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Chemotherapy remains a major treatment for malignant tumors, yet the application of standard dose intensity chemotherapy is limited due to the side effects of cytotoxic drugs, especially in old populations. The underlying mechanisms of cytotoxicity and strategies to increase the safety and tolerance of chemotherapy remain to be explored. Using 5-fluorouracil (5-FU), a cornerstone chemotherapeutic drug, we demonstrate that the main cause of death in ad libitum (AL) fed mice after 5-FU chemotherapy was infection caused by translocation of intestinal opportunistic pathogens. We show that these opportunistic pathogens greatly increase in the intestine after chemotherapy, which was closely related to loss of intestinal lysozyme. Of note, two weeks of dietary restriction (DR) prior to chemotherapy significantly protected the loss of lysozyme and increased the content of the beneficial Lactobacillus genera, resulting in a substantial inhibition of intestinal opportunistic pathogens and their translocation. The rescue effect of DR could be mimicked by Lysozyme or Lactobacillus gavage. Our study provides the first evidence that DR achieved a comprehensive protection of the intestinal physical, biological and chemical barriers, which significantly improved the overall survival of 5-FU-treated mice. Importantly, the above findings were more prominent in old mice. Furthermore, we show that patients over 65 years old have enriched opportunistic pathogens in their gut microbiota, especially after 5-FU based chemotherapy. Our study reveals important mechanisms for the poor chemotherapy tolerance of the elderly population, which can be significantly improved by short-term DR. This study generates new insights into methods for improving the chemotherapeutic prognosis by increasing the chemotherapy tolerance and safety of patients with malignant tumors.
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Traslocación Bacteriana , Fluorouracilo , Microbioma Gastrointestinal , Intestinos , Animales , Ratones , Traslocación Bacteriana/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Intestinos/microbiología , Intestinos/efectos de los fármacos , Muramidasa/metabolismo , Restricción Calórica , Ratones Endogámicos C57BL , Masculino , Lactobacillus , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Bacterias/clasificación , Femenino , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/prevención & control , Infecciones Oportunistas/tratamiento farmacológicoRESUMEN
INTRODUCTION: Cytomegalovirus (CMV) remains a serious opportunistic infection in hematopoietic cell transplant (HCT) and solid-organ transplant (SOT) recipients. Traditional anti-CMV drugs are limited by toxicities and the development of resistance. Letermovir and maribavir are newly approved antivirals for the prevention and treatment of CMV. AREAS COVERED: Prior reviews have discussed use of letermovir for prevention of CMV after HCT and maribavir for resistant or refractory (R/R) CMV post HCT or SOT. Subsequent data have expanded their use including letermovir for primary CMV prophylaxis in high-risk renal transplant recipients and new recommendations for extending prophylaxis through day + 200 in certain HCT patients. Data on the use of maribavir for first asymptomatic CMV infection post-HCT has also been published. This review compares the pharmacology of anti-CMV agents and discusses the updated literature of these new drugs in the prevention and treatment of CMV. EXPERT OPINION: Letermovir and maribavir are much needed tools that spare toxicities of ganciclovir, foscarnet, and cidofovir. High cost is a challenge preventing their integration into clinical practice in resource-limited countries. Transplant centers need to exercise restraint in overuse to avoid resistance, particularly in the setting of high viral loads.
