Risk Factors of Daptomycin-Induced Eosinophilic Pneumonia in a Population with Osteoarticular Infection

Background: Daptomycin-induced eosinophilic pneumonia (DEP) is a rare but severe adverse effect and the risk factors are unknown. The aim of this study was to determine risk factors for DEP. Methods: A retrospective cohort study was performed at the Bone and Joint Infection Unit of the Hospital Universitari Bellvitge (January 2014-December 2018). To identify risk factors for DEP, cases were divided into two groups: those who developed DEP and those without DEP. Results: Among the whole cohort (n = 229) we identified 11 DEP cases (4.8%) and this percentage almost doubled in the subgroup of patients ≥70 years (8.1%). The risk factors for DEP were age ≥70 years (HR 10.19, 95%CI 1.28-80.93), therapy >14 days (7.71, 1.98-30.09) and total cumulative dose of daptomycin ≥10 g (5.30, 1.14-24.66). Conclusions: Clinicians should monitor cumulative daptomycin dosage to minimize DEP risk, and be cautious particularly in older patients when the total dose of daptomycin exceeds 10 g

Measurement uncertainty of β-lactam antibiotics results: estimation and clinical impact on therapeutic drug monitoring

Background: Despite that measurement uncertainty data should facilitate an appropriate interpretation of measured values, there are actually few reported by clinical laboratories. We aimed to estimate the measurement uncertainty of some β-lactam antibiotics (β-LA), and to evaluate the impact of reporting the measurement uncertainty on clinicians' decisions while guiding antibiotic therapy. Methods: Measurement uncertainty of β-LA (aztreonam [ATM], cefepime [FEP], ceftazidime [CAZ], and piperacillin [PIP]) values, obtained by an UHPLC-MS/MS based-method, was estimated using the top-down approach called the single laboratory validation approach (EUROLAB guidelines). Main uncertainty sources considered were related to calibrators' assigned values, the intermediate precision, and the bias. As part of an institutional program, patients with osteoarticular infections are treated with β-LA in continuous infusion and monitored to assure values at least 4 times over the minimal inhibitory concentration (4×MIC). We retrospectively evaluated the impact of two scenarios of laboratory reports on clinicians' expected decisions while monitoring the treatment: reports containing only the β-LA values, or including the β-LA coverage intervals (β-LA values and their expanded measurement uncertainties). Results The relative expanded uncertainties for ATM, FEP, CAZ and PIP were lower than 26.7%, 26.4%, 28.8%, and 25.5%, respectively. Reporting the measurement uncertainty, we identified that clinicians may modify their decision especially in cases where 4×MIC values were within the β-LA coverage intervals. Conclusions: This study provides a simple method to estimate the measurement uncertainty of β-LA values that can be easily applied in clinical laboratories. Further studies should confirm the potential impact of reporting measurement uncertainty on clinicians' decision-making while guiding antibiotic therapy

Long-Term Use of Tedizolid in Osteoarticular Infections: Benefits among Oxazolidinone Drugs

Background: To evaluate the efficacy and safety of long-term use of tedizolid in osteoarticular infections. Methods: Multicentric retrospective study (January 2017–March 2019) of osteoarticular infection cases treated with tedizolid. Failure: clinical worsening despite antibiotic treatment or the need of suppressive treatment. Results: Cases (n = 51; 59% women, mean age of 65 years) included osteoarthritis (n = 27, 53%), prosthetic joint infection (n = 17, 33.3%), and diabetic foot infections (n = 9, 18%); where, 59% were orthopedic device-related. Most frequent isolates were Staphylococcus spp. (65%, n = 47; S. aureus, 48%). Reasons for choosing tedizolid were potential drug-drug interaction (63%) and cytopenia (55%); median treatment duration was 29 days (interquartile range -IQR- 15–44), 24% received rifampicin (600 mg once daily) concomitantly, and adverse events were scarce (n = 3). Hemoglobin and platelet count stayed stable throughout treatment (from 108.6 g/L to 116.3 g/L, p = 0.079; and 240 × 109/L to 239 × 109/L, p = 0.942, respectively), also in the subgroup of cases with cytopenia. Among device-related infections, 33% were managed with implant retention. Median follow-up was 630 days and overall cure rate 83%; among failures (n = 8), 63% were device-related infections. Conclusions: Long-term use of tedizolid was effective, showing a better safety profile with less myelotoxicity and lower drug-drug interaction than linezolid. Confirmation of these advantages could make tedizolid the oxazolidinone of choice for most of osteoarticular infections

