ABSTRACT

Objective.

To assess antibiotic use in three hospitals in three Caribbean countries based on data from 2013 and 2018 using the World Health Organization Essential Medicines List “Access, Watch, Reserve” (AWaRe) classification.

Methods.

A retrospective observational study, which analyzed the World Health Organization Point Prevalence Survey data from three hospitals in three Caribbean countries, to examine proportional AWaRe group antibiotic use for the top ten inpatient indications. The Access-to-Watch ratio was calculated, and the top three antibiotics prescribed in each hospital were determined.

Results.

The final data set included 376 prescriptions for the top ten indications in 766 inpatients. The hospital antibiotic use point prevalence for Hospital 1 was 35.6%, Hospital 2 was 48.6%, and Hospital 3 was 47.1%. The Access-to-Watch ratio for the top ten indications was 2.45, 1.36, and 1.72 in the three hospitals. Access group prevalence was 71.0% in Hospital 1, 57.6% in Hospital 2, and 63.2% in Hospital 3. There were no Reserve antibiotics prescribed in any of the institutions. The most common indication for Watch prescription was skin and soft tissue infections in Hospital 1 and pneumonia in Hospital 2 and 3.

Conclusions.

This study draws urgent attention to evidence of a high proportion of Watch antibiotic prescribing and lack of Reserve group antibiotics in three Caribbean countries. This research provides data that may inform national formulary and antimicrobial stewardship policy-making across the settings analyzed and the wider region.

Keywords
Anti-infective agents; antimicrobial stewardship; drug resistance, microbial; pharmacopoeia; access to essential medicines and health technologies; Caribbean region

RESUMEN

Objetivo.

Evaluar el consumo de antibióticos en tres hospitales de tres países del Caribe según datos del período 2013-2018 mediante la clasificación de acceso, control y reserva (AWaRe, por su sigla en inglés) de la lista de medicamentos esenciales de la Organización Mundial de la Salud.

Métodos.

Se realizó un estudio observacional retrospectivo, que analizó los datos de la encuesta de prevalencia puntual de la Organización Mundial de la Salud de tres hospitales en tres países del Caribe, a fin de evaluar el consumo proporcional de antibióticos por grupo de la clasificación AWaRe para las diez principales indicaciones en pacientes hospitalizados. Se calculó la relación entre los grupos de acceso y de control y se determinó cuáles eran los tres principales antibióticos prescritos en cada hospital.

Resultados.

El conjunto final de datos incluyó 376 recetas para las diez indicaciones principales en 766 pacientes hospitalizados. La prevalencia puntual del consumo de antibióticos en el hospital 1 fue 35,6%, en el hospital 2 fue 48,6% y en el hospital 3 fue 47,1%. La relación entre los grupos de acceso y de control correspondientes a las diez principales indicaciones fue 2,45, 1,36 y 1,72 en los tres hospitales. La prevalencia del grupo de acceso fue 71,0% en el hospital 1, 57,6% en el hospital 2 y 63,2% en el hospital 3. No se prescribieron antibióticos del grupo de reserva en ninguna de las instituciones. La indicación más común para la prescripción de antibióticos en el grupo de control fue infecciones en la piel y los tejidos blandos en el hospital 1 y neumonía en los hospitales 2 y 3.

Conclusiones.

Este estudio busca llamar la atención urgentemente sobre la evidencia de una alta proporción de prescripción de antibióticos del grupo de control y la carencia de antibióticos del grupo de reserva en tres países del Caribe. Esta investigación proporciona datos que pueden fundamentar el formulario nacional y la elaboración de políticas para la optimización del uso de antimicrobianos en los entornos analizados y en la región en general.

Palabras clave
Antiinfecciosos; programas de optimización del uso de los antimicrobianos; farmacorresistencia microbiana; farmacopea; acceso a medicamentos esenciales y tecnologías sanitarias; región del Caribe

RESUMO

Objetivo.

Avaliar o uso de antibióticos em três hospitais de três países do Caribe, com base em dados de 2013 e 2018, usando a classificação "Acesso, Vigilância e Reserva" (AWaRe) da Lista de Medicamentos Essenciais da Organização Mundial da Saúde.

