COVID-19-associated serum and cerebrospinal fluid cytokines in post- versus para-infectious SARS-CoV-2-related Guillain-Barré syndrome.

INTRODUCTION: Guillain-Barré syndrome associated with Coronavirus-2-related severe acute respiratory syndrome (COV-GBS) occurs as para- or post-infectious forms, depending on the timing of disease onset. In these two forms, we aimed to compare the cerebrospinal fluid (CSF) and serum proinflammatory cytokine profiles to evaluate differences that could possibly have co-pathogenic relevance. MATERIALS AND METHODS: We studied a retrospective cohort of 26 patients with either post-COV-GBS (n = 15), with disease onset occurring > 7 days after SARS-CoV-2 infection, or para-COV-GBS (n = 11), with disease onset 7 days or less. TNF-α, IL-6, and IL-8 were measured in the serum with SimplePlex™ Ella™ immunoassay. In addition to the para-/post-COV-GBS patients, serum levels of these cytokines were determined in those with non-COVID-associated-GBS (NC-GBS; n = 43), paucisymptomatic SARS-CoV-2 infection without GBS (COVID, n = 20), and in healthy volunteers (HV; n = 12). CSF cytokine levels were measured in patients with para-/post-COV-GBS, in those with NC-GBS (n = 29), or with Alzheimer's disease (AD; n = 24). RESULTS: Serum/CSF cytokine levels did not differ in para- vs post-COV-GBS. We found that SARS-CoV-2 infection raises the serum levels of TNF-α, IL-6, and IL-8, as well as an increase of IL-6 (in serum and CSF) and IL-8 (in CSF) in either NC-GBS or COV-GBS than controls. CSF and serum cytokine levels resulted independent one with another. CONCLUSIONS: The change of cytokines linked to SARS-CoV-2 in COV-GBS appears to be driven by viral infection, although it has unique characteristics in GBS as such and does not account for cases with para- or post-infectious onset.

Innovative Approaches to Monitor Central Line Associated Bloodstream Infections (CLABSIs) Bundle Efficacy in Intensive Care Unit (ICU): Role of Device Standardized Infection Rate (dSIR) and Standardized Utilization Ratio (SUR)-An Italian Experience.

In several settings, the COVID-19 pandemic determined a negative impact on the occurrence of healthcare-associated infection, particularly for on central lines associated bloodstream infections (CLABSI). In our setting, we observed a significant increase in CLABSI in our intensive care unit (ICU) during 2020 and 2021 vs. 2018 to 2019. A refresher training activity on central venous catheter (CVC) management bundles was carried out in September-October 2021 for the ICU health staff. We assessed the impact of bundle implementation by means of standardized indicators, such as the Device Utilization Ratio (DUR), in this case, the Central Line Utilization Ratio, the Standardized Utilization Ratio (SUR), and the device Standardized Infection Ratio (dSIR). Standardized ratios for device use and infection ratio were computed using data from 2018 and 2019 as expectation data. After bundle implementation, we observed a significant reduction of dSIR (p < 0.001), which dropped from 3.23 and 2.99 in the 2020-2021 biennium to 1.11 in 2022 (CLABSI in the first quarter only); no more CLABSI were observed afterwards. Standardized ratios proved helpful in identify increasing trends of CLABSI in the ICU and monitoring the impact of a simple effective tool, i.e., training on and implementation of a bundle for CVC management.

An Overview on Candida auris in Healthcare Settings.

Candida auris has become a major concern in critical care medicine due to the increasing number of immunocompromised patients and candidiasis is the most frequent cause of fungal infections. C. auris and other fungal pathogens are responsible for at least 13 million infections and 1.5 million deaths globally per year. In immunocompromised patients, infections can quickly become severe, causing wound infections, otitis and candidemia, resulting in high morbidity and mortality. The clinical presentation of C. auris is often non-specific and similar to other types of systemic infections; in addition, it is harder to identify from cultures than other, more common types of Candida spp. Some infections are particularly difficult to treat due to multi-resistance to several antifungal agents, including fluconazole (and other azoles), amphotericin B and echinocandins. This entails treatment with more drugs and at higher doses. Even after treatment for invasive infections, patients generally remain colonized for long periods, so all infection control measures must be followed during and after treatment of the C. auris infection. Screening patients for C. auris colonization enables facilities to identify individuals with C. auris colonization and to implement infection prevention and control measures. This pathogenic fungus shows an innate resilience, enabling survival and persistence in healthcare environment and the ability to rapidly colonize the patient's skin and be easily transmitted within the healthcare setting, thus leading to a serious and prolonged outbreak.

