Opportunities and challenges in antimicrobial resistance policy including animal production systems and humans across stakeholders in Argentina: a context and qualitative analysis.

INTRODUCTION: Gaps in antimicrobial resistance (AMR) surveillance and control, including implementation of national action plans (NAPs), are evident internationally. Countries' capacity to translate political commitment into action is crucial to cope with AMR at the human-animal-environment interface. METHODS: We employed a two-stage process to understand opportunities and challenges related to AMR surveillance and control at the human-animal interface in Argentina. First, we compiled the central AMR policies locally and mapped vital stakeholders around the NAP and the national commission against bacterial resistance. Second, we conducted qualitative interviews using a semistructured questionnaire covering stakeholders' understanding and progress towards AMR and NAP. We employed a mixed deductive-inductive approach and used the constant comparative analysis method. We created categories and themes to cluster subthemes and determined crucial relationships among thematic groups. RESULTS: Crucial AMR policy developments have been made since 1969, including gradually banning colistin in food-producing animals. In 2023, a new government decree prioritised AMR following the 2015 NAP launch. Our qualitative analyses identified seven major themes for tackling AMR: (I) Cultural factors and sociopolitical country context hampering AMR progress, (II) Fragmented governance, (III) Antibiotic access and use, (IV) AMR knowledge and awareness throughout stakeholders, (V) AMR surveillance, (VI) NAP efforts and (VII) External drivers. We identified a fragmented structure of the food production chain, poor cross-coordination between stakeholders, limited surveillance and regulation among food-producing animals and geographical disparities over access, diagnosis and treatment. The country is moving to integrate animal and food production into its surveillance system, with most hospitals experienced in monitoring AMR through antimicrobial stewardship programmes. CONCLUSION: AMR accountability should involve underpinning collaboration at different NAP implementation levels and providing adequate resources to safeguard long-term sustainability. Incorporating a multisectoral context-specific approach relying on different One Health domains is crucial to strengthening local AMR surveillance.

[Comparative analysis of clinical characteristics, evolution and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID Study)]. / Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (Registro ECCOVID).

INTRODUCTION: Clinical features and outcomes of SARSCoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. METHODS: Multicenter and prospective registry of patients =18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. RESULTS: A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized patients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hospitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hospitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. CONCLUSION: Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 during the second wave in Argentina were more seriously ill and had a higher mortality.

Introducción: Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos: Registro multicéntrico y prospectivo de pacientes = 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolución a 30 días. Resultados: Se incluyeron un total de 1691 pacientes (primera ola n = 809, segunda ola n = 882). Los pacientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospitalización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p < 0,001) y presentaron mayor mortalidad (11% vs. 26%, p < 0.001). Comparando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión: Comparados con los pacientes internados durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

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.

RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 infection in a Latin American country: Results from the ECCOVID multicenter prospective study.

BACKGROUND: Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina. METHODS: Multicenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU). RESULTS: A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27). CONCLUSIONS: This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.

[Intersociety guidelines for diagnosis, treatment and prevention of Clostridioides difficile infections]. / Recomendaciones intersociedades para diagnóstico, tratamiento y prevención de las infecciones por Clostridioides difficile.

Clostridioides difficile infections (CDI) are among the leading causes of health care-associated infections. The epidemiology of CDI has undergone major changes in the last decade, showing an increase in incidence, severity, and rate of relapse. These guidelines were developed by specialists from four scientific societies: Sociedad Argentina de Infectología (SADI), Sociedad Argentina de Gastroenterología (SAGE), Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas (SADEBAC) and Asociación de Enfermeras en Control de Infecciones (ADECI). The objective of these intersociety guidelines is to provide national recommendations on CDI diagnosis, treatment and prevention. The methodology used involved the systematic review of the bibliography available up to December 2018, which was performed by six groups formed ad hoc: Epidemiology, Diagnosis, Treatment, Fecal Microbiota Transplantation, Special Populations, and Infection Control. The conclusions were presented and discussed in meetings held by each individual group and plenary meetings. In this document, updated diagnosis algorithms, therapeutic options (including fecal microbiota transplant) for immunocompetent and immunocompromised patients are presented, as well as strategies for the control of C. difficile infection.