Métodos.

Estudo observacional retrospectivo com análise de dados do Estudo de Prevalência Pontual da Organização Mundial da Saúde, coletados em três hospitais de três países do Caribe para examinar o uso proporcional de antibióticos dos grupos AWaRe para as dez indicações mais frequentes em pacientes internados. A razão entre os grupos Acesso e Vigilância foi calculada e determinou-se quais eram os três antibióticos mais prescritos em cada hospital.

Resultados.

O conjunto final de dados incluiu 376 medicamentos prescritos para as dez indicações mais frequentes em 766 pacientes internados. A prevalência pontual de uso de antibióticos foi de 35,6% no hospital 1, 48,6% no hospital 2 e 47,1% no hospital 3. A razão entre Acesso e Vigilância nas dez indicações mais frequentes foi 2,45, 1,36, e 1,72 nos três hospitais. A prevalência do grupo Acesso foi de 71,0% no hospital 1, 57,6% no hospital 2 e 63,2% no hospital 3. Nenhum antibiótico da categoria Reserva foi prescrito em nenhuma das instituições. A indicação mais comum dos medicamentos prescritos no grupo Vigilância foram infecções de pele e tecidos moles no hospital 1 e pneumonia nos hospitais 2 e 3.

Conclusões.

Este estudo chama urgentemente a atenção para evidências de uma grande proporção de antibióticos prescritos no grupo Vigilância e a carência de antibióticos do grupo Reserva em três países do Caribe. Esta pesquisa fornece dados que podem guiar a criação de políticas para o formulário terapêutico nacional e o uso racional de antimicrobianos nos cenários analisados e na região como um todo.

Palavras-chave
Anti-infecciosos; gestão de antimicrobianos; resistência microbiana a medicamentos; farmacopeia; acesso a medicamentos essenciais e tecnologias em saúde; região do Caribe

The growing global threat of antimicrobial resistance (AMR) disproportionately affects low- and middle-income countries, like 79% of those in Latin America and the Caribbean (¹1. World Bank [Internet]. Washington, DC: World Bank: 2021 (accessed 13 June 2021). TCdata360. Country rank and value in the ITU ICT Development Index. Available from: https://tcdata360.worldbank.org/indicators/h2e1ddd20?country=BRA&indicator=24719&viz=bar_chart&years=2015
https://tcdata360.worldbank.org/indicato... , ²2. Pan American Health Organization. WHO/PAHO Hospital Antimicrobial Use Point Prevalence Survey on Antibiotic Use in Hospitals in Latin American and Caribbean Regions. Washington, DC: PAHO; 2018.). Following the collective commitment by the Caribbean Community (CARICOM) to develop national action plans on AMR by 2017, the Pan American Health Organization (PAHO) has supported a series of strategic activities for focused outcomes in the health of people, animals, and ecosystems (³3. World Health Organization. Driving change in antimicrobial stewardship in a low-resource setting. WHO Glob Action Plan AMR Newsl. 2017;20:1.–⁵5. World Health Organization [Internet]. Geneva: WHO; 2017 Sep 21 (accessed 16 March 2022). One Health. Available from: https://www.who.int/news-room/questions-and-answers/item/one-health
https://www.who.int/news-room/questions-... ). PAHO thus recognized a need to conduct a pre-implementation assessment of antibiotic use in acute care settings using the World Health Organization (WHO) Point Prevalence Survey (PPS), developed to guide decision-making (²2. Pan American Health Organization. WHO/PAHO Hospital Antimicrobial Use Point Prevalence Survey on Antibiotic Use in Hospitals in Latin American and Caribbean Regions. Washington, DC: PAHO; 2018.). In acute care institutions across Latin America, this tool has sensitized prescribers to important AMR indicators, consequently adding credibility and context to the AMR plans of action among policymakers and decisionmakers (⁴4. Hsieh J, Sati H, Ramon-Pardo P, Bruinsma N, Galas MF, Rwangabwoba JM, et al. 2034. Standardized Point Prevalence Survey on Antibiotic Use to Inform Antimicrobial Stewardship Strategies in the Caribbean. Open Forum Infect Dis. 2019;6(Suppl 2):S683–S684.).

