Actualización sobre la resistencia antimicrobiana en instituciones de salud de nivel III y IV en Colombia entre enero del 2018 y diciembre del 2021

Introducción. El comportamiento de la resistencia antimicrobiana es fundamental en el mejoramiento y ajuste de los programas de optimización de uso de antimicrobianos, la implementación de las guías terapéuticas y las precauciones que limitan la transmisión cruzada de bacterias resistentes entre pacientes. Desde el inicio del 2020, la pandemia del SARS-CoV-2 desafió profundamente al sistema de salud y, según algunos reportes, aumentó las tasas de resistencia antimicrobiana. Objetivo. Describir el comportamiento de la resistencia antimicrobiana en los microrganismos más frecuentes en veinte hospitales colombianos durante el periodo 2018-2021. Materiales y métodos. Se trata de un estudio descriptivo basado en la información microbiológica reportada por veinte instituciones de salud de nivel III y IV, entre enero de 2018 y diciembre de 2021, en doce ciudades de Colombia, las cuales hacen parte del "Grupo para el estudio de la resistencia nosocomial en Colombia", liderado por la Universidad El Bosque. La identificación de género y especie de los microorganismos más frecuentes, junto con su perfil de resistencia frente a antibióticos marcadores, se determinaron mediante el análisis de los datos vía WHONET. Resultados. En general, los 10 microorganismos más frecuentes analizados a lo largo de los 4 años no presentaron cambios estadísticamente significativos en sus perfiles de resistencia durante los cuatro años del periodo evaluado, de 2018 a 2021. En contraste, Pseudomonas aeruginosa aumentó su resistencia frente a piperacilinatazobactam y carbapenémicos, lo cual fue estadísticamente significativo. Conclusiones. Los cambios en la resistencia antimicrobiana en estos años no han sido estadísticamente significativos, excepto para P. aeruginosa, bacteria que mostró un incremento en las tasas de resistencia a piperacilina-tazobactam y carbapenémicos.

Introduction. Antimicrobial resistance surveillance is a fundamental tool for the development, improvement, and adjustment of antimicrobial stewardship programs, therapeutic guidelines, and universal precautions to limit the cross-transmission of resistant bacteria between patients. Since the beginning of 2020, the SARS-CoV-2 pandemic profoundly challenged the health system and, according to some reports, increased the rates of antimicrobial resistance. Objective. To describe the behavior of antimicrobial resistance of the most frequent bacterial pathogens in twenty Colombian hospitals from January 2018 to December 2021. Materials and methods. We conducted a descriptive study based on the microbiological information recorded from January 2018 to December 2021 in twenty levels III and IV health institutions in twelve Colombian cities. We identified the species of the ten most frequent bacteria along with their resistance profile to the antibiotic markers after analyzing the data through WHONET. Results. We found no statistically significant changes in most pathogens' resistance profiles from January 2018 to December 2021. Only Pseudomonas aeruginosa had a statistically significant increase in its resistance profile, particularly to piperacillin/ tazobactam and carbapenems. Conclusions. The changes in antimicrobial resistance in these four years were not statistically significant except for P. aeruginosa to piperacillin/tazobactam and carbapenems.

Update of antimicrobial resistance in level III and IV health institutions in Colombia between January 2018 and December 2021 / Actualización sobre la resistencia antimicrobiana en instituciones de salud de nivel III y IV en Colombia entre enero del 2018 y diciembre del 2021

Introduction: Antimicrobial resistance surveillance is a fundamental tool for the development, improvement, and adjustment of antimicrobial stewardship programs, therapeutic guidelines, and universal precautions to limit the cross-transmission of resistant bacteria between patients. Since the beginning of 2020, the SARS-CoV-2 pandemic profoundly challenged the health system and, according to some reports, increased the rates of antimicrobial resistance. Objective: To describe the behavior of antimicrobial resistance of the most frequent bacterial pathogens in twenty Colombian hospitals from January 2018 to December 2021. Materials and methods: We conducted a descriptive study based on the microbiological information recorded from January 2018 to December 2021 in twenty levels III and IV health institutions in twelve Colombian cities. We identified the species of the ten most frequent bacteria along with their resistance profile to the antibiotic markers after analyzing the data through WHONET. Results: We found no statistically significant changes in most pathogens' resistance profiles from January 2018 to December 2021. Only Pseudomonas aeruginosa had a statistically significant increase in its resistance profile, particularly to piperacillin/tazobactam and carbapenems. Conclusions: The changes in antimicrobial resistance in these four years were not statistically significant except for P. aeruginosa to piperacillin/tazobactam and carbapenems.