Impact of the COVID-19 Pandemic on Epidemiology of Antibiotic Resistance in an Intensive Care Unit (ICU): The Experience of a North-West Italian Center.

The SARS-CoV-2 pandemic caused an increase in intensive care unit (ICU) hospitalizations with a rise in morbidity and mortality; nevertheless, there is still little evidence on the impact of the pandemic on antibiotic resistance in ICUs. This is a retrospective, monocentric epidemiological study. The aim of the study was to describe and analyze the impact of the SARS-CoV-2 pandemic on ICU bacterial resistance patterns. All bacteria isolated from all patients admitted to the E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. A total of 1021 microorganisms were identified, of which 221 (12.47%) had a resistance pattern (resistant organisms; ROs). In this time, there were 1679 patients with a total of 12,030 hospitalization days. The majority of microorganisms were Gram-negative (79.66% in 2018, 77.29% in 2019, 61.83% in 2020, 62.56% in 2021, and 60.75% in 2022), but an increase in Gram-positive microorganisms was observed (20.34 to 39.25% between 2018 and 2022). The prevalence of AR was 19.44% in 2018, 11.54% in 2019, 38.04% in 2020, 34.15% in 2021, and 39.29% in 2022 for Gram-positive microorganisms and 19.86% in 2018, 13.56% in 2019, 18.12% in 2020, 12.41% in 2021, and 12.31% in 2012 for Gram-negative microorganisms. The incidence of ROs showed a COVID-19-related increase in 2020-2021, followed by a lowering trend since 2021, and a new increase in 2022. Possible explanations are antibiotic overtreatment and a decrease in containment measures. An interesting finding was the cumulative lowering trend of carbapenem-resistant K. pneumoniae and P. aeruginosa, probably due to different patient features.

[Characterization of the drug supply in Argentina]. / Caracterización de la oferta de medicamentos en la República Argentina.

INTRODUCTION: Knowing the characteristics of the pharmaceutical market allows obtaining sensitive information to understand the supply, demand and access of the population to medicines. In order to provide primary data regarding the marketing of drugs in Argentina, the following research was performed. METHOD: This is a cross-sectional quantitative-qualitative descriptive study of the Argentine pharmaceutical market, taking into account 30 years of official information provided by the National Regulatory Agency (ANMAT). RESULTS: Two hundred and sixteen laboratories (182 national) drug producers / importers, 53 distributors and 479 drugstores (wholesale drug distribution establishments) were identified. A high concentration of marketing was detected, grouping 90% in only 5 intermediaries. There are currently 6670 products/certificates in the country, an amount that fluctuated over the last 30 years. Six laboratories are owners of between 116 and 208 certificates; 84% of these products come from national laboratories, 5002 are mono-drugs, while 83% are marketed under a fancy name. The three main indications for which the registration of drugs in Argentina is intended are diseases of digestive system, nervous system and infectious diseases; 58% of the marketed products consist of oral formulations. DISCUSSION: Based on data provided by this study, it is possible to assert that the Argentinian pharmaceutical market has a majority share of national capital, with a great concentration in a few pharmaceutical companies and distributors. The products are mostly available as non-combined drugs, in their oral form, and available by their brand names.

Introducción: Conocer las características del mercado farmacéutico permite obtener información sensible para entender la oferta, la demanda y el acceso de la población a los medicamentos. Con el objetivo de aportar datos primarios respecto a la comercialización de fármacos en Argentina, se desarrolló la siguiente investigación. Métodos: Se trata de un estudio descriptivo cuantitativo-cualitativo transversal del mercado farmacéutico argentino, tomando en cuenta 30 años de información oficial aportada por la Agencia Reguladora Nacional (ANMAT). Resultados: Se identificaron 216 laboratorios (182 nacionales) productores/importadores de medicamentos, 53 distribuidores y 479 droguerías (establecimientos de distribución de medicamentos al por mayor). Se detectó una alta concentración de la comercialización, agrupándose el 90% de la misma, en solo 5 intermediarios. En el país existen actualmente 6670 productos/certificados, cantidad que fluctuó a lo largo de los últimos 30 años. Seis laboratorios son dueños de entre 116 y 208 certificados. El 84% de estos productos provienen de laboratorios nacionales, 5002 son monofármacos, mientras que el 83% se comercializa bajo un nombre de fantasía. Las tres principales indicaciones a las que se destina el registro de medicamentos en la Argentina son enfermedades del aparato digestivo, sistema nervioso, e infecciosas; el 58% es comercializado como formulaciones orales. Discusión: el presente trabajo muestra que el mercado farmacéutico argentino tiene una participación mayoritaria de capitales nacionales, existiendo gran concentración en pocas empresas productoras y distribuidoras. Los productos son mayormente monodrogas comercializadas en forma oral y ofrecidas por su nombre de fantasía.