Sharland et al. (⁶6. Sharland M, Pulcini C, Harbarth S, Zeng M, Gandra S, Mathur S, et al. Classifying antibiotics in the WHO Essential Medicines List for optimal use—be AWaRe. Lancet Infect Dis. 2018;18(1):18–20.) categorized the 180 antimicrobials on the WHO Essential Medicines List (EML) using the Access, Watch, and Reserve (AWaRe) classification as a tool to guide their safe and effective prescription. The drugs in the Access (green) group of antimicrobials are first- or second-line agents meant to be widely available, as they are recommended in the empiric treatment of several common infectious diseases (⁶6. Sharland M, Pulcini C, Harbarth S, Zeng M, Gandra S, Mathur S, et al. Classifying antibiotics in the WHO Essential Medicines List for optimal use—be AWaRe. Lancet Infect Dis. 2018;18(1):18–20., ⁷7. Hsia Y, Lee BR, Versporten A, Yang Y, Bielicki J, Jackson C, et al. Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries. Lancet Glob Health. 2019;7(7):e861–e871.). The antibiotics in the Watch (amber) group, such as carbapenems, have shown a greater risk of selecting for resistance, and so are recommended as first- or second-line drugs for a limited number of indications (⁶6. Sharland M, Pulcini C, Harbarth S, Zeng M, Gandra S, Mathur S, et al. Classifying antibiotics in the WHO Essential Medicines List for optimal use—be AWaRe. Lancet Infect Dis. 2018;18(1):18–20., ⁷7. Hsia Y, Lee BR, Versporten A, Yang Y, Bielicki J, Jackson C, et al. Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries. Lancet Glob Health. 2019;7(7):e861–e871.). The third Reserve (red) group comprises antibiotics of last resort that should only be used in specific life-threatening clinical scenarios (⁶6. Sharland M, Pulcini C, Harbarth S, Zeng M, Gandra S, Mathur S, et al. Classifying antibiotics in the WHO Essential Medicines List for optimal use—be AWaRe. Lancet Infect Dis. 2018;18(1):18–20., ⁷7. Hsia Y, Lee BR, Versporten A, Yang Y, Bielicki J, Jackson C, et al. Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries. Lancet Glob Health. 2019;7(7):e861–e871.). Furthermore, medicines in the Watch and Reserve groups must be closely monitored through antimicrobial stewardship programs to ensure their continued effectiveness (⁸8. World Health Organization [Internet]. Geneva: WHO; c2022 (accessed 2 July 2022). AWaRe. WHO Antibiotic Categorization. Available from: https://aware.essentialmeds.org/groups
https://aware.essentialmeds.org/groups... ).

The WHO global action plan (⁹9. World Health Organization. Global action plan on antimicrobial resistance. Geneva: WHO; 2015. Available from: https://www.who.int/publications/i/item/9789241509763
https://www.who.int/publications/i/item/... ) highlights a need for AMR surveillance networks and centers that collaborate to create or strengthen regional and international surveillance and response. Systematic Global PPS reviews have subsequently combined and categorized overall and condition-specific antibiotic use patterns by AWaRe classification worldwide (⁷7. Hsia Y, Lee BR, Versporten A, Yang Y, Bielicki J, Jackson C, et al. Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries. Lancet Glob Health. 2019;7(7):e861–e871., ¹⁰10. Pauwels I, Versporten A, Drapier N, Vlieghe E, Goosens H, Global-PPS network. Hospital antibiotic prescribing patterns in adult patients according to the WHO Access, Watch and Reserve classification (AWaRe): Results from a worldwide point prevalence survey in 69 countries. J Antimicrob Chemother. 2021;76(6):1614–24.). This research suggests that AWaRe classification might be a more straightforward metric to monitor patterns of antibiotic use and an evaluative antimicrobial stewardship tool to guide institutional and national policy advancement. Reporting proportional AWaRe use aids the assessment of prescriber patterns, highlighting educational gaps, stock-outs, and questions of access and appropriateness, to support guideline recommendations (⁶6. Sharland M, Pulcini C, Harbarth S, Zeng M, Gandra S, Mathur S, et al. Classifying antibiotics in the WHO Essential Medicines List for optimal use—be AWaRe. Lancet Infect Dis. 2018;18(1):18–20., ⁸8. World Health Organization [Internet]. Geneva: WHO; c2022 (accessed 2 July 2022). AWaRe. WHO Antibiotic Categorization. Available from: https://aware.essentialmeds.org/groups
https://aware.essentialmeds.org/groups... ).

