Beneficio del empleo precoz de la oxigenoterapia nasal de alto flujo (ONAF) en pacientes con neumonía por SARS-CoV-2 / Benefits of early use of high-flow-nasal-cannula (HFNC) in patients with COVID-19 associated pneumonia

Introducción:La COVID-19 grave se asocia con una neumonía bilateral hipoxemiante, que desemboca en la necesidad de ventilación mecánica en un considerable número de pacientes. Hasta la fecha no existen recomendaciones acerca del momento óptimo para el inicio de la ONAF.Pacientes y métodos:Estudio retrospectivo de todos los pacientes ingresados por neumonía por COVID-19 y que precisaron ONAF entre marzo de 2020 y febrero de 2021. Se agruparon los pacientes en función del momento de inicio de la ONAF de acuerdo con la PaFi modificada.Resultados:Se incluyeron 53 pacientes, en 44 se inició la ONAF precozmente y en nueve de ellos se inició tardíamente. No existieron diferencias clínico-epidemiológicas significativas. La utilización precoz de la ONAF se asoció con una disminución de la necesidad de intubación (29,5 vs. 66,6%, p = 0,044), de la estancia hospitalaria (18,8 d vs. 36 d, p = 0,022) y de la mortalidad (22,7 vs. 55,5%, p = 0,061).Conclusiones:El empleo precoz de la ONAF se asocia con una disminución de la necesidad de intubación, de la mortalidad y de la estancia hospitalaria global. (AU)

Introduction:Severe COVID-19 is associated with hypoxemic bilateral pneumonia that leads to mechanical ventilation in a considerable proportion of patients. To the best of our knowledge, there are no recommendations about the best time to initiate high flow nasal cannula (HFNC).Patients and methods:Retrospective study of all patients admitted for COVID-19 pneumonia who required HNFO between March 2020 and February 2021. Patients were grouped in early HNFC or late HNFC, according to the modified Kirby index.Results:53 patients were included. Forty-four of them were included in the early HFNC and 9 in late HNFC. There were no statistically significant clinical-epidemiological differences. Early use of HFNC was associated with a decrease in the need for intubation (29.5 vs. 66.6%, p = 0.044), hospital stay (18.8 d vs. 36 d, p = 0.022) and mortality (22.7 vs. 55.5%, p = 0.061).Conclusions:Early HFNC use is associated with a decrease in the need for intubation, mortality and overall hospital stay. (AU)

Benefits of early use of high-flow-nasal-cannula (HFNC) in patients with COVID-19 associated pneumonia.

Introduction: Severe COVID-19 is associated with hypoxemic bilateral pneumonia that leads to mechanical ventilation in a considerable proportion of patients. To the best of our knowledge, there are no recommendations about the best time to initiate high flow nasal cannula (HFNC). Patients and methods: Retrospective study of all patients admitted for COVID-19 pneumonia who required HNFO between March 2020 and February 2021. Patients were grouped in early HNFC or late HNFC, according to the modified Kirby index. Results: 53 patients were included. Forty-four of them were included in the early HFNC and 9 in late HNFC. There were no statistically significant clinical-epidemiological differences. Early use of HFNC was associated with a decrease in the need for intubation (29.5 vs. 66.6%, p = 0.044), hospital stay (18.8 d vs. 36 d, p = 0.022) and mortality (22.7 vs. 55.5%, p = 0.061). Conclusions: Early HFNC use is associated with a decrease in the need for intubation, mortality and overall hospital stay.

Introducción: La COVID-19 grave se asocia con una neumonía bilateral hipoxemiante, que desemboca en la necesidad de ventilación mecánica en un considerable número de pacientes. Hasta la fecha no existen recomendaciones acerca del momento óptimo para el inicio de la ONAF. Pacientes y métodos: Estudio retrospectivo de todos los pacientes ingresados por neumonía por COVID-19 y que precisaron ONAF entre marzo de 2020 y febrero de 2021. Se agruparon los pacientes en función del momento de inicio de la ONAF de acuerdo con la PaFi modificada. Resultados: Se incluyeron 53 pacientes, en 44 se inició la ONAF precozmente y en nueve de ellos se inició tardíamente. No existieron diferencias clínico-epidemiológicas significativas. La utilización precoz de la ONAF se asoció con una disminución de la necesidad de intubación (29,5 vs. 66,6%, p = 0,044), de la estancia hospitalaria (18,8 d vs. 36 d, p = 0,022) y de la mortalidad (22,7 vs. 55,5%, p = 0,061). Conclusiones: El empleo precoz de la ONAF se asocia con una disminución de la necesidad de intubación, de la mortalidad y de la estancia hospitalaria global.

