Socioeconomic and Behavioral Factors Leading to Acquired Bacterial Resistance to Antibiotics in Developing Countries.In developing countries, acquired bacterial resistance to antimicrobial agents Antimicrobial agents
Chemical compounds biosynthetically or synthetically produced which either destroy or usefully suppress the growth or metabolism of a variety of microscopic or submicroscopic forms of life. is common in isolates from healthy persons and from persons with community-acquired infections. Complex socioeconomic and behavioral factors associated with antibiotic resistance antibiotic resistance,
n the ability of certain strains of microorganisms to develop resistance to antibiotics.
antibiotic resistance , particularly regarding diarrheal and respiratory pathogens, in developing tropical countries, include misuse of antibiotics by health professionals, unskilled practitioners, and laypersons; poor drug quality; unhygienic conditions accounting for spread of resistant bacteria; and inadequate surveillance.
Acquired bacterial resistance is common in isolates from healthy persons and from patients with community-acquired infections in developing countries, where the need for antibiotics is driven by the high incidence of infectious disease Infectious disease
A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. (1). Among isolates of diarrheal, respiratory, and commensal commensal /com·men·sal/ (kom-men´sil)
1. living on or within another organism, and deriving benefit without harming or benefiting the host.
2. a parasite that causes no harm to the host. enteric enteric /en·ter·ic/ (en-ter´ik) within or pertaining to the small intestine.
1. Of, relating to, or within the intestine.
2. pathogens (2-5), resistance is increasing, particularly to first-line, inexpensive, broad-spectrum antibiotics (Table 1). Furthermore, introduction of newer drugs (e.g., fluoroquinones) has been followed relatively quickly by the emergence and dissemination of resistant strains (5). The selection and spread of resistant organisms in developing countries, which can often be traced to complex socioeconomic and behavioral antecedents, contribute to the escalating problem of antibiotic resistance worldwide.
Table 1. Pathogens with a steadily increasing prevalence of acquired antibiotic resistance in developing tropical countries
Pathogen Drug(s) Shigella flexneri, ampicillin, S. dysenteriae sulfonamides (alone or with trimethoprim), nalidixic acid Vibrio cholerae cotrimethoxazole, nalidixic acid, ampicillin Salmonella typhi ampicillin, chloramphenicol, cotrimethoxazole Salmonella cotrimethoxazole (nontyphoidal) Enterotoxigenic cotrimethoxazole Escherichia coli Campylobacter fluoroquinolones Mycobacterium isoniazid, streptomycin, tuberculosis rifampicin (primary resistance) Pathogen Country (years) Ref. Shigella flexneri, Bangladesh (1983-1990) (6) S. dysenteriae (7) Brazil (1988-1993) (8) Rwanda (1983-1993) (5) Thailand (1981-1995) Vibrio cholerae Guinea-Bissau (1987-1995) India (1993-1995) (9) (10) Salmonella typhi Bangladesh (1989-1993) (3) Salmonella Thailand (1981 - 1995) (5) (nontyphoidal) Enterotoxigenic Thailand (1981-1995) (5) Escherichia coli Campylobacter Thailand (1987-1995) (5) Mycobacterium Kenya (1981-1990) (11) tuberculosis Morocco (1992-1994) (12)
Misuse of Antibiotics by Physicians in Clinical Practice
Antibiotic use provides selective pressure favoring resistant bacterial strains; inappropriate use increases the risk for selection and dissemination of antibiotic-resistant bacteria, which are placed at a competitive advantage. Therefore, one would expect that drugs more commonly affected by bacterial resistance in developing countries are generally inexpensive and popular broad-spectrum agents (2-5,] 3). However, the relationship between antibiotic use and the emergence and spread of resistance is complex. Antibiotic use in clinical practice alone cannot explain the high frequency of resistant organisms in developing countries (14,15). Nevertheless, excessive clinical use (a form of misuse) is at least partially responsible for the escalating rates of resistance, especially in hospital settings, worldwide. The unnecessary prescription of antibiotics seen in industrialized in·dus·tri·al·ize
v. in·dus·tri·al·ized, in·dus·tri·al·iz·ing, in·dus·tri·al·iz·es
1. To develop industry in (a country or society, for example).
2. nations has also been documented in many developing countries, particularly in cases of acute infantile diarrhea and viral respiratory infections (16-22). Clinical misuse of antibiotics may be more common among private practitioners than among public health personnel--private practitioners charge higher fees, the demand for antibiotics seen in private patients is higher, and more drugs are available in private clinics than in public hospitals (23-25).
