Author response to comment on: Treatment gaps and risk factors for multidrug-resistant enterobacterales in Belize: A 6-year (2018–2023) nationwide retrospective analysis

Dear Editor,

We thank Drs Moragas and Llor for their thoughtful letter regarding our recent article. ¹ Their comments provide a valuable opportunity to expand upon the contextual factors that informed our analysis and recommendations. We address each of their queries in turn.

First-line therapy and the use of fluoroquinolones

The correspondents ask why ciprofloxacin and trimethoprim-sulfamethoxazole remain the principal oral antibiotics prescribed for uncomplicated UTIs in Belize, despite resistance rates exceeding 40%. We acknowledge that this is a critical question and one that our study was designed to illuminate rather than fully resolve. Several factors likely contribute to this practice pattern.

First, as documented in the Belize National Antimicrobial Resistance Strategic Plan 2025–2029 (Belize Ministry of Health and Wellness, 2024), Belize has historically lacked national treatment guidelines for common infectious diseases (Supplementary Material S1). The Plan explicitly identifies “no guidelines for appropriate use of antibiotics in human and animals” as a key gap and prioritizes the development of “treatment guidelines for management of common infectious diseases based on local resistance patterns”. ² In the absence of such guidance, prescribers have necessarily relied on historical practice patterns, international guidelines that may not account for local resistance epidemiology, and the antibiotics most readily available through the public health supply chain.

Second, the correspondents correctly note that international guidelines recommend nitrofurantoin, fosfomycin trometamol, and pivmecillinam as first-line agents for uncomplicated cystitis. ³ However, the translation of these recommendations into practice in Belize is constrained by drug availability. While nitrofurantoin is included in Belize’s National Drug Formulary, fosfomycin trometamol and pivmecillinam may not be consistently available or may be prohibitively costly. Our recommendation that nitrofurantoin “be strongly prioritized for cystitis” was intended precisely to signal a shift toward these guideline-concordant, narrower-spectrum agents, but we recognize that such a shift requires parallel investments in supply chain strengthening.

Third, as our data demonstrate, the organism itself is a major determinant of empirical treatment failure. ¹ For infections caused by K. pneumoniae or E. cloacae, which together accounted for nearly one-third of isolates in our cohort, nitrofurantoin has limited activity, and broader coverage may be necessary. The correspondents’ focus on uncomplicated cystitis is appropriate, but our dataset included all urinary isolates, some of which may represent complicated infections or pyelonephritis for which fluoroquinolones or cephalosporins remain indicated. This distinction underscores the importance of developing differentiated treatment algorithms based on infection severity, patient risk factors, and, where available, rapid organism identification.

The role of community pharmacies and over-the-counter antibiotic sales

The correspondents raise an essential point regarding the role of community pharmacies in Belize. We agree entirely that understanding which antibiotics are dispensed without prescription is critical to interpreting resistance patterns and designing effective stewardship interventions.

Previous research from Belize has documented that over-the-counter sales of antibiotics are prevalent. A simulated client study conducted across 36 community pharmacies in four districts of Belize found that the majority of antibiotics obtained were from direct patient demand rather than following presentation of an infectious scenario. ⁴ These findings point to the need for additional attention to antibiotic dispensing practices in community pharmacies.

The National AMR Strategic Plan explicitly addresses this challenge (Belize Ministry of Health and Wellness, 2024). Strategic Objective 5 of the Plan, “Optimize the use of antimicrobial medicines in human and animal health”, includes activities to “strengthen laws and regulations that govern the use of antimicrobials”, “develop policies on the prudent use of antimicrobials”, and “enhance awareness among target groups on AMR impacts, and antimicrobial best practices and policies”. The Plan also identifies the need to “strengthen the ability to identify and intercept antimicrobials entering the country through illegal channels”.

Critically, the Belize Ministry of Health and Wellness has recently reaffirmed that antibiotics “remain strictly outside” any over-the-counter transition framework and “continue to require valid prescriptions at all times”. ⁵ The Ministry has also reopened the over-the-counter medicines list for review and has requested evidence-based recommendations aligned with international standards for future policy updates. These developments indicate that the regulatory environment is evolving in precisely the direction the correspondents advocate.

Data on community pharmacy dispensing practices

We concur with the correspondents that data on which antibiotics are dispensed by community pharmacies in Belize would substantially strengthen the evidence base. Our study was limited to laboratory isolates and did not include pharmacy dispensing data ^1. However, the National AMR Strategic Plan includes specific activities to address this gap. ² The Plan calls for developing a “monitoring tool to track usage of antimicrobials and share with all health facilities (including pharmaceutical facilities) for monthly reporting” and creating “a shared platform with virtual link to allow input and reconciliation of information regarding the registration, importation, and usage of antimicrobials”.

We strongly support these initiatives and view them as essential complements to laboratory-based surveillance. Understanding the concordance, or discordance, between what is prescribed, what is dispensed, and what is actually consumed will be vital for designing targeted stewardship interventions.^6,7

Revision of national treatment guidelines

The correspondents ask whether Belize’s national treatment guidelines are under review. The National AMR Strategic Plan 2025–2029 explicitly includes, under Strategic Intervention 5.6, the activity to “Develop treatment guidelines for management of common infectious diseases based on local resistance patterns” ^2. This activity is costed and included in the Plan’s operational budget. The Plan further specifies that clinical staff will be sensitized on these guidelines once developed.

Our study was designed to provide the very evidence base that makes such guideline development possible. ¹ The finding that over 40% of urinary isolates are resistant to both ciprofloxacin and trimethoprim-sulfamethoxazole is precisely the kind of data that should compel an update to empirical treatment algorithms. We are encouraged that the National AMR Sub-Committee, which includes representation from the University of Belize, the Ministry of Health and Wellness, and the Karl Heusner Memorial Hospital, is positioned to translate these findings into policy.

Conclusion

We are grateful to Drs Moragas and Llor for their engagement with our work. Their questions have allowed us to clarify the contextual factors, including the absence of prior national guidelines, constraints in drug availability and supply chains, and the evolving regulatory environment, that shape antibiotic prescribing practices in Belize. We share their concern that fluoroquinolones and trimethoprim-sulfamethoxazole remain widely used despite high resistance rates, and we view our study as a call to accelerate the revision of national treatment guidelines, strengthen community pharmacy regulation, and expand surveillance to include dispensing data. The National AMR Strategic Plan 2025–2029 provides the policy framework for these actions; our study provides the evidence to justify their urgency.

Data Availability Statement

All data generated and associated with this research has been provided in this article.*