Stability of meropenem in portable elastomeric infusion devices: which protocol should be implemented in clinical practice?

IMPORTANCE: Although outpatient parenteral antibiotic therapy can be a good approach to treating infections, a lack of data regarding antibiotic stability in portable elastomeric infusion devices restricts its safe and effective use. Actually, meropenem is used for prolonged periods above 24 h, and it is not physicochemically stable, which can compromise efficacy and toxicity. This work is of high importance to show the clinicians the real shelf life of meropenem when administered in portable elastomeric infusion devices. We propose several administration protocols for meropenem in portable elastomeric infusion devices in clinical practice, according to the stability drug results obtained in our study.

Antibiotic stability in portable elastomeric infusion devices: A systematic review.

PURPOSE: Although outpatient parenteral antibiotic therapy (OPAT) can be a good approach to treatment of infections, a lack of data regarding antibiotic stability in portable elastomeric infusion devices restricts its safe, appropriate, and effective use. The objective of this work was to complete a systematic peer-reviewed analysis of published articles about antibiotic stability in elastomeric infusion devices that provide evidence supporting their use in OPAT. SUMMARY: A systematic review following PRISMA guidelines was conducted in January 2021 to identify published articles about antibiotic stability in portable elastomeric infusion devices. The databases used were PubMed, Embase, Web of Science, and a Cochrane database. A total of 1,615 original studies and conference communications were found. After title, abstract, and full-text review, 33 articles met the inclusion criteria. The data obtained included information about the stability of 30 different antibiotics. To our knowledge, this is the first review to summarize the available published data on the stability of antibiotics in portable elastomeric infusion devices. The results highlight the poor stability of some antibiotics in solution and the variability of the laboratory conditions in the included studies. CONCLUSION: This systematic review can serve as a useful resource for healthcare professionals involved in providing OPAT using portable elastomeric infusion devices. However, further stability studies should be performed, especially high-quality studies simulating real-life time and temperature conditions.

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study.

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.

Nocardiosis sistémica en pacientes con aplasia medular adquirida: descripción de 2 casos / Systemic nocardiosis in acquired aplastic anaemia: Report of 2 cases

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Úlcera negra en pierna / Black ulcer in leg

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Donor-derived multiorgan transmission of mixed P. malariae and P. ovale infection: Impact of globalization on post-transplant infections.

A 57-year-old man was admitted with fever and thrombocytopenia 1 month after renal transplantation. He had never received a blood transfusion or travelled outside Spain. A peripheral blood smear revealed Plasmodium malariae and P. ovale parasites, diagnosis confirmed later by malaria PCR. The donor, from Equatorial Guinea, had negative thick and thin blood smears and rapid malaria antigen test prior to organ donation. Peripheral blood malaria PCR was not performed during donor screening. The second renal recipient and the liver recipient were evaluated and were found to be asymptomatic. Thick and thin films and rapid malaria diagnostic tests were negative for both patients and blood for malaria PCR was sent to the referral laboratory. The index patient was treated with oral chloroquine diphosphate, with a favorable outcome and was considered cured. Malaria PCR was negative for the other renal recipient and positive for P. malariae and P. ovale curtisi for the liver transplant patient. Both were treated with oral chloroquine and the liver recipient also completed treatment with primaquine phosphate. This reported case of multiorgan transmission of mixed malaria infection highlights the importance of PCR-based tests for Plasmodium in the screening of donors from endemic areas.

Profilaxis de la infección por citomegalovirus en el trasplante de páncreas / Prophylaxis of cytomegalovirus infection in intestinal transplantation