Introducción: El comportamiento de la resistencia antimicrobiana es fundamental en el mejoramiento y ajuste de los programas de optimización de uso de antimicrobianos, la implementación de las guías terapéuticas y las precauciones que limitan la transmisión cruzada de bacterias resistentes entre pacientes. Desde el inicio del 2020, la pandemia del SARS-CoV-2 desafió profundamente al sistema de salud y, según algunos reportes, aumentó las tasas de resistencia antimicrobiana. OBJETIVO: Describir el comportamiento de la resistencia antimicrobiana en los microrganismos más frecuentes en veinte hospitales colombianos durante el periodo 2018-2021. Materiales y métodos: Se trata de un estudio descriptivo basado en la información microbiológica reportada por veinte instituciones de salud de nivel III y IV, entre enero de 2018 y diciembre de 2021, en doce ciudades de Colombia, las cuales hacen parte del "Grupo para el estudio de la resistencia nosocomial en Colombia", liderado por la Universidad El Bosque. La identificación de género y especie de los microorganismos más frecuentes, junto con su perfil de resistencia frente a antibióticos marcadores, se determinaron mediante el análisis de los datos vía WHONET. RESULTADOS: En general, los 10 microorganismos más frecuentes analizados a lo largo de los 4 años no presentaron cambios estadísticamente significativos en sus perfiles de resistencia durante los cuatro años del periodo evaluado, de 2018 a 2021. En contraste, Pseudomonas aeruginosa aumentó su resistencia frente a piperacilina-tazobactam y carbapenémicos, lo cual fue estadísticamente significativo. CONCLUSIONES: Los cambios en la resistencia antimicrobiana en estos años no han sido estadísticamente significativos, excepto para P. aeruginosa, bacteria que mostró un incremento en las tasas de resistencia a piperacilina-tazobactam y carbapenémicos.

Antimicrobial Stewardship Programs in Latin America and the Caribbean: A Story of Perseverance, Challenges, and Goals.

Antimicrobial resistance is one of the major global health threats. Antimicrobial stewardship (AMS) has been set as a priority within international action plans to combat this issue. The region of Latin America and the Caribbean are recognized for their high antimicrobial resistance rates; nevertheless, a low number of studies describing implemented interventions for this topic have been published. This review aims to provide an overview of the status of AMS in our region, focusing on the main progress achieved and describing the different published efforts made by countries towards the implementation of antimicrobial stewardship programs (ASP). Common areas of intervention included were (a) education approaches, (b) antimicrobial guideline implementation and monitoring, (c) diagnostic stewardship, (d) technological tools: electronic clinical decision support systems in AMS, (e) pharmacy-driven protocols and collaborative practice agreements, and (f) economic impact. The search demonstrated the varied interventions implemented in diverse healthcare settings; the results accentuate their influence on antimicrobial consumption, antimicrobial resistance, clinical outcomes, and direct economic impact. The integration of multiple strategies within each hospital was highlighted as an essential key to ASP success. Even though the literature found demonstrated clear progress, there is still a special need for strengthening leadership from the top down, defining goals based on needs, and gaining support through policy and financing in LAC.

Antimicrobial stewardship programs in seven Latin American countries: facing the challenges.