Las infecciones por Clostridioides difficile están entre las principales causas de infecciones asociadas al sistema de salud. Su epidemiología ha sufrido importantes cambios en la última década con aumento en incidencia, gravedad y frecuencia de recidivas. El objetivo de este documento es brindar recomendaciones nacionales para el diagnóstico, el tratamiento y la prevención de las infecciones por C. difficile. Estas recomendaciones fueron elaboradas por especialistas pertenecientes a cuatro sociedades científicas de la República Argentina: Sociedad Argentina de Infectología (SADI), Sociedad Argentina de Gastroenterología (SAGE), Sociedad Argentina de Bacteriología, Micología y Parasitología Clínica (SADEBAC) y Asociación de Enfermeros en Control de Infecciones (ADECI). La metodología utilizada consistió en la revisión sistemática de la evidencia publicada hasta diciembre 2018. Seis grupos de especialistas fueron formados a tal fin: Epidemiología, Diagnóstico, Tratamiento, Trasplante de Microbiota Fecal, Poblaciones Especiales y Control de Infecciones. En reuniones individuales de grupo y plenarias se presentaron y discutieron las conclusiones y se elaboraron las recomendaciones. En este documento se actualizan los algoritmos diagnósticos, las opciones terapéuticas, incluido el trasplante de microbiota fecal, en paciente inmunocompetentes e inmunocomprometidos, y las medidas de control de infecciones por C. difficile.

[Consenso Argentino Intersociedades de Infección Urinaria 2018-2019 - Parte I]. / Argentine Intersociety Consensus on Urinary Infection 2018-2019 - Part I.

The Argentine Society of Infectious Diseases and other scientific societies have updated these recommendations based on data on urinary tract infections in adults obtained from a prospective multicenter study conducted in Argentina during 2016-2017. Asymptomatic bacteriuria should be treated only in pregnant women, who should also be systematically investigated; the antibiotics of choice are nitrofurantoin, amoxicillin, clavulanic/amoxicillin, cephalexin and trimethoprim-sulfamethoxazole. In procedures involving injury to the urinary tract with bleeding, it is recommended to request urine culture and, in the presence of bacteriuria, antimicrobial treatment according to sensitivity should be prescribed from immediately before up to 24 hours after the intervention. In women, cystitis can be treated with nitrofurantoin, cephalexin or fosfomycin, while trimethoprim-sulfamethoxazole and fluoroquinolones are not recommended; pyelonephritis can be treated with ciprofloxacin, cefixime or cephalexin in ambulatory women or ceftriaxone, cefazolin or amikacin in those who are hospitalized. In men, urinary tract infections are always considered complicated; nitrofurantoin or cephalexin are recommended for 7 days, alternatively fosfomycin should be given in a single dose. In men, ciprofloxacin, ceftriaxone or cefixime are suggested for pyelonephritis on ambulatory treatment whereas ceftriaxone or amikacin are recommended for hospitalized patients. Acute bacterial prostatitis can be treated with ceftriaxone or gentamicin. Fluoroquinolones were the choice treatment for chronic bacterial prostatitis until recently; they are no longer recommended due to the increasing resistance and recent concerns regarding the safety of these drugs; alternative antibiotics such as fosfomycin are to be considered.

La Sociedad Argentina de Infectología y otras sociedades científicas han actualizado estas recomendaciones utilizando, además de información internacional, la de un estudio multicéntrico prospectivo sobre infecciones del tracto urinario del adulto realizado en Argentina durante 2016-2017. La bacteriuria asintomática debe ser tratada solo en embarazadas, a quienes también se las debe investigar sistemáticamente; los antibióticos de elección son nitrofurantoína, amoxicilina, amoxicilina-clavulánico, cefalexina y trimetoprimasulfametoxazol. Ante procedimientos que impliquen lesión con sangrado del tracto urinario se recomienda solicitar urocultivo para pesquisar bacteriuria asintomática, y, si resultara positivo, administrar antimicrobianos según sensibilidad desde inmediatamente antes hasta 24 horas luego de la intervención. En mujeres, la cistitis puede ser tratada con nitrofurantoina, cefalexina, o fosfomicina y no se recomienda usar trimetoprima-sulfametoxazol o fluoroquinolonas; en pielonefritis puede emplearse ciprofloxacina, cefixima o cefalexina si el tratamiento es ambulatorio o ceftriaxona, cefazolina o amikacina si es hospitalario. En los hombres, las infecciones del tracto urinario se consideran siempre complicadas. Se recomienda tratamiento con nitrofurantoina o cefalexina por 7 días, o bien monodosis con fosfomicina. Para la pielonefritis en hombres se sugiere ciprofloxacina, ceftriaxona o cefixima si el tratamiento es ambulatorio y ceftriaxona o amikacina si es hospitalario. Se sugiere tratar las prostatitis bacterianas agudas con ceftriaxona o gentamicina. En cuanto a las prostatitis bacterianas crónicas, si bien su tratamiento de elección hasta hace poco fueron las fluoroquinolonas, la creciente resistencia y ciertas dudas sobre la seguridad de estas drogas obligan a considerar el uso de alternativas como fosfomicina.

[Argentine Intersociety Consensus on Urinary Infection 2018-2019 - Part II]. / Consenso Argentino Intersociedades de Infección Urinaria 2018-2019 - Parte II.