[Benefits of early use of high-flow-nasal-cannula (HFNC) in patients with COVID-19 associated pneumonia]. / Beneficio del empleo precoz de la oxigenoterapia nasal de alto flujo (ONAF) en pacientes con neumonía por SARS-CoV-2.

INTRODUCTION: Severe COVID-19 is associated with hypoxemic bilateral pneumonia that leads to mechanical ventilation in a considerable proportion of patients. To the best of our knowledge, there are no recommendations about the best time to initiate high flow nasal cannula (HFNC). PATIENTS AND METHODS: Retrospective study of all patients admitted for COVID-19 pneumonia who required HNFO between March 2020 and February 2021. Patients were grouped in early HNFC or late HNFC, according to the modified Kirby index. RESULTS: 53 patients were included. Forty-four of them were included in the early HFNC and 9 in late HNFC. There were no statistically significant clinical-epidemiological differences. Early use of HFNC was associated with a decrease in the need for intubation (29.5 vs. 66.6%, p = 0.044), hospital stay (18.8 d vs. 36 d, p = 0.022) and mortality (22.7 vs. 55.5%, p = 0.061). CONCLUSIONS: Early HFNC use is associated with a decrease in the need for intubation, mortality and overall hospital stay.

Clinical efficacy of fosfomycin combinations against a variety of gram-positive cocci / Eficacia clínica de las combinaciones de fosfomicina contra una variedad de cocos grampositivos

Introduction: Over recent years we have witnessed an increase in the resistance of microorganisms to the available antimicrobials and a decrease in the number of new antimicrobials. Fosfomycin is a safe and cheap broad-spectrum antibiotic which has shown very promising results in combination therapy, mainly against gram-negative microorganisms. Little is known, however, about its clinical efficacy against gram-positive microorganisms. Methods: We performed a retrospective review of all patients with severe gram-positive infections who received fosfomycin as part of their treatment from 2011 to 2017. We also performed in vitro time-kill assays to study the behaviour of fosfomycin with different antimicrobials against two strains of methicillin-resistant Staphylococcus aureus (MRSA) and two strains of methicillin-susceptible S. aureus (MSSA). Results: Seventy-five patients were treated with different fosfomycin combinations. Among them, 61 (81%) were successfully treated. Daptomycin plus fosfomycin was the most effective combination. Overall, the treatment with fosfomycin was safe, and side effects were minor. There was only one major side effect that resolved after discontinuation of therapy. Time-kill studies demonstrated increased activity of fosfomycin combinations, with daptomycin-fosfomycin being the most active combination against both MRSA and MSSA strains. Conclusions: Our results suggest that antimicrobial combinations including fosfomycin are an alternative and effective approach for gram-positive infections

Introducción: En los últimos años se ha ido produciendo un aumento de la resistencia de los microorganismos a los antimicrobianos disponibles, y una disminución en el número de nuevos antimicrobianos. La fosfomicina es un antibiótico seguro y barato con un amplio espectro de actividad, que ha mostrado resultados muy prometedores en terapia de combinación, principalmente contra microorganismos gramnegativos. Sin embargo, poco se conoce sobre su eficacia clínica frente a microorganismos grampositivos. Métodos: Revisión retrospectiva de todos los pacientes con infecciones graves por microorganismos grampositivos que recibieron fosfomicina como parte de su tratamiento, entre los años 2011 y 2017. También se realizaron curvas de letalidad in vitro para estudiar el comportamiento de la fosfomicina con diferentes antimicrobianos, frente a 2 cepas de Staphylococcus aureus resistentes a meticilina (SARM) y 2 cepas de S. aureus sensible a la meticilina (SASM). Resultados: Setenta y cinco pacientes recibieron tratamiento con diferentes combinaciones de fosfomicina. De ellos, 61 (81%) fueron tratados con éxito. Daptomicina más fosfomicina fue la combinación más efectiva. En general, el tratamiento con fosfomicina fue seguro, con efectos secundarios menores. Hubo solo un efecto secundario importante que se resolvió tras la suspensión del tratamiento. Las curvas de letalidad demostraron buena actividad de las combinaciones de fosfomicina, siendo la combinación daptomicina-fosfomicina la más activa, tanto frente a las cepas de SARM como de SASM. Conclusiones: Nuestros resultados sugieren que combinaciones con fosfomicina, pueden ser un tratamiento alternativo y efectivo en infecciones por grampositivos

Clinical efficacy of fosfomycin combinations against a variety of gram-positive cocci.