El trasplante de páncreas presenta un mayor riesgo de enfermedad por citomegalovirus (CMV) si se compara con el trasplante renal aislado. El manejo de la enfermedad por CMV en el trasplante de páncreas dependerá del riesgo según los perfiles de serología (IgG para CMV) del donante y receptor, y del uso de anticuerpos como terapia inmunosupresora (especialmente timoglobulina). La mayoría de las guías clínicas recomienda el uso de la estrategia de profilaxis frente al tratamiento anticipado en el trasplante de páncreas, tanto en D+/R– como en D+/R+. En los de mayor riesgo (D+/R–) se recomienda profilaxis con valganciclovir 900mg/día de 3 a 6 meses, ajustado según función renal. En los D+/R+, si se utilizó terapia con un anticuerpo en el trasplante o en algún rechazo, también se recomienda profilaxis con valgancioclovir de 1 a 3 meses. Al finalizar la profilaxis se realizará en ambos casos determinación de carga viral (PCR cuantitativa de CMV) o antigenemia durante el primer año. En los D–/R– puede plantearse terapia anticipada con determinaciones de carga viral o antigenemia en cada revisión hasta el primer año. Se pondrá especial atención en la vigilancia ante la aparición de enfermedad tardía por CMV tras la supresión de la profilaxis (AU)

Intestinal transplant recipients are at high risk of cytomegalovirus (CMV) disease due to the specific characteristics of the graft and the intense cellular immunosuppression caused by immunosuppressive induction therapy in this type of transplantation. The most frequent form of CMV disease is graft enteritis. Diagnosis of this entity is not always straightforward given that antigenemia for CMV is frequently low grade or negative and the pathological findings can be confused with those of rejection. Diagnosis is aided by immunohistochemistry or molecular biological detection in biopsies of the colon. Current recommendations for the preventive management of CMV disease are based on sporadic experiences and expert opinion, given the lack of specifically-designed, high-quality studies in this type of transplant recipient. In general, universal prophylaxis against CMV is preferred in these patients, initially with intravenous ganciclovir and subsequently with oral valganciclovir for a minimum of 6 months, although this prophylaxis can be prolonged for up to 1 year depending on the type of immunosuppressive therapy used. Several groups also use CMV-specific immunoglobulin (AU)

Recommendations for the treatment of invasive fungal infection caused by filamentous fungi in the hematological patient

El tratamiento antifúngico del paciente hematológico ha alcanzado una gran complejidad con la llegada de nuevos antifúngicos y pruebas diagnósticas que han dado lugar a diferentes estrategias terapéuticas. La utilización del tratamiento más adecuado en cada caso es fundamental en infecciones con tanta mortalidad. La disponibilidad de recomendaciones como éstas, realizadas con la mejor evidencia por un amplio panel de 48 expertos, en las que se intenta responder a cuándo está indicado tratar y con qué hacerlo considerando diferentes aspectos del paciente (riesgo de infección fúngica, manifestaciones clínicas, galactomanano, TC de tórax y profilaxis realizada), puede ayudar a los clínicos a mejorar los resultados(AU)

Antifungal treatment in the hematological patient has reached a high complexity with the advent of new antifungals and diagnostic tests, which have resulted in different therapeutic strategies. The use of the most appropriate treatment in each case is essential in infections with such a high mortality. The availability of recommendations as those here reported based on the best evidence and developed by a large panel of 48 specialists aimed to answer when is indicated to treat and which agents should be used, considering different aspects of the patient (risk of fungal infection, clinical manifestations, galactomanann test, chest CT scan and previous prophylaxis) may help clinicians to improve the results(AU)

[Prophylaxis of cytomegalovirus infection in intestinal transplantation]. / Profilaxis de la infección por citomegalovirus en el trasplante intestinal.

Intestinal transplant recipients are at high risk of cytomegalovirus (CMV) disease due to the specific characteristics of the graft and the intense cellular immunosuppression caused by immunosuppressive induction therapy in this type of transplantation. The most frequent form of CMV disease is graft enteritis. Diagnosis of this entity is not always straightforward given that antigenemia for CMV is frequently low grade or negative and the pathological findings can be confused with those of rejection. Diagnosis is aided by immunohistochemistry or molecular biological detection in biopsies of the colon. Current recommendations for the preventive management of CMV disease are based on sporadic experiences and expert opinion, given the lack of specifically-designed, high-quality studies in this type of transplant recipient. In general, universal prophylaxis against CMV is preferred in these patients, initially with intravenous ganciclovir and subsequently with oral valganciclovir for a minimum of 6 months, although this prophylaxis can be prolonged for up to 1 year depending on the type of immunosuppressive therapy used. Several groups also use CMV-specific immunoglobulin.

