ABSTRACT

Objective.

To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia.

Methods.

This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared.

Results.

There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all antibiotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days).

Conclusions.

While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in community-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.

Keywords
Drug resistance, microbial; anti-bacterial agents/therapeutic use; COVID-19; Colombia

RESUMEN

Objetivo.

Evaluar los cambios en la resistencia a los antibióticos de ocho de las combinaciones de fármacos y agentes patógenos incluidos en la lista prioritaria de la Organización Mundial de la Salud y el consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropenem, ciprofloxacina, vancomicina) antes de la pandemia de COVID-19 (de marzo del 2018 a julio del 2019) y durante la pandemia (de marzo del 2020 a julio del 2021) en 31 hospitales del Valle del Cauca (Colombia).

Métodos.

En este estudio se analiza el antes y el después empleando datos recopilados de forma rutinaria. Para el consumo de antibióticos, se compararon las dosis diarias definidas (DDD) por 100 días-cama.

Resultados.

Hubo 23 405 cepas bacterianas aisladas prioritarias con datos sobre la resistencia a los antibióticos. El número total de cepas aisladas aumentó de 9 774 antes de la pandemia a 13 631 durante la pandemia. Si bien la resistencia disminuyó significativamente en las cuatro combinaciones seleccionadas de agentes patógenos y fármacos (Klebsiella pneumoniae, productora de betalactamasa de espectro extendido [BLEE], de 32% a 24%; K. pneumoniae, resistente a los carbapenémicos, de 4% a 2%; Pseudomonas aeruginosa, resistente a los carbapenémicos, de 12% a 8%; Acinetobacter baumannii, resistente a los carbapenémicos, de 23% a 9%), el nivel de resistencia de Enterococcus faecium a la vancomicina aumentó significativamente (de 42% a 57%). No hubo cambios en la resistencia en las tres combinaciones restantes (Staphylococcus aureus, resistente a la meticilina; Escherichia coli, productora de BLEE; E. coli, resistente a los carbapenémicos). El consumo de todos los antibióticos aumentó. Sin embargo, el consumo de meropenem disminuyó en los entornos de las unidades de cuidados intensivos (de 8,2 a 7,1 DDD por 100 días-cama).

Conclusiones.

Aunque el consumo de antibióticos aumentó, se observó una disminución en la resistencia a los antibióticos de cuatro combinaciones de agentes patógenos y medicamentos durante la pandemia, que posiblemente se debió a un aumento en las infecciones adquiridas en la comunidad. Es necesario vigilar el aumento de la resistencia de E. faecium a la vancomicina. Los resultados de este estudio son esenciales para que sirvan de orientación en los programas de optimización del uso de los antibióticos en los entornos hospitalarios de Colombia y en contextos similares en otros lugares.

Palabras clave
Farmacorresistencia microbiana; antibacterianos/uso terapéutico; COVID-19; Colombia

RESUMO

Objetivo.

Avaliar as mudanças na resistência a antibióticos em oito das combinações microrganismo/antimicrobiano prioritárias da Organização Mundial da Saúde e o consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropeném, ciprofloxacino, vancomicina) antes (março de 2018 a julho de 2019) e durante (março de 2020 a julho de 2021) a pandemia de COVID-19 em 31 hospitais em Valle del Cauca, Colômbia.

Métodos.

Este foi um estudo antes/depois utilizando dados coletados rotineiramente. Para avaliar o consumo de antibióticos, foram comparadas doses diárias definidas (DDD) por 100 leitos-dias.

Resultados.

Havia dados sobre resistência a antibióticos para 23.405 isolados bacterianos prioritários. O número total de isolados aumentou de 9.774 para 13.631 antes e durante a pandemia, respectivamente. Embora a resistência tenha diminuído significativamente para quatro das combinações microrganismo/antimicrobiano selecionadas (Klebsiella pneumoniae, produtora de betalactamase de espectro estendido [ESBL], 32% a 24%; K. pneumoniae, resistente a carbapenêmicos, 4% a 2%; Pseudomonas aeruginosa, resistente a carbapenêmicos, 12% a 8%; Acinetobacter baumannii, resistente a carbapenêmicos, 23% a 9%), o nível de resistência de Enterococcus faecium a vancomicina aumentou significativamente (42% a 57%). Não houve mudança na resistência para as três combinações restantes (Staphylococcus aureus, resistente a meticilina; Escherichia coli, produtora de ESBL; E. coli, resistente a carbapenêmicos). O consumo de todos os antibióticos aumentou. Entretanto, o consumo de meropeném nas unidades de terapia intensiva diminuiu (de 8,2 para 7,1 DDD por 100 leitos-dias).