INTRODUCTION: Over recent years we have witnessed an increase in the resistance of microorganisms to the available antimicrobials and a decrease in the number of new antimicrobials. Fosfomycin is a safe and cheap broad-spectrum antibiotic which has shown very promising results in combination therapy, mainly against gram-negative microorganisms. Little is known, however, about its clinical efficacy against gram-positive microorganisms. METHODS: We performed a retrospective review of all patients with severe gram-positive infections who received fosfomycin as part of their treatment from 2011 to 2017. We also performed in vitro time-kill assays to study the behaviour of fosfomycin with different antimicrobials against two strains of methicillin-resistant Staphylococcus aureus (MRSA) and two strains of methicillin-susceptible S. aureus (MSSA). RESULTS: Seventy-five patients were treated with different fosfomycin combinations. Among them, 61 (81%) were successfully treated. Daptomycin plus fosfomycin was the most effective combination. Overall, the treatment with fosfomycin was safe, and side effects were minor. There was only one major side effect that resolved after discontinuation of therapy. Time-kill studies demonstrated increased activity of fosfomycin combinations, with daptomycin-fosfomycin being the most active combination against both MRSA and MSSA strains. CONCLUSIONS: Our results suggest that antimicrobial combinations including fosfomycin are an alternative and effective approach for gram-positive infections.

Clinical predictors of candidemia in medical non-neutropenic, non-ICU patients. The CaMed score.

INTRODUCTION: Candida species are the leading cause of invasive fungal infections in hospitalised patients and are the fourth most common isolates recovered from patients with bloodstream infection. Few data exist on risk factors for candidemia in non-ICU patients. We performed a population-based case-control study to evaluate the main predictors for candidemia in non-ICU patients. METHODS AND FINDINGS: We included all non-neutropenic, non-critically ill and non-surgical adult patients with candidemia between January 2010 and June 2014. Patients with positive, non-candidal blood culture obtained at the same day (±2 days) were selected as controls. Cases and controls were matched according to hospital ward and clinical characteristics. Risk factors for candidemia were identified through a logistic regression. We included 56 candidemic and 512 bacteriemic non-candidemic patients. Most of candidemic patients (52) had received antibiotics prior to candidemia. Among them, the 30-day mortality rate was 34% (19/56). Multivariate analysis identified male sex, prior use of steroids, prior use of antibiotics, total parenteral nutrition and urinary catheterisation as independent predictors of candidemia. To develop the CaMed score, we rounded up weights of different risk factors as follows; total parenteral nutrition (+2), prior antibiotic therapy (+5), each of the other risk factors (+1). A score ≥ 7 identified patients at high risk of candidemia (P < 0.001; RR 29.805; CI 95% 10.652-83.397; sensitivity 79.2, specificity 82.6%, Youden index 0,62). CONCLUSIONS: Our set of easy independent predictors of candidemia in non-neutropenic, non-ICU, non-surgical patients provide a rationale for early initiation of antifungals and could reduce candidemia-related mortality.

In vitro efficacy of daptomycin and teicoplanin combined with ethanol, clarithromycin or gentamicin as catheter lock solutions.

