Ceftazidime, Carbapenems, or Piperacillin-tazobactam as Single Definitive Therapy for Pseudomonas aeruginosa Bloodstream Infection: A Multisite Retrospective Study.

BACKGROUND: The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although ß-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. METHODS: A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with ß-lactam monotherapy during 2009-2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. RESULTS: Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52-2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67-2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). CONCLUSIONS: No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection.

Extended-pulsed fidaxomicin versus vancomycin in patients 60 years and older with Clostridium difficile infection: cost-effectiveness analysis in Spain.

The cost of treating Clostridium difficile infection (CDI) in Spain is substantial. Findings from the randomised, controlled, open-label, phase 3b/4 EXTEND study showed that an extended-pulsed fidaxomicin (EPFX) regimen was associated with improved sustained clinical cure and reduced recurrence of CDI versus vancomycin in patients aged 60 years and older. We assessed the cost-effectiveness of EPFX versus vancomycin for the treatment of CDI in patients aged 60 years and older from the perspective of the National Health System (NHS) in Spain. We used a Markov model with six health states and 1-year time horizon. Health resources, their unit costs and utilities were based on published sources. Key efficacy data and transition probabilities were obtained from the EXTEND study and published sources. A panel of Spanish clinical experts validated all model assumptions. In the analysis, 0.638 and 0.594 quality-adjusted life years (QALYs) per patient were obtained with EPFX and vancomycin, respectively, with a gain of 0.044 QALYs with EPFX. The cost per patient treated with EPFX and vancomycin was estimated to be €10,046 and €10,693, respectively, with a saving of €647 per patient treated with EPFX. For willingness-to-pay thresholds of €20,000, €25,000 and €30,000 per QALY gained, the probability that EPFX was the most cost-effective treatment was 99.3%, 99.5% and 99.9%, respectively. According to our economic model and the assumptions based on the Spanish NHS, EPFX is cost-effective compared with vancomycin for the first-line treatment of CDI in patients aged 60 years and older.

Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: Guidelines by the Spanish Society of Chemotherapy / Elección del tratamiento antibiótico en la infección invasiva aguda por Pseudomonas aeruginosa: Guía de la Sociedad Española de Quimioterapia

Pseudomonas aeruginosa is characterized by a notable intrinsic resistance to antibiotics, mainly mediated by the expression of inducible chromosomic β-lactamases and the production of constitutive or inducible efflux pumps. Apart from this intrinsic resistance, P. aeruginosa possess an extraordinary ability to develop resistance to nearly all available antimicrobials through selection of mutations. The progressive increase in resistance rates in P. aeruginosa has led to the emergence of strains which, based on their degree of resistance to common antibiotics, have been defined as multidrug resistant, extended-resistant and panresistant strains. These strains are increasingly disseminated worldwide, progressively complicating the treatment of P. aeruginosa infections. In this scenario, the objective of the present guidelines was to review and update published evidence for the treatment of patients with acute, invasive and severe infections caused by P. aeruginosa. To this end, mechanisms of intrinsic resistance, factors favoring development of resistance during antibiotic exposure, prevalence of resistance in Spain, classical and recently appeared new antibiotics active against P. aeruginosa, pharmacodynamic principles predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment were reviewed to elaborate recommendations by the panel of experts for empirical and directed treatment of P. aeruginosa invasive infections (AU)

Pseudomonas aeruginosa se caracteriza por una notable resistencia intrínseca a los antibióticos mediada fundamentalmente por la expresión de β-lactamasas cromosómicas inducibles y la producción constitutiva o inducible de bombas de expulsión. Además de esta resistencia intrínseca, P. aeruginosa posee una extraordinaria capacidad para desarrollar resistencia a prácticamente todos los antimicrobianos disponibles a través de la selección de mutaciones. El aumento progresivo de la resistencia en P. aeruginosa ha llevado a la aparición de cepas que, de acuerdo con el grado de resistencia frente a los antibióticos habituales, se han definido como multirresistentes, extensamente resistentes y panresistentes. Estas cepas se están diseminando mundialmente, complicando progresivamente el tratamiento de las infecciones por P. aeruginosa. En este escenario, el objetivo de las presentes recomendaciones es la revisión y puesta al día de la evidencia publicada para el tratamiento de pacientes con infección aguda, invasiva y grave por P. aeruginosa. Con este fin, se han revisado los mecanismos de resistencia intrínseca, factores que favorecen el desarrollo de resistencia durante la exposición a antibióticos, prevalencia de la resistencia en España, antibióticos clásicos así como los de reciente introducción activos frente a P. aeruginosa, principios farmacodinámicos predictores de eficacia, experiencia clínica con tratamientos en monoterapia o terapia combinada y principios del tratamiento antibiótico para elaborar por un panel de xpertos recomendaciones para el tratamiento empírico o dirigido de infecciones invasivas por P. aeruginosa (AU)

