Drug interactions of anti-microbial agents used in hematopoietic stem cell transplantation

Guastaldi, Rosimeire Barbosa Fonseca; Secoli, Sílvia Regina

doi:10.1590/s0104-11692011000400015

Cited by 11 publications

(8 citation statements)

References 17 publications

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“…Infections in transplant patients are a common complication, accounting for 15% to 20% of deaths. 33 Many of the antimicrobial agents used to treat or prevent such infections have certain pharmacokinetic characteristics that predispose to DDIs. 34 All antifungal azoles inhibit the metabolism of CsA, TAC, SRL, and EVE due to inhibition of the CYP3A4 enzyme.…”

Section: Discussionmentioning

confidence: 99%

Real clinical impact of drug–drug interactions of immunosuppressants in transplant patients

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Cárdenas

et al. 2021

Pharmacology Res & Perspec

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The main objective was to determine the prevalence of real drug–drug interactions (DDIs) of immunosuppressants in transplant patients. We conducted a prospective, observational 1‐year study at a tertiary hospital, including all transplanted patients. We evaluated data from monitoring blood concentrations of immunosuppressive drugs and adverse drug events (ADEs) caused by DDIs. The DDIs were classified as C, D, or X according to their Lexi‐Interact rating (C = monitor therapy, D = consider therapy modification, X = avoid combination). The clinical importance of real DDIs was expressed in terms of patient outcomes. The causality of DDIs was determined using Drug Interaction Probability Scale. The data were analyzed using Statistical Package for Social Sciences v. 25.0. A total of 309 transplant patients were included. Their mean age was 52.0 ± 14.7 years (18–79) and 69.9% were male. The prevalence of real DDIs was 21.7%. Immunosuppressive drugs administered with antifungal azoles and tacrolimus (TAC) with nifedipine have a great clinical impact. Real DDIs caused ADEs in 22 patients. The most common clinical outcome was nephrotoxicity (1.6%; n = 5), followed by hypertension (1.3%; n = 4). Suggestions for avoiding category D and X DDIs included: changing the immunosuppressant dosage, using paracetamol instead of non‐steroidal anti‐inflammatory drugs, and interrupting atorvastatin. The number of drugs prescribed and having been prescribed TAC was associated with an increased risk of real DDIs. There are many potential DDIs described in the literature but only a small percentage proved to be real DDIs, based on the patients´ outcomes.

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Section: Discussionmentioning

confidence: 99%

Real clinical impact of drug–drug interactions of immunosuppressants in transplant patients

GAGO

Font

Cárdenas

et al. 2021

Pharmacology Res & Perspec

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“…Antimicrobials that induce or inhibit CYP enzymes and that are concurrently administered with cyclosporine-A are likely to alter blood levels of cyclosporine-A (74). Thus, drugs that increase blood levels of cyclosporine-A are likely to potentiate its side effects particularly nephrotoxicity, while antimicrobials that decrease blood levels of cyclosporine-A are likely to cause graft rejection (75). Examples of antimicrobials that alter blood levels of cyclosporine-A include (1) macrolides such as ciprofloxacin, (2) cephalosporins such as cefepime, (3) azoles such as fluconazole, and (4) TMP–SMZ (74, 75).…”

Section: Interactions Between Hsct Therapies and Antimicrobialsmentioning

confidence: 99%

“…The following antimicrobials that are used in the treatment of NTM infections have been reported to interact with tacrolimus (1) macrolides such as clarithromycin and azithromycin, (2) aminoglycosides such as tobramycin, amikacin, and streptomycin, (3) quinolones such as ofloxacin and ciprofloxacin, (4) anti-mycobacterial agents such as rifampin, rifabutin, ethambutol, and pyrazinamide, and (5) other antimicrobials such as aztreonam, meropenem, sulfonamides, and tetracyclines (76). Therefore, it is essential to (1) modify doses of antimicrobials as well as immunosuppressive therapies as needed and (2) have rigorous monitoring of not only adverse effects but also drug levels of medications used in HSCT recipients (75). …”

Section: Interactions Between Hsct Therapies and Antimicrobialsmentioning

confidence: 99%

Infections Caused by Non-Tuberculous Mycobacteria in Recipients of Hematopoietic Stem Cell Transplantation

2014

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Non-tuberculous mycobacteria (NTM) are acid-fast bacteria that are ubiquitous in the environment and can colonize soil, dust particles, water sources, and food supplies. They are divided into rapidly growing mycobacteria such as Mycobacterium fortuitum, Mycobacterium chelonae, and Mycobacterium abscessus as well as slowly growing species such as Mycobacterium avium, Mycobacterium kansasii, and Mycobacterium marinum. About 160 different species, which can cause community acquired and health care-associated infections, have been identified. NTM are becoming increasingly recognized in recipients of hematopoietic stem cell transplantation (HSCT) with incidence rates ranging between 0.4 and 10%. These infections are 50–600 times commoner in transplant recipients than in the general population and the time of onset ranges from day 31 to day 1055 post-transplant. They have been reported following various forms of HSCT. Several risk factors predispose to NTM infections in recipients of stem cell transplantation and these are related to the underlying medical condition and its treatment, the pre-transplant conditioning therapies as well as the transplant procedure and its complications. Clinically, NTM may present with: unexplained fever, lymphadenopathy, osteomyelitis, soft tissue and skin infections, central venous catheter infections, bacteremia, lung, and gastrointestinal tract involvement. However, disseminated infections are commonly encountered in severely immunocompromised individuals and bloodstream infections are almost always associated with catheter-related infections. It is usually difficult to differentiate colonization from true infection, thus, the threshold for starting therapy remains undetermined. Respiratory specimens such as sputum, pleural fluid, and bronchoalveolar lavage in addition to cultures of blood, bone, skin, and soft tissues are essential diagnostically. Susceptibility testing of mycobacterial isolates is a basic component of optimal care. Currently, there are no guidelines for the treatment of NTM infections in recipients of stem cell transplantation, but such infections have been successfully treated with surgical debridement, removal of infected or colonized indwelling intravascular devices, and administration of various combinations of antimicrobials. Monotherapy can be associated with development of drug resistance due to new genetic mutation. The accepted duration of treatment is 9 months in allogeneic stem cell transplantation and 6 months in autologous setting. Unfortunately, eradication of NTM infections may be impossible and their treatment is often complicated by adverse effects and interactions with other transplant-related medication.