BACKGROUND: Despite widespread use, optimum choice of antimicrobial agents, concentrations, combinations and exposure times have not been determined for antibiotic lock technique (ALT). Our objective was to evaluate the efficacy of different antibiotic combinations using an in vitro model of catheter-related infection. Daptomycin (DAP) 5 mg/mL, teicoplanin (TEC) 5 mg/mL, both alone and combined with gentamicin (GM) 2.5 mg/mL, clarythromycin (CLA) 5 mg/mL or ethanol 35 % were evaluated against four clinical strains of methicillin resistant coagulase negative staphylococci. Lock solutions were renewed every 24 h. RESULTS: After 72 h catheters were reincubated with culture media to investigate bacterial regrowth. All antibiotic combinations resulted in significant reductions (p < 0.05) of Log(10) cfu/mL at 72 h for both organisms compared with controls. DAP resulted in significant reductions of Log(10) for all organism versus TEC (p = 0.001). Only DAP reached the limit of detection at 72 h, however did not prevent regrowth after 24 h of ALT removal. DAP + Ethanol and TEC + ethanol eradicated biofilm at 72 h, but only DAP + ethanol (against all strains) and DAP + CLA (against two strains) prevented regrowth at 24 h after ALT removal. CONCLUSIONS: Based on these data, ALT with DAP + ethanol and DAP + CLA should be explored in clinical trials.

Nebulized medication is not associated with nosocomial infections. A pilot study.

INTRODUCTION: Nebulized devices are commonly used in the treatment of respiratory infection, and other respiratory diseases. It has been reported nosocomial infections in cystic fibrosis patients as a result of the use of contaminated devices. However, little is known about nosocomial infections secondary to aerosolized therapy in COPD patients admitted for acute exacerbation. METHODS: Thirty consecutive patients (13 males) were included. All of them received aerosolized medication. Each patient used their own facemask and nebulizer cup, which were stored in the room after its use. Samples from nebulizer cups were obtained on days 0, 4 and 7. In addition, sputum samples were obtained on day 0 (prior to any nebulization) and on day 7, and cultivated in enriched media. RESULTS: Only nine nebulizer cups had positive microbiological cultures. Coagulase negative staphylococci (CoNS) were isolated in all cases. Sputum samples could be obtained in 27 patients. None grew CoNS after 7 days of aerosolized therapy. Gram-negative non-fermenting bacilli were isolated in three patients without concomitant grown in nebulizer cups. CONCLUSIONS: We did not find any nosocomial infection related to aerosolize medications in COPD patients admitted for acute exacerbation.

Nebulized medication is not associated with nosocomial infections. A pilot study / / El empleo de nebulizaciones no se asocia con infecciones respiratorias nosocomiales. Un estudio piloto

Introduction. Nebulized devices are commonly used in the treatment of respiratory infection, and other respiratory diseases. It has been reported nosocomial infections in cystic fibrosis patients as a result of the use of contaminated devices. However, little is known about nosocomial infections secondary to aerosolized therapy in COPD patients admitted for acute exacerbation. Methods. Thirty consecutive patients (13 males) were included. All of them received aerosolized medication. Each patient used their own facemask and nebulizer cup, which were stored in the room after its use. Samples from nebulizer cups were obtained on days 0, 4 and 7. In addition, sputum samples were obtained on day 0 (prior to any nebulization) and on day 7, and cultivated in enriched media. Results. Only nine nebulizer cups had positive microbiological cultures. Coagulase negative staphylococci (CoNS) were isolated in all cases. Sputum samples could be obtained in 27 patients. None grew CoNS after 7 days of aerosolized therapy. Gram-negative non-fermenting bacilli were isolated in three patients without concomitant grown in nebulizer cups. Conclusions. We did not find any nosocomial infection related to aerosolize medications in COPD patients admitted for acute exacerbation (AU)

Introducción. Los dispositivos para nebulizaciones se emplean frecuentemente en el tratamiento de las infecciones, y otras patologías respiratorias. Existen comunicaciones sobre infecciones nosocomiales en pacientes con fibrosis quística como resultado de la utilización de dispositivos contaminados. Sin embargo, poco se sabe acerca de las infecciones nosocomiales secundarias a la terapia en aerosol en pacientes con EPOC ingresados por exacerbación aguda. Métodos. Treinta pacientes consecutivos (13 varones) fueron incluidos. Todos ellos recibieron la medicación en forma de aerosol. Cada paciente utilizó su propia máscara y cazoletas de nebulización, que se dejaron en la habitación después de su uso. Las muestras de las cazoletas de nebulización se obtuvieron en los días 0, 4 y 7. Además, se obtuvieron muestras de esputo en el día 0 (antes de cualquier nebulización) y en el día 7, cultivándose en medio enriquecido. Resultados. Sólo nueve cazoletas de nebulización tuvieron algún cultivo positivo, siendo estafilococos coagulasa negativos (ECN) en todos los casos. Se obtuvieron muestras de esputo en 27 pacientes. En ningún caso se obtuvo crecimiento de ECN tras 7 días de tratamiento con aerosolterapia. Finalmente en tres pacientes se obtuvo crecimiento de un bacilo gramnegativo no fermentador en el esputo sin crecimiento en las muestras de las cazoletas de nebulización. Conclusiones. En nuestro estudio no se demostró ninguna infección nosocomial relacionada con el empleo de aerosolterapia en los pacientes con EPOC ingresados por exacerbación aguda (AU)

Rational application of adenosine deaminase activity in cerebrospinal fluid for the diagnosis of tuberculous meningitis.