BACKGROUND: Studies have shown that more than 50% of the antibiotics used in hospitals are unnecessary or inappropriate and, that antimicrobial resistance may cost up to 20 billion USD in excess medical costs each year. On the other hand, Antimicrobial Stewardship Programs (ASP) significantly reduce inappropriate antimicrobial use, emergence of antimicrobial resistance, healthcare associated infections, and costs in hospital settings. OBJECTIVE: To evaluate the development of ASP and antibiotic savings in 7 Latin American hospitals using standardized quantitative indicators in all the participating health care institutions. METHODS: An interventional study was conducted, where pre- and post- evaluations were performed using a standardized score tool adapted from the Joint Commission International accreditation standards and, the Colombian Institute of Technical Standards and Certification. We evaluated ASP from 7 Latin American hospitals between 2019 and 2020. A pre-intervention evaluation was done in each hospital to quantify the degree of development of the ASP (ASP Development score). Based on these results, tailored on-site training was implemented in each hospital, followed by a post-intervention evaluation to quantify improvement of ASP-development indicators. In addition, monetary savings in antimicrobials derived from the ASP intervention were estimated. RESULTS: In the pre-intervention evaluation, the average ASP development score for the 7 institutions was 65.8% (40-94.3%). The items with the lowest development score were those related to monitoring and communicating the ASP progress and success. For the post-intervention evaluation, 2 institutions couldn't participate due to the pressure imposed by the COVID-19 pandemic. For the remaining 5/7 hospitals, the average ASP development score was 82.3% with an increase of 12.0% when compared to the pre-intervention measurement of the same institutions (average pre-intervention score 70.3% (48.2%-94.3%) The items with a significant increase were key performance indicators, AMS education and training of the prescribers. Three of the seven (3/7) hospitals reported antibiotic monetary savings associated to the ASP intervention. CONCLUSIONS: The use of the tool described shown to be useful to evaluate specific areas of ASP-development that were lacking and tailor interventions for the participating hospitals, consequently, it helped improve ASP-development in the institutions that underwent pre- intervention and post-intervention analysis. In addition, the strategies showed monetary savings on antimicrobial costs when measured.

Rapid Diagnostic Test Value and Implementation in Antimicrobial Stewardship Across Low-to-Middle and High-Income Countries: A Mixed-Methods Review.

Despite technological advancements in infectious disease rapid diagnostic tests (RDTs) and use to direct therapy at the per-patient level, RDT utilisation in antimicrobial stewardship programmes (ASPs) is variable across low-to-middle income and high-income countries. Key insights from a panel of seven infectious disease experts from Colombia, Japan, Nigeria, Thailand, the UK, and the USA, combined with evidence from a literature review, were used to assess the value of RDTs in ASPs. From this, a value framework is proposed which aims to define the benefits of RDT use in ASPs, separate from per-patient benefits. Expert insights highlight that, to realise the value of RDTs within ASPs, effective implementation is key; actionable advice for choosing an RDT is proposed. Experts advocate the inclusion of RDTs in the World Health Organization Model List of essential in vitro diagnostics and in iterative development of national action plans.

Identification of mcr-1 Genes and Characterization of Resistance Mechanisms to Colistin in Escherichia coli Isolates from Colombian Hospitals.

We report the presence of the mcr-1 gene among 880 Escherichia coli clinical isolates collected in 13 hospitals from 12 Colombian cities between 2016 and 2019. Seven (0.8%) isolates were colistin resistant (MIC ≥ 4 µg/mL). These colistin-resistant isolates were screened for the presence of the mcr-1 gene; five carried the gene. These five isolates were subjected to whole genome sequencing (WGS) to identify additional resistomes and their ST. In addition, antimicrobial susceptibility testing revealed that all E. coli isolates carrying mcr-1 were susceptible to third generation-cephalosporin and carbapenems, except one, which carried an extended-spectrum ß-lactamase (CTX-M-55), along with the fosfomycin resistance encoding gene, fosA. WGS indicated that these isolates belonged to four distinct sequence types (ST58, ST46, ST393, and a newly described ST14315) and to phylogroups B1, A, and D. In this geographic region, the spread of mcr-1 in E. coli is low and has not been inserted into high-risk clones such as ST131, which has been present in the country longer.

Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals.