Conclusões.

Embora o consumo de antibióticos tenha aumentado, observou-se uma diminuição na resistência a antibióticos de quatro combinações microrganismo/antimicrobiano durante a pandemia. Isso ocorreu possivelmente devido a um aumento nas infecções adquiridas na comunidade. O aumento da resistência de E. faecium à vancomicina deve ser monitorado. Os achados deste estudo são essenciais para guiar os programas de gerenciamento de antimicrobianos em ambientes hospitalares da Colômbia e em outros contextos similares.

Palavras-chave
Resistência microbiana a medicamentos; antibacterianos/uso terapêutico; COVID-19; Colômbia

Antimicrobial resistance (AMR), the ability of microbes to survive in the presence of antimicrobials, is a major public health problem (¹1. Lim C, Takahashi E, Hongsuwan M, Wuthiekanun V, Thamlikitkul V, Hinjoy S, et al. Epidemiology and burden of multidrug-resistant bacterial infection in a developing country. Elife. 2016 Sep 6;5:e18082.). Worldwide in 2019, AMR was the reason for 4.9 million deaths (²2. Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629–55.), and this is expected to reach 10 million by 2050 (³3. Barchitta M, Quattrocchi A, Maugeri A, La Rosa MC, La Mastra C, Sessa L, et al. Antibiotic Consumption and Resistance during a 3-Year Period in Sicily, Southern Italy. Int J Environ Res Public Health. 2019;16(13):2253.). In addition to its health implications, AMR increases the financial burden on both patients and health systems (³3. Barchitta M, Quattrocchi A, Maugeri A, La Rosa MC, La Mastra C, Sessa L, et al. Antibiotic Consumption and Resistance during a 3-Year Period in Sicily, Southern Italy. Int J Environ Res Public Health. 2019;16(13):2253.).

The primary reason for the emergence and spread of AMR is the inappropriate use of antibiotics. This includes irrational prescribing, inadequate disease prevention and control measures, and poor access to accurate diagnostics (⁴4. Castro-Sánchez E, Moore LSP, Husson F, Holmes AH. What are the factors driving antimicrobial resistance? Perspectives from a public event in London, England. BMC Infect Dis. 2016;16:465. https://doi.org/10.1186/s12879-016-1810-x
https://doi.org/10.1186/s12879-016-1810-... , ⁵5. McEwen SA, Collignon PJ. Antimicrobial Resistance: a One Health Perspective. Microbiol Spectr. 2018;6(2):1–26. https://doi.org/10.1128/microbiolspec.ARBA-0009-2017
https://doi.org/10.1128/microbiolspec.AR... ). Appropriate prescriptions, optimized use of antibiotics, quality diagnosis and treatment, and infection prevention and control are the guiding principles of antimicrobial stewardship programs (⁶6. Getahun H, Smith I, Trivedi K, Paulin S, Balkhy HH. Tackling antimicrobial resistance in the COVID-19 pandemic. Bull World Health Organ [Internet]. 2020 Jul 1 [cited 2022 May 19];98(7):442. https://doi.org/10.2471/blt.20.268573
https://doi.org/10.2471/blt.20.268573... ).

The World Health Organization (WHO) developed a list of priority bacteria and resistance patterns (so-called bug-drug combinations) that should be closely monitored because of their threat to human health. The most critical ones are bacteria that pose a particular threat in hospital and extended-stay facilities, and among patients whose care requires devices such as ventilators and blood catheters (⁷7. World Health Organization [Internet]. Geneva: WHO; 2017 Feb 27 [cited 2022 May 19]. WHO publishes list of bacteria for which new antibiotics are urgently needed. Available from: https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed
https://www.who.int/news/item/27-02-2017... , ⁸8. World Health Organization. GLASS method for estimating attributable mortality of antimicrobial resistant bloodstream infections. Geneva: WHO; 2020;65. Available from: https://www.who.int/publications/i/item/9789240000650
https://www.who.int/publications/i/item/... ). Monitoring the resistance of these priority bacteria to tracer antibiotics is essential to enable corrective actions to be taken.

