Daptomycin-induced Eosinophilic Pneumonia Research Articles

Daptomycin-induced eosinophilic pneumonia.

Daptomycin-induced eosinophilic pneumonia (DIEP) is a rare complication of daptomycin use. Manifestations most commonly include fever, hypoxia, dyspnea, cough, eosinophilia, and lung changes on radiographs and CT. Patients typically have had recent daptomycin exposure and develop fever, dyspnea, infiltrates on chest radiograph, more than 25% eosinophils on bronchoalveolar lavage, and improvement of symptoms after withdrawal of daptomycin. Treatment includes discontinuation of daptomycin, corticosteroids, and supportive measures such as supplemental oxygen. Clinicians should have a high index of suspicion for DIEP in patients who develop new onset of pulmonary and systemic signs and symptoms after initiation of daptomycin.

Is a high baseline inflammatory burden the major driver in causing daptomycin-induced eosinophilic pneumonia and muscular toxicity?

Is a high baseline inflammatory burden the major driver in causing daptomycin-induced eosinophilic pneumonia and muscular toxicity?

Daptomycin Exposure as a Risk Factor for Daptomycin-Induced Eosinophilic Pneumonia and Muscular Toxicity.

High-dose daptomycin is increasingly used in patients with bone and joint infection (BJI). This raises concerns about a higher risk of adverse events (AEs), including daptomycin-induced eosinophilic pneumonia (DIEP) and myotoxicity. We aimed to examine pharmacokinetic and other potential determinants of DIEP and myotoxicity in patients with BJI receiving daptomycin. All patients receiving daptomycin for BJI were identified in a prospective cohort study. Cases were matched at a 1:3 ratio, with controls randomly selected from the same cohort. Bayesian estimation of the daptomycin daily area under the concentration-time curve over 24 hours (AUC24h) was performed with the Monolix software based on therapeutic drug monitoring (TDM) data. Demographic and biological data were also collected. Risk factors of AEs were analyzed using Cox proportional hazards model. From 1130 patients followed over 7 years, 9 with DIEP, 26 with myotoxicity, and 106 controls were included in the final analysis. Daptomycin AUC24h, C-reactive protein, and serum protein levels were associated with the risk of AEs. The adjusted hazard ratio of DIEP or myotoxicity was 3.1 (95% confidence interval [CI], 1.48-6.5; P < .001) for daptomycin AUC24h > 939 mg/h/L, 9.8 (95% CI, 3.94-24.5; P < .001) for C-reactive protein > 21.6 mg/L, and 2.4 (95% CI, 1.02-5.65; P = .04) for serum protein <72 g/L. We identified common determinants of DIEP and myotoxicity in patients with BJI. Because the risk of AEs was associated with daptomycin exposure, daptomycin TDM and model-informed precision dosing may help optimize the efficacy and safety of daptomycin treatment in this setting. A target AUC24h range of 666 to 939 mg/h/L is suggested.

A Case of Daptomycin-Induced Eosinophilic Pneumonia

Daptomycin is commonly used for methicillin-resistant Staphylococcus aureus infections, but 1 rarely reported adverse reaction for its use is daptomycin-induced eosinophilic pneumonia. It is unclear how or why the drug produces this reaction. Workup includes ruling out other infectious causes and discontinuing daptomycin, and bronchoscopy showing more than 25% eosinophils is diagnostic. Here, we report a rarely described patient case of daptomycin-induced eosinophilic pneumonia and discuss its management.

Clinical characteristics, management, and outcome of eosinophilic pneumonia associated with daptomycin

ObjectiveThe association between daptomycin exposure and eosinophilic pneumonia (EP) is mainly based on case reports. The purpose of this study was to evaluate the clinical characteristics and provide more evidence for better identify and management of daptomycin-induced eosinophilic pneumonia in clinical practice. MethodsLiterature from 1991 to October 31, 2021 on EP induced by daptomycin were collected for retrospective analysis. ResultsA total of 47 patients (40 male and 7 female) from 35 studies were included. The median age was 67 years (range 28–89), and 78.7% of patients were ≥60 years. Daptomycin was mainly used in patients undergoing osteoarticular infections (63.8%). Typical initial symptoms were fever (91.5%), cough (55.3%) and dyspnea (59.6%). The median onset time of symptom was 3 weeks. EP recurred in 14.9% of patients after the re-administration of daptomycin, and 57.1% of EP recurred within 24h. Most cases were accompanied by marked accumulation of eosinophils in peripheral (41 cases) and/or bronchoalveolar lavage fluid (27 cases). The main radiological features were pulmonary infiltration, ground glass opacity or consolidation in CT/CXR. All patients had symptom resolution after discontinuation of daptomycin except for one patient died due to the progression of the primary disease, the median time to symptoms relief was 3 days. Corticosteroids have been shown to help symptoms relief in some cases (59.6%). ConclusionDaptomycin-induced eosinophilic pneumonia is a rare and serious complication. Physicians should consider eosinophilic pneumonia as a differential diagnosis when receiving daptomycin therapy, particularly in elderly male patients.

621. Pharmacokinetics Determinant and Risk Factors of Daptomycin Induced Eosinophilic Pneumonia and Muscular Toxicity: A Survival Analysis in patients treated for Bone and Joint Infection.