PURPOSE: Tuberculous meningitis (TBM) is one of the most serious and difficult to diagnose manifestations of TB. An ADA value >9.5 IU/L has great sensitivity and specificity. However, all available studies have been conducted in areas of high endemicity, so we sought to determine the accuracy of ADA in a low endemicity area. METHODS: This retrospective study included 190 patients (105 men) who had ADA tested in CSF for some reason. Patients were classified as probable/certain TBM or non-TBM based on clinical and Thwaite's criteria. Optimal ADA cutoff was established by ROC curves and a predictive algorithm based on ADA and other CSF biochemical parameters was generated. RESULTS: Eleven patients were classified as probable/certain TBM. In a low endemicity area, the best ADA cutoff was 11.5 IU/L with 91 % sensitivity and 77.7 % specificity. We also developed a predictive algorithm based on the combination of ADA (>11.5 IU/L), glucose (<65 mg/dL) and leukocytes (≥13.5 cell/mm(3)) with increased accuracy (Se: 91 % Sp: 88 %). CONCLUSIONS: Optimal ADA cutoff value in areas of low TB endemicity is higher than previously reported. Our algorithm is more accurate than ADA activity alone with better sensitivity and specificity than previously reported algorithms.

Características de la tuberculosis en la población inmigrante en el Área de Salud Sur de Granada / Characteristics of tuberculosis in the immigrant population in South Granada Health Area

INTRODUCCIÓN: La incidencia de la tuberculosis (TB) en la población autóctona en España continúa descendiendo, aumentando la proporción de casos en extranjeros. El objetivo de este estudio fue identificar las características diferenciales de la TB en la población inmigrante con respecto a la autóctona en el Área de Salud Sur de Granada, España. MÉTODOS: Estudio descriptivo incluyendo todos los casos de TB diagnosticados durante el período 2003-2010 a partir de una base de datos prospectiva. Se realizó un análisis de regresión logística para determinar las características diferenciales.: RESULTADOS: De los 319 casos de TB diagnosticados, 247 autóctonos y 72 (22,6%) inmigrantes, 272 eran pulmonares. Las siguientes variables se asociaron significativamente con los casos de TB en inmigrantes: edad < 35 años (OR = 4,75; IC:2,72-8,31), mayor porcentaje de cavitación en la radiografía torácica (OR = 2,26; IC:1,20-4,20), mayor porcentaje de TB pulmonar bacilífera (OR = 1,80; IC:1,02-3,16), mayor retraso diagnóstico en TB pulmonar bacilífera (mediana 32 días vs. 21 días; p = 0,043) y menor letalidad total (OR = 0,12; IC:0,01-0,89). CONCLUSIONES: La incidencia de la TB se ha mantenido constante en el Área Sur de Granada a expensas de los casos en población inmigrante. Comparados con los autóctonos, los pacientes inmigrantes con TB eran más jóvenes, tenían enfermedad más avanzada (mayor porcentaje de bacilíferos y de cavitación radiológica) y más retraso diagnóstico en TB pulmonar bacilífera, indicando peor control de la enfermedad. Son necesarias estrategias para un diagnóstico más precoz de la TB en la población inmigrante