The unprecedented coronavirus disease 2019 (COVID-19) pandemic has posed a tremendous challenge to health systems, with potential threats that could affect antimicrobial stewardship programs. Prescription of antibiotics for COVID-19 patients when they were not required has been widely documented (⁹9. World Health Organization. Clinical management of COVID-19: interim guidance, 27 May 2020. Geneva: WHO; 2020. Available from: https://apps.who.int/iris/handle/10665/332196
https://apps.who.int/iris/handle/10665/3... –¹²12. Giacomelli A, Ridolfo AL, Oreni L, Vimercati S, Albrecht M, Cattaneo D, et al. Consumption of antibiotics at an Italian university hospital during the early months of the COVID-19 pandemic: Were all antibiotic prescriptions appropriate? Pharmacol Res [Internet]. 2021 Feb 1 [cited 2022 May 20];164:105403. https://doi.org/10.1016/j.phrs.2020.105403
https://doi.org/10.1016/j.phrs.2020.1054... ). The impact of the COVID-19 pandemic on antibiotic consumption has also been reported for different settings. While consumption increased during the pandemic in hospitals in Belgium (¹³13. Van Laethem J, Wuyts S, Van Laere S, Koulalis J, Colman M, Moretti M, et al. Antibiotic prescriptions in the context of suspected bacterial respiratory tract superinfections in the COVID-19 era: a retrospective quantitative analysis of antibiotic consumption and identification of antibiotic prescription drivers. Intern Emerg Med [Internet]. 2022 Jan 1 [cited 2022 May 20];17(1):141–51. https://doi.org/10.1007/s11739-021-02790-0
https://doi.org/10.1007/s11739-021-02790... ), it decreased for infections acquired in the community within Europe (¹⁴14. Högberg LD, Vlahović-Palčevski V, Pereira C, Weist K, Monnet DL; ESAC-Net study group; ESAC-Net study group participants. Decrease in community antibiotic consumption during the COVID-19 pandemic, EU/EEA, 2020. Euro Surveill [Internet]. 2021 Nov 18 [cited 2022 May 20];26(46):2101020. https://doi.org/10.2807/1560-7917.es.2021.26.46.2101020
https://doi.org/10.2807/1560-7917.es.202... ).

In Colombia, like many other settings in the world, AMR is a growing public health problem (¹⁵15. Fleming A, Sáenz V. Resultados de la vigilancia de la resistencia bacteriana, Año 2018, Componente pediátrico y adulto. Boletín Informativo Grebo [Internet]. 2019 [cited 2022 May 19];11. Available from: https://www.grupogrebo.org/wp-content/uploads/2020/02/Boletin-11.pdf
https://www.grupogrebo.org/wp-content/up... , ¹⁶16. Buitrago EM, Hernández C, Pallares C, Pacheco R, Hurtado K, Recalde M. Frecuencia de aislamientos microbiológicos y perfil de resistencia bacteriana en 13 clínicas y hospitales de alta complejidad en Santiago de Cali - Colombia. Infectio [Internet]. 2014;18(1):3–11. https://doi.org/10.1016/S0123-9392(14)70734-9
https://doi.org/10.1016/S0123-9392(14)70... ). Therefore, the Ministry of Health in Colombia developed national guidelines for the clinical management of COVID-19 patients. The guidelines recommend the use of antibiotics only for patients with bacterial coinfection. The guidelines do not recommend specific antibiotics but indicate that the choice of antibiotics should be guided by the result of culture and antibiotic susceptibility testing (¹⁷17. Monnet DL, Harbarth S. Will coronavirus disease (COVID-19) have an impact on antimicrobial resistance? Euro Surveill [Internet]. 2020;25(45):1–6. https://doi.org/10.2807/1560-7917.ES.2020.25.45.2001886
https://doi.org/10.2807/1560-7917.ES.202... ).