The second part of the Inter-Society Argentine Consensus on Urinary Tract Infection (UTI) includes the analysis of special situations. In patients with urinary catheter, urine culture should be requested only in the presence of UTI symptomatology, before instrumentation of the urinary tract, or as a post-transplant control. The antibiotics recommended for empirical treatment in patients without risk factors are third-generation cephalosporins or aminoglycosides. UTIs associated with stones are always considered complicated. In case of obstruction with urosepsis, an emergency drainage should be performed via a percutaneous nefrostomy or ureteral stenting. In patients with stents or ureteral prostheses, such as double J catheters, empirical treatment should be based on epidemiology, prior antibiotics, and clinical status. Before the extracorporeal lithotripsy procedure, bacteriuria should be investigated and antibiotic prophylaxis should be administered in case of positive result, according to the antibiogram. First generation cephalosporins or aminoglycosides are valid alternatives. The use of antibiotic prophylaxis with first-generation cephalosporins or aminoglycosides before percutaneous nephrolithotomy is recommended. Transrectal prostatic biopsy can be associated with infectious complications, such as UTI or acute prostatitis, mainly due to Escherichia coli or other enterobacteria. In patients without risk factors for multiresistant bacteria and negative urine culture, prophylaxis with intravenous amikacin or ceftriaxone is recommended. In patients with positive urine culture, prophylaxis will be performed according to the antibiogram, from 24 hours before to 24 hours post-procedure. For the targeted treatment of post-transrectal biopsy prostatitis, carbapenems for 3-4 weeks are the treatment of choice.

La segunda parte del Consenso Argentino Intersociedades de Infección Urinaria incluye el análisis de situaciones especiales. En pacientes con sonda vesical se debe solicitar urocultivo solo cuando hay signo-sintomatología de infección del tracto urinario, antes de instrumentaciones de la vía urinaria o como control en pacientes post-trasplante renal. El tratamiento empírico recomendado en pacientes sin factores de riesgo es cefalosporinas de tercera generación o aminoglucósidos. Las infecciones del tracto urinario asociadas a cálculos son siempre consideradas complicadas. En caso de obstrucción con urosepsis, deberá realizarse drenaje de urgencia por vía percutánea o ureteral. En pacientes con stents o prótesis ureterales, como catéteres doble J, el tratamiento empírico deberá basarse en la epidemiología, los antibióticos previos y el estado clínico. Antes del procedimiento de litotricia extracorpórea se recomienda pesquisar la bacteriuria y, si es positiva, administrar profilaxis antibiótica según el antibiograma. Cefalosporinas de primera generación o aminoglúcosidos son opciones válidas. Se recomienda aplicar profilaxis antibiótica con cefalosporinas de primera generación o aminoglúcosidos antes de la nefrolitotomía percutánea. La biopsia prostática trans-rectal puede asociarse a complicaciones infecciosas, como infecciones del tracto urinario o prostatitis aguda, principalmente por Escherichia coli u otras enterobacterias. En pacientes sin factores de riesgo para gérmenes multirresistentes y urocultivo negativo se recomienda realizar profilaxis con amikacina o ceftriaxona endovenosas. En pacientes con urocultivo positivo, se realizará profilaxis según antibiograma, 24 horas previas a 24 horas post-procedimiento. Para el tratamiento dirigido de la prostatitis post-biopsia trans-rectal, los carbapenémicos durante 3-4 semanas son el tratamiento de elección.

[Betalactam antibiotics combined with bectalactamases inhibitors. Amoxicillin-sulbactam]. / Betalactámicos con inhibidores de betalactamasas. Amoxicilina-sulbactam.

Betalactamases production is one of the main bacterial resistance mechanisms to betalactam antibiotics. The use of bectalactamases inhibitors combined with betalactam antibiotics allows the inactivation of certain betalactamases produced by Gram positive, Gram negative and anaerobic organisms, and even by mycobacteria. Betalactamases inhibitors are an improved therapeutic alternative compared with the other betalactam since, in most cases, they cover a wider antimicrobial spectrum than their analogues. Betalactamases enzimatic activity is specifically directed to the betalactam ring hydrolisis, producing a compound without antibacterial activity. According to their genomic position within microorganisms, betalactamases can be either chromosomic or plasmidic. Currently there are three betalactamases inhibitors locally available: clavulanic acid, sulbactam and tazobactam. Of them, only sulbactam has an intrinsic antimicrobial activity against penicillin binding proteins. The clinical experience from over 20 years confirms that the combination of betalactam antibiotics is effective in the empirical initial treatment of respiratory, intraabdominal, urinary tract and gynecologic infections, including those of polymicrobial origin. In the specific case of amoxicillin-sulbactam, experiences have shown the effectiveness of the combination in the treatment of peritonsillar abscess, otitis media, sinusitis, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonar disease (COPD), urinary tract infection and obstetric/gynecologic infections. The spectrum and pharmacologic properties of this combination makes it also an excellent option for the treatment of skin/soft tissue and intraabdominal infections.

Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (REGISTRO ECCOVID) / Comparative analysis of clinical characteristics, evolu tion and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID STUDY)

Resumen Introducción : Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos : Registro multicéntrico y prospectivo de pacientes ≥ 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolu ción a 30 días. Resultados : Se incluyeron un total de 1691 pacien tes (primera ola n = 809, segunda ola n = 882). Los pa cientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospi talización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p <0,001) y presen taron mayor mortalidad (11% vs. 26%, p < 0.001). Compa rando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión : Comparados con los pacientes interna dos durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

Abstract Introduction : Clinical features and outcomes of SARS-CoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. Methods : Multicenter and prospective registry of patients ≥18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. Results : A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized pa tients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hos pitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hos pitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. Conclusion : Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 dur ing the second wave in Argentina were more seriously ill and had a higher mortality.

[Cytomegalovirus infection with hepatic involvement in immunocompetent adults]. / Infección por citomegalovirus con compromiso hepático en adultos inmunocompetentes.

We retrospectively evaluated 73 immunocompetent adult patients assisted at our Infectious Diseases Clinic between March 1999 and March 2004 who presented fever and asthenia, mild to moderate increase of transaminases and serological findings compatible with recent cytomegalovirus infection. We excluded patients with a history of transfusions, drug abuse, immunodeficiencies, preexistent hepatic impairment or serological findings compatible with acute hepatitis A, B and C (HAV, HBV, HCV) and Epstein-Barr virus (EBV). The laboratory diagnosis of recent cytomegalovirus infection was made by especific IgM detection (ELISA) or a significant increase of specific IgG. The most frequent symptoms were fever (85%) and asthenia (83%), followed by cephalea (25%), splenomegaly (20%), adenomegalies (22%), pharyngitis (25%), myalgias (25%) and hepatomegaly (19%). All the patients showed moderate increase of transaminases and lymphomonocytosis (73/73). In average, ALT was increased by 6 fold and AST by 3.5 fold. The clinical characteristics that differentiate CMV infection from Epstein-Barr infection are the lesser frequency of adenomegalies and pharyngitis in the former. The differential diagnosis of CMV infection with hepatic involvement from acute hepatitis A and B, is based on the absence of jaundice, the lower elevation of transaminases, the intense lymphomonocytosis and the presence of specific IgM against CMV that are characteristic of CMV infection. In conclusion, in previously healthy young adults with fever, intense asthenia, lymphomonocytosis and moderate increase in transaminases levels, cytomegalovirus infection should be investigated.

Nuevos antibióticos en la era de la multiresistencia: revisión sobre ceftolozano/tazobactam y ceftazidima/avibactam / New antibiotics in the multiresistance era: review about ceftolozane/tazobactam and ceftazidime/avibactamISSN 2314-3193. Actualizaciones en sida e infectología. Buenos Aires. noviembre 2020. volumen 28. número 103: 57-71

En los últimos años se han desarrollado nuevos antimicrobianos destinados a combatir infecciones causadas por microorganismos multirresistentes a drogas (MDR), incluyendo combinaciones entre agentes ß-lactámicos (BL) e inhibidores de ß-lactamasas (IBL). En nuestro país se encuentran disponibles dos nuevas combinaciones de BL/IBL: ceftolozano/tazobactam (C/T) y ceftazidima/avibactam (CAZ/AVI). La adición de tazobactam a ceftolozano incrementa la actividad in vitro contra microorganismos productores de BL de espectro extendido (BLEE), por lo que la combinación presenta una potente actividad intrínseca frente a P. aeruginosa. Por su parte, CAZ/AVI conserva las características que definen el perfil de actividad de ceftazidima, por lo que con el agregado de avibactam presenta una potente actividad inhibidora frente a las BLEE y carbapenemasas (KPC, ß-lactamasas de clase C y algunas de clase D). Se presenta a continuación una revisión de la evidencia publicada. A partir de la misma, y considerando la situación actual de tasas crecientes de resistencia antimicrobiana, particularmente en bacilos Gram negativos, se considera que el uso de C/T o CAZ/AVI constituye una excelente alternativa para el manejo de infecciones graves causadas por microorganismos multirresistentes. Sin embargo, su utilización en forma empírica no es recomendable, salvo en situaciones puntuales y estrictamente seleccionadas, y en el contexto un programa de uso racional de antibióticos, bajo el control por parte del equipo de infectología responsable

