Linezolid vs glycopeptides in the treatment of glycopeptide-susceptible Enterococcus faecium bacteraemia: A propensity score matched comparative study.

BACKGROUND: The incidence of ampicillin-resistant Enterococcus faecium bacteraemia is increasing. Vancomycin remains the first-line treatment in areas with a high prevalence of glycopeptide-susceptible isolates, but data comparing its clinical outcomes with other treatments are lacking. The objective of this study was to compare the effectiveness and safety of linezolid and glycopeptides for the treatment of glycopeptide-susceptible E. faecium bloodstream infection (GSEF-BSI). METHODS: This retrospective observational cohort study was conducted from January 2006 to May 2018 at the Hospital del Mar, Barcelona, Spain, and compared the clinical outcomes and safety of linezolid and glycopeptides in adult patients with GSEF-BSI. The main outcomes included clinical cure at the end of therapy, 30-day mortality, microbiological eradication and attributable length of stay (LOS). Propensity score matching was performed to reduce potential confounders among groups. RESULTS: In total, 105 patients with GSEF-BSI were included (linezolid, n=38; glycopeptides, n=67). After propensity score matched analysis, 56 (53.3%) patients, 28 in each cohort, entered the final analysis. No differences were observed in any of the main clinical outcomes among patients treated with linezolid or glycopeptides: clinical cure [16/28 (57.1%) vs 13/28 (46.4%), P=0.593], 30-day mortality [8/28 (28.6%) vs 12/28 (42.9%), P=0.403], microbiological eradication [22/28 (78.6%) vs 20/28 (71.4%), P=0.758] and median attributable LOS (18.0 vs 17.0 days, P=0.924). Adverse events were similar in both groups. CONCLUSIONS: Linezolid and glycopeptides showed similar clinical effectiveness and safety in the treatment of GSEF-BSI. Linezolid could be an alternative to glycopeptides in the treatment of GSEF-BSI.

Targeted cancer therapy: interactions with other medicines

Targeted therapy drugs, mainly those within the signal transduction inhibitors, are used more chronically than cytotoxic drugs and are metabolised by cytochrome P450 isozymes so patients are at high risk of having drug-drug interactions (DDI). Not only this, as the majority of them are given orally, new drug-drug interactions concerning gastrointestinal absorption can occur (e.g., with proton pump inhibitors). DDI can lead to changed systemic exposure, resulting in variations in drug response of the co-administered. In addition, concomitant ingestion of dietary supplements could also alter systemic exposure of drugs, thus leading to adverse drug reactions or loss of efficacy. In this review, we give an overview of the current existing data of known or suspected DDI between targeted therapy and other medicines. A review of package inserts was performed to identify drug-drug interactions for all targeted antineoplastic agents. Tertiary databases such as Lexicomp®, Drugs, Martindale, Facts and Comparisons®, and AHFS Drug Information were also referenced. This study covered 40 targeted antineoplastic agents (28 signal transduction inhibitors, 9 monoclonal antibodies and 3 other drugs, 2 monoclonal antibody conjugates and 1 fusion protein). Most of targeted therapy drugs are major CYP3A4 substrates with P-gp playing an important role in disposition too. Thus, there is a very common thread here that these agents will likely be sensitive victims to strong CYP3A4/P-gp inhibitors and inducers. It is essential that health care providers monitor patients for potential DDI to avoid a loss in efficacy or risk of greater toxicity from targeted therapy (AU)

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Targeted cancer therapy: interactions with other medicines.

Targeted therapy drugs, mainly those within the signal transduction inhibitors, are used more chronically than cytotoxic drugs and are metabolised by cytochrome P450 isozymes so patients are at high risk of having drug-drug interactions (DDI). Not only this, as the majority of them are given orally, new drug-drug interactions concerning gastrointestinal absorption can occur (e.g., with proton pump inhibitors). DDI can lead to changed systemic exposure, resulting in variations in drug response of the co-administered. In addition, concomitant ingestion of dietary supplements could also alter systemic exposure of drugs, thus leading to adverse drug reactions or loss of efficacy. In this review, we give an overview of the current existing data of known or suspected DDI between targeted therapy and other medicines. A review of package inserts was performed to identify drug-drug interactions for all targeted antineoplastic agents. Tertiary databases such as Lexicomp®, Drugs, Martindale, Facts and Comparisons®, and AHFS Drug Information were also referenced. This study covered 40 targeted antineoplastic agents (28 signal transduction inhibitors, 9 monoclonal antibodies and 3 other drugs, 2 monoclonal antibody conjugates and 1 fusion protein). Most of targeted therapy drugs are major CYP3A4 substrates with P-gp playing an important role in disposition too. Thus, there is a very common thread here that these agents will likely be sensitive victims to strong CYP3A4/P-gp inhibitors and inducers. It is essential that health care providers monitor patients for potential DDI to avoid a loss in efficacy or risk of greater toxicity from targeted therapy.