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“…Nestas situações, outros antimicrobianos, são acrescentados à terapêutica do paciente, os quais podem causar ou potencializar EA relacionados à piora da função renal e/ou hepática (89,90) .…”

Section: Eventos Adversos Por Tipo E Fase Do Tcthunclassified

Eventos adversos e carga de trabalho de enfermagem em pacientes submetidos ao transplante de células-tronco hematopoiéticas: estudo de coorte

Silva¹

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Silva, JB. Eventos adversos e carga de trabalho de enfermagem em pacientes submetidos ao transplante de células-tronco hematopoiéticas: estudo de coorte [Tese]. São Paulo (SP): Escola de Enfermagem, Universidade de São Paulo; 2015. RESUMO Introdução: No paciente submetido ao transplante de células tronco-hematopoiéticas (TCTH), os eventos adversos (EA) representam ocorrência relevante, porém inerente ao procedimento. Tais EA interferem no status clínico do paciente e, possivelmente, na carga de trabalho de enfermagem. Objetivo: Avaliar a relação entre ocorrência de EA e a carga de trabalho de enfermagem demandada por pacientes submetidos ao TCTH. Método: Coorte prospectiva realizada com pacientes internados na unidade de TCTH do Hospital de Clínicas da Universidade Estadual de Campinas. A amostra foi composta por 62 pacientes; os dados foram obtidos pela análise diária dos prontuários. A variável dependente foi carga de trabalho de enfermagem, mensurada pelo Nursing Activities Score (NAS), e as variáveis independentes foram as demográfico-clínicas, dentre as quais a ocorrência e gravidade de EA, que foram identificados e classificados de acordo com Common Terminology Criteria for Adverse Events. Na análise dos dados utilizaram-se os testes Quiquadrado ou Exato de Fisher, os não-paramétricos Mann-Whitney e Kruskal-Wallis e o coeficiente de correlação de Spearman. Para estudar as relações entre a variável NAS e as variáveis independentes foram construídos modelos de regressão linear múltipla. Resultados: Verificou-se incidência de 100% de EA relativos a 'investigações laboratoriais', 'trato-gastrointestinal' e 'sistema sanguíneo e linfático' nos grupos de TCTH autólogo e alogênico. A incidência dos EA 'vasculares' foi de 100% no grupo de alogênicos e, no de autólogos, estiveram presentes desde o início do tratamento, o que implicou em inexistência de casos novos. Os pacientes de TCTH alogênico apresentaram em média, na fase do condicionamento (CT) e infusão (IF), maior número de EA nas seguintes categorias: 'gerais e sítio de administração' (p=0,0047), 'investigações laboratoriais' (p=0,0061), 'nutrição e metabolismo' (p=0,0280), 'sistema nervoso' (p=0,0080), 'vasculares' (p=0,0442) e no 'sistema sanguíneo e linfático' (CT: p=0,0062; IF: p=0,0020). Na IF pacientes de TCTH autólogo apresentaram maior número médio de EA relacionados ao 'sistema renal e vias urinárias' (p=0,0003). Na fase pós-TCTH (PT) não houve diferença estatística significante entre os grupos quanto ao número médio de EA. Em relação à gravidade dos EA, nas fases de CT e IF os pacientes de TCTH alogênico apresentaram EA de maior gravidade relacionados às 'investigações laboratoriais' (CT: p=0,0091; IF: p=0,0427) e ao 'sistema sanguíneo e linfático' (CT: p=0,0088; IF: p=0,0100). Na fase PT o grupo de pacientes de TCTH autólogo apresentou maior gravidade nos EA relativos a: 'investigações laboratoriais' (p=0,0156), 'nutrição e metabolismo' (p=0,0118), 'sistema nervoso' (p=0,0491); no período PT os pacientes de TCTH autólogo apresentaram maior gravidad...

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Drug interactions of anti-microbial agents used in hematopoietic stem cell transplantation

Cited by 11 publications

References 17 publications

Real clinical impact of drug–drug interactions of immunosuppressants in transplant patients

Real clinical impact of drug–drug interactions of immunosuppressants in transplant patients

Infections Caused by Non-Tuberculous Mycobacteria in Recipients of Hematopoietic Stem Cell Transplantation

Eventos adversos e carga de trabalho de enfermagem em pacientes submetidos ao transplante de células-tronco hematopoiéticas: estudo de coorte

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