Several strategies have been proposed for combating the inappropriate use of antibiotics by clinicians (26). Antibiotic monitoring systems and hospital formularies or antibiotic treatment protocols often reduce antibiotic prescription rates (24,27). Adoption of a national essential drug list can limit the antibiotics available to prescribers (28,29). However, implementation of these strategies does not guarantee optimal antibiotic use by clinicians in developing countries because the irregular drug supply, availability of drugs from unofficial sources, and financial constraints also affect antibiotic choices (30-32).
Continuing medical education continuing medical education See CME. changes the attitude of clinicians. Studies of antibiotic misuse in Cuba and Pakistan (33,34) recommend continuing medical education for health workers as the single most important tool for combating antibiotic misuse. A study in Zambia has demonstrated the efficacy of education in reducing antibiotic prescription rates (35). However, education has not been successfully implemented in many developing countries, where too often, governments and health workers cannot afford the time and money required for continuing medical education (36).
Health workers in many developing countries have almost no access to objective health information (24). Pharmaceutical company representatives typically outnumber practitioners and often adversely influence their prescription habits (37), as reflected by sales of nonessential non·es·sen·tial
Being a substance required for normal functioning but not needed in the diet because the body can synthesize it. drugs and drug combinations (38). Drug labels and package inserts often fail to provide accurate information (39), and in industrialized countries, patients often pressure physicians to prescribe antibiotics (19).
Misuse of Antibiotics by Unskilled Practitioners
In many developing countries, well-trained health personnel are scarce and cannot serve the entire population, especially in rural areas. Community health workers and others with minimal training treat minor ailments (40). The qualifications and training of community health workers, as well as the quality of care they provide, vary from country to country. Unskilled personnel are less aware of the deleterious effects of inappropriate antibiotic use. For example, pharmacy technicians in Thailand prescribed rifampicin rifampicin /rif·am·pi·cin/ (rif´am-pi-sin) rifampin.
a derivative of rifamycin; an antibacterial and antifungal agent used in the treatment of mycobacterial infections, actinomycosis and histoplasmosis. for urethritis Urethritis Definition
Urethritis is an inflammation of the urethra that is usually caused by an infection.
The urethra is the canal that moves urine from the bladder to the outside of the body. and tetracycline tetracycline (tĕ'trəsī`klēn), any of a group of antibiotics produced by bacteria of the genus Streptomyces. They are effective against a wide range of Gram positive and Gram negative bacteria, interfering with protein for young children (41). Unqualified drug sellers offer alternative drugs when the prescribed drugs are out of stock or refill prescriptions without consulting the prescriber (42,43). In India, traditional healers often dispense antibiotics (44). A high proportion of patients in some developing countries are treated by untrained practitioners simultaneously with oral and injectable in·ject·a·ble
Capable of being injected. Used of a drug.
A drug or medicine that can be injected. antibiotics administered with contaminated contaminated,
v 1. made radioactive by the addition of small quantities of radioactive material.
2. made contaminated by adding infective or radiographic materials.
3. an infective surface or object. needles and syringes (45-47) for misdiagnosed noninfectious diseases (48).
Misuse of Antibiotics by the Public
In most developing countries, antibiotics can be purchased without prescription, even when the practice is not legal. In many African, Asian, and Latin American countries List of American countries
A region of western Africa between the Sahara Desert and the Gulf of Guinea. It was largely controlled by colonial powers until the 20th century.
West African adj. & n. countries such as Cameroon (49) and Nigeria (Okeke and Lamikanra, pers. obs.), the vendor (usually a medically untrained salesman) tries to convince potential buyers to purchase the drug, even if they are not ill.
To save time and keep drug-hunting to a minimum, a patient may start at a source more likely to stock the desired drug, forgoing the expertise of a doctor. Unofficial sources are generally more accessible than official sources. For example, in Nepal, retail drug outlets are four times as numerous as government health posts and hospitals (46). Alternate sources offer the option of purchasing small quantities of medicines, while hospitals require purchase of the complete 5- or 7-day antibiotic regimen (17,43,52). The purchase of small samples is exceedingly common, particularly for most customers, who buy without prescription (52). These subinhibitory antibiotic regimens predispose pre·dis·pose
To make susceptible, as to a disease. for selection of resistant bacterial strains.