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Antivirales , Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Trasplante de Órganos , Humanos , Acetatos/uso terapéutico , Acetatos/efectos adversos , Acetatos/farmacología , Antivirales/uso terapéutico , Antivirales/efectos adversos , Antivirales/farmacología , Bencimidazoles/uso terapéutico , Bencimidazoles/efectos adversos , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/prevención & control , Diclororribofuranosil Benzoimidazol/análogos & derivados , Farmacorresistencia Viral , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Oportunistas/prevención & control , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/virología , Trasplante de Órganos/efectos adversos , Quinazolinas/uso terapéutico , Quinazolinas/farmacología , Ribonucleósidos/uso terapéutico , Ribonucleósidos/farmacología , Carga Viral/efectos de los fármacosRESUMEN
Over one million people in The Netherlands are estimated having an immunodeficiency, of which the majority has an acquired immunodeficiency due to immunosuppressive medication. These patients are at risk for a more severe course of common infections, and also for opportunistic infections and viral reactivations. The following topics are discussed: types of immunodeficiency and how to estimate its severity; commonly seen infections in immunocompromised patients; recommended screening before start of immunosuppressive medication; pitfalls in clinical clues and diagnostics, and safety and immunogenicity of vaccination in these patients. Conclusively, recognition of an immunodeficiency and awareness of the risks and preventive measures are required. This article attempts to provide a pragmatic classification on the infection risk per type of immunosuppressive medication for clinical practice.
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Huésped Inmunocomprometido , Infecciones Oportunistas , Humanos , Países Bajos , Infecciones Oportunistas/prevención & control , VacunaciónRESUMEN
Infection and lymphopenia are established bendamustine-related complications. The relationship between lymphopenia severity and infection risk, and the role of antimicrobial prophylaxis, is not well described. This multicentre retrospective study analysed infection characteristics and antimicrobial prophylaxis in 302 bendamustine-treated indolent non-Hodgkin lymphoma patients. Lymphopenia (<1 × 109/L) was near universal and time to lymphocyte recovery correlated with cumulative bendamustine dose. No association between lymphopenia severity and duration with infection was observed. Infections occurred in 44% of patients (50% bacterial) with 27% hospitalised; 32% of infections occurred ≥3 months post bendamustine completion. Infection was associated with obinutuzumab and/or maintenance anti-CD20 therapy, prior therapy and advanced stage. Twenty-four opportunistic infections occurred in 21 patients: ten varicella zoster virus (VZV), seven herpes simplex virus (HSV), one cytomegalovirus, one progressive multifocal leucoencephalopathy, one nocardiosis, one Pneumocystis jiroveci pneumonia (PJP) and three other fungal infections. VZV/HSV and PJP prophylaxis were prescribed to 42% and 54% respectively. Fewer VZV/HSV infections occurred in patients receiving prophylaxis (HR 0.14, p = 0.061) while PJP prophylaxis was associated with reduced risk of bacterial infection (HR 0.48, p = 0.004). Our study demonstrates a significant infection risk regardless of lymphopenia severity and supports prophylaxis to mitigate the risk of early and delayed infections.
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Clorhidrato de Bendamustina , Linfoma no Hodgkin , Linfopenia , Infecciones Oportunistas , Humanos , Clorhidrato de Bendamustina/uso terapéutico , Clorhidrato de Bendamustina/efectos adversos , Clorhidrato de Bendamustina/administración & dosificación , Masculino , Linfoma no Hodgkin/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Linfopenia/inducido químicamente , Adulto , Infecciones Oportunistas/prevención & control , Anciano de 80 o más Años , Profilaxis Antibiótica/métodos , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéuticoRESUMEN
The objective of this study is to provide practical recommendations on the management of pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The recommendations specifically address the cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, invasive fungal disease). A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify publications on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The results were presented and discussed in a nominal group meeting, comprising a committee of 12 pediatric rheumatologists from the Infection Prevention and Treatment Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process; this was extended to members of the Spanish Society of Pediatric Rheumatology and Spanish Society of Pediatric Infectious Disease of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (totally disagree) to 10 (totally agree). Agreement was defined as a vote ≥ 7 by at least 70% of participants. The literature review included more than 400 articles. Overall, 63 recommendations (19 on surgery, fever, and opportunistic infections) were generated and voted by 59 pediatric rheumatologists and other pediatric specialists. Agreement was reached for all 63 recommendations. The recommendations on special situations cover management in cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, and invasive fungal disease). Conclusions: Hereby, we provided consensus and updated of recommendations about the management of special situations such as surgery, fever, and opportunistic in children with immune-mediated rheumatic diseases receiving immunosuppressive therapies. Several of the recommendations depend largely on clinical judgement and specific balance between risk and benefit for each individual and situation. To assess this risk, the clinician should have knowledge of the drugs, the patient's previous situation as well as the current infectious disease, in addition to experience. What is Known: ⢠Infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. ⢠Information on how to manage the treatment in situations of fever, opportunistic infections, and surgery in children is limited, and guidelines for action are often extrapolated from adults. What is New: ⢠In the absence of strong evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could support the clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists.