Enterococcal bloodstream infection. Design and validation of a mortality prediction rule.

BACKGROUND: To develop a prediction rule to describe the risk of death as a result of enterococcal bloodstream infection. METHODS: A prediction rule was developed by analysing data collected from 122 patients diagnosed with enterococcal BSI admitted to the Clínica Universidad de Navarra (Pamplona, Spain); and validated by confirming its accuracy with the data of an external population (Hospital del Mar, Barcelona). RESULTS: According to this model, independent significant predictors for the risk of death were being diabetic, have received appropriate treatment, severe prognosis of the underlying diseases, have renal failure, received solid organ transplant, malignancy, source of the bloodstream infection and be immunosuppressed. The prediction rule showed a very good calibration (Hosmer-Lemeshow statistic, P = 0.93) and discrimination for both training and testing sets (area under ROC curve = 0.84 and 0.83 respectively). CONCLUSIONS: The predictive rule was able to predict risk of death as a result of enterococcal bloodstream infection as well as to identify patients, who being below the threshold value, will have a low risk of death with a negative predictive value of 96%.

Treatment of athracycline extravasations using dexrazoxane

Extravasation of cytotoxic agents is a true medical emergency. Dexrazoxane is the only licensed drug for the treatment of anthracycline extravasations. Dexrazoxane proved to be effective and moderately well tolerated. However, alternative approaches for the management of anthracycline extravasations are available such as topical DMSO and cooling. There appears to be general agreement about dexrazoxane usefulness when extravasations involve large volumes of anthracycline and/or central venous access device. Nevertheless, the non-invasive combination of DMSO and cooling is the most commonly described therapy, particularly in small anthracycline extravasations. Further research is still needed to establish unequivocal situations where dexrazoxane must be initiated (AU)

No disponible

Treatment of anthracycline extravasations using dexrazoxane.

Extravasation of cytotoxic agents is a true medical emergency. Dexrazoxane is the only licensed drug for the treatment of anthracycline extravasations. Dexrazoxane proved to be effective and moderately well tolerated. However, alternative approaches for the management of anthracycline extravasations are available such as topical DMSO and cooling. There appears to be general agreement about dexrazoxane usefulness when extravasations involve large volumes of anthracycline and/or central venous access device. Nevertheless, the non-invasive combination of DMSO and cooling is the most commonly described therapy, particularly in small anthracycline extravasations. Further research is still needed to establish unequivocal situations where dexrazoxane must be initiated.

Actualización del manejo de extravasaciones de agentes citostáticos / Update in the management of extravasations of cytocytostatic agent

Objetivo Presentar las novedades descritas hasta la actualidad del manejo específico de las extravasaciones de los agentes citostáticos una vez extravasados. MétodoSe realizó una búsqueda en PubMed, Medline e IDIS-Iowa para identificar los trabajos redactados en inglés y/o español que describieron novedades de las medidas específicas para el manejo de sus extravasaciones. Se revisaron también las referencias incluidas en estos trabajos, así como fuentes terciarias recientes relacionadas con oncología o citostáticos. La búsqueda abarcó el periodo comprendido entre 1997 y 2010.ResultadosÚnicamente 22 agentes citostáticos cuentan con algún tipo de medida específica como tratamiento de su extravasación. Se presentan esta medidas en función del citostático de interés, clasificado según su grupo farmacológico. Conclusiones A pesar de que hasta ahora no hay un consenso general en el tratamiento específico de los agentes citostáticos al extravasarse, esta revisión recopila y esquematiza la información publicada actualmente para que pueda servir a cualquier centro sanitario nacional donde se prescriban, manipulen o administren fármacos citostáticos (AU)

Objective To present current developments in the specific management of extravasations of antineoplastic agents after the extravasation. Method We conducted a search in PubMed, Medline and IDIS-Iowa to identify papers written in English or Spanish that described new specific measures for the management of extravasations. We also reviewed the references given in these papers and recent tertiary sources related to oncology or cytostatic agents. The search covered the period between 1997 and 2010.ResultsThere are only specific measures for the treatment of extravasations of 22 cytostatic agents. These measures are presented for each cytostatic agent, according their drug group. Conclusions Although currently there is no general consensus on the specific management of antineoplastic agents after extravasation, this review outlines the information collected and published so far, so that it may be of use to any national health centre where cytostatic drugs are prescribed, handled or administered(AU)

[Update in the management of extravasations of cytocytostatic agent]. / Actualización del manejo de extravasaciones de agentes citostáticos.