INTRODUCTION: The incidence of tuberculosis (TB) among the native population in Spain continues to decrease, resulting in a higher proportion of foreign-born cases. The aim of this study was to identify the differential TB characteristics within the immigrant population with respect to the native population in the South Granada Health Area, Spain. METHODS: This was a descriptive study, including all cases of TB diagnosed during the period 2003-2010. Cases were identified through a prospective database. A logistic regression analysis was performed to determine differential characteristics. RESULTS: From 319 TB cases diagnosed, 247 were natives and 72 (22.6%) immigrants, and 272 were pulmonary tuberculosis. The following variables were significantly associated with immigrant TB cases: age < 35 years (OR = 4.75, CI: 2.72-8.31), higher percentage of cavitated chest X-ray (OR = 2.26, CI: 1.20-4.20), higher percentage of smear-positive cases (OR = 1.80, CI: 1.02-3.16), longer diagnostic delay in smear-positive pulmonary TB (median 32 days vs. 21 days P = .043), and lower total lethality (OR = 0.12; CI: 0.01-0.89). CONCLUSIONS: The incidence of TB has remained constant in the South Granada Health Area due to the increase in cases among immigrants. Compared with native TB patients, immigrant patients were younger and had more advanced disease (higher percentage of smear-positive cases and higher percentage of cavitated chest X-ray) and longer diagnostic delay in smear-positive pulmonary TB, indicating poorer TB control. Strategies for earlier diagnosis of TB in immigrants are essential

[Characteristics of tuberculosis in the immigrant population in South Granada Health Area]. / Características de la tuberculosis en la población inmigrante en el Área de Salud Sur de Granada.

INTRODUCTION: The incidence of tuberculosis (TB) among the native population in Spain continues to decrease, resulting in a higher proportion of foreign-born cases. The aim of this study was to identify the differential TB characteristics within the immigrant population with respect to the native population in the South Granada Health Area, Spain. METHODS: This was a descriptive study, including all cases of TB diagnosed during the period 2003-2010. Cases were identified through a prospective database. A logistic regression analysis was performed to determine differential characteristics. RESULTS: From 319 TB cases diagnosed, 247 were natives and 72 (22.6%) immigrants, and 272 were pulmonary tuberculosis. The following variables were significantly associated with immigrant TB cases: age<35 years (OR=4.75, CI: 2.72-8.31), higher percentage of cavitated chest X-ray (OR=2.26, CI: 1.20-4.20), higher percentage of smear-positive cases (OR=1.80, CI: 1.02-3.16), longer diagnostic delay in smear-positive pulmonary TB (median 32 days vs. 21 days P=.043), and lower total lethality (OR=0.12; CI: 0.01-0.89). CONCLUSIONS: The incidence of TB has remained constant in the South Granada Health Area due to the increase in cases among immigrants. Compared with native TB patients, immigrant patients were younger and had more advanced disease (higher percentage of smear-positive cases and higher percentage of cavitated chest X-ray) and longer diagnostic delay in smear-positive pulmonary TB, indicating poorer TB control. Strategies for earlier diagnosis of TB in immigrants are essential.

High doses of daptomycin (10 mg/kg/d) plus rifampin for the treatment of staphylococcal prosthetic joint infection managed with implant retention: a comparative study.

We aimed to analyze the efficacy and safety of high doses of daptomycin (10 mg/kg/d) plus rifampin (D10 + R) for prosthetic joint infection (PJI). This was an observational retrospective multicenter study (2010-2012) including all patients with acute PJI by fluoroquinolone-resistant staphylococci managed with implant retention and D10 + R. Twenty cases were included: 2 (10%) were withdrawn due to toxicity, leaving 18 cases for efficacy evaluation: 13 (72%) women, age 79 years (range 58-90). Clinical failure was observed in 9 (50%) patients: in 5 cases, staphylococci were recovered (28% of microbiological failures); no modification of daptomycin-MIC was observed. These 18 cases were compared with 44 matched historical cases: failure rate was similar, but whereas in the historical series, failure occurred fundamentally during therapy, in the present series, it was recorded after discontinuation of antibiotics. In summary, D10 + R may be the initial treatment of choice for PJI by fluoroquinolone-resistant staphylococci managed with implant retention.

Protease inhibitor monotherapy is not associated with increased viral replication in lymph nodes.

There are concerns about residual viremia in sanctuary sites among patients on protease inhibitor monotherapy, so we aimed to study viro-immunological parameters in tonsil's lymphoid tissue of patients on highly active antiretroviral therapy (HAART) and on protease inhibitor monotherapy. Despite fully suppressed serum HIV viral load, we found viral replication in both groups; in addition, more patients had detectable proviral DNA among those on HAART, compared to those on protease inhibitor monotherapy (P = 0.08), supporting the absence of a deleterious effect of protease inhibitor monotherapy.