In recent years, new antimicrobials have been developed to combat infections caused by multidrug-resistant microorganism (MDR), including combinations between ß-lactam agents (BL) and ß-lactamase inhibitors (IBL). Two new combinations of BL / IBL are available in our country: ceftolozano / tazobactam (C / T) and ceftazidime / avibactam (CAZ / AVI). The addition of tazobactam to ceftolozano increases in vitro activity against microorganisms producing extended spectrum BL (ESBL), so the combination has a potent intrinsic activity against P. aeruginosa. For its part, CAZ / AVI retains the characteristics that define the activity profile of ceftazidime, to which with the addition of avibactam it presents a potent inhibitory activity against ESBL and carbapenemases (KPC, ß-lactamases of class C and some of class D). A review of the published evidence is presented below. Based on this, and considering the current situation of increasing rates of antimicrobial resistance, particularly in Gram-negative bacilli, we consider that the use of C/T or CAZ/AVI is an excellent alternative for the management of serious infections caused by multi-resistant microorganisms. However, its use empirically is not recommended, except in specific and strictly selected situations, and in the context of a program for the rational use of antibiotics, under the control of the responsible infectious disease team

Consenso Argentino intersociedades de Infección Urinaria 2018-2019 - Parte I / Consenso Argentino Intersociedades de Infección Urinaria 2018-2019 - Parte I

La Sociedad Argentina de Infectología y otras sociedades científicas han actualizado estas recomendaciones utilizando, además de información internacional, la de un estudio multicéntrico prospectivo sobre infecciones del tracto urinario del adulto realizado en Argentina durante 2016-2017. La bacteriuria asintomática debe ser tratada solo en embarazadas, a quienes también se las debe investigar sistemáticamente; los antibióticos de elección son nitrofurantoína, amoxicilina, amoxicilina-clavulánico, cefalexina y trimetoprima-sulfametoxazol. Ante procedimientos que impliquen lesión con sangrado del tracto urinario se recomienda solicitar urocultivo para pesquisar bacteriuria asintomática, y, si resultara positivo, administrar antimicrobianos según sensibilidad desde inmediatamente antes hasta 24 horas luego de la intervención. En mujeres, la cistitis puede ser tratada con nitrofurantoina, cefalexina, o fosfomicina y no se recomienda usar trimetoprima-sulfametoxazol o fluoroquinolonas; en pielonefritis puede emplearse ciprofloxacina, cefixima o cefalexina si el tratamiento es ambulatorio o ceftriaxona, cefazolina o amikacina si es hospitalario. En los hombres, las infecciones del tracto urinario se consideran siempre complicadas. Se recomienda tratamiento con nitrofurantoina o cefalexina por 7 días, o bien monodosis con fosfomicina. Para la pielonefritis en hombres se sugiere ciprofloxacina, ceftriaxona o cefixima si el tratamiento es ambulatorio y ceftriaxona o amikacina si es hospitalario. Se sugiere tratar las prostatitis bacterianas agudas con ceftriaxona o gentamicina. En cuanto a las prostatitis bacterianas crónicas, si bien su tratamiento de elección hasta hace poco fueron las fluoroquinolonas, la creciente resistencia y ciertas dudas sobre la seguridad de estas drogas obligan a considerar el uso de alternativas como fosfomicina.

The Argentine Society of Infectious Diseases and other scientific societies have updated these recommendations based on data on urinary tract infections in adults obtained from a prospective multicenter study conducted in Argentina during 2016-2017. Asymptomatic bacteriuria should be treated only in pregnant women, who should also be systematically investigated; the antibiotics of choice are nitrofurantoin, amoxicillin, clavulanic/amoxicillin, cephalexin and trimethoprim-sulfamethoxazole. In procedures involving injury to the urinary tract with bleeding, it is recommended to request urine culture and, in the presence of bacteriuria, antimicrobial treatment according to sensitivity should be prescribed from immediately before up to 24 hours after the intervention. In women, cystitis can be treated with nitrofurantoin, cephalexin or fosfomycin, while trimethoprim-sulfamethoxazole and fluoroquinolones are not recommended; pyelonephritis can be treated with ciprofloxacin, cefixime or cephalexin in ambulatory women or ceftriaxone, cefazolin or amikacin in those who are hospitalized. In men, urinary tract infections are always considered complicated; nitrofurantoin or cephalexin are recommended for 7 days, alternatively fosfomycin should be given in a single dose. In men, ciprofloxacin, ceftriaxone or cefixime are suggested for pyelonephritis on ambulatory treatment whereas ceftriaxone or amikacin are recommended for hospitalized patients. Acute bacterial prostatitis can be treated with ceftriaxone or gentamicin. Fluoroquinolones were the choice treatment for chronic bacterial prostatitis until recently; they are no longer recommended due to the increasing resistance and recent concerns regarding the safety of these drugs; alternative antibiotics such as fosfomycin are to be considered.