However, data on proportional AWaRe use in the English-speaking Caribbean is limited, as countries with PPS data from fewer than three hospitals are sometimes excluded from global analyses (¹⁰10. Pauwels I, Versporten A, Drapier N, Vlieghe E, Goosens H, Global-PPS network. Hospital antibiotic prescribing patterns in adult patients according to the WHO Access, Watch and Reserve classification (AWaRe): Results from a worldwide point prevalence survey in 69 countries. J Antimicrob Chemother. 2021;76(6):1614–24.). Consequently, standardized antimicrobial stewardship program recommendations based on AWaRe are not supported or advanced by data from the subregion; therefore, a study of this type is both novel and timely.

We utilized secondary WHO PPS data from tertiary care institutions obtained between 2013 and 2018 from three CARICOM States that were early adopters of this tool to illustrate and analyze proportional AWaRe use in acute care inpatients. We aim to describe prescriber patterns using this recommended classification system for the most common indications, outlining the strengths and challenges at this level of patient care. In addition, we underline key opportunities for AMR action from the analyses to inform the development of access-centered policy in the Caribbean and contribute to global antimicrobial stewardship activities.

MATERIALS AND METHODS

Study setting and data collection

This retrospective observational study utilized data from previous WHO PPS research carried out in the three countries outlined in Table 1. Institutions were anonymized to avoid overt comparisons. A PAHO-affiliated survey research team at the three hospitals under review (Hospital 1 in 2013, Hospital 2 in 2018, Hospital 3 in 2018) had been established for each institution. There was at least one individual with clinical expertise and familiarity with the setting on each team. Each inpatient at the time of the study was targeted for inclusion unless they did not meet the necessary criteria of the PAHO Hospital Antimicrobial Use PPS (HAMU-PPS) methodology (²2. Pan American Health Organization. WHO/PAHO Hospital Antimicrobial Use Point Prevalence Survey on Antibiotic Use in Hospitals in Latin American and Caribbean Regions. Washington, DC: PAHO; 2018.). Survey data were collected using the Research Electronic Data Capture tool (REDCap) developed by researchers at Vanderbilt University (¹⁵15. Kaiser Permanente Institute for Health Research [Internet]. Aurora, CO: KP; 2018 (accessed 14 July 2021). IHR REDCap. REDCap Security Overview. Available from: http://kpco-ihr.org/redcap/citing.html
http://kpco-ihr.org/redcap/citing.html... ).

Data analysis

All data collected at these hospitals in 2013 and 2018 were analyzed. Descriptive analyses were performed separately for each institution, exporting the data from REDCap to a Microsoft Excel 2016 database (Microsoft Corporation, Redmond, WA) and R software. Categorical variables were presented as frequencies and percentages, and 95% confidence intervals (CI) were calculated. Prevalence of antibiotic use was defined as the ratio of the number of patients on antibiotics to the total number of eligible patients included in the survey sample. Based on the 2019 EML AWaRe criteria, antibiotics were classified as Access, Watch, or Reserve. Antimycotics, antifungals, tuberculosis (TB) drugs, antivirals, intestinal anti-infectives, antimalarials, and other antiprotozoals were not analyzed. Proportional AWaRe use and Access-to-Watch ratios were calculated for each institution’s top ten treatment indications (WHO disease classification). Proportional Access, Watch, and Reserve use was assessed by calculating the number of prescriptions in each category relative to the total number of prescriptions in the top ten clinical indications. A unique prescription was defined as one antibiotic given by one route of administration. The top three antibiotic prescriptions with their AWaRe categories are reported.

