scholarly journals Clarithromycin–rifampin-based treatment for nontuberculous mycobacteria infections in immunocompromised patients who require concomitant CYP-metabolized medications

2021 ◽  
Author(s):  
Isabel H Gonzalez-Bocco ◽  
Muneerah M Aleissa ◽  
Eric Zhou ◽  
Jennifer  Manne-Goehler ◽  
Sophia Koo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Nontuberculous Mycobacteria ◽  
Immunocompromised Patients ◽  
Cyp Induction

Abstract Clarithromycin (CYP inhibitor) can be used instead of azithromycin for nontuberculous mycobacteria therapy in patients requiring CYP-substrates, to mitigate rifampin’s CYP induction. We found no differences in adverse events (10/13 vs. 14/17; p=0.73), drug intolerability (1/5 vs. 4/11; p=1), or 90-day mortality (0/13 vs. 1/17; p=1) in patients receiving clarithromycin vs. azithromycin

Nontuberculous Mycobacteria Infections in Immunocompromised Patients

2009 ◽  
Vol 31 (8) ◽  
pp. 556-560 ◽  
Author(s):  
Michael C. Wei ◽  
Niaz Banaei ◽  
Mitchell A. Yakrus ◽  
Tracey Stoll ◽  
Kathleen M. Gutierrez ◽  
...  
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Immunocompromised Patients

scholarly journals The Aerogen® Solo Is an Alternative to the Small Particle Aerosol Generator (SPAG-2) for Administration of Inhaled Ribavirin

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1163
Author(s):  
Ronald H. Dallas ◽  
Jason K. Rains ◽  
Keith Wilder ◽  
William Humphrey ◽  
Shane J. Cross ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Adverse Events ◽  
Delivery System ◽  
Small Particle ◽  
Mortality Rates ◽  
Adverse Outcomes ◽  
Immunocompromised Patients ◽  
Aerosol Generator ◽  
Syncytial Virus ◽  
Set Up

Respiratory syncytial virus (RSV) is associated with adverse outcomes among immunocompromised patients. Inhaled ribavirin has been shown to improve mortality rates. The Small-Particle Aerosol Generator delivery system (SPAG-2) is the only FDA-cleared device to deliver inhaled ribavirin. However, it is difficult to set up and maintain. We developed a method for delivery of this medication using the vibrating mesh nebulizer (Aerogen®). We did not observe any adverse events with this method.

scholarly journals Study of Delayed Antibiotic in Pediatric Febrile Immunocompromised Patients and Adverse Events

2019 ◽  
Vol 9 (5) ◽  
pp. 379-386
Author(s):  
Nafeh Fananapazir ◽  
Christopher Dandoy ◽  
Terri Byczkowski ◽  
Adam Lane ◽  
Rajaram Nagarajan ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immunocompromised Patients

scholarly journals The Aerogen® Solo is an Alternative to the Small Particle Aerosol Generator (SPAG-2) for Administration of Inhaled Ribavirin

2020 ◽  
Author(s):  
Ronald H Dallas ◽  
Jason K Rains ◽  
Keith Wilder ◽  
William Humphrey ◽  
Shane J Cross ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Adverse Events ◽  
Delivery System ◽  
Small Particle ◽  
Mortality Rates ◽  
Adverse Outcomes ◽  
Immunocompromised Patients ◽  
Aerosol Generator ◽  
Syncytial Virus ◽  
Set Up

Respiratory syncytial virus (RSV) is associated with adverse outcomes among immunocompromised patients. Inhaled ribavirin has been shown to improve mortality rates. The Small-Particle Aerosol Generator delivery system (SPAG-2) is the only FDA-cleared device to deliver inhaled ribavirin. However, it is difficult to set up and maintain. We developed a method for delivery of this medication using the vibrating mesh nebulizer (Aerogen®). We did not observe any adverse events with this method.

Treatment of Other Nontuberculous Mycobacteria

2018 ◽  
Vol 39 (03) ◽  
pp. 377-382 ◽  
Author(s):  
Damien Basille ◽  
Vincent Jounieaux ◽  
Claire Andréjak
Keyword(s):  
Adverse Events ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Nontuberculous Mycobacteria ◽  
Optimal Treatment ◽  
Northern Europe ◽  
Scientific Societies ◽  
Culture Conversion ◽  
Efficacy Of Treatment ◽  
Benefit And Risk

AbstractNontuberculous mycobacteria (NTM) are numerous, and for the vast majority of them, randomized studies are lacking and data regarding optimal treatment are limited. When Mycobacterium avium complex (MAC) and M. abscessus are excluded, the main NTM are M. xenopi, M. kansasii, M. malmoense, M. szulgai, and M. simiae. Treatment is long (at least 12 months after culture conversion according to recommendations by scientific societies) and difficult (at least three drugs are required, each of which have potential adverse events). Moreover, optimal treatment is unknown for the vast majority of NTM and efficacy of treatment is not 100%. That is why, balance between benefit and risk is fundamental. For M. xenopi, the second most common NTM isolated in Europe, treatment is classically based on macrolides or fluoroquinolones, associated with ethambutol and rifampicin. For M. kansasii, the cornerstone of treatment is rifampicin, which should be associated with two other drugs: ethambutol plus isoniazid or clarithromycin. M. malmoense, which is common in Northern Europe, can be treated by rifampicin, ethambutol, and clarithromycin and/or fluoroquinolones.