Consenso Argentino intersociedades de Infección Urinaria 2018-2019 - Parte II / Argentine Intersociety Consensus on Urinary Infection 2018-2019 - Part II

La segunda parte del Consenso Argentino Intersociedades de Infección Urinaria incluye el análisis de situaciones especiales. En pacientes con sonda vesical se debe solicitar urocultivo solo cuando hay signo-sintomatología de infección del tracto urinario, antes de instrumentaciones de la vía urinaria o como control en pacientes post-trasplante renal. El tratamiento empírico recomendado en pacientes sin factores de riesgo es cefalosporinas de tercera generación o aminoglucósidos. Las infecciones del tracto urinario asociadas a cálculos son siempre consideradas complicadas. En caso de obstrucción con urosepsis, deberá realizarse drenaje de urgencia por vía percutánea o ureteral. En pacientes con stents o prótesis ureterales, como catéteres doble J, el tratamiento empírico deberá basarse en la epidemiología, los antibióticos previos y el estado clínico. Antes del procedimiento de litotricia extracorpórea se recomienda pesquisar la bacteriuria y, si es positiva, administrar profilaxis antibiótica según el antibiograma. Cefalosporinas de primera generación o aminoglúcosidos son opciones válidas. Se recomienda aplicar profilaxis antibiótica con cefalosporinas de primera generación o aminoglúcosidos antes de la nefrolitotomía percutánea. La biopsia prostática trans-rectal puede asociarse a complicaciones infecciosas, como infecciones del tracto urinario o prostatitis aguda, principalmente por Escherichia coli u otras enterobacterias. En pacientes sin factores de riesgo para gérmenes multirresistentes y urocultivo negativo se recomienda realizar profilaxis con amikacina o ceftriaxona endovenosas. En pacientes con urocultivo positivo, se realizará profilaxis según antibiograma, 24 horas previas a 24 horas post-procedimiento. Para el tratamiento dirigido de la prostatitis post-biopsia trans-rectal, los carbapenémicos durante 3-4 semanas son el tratamiento de elección.

The second part of the Inter-Society Argentine Consensus on Urinary Tract Infection (UTI) includes the analysis of special situations. In patients with urinary catheter, urine culture should be requested only in the presence of UTI symptomatology, before instrumentation of the urinary tract, or as a post-transplant control. The antibiotics recommended for empirical treatment in patients without risk factors are third-generation cephalosporins or aminoglycosides. UTIs associated with stones are always considered complicated. In case of obstruction with urosepsis, an emergency drainage should be performed via a percutaneous nefrostomy or ureteral stenting. In patients with stents or ureteral prostheses, such as double J catheters, empirical treatment should be based on epidemiology, prior antibiotics, and clinical status. Before the extracorporeal lithotripsy procedure, bacteriuria should be investigated and antibiotic prophylaxis should be administered in case of positive result, according to the antibiogram. First generation cephalosporins or aminoglycosides are valid alternatives. The use of antibiotic prophylaxis with first-generation cephalosporins or aminoglycosides before percutaneous nephrolithotomy is recommended. Transrectal prostatic biopsy can be associated with infectious complications, such as UTI or acute prostatitis, mainly due to Escherichia coli or other enterobacteria. In patients without risk factors for multiresistant bacteria and negative urine culture, prophylaxis with intravenous amikacin or ceftriaxone is recommended. In patients with positive urine culture, prophylaxis will be performed according to the antibiogram, from 24 hours before to 24 hours post-procedure. For the targeted treatment of post-transrectal biopsy prostatitis, carbapenems for 3-4 weeks are the treatment of choice.

Indications of a new antibiotic in clinical practice: results of the tigecycline initial use registry.

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22%) received tigecycline for approved indications, and 88 (78%) for "off label" indications (56% with scientific support and 22% with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93%). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50% of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76%). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.

Mortalidad en pacientes con neumonía provenientes de geriátrico: estudio caso-control / Mortality in Patients with Pneumonia from Nursing Homes: Case-control Study

Introducción: La neumonía en adultos mayores institucionalizados en geriátricos presenta elevada incidencia y mortalidad. Conocer sus características permite optimizar conductas terapéuticas. Objetivo: Comparar severidad, etiología, regímenes antibióticos utilizados y evolución de una cohorte de pacientes hospitalizados por neumonía provenientes de geriátrico, con un grupo de pacientes de igual edad no residentes en geriátricos. Material y métodos: Estudio multicéntrico, retrospectivo, caso-control, sobre la base de datos internacional CAPO. Se incluyeron 534 pacientes internados en hospitales de Argentina por neumonía, periodo 6/2001-12/2007; 30 pacientes provinieron de geriátrico (casos); por cada caso se seleccionaron 3 controles de edad similar. Análisis estadístico: ?2 y F-ANOVA. Se aplicó análisis univariado y multivariado. Resultados: Edad media 85,7 (DS 6.46) y 84.8 (DS 5.8) años para casos y controles respectivamente, pNS. Los casos presentaron categorías de PSI significativamente mayores (p < 0.0001). La etiología se determinó en 17% de casos y 27% de controles. Los antibióticos utilizados fueron similares en ambos grupos (p = 0.7). No hubo diferencias significativas en tiempo a la estabilidad clínica ni duración de estadía hospitalaria. La mortalidad global en los casos fue 50% vs 26% en controles; (p = 0.02) y la atribuible 43.3% vs 15.5%; (p = 0.002). Análisis multivariado: Accidente cerebro vascular (ACV) (p = 0.05), estado mental alterado (EMA) (p = 0.01) e hipotensión arterial (p = 0.04) fueron las variables significativamente asociadas a mortalidad. Conclusiones: los pacientes provenientes de geriátrico presentaron neumonías más severas y mayor mortalidad. Esta se asoció con la presencia de ACV previo, EMA e hipotensión arterial al ingreso, y no con la condición de provenir de geriátrico.