La infección intraabdominal en el paciente inmunodeprimido / Intraabdominal infection in inmunodepressed patients

Las enfermedades gastrointestinales son frecuentes en los pacientes inmunodeprimidos. La flora endógena constituye la principal fuente de infección en el hombre, pero es especialmente relevante cuando los mecanismos de barrera de la mucosa digestiva se ven afectados por diversos factores. La translocación bacteriana, los traumatismos, los procesos isquémicos o las intervenciones quirúrgicas son eventos que pueden afectar a la población general. Además de éstos, la infiltración tumoral, la mucositis posquimio o radioterapia, la hipoproteinemia, la neutropenia o el déficit de la función linfocitaria constituyen, entre otros, factores agravantes para el desarrollo de infección intraabdominal en determinados pacientes. Las formas clínicas de estas infecciones son muy variadas, dependiendo del tipo de paciente en el que concurran y el escenario en el que se desarrollen, incluido el ambiente hospitalario. En este capítulo se revisan las características diferenciales de las complicaciones infecciosas intraabdominales en los pacientes con diferentes tipos de inmunosupresión

Diseases of the gastrointestinal system frequently complicate immunosuppressed patients. Endogenous flora is the principal source of infection in humans, especially in patients with dysfunction of the digestive epithelial barrier due to various factors. Bacterial translocation, traumatisms, ischemia and surgery are frequent events in the general population. In addition, important risk factors for abdominal infections in specific patients include tumoral infiltration, mucositis complicating chemotherapy and/or radiotherapy, hypoproteinemia, neutropenia and lymphocyte deficiency. Clinical pictures vary according to patients' baseline condition and the environmental setting, including nosocomial infections. The differential clinical characteristics of abdominal infections observed in distinct types of immunosuppressed patients are reviewed

[Micafungin for therapy of invasive candidiasis in solid organ transplant recipients]. / La micafungina en el tratamiento de la candidiasis invasiva en pacientes sometidos a trasplante de órgano sólido.

BACKGROUND: Micafungin is an echinocandin approved for the prevention of Candida spp. infection in hematopoietic stem cell transplantation and therapy of oesophageal candidiasis, disseminated candidiasis and candidemia in adults, children and neonates. AIMS: To evaluate the role of micafungin for candidiasis therapy in solid organ transplant recipients. METHODS: A medical literature review according to micafungin role for candidiasis therapy in transplant patients is performed. RESULTS: Micafungin has shown fungicide activity against Candida species, including strains resistant or poorly susceptible to fluconazole. No dose adjustment is required when micafungin is administered in combination with other drugs used in transplant patients, excluding sirolimus, nifedipine and itraconazol. With these drugs, a minimal dose reduction is recommended. The results observed in transplant patients included in clinical trials are favourable and similar to results obtained in other kind of patients. CONCLUSIONS: The clinical results, its safety profile and the low grade of medical interactions permit micafungin to be considered for therapy in specific groups of transplant patients.

La micafungina en el tratamiento de la candidiasis invasiva en pacientes sometidos a trasplante de órgano sólido / Micafungin for therapy of invasive candidiasis in solid organ transplant recipients

Antecedentes: La micafungina es una equinocandina aprobada para la prevención de infecciones por Candida en pacientes sometidos a trasplante de progenitores hematopoyéticos y tratamiento de candidiasis esofágica, candidiasis y/o candidemia, tanto en adultos como en niños, incluidos neonatos. Objetivos: El presente trabajo analiza su posible papel en el tratamiento de candidiasis invasivas en trasplantados de órgano sólido. Métodos: Se revisan los aspectos más destacables de la micafungina publicados en la bibliografía médica en relación con el tratamiento de candidiasis en trasplantados. Resultados: La actividad de la micafungina frente a Candida es fungicida y su concentración mínima inhibitoria no varía entre los aislamientos de Candida resistente a azoles. La utilización conjunta con otros fármacos implicados en el trasplante no requiere ajuste de dosis, excepto en los casos de sirolimus, nifedipina e itraconazol, que requieren una leve reducción de las dosis de éstos. Los resultados clínicos observados en pacientes trasplantados en los ensayos clínicos son favorables y similares a los observados en el resto de la población analizada. Conclusiones: Los estudios clínicos, su buen perfil de seguridad y el nivel bajo de interacciones posibilitan un adecuado uso de la micafungina en la candidiasis invasiva y con posible aplicación para el tratamiento de pacientes trasplantados (AU)