However, during the early phase of the pandemic, government initiatives in Latin America suggested that early initiation of antibiotics for COVID-19 patients was useful, irrespective of the clinical suspicion of bacterial coinfection (¹⁸18. Honduras, Gobierno de la República, Salud [Internet]. Tegucigalpa: Gobierno de la República; 2020 Jun 3 [cited 2022 May 19]. Gobierno envía los primeros 22.000 tratamientos Maíz y Catracho para atender a pacientes de covid-19. Available from: https://www.salud.gob.hn/site/index.php/component/k2/item/1708-gobierno-envia-los-primeros-22–000-tratamientos-maiz-y-catracho-para-atender-a-pacientes-de-covid-19
https://www.salud.gob.hn/site/index.php/... ). This has raised concern that such practices might have led to the irrational use of antibiotics, especially those most frequently used in Colombia (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, and vancomycin) (¹⁹19. Colombia, Instituto Nacional de Salud. Consumo de antibióticos en el ámbito hospitalario. Bogotá: INS; 2019.). These antibiotics are in the Watch category (these are antibiotics with a higher potential to develop resistance, and their use as first and second choice treatment should be limited) of the WHO AwaRe categories, and their use should be closely monitored (²⁰20. World Health Organization [Internet]. Geneva: WHO; c2022 [cited 2022 May 19]. WHO Antibiotic Categorization. Available from: https://aware.essentialmeds.org/groups
https://aware.essentialmeds.org/groups... ). During COVID-19, data from the National Institute of Health of Colombia show an increase in the consumption of broad-spectrum antibiotics, especially in intensive care units (ICUs) (²¹21. Colombia, Instituto Nacional de Salud. Consumo de antibioticos 2021. Bogotá: INS; 2022.).

To date, there has been no published study from Colombia assessing whether there was a change in bacterial resistance and consumption of antibiotics before and during the COVID-19 pandemic. Therefore, this study was carried out to assess the change in antibiotic resistance of selected priority bug-drug combinations and the consumption of commonly used antibiotics before and during the COVID-19 pandemic in tertiary-level hospitals of Valle del Cauca, Colombia.

MATERIALS AND METHODS

Study design, period, and population

This was a before and after study using routinely collected secondary surveillance data.¹1Data are available upon request to the corresponding author. The study period included “before” (1 March 2018 to 31 July 2019) and “during” (1 March 2020 to 31 July 2021) the COVID-19 pandemic in Valle del Cauca, western Colombia. Bacterial isolates for six priority bacteria (commonly found in Colombia) were included, with data available on resistance to the tracer antibiotic(s) (Table 1) from all 31 tertiary-level hospitals in Valle del Cauca. Included were isolates from blood, respiratory specimens (sputum, bronchial lavage), and cerebrospinal fluid (CSF). For antibiotic consumption, aggregate consumption data were used (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) separately for the before and during COVID-19 pandemic period.

Setting

The 31 tertiary hospitals in Valle del Cauca included 25 private and 6 public hospitals. Twenty-four of the study hospitals were located in the principal/capital city of Valle del Cauca (Santiago de Cali, home to 51% of Valle del Cauca’s population), serving a population of approximately 2.8 million, while 7 were from other surrounding cities. These 31 hospitals had 1 114 ICU beds (74% in the principal city and 26% in the other cities) and 3 254 non-ICU beds (81% in the principal city and 19% in the other cities). In the 17-month study period “during” the COVID-19 pandemic, there were 383 348 reported COVID-19 cases and 11 193 reported COVID-19 deaths in Valle del Cauca (²²22. Gobernación del Valle del Cauca [Internet]. Cali: Gobernación del Valle del Cauca; 2021 [cited 2022 May 23]. Boletines Covid-19 Año 2021; 7. Mes de julio de 2021 [Internet]. Available from: https://www.valledelcauca.gov.co/documentos/13130/7-mes-de-julio-de-2021/.
https://www.valledelcauca.gov.co/documen... ).

Surveillance of bacterial resistance. In 2012, the National Institute of Health of Colombia established the surveillance of all pathogens responsible for infections in hospitals. All laboratories from secondary and tertiary level institutions (public and private) contribute to the surveillance. Each institution also submits data to the WHONET microorganism database every month, which includes all isolates showing growth from all samples sent for testing, including bacterial species, sample type, and all the useful antibiotics to treat the bacteria, and the tests undertaken according to the Clinical and Laboratory Standards Institute (CLSI) guidance (²³23. Clinical and Laboratory Standards Institute. M100 Performance Standards for Antimicrobial Susceptibility Testing. 31st edition. Berwyn, PA: CLSI; 2021 Mar [cited 2022 May 20]; Available from: https://www.clsi.org
https://www.clsi.org... , ²⁴24. Colombia, Instituto Nacional de Salud. Resistencia bacteriana en el ámbito hospitalario. Bogotá: INS; 2018.).