Ethical clearance

The data were used under approval from the Ethics Review Committee of PAHO. Each participating ministry and hospital governing body approved the secondary data usage.

RESULTS

The total reported inpatients for Hospital 1 was 312, Hospital 2 had 333, and Hospital 3 had 121. The final data set included 376 prescriptions for the top ten indications in 766 inpatients: 131 in Hospital 1, 177 in Hospital 2, and 68 in Hospital 3. The hospital antibiotic use point prevalence for Hospital 1 was 35.6%, 95% CI (30.5, 41.0); Hospital 2 was 48.6% (43.3, 54.0); and Hospital 3 was 47.1% (38.4, 56.0) (Table 2). Proportional AWaRe use for the top ten indications is outlined in Figure 1 and Table 3. Access group prevalence was 71.0%, 95% CI (62.7, 78.0) in Hospital 1; 57.6% (50.3, 64.7) in Hospital 2; and 63.2% (51.4, 73.7) in Hospital 3. There were no Reserve antibiotics prescribed in any of the institutions.

Top indications

The top ten indications for antibiotic prescription represented 82.4%, 67.6%, and 78.2% of total prescriptions in Hospital 1, 2, and 3, respectively. The Access-to-Watch ratio for the top ten indications was 2.45, 1.36, and 1.72 in Hospital 1, 2, and 3, respectively. Overall, cellulitis, wound, and deep soft tissue not involving bone, not related to surgery (SST-O) was the most common indication for antibiotic prescription in Hospital 1, accounting for 22.1% (n = 29) of top prescriptions. Clinical sepsis (CSEP) was the most common indication for antibiotic prescription in Hospital 2 and 3, accounting for 28.2% (n = 50) of top prescriptions in Hospital 2 and 20.6% (n = 14) in Hospital 3. The most common indication for Watch prescription was SST-O in Hospital 1 and pneumonia (PNEU) in Hospital 2 and 3 (Table 3).

Top prescriptions

Amoxicillin/clavulanic acid (Access), ciprofloxacin (Watch), and metronidazole (Access) were the top three antibiotic prescriptions in Hospital 1, representing 21.4%, 12.6%, and 11.9% of total prescriptions, respectively. Ceftriaxone (Watch), gentamicin (Access), and ampicillin (Access) were the top three antibiotic prescriptions in Hospital 2, representing 20.9%, 10.3%, and 9.1% of total prescriptions, respectively. Amoxicillin/clavulanic acid (Access), cefuroxime (Access), and metronidazole (Access) were the top three antibiotic prescriptions in Hospital 3, representing 18.4%, 18.4%, and 18.4% of total prescriptions, respectively (Figure 2).