Prosthetic shoulder joint infection by Cutibacterium acnes: does rifampin improve prognosis? a retrospective, multicenter, observational study.

This retrospective, multicenter observational study aimed to describe the outcomes of surgical and medical treatment of C. acnes-related prosthetic joint infection (PJI) and the potential benefit of rifampin-based therapies. Patients with C. acnes-related PJI who were diagnosed and treated between January 2003 and December 2016 were included. We analyzed 44 patients with C. acnes-related PJI (median age, 67.5 years (IQR, 57.3-75.8)); 75% were men. The majority (61.4%) had late chronic infection according to the Tsukayama classification. All patients received surgical treatment, and most antibiotic regimens (43.2%) included β-lactam. Thirty-four patients (87.17%) were cured; five showed relapse. The final outcome (cure vs. relapse) showed a nonsignificant trend toward higher failure frequency among patients with previous prosthesis (OR: 6.89; 95% CI: 0.80-58.90) or prior surgery and infection (OR: 10.67; 95% IC: 1.08-105.28) in the same joint. Patients treated with clindamycin alone had a higher recurrence rate (40.0% vs. 8.8%). Rifampin treatment did not decrease recurrence in patients treated with β-lactams. Prior prosthesis, surgery, or infection in the same joint might be related to recurrence, and rifampin-based combinations do not seem to improve prognosis. Debridement and implant retention appear a safe option for surgical treatment of early PJI

Problemática de la antibioterapia en la infección de prótesis articular. Una aproximación mediante un modelo animal de infección de cuerpo extraño por «Staphylococcus aureus» meticilín-sensible