Ceftazidime-avibactam (CZA) is the combination of a third-generation cephalosporin and a new non-ß-lactam ß-lactamase inhibitor capable of inactivating class A, C, and some D ß-lactamases. From a collection of 2,727 clinical isolates of Enterobacterales (n = 2,235) and P. aeruginosa (n = 492) that were collected between 2016 and 2017 from five Latin American countries, we investigated the molecular resistance mechanisms to CZA of 127 (18/2,235 [0.8%] Enterobacterales and 109/492 [22.1%] P. aeruginosa). First, by qPCR for the presence of genes encoding KPC, NDM, VIM, IMP, OXA-48-like, and SPM-1 carbapenemases, and second, by whole-genome sequencing (WGS). From the CZA-resistant isolates, MBL-encoding genes were detected in all 18 Enterobacterales and 42/109 P. aeruginosa isolates, explaining their resistant phenotype. Resistant isolates that yielded a negative qPCR result for any of the MBL encoding genes were subjected to WGS. The WGS analysis of the 67 remaining P. aeruginosa isolates showed mutations in genes previously associated with reduced susceptibility to CZA, such as those involved in the MexAB-OprM efflux pump and AmpC (PDC) hyperproduction, PoxB (blaOXA-50-like), FtsI (PBP3), DacB (PBP4), and OprD. The results presented here offer a snapshot of the molecular epidemiological landscape for CZA resistance before the introduction of this antibiotic into the Latin American market. Therefore, these results serve as a valuable comparison tool to trace the evolution of the resistance to CZA in this carbapenemase-endemic geographical region. IMPORTANCE In this manuscript, we determine the molecular mechanisms of ceftazidime-avibactam resistance in Enterobacterales and P. aeruginosa isolates from five Latin American countries. Our results reveal a low rate of resistance to ceftazidime-avibactam among Enterobacterales; in contrast, resistance in P. aeruginosa has proven to be more complex, as it might involve multiple known and possibly unknown resistance mechanisms.

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. FINDINGS: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING: National Institutes of Health.

Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries.

Objectives: Identify molecular mechanisms responsible for the in vitro non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of Pseudomonas aeruginosa from five Latin American countries collected before the introduction of TOL into the clinical practice. Methods: Clinical isolates of P. aeruginosa (n = 504) were collected between January 2016 and October 2017 from 20 hospitals located in Argentina, Brazil, Chile, Colombia, and Mexico. Minimum inhibitory concentrations (MICs) to TOL were determined by standard broth microdilution and interpreted according to CLSI breakpoints. Initially, production of carbapenemases in TOL non-susceptible isolates was assessed by Rapidec® followed by qPCR to detect bla KPC, bla NDM-1, bla VIM, and bla IMP. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases. Results: A total of 158 (31.3%) isolates were non-susceptible to TOL. In 74 (46.8%) of these isolates, non-susceptibility to TOL was explained by the production of at least one carbapenemase. WGS revealed that some isolates carried ESBLs, mutated bla PDC and ampD, associated with decreased susceptibility to TOL. Conclusion: Substitutions found in PDC and carbapenemase production were the most common presumed mechanisms of resistance to TOL detected in this study. This study shows that epidemiological surveillance is warranted to monitor the emergence of novel mechanisms of resistance to TOL that might compromise its clinical utility.

Gaps and barriers in the implementation and functioning of antimicrobial stewardship programmes: results from an educational and behavioural mixed methods needs assessment in France, the United States, Mexico and India.