Introduction: Community-acquired pneumonia (CAP) in institutions for elderly patients presents high incidence and mortality. Defining its characteristics will contribute to optimize therapeutic measures. Objective: To compare severity, etiology, antibiotic regimens used and outcome of a cohort of nursing home residents with CAP with a group of age-matched patients who are not resident at a nursing home. Methods: Multicenter, retrospective, case-control study. Information was taken from the international database CAPO. We included 534 patients hospitalized for CAP in Argentina, from June 2001 to December 2007. Among them, 30 cases were residents in nursing homes (cases). For each case, three controls of similar age were selected. Statistical analysis: ?2 and F-ANOVA. Univariate and multivariate analyses were performed. Results: Mean age was 85.7 (SD 6.46) and 84.8 (SD 5.8) years for cases and controls respectively, p NS. Cases had significantly higher PSI scores (p < 0.0001). The etiology was determined in 17% of cases and 27% of controls. The antibiotics used were similar in both groups (p = 0.7). There was no significant difference in time to reach clinical stability or in length of hospital stay. Overall mortality was 50% in cases vs 26% in controls, (p = 0.02) and attributable mortality was 43.3% and 15.5% respectively (p = 0.002). In the multivariate analysis, stroke (p = 0.05), confusion (p = 0.01) and hypotension (p = 0.04) were associated significantly with mortality. Conclusions: nursing home residents presented more frequently severe pneumonia with increased mortality. This incidence was associated with the presence of previous stroke, confusion and hypotension on admission; it was not associated with residence in a nursing home.

Mortalidad en pacientes con neumonía provenientes de geriátrico: estudio caso-control

Introducción: La neumonía en adultos mayores institucionalizados en geriátricos presenta elevada incidencia y mortalidad. Conocer sus características permite optimizar conductas terapéuticas. Objetivo: Comparar severidad, etiología, regímenes antibióticos utilizados y evolución de una cohorte de pacientes hospitalizados por neumonía provenientes de geriátrico, con un grupo de pacientes de igual edad no residentes en geriátricos. Material y métodos: Estudio multicéntrico, retrospectivo, caso-control, sobre la base de datos internacional CAPO. Se incluyeron 534 pacientes internados en hospitales de Argentina por neumonía, periodo 6/2001-12/2007; 30 pacientes provinieron de geriátrico (casos); por cada caso se seleccionaron 3 controles de edad similar. Análisis estadístico: ?2 y F-ANOVA. Se aplicó análisis univariado y multivariado. Resultados: Edad media 85,7 (DS 6.46) y 84.8 (DS 5.8) años para casos y controles respectivamente, pNS. Los casos presentaron categorías de PSI significativamente mayores (p < 0.0001). La etiología se determinó en 17% de casos y 27% de controles. Los antibióticos utilizados fueron similares en ambos grupos (p = 0.7). No hubo diferencias significativas en tiempo a la estabilidad clínica ni duración de estadía hospitalaria. La mortalidad global en los casos fue 50% vs 26% en controles; (p = 0.02) y la atribuible 43.3% vs 15.5%; (p = 0.002). Análisis multivariado: Accidente cerebro vascular (ACV) (p = 0.05), estado mental alterado (EMA) (p = 0.01) e hipotensión arterial (p = 0.04) fueron las variables significativamente asociadas a mortalidad. Conclusiones: los pacientes provenientes de geriátrico presentaron neumonías más severas y mayor mortalidad. Esta se asoció con la presencia de ACV previo, EMA e hipotensión arterial al ingreso, y no con la condición de provenir de geriátrico.(AU)