[spa] La infección de material protésico en Ortopedia y Traumatología supone un gran problema clínico y es actualmente un reto terapéutico para un equipo médico. Con estas premisas, el objetivo del presente proyecto fue conocer las posibilidades terapéuticas de mayor eficacia en este ámbito utilizando como instrumento de aproximación un modelo animal de infección asociada a cuerpo extraño por S. aureus meticilin sensible. METODOLOGÍA. Utilizando ratas macho Wistar, se les implantó dos cajas de Teflón subcutáneamente y se produjo la infección mediante la inoculación en su interior de 0,2-2x106 UFC/ml de S. aureus. Las distintas pautas antibióticas se administraron durante 7, 10 ó 15 días, por vía intraperitoneal. La diferencia entre los recuentos bacterianos antes de iniciar el tratamiento y al finalizar el mismo se usó como criterio de eficacia de la pauta antibiótica. Se estudió el desarrollo de resistencias en el líquido de las cajas durante el tratamiento. Se llevaron a cabo estudios in vitro de la eficacia antibiótica frente a bacterias en fase exponencial y fase estacionaria. RESULTADOS. 1. Estandarización del modelo experimental de infección de cuerpo extraño en rata. El modelo reprodujo los elementos característicos de este tipo de infección: a/ persistencia de la infección estable en el tiempo; b/ expresión de tolerancia antibiótica de las bacterias en contacto con el cuerpo extraño; c/ presencia de un biofilm macroscópico; d/ presencia de bacterias adherentes al cuerpo extraño; y e/ presencia de bacterias intracelulares. 2. Estudio de eficacia de los distintos tratamientos en monoterapia. Levofloxacino a dosis altas (equivalente a dosis 750-1000 mg/d en humanos) fue el tratamiento más eficaz, siendo especialmente relevante los parámetros farmacodinámicos alcanzados en comparación con las dosis convencionales de levofloxacino (equivalente a 500 mg/d en humanos). Rifampicina fue el segundo antibiótico más activo y linezolid resultó ser el menos eficaz . Los estudios in vitro realizados con bacterias en fase estacionaria se correlacionaron mejor con los estudios de eficacia in vivo que los realizados con bacterias en fase exponencial. 3. Estudio de eficacia de las fluoroquinolonas y relación con los parámetros farmacodinámicos. Moxifloxacino a dos dosificaciones (equivalentes a las dosis en humanos de 400 y 800 mg/d) mejoró los parámetros farmacodinámicos (AUC/MIC de 431 y 568, respectivamente) de levofloxacino a altas dosis (AUC/MIC de 234), pero ello no se tradujo en una mayor eficacia in vivo. 4. Estudio del antagonismo de la combinación levofloxacino-rifampicina. Los estudios in vivo mostraron que levofloxacino a dosis altas en solitario fue el tratamiento más eficaz, significativamente mejor que levofloxacino a dosis convencionales y que las combinaciones de ambas dosis de levofloxacino con rifampicina. El estudio de resistencias demostró la protección mutua entre levofloxacino y rifampicina frente al desarrollo de cepas resistentes. La dosis de levofloxacino no fue relevante en la eficacia de la combinación levofloxacino-rifampicina. 5. Estudio de la eficacia de linezolid solo y en combinación con rifampicina frente a SAMS. A los 7 días rifampicina en solitario (a pesar del desarrollo de resistencias) fue similar a su combinación con linezolid y superior a linezolid en solitario. A los 10 días la terapia más efectiva fue la combinación de linezolid y rifampicina (en la que no aparecieron cepas resistentes); rifampicina fue ineficaz por la aparición de bacterias resistentes. CONCLUSIONES. Respecto al modelo de infección de cuerpo extraño en ratas observamos que reproduce adecuadamente las características principales de una infección de prótesis articular y se mostró adecuado para valorar la eficacia de diferentes antibioterapias; asimismo, se halló un componente elevado de bacterias de localización intracelular que sugeriría que la actividad antibiótica intracelular debería ser un factor limitante en la eficacia final de una determinada pauta terapéutica. Respecto a la evaluación de la eficacia antibiótica, los resultados obtenidos aportan una clara evidencia para el potencial uso de levofloxacino a altas dosis en solitario en la infección estafilocócica de cuerpo extraño. Moxifloxacino, no mejora estos resultados, apoyando el concepto del efecto máximo en la eficacia de las fluoroquinolonas cuando se consiguen unos determinados parámetros farmacodinámicos considerados óptimos. Rifampicina en solitario se mostró como un tratamiento eficaz in vivo, aunque su uso en monoterapia no se debe considerar por el desarrollo de resistencias. La repercusión clínica del efecto antagónico de la combinación de quinolonas y rifampicina debería tenerse en cuenta cuando se usan nuevas fluoroquinolonas con alta eficacia frente a bacterias en fase estacionaria, como levofloxacino

Conversion of sugars to methyl lactate with exfoliated layered stannosilicate UZAR-S4

Biomass has been shown as an alternative to fossil fuels for obtaining chemicals. In this work, the transformation of sugars into methyl lactate (ML) at 160 °C was carried out using the layered stannosilicate UZAR-S3 (University of Zaragoza-solid number 3) and the delaminated material UZAR-S4 (University of Zaragoza-solid number 4) obtained from its exfoliation. The exfoliation of UZAR-S3 to UZAR-S4 increased the accessibility of the compounds to the catalytic sites and the medium-strength acidity. Thus, the yield to ML for sucrose transformation increased from 8% for UZAR-S3 to 49.9 % for UZAR-S4. In the reusability tests, the UZAR-S4 catalyst was characterized before and after reaction by several techniques such as X-ray diffraction, thermogravimetry analysis, scanning electronic microscopy, energy dispersive X-ray spectroscopy and nitrogen adsorption. A deactivation of the catalyst was observed, which was related to carbonaceous deposits that decreased the specific surface area and the pore volume of the catalyst.Financial support from the Research Projects MAT2016-77290-R (AEI/FEDER, UE) and T43-17R (the Aragón Government and the ESF) is gratefully acknowledged.Peer reviewe