DISCUSSION

Access, Watch, and Reserve prescribing

We used the AWaRe classification as a framework to assess narrow- and broad-spectrum antibiotic use patterns in three Caribbean hospitals. To our knowledge, this study is the first to report on proportional AWaRe use in the Caribbean subregion. The alternative of using institutional antimicrobial consumption as a measure poses technical and logistical challenges and excludes pediatric patient populations (⁷7. Hsia Y, Lee BR, Versporten A, Yang Y, Bielicki J, Jackson C, et al. Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries. Lancet Glob Health. 2019;7(7):e861–e871.). One of the goals of the WHO essential medicines campaign is to increase the proportion of antibiotics consumed globally from the Access category to 60% (¹⁶16. World Health Organization. 2021 AWaRe classification [Internet]. Geneva: WHO; 2021. Available from: https://www.who.int/publications/i/item/2021-aware-classification (accessed 5 July 2022).
https://www.who.int/publications/i/item/... ). Based on the reported Access-to-Watch ratios, prescribers in these settings appear to utilize Access medicines more frequently. One limitation of reporting on this Access-to-Watch ratio alone, however, is that it illustrates an oversimplification of AWaRe group usage. For instance, Watch antibiotics were among the top three medicines used overall across these institutions. In Hospital 2 and 3, cephalosporins were the most prescribed antibiotics overall. Ceftriaxone, a third-generation cephalosporin and Watch antibiotic, was prescribed in one-fifth of indications in Hospital 2 (Figure 2). This finding is in keeping with a region-wide PPS and laboratory surveillance study carried out in 2017 in 12 hospitals across nine Caribbean countries and territories (not including those in this study), which revealed that beta-lactams were by far the most-used intravenous antimicrobials, representing 60.6% of those prescribed (¹⁷17. Heinz E, Brindle R, Morgan-McCalla A, Peters K, Thomson NR. Caribbean multi-centre study of Klebsiella pneumoniae: whole-genome sequencing, antimicrobial resistance and virulence factors. Microb Genom. 2019;5(5):e000266.). A significant proportion of the isolates from the same study were resistant to fluoroquinolones and trimethoprim, which represent critical antibiotic classes used in treating Gram-negative priority infections (¹⁷17. Heinz E, Brindle R, Morgan-McCalla A, Peters K, Thomson NR. Caribbean multi-centre study of Klebsiella pneumoniae: whole-genome sequencing, antimicrobial resistance and virulence factors. Microb Genom. 2019;5(5):e000266., ¹⁸18. World Health Organization. Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Geneva: WHO; 2017. Available from: https://apps.who.int/iris/handle/10665/311820
https://apps.who.int/iris/handle/10665/3... ). A high number of Watch antibiotic fluoroquinolone prescriptions for indications such as skin and soft tissue infections and pneumonia (see Table 2) is of particular concern in TB-endemic countries, where these medicines remain crucial in the treatment of multidrug-resistant TB (¹⁹19. Wright J. Audit of missed or delayed antimicrobial drugs. Nurs Times. 2013;109(42):11–14.).

There was no documented use of Reserve antibiotics based on the 2019 AWaRe classification. From a recent global assessment of national EMLs, those of Barbados and Saint Lucia did not contain Reserve antibiotics, and the Guyana national EML included only one (²⁰20. Adekoya I, Maraj D, Steiner L, Yaphe H, Moja L, Magrini N, et al. Comparison of antibiotics included in national essential medicines lists of 138 countries using the WHO Access, Watch, Reserve (AWaRe) classification: a cross-sectional study. Lancet Infect Dis. 2021;21(10):1429–40.). Although these countries have access to antibiotic treatment for priority infections, this lack of Reserve antibiotics is alarming, as countries in the Caribbean are already facing widespread multidrug resistance.

In Hospital 1, fluoroquinolones (the commonest Watch medication used in this institution; 12.6%) predicted carbapenem-resistant Klebsiella pneumoniae carriage in a one-year prevalence study that followed this WHO PPS research in 2013 (²¹21. Forde C, Stierman B, Ramon-Pardo P, dos Santos Y, Singh N. Carbapenem-resistant Klebsiella pneumoniae in Barbados: Driving change in practice at the national level. PLoS One. 2017;12(5):e0176779.). Researchers in a Caribbean-wide, 15-hospital laboratory evaluation of K. pneumoniae describe a high number and diversity of acquired drug resistance in extended-spectrum b-lactamase genes and carbapenemases among isolates (¹⁷17. Heinz E, Brindle R, Morgan-McCalla A, Peters K, Thomson NR. Caribbean multi-centre study of Klebsiella pneumoniae: whole-genome sequencing, antimicrobial resistance and virulence factors. Microb Genom. 2019;5(5):e000266.). Carbapenem-resistant K. pneumoniae is among the WHO critical priority pathogens, and hypervirulent strains may cause severe community-acquired infections such as pneumonia and meningitis (¹⁷17. Heinz E, Brindle R, Morgan-McCalla A, Peters K, Thomson NR. Caribbean multi-centre study of Klebsiella pneumoniae: whole-genome sequencing, antimicrobial resistance and virulence factors. Microb Genom. 2019;5(5):e000266., ²²22. Melot B, Brisse S, Breurec S, Passet V, Malpote E, Lamaury I, et al. Community-acquired meningitis caused by a CG86 hypervirulent Klebsiella pneumoniae strain: First case report in the Caribbean. BMC Infect Dis. 2016;16(1):736.). Carbapenemases increase patient mortality by over 50%, extend hospital stay by almost 50%, and increase the cost of hospitalization by 50% (²³23. Luna CM, Rodriguez-Noriega E, Bavestrello L, Guzmán-Blanco M. Gram-Negative Infections in Adult Intensive Care Units of Latin America and the Caribbean. Crit Care Res Pract. 2014;2014:480463.–²⁶26. Savard P, Carroll KC, Wilson LE, Perl TM. The challenges of carbapenemase-producing Enterobacteriaceae and infection prevention: protecting patients in the chaos. Infect Control Hosp Epidemiol. 2013;34(7):730–9.). Detailed mapping of antibiotic use, coupled with laboratory surveillance to inform locally applicable guidelines, could positively affect patient outcomes. Ultimately, these figures underline the importance of securing Reserve antibiotics on national formularies for use as last-resort options in treating life-threatening MDR infections.