Background: Evidence shows limited adherence to antimicrobial stewardship (AMS) principles. Objectives: To identify educational gaps and systemic barriers obstructing adherence to AMS principles. Methods: A mixed-methods study combining a thematic analysis of qualitative interviews (January-February 2021) and inferential analysis of quantitative surveys (May-June 2021) was conducted. Participants from France, the USA, Mexico and India were purposively sampled from online panels of healthcare professionals to include infectious disease physicians, infection control specialists, clinical microbiologists, pharmacologists or pharmacists expected to apply AMS principles in their practice setting (e.g. clinic, academic-affiliated or community-based hospital). A gap analysis framework guided this study. Results: The final sample included 383 participants (n = 33 interviews; n = 350 surveys). Mixed-methods findings indicated suboptimal knowledge and skills amongst participants to facilitate personal and collective application of AMS principles. Survey data indicated a gap in ideal versus current knowledge of AMS protocols, especially amongst pharmacologists (Δ0.95/4.00, P < 0.001). Gaps in ideal versus current skill levels were also measured and were highest amongst infectious control specialists (Δ1.15/4.00, P < 0.001), for convincing hospital executives to allocate resources to AMS programmes. Already existing systemic barriers (e.g. insufficient dedicated time/funding/training) were perceived as being aggravated during the COVID-19 pandemic (72% of survey participants agreed). Reported gaps were highest in India and France. Conclusions: The educational needs of professionals and countries included in this study can inform future continuous professional development activities in AMS. Additional funding should be considered to address perceived systemic barriers. Local assessments are warranted to validate results and suitability of interventions.

Early appropriate diagnostics and treatment of MDR Gram-negative infections.

The term difficult-to-treat resistance has been recently coined to identify Gram-negative bacteria exhibiting resistance to all fluoroquinolones and all ß-lactam categories, including carbapenems. Such bacteria are posing serious challenges to clinicians trying to identify the best therapeutic option for any given patient. Delayed appropriate therapy has been associated with worse outcomes including increase in length of stay, increase in total in-hospital costs and ∼20% increase in the risk of in-hospital mortality. In addition, time to appropriate antibiotic therapy has been shown to be an independent predictor of 30 day mortality in patients with resistant organisms. Improving and anticipating aetiological diagnosis through optimizing not only the identification of phenotypic resistance to antibiotic classes/agents, but also the identification of specific resistance mechanisms, would have a major impact on reducing the frequency and duration of inappropriate early antibiotic therapy. In light of these considerations, the present paper reviews the increasing need for rapid diagnosis of bacterial infections and efficient laboratory workflows to confirm diagnoses and facilitate prompt de-escalation to targeted therapy, in line with antimicrobial stewardship principles. Rapid diagnostic tests currently available and future perspectives for their use are discussed. Early appropriate diagnostics and treatment of MDR Gram-negative infections require a multidisciplinary approach that includes multiple different diagnostic methods and further consensus of algorithms, protocols and guidelines to select the optimal antibiotic therapy.

Comparative In Vitro Activity of Ceftolozane/Tazobactam against Clinical Isolates of Pseudomonas aeruginosa and Enterobacterales from Five Latin American Countries.

BACKGROUND: Ceftolozane/tazobactam (C/T) is a combination of an antipseudomonal oxyiminoaminothiazolyl cephalosporin with potent in vitro activity against Pseudomonas aeruginosa and tazobactam, a known ß-lactamase inhibitor. The aim of this study was to evaluate the activity of C/T against clinical isolates of P. aeruginosa and Enterobacterales collected from five Latin American countries between 2016 and 2017, before its clinical use in Latin America, and to compare it with the activity of other available broad-spectrum antimicrobial agents. METHODS: a total of 2760 clinical isolates (508 P. aeruginosa and 2252 Enterobacterales) were consecutively collected from 20 hospitals and susceptibility to C/T and comparator agents was tested and interpreted following the current guidelines. RESULTS: according to the CLSI breakpoints, 68.1% (346/508) of P. aeruginosa and 83.9% (1889/2252) of Enterobacterales isolates were susceptible to C/T. Overall, C/T demonstrated higher in vitro activity than currently available cephalosporins, piperacillin/tazobactam and carbapenems when tested against P. aeruginosa, and its performance in vitro was comparable to fosfomycin. When tested against Enterobacterales, it showed higher activity than cephalosporins and piperacillin/tazobactam, and similar activity to ertapenem. CONCLUSIONS: these results show that C/T is an active ß-lactam agent against clinical isolates of P. aeruginosa and Enterobacterales.

Clinical data from studies involving novel antibiotics to treat multidrug-resistant Gram-negative bacterial infections.