Selective sugar conversion to mehyl lactate with heterogeneous nanostructured catalysts

Trabajo presentado a la 20th International Zeolite Conference, celebrada en Valencia (España) del 3 al 8 de julio de 2022.Grant PID2019-104009RB-I00 funded by MCIN/AEI/10.13039/501100011033 is gratefully acknowledged.Peer reviewe

Pyogenic arthritis of native joints due to Bacteroides fragilis: Case report and review of the literature

Pyogenic arthritis of native joints due to Bacteroides fragilis seems to be an infrequent disease. We analyzed the cases diagnosed in a tertiary hospital during a 22-year period and reviewed the literature to summarize the experience with this infectious entity.In our institution, of 308 patients with pyogenic arthritis of native joints, B fragilis was the causative organism in 2 (0.6%) cases. A MEDLINE search (1981-2015) identified 19 additional cases.Of the 21 patients available for review (13 men and 8 women, with a mean age, of 54.417 years), 19 (90%) presented a systemic predisposing factor for infection; the most common associated illness was rheumatoid arthritis (8 patients). Bacteremia was documented in 65% (13/20) of cases. In 5 patients (24%), 1 or more concomitant infectious process was found. Metronidazole was the most frequently used antibiotic. Surgical drainage was performed in 11 cases (52%). The overall mortality rate was 5%.Pyogenic arthritis of native joints due to B fragilis is an infrequent disease that mainly affects elderly patients with underlying medical illnesses and in whom bacteremia and the presence of a concomitant infectious process are frequent conditions

Pyogenic arthritis of native joints due to Bacteroides fragilis: Case report and review of the literature

Pyogenic arthritis of native joints due to Bacteroides fragilis seems to be an infrequent disease. We analyzed the cases diagnosed in a tertiary hospital during a 22-year period and reviewed the literature to summarize the experience with this infectious entity.In our institution, of 308 patients with pyogenic arthritis of native joints, B fragilis was the causative organism in 2 (0.6%) cases. A MEDLINE search (1981-2015) identified 19 additional cases.Of the 21 patients available for review (13 men and 8 women, with a mean age, of 54.417 years), 19 (90%) presented a systemic predisposing factor for infection; the most common associated illness was rheumatoid arthritis (8 patients). Bacteremia was documented in 65% (13/20) of cases. In 5 patients (24%), 1 or more concomitant infectious process was found. Metronidazole was the most frequently used antibiotic. Surgical drainage was performed in 11 cases (52%). The overall mortality rate was 5%.Pyogenic arthritis of native joints due to B fragilis is an infrequent disease that mainly affects elderly patients with underlying medical illnesses and in whom bacteremia and the presence of a concomitant infectious process are frequent conditions

Pyogenic arthritis of native joints due to Bacteroides fragilis: Case report and review of the literature

Pyogenic arthritis of native joints due to Bacteroides fragilis seems to be an infrequent disease. We analyzed the cases diagnosed in a tertiary hospital during a 22-year period and reviewed the literature to summarize the experience with this infectious entity.In our institution, of 308 patients with pyogenic arthritis of native joints, B fragilis was the causative organism in 2 (0.6%) cases. A MEDLINE search (1981-2015) identified 19 additional cases.Of the 21 patients available for review (13 men and 8 women, with a mean age, of 54.417 years), 19 (90%) presented a systemic predisposing factor for infection; the most common associated illness was rheumatoid arthritis (8 patients). Bacteremia was documented in 65% (13/20) of cases. In 5 patients (24%), 1 or more concomitant infectious process was found. Metronidazole was the most frequently used antibiotic. Surgical drainage was performed in 11 cases (52%). The overall mortality rate was 5%.Pyogenic arthritis of native joints due to B fragilis is an infrequent disease that mainly affects elderly patients with underlying medical illnesses and in whom bacteremia and the presence of a concomitant infectious process are frequent conditions