scholarly journals A Pilot Study of Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy with Ex Vivo Generated Polyomavirus-Specific T-Cells

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4535-4535
Author(s):  
Irene Cortese ◽  
Austin John Barrett ◽  
David F. Stroncek ◽  
Steven Highfill ◽  
Erin Beck ◽  
...  
Keyword(s):  
T Cells ◽  
Pilot Study ◽  
Adverse Events ◽  
Adoptive Immunotherapy ◽  
Safety Monitoring ◽  
Fixed Dose ◽  
Genetic Defects ◽  
Immunocompromised Patients ◽  
Monitoring Period

Abstract Background: Progressive Multifocal Encephalopathy (PML) is a subacute infection of the central nervous system (CNS) mediated by John Cunningham (JC) polyomavirus (PyV). The disease is frequently fatal, unless adaptive immunity to JC virus is restored. The disease typically occurs in immunosuppressed patients (e.g. HIV/AIDS). In the modern era, patients with hematological malignancies treated with rituximab and/or fludarabine or following immunosuppressive therapy for transplant or autoimmunity (e.g. multiple sclerosis (MS) or Crohn's disease) are also at risk. JC-PML can also occur in patients with genetic defects of immunity. Specific treatments do not exist and immunocompromised patients with history of cancer or genetic defects of immunity have no realistic chance for rapid recovery of their ability to fight infections. In subjects with Rituximab-related PML the case-fatality ratio is >90%. Survivors can be left with severe neurological disabilities. Methods: Based on our previously established procedure for generation of multi-virus virus-specific T cells using overlapping peptide libraries (pepmixes) as immunogens, we have developed dedicated polyomavirus-specific T cells (PyVST) targeting polyomavirus BK large T (LT) and Viral Protein 1 (VP1) antigens and highly cross-reactive with the structurally-homologous JC LT and VP1 proteins (see Figure). We hypothesized that adoptive transfer of donor-derived PyVSTs could be safely used for therapy of patients with refractory JC-PML. We have developed a pilot study to test the feasibility and safety of adoptive immunotherapy strategy using PyVSTs from the partially matched healthy 1st degree relative donors (sibling, parent or offspring; NIH study 16-N-0072). Adults diagnosed with PML who have no other treatment options were eligible. Patients with MS or HIV were excluded. PyVSTs were generated from donor blood leukocytes cultured for 14 days in G-rex flasks upon stimulation with BK LT and VP1 pepmixes. Subjects underwent baseline physical examination, MRI and lumbar puncture. Upon enrollment subjects received an intravenous infusion of a fixed dose of 1x10e6 (+/-10%) PyVST cells/kg. Safety monitoring period was 28 days after each infusion. Subjects were eligible for up to two additional infusions (dose 2x10e6 PyVSTs/kg) a minimum of 28 days apart if no toxicities were observed. Serial MRI and lumbar punctures were performed to monitor response. Subjects were followed for 12 months after the last infusion. Results: Nine subjects have been enrolled and treated with at least one infusion of PyVSTs under this protocol and the trial is still accruing subjects. No immediate infusion reactions or adverse events have been observed within the safety monitoring period. No CNS immune system reconstitution syndrome (IRIS) has occurred. One subject received a single infusion and withdrew from the study following Day 14 visit due to unwillingness to travel. One subject received two doses of PyVSTs with stabilization of the disease, not requiring the 3rd infusion. This subject was withdrawn from the study just prior to the 1 year follow up visit, as he was diagnosed with the stage IV lung cancer and entered hospice. Seven subjects received 3 infusions of PyVSTs. 3 of these 7 patients died of refractory PML, all >30 days after the 3rd dose of T cells. At the time of this report one subject completed the study at one year with stable PML. The remaining subjects are in the follow-up phase of the protocol. Conclusions: We report that partially matched T cells targeting PyVs generated from healthy related donors can be safely used for adoptive immunotherapy of severely immunocompromised patients with PML. Multiple infusions of T cells are very well tolerated at the doses of up to 2x10e6 PyVST cells/kg, displaying excellent safety profile without adverse events. Furthermore, our data suggest possible efficacy of this strategy as a life-saving therapy for patients who otherwise face a dismal prognosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals 1399. Clarithromycin–Rifampin-based Treatment for Non-tuberculous Mycobacterial Infections in Immunocompromised Patients Who Require Concomitant CYP-Metabolized Medications

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S784-S784
Author(s):  
Isabel H Gonzalez-Bocco ◽  
Muneerah M Aleissa ◽  
Matthew Cheng ◽  
Jennifer Manne-Goehler ◽  
Francisco M Marty
Keyword(s):  
Adverse Events ◽  
Treatment Guidelines ◽  
Panel Member ◽  
Positive Culture ◽  
Good Alternative ◽  
Drug Regimen ◽  
Current Treatment ◽  
Review Panel ◽  
Cyp Induction ◽  
Immunocompromised Hosts