Antibiotic use in developing countries is underestimated. The quantity of drugs distributed within a country is calculated under the assumption that each person purchases a complete regimen (56). However, medication can be purchased in small aliquots from roadside stalls, and distribution of locally produced or counterfeit antibiotics is not recorded. The motives for self-medication and antibiotic overuse overuse Health care The common use of a particular intervention even when the benefits of the intervention don't justify the potential harm or cost–eg, prescribing antibiotics for a probable viral URI. Cf Misuse, Underuse. by laypersons are similar to those for clinical abuse by health professionals: to cut costs and act expeditiously ex·pe·di·tious
Acting or done with speed and efficiency. See Synonyms at fast1.
ex to treat confirmed or suspected bacterial infection (57). For example, 50% to 80% of Bangladeshi patients infected with Shigella shigella
Any of the rod-shaped bacteria that make up the genus Shigella, which are normal inhabitants of the human intestinal tract and can cause dysentery, or shigellosis. Shigellae are gram-negative (see gram stain), non-spore-forming, stationary bacteria. S. admitted that they had-taken at least one antibiotic in the 15 days before a hospital visit (58), as had 18% to 70% of pediatric patients with acute respiratory infection in two Chinese studies (20,59). The proportion of patients who self-medicate is probably higher, because patients are often reluctant to admit having taken antibiotics before visiting a hospital (60).
Common cultural beliefs about antibiotics include the notions that there is a pill for every symptom; antibiotics can heal many illnesses, including dyspepsia dyspepsia: see indigestion. and headaches; and injections are more powerful than pills. The misuse of antibiotics frequently becomes integrated into the local culture (62) (e.g., antibiotics are used to prevent diarrhea after eating suspected contaminated foods or [by prostitutes] to prevent sexually transmitted diseases Sexually transmitted diseases
Infections that are acquired and transmitted by sexual contact. Although virtually any infection may be transmitted during intimate contact, the term sexually transmitted disease is restricted to conditions that are largely [52,63]).
Another cause of antibiotic abuse and selection for resistant bacteria is poor patient compliance. First, physician-patient interactions are often inadequate. They can be short (e.g., a mean of 54 sec was recorded in a Bangladeshi study ) and of poor quality (e.g., in Mexico, poor patient-physician communication was partially responsible for the noncompliance noncompliance
failure of the owner to follow instructions, particularly in administering medication as prescribed; a cause of a less than expected response to treatment.
noncompliance of patients with antibiotic regimens ). Second, because patients often travel long distances and incur large expenses for medical care, they are unlikely to return for follow-up visits. The reverse situation--the prescriber visiting his patient--is difficult logistically, especially in rural Africa (64). In addition, the patient may be unable to read medicine labels. Finally, because many drugs are expensive, indigent indigent 1) n. a person so poor and needy that he/she cannot provide the necessities of life (food, clothing, decent shelter) for himself/herself. 2) n. one without sufficient income to afford a lawyer for defense in a criminal case. patients purchase incomplete regimens whenever possible and discontinue treatment when symptoms disappear but before the pathogen is eliminated (52).
Poor Quality of Antibiotics
Lack of Quality Compliance and Monitoring
Besides the risk for therapeutic failure, degradation products or adulterants in poor quality antibiotics can produce subinhibitory concentrations in vivo in vivo /in vi·vo/ (ve´vo) [L.] within the living body.
Within a living organism.
in vivo adv. , which increase the selection of resistant strains. Drugs that do not comply with minimum standards are illegal in all countries. However, the quality of many antibiotics and other drugs in developing countries is often below standards in the formulary formulary /for·mu·lary/ (for´mu-lar?e) a collection of recipes, formulas, and prescriptions.
National Formulary see under N.
n. . In Nigeria for example, substandard ampicillin ampicillin (ăm'pĭsĭl`ĭn), a penicillin-type antibiotic that is effective against both gram-negative microorganisms and gram-positive microorganisms such as Escherichia coli. , ampicillin/cloxacillin, tetracycline, and oxytetracycline oxytetracycline /oxy·tet·ra·cy·cline/ (ok?se-tet?rah-si´klen) a broad-spectrum tetracycline antibiotic produced by Streptomyces rimosus, used as the base or the hydrochloride salt. capsules have been detected (53,65-67). In many cases, therapeutic failure is the only indication of substandard drugs. Analytic laboratories to detect substandard drugs are uncommon, and when they exist, health workers, distributors, and consumers are often unaware of them.