Caracterización de la oferta de medicamentos en la República Argentina / Characterization of the drug supply in Argentina

Resumen Introducción : Conocer las características del mercado farmacéutico permite obtener información sensible para entender la oferta, la demanda y el acceso de la pobla ción a los medicamentos. Con el objetivo de aportar da tos primarios respecto a la comercialización de fármacos en Argentina, se desarrolló la siguiente investigación. Métodos : Se trata de un estudio descriptivo cuanti tativo-cualitativo transversal del mercado farmacéutico argentino, tomando en cuenta 30 años de información oficial aportada por la Agencia Reguladora Nacional (ANMAT). Resultados : Se identificaron 216 laboratorios (182 nacionales) productores/importadores de medicamentos, 53 distribuidores y 479 droguerías (establecimientos de distribución de medicamentos al por mayor). Se detectó una alta concentración de la comercialización, agrupán dose el 90% de la misma, en solo 5 intermediarios. En el país existen actualmente 6670 productos/certificados, cantidad que fluctuó a lo largo de los últimos 30 años. Seis laboratorios son dueños de entre 116 y 208 certifica dos. El 84% de estos productos provienen de laboratorios nacionales, 5002 son monofármacos, mientras que el 83% se comercializa bajo un nombre de fantasía. Las tres principales indicaciones a las que se destina el registro de medicamentos en la Argentina son enfermedades del aparato digestivo, sistema nervioso, e infecciosas; el 58% es comercializado como formulaciones orales. Discusión : el presente trabajo muestra que el mer cado farmacéutico argentino tiene una participación mayoritaria de capitales nacionales, existiendo gran concentración en pocas empresas productoras y distri buidoras. Los productos son mayormente monodrogas comercializadas en forma oral y ofrecidas por su nombre de fantasía.

Abstract Introduction : Knowing the characteristics of the phar maceutical market allows obtaining sensitive informa tion to understand the supply, demand and access of the population to medicines. In order to provide primary data regarding the marketing of drugs in Argentina, the following research was performed. Method : This is a cross-sectional quantitative-quali tative descriptive study of the Argentine pharmaceutical market, taking into account 30 years of official information provided by the National Regulatory Agency (ANMAT). Results : Two hundred and sixteen laboratories (182 national) drug producers/importers, 53 distributors and 479 drugstores (wholesale drug distribution establishments) were identified. A high concentration of market ing was detected, grouping 90% in only 5 intermediaries. There are currently 6670 products/certificates in the country, an amount that fluctuated over the last 30 years. Six laboratories are owners of between 116 and 208 certificates; 84% of these products come from na tional laboratories, 5002 are mono-drugs, while 83% are marketed under a fancy name. The three main indica tions for which the registration of drugs in Argentina is intended are diseases of digestive system, nervous system and infectious diseases; 58% of the marketed products consist of oral formulations. Discussion : Based on data provided by this study, it is possible to assert that the Argentinian pharmaceutical market has a majority share of national capital, with a great concentration in a few pharmaceutical companies and distributors. The products are mostly available as non-combined drugs, in their oral form, and available by their brand names.

The use of continuous positive airway pressure during the second and third waves of the COVID-19 pandemic.