Non-antibiotic treatment for infectious diseases / Tratamiento no antibiótico de las enfermedades infecciosas

The abuse and uncontrolled use of antibiotics has resulted in the emergence and spread of resistant bacteria. The utility of conventional antibiotics for the treatment of bacterial infections has become increasingly strained due to increased rates of resistance coupled with reduced rates of development of new agents. As a result, multidrug-resistant, extensively drug-resistant, and pan-drug-resistant bacterial strains are now frequently encountered. This has led to fears of a 'post-antibiotic era' in which many bacterial infections could be untreatable. Alternative non-antibiotic treatment strategies need to be explored to ensure that a robust pipeline of effective therapies is available to clinicians. The new therapeutic approaches for bacterial infections (beyond antibiotics) may provide a way to extend the usefulness of current antibiotics in an era of multidrug-resistant (MDR) bacterial infections (AU)

La utilidad de los antibióticos convencionales en el tratamiento de las infecciones bacterianas se ha visto comprometida debido a las elevadas tasas de resistencia junto con la reducción en el número de nuevos agentes en desarrollo. Como resultado, ahora es frecuente encontrar cepas bacterianas multirresistentes, extensamente resistentes o panrresistentes. Esto nos transporta a una era post-antibiótica en la cual muchas infecciones bacterianas podrían ser intratables. Se necesitan explorar estrategias de tratamiento alternativas a los antibióticos que aseguren un 'pipeline' robusto de terapias efectivas que lleguen a estar disponibles para los clínicos. De esta forma, las nuevas estrategias terapéuticas (más allá de los antibióticos) aportarán una vía para extender la utilidad de los antibióticos actuales en una era de infecciones por bacterias multirresistentes (MDR) (AU)

Papel de la daptomicina en el tratamiento de las infecciones en el paciente oncohematológico / Role of daptomycin in the treatment of infections in patients with hematological malignancies

Introducción: Las infecciones bacterianas en pacientes con neoplasias hematológicas conllevan una alta morbimortalidad. Los microorganismos grampositivos pueden causar más de la mitad de los episodios infecciosos bacterianos del enfermo con neutropenia febril, especialmente cuando se trata de bacteriemias. Se precisa una cobertura eficaz frente a tales infecciones en estos huéspedes especialmente inmunodeprimidos. Pacientes y métodos: Se revisa la literatura científica reciente de la última década sobre infecciones en pacientes oncohematológicos, con o sin neutropenia febril, y se destacan las publicaciones que atienden los procesos causados por grampositivos y el manejo de estas infecciones, sean o no bacteriémicas, mediante los fármacos tradicionales (glucopéptidos) y los nuevos antibióticos (linezolid, tigeciclina y daptomicina). Resultados: Se evidencia una llamativa escasez de estudios sobre el tratamiento de estas infecciones por microorganismos grampositivos en pacientes con cáncer mediante los nuevos antimicrobianos; destaca especialmente la carencia de ensayos comparativos. En concreto, para el caso de la daptomicina no se dispone de estudios aleatorizados comparativos en pacientes con neutropenia febril, aunque sí de estudios observacionales retrospectivos y de registro de casos (EUCORE) con un amplio número de pacientes oncohematoló- gicos (en torno a 200). En cuanto a la eficacia, las tasas de respuesta global favorable se sitúan entre el 65 y el 90% en los tres estudios principales, con un porcentaje de éxito terapéutico del 85% en pacientes con neutropenia febril grave. Simultáneamente, el perfil de seguridad de la daptomicina se mostró muy apropiado, con una buena tolerancia y una baja tasa de efectos secundarios (< 10% para los directamente relacionados con el antibiótico) que, en muy pocas ocasiones, fueron graves u obligaron a la interrupción del tratamiento. La tasa de nefrotoxicidad fue mucho más baja respecto a la causada por vancomicina en grupos de control históricos comparativos, aunque no alcanzaron la significación estadística. Conclusiones: La daptomicina es una alternativa terapéutica eficaz y segura en el tratamiento de las infecciones bacterianas por microorganismos grampositivos en los pacientes con cáncer, con o sin neutropenia, si bien se precisan datos más sólidos y definitivos para apoyar su inclusión en el tratamiento empírico de la neutropenia febril (AU)

