|
Antimicrobial use and antimicrobial
resistance among healthy children in Bolivia
Alessandro Bartoloni
Clinica Malattie Infettive, Università di Firenze, Italia
Resistance to antimicrobials is now a world-wide problem which may be particularly serious in developing countries,
where alternative antimicrobials are often not available or are too expensive (1). Inappropriate use of antibiotics
is probably the main responsible factor for the bacterial resistance problem. Other factors include the self-administration
of antibiotics, as well as the availability of drugs without prescription for purchase in pharmacies or open-air
markets. If inappropriate use of antimicrobial agents favours the emergence of resistant bacteria, crowding, poor
sanitary conditions, and sexual contact are responsible for their rapid spread in poor and developing areas (2).
Epidemiological studies of bacterial resistance are difficult to carry out in developing countries, and only limited
data are available from these areas. Most studies of antibiotic resistance have included strains isolated from
patients attending hospital. Fewer studies have been conducted in healthy people. The commensal flora of the gut
are considered the most important reservoir for antimicrobial resistance genes in both the community and hospital
environments (3,4). These genes can be transferred from commensal to pathogenic organisms (5), as well as from
one host to another (6).
The prevalence of antimicrobial resistant non-pathogenic Escherichia
coli among healthy children, aged 6-72 months, was determined
in a study carried out in urban and rural areas of the Cordillera province, south-eastern Bolivia (7). Camiri,
the urban town has a population of approximately 28,000, has 3 main hospital, 12 smaller hospitals and 12 private
pharmacies. Javillo, rural community of about 100 people, is situated in an isolated area of the jungle north-east
of Camiri. A selective screening method employed in earlier studies was used to detect resistant bacteria in stool
samples from these areas (3,8). Stool samples were collected from 321 children (296 in Camiri and 25 in Javillo).
Children were eligible if they had no gastrointestinal symptoms on the day of enrollment and had no personal history
of hospitalization, antimicrobial therapy or travel outside the country within the last 4 months. The similar resistance
rates in children who received no antibiotics within the past 4 months and children who never received antibiotics,
suggested that the former are representative of health members of the community (3).
A very high prevalence of children from the urban area carried E.coli resistant to the commonly dispensed antimicrobials (Table 1): 97% to ampicillin,
94% to trimethoprim-sulfmethoxazole (TMP/SMX), and 92% to tetracycline. Resistance was also high to chloramphenicol
(69%) and piperacillin (54%). Lower prevalence of resistance was found to cephalotin (10%), gentamicin (5%), nitrofurantoin
(5%), nalidixic acid (4%), amikacin (0%), cefotaxime (0%), and ciprofloxacin (0%). In the rural area the prevalence
of resistance was also high although significantly lower than that of the urban area for ampicillin (87%), TMP/SMX
(71%) and piperacillin (33%). Overall, 63% of children carried E.coli with multiple resistance to ampicillin, TMP/SMX, tetracycline and chloramphenicol.
An additional arm of the study examined antibiotic usage patterns using simulated patient scenarios. Study personnel
presented one of six clinical scenarios at each of the district pharmacies in Camiri. In each case they recorded
the name and quantity of the medications dispensed by the pharmacist and any advice given. The six scenarios included:1)
a 6-month old with acute watery diarrhea without fever, 2) an adult with acute watery diarrhea without fever, 3)
a 2-year old with low grade fever and rhinorrhea, 4) an 8-year old with fever and sore throat, 5) an adult female
with acute dysuria and fever, and 6) an adult male with purulent urethral discharge. In this simulated patients
study, over two-thirds of the pharmacies dispensed antimicrobials without a medical prescription, and the quantity
dispensed varied according to the patient's ability to pay.
Antimicrobials were dispensed inappropriately for 92% of adults and 40% of children with watery diarrhea. Sixty
percent of the pharmacies also gave antidiarrheals to children while none gave oral rehydration salts. Tetracycline
was the most commonly dispensed antimicrobial in adults with diarrhea and in one case it was given to a six-month
old child. Furazolidone, sulphoguanide, sulphathiazol, neomycin, and streptomycin were the other antimicrobials
dispensed. All pharmacies only dispensed enough antibiotics for two days or less. For the mock illnesses for which
antimicrobial therapy is indicated, antimicrobials were dispensed to 67% of males with purulent urethral discharge.