Surveillance of antimicrobial consumption. Surveillance of the consumption of the main antibiotics used in hospital practice was established in 2012. The antibiotics under surveillance are all those for systemic use (ATC J01) (¹⁶16. Buitrago EM, Hernández C, Pallares C, Pacheco R, Hurtado K, Recalde M. Frecuencia de aislamientos microbiológicos y perfil de resistencia bacteriana en 13 clínicas y hospitales de alta complejidad en Santiago de Cali - Colombia. Infectio [Internet]. 2014;18(1):3–11. https://doi.org/10.1016/S0123-9392(14)70734-9
https://doi.org/10.1016/S0123-9392(14)70... , ²⁵25. Baditoiu L, Axente C, Lungeanu D, Muntean D, Horhat F, Moldovan R, et al. Intensive care antibiotic consumption and resistance patterns: a cross-correlation analysis. Ann Clin Microbiol Antimicrob. 2017;16:71.). The surveillance reports are received from institutional laboratories of tertiary institutions monthly and are consolidated from the municipal territorial entities.

The daily defined dose (DDD) is the standard medicine unit of measure, the average corresponding to the maintenance dose per day expected for the main indication of a medicine in adults. The formula for calculating DDD per 100 bed-days is as follows (²⁴24. Colombia, Instituto Nacional de Salud. Resistencia bacteriana en el ámbito hospitalario. Bogotá: INS; 2018.):

Data extraction

For the eight bug-drug combinations (Table 1), individual isolate level microbiological data were extracted from the WHONET database at the Valle del Cauca Secretariat of Health. The first isolate per patient and per sample reported were utilized to determine susceptibility. Repeat isolates were excluded. If a patient had more than one priority bacteria in the specimen (Table 1), all the bacteria were considered for the analysis. Antibiotic consumption data were extracted from the antibiotic consumption database of Valle del Cauca.

Statistical analysis

Data were analyzed using SPSS software (IBM Corp., Armonk, NY). Resistance to a bug-drug combination was defined as the number (%) of priority bacterial isolates with resistance to the tracer antibiotic(s) (Table 1). For each of the eight bug-drug combinations, the “before and during” percentage of resistance were compared overall, as well as stratified by specimen type and the location (within or outside the principal city) and type (public/private) of hospital, using the Z-test for proportions. Significance levels were set at p < 0.05.

The consumption data were calculated using the DDD per 100 bed-days for each antibiotic under surveillance for each month of the year. The “before and during” consumption for each antibiotic (DDD per 100 bed-days), overall and stratified by the type and location of hospital, are reported.

Ethics

Clearance was provided by the Valle del Cauca Secretariat of Health to obtain all data, and ethical approval was granted by the Institutional Review Board of the Valle del Cauca Secretariat of Health (No. 18-21, dated 3 November 2021) and The Union Ethics Advisory Group, Paris (No. 22/21, dated 2 September 2021).

RESULTS

Characteristics of priority bacterial isolates

There were 23 405 priority bacterial isolates with data available on resistance to the tracer antibiotic(s). The distribution by bacterial isolate type, period (before and during the COVID-19 pandemic), specimen type, hospital location and type are shown in Table 2. The total number of isolates increased from 9 774 before the pandemic to 13 631 during the pandemic (a 40% increase). The largest proportion of isolates from both before/during the pandemic were from blood specimens. The most common bacteria isolated in both periods was Klebsiella pneumoniae. The proportion of isolates reported from private hospitals increased from 75% before the pandemic to 82% during the pandemic.

Bug-drug combination resistance

During the pandemic, out of the eight bug-drug combinations, there was no change in resistance for three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant) when compared to before the pandemic. The resistance levels significantly changed for five bug-drug combinations. While the level of resistance for four selected bug-drug combinations significantly decreased (K. pneumoniae, ESBL-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%) (Table 3).

The significant change in the level of resistance of the five bug-drug combinations was also observed when stratifying bacterial isolates by specimen (blood, respiratory, and CSF). The exception was for K. pneumoniae isolates obtained from respiratory specimens, where no change was observed in the resistance to carbapenem during the two periods (Table 3).

The significant overall change in the level of resistance of the five bug-drug combinations was also observed in principal city hospitals and private hospitals. The overall decreasing resistance of P. aeruginosa to carbapenem and A. baumannii to carbapenem was also observed in public hospitals. A significant increase in resistance of P. aeruginosa to carbapenem was observed in hospitals located in other cities (Table 4).