OBJECTIVE: To present current developments in the specific management of extravasations of antineoplastic agents after the extravasation. METHOD: We conducted a search in PubMed, Medline and IDIS-Iowa to identify papers written in English or Spanish that described new specific measures for the management of extravasations. We also reviewed the references given in these papers and recent tertiary sources related to oncology or cytostatic agents. The search covered the period between 1997 and 2010. RESULTS: There are only specific measures for the treatment of extravasations of 22 cytostatic agents. These measures are presented for each cytostatic agent, according their drug group. CONCLUSIONS: Although currently there is no general consensus on the specific management of antineoplastic agents after extravasation, this review outlines the information collected and published so far, so that it may be of use to any national health centre where cytostatic drugs are prescribed, handled or administered.

Clinical characteristics and outcomes of patients with vancomycin-susceptible Enterococcus faecalis and Enterococcus faecium bacteraemia in cancer patients.

The purpose of this investigation was to compare the risk factors, clinical features and outcomes in cancer patients with bacteraemia caused by vancomycin-susceptible Enterococcus faecalis and E. faecium. A retrospective, observational 7-year study was carried out in a 450-bed, acute-care university-affiliated hospital. We performed univariate comparisons between the two groups and then multivariate analysis to identify patient risk factors for E. faecium isolation. Seventy-three patients were included in the analysis: 54 (74.0%) with bacteraemia caused by E. faecalis and 19 (26.0%) by E. faecium. The Simplified Acute Physiological Score (SAPS) value was significantly greater in E. faecium isolates (40.7 vs. 35.2; p = 0.009). Diabetes mellitus was more frequently diagnosed in patients with E. faecium bacteraemia (52.6% vs. 24.1%; p = 0.021). Prior penicillin exposure was more frequent in patients with E. faecium bacteraemia (68.4% vs. 29.6%; p = 0.003). There was a trend toward higher mortality in E. faecium bacteraemia patients (47.4% vs. 25.9%; p = 0.084). Independent patient risk factors for E. faecium isolation were prior penicillin exposure (odds ratio [OR], 6.479; p = 0.003) and SAPS > 34 (OR, 6.896; p = 0.009). When compared to E. faecalis bacteraemia, E. faecium bacteraemia in cancer patients is independently associated with more severe illness and prior use of penicillins; therefore, empiric treatment which would cover E. faecium should be considered in cancer patients suspected of having bacteraemia.

Factors associated with adherence to guidelines for the use of tigecycline in a tertiary care hospital.

We assessed the adherence to the prescribing hospital protocol for tigecycline and factors associated with noncompliance. A total of 103 patients were included in the study. In 23 (22.3%) patients, tigecycline was not administered according to the protocol, mostly because of the availability of other therapeutic alternatives and prescription for indications that were not included in the guidelines. factors independently associated with nonadherence to the protocol were community-acquired infection (OR, 14.01; 95% CI, 1.54-127.12; P=0.019), and empirical tigecycline treatment (OR, 6.97; 95% CI, 0.88-55.40; P=0.066). penicillin allergy (OR, 0.004; 95% CI, 0.000-0.071; P=0.001) and previous antibiotic treatment (OR, 0.025; 95% CI, 0.003-0.233; P=0.001) were factors associated with adherence to the hospital protocol. A positive time trend between total number of prescriptions and non-compliant prescriptions with the protocol was observed (Spearman's rho coefficient 0.971; P=0.001). Adherence to tigecycline protocol could be improved by focusing on protocols for community-acquired infections, mainly skin and soft tissue infections.

[Differences in the use of tigecycline between ICU patients and non-ICU patients]. / Diferencias en el uso de tigeciclina entre pacientes críticos y no críticos.

BACKGROUND: Tigecycline is a new broad spectrum antibiotic that is predominantly used for the treatment of severe infections both in critically ill patients admitted to the ICU and in non-ICU patients with less severe clinical conditions. OBJECTIVE: To assess differences in the use of tigecycline between ICU patients and non-ICU patients treated with this antibiotics. MATERIALS AND METHODS: Retrospective, cohort, observational study in which cases were defined as patients who received one or more doses of tigecycline over the first 18 months after approval of the drug in a general hospital. Clinical characteristics, indications, route of administration, clinical response, tolerability and outcome were recorded in the groups of ICU and non-ICU patients. Descriptive data and results of the comparison of both cohorts are presented. RESULTS: A total of 103 were included in the study, 34(33%) of which received tigecycline during their stay in the ICU. ICU patients compared to non-ICU patients had a higher SAPS II score on admission (39.0 +/- 11.8 vs 26.3 +/- 8.0, p < 0.001) and at the time of starting tigecycline treatment (42.2 +/- 12.6 vs 25.6 +/- 8.2, p < 0.001), were treated with antibiotics for more days (21.4 +/- 30.6 vs 13.6 +/- 30.5 days, p < 0.012) and received a greater number of antibiotic agents concomitantly (85.3% vs 47.8%,p < 0.001), presented a higher selection of emerging bacterial flora (41.2% vs 15.9%, p =0.005), particularly Pseudomonas aeruginosa (20.6%vs 2.9%, p =0.006), higher rate of clinical failure (58.8%vs 21.7%, p < 0.001), longer hospitalization (51.2 +/- 39.4 vs 28.7 +/- 26.3 days, p < 0.001) and higher overall mortality rate (50% vs 14.5%, p < 0.001) and infection-attributed mortality (20.6% vs 7.2%, p =0.047). CONCLUSIONS: The patient that receives tigecycline in the ICU has a higher severity level and worse clinical outcome than the non-ICU patient treated with this antibiotic. It is necessary to optimize the indications of tigecycline in the ICU to improve the clinical results.