The shelf lives of drugs developed and marketed in temperate countries are determined by storage temperatures. During distribution in tropical countries, conditions of transport and storage are poorly controlled, and the drugs may be degraded. Ballereau et al. (68) recorded temperatures of 26 [degrees] C to 40 [degrees] C and 30% and 90% humidity in Guinea-Bissau during a 2-year period (temperatures of greater than 25 [degrees] C can degrade antibiotics). Many antibiotics, being heat- and moisture-labile, are particularly vulnerable. Of seven drugs that lost 10% or more of their active constituents when stored in pharmacies in Guinea-Bissau for 2 years, six were antimicrobial drugs (68). Drug consignments are exposed to such adverse conditions during shipment (69) or at tropical ports while they await lengthy port clearance. Drugs are often handled by untrained workers who may store them incorrectly. Hawkers and small traders in Nigeria frequently display large glass jars containing different types of antibiotic capsules mixed together, fully exposed to harsh sunlight and high ambient temperature Outside temperature at any given altitude, preferably expressed in degrees centigrade. and humidity. In a Nigerian study of eight batches of tetracycline capsules, only the batch obtained directly from the manufacturer was not excessively degraded and contained active drug levels within formulary limits (Table 2) (53,70). Studies conducted in Thailand and Nigeria demonstrated similar degradation of chloroquine chloroquine /chlo·ro·quine/ (klor´o-kwin) an antiamebic and anti-inflammatory used in the treatment of malaria, giardiasis, extraintestinal amebiasis, lupus erythematosus, and rheumatoid arthritis; used also as the hydrochloride and and amoxicillin amoxicillin /amox·i·cil·lin/ (ah-mok?si-sil´in) a semisynthetic derivative of ampicillin effective against a broad spectrum of gram-positive and gram-negative bacteria.
Table 2. Source and quality of tetracycline capsules in a Nigerian suburban town (compiled with data from )
Tetracycline content (%of label Content of Bioavailability Sample Source claim) ATC(a) (%) (%)(b) C1 Manufacturer(C) 105.9 None 100 detected C2 Hospital 107.5 5.3 63.4(d) C3 Roadside stall 104.5 1.1 80.5(d) C4 Pharmacy 66.1 2.4 65.2(d) C5 Patent medicine 84.5 1.9 87.6(d) stall C6 Roadside stall 67.8 1.5 Not tested C7 Patent medicine 89.6 1.8 Not tested stall
(a) Anhydrotetracycline, one of four tetracycline degradation products.
(b) Measured from cumulative excretion of tetracycline in the urine of five volunteers.
(c) Reference standard obtained from the manufacturer.
(d) Significantly different from C1 (p = 0.01, Wilcoxon signed rank test).
Some pharmacologically active drugs produced in industrialized countries have expired when distributed When distributed
When issued. in developing countries--they were shipped at the end of the drugs' shelf lives or their clearance and distribution after transcontinental shipment were delayed. Expired drugs may receive new labels, be dumped without a label change, or be donated rather than sold (71-73). Tax deductions and the cost of liquidation are incentives for donating expired or near-expired drugs. Effective enforcement of the World Health Organization (WHO) guidelines on drug donations may curtail such practices (74).
Some drugs sold in developing countries do not contain the concentration of active substances stated on their labels, even at the time of manufacture. These counterfeit drugs flourish, despite efforts of local regulatory agencies to stop their production and distribution (75-77). Approximately 65% of the 751 instances of counterfeit pharmaceuticals reported to WHO or to Interpol from 28 countries in the past 15 years were produced in developing countries (77). Counterfeit drugs include products with little or no active ingredients (e.g., in Nigeria, Indonesia, Brazil, Thailand, Bangladesh, Malaysia, and Francophone African countries [39,76,78,79]) or products for which excipients excipients,
n.pl all the constituents of a remedy that lack medicinal properties. See also adjuvant, auxiliary substance, and vehicle. have been replaced by less expensive alternatives (e.g., substitution of ethylene glycol ethylene glycol: see glycol.