Antibiotic consumption

The consumption of antibiotics increased in ICUs during the pandemic, except for meropenem. In both the private and public facilities, the use of meropenem decreased from 23.6/DDD bed-days before to 18.5/DDD bed-days during the pandemic. In non-ICU settings, the overall consumption of all selected antibiotics, except meropenem, increased during the pandemic (Table 5).

DISCUSSION

This is the first study from Colombia to document the change in resistance of selected bug-drug combinations and the consumption of frequently used antibiotics during the COVID-19 pandemic.

Overall, there was an increase in the absolute number of bacterial isolates during the pandemic when compared to before; this could be attributed to an increase in community-acquired infections related to COVID-19. There is a growing number of reports of bacterial infections acquired by patients with severe COVID-19 (²⁶26. O’Toole RF. The interface between COVID-19 and bacterial healthcare-associated infections. Clin Microbiol Infect [Internet]. 2021 Dec [cited 2022 May 24];27(12):1772–6. https://doi.org/10.1016/j.cmi.2021.06.001
https://doi.org/10.1016/j.cmi.2021.06.00... , ²⁷27. Kariyawasam RM, Julien DA, Jelinski DC, Larose SL, Rennert-May E, Conly JM, et al. Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019–June 2021). Antimicrob Resist Infect Control [Internet]. 2022;11(1):45. https://doi.org/10.1186/s13756-022-01085-z
https://doi.org/10.1186/s13756-022-01085... ). Another possible reason for the increase in isolates could be the high number of invasive procedures performed on COVID-19 patients, which could lead to increased risk of bacterial infection.

We observed a decrease in the prevalence of resistance in four of the eight bug-drug combinations: K. pneumoniae, ESBL-producing; K. pneumoniae, carbapenem-resistant; P. aeruginosa, carbapenem-resistant; and A. baumannii, carbapenem-resistant—especially when bacteria were isolated from blood (²⁸28. van Duin D, Barlow G, Nathwani D. The impact of the COVID-19 pandemic on antimicrobial resistance: a debate. JAC Antimicrob Resist. 2020 Sep;2(3):dlaa053.–³⁰30. Rodríguez-Baño J, Rossolini GM, Schultsz C, Tacconelli E, Murthy S, Ohmagari N, et al. Key considerations on the potential impacts of the COVID-19 pandemic on antimicrobial resistance research and surveillance. Trans R Soc Trop Med Hyg [Internet]. 2021 Oct 1 [cited 2022 May 23];115(10):1122–9. https://doi.org/10.1093/trstmh/trab048
https://doi.org/10.1093/trstmh/trab048... ). Other studies have also reported a decrease in antibiotic resistance during the COVID-19 pandemic, especially for Gram-negative bacteria (²⁷27. Kariyawasam RM, Julien DA, Jelinski DC, Larose SL, Rennert-May E, Conly JM, et al. Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019–June 2021). Antimicrob Resist Infect Control [Internet]. 2022;11(1):45. https://doi.org/10.1186/s13756-022-01085-z
https://doi.org/10.1186/s13756-022-01085... , ³¹31. Hamidi AA, Yilmaz Ş. Antibiotic consumption in the hospital during COVID-19 pandemic, distribution of bacterial agents and antimicrobial resistance: A single-center study. J Surg Med. 2021;5(2):124–7.). In all four bug-drug combinations, the increase in isolates from the principal city (likely more community-acquired infection during COVID-19) possibly resulted in a decrease in resistance (³²32. Ho PL, Cheng VCC, Chu CM. Antibiotic resistance in community-acquired pneumonia caused by Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and Acinetobacter baumannii. Chest [Internet]. 2009 Oct [cited 2022 May 25];136(4):1119–27. https://doi.org/10.1378/chest.09-0285
https://doi.org/10.1378/chest.09-0285... , ³³33. Mancini A, Pucciarelli S, Lombardi FE, Barocci S, Pauri P, Lodolini S. Differences between Community - and Hospital - acquired urinary tract infections in a tertiary care hospital. New Microbiol [Internet]. 2020 Jan [cited 2022 May 25];43(1):17–21. Available from: https://pubmed.ncbi.nlm.nih.gov/31814033/.
https://pubmed.ncbi.nlm.nih.gov/31814033... ). Additionally, COVID-19-related policies such as social distancing, mobility restrictions, promotion of hand hygiene, and adherence to contact and respiratory precautions may have contributed to a decrease in the transmission of resistant bacteria.