Introduction: Bacterial infections in patients with hematological neoplasms carry high morbidity and mortality. Gram-positive microorganisms can cause more than half of the bacterial infections in patients with febrile neutropenia, especially bacteremias. Effective coverage against these infections in these hosts, especially the immunodepressed, is required. Patients and methods: We reviewed the literature published in the last decade on infections in patients with hematological malignancies, with or without febrile neutropenia. Emphasis was placed on publications analyzing the processes caused by Gram-positive microorganisms and the management of these infections (whether bacteremic or otherwise) through traditional drugs (glycopeptides) and the new antibiotics (linezolid, tigecycline and daptomycin). Results: There was a notable scarcity of studies on the treatment of infections due to Gram-positive microorganisms in patients with cancer through treatment with the new antimicrobial drugs. Especially striking was the lack of comparative studies. Specifically, in the case of daptomycin, there were no randomized comparative trials in patients with febrile neutropenia, although there were observational retrospective studies or case studies [European Cubicin® Outcome Registry and Experience (EUCORE)] with a large number of patients (around 200) with oncological malignancies. In the three main studies, the overall favorable response rates were between 65% and 90%, with a therapeutic success rate of 85% in patients with severe febrile neutropenia. At the same time, the safety profile of daptomycin was shown to be highly favorable with good tolerability and a low rate of adverse effects (< 10% for those directly related to the antibiotic) which, on very few occasions, were severe or led to treatment withdrawal. The nephrotoxicity rate was much lower than that caused by vancomycin in historical control groups, although there were no statistically significant differences. Conclusions: Daptomycin is a safe and effective therapeutic alternative in the treatment of bacterial infections due to Gram-positive microorganisms in patients with cancer, with or without neutropenia. However, further studies are required to support the use of this drug in the empirical treatment of febrile neutropenia (AU)

[Role of daptomycin in the treatment of infections in patients with hematological malignancies]. / Papel de la daptomicina en el tratamiento de las infecciones en el paciente oncohematológico.

INTRODUCTION: Bacterial infections in patients with hematological neoplasms carry high morbidity and mortality. Gram-positive microorganisms can cause more than half of the bacterial infections in patients with febrile neutropenia, especially bacteremias. Effective coverage against these infections in these hosts, especially the immunodepressed, is required. PATIENTS AND METHODS: We reviewed the literature published in the last decade on infections in patients with hematological malignancies, with or without febrile neutropenia. Emphasis was placed on publications analyzing the processes caused by Gram-positive microorganisms and the management of these infections (whether bacteremic or otherwise) through traditional drugs (glycopeptides) and the new antibiotics (linezolid, tigecycline and daptomycin). RESULTS: There was a notable scarcity of studies on the treatment of infections due to Gram-positive microorganisms in patients with cancer through treatment with the new antimicrobial drugs. Especially striking was the lack of comparative studies. Specifically, in the case of daptomycin, there were no randomized comparative trials in patients with febrile neutropenia, although there were observational retrospective studies or case studies [European Cubicin(®) Outcome Registry and Experience (EUCORE)] with a large number of patients (around 200) with oncological malignancies. In the three main studies, the overall favorable response rates were between 65% and 90%, with a therapeutic success rate of 85% in patients with severe febrile neutropenia. At the same time, the safety profile of daptomycin was shown to be highly favorable with good tolerability and a low rate of adverse effects (< 10% for those directly related to the antibiotic) which, on very few occasions, were severe or led to treatment withdrawal. The nephrotoxicity rate was much lower than that caused by vancomycin in historical control groups, although there were no statistically significant differences. CONCLUSIONS: Daptomycin is a safe and effective therapeutic alternative in the treatment of bacterial infections due to Gram-positive microorganisms in patients with cancer, with or without neutropenia. However, further studies are required to support the use of this drug in the empirical treatment of febrile neutropenia.

