Lack of acceptance from physicians

We encountered reluctance and resistance from many physicians during the introduction and initial implementation of the ASP. One prominent concern was that the ASP undermined professional autonomy. In the setting of specific patient scenarios, concerns were also voiced by the ASP team and/or prescribing physicians regarding the rationale and/or evidence of various proposed antibiotic plans. These concerns provided an opportunity for discussion and review of clinical guidelines, which served a continuing medical education function for all those involved and improved the quality of patient care. Discussions related to how clinical guidelines are applied outside Nepal were especially important in our setting.

We addressed these issues by ensuring that senior members of the medical staff, including the infectious disease specialist, were included in the approval team. Occasionally, discussions with individual physicians were necessary to address concerns; these discussions were often effective in reaching a mutually acceptable plan regarding antibiotic use. High-level administrative support was also key in addressing such situations. One particularly effective strategy was utilizing ASP champions within a physician’s specialty to help engage the physician in discussions regarding antibiotic use for conditions specific to their specialty. Despite these efforts, some instances remained in which the ASP recommendations were not accepted. In such cases, ASP members, the prescribing physician, and administration discussed the specific case to help facilitate a mutually agreeable plan. This experience is not unique to our program or Nepal. Several qualitative studies have also revealed physician behavior toward hospital antibiotic policy as a barrier for ASP. ^{Reference Mol, Rutten, Gans, Degener and Haaijer-Ruskamp23,Reference Pakyz, Moczygemba, VanderWielen, Edmond, Stevens and Kuzel24}

Lack of knowledge regarding optimal antibiotics prescribing

Many studies in low- and middle-income countries (LMICs) have demonstrated lack of knowledge among prescribers regarding appropriate use of antibiotics. Several studies have been performed on this subject in Nepal, with similar results. ^{Reference Shrestha25,Reference Sarraf, Rai and Rauniar26} Our program benefitted from having both an infectious disease specialist and a doctor of pharmacy on the team. Educational programming, group discussions, and individual discussions were helpful in addressing this challenge but required significant time and effort.

Lack of support

Interventions like an ASP require substantial time and dedication, especially in the initial implementation phase. The development of a restricted formulary (with rationale) and a reference antibiotics guide tailored to our institution was time-consuming. Because it was a new concept in our practice setting and physicians had limited time given competing professional responsibilities, it was challenging to coordinate and communicate with stakeholders. However, our ASP program benefitted from early and consistent support from high-level hospital administration as well as committed ASP team members, which were key supports to our program.

Diagnostic barriers

The capacity and expertise of the microbiology laboratory is a key support for the ASP because the ASP relies on accurate and timely microbiology data to guide appropriate antibiotic therapy. Our hospital has a clinical microbiology laboratory capable of performing Gram staining, organism identification from culture results, and susceptibility testing via disc diffusion. But the laboratory does not have access to molecular or rapid organism identification testing. The lack of availability of rapid, automated, or molecular testing represents a limitation of identification and antibiotic sensitivity testing of a microorganism. ²⁷ However, the GIH microbiology laboratory provides services that many other hospitals in Nepal do not provide. Lack of microbiological laboratory support is a very significant barrier in LMICs that has been associated with increased mortality. ^{Reference Petti, Polage, Quinn, Ronald and Sande28}

Documentation process

The recommendations made by the ASP were documented by the approval team to provide data regarding recommendations and if the recommendations are followed. This step is critical for process analysis and improvement. A dedicated form was developed to record the recommendation, but it was often challenging to use because calls for approval occurred around the clock and sometimes ASP members did not have the forms available. As a result, some gaps in documentation occurred, and the exact recommendation made by the ASP was not always documented.

Availability of antibiotics

Our ASP not only advocated for minimizing unnecessary use of antibiotics but also supported appropriate and prompt use of antibiotics when clinically necessary. Antibiotic unavailability can contribute to the use of broad-spectrum antibiotics when a narrower antibiotic is not available. ^{Reference Kakkar, Shafiq and Malhotra29} In some instances, lack of some antibiotics within the context of Nepal (eg, aztreonam or echinocandins) made the development of empiric guidelines challenging. On the other hand, availability of broad-spectrum β-lactam–β-lactamase inhibitor combination antibiotics (eg, ceftriaxone+tazobactam and cefepime+tazobactam) required sustained educational efforts and discussion to discourage use when alternatives existed. The promotion of the wider use of such broad-spectrum antibiotics, often in unnecessary settings, was often driven by the influence of pharmaceutical companies either directly or indirectly on prescribers. The barriers we faced while implementing our ASP are similar to barriers encountered by other centers. ^{Reference Schuts, Hulscher and Mouton7}

Change in carbapenem resistance

The most common microorganisms isolated in our hospital are Acinetobacter, Klebsiella, and Pseudomonas. We detected a decrease in percentage of carbapenem-resistant bacteria immediately after implementing the ASP program (Table 2). Possibly, this decrease in carbapenem resistance may have been due to decreased carbapenem utilization and thus drug selective pressure, among other possible causes.