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) pose a critical threat to global healthcare, worsening outcomes and increasing mortality among infected patients. Carbapenemase- and extended-spectrum ß-lactamase-producing Enterobacterales, as well as carbapenemase-producing Pseudomonas and Acinetobacter spp., are common MDR pathogens. New antibiotics and combinations have been developed to address this threat. Clinical trial findings support several combinations, notably ceftazidime-avibactam (CZA, a cephalosporin-ß-lactamase inhibitor combination), which is effective in treating complicated urinary tract infections (cUTI), complicated intra-abdominal infections and hospital-acquired and ventilator-associated pneumonia caused by GNBs. Other clinically effective combinations include meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T) and imipenem-relebactam (I-R). Cefiderocol is a recent siderophore ß-lactam antibiotic that is useful against cUTIs caused by carbapenem-resistant Enterobacterales (CRE) and is stable against many ß-lactamases. Carbapenem-resistant Enterobacterales are a genetically heterogeneous group that vary in different world regions and are a substantial cause of infections, among which Klebsiella pneumoniae are the most common. Susceptible CRE infections can be treated with fluoroquinolones, aminoglycosides or fosfomycin, but alternatives include CZA, MVB, I-R, cefiderocol, tigecycline and eravacycline. Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are increasingly common pathogens producing a range of different carbapenemases, and infections are challenging to treat, often requiring novel antibiotics or combinations. Currently, no single agent can treat all MDR-GNB infections, but new ß-lactam-ß-lactamase inhibitor combinations are often effective for different infection sites and, when used appropriately, have the potential to improve outcomes. This article reviews clinical studies investigating novel ß-lactam approaches for treatment of MDR-GNB infections.

Impact of antimicrobial stewardship programs on antibiotic consumption and antimicrobial resistance in four Colombian healthcare institutions.

BACKGROUND: Antimicrobial stewardship programs (ASPs) have become a fundamental pillar in optimizing antimicrobial usage, improving patient care, and reducing antimicrobial resistance (AMR). Herein we evaluated the impact of an ASP on antimicrobial consumption and AMR in Colombia. METHODS: We designed a retrospective observational study and measured trends in antibiotic consumption and AMR before and after the implementation of an ASP using interrupted time series analysis over a 4-year period (24 months before and 24 months after ASP implementation). RESULTS: ASPs were implemented according to the available resources in each of the institutions. Before ASP implementation, there was a trend toward an increase in the antibiotic consumption of all measured antimicrobials selected. Afterward, an overall decrease in antibiotic consumption was observed. The use of ertapenem and meropenem decreased in hospital wards, while a decrease in the use of ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, and vancomycin was observed in intensive care units. After ASP implementation, the trend toward an increase of oxacillin-resistant Staphylococcus aureus, ceftriaxone-resistant Escherichia coli, and meropenem-resistant Pseudomonas aeruginosa was reversed. CONCLUSIONS: In our study, we showed that ASPs are a key strategy in tackling the emerging threat of AMR and have a positive impact on antibiotic consumption and resistance.

Global resilience and new strategies needed for antimicrobial stewardship during the COVID-19 pandemic and beyond.

Resilience is having the ability to respond to adversity proactively and resourcefully. The coronavirus disease 2019 (COVID-19) pandemic's profound impact on antimicrobial stewardship programs (ASP) requires clinicians to call on their own resilience to manage the demands of the pandemic and the disruption of ASP activities. This article provides examples of ASP resilience from pharmacists and physicians from seven countries with different resources and approaches to ASP-The United States, The United Kingdom, Canada, Nigeria, Lebanon, South Africa, and Colombia. The lessons learned pertain to providing ASP clinical services in the context of a global pandemic, developing new ASP paradigms in the face of COVID-19, leveraging technology to extend the reach of ASP, and conducting international collaborative ASP research remotely. This article serves as an example of how resilience and global collaboration is sustaining our ASPs by sharing new "how to" do antimicrobial stewardship practices during the COVID-19 pandemic.

Multicenter, Prospective Validation of a Phenotypic Algorithm to Guide Carbapenemase Testing in Carbapenem-Resistant Pseudomonas aeruginosa Using the ERACE-PA Global Surveillance Program.