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Varicela , Enfermedades Transmisibles , Herpes Zóster , Micosis , Infecciones Oportunistas , Enfermedades Reumáticas , Tuberculosis , Niño , Humanos , Varicela/diagnóstico , Varicela/prevención & control , Enfermedades Transmisibles/complicaciones , Herpes Zóster/complicaciones , Terapia de Inmunosupresión/efectos adversos , Micosis/complicaciones , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/prevención & control , Infecciones Oportunistas/complicaciones , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Tuberculosis/complicaciones , Vacunación/efectos adversosRESUMEN
Post-transplantation cyclophosphamide (PTCy) is an effective strategy for graft-versus-host disease (GVHD) prophylaxis and is the standard of care for haploidentical hematopoietic cell transplantation (HCT). It is increasingly used for matched and mismatched unrelated donor (MUD/MMUD) HCT, but infections remain a concern. The objective of this study was to evaluate the characteristics and risk factors for infections in haploidentical and unrelated donor HCT recipients treated with PTCy-based GVHD prophylaxis. This single-center retrospective study examined 354 consecutive adults undergoing HCT with PTCy-based GVHD prophylaxis (161 MUD/MMUD; 193 haploidentical) between 2015 and 2022. Opportunistic infections (OIs), including cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and invasive fungal disease (IFD), were assessed from day 0 through day +365. The 1-year cumulative incidence functions of OIs and nonrelapse mortality (NRM) were calculated using dates of relapse and repeat HCT as competing risks. Secondary analysis evaluated risk factors for OIs and NRM using univariate and multivariable Cox regression models. Haploidentical HCT recipients had an increased risk of OIs compared to unrelated donor allograft recipients (39% for haploidentical versus 25% for MUD/MMUD; hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.16 to 2.49; P = .006). On multivariable analysis, haploidentical donor (HR, 1.50; 95% CI, 1.01 to 2.23; P = .046), prior HCT (HR, 1.99; 95% CI, 1.29 to 3.09; P = .002), and diagnosis of aGVHD (HR, 1.47; 95% CI, 1.02 to 2.14; P = .041) were associated with increased risk of OIs. NRM within the first year was not significantly different between the 2 cohorts (HR, 1.11; 95% CI, .64 to 1.93; P = .70). Overall, haploidentical donor was a significant risk factor for OIs in patients receiving PTCy, although 1-year NRM was not different between haploidentical HCT and MUD/MMUD HCT recipients. CMV and AdV infections were significantly increased among haploidentical HCT recipients, whereas the incidences of EBV infection and IFD were similar in the 2 cohorts. Our findings may have implications for infection monitoring and prophylaxis in the setting of PTCy, particularly in haploidentical HCT recipients.