Background: In a preliminary study during the first COVID-19 pandemic wave, we reported a high rate of success with continuous positive airway pressure (CPAP) in preventing death and invasive mechanical ventilation (IMV). That study, however, was too small to identify risk factors for mortality, barotrauma and impact on subsequent IMV. Thus, we re-evaluated the efficacy of the same CPAP protocol in a larger series of patients during second and third pandemic waves. Methods: 281 COVID-19 patients with moderate-to-severe acute hypoxaemic respiratory failure (158 full-code and 123 do-not-intubate (DNI)), were managed with high-flow CPAP early in their hospitalisation. IMV was considered after 4 days of unsuccessful CPAP. Results: The overall recovery rate from respiratory failure was 50% in the DNI and 89% in the full-code group. Among the latter, 71% recovered with CPAP-only, 3% died under CPAP and 26% were intubated after a median CPAP time of 7 days (IQR: 5-12 days). Of the patients who were intubated, 68% recovered and were discharged from the hospital within 28 days. Barotrauma occurred during CPAP in <4% of patients. Age (OR 1.128; p <0.001) and tomographic severity score (OR 1.139; p=0.006) were the only independent predictors of mortality. Conclusions: Early treatment with CPAP is a safe option for patients with acute hypoxaemic respiratory failure due to COVID-19.

Ceftobiprole and daptomycin concentrations in valve tissue in a patient with mitralic native valve endocarditis.

Ceftobiprole (CFB), especially in combination, could be a promising alternative treatment for infective endocarditis. A main determinant of clinical response to antibiotic treatment is drug concentration at the infected site. Data on CFB and Daptomycin (DPT) heart valve penetration are lacking.Here we report a clinical case of CFB and DPT treatment combination for endocarditis. Then, we measured CFB and DPT concentrations in a native infected valve to verify their pharmacokinetic penetration and relationship with pharmacodynamic microbiological markers.The isolated microorganism was a MRSA with CFB and DPT MIC < 2 mg/L and <1 mg/L, respectively. The CFB and DPT plasma concentrations were 36.2 and 14.1 mg/L, respectively and the extrapolated concentration, based on each half-life, at the operatory time were 16.4 and 19.1 mg/L for CFB and DPT, respectively; the corresponding median CFB and DPT valve concentrations were 2.26 (IQR 2.14-2.69) and 12.9 µg/g (IQR 5.69-20.9), respectively; the estimated tissue/plasma ratios for CFB and DTP were 0.14 and 0.67, respectively.The association of CFB and DPT showed a good efficacy in this single endocarditis clinical case, confirmed by plasma and tissue PK/PD data.This report shows the first data on CFB valve tissue penetration, and it needs to be confirmed in other patient valve tissues. Moreover, relative studies of correlation with clinical efficacy are needed.

Antimicrobial Consumption in Latin American Countries: First Steps of a Long Road Ahead.

BACKGROUND: Irrational antimicrobial consumption (AMC) became one of the main global health problems in recent decades. OBJECTIVE: In order to understand AMC in Latin-American Region, we performed the present research in 6 countries. METHODS: Antimicrobial consumption (J01, A07A, P01AB groups) was registered in Argentina, Chile, Colombia, Costa Rica, Paraguay, and Peru. Source of information, AMC type, DDD (Defined Daily Doses), DID (DDD/1000 inhabitants/day), population were variables explored. Data was analyzed using the Global Antimicrobial Resistance and Use Surveillance System (GLASS) tool. RESULTS: Source of information included data from global, public, and private sectors. Total AMC was highly variable (range 1.91-36.26 DID). Penicillin was the most consumed group in all countries except in Paraguay, while macrolides and lincosamides were ranked second. In terms of type of AMC according to the WHO-AWaRe classification, it was found that for certain groups like "Reserve," there are similarities among all countries. CONCLUSION AND RELEVANCE: This paper shows the progress that 6 Latin-American countries made toward AMC surveillance. The study provides a standardized approach for building a national surveillance system for AMC data analysis. These steps will contribute to the inclusion of Latin-America among the regions of the world that have periodic, regular, and quality data of AMC.

Association between Consumption of Fluoroquinolones and Carbapenems and Their Resistance Rates in Pseudomonas aeruginosa in Argentina.

