Perfil de uso de tigeciclina en un hospital universitario en Chile / Profile of tigecycline use in a university hospital in Chile

INTRODUCCIÓN: El uso de tigeciclina ha ido en aumento en los últimos años, debido al incremento de la resistencia bacteriana y la escasez de alternativas terapéuticas. OBJETIVO: Caracterizar y evaluar las prescripciones de tigeciclina en pacientes internados en un hospital universitario, durante los años 2017 y 2018. METODOLOGÍA: Estudio observacional retrospectivo, donde se caracterizaron los pacientes, las terapias, la microbiología asociada, los desenlaces clínicos y las reacciones adversas asociadas a los tratamientos con tigeciclina. Se determinó la proporción de prescripciones apropiadas por un comité de expertos y el consumo de tigeciclina medido en DDD/100 camas-día. RESULTADOS: Se caracterizaron 89 pacientes, de los cuales 67 (75,3%) cumplieron los criterios de selección. El 53,7% de los pacientes eran hombres, con una edad promedio de 60 ± 15 años. El principal motivo de hospitalización fue quirúrgico (65,7%). El 67,1% de los tratamientos con tigeciclina se inició en una Unidad de Paciente Critico y el foco de infección predominante fue abdominal (64,3%). El 50% de las terapias con tigeciclina fueron dirigidas según la microbiología identificada. En 65,7% de los casos se usó tigeciclina como monoterapia en la dosis habitual (62,9%). Náuseas (8,6%), diarrea (7,1%) y vómitos (4,3%) fueron los efectos adversos más reportados. El 84,3% de los tratamientos se consideraron apropiados. El año 2017 se consumió 0,4 DDD/100 camas-día y 0,6 DDD/100 camas/día el 2018, siendo la UCI el servicio que presentó el mayor uso en ambos años. DISCUSIÓN: Tigeciclina fue utilizada principalmente en monoterapia para el tratamiento de infecciones intraabdominales en pacientes hospitalizados, por motivos quirúrgicos, en una unidad de paciente crítico, en las dosis habituales recomendadas de 100 mg como dosis de carga seguida de 50 mg cada 12 hs IV. En 50% de los casos, la terapia fue dirigida según microbiología. Los eventos adversos más habituales fueron los gastrointestinales. CONCLUSIÓN: La mayoría de las terapias prescritas fueron consideradas apropiadas por el comité de expertos.

BACKGROUND: The use of tigecycline has been increasing in recent years, due to increase in bacterial resistance and the scarcity of therapeutics alternatives. AIM: To characterize and evaluate the tigecycline prescriptions of patients hospitalized in a university hospital, during the years 2017 and 2018. METHODS: A retrospective observational study was carried out, where the patients, the therapies, the associated microbiology, the clinical outcomes and the adverse reactions associated with tigecycline were characterized. The proportion of appropriate prescriptions was determined by committee of experts and the consumption of tigecycline measure in DDD/100 bed-days. RESULTS: 89 patients who used tigecycline were characterized, of which 67 (75.3%) met the selection criteria. 53.7% of the patients were male, with a mean age of 60 +/- 15 years The main reason for hospitalization was surgical (65.7%). 67.1% of the treatments with tigecycline were started in a critical patient unit and the predominant focus of the infection was the abdomen (64.3%). 50% of the therapies with tigecycline were ordered according to the identified microbiology. In 65.7% of the cases, tigecyclin was used as monotherapy at the usual dose (62.9%). Nausea (8.6%), diarrhea (7.1%) and vomiting (4.3%) were the most reported adverse events. 84.3% of the treatments were considered appropriate. In 2017, 0.4 DDD/100 bed/days were consumed and 0.6 DDD/100 bed/days in 2018, with de ICU being the service that presented the highest use in both years. DISCUSSION: Tigecycline was mainly used as monotherapy for the treatment of intra-abdominal infections in patients hospitalized for surgical reasons in a critical patient unit at the usual doses of 100 mg loading followed by 50 mg every 12 hours IV. In 50% of the case the therapy was directed according to microbiology. The most common adverse events were gastrointestinal. CONCLUSION: Most of the prescribed therapies were considered appropriate by the expert committee.

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

Efficacy and safety of ceftazidime-avibactam in the treatment of complicated intra-abdominal infections (CIAIs) and complicated urinary tract infections (CUTIs): A meta-analysis of randomized controlled trials

Summary Objective: The aim of this study was to assess the efficacy and safety of ceftazidime-avibactam in the treatment of complicated intra-abdominal infections (CIAIs) and complicated urinary tract infections (CUTIs) with meta-analysis method. Method: We included six randomized clinical trials identified from Medline, Embase, Cochrane Library, "ISRCTN Register" and "ClinicalTrials.gov" which compared ceftazidime-avibactam with comparison group. The meta-analysis was performed using Review Manager software version 5.3. Results: Ceftazidime-avibactam versus active comparisons demonstrated a statistically significant higher rate of microbiological response success on microbiological evaluable populations at the test-of-cure visit (95CI 1.10-2.38, p=0.02) and late-follow-up visit (95CI 1.09-2.23, p=0.02) for the treatment of CUTIs. Ceftazidime-avibactam versus active comparisons demonstrated a statistically significant higher rate of microbiological response success on EME populations at the test-of-cure visit (95CI 1.08-4.27, p=0.03) and late-follow-up visit (OR=1.75, 95CI 1.33-2.29, p<0.0001) for the treatment of CUTIs. Similar results were obtained at the late-follow-up visit (OR = 1.58, 95CI 1.26-1.97, p<0.0001) on microbiologically modified intent-to-treat (mMITT) populations for the treatment of CUTIs. We can find better eradication rates for E. coli and Klebsiella pneumoniae based on mMITT populations. In terms of AEs, SAEs and mortality, ceftazidime-avibactam had a safety and tolerability profile broadly similar to the comparison group. Conclusion: This meta-analysis provides evidence of the efficacy of ceftazidime-avibactam as a potential alternative for the treatment of patients with CUTIs, and CIAIs.