BACKGROUND: Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) is a global challenge. However, detection efforts can be laborious because numerous mechanisms produce carbapenem resistance. A minimum inhibitory concentration-based algorithm (imipenem- or meropenem-resistant plus ceftazidime-nonsusceptible plus cefepime-nonsusceptible) was proposed to identify the isolates most likely to harbor a carbapenemase; however, prospective validation in geographies displaying genotypic diversity and varied carbapenemase prevalence is warranted. METHODS: CRPA isolates were collected during the Enhancing Rational Antimicrobials for P. aeruginosa (ERACE-PA) global surveillance program from 17 sites in 12 countries. Isolates underwent susceptibility testing following local standards to ceftazidime, cefepime, and ceftolozane/tazobactam. Isolates underwent initial phenotypic carbapenemase screening followed by molecular testing if positive. The primary algorithm criteria were applied, and results were compared with phenotypic carbapenemase results to assess the performance of the algorithm. A secondary criterion, the algorithm criterion or imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible, was assessed. RESULTS: A total of 807 CRPA were assessed, and 464 isolates met the algorithm criteria described above. Overall, testing was reduced by 43% compared with testing all CRPA. Carbapenemase-positive isolates missed by the algorithm were largely driven by Guiana extended spectrum (GES). Addition of the criterion of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible decreased the number of CP-CRPA missed by the algorithm (21 vs 40 isolates, respectively), reducing number of isolates tested by 39%. CONCLUSIONS: Application of the initial algorithm (imipenem- or meropenem-resistant plus ceftazidime-nonsusceptible plus cefepime-nonsusceptible) performed well in a global cohort, with 33% phenotypically carbapenemase-positive isolates. The addition of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible reduced the number of phenotypically carbapenemase-positive isolates missed and may be useful in areas with a prominence of GES.

Microbiological and Clinical Aspects of Raoultella spp.

The genus Raoultella was established in 2001. Species of Raoultella and Klebsiella share many ecological, biochemical, clinical, and microbiological features. Given the shortcomings of available technology for species identification in the clinical microbiology laboratory, are practically indistinguishable. Since the late 2000s there has been an increase in case reports of human Raoultella infections. Therefore, several authors are postulating that Raoultella spp. are rare and/or emerging pathogens. Conclusions:Raoultella spp. are very similar to Klebsiella spp. The epidemiology and the clinical relevance of the human Raoultella spp. infections is uncertain and further studies are required. The previous difficulties in the identification of Raoultella spp. and the introduction of more precise identification techniques may explain the recent increase in the number of case reports. Raoultella spp. might be rather underdiagnosed than rare or emerging pathogens.

Elevated MICs of Susceptible Antipseudomonal Cephalosporins in Non-Carbapenemase-Producing, Carbapenem-Resistant Pseudomonas aeruginosa: Implications for Dose Optimization.

The present study evaluated the in vitro potency of ceftazidime and cefepime among carbapenem-resistant Pseudomonas aeruginosa isolates collected as part of a global surveillance program and assessed the pharmacodynamic implications using previously published population pharmacokinetics. When susceptible, MICs resulted at the high end of distribution for both ceftazidime and cefepime, thus 6 g/day was required to achieve optimal pharmacodynamic profiles. These findings should be considered in the clinic and for the application of CLSI susceptibility breakpoints.

Should ceftriaxone-resistant Enterobacterales be tested for ESBLs? A PRO/CON debate.

ESBLs are a group of plasmid-mediated, diverse, complex and rapidly evolving enzymes that pose a therapeutic challenge today in hospital- and community-acquired infections. Thirty-six years after the first report, diagnostic and therapeutic approaches for ESBLs are still the subject of controversy. Detection of these enzymes is recommended for epidemiological purposes and facilitates targeted therapy, necessary for antimicrobial stewardship. On the other hand, ESBLs are not confined to specific species, phenotypic detection methods have pitfalls, and concerns exist about the accuracy of antimicrobial susceptibility testing systems to rely on MIC values for cephalosporins and ß-lactam combination agents. In this issue, we present a PRO/CON debate on ESBL testing for ceftriaxone-non-susceptible Enterobacterales.