BACKGROUND: Irrational use of antimicrobials (ATMs) triggers microbial resistance (AMR) which has severe consequences for human health. ATM consumption varies among countries and within each territory. These data should be known, in order to perform local policies towards AMR reduction. This work aimed to expose the association of the level of consumption of carbapenems and fluoroquinolones with their resistance rates in Pseudomonas aeruginosa in Argentina. METHOD: Consumption of antimicrobials was expressed by defined daily dose (DDD)/1000 inhabitants for each ATM during one year period, discriminating by each country region. Resistance of P. aeruginosa to carbapenems/fluoroquinolones groups was recorded. Consumption/resistance ratio "R" was calculated for each region of the country, comparing results with other countries. RESULTS: P. aeruginosa resistance rate to fluoroquinolone (F) was 26.4% in blood samples and 29.7% in urine samples, whereas resistance rates to carbapenems (C) were 19.9 and 17.7% in blood and urine, respectively. Correlation between consumption and resistance was demonstrated for both antimicrobials (C : R = 0.58; p=0.003 and F : R = 0.77; p=0.0001). Great fluctuations of resistance levels were seen among regions within the country, always correlating resistance with areas in which a higher level of ATM consumption was detected. CONCLUSION: P. aeruginosa resistance to fluoroquinolone/carbapenems in Argentina directly correlated with antimicrobial consumption levels. A great heterogeneity in resistance profile was observed among areas where ATMs were widely used. Global data at the national level might mask local realities that require specific health policies in order to control the irrational use of ATMs.

Riding the COVID Waves: Clinical Trends, Outcomes, and Remaining Pitfalls of the SARS-CoV-2 Pandemic: An Analysis of Two High-Incidence Periods at a Hospital in Northern Italy.

BACKGROUND: Italy was the first western country to face an uncontrolled outbreak of SARS-CoV-2 infection. The epidemic began in March 2020 within a context characterised by a general lack of knowledge about the disease. The first scientific evidence emerged months later, leading to treatment changes. The aim of our study was to evaluate the effects of these changes. METHODS: Data from a hospital in Genoa, Italy, were analysed. Patients deceased from SARS-CoV-2 infection were selected. Data were compared by dividing patients into two cohorts: "phase A" (March-May 2020) and "phase B" (October-December 2020). RESULTS: A total of 5142 patients were admitted. There were 274 SARS-CoV-2-related deaths (162 phase A and 112 phase B). No differences were observed in terms of demographics, presentation, or comorbidities. A significant increase was recorded in corticosteroid use. Mortality was 33.36% during phase A, falling to 21.71% during phase B. When subdividing the trend during the two phases by age, we found a difference in people aged 65-74 years. CONCLUSIONS: There is scarce evidence regarding treatment for SARS-CoV-2 (especially for severe infection). However, treatment changes improved the prognosis for people under the age of 75. The prognosis for older people remains poor, despite the improvements achieved.

The importance of thinking about Guillain-Barré syndrome during the COVID-19 pandemic: a case with pure dysautonomic presentation.

Guillain-Barré syndrome (GBS) is a peripheral nervous system disease caused by an immune-mediated inflammatory mechanism, usually triggered by a previous infectious process or vaccine; its typical presentation is a rapid and progressive bilateral limb hyposthenia, associated with sensory deficits and reduction or absence of osteotendinous reflexes. However, also autonomic nervous system can be involved with heart rate fluctuations, blood pressure instability, pupillary dysfunction, and urinary retention. Since the beginning of COVID-19 pandemic, GBS has been reported among neurological complications of SARS-CoV-2 infection, although etiopathological mechanisms still have to be clearly defined. We report the case of a 79-year-old man with multiple comorbidities, including diabetes, who was affected by SARS-CoV-2 interstitial pneumonia and developed dysautonomic symptoms after 10 days of hospitalization. A neurological evaluation was performed, and GBS was considered as a possible cause of the clinical manifestations. This hypothesis was confirmed by electrophysiological study and further supported, ex-juvantibus, by the satisfactory response to immunoglobulin treatment. In our opinion, this case of pure dysautonomic presentation of GBS in a SARS-CoV-2 positive patient is relevant because it suggests to consider GBS upon SARS-CoV-2 infection even if the symptoms have uncommon characteristics (e.g., pure vegetative manifestations) and if there are confounding factors which could lead to a misdiagnosis (e.g., old age, SARS-CoV-2 infection consequences and diabetes).

Disparities in antimicrobial consumption and resistance within a country: the case of beta-lactams in Argentina.