Opportunities in the context of COVID-19

The COVID-19 pandemic presents an opportunity for more comprehensive antimicrobial use surveillance. In the clinical management of COVID-19, increases in unnecessary antimicrobial use could potentiate future AMR risks by driving the selection of multidrug resistant and extensively drug-resistant organisms (⁴4. Hsieh J, Sati H, Ramon-Pardo P, Bruinsma N, Galas MF, Rwangabwoba JM, et al. 2034. Standardized Point Prevalence Survey on Antibiotic Use to Inform Antimicrobial Stewardship Strategies in the Caribbean. Open Forum Infect Dis. 2019;6(Suppl 2):S683–S684., ²⁷27. Majumder MAA, Rahman S, Cohall D, Bharatha A, Singh K, Haque M, et al. Antimicrobial Stewardship: Fighting Antimicrobial Resistance and Protecting Global Public Health. Infect Drug Resist. 2020;13:4713–38.). Through an international web-based survey of physicians involved in the treatment of COVID-19, Beovi et al. (²⁸28. B, Doušak M, Ferreira-Coimbra J, Nadrah K, Rubulotta F, Belliato M, et al. Antibiotic use in patients with COVID-19: a ‘snapshot’ Infectious Diseases International Research Initiative (ID-IRI) survey. J Antimicrob Chemother. 2020;75(11):3386–90.) concluded early in the pandemic that broad-spectrum antibiotic use in patients with COVID-19 was widespread. In a November 2021 Latin America and Caribbean update, PAHO data indicated that over 90% of inpatient COVID-19 cases were treated with antimicrobials, while only 7% had a secondary infection (²⁹29. American Health Organization [Internet]. Washington, DC: PAHO: 2021 Nov 17 (accessed 14 December 2021). Americas report surge in drug-resistant infections due to misuse of antimicrobials during pandemic. Available from: https://www.paho.org/en/news/17-11-2021-americas-report-surge-drug-resistant-infections-due-misuse-antimicrobials-during
https://www.paho.org/en/news/17-11-2021-... ). Among the most common antibiotics used were piperacillin-tazobactam (AWaRe Watch), which Forde et al. demonstrated in 2013 was a predictor for carbapenem-resistant K. pneumoniae carriage in the Caribbean (⁴4. Hsieh J, Sati H, Ramon-Pardo P, Bruinsma N, Galas MF, Rwangabwoba JM, et al. 2034. Standardized Point Prevalence Survey on Antibiotic Use to Inform Antimicrobial Stewardship Strategies in the Caribbean. Open Forum Infect Dis. 2019;6(Suppl 2):S683–S684., ²¹21. Forde C, Stierman B, Ramon-Pardo P, dos Santos Y, Singh N. Carbapenem-resistant Klebsiella pneumoniae in Barbados: Driving change in practice at the national level. PLoS One. 2017;12(5):e0176779.).