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Infecciones por Citomegalovirus , Infecciones por Virus de Epstein-Barr , Enfermedad Injerto contra Huésped , Infecciones Oportunistas , Adulto , Humanos , Donante no Emparentado , Estudios Retrospectivos , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Herpesvirus Humano 4 , Recurrencia Local de Neoplasia/complicaciones , Ciclofosfamida/uso terapéutico , Aloinjertos , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/etiología , Infecciones Oportunistas/prevención & control , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & controlRESUMEN
Despite their widespread clinical use, oral corticosteroids (OCSs) are well known to be associated with a myriad of adverse effects, including immunosuppression. By inhibiting transcription factors and affecting leukocyte function, prolonged OCS use leads to significant CD4 lymphopenia and often a decrease in serum immunoglobulin (Ig)G. Conversely, OCS use has minimal impact on circulating B cell, serum IgM, or serum IgA levels. Although there is a paucity of literature, individuals treated with prolonged OCS seem to typically maintain humoral response to various vaccinations despite hypogammaglobinemia, but this area warrants additional research, especially in the setting of the coronavirus disease 2019 pandemic. Individuals treated with prolonged OCS use are most at risk for opportunistic infections, especially those with underlying malignancy and history of bone marrow transplant. Risk mitigation strategies to decrease infectious complication with OCS use include limiting the dose and duration of therapy, appropriately completing a full vaccination series, consideration for passive immunization, and prophylaxis against opportunistic infections.
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COVID-19 , Infecciones Oportunistas , Humanos , Esteroides , Corticoesteroides/uso terapéutico , Trasplante de Médula Ósea , Infecciones Oportunistas/prevención & control , Infecciones Oportunistas/tratamiento farmacológicoRESUMEN
OBJECTIVES: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. RESULTS: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks. CONCLUSIONS: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.
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Antirreumáticos , Infecciones Oportunistas , Enfermedades Reumáticas , Humanos , Adulto , Antirreumáticos/uso terapéutico , Inmunosupresores/uso terapéutico , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/prevención & control , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Antivirales/uso terapéuticoRESUMEN
INTRODUCTION: Pneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity. METHODS: The self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression. RESULTS: Fifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01-0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration. CONCLUSION: Our study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA.
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Artritis Reumatoide , Infecciones Oportunistas , Neumonía por Pneumocystis , Sulfasalazina , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Metotrexato , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/prevención & control , Pneumocystis carinii , Neumonía por Pneumocystis/tratamiento farmacológico , Neumonía por Pneumocystis/prevención & control , Estudios Retrospectivos , Sulfasalazina/uso terapéutico , HumanosRESUMEN
OBJECTIVE: To conduct a systematic literature review (SLR) on the screening and prophylaxis of opportunistic and chronic infections in autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: SLR (inception-12/2021) based on the following search domains: (1) infectious agents, (2) AIIRD, (3) immunosuppressives/immunomodulators used in rheumatology, (4) screening terms and (5) prophylaxis terms. Articles were retrieved having the terms from (1) AND (2) AND (3) plus terms from (4) OR(5). Databases searched: PubMed, Embase and Cochrane Library. EXCLUSION CRITERIA: studies on postoperative infections, paediatric AIIRD, COVID-19, vaccinations and non-Εnglish literature. Study quality was assessed with Newcastle-Ottawa scale for non-randomised controlled trials (RCTs), RoB-Cochrane for RCTs, AMSTAR2 for SLRs. RESULTS: From 5641 studies were retrieved, 568 full-text articles were assessed for eligibility, with 194 articles finally included. For tuberculosis, tuberculin skin test (TST) is affected by treatment with glucocorticoids and conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and its performance is inferior to interferon gamma release assay (IGRA). Agreement between TST and IGRA is moderate to low. For hepatitis B virus (HBV): risk of reactivation is increased in patients positive for hepatitis B surface antigen. Anti-HBcore positive patients are at low risk for reactivation but should be monitored periodically with liver function tests and/or HBV-viral load. Risk for Hepatitis C reactivation is existing but low in patients treated with biological DMARDs. For Pneumocystis jirovecii, prophylaxis treatment should be considered in patients treated with prednisolone ≥15-30 mg/day for >2-4 weeks. CONCLUSIONS: Different screening and prophylaxis approaches are described in the literature, partly determined by individual patient and disease characteristics.