OBJECTIVE: To describe bacterial resistance and antimicrobial consumption ratio at the subnational level in Argentina during 2018, considering beta-lactams group as a case-study. METHODS: Antimicrobial consumption was expressed as defined daily doses (DDD)/1000 inhabitants. Resistance of Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus to beta-lactams was recorded. Resistance/consumption ratio was estimated calculating "R" for each region of Argentina, and this data was compared with other countries. RESULTS: The most widely consumed beta-lactams in Argentina were amoxicillin (3.64) for the penicillin sub-group, cephalexin (0.786) for first generation cephalosporins, cefuroxime (0.022) for second generation; cefixime (0.043) for third generation and cefepime (0.0001) for the fourth generation group. Comparison between beta-lactams consumption and bacterial resistance demonstrated great disparities between the six regions of the country. CONCLUSIONS: The case-study of Argentina shows that antimicrobial consumption and resistance of the most common pathogens differed among regions, reflecting different realities within the same country. Because this situation might also be occurring in other countries, this data should be taken into account to target local efforts towards better antimicrobial use, to improve antimicrobial stewardship programs and to propose more suitable sales strategies in order to prevent and control antimicrobial resistance.

Disparities in antimicrobial consumption and resistance within a country: the case of beta-lactams in Argentina

[RESUMO]. Objetivo. Descrever a relação entre o consumo de antimicrobianos e a resistência bacteriana no nível subna-cional na Argentina em 2018, considerando o grupo dos betalactâmicos no estudo de caso.Métodos. O consumo de antimicrobianos foi representado por doses diárias definidas (DDD) por 1.000 habi-tantes. Foi registrada a resistência de Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae e Staphylococcus aureus aos betalactâmicos. A relação entre consumo e resistência foi calculada com base no “R” para cada região do país e os dados da Argentina foram comparados aos de outros países.Resultados. Os betalactâmicos de maior consumo na Argentina foram amoxicilina (3,64) no grupo das pen-icilinas, cefalexina (0,786) no grupo das cefalosporinas de primeira geração, cefuroxima (0.022) no grupo das cefalosporinas de segunda geração, cefixima (0.043) no grupo das cefalosporinas de terceira geração e cefepima (0.0001) no grupo das cefalosporinas de quarta geração. Ao se comparar o consumo de betalac-tâmicos e a resistência bacteriana, observou-se grande disparidade entre as seis regiões do país.Conclusões. O estudo de caso revela diferenças no consumo de antimicrobianos e na resistência dos patógenos mais comuns entre as regiões da Argentina, refletindo realidades distintas dentro do mesmo país. Como esta mesma situação pode estar ocorrendo em outros países, estes achados devem servir para dire-cionar os esforços locais a uma melhor utilização dos antimicrobianos, aperfeiçoar os programas de gestão do uso destes medicamentos e propor estratégias de venda mais apropriadas, visando a prevenir e controlar a resistência aos antimicrobianos.

[ABSTRACT]. Objective. To describe bacterial resistance and antimicrobial consumption ratio at the subnational level in Argentina during 2018, considering beta-lactams group as a case-study. Methods. Antimicrobial consumption was expressed as defined daily doses (DDD)/1000 inhabitants. Resistance of Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus to beta-lactams was recorded. Resistance/consumption ratio was estimated calculating “R” for each region of Argentina, and this data was compared with other countries. Results. The most widely consumed beta-lactams in Argentina were amoxicillin (3.64) for the penicillin sub-group, cephalexin (0.786) for first generation cephalosporins, cefuroxime (0.022) for second generation; cefixime (0.043) for third generation and cefepime (0.0001) for the fourth generation group. Comparison between beta-lactams consumption and bacterial resistance demonstrated great disparities between the six regions of the country. Conclusions. The case-study of Argentina shows that antimicrobial consumption and resistance of the most common pathogens differed among regions, reflecting different realities within the same country. Because this situation might also be occurring in other countries, this data should be taken into account to target local efforts towards better antimicrobial use, to improve antimicrobial stewardship programs and to propose more suitable sales strategies in order to prevent and control antimicrobial resistance.