Introduction: Community-acquired pneumonia (CAP) in institutions for elderly patients presents high incidence and mortality. Defining its characteristics will contribute to optimize therapeutic measures. Objective: To compare severity, etiology, antibiotic regimens used and outcome of a cohort of nursing home residents with CAP with a group of age-matched patients who are not resident at a nursing home. Methods: Multicenter, retrospective, case-control study. Information was taken from the international database CAPO. We included 534 patients hospitalized for CAP in Argentina, from June 2001 to December 2007. Among them, 30 cases were residents in nursing homes (cases). For each case, three controls of similar age were selected. Statistical analysis: ?2 and F-ANOVA. Univariate and multivariate analyses were performed. Results: Mean age was 85.7 (SD 6.46) and 84.8 (SD 5.8) years for cases and controls respectively, p NS. Cases had significantly higher PSI scores (p < 0.0001). The etiology was determined in 17% of cases and 27% of controls. The antibiotics used were similar in both groups (p = 0.7). There was no significant difference in time to reach clinical stability or in length of hospital stay. Overall mortality was 50% in cases vs 26% in controls, (p = 0.02) and attributable mortality was 43.3% and 15.5% respectively (p = 0.002). In the multivariate analysis, stroke (p = 0.05), confusion (p = 0.01) and hypotension (p = 0.04) were associated significantly with mortality. Conclusions: nursing home residents presented more frequently severe pneumonia with increased mortality. This incidence was associated with the presence of previous stroke, confusion and hypotension on admission; it was not associated with residence in a nursing home.(AU)

Betalactámicos con inhibidores de betalactamasas: Amoxicilina-sulbactam / Betalactam antibiotics combined with bectalactamases inhibitors: Amoxicillin-sulbactam

La producción de betalactamasas constituye uno de los principales mecanismos de resistencia bacteriana a los antibióticos betalactámicos. La utilización de inhibidores de betalactamasas en combinación con antibióticos betalactámicos permite la inactivación de determinadas betalactamasas producidas por gérmenes Gram positivos, Gram negativos, anaerobios, y aun por micobacterias. Los inhibidores de betalactamasas representan una alternativa terapéutica mejorada respecto del resto de los betalactámicos al asegurar, en la mayoría de los casos, un mayor espectro antimicrobiano comparado con el de sus análogos. La actividad enzimática de las betalactamasas está dirigida específicamente a la hidrólisis del anillo betalactámico, con producción de un compuesto sin actividad antibacteriana. De acuerdo con su posición genómica dentro de los microorganismos, las betalactamasas pueden ser cromosómicas o plasmídicas. Actualmente existen tres inhibidores de betalactamasas localmente disponibles: ácido clavulánico, sulbactam y tazobactam. De ellos, sólo el sulbactam posee actividad antimicrobiana intrínseca sobre las proteínas ligadoras de penicilina. La experiencia clínica acumulada durante más de 20 años confirma que las combinaciones de betalactámicos-inhibidores de betalactamasas son efectivas en el tratamiento empírico inicial de infecciones respiratorias, intraabdominales, urinarias y ginecológicas, incluidas las de origen polimicrobiano. En el caso particular de amoxicilina-sulbactam, la evidencia citada indica que esta combinación es efectiva para el tratamiento de absceso periamigdalino, otitis media, sinusitis, neumonía extrahospitalaria, exacerbación aguda de enfermedad pulmonar obstructiva crónica (EPOC), infección del tracto urinario e infecciones ginecoobstétricas. Por su espectro y propiedades farmacológicas, la combinación amoxicilina-sulbactam constituye una excelente opción también para el tratamiento de infecciones de piel y partes blandas e infecciones intraabdominales.

Betalactamases production is one of the main bacterial resistance mechanisms to betalactam antibiotics. The use of bectalactamases inhibitors combined with betalactam antibiotics allows the inactivation of certain betalactamases produced by Gram positive, Gram negative and anaerobic organisms, and even by mycobacteria. Betalactamases inhibitors are an improved therapeutic alternative compared with the other betalactam since, in most cases, they cover a wider antimicrobial spectrum than their analogues. Betalactamases enzimatic activity is specifically directed to the betalactam ring hydrolisis, producing a compound without antibacterial activity. According to their genomic position within microorganisms, betalactamases can be either chromosomic or plasmidic. Currently there are three betalactamases inhibitors locally available: clavulanic acid, sulbactam and tazobactam. Of them, only sulbactam has an intrinsic antimicrobial activity against penicillin binding proteins. The clinical experience from over 20 years confirms that the combination of betalactam antibiotics is effective in the empirical initial treatment of respiratory, intraabdominal, urinary tract and gynecologic infections, including those of polymicrobial origin. In the specific case of amoxicillin-sulbactam, experiences have shown the effectiveness of the combination in the treatment of peritonsillar abscess, otitis media, sinusitis, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonar disease (COPD), urinary tract infection and obstetric/ gynecologic infections. The spectrum and pharmacologic properties of this combination makes it also an excellent option for the treatment of skin/soft tissue and intraabdominal infections.

Indications of a new antibiotic in clinical practice: results of the tigecycline initial use registry

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22 percent) received tigecycline for approved indications, and 88 (78 percent) for "off label" indications (56 percent with scientific support and 22 percent with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93 percent). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50 percent of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76 percent). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.