Antimicrobial Stewardship in the Developing World: A Real Possibility?

By Brian G. Blackburn, MD, Clinical Assistant Professor in the Division of Infectious Diseases and Geographic Medicine at Stanford University, is Associate Editor of Infectious Disease Alert.

Dr. Blackburn reports no financial relationships in this field of study.

Synopsis: Although difficult to implement in resource-limited settings, several successful antimicrobial stewardship programs have recently been reported in the developing world.

Effective antimicrobial stewardship is of particular importance in the developing world. In many developing countries, inappropriate antimicrobial use has led to widespread drug resistance among not only bacterial isolates, but also among parasites and other infectious agents. This in turn becomes a global problem, as resistance frequently then disseminates to the rest of the world. Impediments to successful stewardship programs in developing settings include a dearth of human and technological resources, limited microbiology laboratory support (and thus limited surveillance data), and a lack of support from policymakers and funding sources. The large burden of infectious diseases combined with the scale of poor stewardship in many developing countries (where not only are hospitals and clinics to blame, but patients can often purchase antibiotics directly from pharmacies without a physician's prescription) creates a fertile environment for the rapid development of antimicrobial resistance. The need for effective antimicrobial stewardship programs in these settings is therefore great, perhaps even more acute than in the developed world. Unfortunately, examples of successful programs in developing countries have been sparse to date.

Some have questioned whether it is even possible to successfully administer such programs in these settings. A recent review of antibiotic resistance and stewardship in Africa reported that 32% of patients who receive antibiotics in Africa obtain them without a prescription.1 Widespread resistance to most first-line antibacterials (e.g., ampicillin, trimethoprim/sulfamethoxazole, tetracycline) has long been documented among multiple bacterial pathogens in all regions of Africa.1 The authors note the dire need for antimicrobial stewardship programs in Africa, and that these programs should include educational components and practice guidelines; however, no such programs are mentioned in this review.

Fortunately, other reports suggest that with enough advocacy and determination, antimicrobial stewardship programs can be successful in the developing world. One recent report from a specialty hospital in Chennai, India described restricting the use of carbapenems, colistin, and tigecycline; when these antibacterials were used, an infectious diseases consultation was required within 48 hours of the first dose.2 A pharmacy team tracked use of these drugs, and non-compliers with this policy were contacted by the team and/or medical leadership of the hospital. In addition, an educational program regarding antimicrobial stewardship and resistance was launched, and better infection control policies involving isolation protocols and hand-washing were instituted. Although no comment was made about the increased burden this might have placed on the infectious disease consulting service at this center, the program appears to have been successful. Carbapenem use decreased 22% after initiation of the policy, with a concomitant reduction in carbapenem-resistant E. coli (from 3.7% to 1.6% of isolates) over the same period; carbapenem-resistant Klebsiella spp. decreased as well (from 6.0% to 3.6% of isolates).2

A group in Lebanon recently reported a 50% cost savings after their pharmacy staff began spending extra time each week promoting rational antibiotic use at a tertiary care university hospital in Beirut.3 Their interventions included contacting clinicians to provide recommendations on length of therapy, conversion from intravenous to oral therapy when appropriate, drug modification, and correcting dosing frequency.

In Thailand, another group devised an antimicrobial stewardship program aimed at decreasing unnecessary antibiotic use in patients with mild respiratory and diarrheal infections. The intervention consisted of an educational program that targeted physicians, provision of clinical treatment guidelines, and increasing the availability of cultures. This resulted in decreased antibiotic use among patients presenting with acute diarrhea and upper respiratory infections (URIs) to the outpatient department of a hospital in Bangkok.4 Antibiotic use decreased dramatically after implementation of the program, from 74% of patients with URIs to 13%, and from 78% of patents with diarrhea to 19%; clinical outcomes were unchanged despite the decreased antibiotic use.4

In Argentina, a group recently launched a stewardship program in which the use of seven antibacterials (ceftriaxone, ceftazidime, cefepime, piperacillin-tazobactam, imipenem, colistin, and vancomycin) required approval by an infectious diseases (ID) physician at a Buenos Aires university hospital.5 In addition, pharmacy staff monitored use of these agents and discussed appropriate use and adherence to hospital guidelines with prescribing physicians; ID physician availability and involvement were also increased. One year after initiation of this program, the requirement for an infectious diseases physician's approval was dropped while the other aspects of the program were retained for an additional year. Use of these drugs after the second year of the program (when no ID physician approval was required) was then compared to use after the first year (when ID physician approval was required), which yielded mixed results. Use of cefepime, colistin, and imipenem significantly increased after the second year (when the requirement for ID physician approval was dropped, suggesting perhaps that having this requirement curbed unnecessary use of these drugs), while use of ceftazidime, ceftriaxone, and vancomycin significantly decreased; piperacillin-tazobactam use remained flat.5 A trend towards an increased frequency of infectious due to multidrug resistant Pseudomonas aeruginosa and Acinetobacter spp. was seen after the requirement for ID physician approval was dropped.5

Commentary

The hurdles that many developing countries must overcome to institute antimicrobial stewardship programs are formidable. However, these examples demonstrate that with enough advocacy and determination, such programs are possible even in resource-limited settings and can have a beneficial impact there. The above example from India demonstrated not only decreased use of the targeted antibacterials, but also lower rates of carbapenem-resistant enterobacteriacae following implementation of the program. Importantly, this study included the simultaneous implementation of better infection control policies, suggesting that combined stewardship / infection control programs might offer the most benefit in these settings. In addition, all of the examples above not only required infectious diseases physician input for use of the restricted antibiotics, but also contained an educational component aimed at making the changes more sustainable. Especially in the developing world, stewardship programs which include a combination of physician input, education, and better infection control seem most likely to succeed. It is also important to consider measures that limit availability of antimicrobials to patients who have a physician's prescription for those drugs.

Perhaps most encouragingly, despite taking place in resource-limited settings in the developing world, these four programs from disparate locations covering three continents were able to mobilize the necessary manpower, advocacy, funding, and institutional buy-in to institute their programs successfully. While such reports have been rare to date, these programs may serve as models for future antimicrobial stewardship programs in the developing world. Hopefully, we will see the proliferation of these programs soon, in these kinds of locations where the need for them is greatest.

References

  1. Kimang'a AN. A situational analysis of antimicrobial drug resistance in Africa: are we losing the battle? Ethiop J Health Sci 2012;22:135-43.
  2. Ghafur A, et al. Save antibiotics, save lives: an Indian success story of infection control through persuasive diplomacy. Antimicrob Resist Infect Control 2012;1:29.
  3. Droubi N, et al. Impact of hospital pharmacists' clinical interventions for promoting rational utilization of anti-infectives in a university hospital in Lebanon. Poster presentation at Infectious Diseases Society of America (IDSA) meeting, San Diego, CA. October 2012.
  4. Boonyasiri A, et al. Effectiveness of multifaceted interventions on rational use of antibiotics for out-patients at Siriraj Hospital, Bangkok, Thailand. Poster presentation at Infectious Diseases Society of America (IDSA) meeting, San Diego, CA. October 2012.
  5. Lopardo G, et al. Antimicrobial stewardship program in a developing country: the epidemiological barrier. Rev Panam Salud Publica 2011;30:667-8.