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Antirreumáticos , COVID-19 , Infecciones Oportunistas , Enfermedades Reumáticas , Adulto , Humanos , Niño , COVID-19/diagnóstico , COVID-19/prevención & control , Antirreumáticos/efectos adversos , Virus de la Hepatitis B , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/etiología , Infecciones Oportunistas/prevención & control , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológicoRESUMEN
BACKGROUND: Immune-related adverse events (irAEs) often require treatment with high-dose systemic steroids (SS) and other immunosuppressive agents (ISAs). NCCN Guidelines recommend prophylactic antibiotics for Pneumocystis jirovecii pneumonia (PJP) for patients receiving prolonged SS/ISAs. However, there is a paucity of evidence regarding the incidence of opportunistic infections (OIs) and non-OIs and the role of prophylactic antibiotics in patients on SS/ISAs for irAEs. METHODS: A retrospective analysis was conducted of patients treated using immune checkpoint inhibitor (ICI) therapy at 5 MedStar Health hospitals from January 2011 to April 2018. OIs were defined per the Infectious Diseases Society of America guidelines for the prevention and treatment of OIs in patients with HIV. The study cohort included patients who received ≥20 mg daily of a prednisone equivalent for ≥4 weeks to manage irAEs. RESULTS: The study cohort identified 112 (15%) of 758 total patients treated using ICIs. Baseline characteristics included the following: median age was 64 years, 74% (n=82) of patients were White, 89% (n=100) had an ECOG performance status ≤1, 61% (n=68) had melanoma, 19% (n=21) had non-small cell lung cancer, 45% (n=50) were treated using an anti-PD-(L)1 ICI, and 33% (n=37) were treated using an anti-PD-1/anti-CTLA-4 combination. The median starting SS dose was 100 mg of a prednisone equivalent, and 25% of patients required additional ISAs, with infliximab (n=15) and mycophenolate mofetil (n=9) being the most common. We found that 20% (n=22) of patients developed any infection, including 7% (n=8) with OIs (oral candidiasis [n=4], nondisseminated varicella zoster infection [n=2], PJP [n=1], and Listeria monocytogenes endophthalmitis [n=1]) and 13% (n=14) with non-OIs (most common: Clostridium difficile and pneumonia [n=5 each]). PJP prophylaxis with sulfamethoxazole/trimethoprim was given to 13% (n=14) patients, of whom 43% (n=6) developed OIs/non-OIs. CONCLUSIONS: Our study highlights the fundamental issues for patients on ICI therapy who require SS/ISAs for irAEs: the degree of immunosuppression and the relative risk of OI. We noted a low incidence of OIs overall and breakthrough infections despite PJP prophylaxis. We question whether PJP prophylaxis is efficacious or necessary. Prospective trials are required to answer these questions.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Infecciones Oportunistas , Pneumocystis carinii , Neumonía por Pneumocystis , Antibacterianos , Profilaxis Antibiótica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Neoplasias Pulmonares/tratamiento farmacológico , Persona de Mediana Edad , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/etiología , Infecciones Oportunistas/prevención & control , Neumonía por Pneumocystis/tratamiento farmacológico , Neumonía por Pneumocystis/epidemiología , Neumonía por Pneumocystis/etiología , Prednisona/uso terapéutico , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Infections are an important warning sign for a weakened immune system. In the internal medical practice acquired (secondary), particularly drug-induced immunodeficiencies, are much more frequent than congenital (primary) immunodeficiencies. The management starts as early as the planning phase before initiation of immunosuppression. The risk of infection should be individually stratified and protective vaccinations should be completed. Depending on the immunosuppressive treatment, there can be a necessity for preventive treatment, e.g. for latent tuberculosis infection or hepatitis B. The serological results on varicella zoster virus and JC polyomavirus must also be considered. The basic immunological diagnostics include differential blood count and the determination of immunoglobulins (IgG, IgA, IgM) prior to and during immunosuppressive treatment. Relevant conspicuous laboratory results before initiation of treatment should prompt advanced immunological work-up for the identification of primary immunodeficiencies, which are often accompanied by clinical signs of immune dysregulation. Depending on the type of pathogen, localization, frequency and duration as well as the severity of the infection, prophylactic antibiotic treatment may be required. Patients with chronic severe lymphocytopenia, in particular with CD4 positive T (helper) cells <â¯200/µl, are at increased risk for opportunistic infections so that an antibiotic prophylaxis is recommended. In patients with significantly increased proneness to infections and detection of a relevant quantitative (IgGâ¯< 4â¯g/l) and/or qualitative antibody deficiency (impaired vaccine response), additional immunoglobulin replacement therapy may be necessary and can be administered intravenously (IVIG) or subcutaneously (SCIG) as home treatment. In accordance with the localization of the infection, multidisciplinary clarification and management is warranted.