Limitations

The increasingly expansive AMR threat requires multilateral, transnational coordination, particularly in the Caribbean—a setting with an interconnected population situated between the regions of North America and South America and considered endemic for several resistant strains (¹⁷17. Heinz E, Brindle R, Morgan-McCalla A, Peters K, Thomson NR. Caribbean multi-centre study of Klebsiella pneumoniae: whole-genome sequencing, antimicrobial resistance and virulence factors. Microb Genom. 2019;5(5):e000266., ³⁰30. García-Betancur JC, Appel TM, Esparza G, Gales AC, Levy-Hara G, Cornistein W, et al. Update on the epidemiology of carbapenemases in Latin America and the Caribbean. Expert Rev Anti Infect Ther. 2021;19(2):197–213.). The findings from this study contribute to a knowledge catalog to address antimicrobial overuse. However, the data we have analyzed are from years ago—approaching a decade for Barbados. Furthermore, at least two of these institutions—through their national action plans and guided by earlier PPS findings—have designed and implemented antimicrobial stewardship programs (²¹21. Forde C, Stierman B, Ramon-Pardo P, dos Santos Y, Singh N. Carbapenem-resistant Klebsiella pneumoniae in Barbados: Driving change in practice at the national level. PLoS One. 2017;12(5):e0176779., ³¹31. Guyana Chronicle [Internet]. Georgetown: Guyana Chronicle; 2019 Sep 24 (accessed 29 August 2022). Antimicrobial resistance programme to roll out this week. Available from: https://guyanachronicle.com/2019/09/24/antimicrobial-resistance-programme-to-roll-out-this-week/.
https://guyanachronicle.com/2019/09/24/a... ). Therefore, revisiting this AWaRe group quality target in evaluating stewardship strategies would be worthwhile.

Another limitation was an inability to disaggregate data to highlight the variation of antibiotic use between community-acquired infection (CAI) and hospital-acquired infection (HAI). These epidemiological data were variably reported using the PPS tool for all three institutions, in keeping with the experiences of other regional investigators. From pilot studies in four Mexican hospitals, Zumaya-Estrada et al. (³²32. Zumaya-Estrada FA, Alpuche-Aranda CM, Saturno-Hernandez PJ. The WHO methodology for point prevalence surveys on antibiotics use in hospitals should be improved: Lessons from pilot studies in four Mexican hospitals. Int J Infect Dis. 2021;108:13–17.) suggest that making estimations and missing HAI/CAI data from WHO PPS could prove misleading. HAI/CAI data remain relevant indicators in antimicrobial use/consumption surveillance, mainly where there are no local guidelines; therefore, improving the capture of this variable in the WHO PPS methodology contributes to public health initiatives.

Conclusion

We have highlighted the patterns of antibiotic use with the WHO AWaRe classification and, in doing so, uncovered opportunities in the new iterations of the WHO PPS methodology, particularly in the COVID-19 pandemic, to interrogate this indicator of quality in healthcare settings in the Caribbean. Our study draws urgent attention to evidence of gaps impacting prudent prescription practices, such as the high proportion of Watch antibiotics and lack of Reserve group antibiotics, providing data that may inform national formulary and antimicrobial stewardship policy-making across the settings analyzed and the wider region. Using the latest iteration of the WHO PPS tool could address shortcomings in data reporting and ensure that critical analyses such as antimicrobial use in HAI/CAI are considered in short- and intermediate-term goal setting. As the WHO Global Policy on AMR emphasizes, regional coordination, such as through CARICOM and its public health arm, may promote AMR research, enhancing the quality of care and health equity.

Disclaimer.

Authors hold sole responsibility for the views expressed in the manuscript, which may not necessarily reflect the opinion or policy of the RPSP/PAJPH and/or those of the Pan American Health Organization (PAHO).

Acknowledgment.

This work was a formal research activity for the MSc International Health and Tropical Medicine dissertation at the University of Oxford, conducted between April and September 2021. It was a collaboration between academics at the University of Oxford and technical experts in the Pan American Health Organization. Dr. Vicki Marsh and Dr. Aronrag Meeyai of the University of Oxford provided academic supervision and guidance toward the design and execution of the research plan. We extend gratitude to the participating countries’ WHO Point Prevalence Survey Investigators Dr. Corey Forde (Barbados), Dr. Jeentendra Mohanlall (Guyana), and Dr. Gemma Chery (Saint Lucia), who granted us permission to revisit these data.

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