Abstract Background Non-tuberculous mycobacteria (NTM) are causes of pulmonary and extrapulmonary disease that frequently affect immunocompromised hosts (ICH). Current treatment guidelines recommend a macrolide-based, multi-drug regimen that includes rifampin. Rifampin is a potent cytochrome P450 (CYP) 3A inducer, which often results in drug-drug interactions in ICH receiving multiple CYP substrates. One way to mitigate rifampin’s CYP induction is to utilize clarithromycin, a CYP inhibitor, as the accompanying macrolide. We evaluated the incidence of NTM treatment-related adverse events (AEs) in patients who received a clarithromycin-based regimen compared to patients who received an azithromycin-based regimen. Methods We conducted a retrospective review of NTM infection in 30 immunocompromised adults. All participants had a positive culture for a NTM and had received a rifamycin (rifampin or rifabutin) with a macrolide (azithromycin or clarithromycin) for treatment at Brigham and Women’s Hospital between 01/01/2011-10/18/2020 or Dana-Farber Cancer Institute between 06/03/2015-07/01/2020. The primary outcome was the incidence of NTM treatment-related AEs in patients who received a clarithromycin-based regimen compared to those who received an azithromycin-based regimen. Results There were no significant differences in the reasons for discontinuation of NTM treatment or 90-day mortality between groups. The number of AEs possibly related to NTM treatment were similar in patients who received a clarithromycin-based regimen and those who received an azithromycin-based one (10/13 vs. 14/17; p=0.73). The most common AE was liver function test abnormalities (Table 1). Additionally, the proportion of patients requiring dose adjustments for interacting medications and patients with out-of-range tacrolimus levels were similar between the two groups (23.1% vs. 29.4%; p=0.76 and 8.0% vs. 6.0%; p=1.00, respectively). Table 1: Adverse events Conclusion A clarithromycin-based regimen for NTM treatment was safe and well tolerated in our patient population. This combination provides a good alternative for patients requiring medications that are CYP substrates, or those who cannot tolerate azithromycin. Disclosures Matthew Cheng, MD, GEn1E Lifesciences (Advisor or Review Panel member)Kanvas Biosciences (Board Member, Shareholder)nplex biosciences (Advisor or Review Panel member)

Outcomes of nontuberculous mycobacteria isolation among lung transplant recipients: A matched case-control with retrospective cohort study

2021 ◽  
Author(s):  
Razelle Grimes ◽  
Lauren Cherrier ◽  
Aasya Nasar ◽  
Michael D Nailor ◽  
Rajat Walia ◽  
...  
Keyword(s):  
Adverse Events ◽  
Drug Interactions ◽  
Diagnostic Criteria ◽  
Lung Transplant ◽  
Nontuberculous Mycobacteria ◽  
Case Control ◽  
Transplant Recipients ◽  
Lung Colonization ◽  
Increased Risk ◽  
Lung Transplant Recipients

Abstract Disclaimer In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Lung transplant recipients are at increased risk for acquiring nontuberculous mycobacteria (NTM), but the clinical significance of NTM isolation, particularly among patients not meeting guideline-endorsed diagnostic criteria for NTM pulmonary disease, is unclear. Methods A case-control study of lung transplant recipients with culture-positive NTM infections treated at a large transplant center during a 7-year period (2013-2019) was performed. Results Twenty-nine cases were matched 1:2 to non-NTM controls. The median time to NTM isolation was 10.7 months post transplant. Only 34.5% of all cases, and half of treated cases, met diagnostic criteria for NTM pulmonary infection. All-cause mortality at 12 months was numerically higher among NTM cases versus controls (20.7% vs 8.6%, P = 0.169); however, no deaths were attributed to NTM. No increase in the 12-month rate of acute rejection was observed (27.6% vs 36.2%, P = 0.477). Recent augmented immunosuppression was associated with increased odds of NTM isolation, while azithromycin prophylaxis was associated with reduced odds of isolation and was not associated with macrolide resistance. Both adverse events and actual or potential drug-drug interactions occurred in more than 90% of treated cases; these events included ocular toxicity, hearing loss, and supratherapeutic calcineurin inhibitor concentrations. Eight of the 14 treated cases (57.1%) required early antibiotic discontinuation due to adverse events or drug-drug interactions. Conclusion Among lung transplant recipients, most patients with NTM isolation did not meet guideline criteria for infection and had outcomes similar to non‒NTM-infected patients, which may reflect transient lung colonization by NTM rather than true disease. As adverse events are common with NTM therapy, limiting unnecessary antibiotic treatment represents an area for future antimicrobial stewardship efforts.

Postvaccination Adverse Events

2010 ◽  
Vol 44 (12) ◽  
pp. 16
Author(s):  
STEPHEN I. PELTON
Keyword(s):  
Adverse Events
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