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Síndromes de Inmunodeficiencia , Infecciones Oportunistas , Humanos , Inmunización Pasiva/métodos , Inmunoglobulina G , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Síndromes de Inmunodeficiencia/terapia , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/prevención & control , VacunaciónRESUMEN
Secondary immunodeficiency is reported in most patients with hematological malignancies such as chronic lymphocytic leukemia and multiple myeloma. The aim of our review was to evaluate the existing literature data on patients with hematological malignancies, with regard to the effect of immunodeficiency on the outcome, the clinical and therapeutic approach, and on the onset of noninfectious complications, including thrombosis, pleural effusion, and orofacial complications. Immunodeficiency in these patients has an intense impact on their risk of infection, in turn increasing morbidity and mortality even years after treatment completion. However, these patients with increased risk of severe infectious diseases could be treated with adequate vaccination coverage, but the vaccines' administration can be associated with a decreased immune response and an augmented risk of adverse reactions. Probably, immunogenicity of the inactivated is analogous to that of healthy subjects at the moment of vaccination, but it undertakes a gradual weakening over time. However, the dispensation of live attenuated viral vaccines is controversial because of the risk of the activation of vaccine viruses. A particular immunization schedule should be employed according to the clinical and immunological condition of each of these patients to guarantee a constant immune response without any risks to the patients' health.
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Síndromes de Inmunodeficiencia/inmunología , Leucemia Linfocítica Crónica de Células B/inmunología , Mieloma Múltiple/inmunología , Infecciones Oportunistas/inmunología , Animales , Humanos , Huésped Inmunocomprometido , Inmunogenicidad Vacunal , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/terapia , Incidencia , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/terapia , Mieloma Múltiple/epidemiología , Mieloma Múltiple/terapia , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/prevención & control , Factores de Riesgo , Vacunación , Eficacia de las Vacunas , Vacunas/administración & dosificación , Vacunas/efectos adversosRESUMEN
Haploidentical stem cell transplantation (haploSCT) has advanced to a common procedure for treating patients with hematological malignancies and immunodeficiency diseases. However, cure is seriously hampered by cytomegalovirus (CMV) infections and delayed immune reconstitution for the majority of haploidentical transplant recipients compared to HLA-matched stem cell transplantation. Three major approaches, including in vivo T-cell depletion (TCD) using antithymocyte globulin for haploSCT (in vivo TCD-haploSCT), ex vivo TCD using CD34 + positive selection for haploSCT (ex vivo TCD-haploSCT), and T-cell replete haploSCT using posttransplant cyclophosphamide (PTCy-haploSCT), are currently used worldwide. We provide an update on CMV infection and CMV-specific immune recovery in this fast-evolving field. The progress made in cellular immunotherapy of CMV infection after haploSCT is also addressed. Groundwork has been prepared for the creation of personalized avenues to enhance immune reconstitution and decrease the incidence of CMV infection after haploSCT.