Conversely, we found a significant increase in the prevalence of E. faecium vancomycin resistance. E. faecium spreads primarily by direct person-to-person contact (including healthcare personnel) and is a common hospital-acquired infection (²⁹29. Collignon P, Beggs JJ. CON: COVID-19 will not result in increased antimicrobial resistance prevalence. JAC Antimicrob Resist. 2020 Sep;2(3):dlaa051.). An increased resistance of this bug-drug combination has been linked to hospital outbreaks (³⁴34. Chamieh A, Zgheib R, El-Sawalhi S, Yammine L, El-Hajj G, Zmerli O, et al. Trends of Multidrug-Resistant Pathogens, Difficult to Treat Bloodstream Infections, and Antimicrobial Consumption at a Tertiary Care Center in Lebanon from 2015-2020: COVID-19 Aftermath. Antibiotics (Basel) [Internet]. 2021 Aug 21 [cited 2022 May 24];10(8):1016. https://doi.org/10.3390/antibiotics10081016
https://doi.org/10.3390/antibiotics10081... , ³⁵35. Kampmeier S, Tönnies H, Correa-Martinez CL, Mellmann A, Schwierzeck V. A nosocomial cluster of vancomycin resistant enterococci among COVID-19 patients in an intensive care unit. Antimicrob Resist Infect Control [Internet]. 2020 Sep 22 [cited 2022 May 24];9(1):154. https://doi.org/10.1186/s13756-020-00820-8
https://doi.org/10.1186/s13756-020-00820... ). In Colombia, E. faecium vancomycin resistance has been a growing problem (¹⁶16. Buitrago EM, Hernández C, Pallares C, Pacheco R, Hurtado K, Recalde M. Frecuencia de aislamientos microbiológicos y perfil de resistencia bacteriana en 13 clínicas y hospitales de alta complejidad en Santiago de Cali - Colombia. Infectio [Internet]. 2014;18(1):3–11. https://doi.org/10.1016/S0123-9392(14)70734-9
https://doi.org/10.1016/S0123-9392(14)70... ). This requires vigilant infection control measures and close monitoring.

In bacterial isolates obtained from hospitals located in other cities, the only significant change observed in our study was the increase in the prevalence of carbapenem-resistant P. aeruginosa. The resistance of this bug-drug combination needs to be monitored over time and measures implemented to limit worsening resistance.

For antibiotic consumption, we observed an increase in the consumption of all antibiotics in all study hospitals during the pandemic in ICU and non-ICU settings, except for meropenem in ICU settings. The most noticeable increase was for piperacillin/tazobactam. It is a broad-spectrum antibiotic that offers coverage against Gram-positive and Gram-negative bacteria, including anaerobes, which makes it attractive for use in pneumonia. It has been widely recommended for use in COVID-19 with bacterial coinfections (³⁶36. Beović 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 [Internet]. 2020 Nov 1 [cited 2022 May 23];75(11):3386–90. https://doi.org/10.1093/jac/dkaa326.
https://doi.org/10.1093/jac/dkaa326... ). Meropenem consumption decreased in both private and public hospitals during the pandemic. The decreased utilization of meropenem may lead to a decrease in resistance for the four drug-bug combinations. An increase in the consumption of antibiotics during the COVID-19 pandemic has been reported by others (³¹31. Hamidi AA, Yilmaz Ş. Antibiotic consumption in the hospital during COVID-19 pandemic, distribution of bacterial agents and antimicrobial resistance: A single-center study. J Surg Med. 2021;5(2):124–7.).

Finally, an important operational finding was the lack of data on the use of ciprofloxacin in ICUs, which precluded assessing its consumption in this setting. Ciprofloxacin is a broad-spectrum antibiotic frequently used in ICU and non-ICU settings. Monitoring the use of ciprofloxacin, particularly in ICU settings, should be improved, and measures to ensure completeness of data on its use and consumption need to be undertaken.

The information provided by this study is essential to inform antimicrobial stewardship programs in hospitals in Colombia and similar contexts elsewhere.

