MA, Lucas-Aquino R, Tupasi TE, et al. Purchase of antibiotics without

prescription in Manila, the Philippines. Inappropriate choices and doses. J Clin

Epidemiol. 1990; 43: 61–7.

30. Mamun KZ.Prevalence and genetics of resistance toc ommonly used antimicrobial

agents in faecal enterobacteriaceae from childreni n Bangladesh [PhD thesis].University

of Liverpool,1991.

31. Phillipson TEconomic epidemiology and infectious diseases. In: Culyer AJ, Newhouse

JP, editors. Handbook of health economics. Amsterdam: Elsevier; 2000. p. 1761-97.

32. Philipson T, Posner RACambridge: Harvard University Press; 1993. Private choices and

public health: the AIDS epidemic in an economic perspective.

33. Howard DH, Rask KJThe impact of resistance on antibiotic demand in patients with ear

infection. In: Laxminarayan R, Brown G, editors. The economics of resistance.

Washington, DC: Resources for the Future; (in press).

34. World Health Organization. Geneva: WHO/MAL94 1070; 1994. Antimalarial drug

policies: data requirements, treatment of uncomplicated malaria and management of

malaria in pregnancy: report of an informal consultation.

35. Phillips M, Phillips-Howard P. Economic implications of resistance to antimalarial

drugs. Pharmacoeconomics 1996;10:225-38.

36. Ellison SF, Hellerstein JK. The economics of antibiotics: an exploratory study. In:

Triplett JE, editor. Measuring the prices of medical treatments. Washington, DC:

Brookings Institution Press; 1999. p. 118-51.

37. Bonheffer S, Lipsitch M, Levin BR. Evaluating treatment protocols to prevent antibiotic

resistance. Proc Natl Acad Sci USA 1997;94:12106-11.

38. Becerra MC, Bayona J, Farmer PE, et al. The global impact of drug resistant TB.

Boston: Harvard Medical School; 1999. Defusing a time-bomb: the challenge of

antituberculous drug resistance in Peru; p. 107-26.

39. Pharmalink, A publication of Ecumenical Pharmaceutical Network, Vol-9: Issue 1-

September 2009

40. Overcoming Antimicrobial Resistance

World Health Report on Infectious Diseases 2000

41. Tapsall JW, Shultz T, Limnios E, et al. Surveillance of antibiotic resistance in invasive

isolates of Neisseria meningitidis in Australia, 1994-1999. Pathology 2001; 33: 359-

361.

42. WHO. Rational Drug Use Strategy and Monitoring. Quick link,

www.mednet3.who.int/eml 2004. [accessed on 12/02/2005]

43. Shamsuzzaman AKM, Musa AKM, Hossain MA, Mahmud MC. Escherichia coli:

emergence of multi-drug resistant strains at Mymensingh Medical College Hospital. J

Com Health Med Res 2003; 7: 19 - 23.

44. Bangladesh J Med Microbiol 2007; 01 (01): 04-09Bangladesh Society of Medical

Microbiologists

45. Malaysian Journal of Microbiology, Vol 5(2) 2009, pp. 109-112

46. Antibiotic use and resistance at in depth centers-Arin Maputo 24th October 2011

47. Antimicrobial Resistance in Organisms Causing Diarrheal Disease - R. Bradley Sack,

Mahbubur Rahman, M. Yunus,and Eradul H. Khan

48. Australia microbiology, Official journal of the australian society for microbiology

inc.Volume 28 No. 4 November 2007

49. From WATCH reports, cited in: Maglione, M, et al. 2007. Antiretroviral (ARV) Drug

Resistance in the Developing World. Evidence Report/Technology Assessment No. 156.

AHRQ Publication No. 07-E014. Rockville, MD: Agency for Healthcare Research and

Quality.

50. Roll Back Malaria. 2005 World Malaria Report. Website:

http://www.rbm.who.int/wmr2005

51. Scott, J.A.G., et al. 2005. Antimicrobial Agents and Chemotherapy. July. Pg. 3021-3024

52. WHO country data, 2000-03; and APUA. 2005. Global Advisory on Antibiotic

Resistance DATA (GAARD Report). Boston: Alliance for the Prudent Use of

Antibiotics.

53. World Health Organization. Containing Antimicrobial Resistance.

WHO/CDS/CSR/DRS/99.2. Geneva, Switzerland: WHO;

1999.http://www.who.int/emc-

documents/antimicrobial_resistance/docs/whocdscsrdrs992.pdf.