Table 2. Profile of Carbapenem Resistance Isolates Among the Most Common Microorganisms, 2015 and 2016

Opportunities provided by ASPs

The initiation and implementation of an ASP has opened opportunities to our healthcare workers to gain experience and education in ASP roles within their own professions and opportunities for interprofessional practice. These opportunities help build professional experience and expertise in ASP for future programs.

Decrease in unnecessary use of antibiotics

Basic interventions employed by the ASP have helped to decrease the unnecessary use of antibiotics. Requiring approval for broad-spectrum antibiotics has sensitized clinicians to use such agents carefully and to reconsider whether they are truly necessary. The purchase of combination antibiotics (eg, cefipime+tazobactam, ceftriaxone+sulbactam, and ampicillin+cloxacillin) drastically decreased after the ASP began. For example, 326 vials of ceftriaxone+sulbactam and 132 vials of ampicillin+cloxacillin were procured in 2015, which decreased to 34 and 59 vials, respectively, in 2016.

Improved knowledge and awareness

Formation of guidelines, education to the providers and publication of data have helped to improve knowledge and awareness among healthcare workers. Utilization of culture reports to guide antibiotic prescribing was incorporated into clinician prescribing practices when previously broad-spectrum antibiotics were commonly used for empiric therapy and further antibiotic management were often not guided by culture sensitivity data once available.

Access to safer alternate antibiotics

The availability of antibiotics is limited in LMICs. ASPs, through development and promotion of antibiotic dosing guides, have not only limited the unnecessary use of unwanted antimicrobials but have also helped to obtain and utilize antimicrobials with less adverse effects, such as echinocandins and teicoplanin, as pharmacy has become involved in the ASP.

Improved healthcare facilities

Many factors mentioned here have ultimately helped decrease morbidity and mortality and have likely decreased the overall cost of treatment. We believe that these steps have contributed to the improvement of overall outcomes of patients.

Improved diagnostic capacity

Implementation of an ASP and its feedback to the hospital and organization can provide an opportunity to establish and improve microbiological laboratory facilities, which can ultimately have a positive impact on patient outcomes. Short-term solutions to improve diagnostic capacity may include partnering of an institution with larger institutions with better microbiology laboratory capabilities. Long-term solutions include expansion of microbiology laboratory facilities via a national action plan with dedicated funding. Global programs such as Strengthening Laboratory Medicine Toward Accreditation (SLMTA) and Stepwise Laboratory Improvement Process Towards Accreditation are working to increase access to microbiology laboratories in LMICs. ^{Reference Nkengasong, Yao and Onyebujoh30} GIH is currently working to purchase an automated system (VITEK-2, bioMèrieux, Marcy-l’Étoile, France) for rapid and accurate identification of pathogen and assessment of antimicrobial susceptibility.

Postprescription review with feedback

Postprescription audit with feedback from the ASP team of other unrestricted antibiotics can be a useful approach for better understanding overall antibiotic utilization in this institution. Studies have shown a higher acceptance rates and improvement in appropriate use of antibiotics when postprescription review with feedback was used compared to preprescription authorization. ^{Reference Tamma, Avdic and Keenan31,Reference Doukas, Cheong, McKew, Gray, McLachlan and Gottlieb32}

Regular training to pharmacists and approval team

We plan to continue training for ASP members and to include new ASP members as staff turnover occurs and to diversify our team. We anticipate that this will strengthen the ASP team and enhance long-term team function.

Establishment of ASP as a priority plan in the national action plan

Starting ASP in one healthcare institution can encourage other institutions to develop an ASP in their own center. However, a national policy is essential to standardize and monitor these programs. The WHO provides a framework for the development of a national action plan, which the WHO also notes ideally starts with developing local ASPs. ³³ Few LMICs have developed national plans to establish ASPs and limit AMRs, but most notably, India has. ^{Reference Cox, Vlieghe and Mendelson8} According to the US Center for Disease Dynamics, Economics and Policy (CDDEP), Nepal has also partnered with the Global Antimicrobial Resistance Partnership (GARP), which provides tools for LMICs to collect data on nationwide trends in antibiotic use and AMR along with supporting stewardship activities. ³⁴ We hope our experience will help support national policy development to explore how to establish and adapt ASPs in other hospitals.

Importance of ongoing research, publication, and dissemination of results

Monitoring the impact of the ASP is extremely important in demonstrating the effectiveness and value of stewardship. Future research at our institution may include further investigation of reductions in antibiotic use due to ASP; appropriateness of antibiotic selection, dose, and duration; decrease in cost; decrease or change in resistance; and overall improvement in clinical outcome. Research and publication are extremely important to advocate adaptation in other institutions or settings and to describe facilitators and barriers to ASP implementation in a variety of settings. It also opens the door for improvement by identifying potential areas of improvement by others who review ASPs in different settings.

In conclusion, our antimicrobial stewardship program was established with all necessary core elements as outlined by the WHO: leadership commitment, accountability and responsibilities, AMS actions, education and training, monitoring, reporting and feedback. The challenges faced by this program could be utilized by other institutions in LMICs to implement their own ASPs in similar settings. We have many plans for our ASP in the areas of monitoring, surveillance, and reporting to better describe our operations and outcomes and to inform ongoing quality improvement.