Elution kinetics, antimicrobial activity, and mechanical properties of 11 different antibiotic loaded acrylic bone cement.

Antibiotic-loaded acrylic bone cements (ALABC) spacers are routinely used in the treatment of prosthetic joint infections. The objectives of our study were to evaluate different ALABC for elution kinetics, thermal stability, and mechanical properties. A 10 or 20% mixture (w/w) beads of medium viscosity bone cement (DePuy, Inc) and vancomycin (VAN), gentamycin (GM), daptomycin (DAP), moxifloxacin (MOX), rifampicin (RIF), cefotaxime (CTX), cefepime (FEP), amoxicillin clavulanate (AmC), ampicillin (AMP), meropenem (MER), and ertapenem (ERT) were formed and placed into wells filled with phosphate-buffered saline. Antibiotic concentrations were determined using high-performance liquid chromatography. Antimicrobial activity was tested against Micrococcus luteus ATCC 9341 or Escherichia coli ATCC 25922. AmC, AMP, and FEP concentration rapidly decreased after day 2, being almost undetectable at day 4. Sustained and high elution rates were observed with VAN, GM, MOX, and RIF for the 30-day duration of the experiment. DAP, MER, ERT, and CTX elution rates constantly decreased from day 4. All antibiotics tested retained antimicrobial activity proving thermal stability. Mechanical properties of ALABC were maintained except when RIF was used.

[Update on hepatitis C therapy. New drugs, treatment response monitoring and emergence of resistance]. / Actualización en la terapia de la hepatitis C. Nuevos fármacos, monitorización de la respuesta y resistencias.

The development of novel direct antiviral agents (DAAs) against hepatitis C virus (HCV) has represented a breakthrough in the treatment of chronic hepatitis C. Telaprevir and boceprevir are the first two protease inhibitor (PI) DAAs to be approved for combination therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). In genotype 1 monoinfected patients, triple PI therapy has increased sustained viral response (SVR) rates by approximately 30% compared with conventional combination therapy. The introduction of these drugs into clinical practice will modify the timing of monitoring parameters in diagnostic laboratories, especially with regard to stopping rules and to faster delivery of results. In the near future, new DAAs, directed against different targets of the HCV cycle (polymerase inhibitors, viral replication complex inhibitors and cyclophilin inhibitors), which are currently in various stages of clinical development, will be available. Some of these DAAs have already reached advanced phases of development, both in combination with PEG-IFN and RBV and in interferon-free therapy, with very high rates of SVR.

Quantification of viral loads lower than 50 copies per milliliter by use of the Cobas AmpliPrep/Cobas TaqMan HIV-1 test, version 2.0, can predict the likelihood of subsequent virological rebound to >50 copies per milliliter.

After 1 year of follow-up, patients on HAART with a baseline viral load (VL) of <20 copies/ml showed significantly lower odds of virological rebound to two consecutive VLs of >50 copies/ml than those with baseline VLs of 20 to 39 and 40 to 49 (P < 0.001). The time to virological rebound was also significantly shorter (P < 0.001) for the groups with baseline VLs of 20 to 39 and 40 to 49.

Actualización en la terapia de la hepatitis C. Nuevos fármacos, monitorización de la respuesta y resistencias / Update on hepatitis C therapy. New drugs, treatment response monitoring and emergence of resistance

El desarrollo de nuevas moléculas de acción antiviral directa (AAD) frente al virus de la hepatitis C (VHC) ha supuesto un gran avance en el tratamiento de la hepatitis crónica por VHC. Boceprevir y telaprevir son los 2 primeros AAD, pertenecientes a los inhibidores de la proteasa, autorizados para el tratamiento en combinación con interferón pegilado (INF-PEG) y ribavirina (RBV). En pacientes monoinfectados con genotipo 1, esta terapia triple consigue un incremento aproximado de un 30% en las tasas de respuesta viral sostenida con respecto a la biterapia. La introducción de estos fármacos en la práctica clínica supone una modificación de los parámetros de monitorización en los laboratorios, en especial en lo que se refiere a reglas de parada y a rapidez en la entrega de resultados. En un futuro cercano, dispondremos de nuevos fármacos AAD dirigidos frente a diferentes dianas del ciclo del VHC (polimerasa viral, complejo de replicación o ciclofilinas), que en la actualidad se encuentran en distintas fases de desarrollo clínico. Algunos de ellos ya han alcanzado fases avanzadas de desarrollo, tanto en combinación con INF-PEG y RBV como en terapias libres de interferón, con muy elevadas tasas de respuesta viral sostenida