Simplest member of the glycol family, also called 1,2-ethanediol (HOCH2CH2OH). It is a colourless, oily liquid with a mild odour and sweet taste. for propylene glycol propylene glycol
a chemical used industrially as an antifreeze, solvent stabilizer, as a preservative in liquid livestock feeds and pharmaceutically as a vehicle or solvent for medicinal preparations. in pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.
Of or relating to pediatrics. paracetamol paracetamol
an analgesic and antipyretic drug in dogs. It is contraindicated for cats because of serious side-effects which include intravascular hemolysis, methemoglobinemia and hepatic necrosis. formulations, which caused many deaths in Nigeria, Argentina, Bangladesh, India, and Haiti [76,78]). Counterfeit drugs, like other counterfeit materials, compete favorably in the markets of developing countries. The analytic facilities available to law enforcement agencies A law enforcement agency (LEA) is a term used to describe any agency which enforces the law. This may be a local or state police, federal agencies such as the Federal Bureau of Investigation (FBI) or the Drug Enforcement Administration (DEA). often cannot detect these drugs before they reach the patient. Multinational pharmaceutical companies, which probably possess the best analytic facilities for in-house quality assurance in developing countries, try to detect counterfeit drugs to protect their income and reputation; however, such efforts are directed primarily at counterfeits of these companies' own products. Because of the profusion of generic drugs in developing countries, a substantial proportion of counterfeit drugs go undetected.
tr.v. a·dul·ter·at·ed, a·dul·ter·at·ing, a·dul·ter·ates
To make impure by adding extraneous, improper, or inferior ingredients.
1. Spurious; adulterated.
2. Adulterous. Drugs
Herbal preparations in developing countries are often adulterated with orthodox medicaments. For example, in one study, 24% of Chinese herbal preparations marketed in Taiwan contained one or more of such adulterants (80). Although the adulteration Mixing something impure with something genuine, or an inferior article with a superior one of the same kind.
Adulteration usually refers to mixing other matter of an inferior and sometimes harmful quality with food or drink intended to be sold. of such products with antibiotics has not been reported, such practices may be common (81). A Nigerian traditional healer, for example, admitted to `augmenting' herbal preparations with tetracycline from commercially available capsules (82).
Bioinequivalent Antibiotics and Biopharmaceutic Interactions
In the last 2 decades, the importance of bioavailability bioavailability /bio·avail·a·bil·i·ty/ (bi?o-ah-val?ah-bil´i-te) the degree to which a drug or other substance becomes available to the target tissue after administration.
n. has been underscored by the recognition that chemically equivalent generic drug formulations do not always deliver the expected amount of drug to the bloodstream. Slowly absorbed and acid-labile antibiotics are particularly prone to bioinequivalence and consequent therapeutic failure. In addition, poorly absorbed antibiotics remain in the gut to facilitate the selection of resistant organisms. The few published studies from the developing world have found bioinequivalence in antibiotic formulations, and the problem may be widespread (Table 2) (53,83). Inexpensive generic antibiotics commonly used in developing countries usually are not subject to bioavailability studies.
The bioavailability of an antibiotic formulation is modulated by conditions surrounding its administration; conditions unique to developing countries are rarely investigated. Drug combinations used in the tropics tropics, also called tropical zone or torrid zone, all the land and water of the earth situated between the Tropic of Cancer at lat. 23 1-2°N and the Tropic of Capricorn at lat. 23 1-2°S. but rarely elsewhere may not be optimally absorbed. For example, coadministration of chloroquine and ampicillin lowers the bioavailability of ampicillin (84). A Nigerian meal lowered the biologic availability of orally administered nitrofurantoin nitrofurantoin /ni·tro·fu·ran·to·in/ (-fu-ran´to-in) an antibacterial effective against many gram-negative and gram-positive organisms; used in urinary tract infections.
n. (85). Chewing of Khat khat: see staff tree.
Slender, straight, East African tree (Catha edulis; family Celastraceae). Reaching a height of 80 ft (25 m), the khat tree has large, oval, finely toothed, bitter-tasting leaves. , a popular Yemeni stimulant, adversely affected the bioavailability of ampicillin and amoxicillin (86). By contrast, the Ayurvedic preparation Trikatu enhanced the absorption of several drugs (87). Whether traditional medicines with antimicrobial properties enhance antibiotic resistance is unknown.