Background: Micafungin is an echinocandin approved for the prevention of Candida spp. infection in hematopoietic stem cell transplantation and therapy of oesophageal candidiasis, disseminated candidiasis and candidemia in adults, children and neonates. Aims: To evaluate the role of micafungin for candidiasis therapy in solid organ transplant recipients. Methods: A medical literature review according to micafungin role for candidiasis therapy in transplant patients is performed. Results: Micafungin has shown fungicide activity against Candida species, including strains resistant or poorly susceptible to fluconazole. No dose adjustment is required when micafungin is administered in combination with other drugs used in transplant patients, excluding sirolimus, nifedipine and itraconazol. With these drugs, a minimal dose reduction is recommended. The results observed in transplant patients included in clinical trials are favourable and similar to results obtained in other kind of patients. Conclusions: The clinical results, its safety profile and the low grade of medical interactions permit micafungin to be considered for therapy in specific groups of transplant patients (AU)

[The role of anidulafungin therapy in solid organ transplant recipients]. / Potencial de anidulafungina en la terapia de receptores de trasplante de órgano sólido.

Anidulafungin is a new echinocandin recently approved for the treatment of esophageal candidiasis, candidemia and other forms of invasive candidiasis, such as peritonitis and intra-abdominal abscesses in non-neutropenic patients. It is fungicidal against Candida spp. and fungistatic against Aspergillus spp. It is active against Pneumocystis jirovecii. In contrast, anidulafungin does not have activity against Cryptococcus neoformans, Zygomycetes or molds, other than Aspergillus spp. The drug is well tolerated, even in patients with renal or hepatic impairment. In contrast to other echinocandins, it does not significantly interfere with the cytochrome P450 pathway and has a low drug-drug interaction profile, including calcineurinic agents and other drugs used in transplant recipients. So far, anidulafungin appears to have an excellent safety profile with few adverse events and it promises a special consideration in the management of fungal infections happening in transplant recipients.

Potencial de anidulafungina en la terapia de receptores de trasplante de órgano sólido / The role of anidulafungin therapy in solid organ transplant recipients

La anidulafungina es una nueva equinocandina aceptada para el tratamientode candidiasis esofágica, candidemia y otras formas de candidiasis, comoperitonitis o abscesos intraabdominales en pacientes no neutropénicos.Como las otras equinocandinas, posee una elevada actividad fungicida frentea la mayoría de las especies de Candida y es fungistático frente aAspergillus spp. También tiene buena actividad frente a Pneumocystis jiroveciiy es poco activa frente a Cryptococcus neoformans, mucorales y otroshongos filamentosos diferentes a Aspergillus spp. Presenta ausencia o mínimatoxicidad renal y/o hepática y, a diferencia de otras equinocandinas y azoles,no sufre metabolización asociada con el citocromo P450. Por tanto, carecede interacciones medicamentosas con los calcineurínicos y otros fármacosutilizados en los pacientes trasplantados. Esta característica permite a laanidulafungina posicionarse como un antifúngico especialmente interesante eneste tipo de pacientes(AU)

Anidulafungin is a new echinocandin recently approved for the treatment ofesophageal candidiasis, candidemia and other forms of invasive candidiasis,such as peritonitis and intra-abdominal abscesses in non-neutropenic patients.It is fungicidal against Candida spp and fungistatic against Aspergillus spp.It is active against Pneumocystis jirovecii. In contrast, anidulafungin does nothave activity against Cryptococcus neoformans, Zygomycetes or molds, otherthan Aspergillus spp. The drug is well tolerated, even in patients with renal orhepatic impairment. In contrast to other echinocandins, it does notsignificantly interfere with the cytochrome P450 pathway and has a lowdrug–drug interaction profile, including calcineurinic agents and other drugsused in transplant recipients. So far, anidulafungin appears to have anexcellent safety profile with few adverse events and it promises a specialconsideration in the management of fungal infections happening in transplantrecipients(AU)