Strengths and limitations

The study limitations are as follows. First, as this study involved secondary data, routine data collection errors cannot be ruled out. Second, we did not investigate whether the increase in consumption of antibiotics was rational and followed the results of culture and susceptibility testing, which was beyond the scope of this study. Third, the study did not include clinical data to disaggregate the isolates by community- and hospital-acquired infections and by COVID-19 and non-COVID-19 patients, or for detecting outbreaks. However, such data are not routinely reported through WHONET, from which data for this study were sourced. Fourth, we did not investigate other factors that might have an impact on resistance, such as change of type of hospitalized patients, access to diagnostic tests, or adherence to contact isolation strategies (¹⁷17. Monnet DL, Harbarth S. Will coronavirus disease (COVID-19) have an impact on antimicrobial resistance? Euro Surveill [Internet]. 2020;25(45):1–6. https://doi.org/10.2807/1560-7917.ES.2020.25.45.2001886
https://doi.org/10.2807/1560-7917.ES.202... , ³⁷37. Rawson TM, Moore LSP, Castro-Sanchez E, Charani E, Davies F, Satta G, et al. COVID-19 and the potential long-term impact on antimicrobial resistance. J Antimicrob Chemother. 2020 Jul 1;75(7):1681–4., ³⁸38. Cantón R, Gijón D, Ruiz-Garbajosa P. Antimicrobial resistance in ICUs: an update in the light of the COVID-19 pandemic. Curr Opin Crit Care. 2020;26(5):433–41.). Finally, there was a lack of data on the use of ciprofloxacin in ICUs in the antibiotic consumption database.

Our study had several strengths. First, data were collected from hospitals under routine surveillance. We believe the findings reflect the operational reality on the ground. Second, we have included a relatively large sample size of bacterial isolates before and during the pandemic. Third, all the tests for antibiotic resistance in bacterial isolates were performed in well-equipped laboratories under surveillance. Resistance testing was completed according to CLSI guidance (²³23. Clinical and Laboratory Standards Institute. M100 Performance Standards for Antimicrobial Susceptibility Testing. 31st edition. Berwyn, PA: CLSI; 2021 Mar [cited 2022 May 20]; Available from: https://www.clsi.org
https://www.clsi.org... , ²⁴24. Colombia, Instituto Nacional de Salud. Resistencia bacteriana en el ámbito hospitalario. Bogotá: INS; 2018.). Finally, we adhered to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for reporting observational studies (³⁹39. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7.).

Conclusion

This study can serve as a baseline in Colombia for assessing the change in resistance of priority bacteria to tracer antibiotics. We recommend that similar studies be carried out in other parts of Colombia to confirm our findings.

While our study demonstrated an increasing consumption of antibiotics during the COVID-19 pandemic, we found an overall reduction in the prevalence of resistance for the selected bug-drug combinations. This was possibly due to an increase in community-acquired infections among patients admitted with moderate to severe COVID-19.

Based on the findings of this study and elsewhere, it is important to develop national-level strategies for antimicrobial stewardship and for the implementation and monitoring of all related measures, to reduce both the clinical and social burden of AMR. This is especially important in the current phase of the COVID-19 pandemic, where we are witnessing an epidemiologic transition to ongoing endemic pathology.

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 the Pan American Health Organization.

Acknowledgment.

This research was conducted through the Structured Operational Research and Training Initiative (SORT IT), a global partnership coordinated by TDR, the Special Program for Research and Training in Tropical Diseases at the World Health Organization. The specific SORT IT program that led to these publication included a partnership of TDR with the WHO Country offices in Colombia and Ecuador and the Regional Office for the Americas of the World Health Organization (the Pan American Health Organization) and was implemented along with the nongovernmental organization Tuberculosis Research and Prevention Center, Armenia; The International Union Against Tuberculosis and Lung Diseases, Paris and South East Asia offices; Médecins sans Frontières–Luxembourg; Médecins sans Frontières–United States of America; ICMR–National Institute of Epidemiology, Chennai, India; Sustainable Health Systems, Freetown, Sierra Leone; Institute of Tropical Medicine, Antwerp, Belgium; the University of Washington, Seattle, United States of America; Damien Foundation, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER); GMERS Medical College, Baroda, India; Sri Manakula Vinayagar Medical College, India; Universidade Federal de Ciencias da Saude de Porto Alegre, Brazil; Ministry of Health of Peru; Universidade de Brasília, Brazil; Central University of Ecuador; Quadram Institute, Norwich, United Kingdom; Universidad de los Andes, Colombia; and California State University, Fullerton, United States of America.

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