Dissemination of Resistant Organisms
Crowding and Unhygienic Conditions
Residents of developing countries often carry antibiotic-resistant fecal commensal organisms (13,88). Visitors to developing countries passively acquire antibiotic-resistant gut Escherichia coli Escherichia coli (ĕsh'ərĭk`ēə kō`lī), common bacterium that normally inhabits the intestinal tracts of humans and animals, but can cause infection in other parts of the body, especially the urinary tract. , even if they are not taking prophylactic antibiotics, which suggests that they encounter a reservoir of antibiotic-resistant strains during travel (89). Apparently healthy people in developing countries carry potentially pathogenic, antibiotic-resistant organisms asymptomatically (90). Several factors, such as urban migration with crowding and improper sewage disposal Sewage disposal
The ultimate return of used water to the environment. Disposal points distribute the used water either to aquatic bodies such as oceans, rivers, lakes, ponds, or lagoons or to land by absorption systems, groundwater recharge, and irrigation. , encourage the exchange of antibiotic-resistant organisms between people and the exchange of resistance genes among bacteria, thereby increasing the prevalence of resistant strains. In Nigeria, resistant E. coli E. coli: see Escherichia coli.
in full Escherichia coli
Species of bacterium that inhabits the stomach and intestines. E. coli can be transmitted by water, milk, food, or flies and other insects. isolates from persons in an urban metropolis (Lagos) were significantly more likely to be resistant to ampicillin and streptomycin streptomycin (strĕp'tōmī`sĭn), antibiotic produced by soil bacteria of the genus Streptomyces and active against both gram-positive and gram-negative bacteria (see Gram's stain), including species resistant to other (p [is less than] 0.05), and possibly more resistant to sulphathiazole and tetracycline (p < 0.10), than isolates from residents of nearby smaller towns and villages (Table 3) (91). Moreover, strains isolated from Lagos were more likely to show resistance to 4 to 6 of 7 antibiotics tested, whereas strains from rural areas were in most cases resistant to only 0 to 3 antibiotics (91).
Table 3. Antibiotic resistance of Escherichia coli strains isolated from residents of an urban area (Lagos) or rural/suburban areas (southwest Nigeria) (from )
Percentage of resistant isolates Antimicrobial Urban Rural/suburban agent (n = 30) (n = 44) Ampicillin(a) 53 27 Chloramphenicol 13 14 Streptomycin(a) 63 32 Sulphathiazole(b) 73 48 Tetracycline(b) 87 64 Trimethoprim 53 41
(a) Significant differences between the two groups at p [is less than] 0.05 (Chi-square test chi-square test: see statistics. )
(b) Significant differences between the two groups at p [is less than] 0.10 (Chi-square test)
In 1991, 80% of residents of developing countries had no sanitary facilities for sewage disposal (92). Pipe-borne water, often scarce in developing countries, is not always potable potable /pot·a·ble/ (po´tah-b'l) fit to drink.
Fit to drink; drinkable.
fit to drink. . The development of sanitation and other facilities is not always proportionate to the rapid rises in urban populations (93,94). As urban migration continues, overcrowding overcrowding
overcrowding of animal accommodation. Many countries now publish codes of practice which define what the appropriate volumetric allowances should be for each species of animal when they are housed indoors. Breaches of these codes is overcrowding. increases and hygiene declines, increasing the probability of spread of antibiotic-resistant and commensal pathogens. Potable water, well-ventilated housing and proper waste disposal should reduce infections, the need for antibiotics, and subsequent development of antibiotic resistance.
Because tropical conditions encourages the survival of bacteria, more pathogens and commensals are found in tropical environments than in temperate climates (95). The warm and humid tropical climate A tropical climate is a type of climate typical in the tropics. Köppen's widely-recognized scheme of climate classification defines it as a non-arid climate in which all twelve months have mean temperatures above 18°C (64.4 °F). and the low levels of health care, hygiene, and sanitation contribute to a relatively high prevalence of infectious disease in developing countries.
Inadequate Hospital Infection Control Practices
Infection control practices in many hospitals in developing countries are rudimentary and often compromised by economic shortfalls and opposing traditional values Traditional values refer to those beliefs, moral codes, and mores that are passed down from generation to generation within a culture, subculture or community. Since the late 1970s in the U.S. (96). The resulting nidus nidus /ni·dus/ (ni´dus) pl. ni´di [L.]