[RESUMEN]. Objetivo. Determinar la razón entre la resistencia bacteriana y el consumo de antimicrobianos a nivel subnacional en Argentina en el 2018, considerando el grupo de los betalactámicos como estudio de caso. Métodos. El consumo de antimicrobianos se expresó como una dosis diaria determinada (DDD) por 1000 habitantes. Se registró la resistencia de Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae y Staphylococcus aureus a los betalactámicos. Se determinó la razón entre la resistencia y el consumo calculando “R” para cada región de Argentina, y estos datos se compararon con los de otros países. Resultados. Los betalactámicos más consumidos en Argentina fueron la amoxicilina (3,64) para el subgrupo de la penicilina; la cefalexina (0,786) para las cefalosporinas de primera generación; la cefuroxima (0.022) para las de segunda generación; la cefixima (0.043) para las de tercera generación, y la cefepima (0.0001) para el grupo de la cuarta generación. La comparación entre el consumo de betalactámicos y la resistencia bacteriana demostró que había grandes disparidades entre las seis regiones del país. Conclusiones. El estudio de caso en Argentina indica que el consumo de antimicrobianos y la resistencia a los patógenos más comunes difería entre las regiones; esto demuestra que hay distintas realidades dentro del mismo país. Como esta situación también se puede dar en otros países, estos datos se deben tener en cuenta para definir las actividades locales destinadas a fomentar un mejor uso de los antimicrobianos, para mejorar los programas de manejo de los antimicrobianos y para proponer estrategias de venta más adecuadas con el fin de prevenir y controlar la resistencia a los antimicrobianos.

[RESUMO]. Objetivo. Descrever a relação entre o consumo de antimicrobianos e a resistência bacteriana no nível subncional na Argentina em 2018, considerando o grupo dos betalactâmicos no estudo de caso. Métodos. O consumo de antimicrobianos foi representado por doses diárias definidas (DDD) por 1.000 habitantes. Foi registrada a resistência de Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae e Staphylococcus aureus aos betalactâmicos. A relação entre consumo e resistência foi calculada com base no “R” para cada região do país e os dados da Argentina foram comparados aos de outros países. Resultados. Os betalactâmicos de maior consumo na Argentina foram amoxicilina (3,64) no grupo das penicilinas, cefalexina (0,786) no grupo das cefalosporinas de primeira geração, cefuroxima (0.022) no grupo das cefalosporinas de segunda geração, cefixima (0.043) no grupo das cefalosporinas de terceira geração e cefepima (0.0001) no grupo das cefalosporinas de quarta geração. Ao se comparar o consumo de betalactâmicos e a resistência bacteriana, observou-se grande disparidade entre as seis regiões do país. Conclusões. O estudo de caso revela diferenças no consumo de antimicrobianos e na resistência dos patógenos mais comuns entre as regiões da Argentina, refletindo realidades distintas dentro do mesmo país. Como esta mesma situação pode estar ocorrendo em outros países, estes achados devem servir para direcionar os esforços locais a uma melhor utilização dos antimicrobianos, aperfeiçoar os programas de gestão do uso destes medicamentos e propor estratégias de venda mais apropriadas, visando a prevenir e controlar a resistência aos antimicrobianos.

Disparities in antimicrobial consumption and resistance within a country: the case of beta-lactams in Argentina / Disparidades en el consumo de antimicrobianos y la resistencia a estos dentro de un país: el caso de los betalactámicos en Argentina / Disparidades internas no consumo e na resistência aos antimicrobianos: o caso dos betalactâmicos na Argentina

ABSTRACT Objective. To describe bacterial resistance and antimicrobial consumption ratio at the subnational level in Argentina during 2018, considering beta-lactams group as a case-study. Methods. Antimicrobial consumption was expressed as defined daily doses (DDD)/1000 inhabitants. Resistance of Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus to beta-lactams was recorded. Resistance/consumption ratio was estimated calculating "R" for each region of Argentina, and this data was compared with other countries. Results. The most widely consumed beta-lactams in Argentina were amoxicillin (3.64) for the penicillin sub-group, cephalexin (0.786) for first generation cephalosporins, cefuroxime (0.022) for second generation; cefixime (0.043) for third generation and cefepime (0.0001) for the fourth generation group. Comparison between beta-lactams consumption and bacterial resistance demonstrated great disparities between the six regions of the country. Conclusions. The case-study of Argentina shows that antimicrobial consumption and resistance of the most common pathogens differed among regions, reflecting different realities within the same country. Because this situation might also be occurring in other countries, this data should be taken into account to target local efforts towards better antimicrobial use, to improve antimicrobial stewardship programs and to propose more suitable sales strategies in order to prevent and control antimicrobial resistance.