Asunto(s)
Infecciones por Citomegalovirus/prevención & control , Citomegalovirus/inmunología , Reconstitución Inmune , Huésped Inmunocomprometido , Depleción Linfocítica , Infecciones Oportunistas/prevención & control , Trasplante de Células Madre/efectos adversos , Acondicionamiento Pretrasplante , Animales , Antígenos CD34/inmunología , Suero Antilinfocítico/uso terapéutico , Ciclofosfamida/uso terapéutico , Citomegalovirus/patogenicidad , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Antígenos HLA/genética , Antígenos HLA/inmunología , Haplotipos , Interacciones Huésped-Patógeno , Humanos , Inmunosupresores/uso terapéutico , Depleción Linfocítica/efectos adversos , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/virología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
The skin is the largest organ in the human body, and due to its barrier function, it is susceptible to multiple injuries. The appearance of infections during the wound healing process is a complication that represents a formidable hospital challenge. The presence of opportunistic bacteria with sophisticated resistance mechanisms is difficult to eradicate and compromises patients' lives. Therefore, the search for new efficacious treatments from natural sources that prevent and counteract infections, in addition to promoting the healing process, has increased in recent years. In this respect, films with the capability to protect wounds and release drugs are the presentation that predominates commercially in the hospital environment. Those films can offer several mechanical advantages such as physical protection to prevent opportunistic bacteria's entry, regulation of gas exchange, and capture of exudate through a swelling process. Wound dressings are generally curative materials easily adaptable to different anatomical regions, with high strength and elasticity, and some are even bioabsorbable. Additionally, the components of the films can actively participate in promoting the healing process. Even more, the film can be made up of carriers with other active participants to prevent and eradicate infections. Therefore, the extensive versatility, practicality, and usefulness of films from natural sources to address infectious processes during wound healing are relevant and recurrent themes. This work presents an analysis of the state-of-the-art of films with natural products focused on preventing and eradicating infections in wound healing.
Asunto(s)
Productos Biológicos/farmacología , Infecciones Oportunistas/prevención & control , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/prevención & control , Heridas y Lesiones/prevención & control , Productos Biológicos/química , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Membranas Artificiales , Infecciones Oportunistas/microbiología , Plastificantes/química , Plastificantes/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Infección de Heridas/microbiología , Heridas y Lesiones/microbiologíaRESUMEN
Infection is the second leading cause of death in patients with cancer. Loss of efficacy in antibiotics due to antibiotic resistance in bacteria is an urgent threat against the continuing success of cancer therapy. In this review, the authors focus on recent updates on the impact of antibiotic resistance in the cancer setting, particularly on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). This review highlights the health and financial impact of antibiotic resistance in patients with cancer. Furthermore, the authors recommend measures to control the emergence of antibiotic resistance, highlighting the risk factors associated with cancer care. A lack of data in the etiology of infections, specifically in oncology patients in United States, is identified as a concern, and the authors advocate for a centralized and specialized surveillance system for patients with cancer to predict and prevent the emergence of antibiotic resistance. Finding better ways to predict, prevent, and treat antibiotic-resistant infections will have a major positive impact on the care of those with cancer.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Neoplasias/complicaciones , Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos , Humanos , Huésped Inmunocomprometido , Infecciones Oportunistas/prevención & control , Mal Uso de Medicamentos de Venta con Receta/prevención & controlRESUMEN
Health care facility water systems have been associated with the transmission of opportunistic premise plumbing pathogens such as Legionella and nontuberculous mycobacteria. These pathogens can enter a building's water system in low numbers and then proliferate when conditions are conducive to their growth. Patients and residents in health care facilities are often at heightened risk for opportunistic infections, and cases and outbreaks in the literature highlight the importance of routine water management programs and occasions for intervention to prevent additional cases. A multidisciplinary proactive approach to water safety is critical for sustained prevention of health care-associated water-related infections.
Asunto(s)
Atención a la Salud , Legionella , Micobacterias no Tuberculosas , Infecciones Oportunistas/prevención & control , Ingeniería Sanitaria , Abastecimiento de Agua/normas , Humanos , Medición de RiesgoRESUMEN
BACKGROUND AND AIMS: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years. CONCLUSIONS: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.