Características clínicas y microbiológicas de la infección intra-abdominal complicada en Colombia: un estudio multicéntrico / Clinical and microbiological characteristics of complicated intra-abdominal infection in Colombia: a multicenter study

Introducción: La infección intra-abdominal complicada adquirida en la comunidad (IIAc-AC) es una causa frecuente de abdomen agudo. Objetivo: Identificar el perfil clínico y microbiológico de la IIAc-AC en cuatro hospitales de Colombia. Métodos: Estudio descriptivo, prospectivo entre 07-2012 y 09-2014 en pacientes de 15 o más años con IIAc-AC. Se midieron las frecuencias de variables socio-demográficas, clínicas, diagnóstico, aislamientos y susceptibilidad antimicrobiana del primer cultivo obtenido asépticamente del sitio de infección. Resultados: 192 pacientes incluidos, 62% hombres, edad media 47,3 años; 38,4% con co-morbilidad, 13% hospitalizados en el último año y 9,4% recibieron antimicrobianos en los últimos seis meses. Fueron admitidos 44,3%, por apendicitis 17,7% por peritonitis y 16,7% por perforación intestinal. El 64,1% de las IIAc-AC fue moderada y tratada con ampicilina/sulbactam (SAM) y ertapenem. En 70,8% se aisló al menos un microorganismo en: 65,1% bacilos gramnegativos (80,0% Escherichia coli, 44,8% susceptible a piperacilina/tazobactam, 65,7% a SAM y 11,2% Klebsiella pneumoniae, 85% susceptibles a SAM) y en 16,7% especies grampositivas (28,1% Streptococcus grupo viridans). La mediana de hospitalización fue siete días y 15,1% fallecieron. Conclusión: Escherichia coli y K. pneumoniae en IIAc-AC son los principales microorganismos a cubrir en la terapia empírica y es necesario conocer la susceptibilidad antimicrobiana en cada región para seleccionar un tratamiento empírico adecuado.

Introduction: Complicated community-acquired intra-abdominal infections (CA-cIAI) are a common cause of acute abdomen. Objective: To identify the clinical and microbiology profile of CA-cIAI in four Colombian hospitals. Methods: This is a prospective, descriptive study, between 08-2012 and 09-2014, including patients with CA-cIAI > 15 years. Data collected included: socio-demographic, clinical, diagnosis, and isolates of the first culture obtained aseptically during surgery with antimicrobial susceptibility. Results: 192 patients were included, 62% men, median age 47.3 years. Co-morbidities were present in 38.4%, 13% had been hospitalized in the previous year 13%, and 9.4% had received antibiotics in the last 6 months; 44.3% were admitted for appendicitis, 17.7% for peritonitis and 16.7% for bowel perforation. CA-cIAI were assessed as moderate in 64.1% of the cases and were treated with ampicillin/sulbactam (SAM) and ertapenem. In 70.8% of cases a bacteria was isolated: 65.1% were gramnegative rods (80.0% Escherichia coli, 44.8% of them susceptible to pipercillin/tazobactam, 65.7% to SAM; 11.2 % were K.pneumoniae, 85% was susceptible for SAM; 16.7% were grampositive cocci (28.1% Streptococci viridans group). The median hospital stay was 7 days and 15.1% died. Conclusions: E. coli, K. pneumoniae and S. viridans were the main organisms to consider in an empiric therapy for CA-cIAI and it is important to know the local epidemiology in order to choose the right antibiotic.

Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc99m-sestamibi biodistribition

PURPOSE: To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis. METHODS: Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis. RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9±0.3%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0±0.2%ID/g), control sham group+ simvastatin (1.2±0.3%ID/g) and control sham group (1.3±0.2%ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups. CONCLUSIONS: Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins. .

La experiencia clínica con tigeciclina: Una breve revisión / Clinical experience with tygecicline: A brief review

The available clinical experience with tigecycline is analyzed under the perspective of a systematic review of the hterature, related to the already approved indications reported in the recent hterature. The safety profile is checked in the above mentioned clinical trials. The available information allows supporting tigecycline efficiency in the managing of complicated skin and soft tissues infections, complicated intrabdominales infections and in community acquired pneumonias.

Se analiza, bajo la perspectiva de una revisión sistemática de la literatura médica, la experiencia clínica con tigeciclina, en las indicaciones ya aprobadas por las entidades reguladoras reportadas en la literatura reciente. Se revisa el perfil de seguridad y tolerabilidad en dichos ensayos clínicos. La información disponible permite avalar su eficacia en el manejo de infecciones de piel y tejidos blandos complicadas, infecciones intra-abdominales complicadas y neumonías adquiridas en la comunidad.