Diferencias en el uso de tigeciclina entre pacientes críticos y no críticos / Differences in the use of tigecycline between ICU patients and non-ICU patients

Tigeciclina es un nuevo antibiótico de amplio espectro quese utiliza predominantemente para el tratamiento deinfecciones graves tanto en pacientes críticos, ingresados enUCI, como en pacientes menos graves.Objetivo. Analizar las diferencias en la utilización detigeciclina dependiendo de la ubicación de los pacientes en UCIo fuera de UCI.Material y método. Estudio observacional, retrospectivo,de cohortes en el que se define como caso los pacientes quehan utilizado una o más dosis de tigeciclina a lo largo de los 18primeros meses de su aprobación en un hospital general. Secomparan las características de los pacientes, indicaciones,formas de empleo del antibiótico, respuesta clínica,tolerabilidad y evolución de los pacientes dependiendo de suingreso en UCI cuando utilizaron tigeciclina Los datos sepresentan de forma descriptiva y mediante la comparación devariables entre las dos cohortes.Resultados. Se han incluido 103 pacientes de los que 34(33,0%) recibieron tigeciclina durante su estancia en UCI. Lospacientes ingresados en UCI tuvieron mayor SAPS II al ingresoen el hospital (39,0 ± 11,8 vs. 26,3 ± 8,0; p<0,001) y al inicio deltratamiento con tigeciclina (42,2 ± 12,6 vs. 25.6 ± 8,2;p=0,001), utilizaron antibióticos de forma previa durante másdías (21,4 ± 30,6 vs. 13,6 ± 30,5; p<0,012) y mas antibióticos deforma concomitante (85,3% vs. 47,8%; p<0,001), presentaronmayor selección de flora emergente (41,2% vs. 15,9%;p=0,005), en especial P. aeruginosa (20,6% vs. 2,9%; p=0,006),mayor fracaso clínico (58,8% vs. 21,7%; p<0,001) y seasociaron con mayor estancia hospitalaria (51,2 ± 39,4 vs. 28,7± 26,3 días; p<0,001) y mayor mortalidad cruda (50,0% vs.14,5%; p<0,001) y atribuida a la infección (20,6% vs. 7,2%;p=0,047)...(AU)

Background. Tigecycline is a new broad spectrumantibiotic that is predominantly used for the treatment ofsevere infections both in critically ill patients admittedto the ICU and in non-ICU patients with less severe clinicalconditions.Objetive. To assess differences in the use of tigecyclinebetween ICU patients and non-ICU patients treatedwith this antibiotics.Materials and methods. Retrospective, cohort, observationalstudy in which cases were defined as patientswho received one or more doses of tigecycline over thefirst 18 months after approval of the drug in a generalhospital. Clinical characteristics, indications, route of administration,clinical response, tolerability and outcomewere recorded in the groups of ICU and non-ICU patients.Descriptive data and results of the comparison ofboth cohorts are presented.Results. A total of 103 were included in the study, 34(33%) of which received tigecycline during their stay inthe ICU. ICU patients compared to non-ICU patients hada higher SAPS II score on admission (39.0 ± 11.8 vs 26.3± 8.0, p < 0.001) and at the time of starting tigecyclinetreatment (42.2 ± 12.6 vs 25.6 ± 8.2, p < 0.001), weretreated with antibiotics for more days (21.4 ± 30.6 vs13.6 ± 30.5 days, p < 0.012) and received a greater numberof antibiotic agents concomitantly (85.3% vs 47.8%, p < 0.001), presented a higher selection of emerging bacterialflora (41.2% vs 15.9%, p = 0.005), particularlyPseudomonas aeruginosa (20.6% vs 2.9%, p = 0.006),higher rate of clinical failure (58.8% vs 21.7%, p <0.001), longer hospitalization (51.2 ± 39.4 vs 28.7 ±26.3 days, p < 0.001) and higher overall mortality rate(50% vs 14.5%, p < 0.001) and infection-attributed mortality(20.6% vs 7.2%, p = 0.047)(AU)