Ciprofloxacin was the most commonly dispensed drug; benzathine penicillin, procaine penicillin, TMP/SMX, and spectinimoycin
were also dispensed. Only spectinomycin was given in appropriate dose. Only fifty-eight percent of pharmacies dispensed
antimicrobials (pipemidic acid, sulphametizol, nitrofurantoin, nalidixic acid, norfloxacin) to women with fever
and dysuria. The recommended duration of therapy ranged from 1 to 5 days but in all cases the quantity of tablets
dispensed were four or less. Thirty-three percent of pharmacies dispensed only phenazopyridine, a urinary analgesic
with no antibacterial activity.
This study documents several problems associated with the use of antimicrobials, including inappropriate and ineffective
regimes dispensed at pharmacies, widespread use of antimicrobials even in a remote rural area of Bolivia, and widespread
carriage of resistant commensal gut bacteria in urban and rural areas. The prevalence of resistance to ampicillin
and TMP/SMX was higher than that previously reported in developing countries. Reports from Chile, Honduras, Costa
Rica, Brazil, and Thailand have reported 38-50% prevalence of resistance to TMP/SMX (9). Our findings for ampicillin
resistance are as high or higher than those reported from India, Venezuela, and China, which have previously documented
some of the highest frequencies of antimicrobials resistant commensal bacteria within a healthy developing country
population (3,10).
Our study confirms that resistance to antimicrobial drugs is particularly troublesome in developing countries.
As infectious diseases are still the major health problem in these areas, indigenous people will most feel the
consequences of this situation. However, considering the increasing mobility of the world population, the existence
of a large reservoir of resistance genes in commensal bacteria of healthy individuals from developing countries
represents a threat for people throughout the planet. Resistant genes can spread easily from commensal faecal flora
to pathogenic bacteria and difficulty in treating patients infected with such strains may occur in both developing
and developed countries. The prevention of infection and the reduction of transmission are the most effective methods
to address the problem of antimicrobial resistance in developing countries. However, urgent measures are needed
now to implement effective drug policies aimed at more rational use of drugs and the development of implementation
programs which include the private sector.
References
- O'Brien TF. Global surveillance of antibiotic resistance.
N Engl J Med 1992;326:339-40.
- Kunin CM. Resistance to antibiotic drugs-a worldwide
calamity. Ann Intern Med 1993;118:557-61.
- Lester SC, Del Pilar Pla M, Wang F, Pere Schael I,
Jiang H, O'Brien TF. The carriage of Escherichia coli resistant to antibiotic agents by healthy children in Boston,
in Caracas, Venezuela and in Qin Pu, China. N Engl J Med 1990;323, 285-9.
- Levy SB, Marshall B, Schleuderberg S, Rowse D, Davis
J. High frequency of antibiotic resistance in human faecal flora. Antimicrob Agents Chemother 1988;32:1801-6.
- Tauxe RV, Cavanagh TR, Cohen ML. Interspecies gene
transfer in vivo producing an outbreak of multiply resistant shigellosis. J Infect Dis 1989;160:1067-70.
- O'Brien TF. The global epidemic nature of antimicrobial
resistance and the need to monitor and manage it locally. Clin Infect Dis 1997; 24(suppl 1):S2-8.
- Bartoloni A, Cutts F, Leoni S, Austin CC, Mantella
A, Guglielmetti P, et al. Patterns of antimicrobial use and antimicrobial resistance among healthy children in
Bolivia. Tropical Medicine and International Health 1998;3:116-23.
- Datta N. Drug resistance and R factor in the bowel
bacteria of London patients before and after admission to hospital. British Med J 1969;ii:407-11.
- Murray BE, Alvarado T, Kim KH, Vorachit M, Jayanetra
P, Levine MM. Increasing resistance to trimethoprim-sulphamethoxazole among isolates of Escherichia coli in developing
countries. J Infect Dis 1985;152:1107-13.
- Amyes SGB, Tait S, Thompson CJ, Payne DJ, Nandivada
LS, Jesudason MV, et al. The incidence of antibiotic resistance in aerobic faecal flora in South India. J Antimicrob
Chemother 1992;29: 415-25.
|