Coinfección oportunista durante el tratamiento con infliximab (antifactor de necrosis tumoral alfa) en un paciente con enfermedad de Crohn / Opportunistic co-infection in a patient with Crohn's disease during infliximab (anti-TNF-alpha) therapy

Objetivos Exponer y concienciar acerca del riesgo potencial de causar infecciones graves, oportunistas o no, inherentes al empleo de tratamientos biológicos y, en concreto, de fármacos bloqueadores del TNF-alfa, a partir de la descripción de un caso de infección fúngica invasiva. Métodos Revisión de la historia clínica a partir de la selección del caso obtenido en la base de datos de pacientes con enfermedades inflamatorias crónicas de base autoinmune, candidatos o a los que se les realizan nuevos tratamientos biológicos, y estudio de los aislamientos microbiológicos procedentes de las muestras clínicas significativas. Resultados Se comunica un caso de infección oportunista dual (nocardiosis y aspergilosis) de difícil diagnóstico y complejo tratamiento en un paciente afectado de enfermedad de Crohn e inmunodeprimido, que se desencadenó tras la administración de infliximab (anticuerpo monoclonal anti-TNF-alfa). Conclusiones Las infecciones fúngicas invasivas, bien con presentación clínica aislada o asociadas a otras infecciones oportunistas, están emergiendo en nuevos grupos de riesgo, como son los pacientes receptores de tratamientos biológicos anticitocinas reguladoras de la inflamación y de la inmunidad. Pueden ser potencialmente graves y se precisa un alto índice de sospecha para su diagnóstico precoz. En los pacientes con mayor riesgo de presentarlas deben investigarse las posibles medidas preventivas para evitar su aparición o minimizar su trascendencia(AU)

Background The biological therapies for chronic inflammatory diseases of autoimmune origin, particularly drugs inhibiting cytokines, such as the antagonists of the tumoral necrosis factor alpha (TNFalpha), are acceptably well tolerated in patients suffering rheumatologic, dermatologic and gastrointestinal pathologies. Nevertheless, pharmacologic vigilance studies have clarified several aspects of their security in daily clinical use. The adverse effects associated with inhibitors of TNFalpha can be related to the target (or class) and to the agent. The adverse effects related to the target include those potentially attributable to the inherent immunosuppressive state due to the blockade of the main cytokine, phenomenon that could increase the susceptibility to the infections and cancer. Aims To expound the potential risk of serious infections, opportunistic or not, inherent to the use of biological therapies and, specifically, antagonistic drugs of TNFalpha, from the description of a case of invasive fungal infection. Methods Revision of clinical records, obtained from the chronic inflammatory disease of autoimmune origin patient database, candidates or recipients of the new biological therapies, and study of the microbiological isolates. Conclusions Invasive fungal infections, with isolated or associated clinical presentation to other opportunistic infections, are emerging in new groups-at-risk as they are the recipients of anti-cytokine biological therapies, regulators of inflammation and immunity. They can be potentially serious in their evolution and a high index of suspicion is needed sometimes for their prompt diagnosis. Possible preventive measures in patients with a high risk of suffering them will have to be investigated(AU)

Blastoschizomyces capitatus infection in patients with leukemia: report of 26 cases.

Twenty-six cases of Blastoschizomyces capitatus infection were diagnosed in 25 patients at 7 tertiary care hematology units in Spain over a 10-year period. Most patients (92%) had acute leukemia and developed infection during a period of severe and prolonged neutropenia. Two patients had esophagitis, and the rest had invasive infection. Fungemia (20 cases) was a common finding, with frequent visceral dissemination. The 30-day mortality associated with this infection was 52%, compared with 57% among patients with systemic infection. In a univariate analysis, the following 3 variables had a positive impact on 30-day survival: removal of the central venous catheter within 5 days after the onset of infection (P=.02), a good performance status (P=.003), and receipt of systemic prophylactic or empirical antifungal therapy before infection onset (P=.006). Outcome for neutropenic patients with B. capitatus infection is still poor. Rapid removal of the central venous catheter and novel antifungal therapies are recommended for treatment of this rare infection.