The development of novel direct antiviral agents (DAAs) against hepatitis C virus (HCV) has represented a breakthrough in the treatment of chronic hepatitis C. Telaprevir and boceprevir are the first two protease inhibitor (PI) DAAs to be approved for combination therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). In genotype 1 monoinfected patients, triple PI therapy has increased sustained viral response (SVR) rates by approximately 30% compared with conventional combination therapy. The introduction of these drugs into clinical practice will modify the timing of monitoring parameters in diagnostic laboratories, especially with regard to stopping rules and to faster delivery of results. In the near future, new DAAs, directed against different targets of the HCV cycle (polymerase inhibitors, viral replication complex inhibitors and cyclophilin inhibitors), which are currently in various stages of clinical development, will be available. Some of these DAAs have already reached advanced phases of development, both in combination with PEG-IFN and RBV and in interferon-free therapy, with very high rates of SVR

Parámetros farmacodinámicos y farmacocinéticos de las fluoroquinolonas respiratorias. Guía para la selección de la fluoroquinolona más apropiada / Pharmacodynamic and pharmacokinetic evaluation of respiratory fluoroquinolones. Guideline to selection of the most appropriate fluoroquinolone

Desde su introducción en el mercado, las fluoroquinolonas se han convertido en los agentes antibacterianos más prescritos. Existe una seria preocupación acerca de la aparición de resistencias en especies bacterianas como Streptococcus pneumoniae, Pseudomonas spp y enterobacterias, especialmente por la existencia de resistencia cruzada entre los miembros de la familia de las quinolonas. En los últimos años se ha realizado un enorme esfuerzo para identificar factores farmacocinéticos (PK) como la concentración máxima (Cmax) y el área bajo la curva de las concentraciones plasmáticas (ABC), y farmacodinámicos (PD) como la concentración mínima inhibitoria (CMI) o la concentración preventiva de mutantes (CPM), que permitan optimizar el empleo de las fluoroquinolonas, especialmente frente a estos microorganismos. De las fluoroquinolonas existentes en España, levofloxacino y moxifloxacino presentan notables diferencias en cuanto a sus parámetros PK (Cmax, vida media, volumen de distribución, etc) y PD (concentración mínima inhibitoria) así como en su relación PK/PD (ABC/CMI; ABC/CPM) que permiten establecer claramente una preferencia de uso de una sobre la otra. La utilización adecuada de las fluoroquinolonas de acuerdo a estos parámetros PK/PD se traducirá en una mejora del tratamiento de las infecciones respiratorias con una disminución de la aparición de resistencias. En este sentido utilizar moxifloxacino, con mejores características PK/PD debe ser una opción preferente sobre el empleo de levofloxacino que, de emplearse debería hacerse utilizando dosis diferentes a las actuales(AU)

Since its approval, fluoroquinolones have become one of the most prescribed antibacterial agents. Because of its widespread use, serious concerns about the emergence of resistance in Streptococcus pneumoniae, Pseudomonas spp, and entrobacteriaceae, has arisen, especially because of cross-resistance between fluoroquinolones. Huge efforts has been done to identify pharmacokinetic (PK) parameters like maximum serum concentration (Cmax), area under the curve of serum concentrations (AUC) and pharmacodynamic (PD) parameters like the minimum inhibitory concentration (MIC) or the mutant prevention concentration (MPC), to optimize the use of the new fluoroquinolones, especially against these difficult to treat microorganisms. The new fluoroquinolones commercially available in Spain, levofloxacin and moxifloxacin, have significant differences in their PK (Cmax, half-life, volume of distribution, etc), PD (MIC, MPC,) and in their PK/PD parameters (AUC/MIC; AUC/MPC) that allow clinicians to establish clear preference for the utilization of one of them. Proper use of these new fluoroquinolones according to these PK/PD parameters will result in better management of respiratory infections with a reduction in the emergence of resistance. Based on data reviewed in this paper moxifloxacin use, with best PK/PD characteristics, should be preferred over levofloxacin. Should levofloxacin be used, alternative dosing strategies would be recommended to avoid selection of resistant variants(AU)