1. the point of origin or focus of a morbid process.
2. nucleus (2). of nosocomial nosocomial /noso·co·mi·al/ (nos?o-ko´me-il) pertaining to or originating in a hospital.
1. Of or relating to a hospital.
2. pathogens and resistant organisms may be disseminated to the outside community. Improper disposal of hospital waste accentuates such spread. Untreated hospital waste in Uganda was often dumped into public sewers or thrown into rubbish heaps ravaged rav·age
v. rav·aged, rav·ag·ing, rav·ages
1. To bring heavy destruction on; devastate: A tornado ravaged the town.
2. by scavengers (97).
Susceptibility Testing and Surveillance
Information from routine susceptibility testing of bacterial isolates and surveillance of antibiotic resistance, which provides information on resistance trends, including emerging antibiotic resistance, is essential for clinical practice and for rational policies against antibiotic resistance. Bacterial infections are often treated after they become life-threatening, which encourages empirical selection of broad-spectrum antibiotics (98,99). The antibiotic susceptibility pattern of bacterial isolates in much of the developing world is unknown, and little guides empirical prescribing. Susceptibility testing cannot be done readily because equipment, personnel, and consumables are scarce and expensive (59,100). In most all infections, no clinical specimens are cultured. Where available, community-based antibiotic surveillance data may be useful to prescribers in the absence of patient-specific antibiotic-susceptibility results. For example, Ringertz et al. (101) demonstrated that resistance among respiratory pathogens was infrequent in parts of Ethiopia. This information would help local Ethiopian prescribers to treat such infections with inexpensive, broad-spectrum antibiotics.
National surveillance programs for antibiotic resistance, the norm in industrialized nations, are less common and less elaborate in developing countries (4). Current inferences about antibiotic resistance trends in developing countries are based on a small number of reports, generated by a handful of microbiology laboratories in urban areas--data not representative of a country, because wide variations in antibiotic resistance patterns may exist within countries (Table 3). Moreover, surveillance should be conducted regularly and continuously because resistance rates can vary in one region of a country over time (Table 1) (102).
Defective Antibiotic Susceptibility Assays
Well-standardized antibiotic susceptibility assays provide more reliable results (103). However, standard bacterial strains with which to assay new batches of antibiotics or antibiotic disks are not available in laboratories in many developing countries. Delayed transportation and breakdown of cold storage also affects the quality of antibiotics used as diagnostic reagents. Degraded antibiotic powders and antibiotic disks used for susceptibility testing lead to exaggerated estimates of bacterial resistance levels. The frequent recovery of bacteria resistant to the beta-lactams or tetracyclines Tetracyclines Definition
Tetracyclines are medicines that kill certain infection-causing microorganisms.
Tetracyclines are called "broad-spectrum" antibiotics, because they can be used to treat a wide variety of in tropical countries could reflect, in part, the temperature and moisture lability lability /la·bil·i·ty/ (lah-bil´i-te)
1. the quality of being labile.
2. in psychiatry, emotional instability.
the quality of being labile. of test reagents. Laboratory scientists in developing countries face difficulties in obtaining research supplies, which often require them to improvise by, for example, using injectable antibiotic formulations to measure MICs when standard antibiotic powders are not available. The report that clinical microbiologists in developing countries make their own disks from "local blotting papers" (104) illustrates how improvisation can lead to inconsistent laboratory results and unreliable data.
Economic and Political Factors
Lack of resources hampers implementation of most strategies against antibiotic resistance. Statistics from the World Bank show that developing countries spent $41 per person on health in 1990, compared with the $1,500 per person spent by industrialized countries. Disease prevalence as measured by disability-adjusted life years Disability-adjusted life years (DALY) is a measure for the overall "burden of disease." Originally developed by the World Health Organization, it is becoming increasingly common in the field of public health and health impact assessment (HIA). and by communicable disease communicable disease
A disease that is transmitted through direct contact with an infected individual or indirectly through a vector. Also called contagious disease. in particular is much greater in developing than in industrialized countries (93,105-107). As a result of such gross underfunding, the drug supply is chronically inadequate or at best erratic in health facilities in many countries, including Nigeria (43,105,106).