RESUMEN Objetivo. Determinar la razón entre la resistencia bacteriana y el consumo de antimicrobianos a nivel subnacional en Argentina en el 2018, considerando el grupo de los betalactámicos como estudio de caso. Métodos. El consumo de antimicrobianos se expresó como una dosis diaria determinada (DDD) por 1000 habitantes. Se registró la resistencia de Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae y Staphylococcus aureus a los betalactámicos. Se determinó la razón entre la resistencia y el consumo calculando "R" para cada región de Argentina, y estos datos se compararon con los de otros países. Resultados. Los betalactámicos más consumidos en Argentina fueron la amoxicilina (3,64) para el subgrupo de la penicilina; la cefalexina (0,786) para las cefalosporinas de primera generación; la cefuroxima (0.022) para las de segunda generación; la cefixima (0.043) para las de tercera generación, y la cefepima (0.0001) para el grupo de la cuarta generación. La comparación entre el consumo de betalactámicos y la resistencia bacteriana demostró que había grandes disparidades entre las seis regiones del país. Conclusiones. El estudio de caso en Argentina indica que el consumo de antimicrobianos y la resistencia a los patógenos más comunes difería entre las regiones; esto demuestra que hay distintas realidades dentro del mismo país. Como esta situación también se puede dar en otros países, estos datos se deben tener en cuenta para definir las actividades locales destinadas a fomentar un mejor uso de los antimicrobianos, para mejorar los programas de manejo de los antimicrobianos y para proponer estrategias de venta más adecuadas con el fin de prevenir y controlar la resistencia a los antimicrobianos.

RESUMO Objetivo. Descrever a relação entre o consumo de antimicrobianos e a resistência bacteriana no nível subnacional na Argentina em 2018, considerando o grupo dos betalactâmicos no estudo de caso. Métodos. O consumo de antimicrobianos foi representado por doses diárias definidas (DDD) por 1.000 habitantes. Foi registrada a resistência de Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae e Staphylococcus aureus aos betalactâmicos. A relação entre consumo e resistência foi calculada com base no "R" para cada região do país e os dados da Argentina foram comparados aos de outros países. Resultados. Os betalactâmicos de maior consumo na Argentina foram amoxicilina (3,64) no grupo das penicilinas, cefalexina (0,786) no grupo das cefalosporinas de primeira geração, cefuroxima (0.022) no grupo das cefalosporinas de segunda geração, cefixima (0.043) no grupo das cefalosporinas de terceira geração e cefepima (0.0001) no grupo das cefalosporinas de quarta geração. Ao se comparar o consumo de betalactâmicos e a resistência bacteriana, observou-se grande disparidade entre as seis regiões do país. Conclusões. O estudo de caso revela diferenças no consumo de antimicrobianos e na resistência dos patógenos mais comuns entre as regiões da Argentina, refletindo realidades distintas dentro do mesmo país. Como esta mesma situação pode estar ocorrendo em outros países, estes achados devem servir para direcionar os esforços locais a uma melhor utilização dos antimicrobianos, aperfeiçoar os programas de gestão do uso destes medicamentos e propor estratégias de venda mais apropriadas, visando a prevenir e controlar a resistência aos antimicrobianos.

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales.

BACKGROUND: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram-negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. METHODS: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≤72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. RESULTS: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P.aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. CONCLUSIONS: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.

Use of colistin in adult patients: A cross-sectional study.

OBJECTIVES: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). METHODS: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. RESULTS: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P = 0.024) was associated with use of colistin monotherapy. CONCLUSION: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

'Emergency exit' of bone-marrow-resident CD34(+)DNAM-1(bright)CXCR4(+)-committed lymphoid precursors during chronic infection and inflammation.

During chronic inflammatory disorders, a persistent natural killer (NK) cell derangement is observed. While increased cell turnover is expected, little is known about whether and how NK-cell homeostatic balance is maintained. Here, flow cytometric analysis of peripheral blood mononuclear cells in chronic inflammatory disorders, both infectious and non-infectious, reveals the presence of a CD34(+)CD226(DNAM-1)(bright)CXCR4(+) cell population displaying transcriptional signatures typical of common lymphocyte precursors and giving rise to NK-cell progenies with high expression of activating receptors and mature function and even to α/ß T lymphocytes. CD34(+)CD226(bright)CXCR4(+) cells reside in bone marrow, hardly circulate in healthy donors and are absent in cord blood. Their proportion correlates with the degree of inflammation, reflecting lymphoid cell turnover/reconstitution during chronic inflammation. These findings provide insight on intermediate stages of NK-cell development, a view of emergency recruitment of cell precursors, and upgrade our understanding and monitoring of chronic inflammatory conditions.