Armed conflicts have recently led to a breakdown in health services health services Managed care The benefits covered under a health contract and sanitation and rapid dissemination of resistant pathogens, particularly in sub-Saharan Africa and Asia (108,109,110). During an outbreak of cholera and bacillary dysentery Bacillary dysentery
A highly contagious intestinal disease caused by rod-shaped bacteria of the genus Shigella. Bacillary dysentery is a significant infection of children in the developing world, where it is transmitted by the fecal-oral route. in Rwandan refugees, resistance to multiple first-line antibiotics in clinical isolates of Vibrio cholerae Vibrio chol·er·ae
A bacterium that causes Asiatic cholera in humans; Koch's bacillus.
Vibrio cholerae Infectious disease The Vibrio and Shigella dysenteriae Shigella dys·en·ter·i·ae
Shigella dysenteriae Shigella group A Microbiology The least commonly isolated and most virulent Shigella serotype contributed to high death rates (109).
Even in developing countries not at war, political corruption and mismanagement mis·man·age
tr.v. mis·man·aged, mis·man·ag·ing, mis·man·ag·es
To manage badly or carelessly.
mis·manage·ment n. of funds, personnel, and development programs have created large populations living in abject poverty and at high risk for infection (111). Medical expenses, days lost from work, and transportation costs account for substantial economic loss. The cost of medical treatment, even subsidized treatment, is beyond the means of many patients. Poorly paid health workers sometimes extort To compel or coerce, as in a confession or information, by any means serving to overcome the other's power of resistance, thus making the confession or admission involuntary. To gain by wrongful methods; to obtain in an unlawful manner, as in to compel payments by means of threats of fees from patients (111). Thus, persons with communicable diseases, unable to afford medical treatment, may infect others. Poverty also interferes with patient compliance, which in turn promotes the emergence of antibiotic resistance during short-term therapy of acute infections and long-term therapy of chronic infections, such as tuberculosis (111).
Combating the Problem of Antibiotic Resistance
The recommendations of WHO for ensuring proper drug use (79) can be adapted to combat the escalation of community-acquired antibiotic resistance in developing countries. The misuse of antibiotics by health-care professionals, unskilled practitioners, and patients can be alleviated by auditing antibiotics, limiting antibiotic choice, developing prescription guidelines, and emphasizing continuing medical and public education. The quality of antibiotics can be improved by emphasizing quality compliance and monitoring antimicrobial drugs manufactured or dispensed. Such reforms will help control substandard drugs that are degraded, counterfeit, or bioinequivalent. Dissemination of resistant organisms in the community can be impeded by improved public sanitation and hygienic hy·gien·ic
1. Of or relating to hygiene.
2. Tending to promote or preserve health.
3. Sanitary. practices and upgraded hospital infection control. Finally, strategies to ensure that these recommendations are adopted and implemented under difficult economic and political conditions can be formulated. Antimicrobial resistance will continue to escalate in developing countries unless corrective measures are instituted.
We thank the International Program in the Chemical Sciences, which supports the current research in antibiotic resistance by I.N. Okeke and A. Lamikanra. Ms. I.N. Okeke thanks the Fulbright Commission and the United States Information Service for a fellowship and Dr. James B. Kaper for his support.
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Iruka N. Okeke,(*) Adebayo Lamikanra,(*) and Robert Edelman([dagger])
(*) Obafemi Awolowo University, Ile-Ife, Nigeria; and ([dagger])University of Maryland University of Maryland can refer to:
Ms. Okeke, lecturer in pharmaceutical microbiology at Obafemi Awolowo University, Ile-Ife, Nigeria, and Ph.D. candidate, is a Fulbright Fellow at the Center for Vaccine Development in Dr. James Kaper's laboratory at the University of Maryland School of Medicine in Baltimore, working on molecular genetics molecular genetics
The branch of genetics that deals with hereditary transmission and variation on the molecular level. of enteric bacteria. Her interests include clinical pharmacology and research on the pharmacology of antibiotics and natural products. She is studying antibiotic resistance and virulence characteristics of enteric organisms in Nigeria.
Address for correspondence: Robert Edelman, Center for Vaccine Development, 685 West Baltimore St., Room 480, Baltimore, MD 21201, USA; fax: 410-706-6205; e-mail: email@example.com.