Abstract Background Daptomycin prescription for patients suffering from Bone and Joint infections increased in recent years. However, the implication between daptomycin exposure, concomitant factor, and the occurrence of either daptomycin-induced eosinophilic pneumonia (DIEP) or CPK elevation is not clearly understood. Methods All patients treated for a bone and joint infection (BJI) between 2014 and 2021 were screened and classified into cases if they experienced a CPK elevation or DIEP. The controls were randomly selected at a 1:3 ratio within the same period of inclusion. Daptomycin levels were obtained from routine therapeutic drug monitoring. In addition, demographic and biology data were also obtained from the computerized file of patients. Those data were used to compute the area under the concentration-time curve (AUC) of daptomycin using a previously developed population pharmacokinetic model. Finally, a univariate analysis was performed and all data with a p-value &amp;lt; 0.1 were included in the multivariate survival analysis using a proportional Cox hazard model. Results A total of 1130 patients were screened from which 16 patients with DIEP, 42 with CPK elevation, and 107 control were included in the final analysis. Age, CRP, Creatinine, Creatinine Clearance, Serum protein, AUC, and through concentrations were significantly different between case and controls. Summary of univariate analysis is available in table 1. After multivariate analysis, only 3 predictors remained significantly associated with the occurrence of DIEP or CPK elevation. The adjusted hazard ratio of developing DIEP of CPK elevation, were 3.1 (95% CI: 1.48 – 6.5, p &amp;lt; 0.001) for a daptomycin AUC &amp;gt; 939 mg.h/L, 9.8 (95% CI 3.94 – 24.5, p &amp;lt; 0.001) for CRP &amp;gt; 21.6mg/L and 2.4 (95% CI 1.02 – 5.65, p = 0.04] for Protein &amp;lt; 72g/L. Survival curves are shown in figure1. Variable identified in the whole population remained significant in DIEP or CPK subgroup analyses. Table 1.Patients characteristics at time of inclusionFigure 1.Survival analysis of the whole population according to AUC and CRP levels. Conclusion The risk of experiencing DIEP or CPK elevation was greater in patients with an AUC0-24 above 939 mg.h/L and a CRP &amp;gt; 21.6mg/L. Daptomycin Therapeutic drug monitoring should be performed and an AUC range of 666 to 939 mg.h/L should be targeted in order to maximize efficacy and minimize the risk of adverse events, especially for patients with an inflammatory syndrome. Disclosures All Authors: No reported disclosures.

Seventeen Cases of Daptomycin-Induced Eosinophilic Pneumonia in a Cohort of Patients Treated for Bone and Joint Infections: Proposal for a New Algorithm.

Daptomycin is increasingly used in the treatment of bone and joint infections (BJIs) and may be responsible for daptomycin-induced eosinophilic pneumonia (DIEP), a potentially severe adverse drug reaction. The aim of this study was to describe DIEP in patients treated at a referral center for the management of BJI, and to revisit current definitions of this disease. Patients treated from 1 January 2012 to 31 March 2021 were included in a prospective cohort (NCT02817711), in which all potential serious adverse events are prospectively recorded. Patients diagnosed with DIEP were retrospectively analyzed using different definitions. In a total of 4664 patients included in the cohort during the study period, 1021 patients (21.9%) received daptomycin, of whom 17 (1.7%) were diagnosed with DIEP. Most patients were male (n = 11 [64.7%]), and periprosthetic joint infection was the commonest BJI (n = 12 [70.6%]). Only 1 patient had bronchoalveolar lavage (BAL) eosinophil count ≥25%, while most patients had peripheral blood eosinophilia (n = 15 [88.2%]). Chest computed tomography (CT) was compatible with eosinophilic pneumonia in 13 of 14 cases (92.9%). All patients recovered upon discontinuation of daptomycin. Using the different definitions available, only a minority of cases fulfilled existing criteria for DIEP. We propose a new algorithm that includes specific CT scan signs, and systemic instead of BAL eosinophilia. DIEP is a rare event that requires prompt discontinuation of the causative antibiotic. Current criteria to diagnose definite DIEP are too restrictive and not easily applicable in clinical practice. A new algorithm is proposed here (Lyon algorithm) to facilitate the early identification of DIEP.

DAPTOMYCIN-INDUCED EOSINOPHILIC PNEUMONITIS

DAPTOMYCIN-INDUCED EOSINOPHILIC PNEUMONITIS

Clinical characteristics, management, and outcome of eosinophilic pneumonia associated with daptomycin

ObjectiveThe association between daptomycin exposure and eosinophilic pneumonia (EP) is mainly based on case reports. The purpose of this study was to evaluate the clinical characteristics and provide more evidence for better identify and management of daptomycin-induced eosinophilic pneumonia in clinical practice. MethodsLiterature from 1991 to October 31, 2021 on EP induced by daptomycin were collected for retrospective analysis. ResultsA total of 47 patients (40 male and 7 female) from 35 studies were included. The median age was 67 years (range 28–89), and 78.7% of patients were ≥60 years. Daptomycin was mainly used in patients undergoing osteoarticular infections (63.8%). Typical initial symptoms were fever (91.5%), cough (55.3%) and dyspnea (59.6%). The median onset time of symptom was 3 weeks. EP recurred in 14.9% of patients after the re-administration of daptomycin, and 57.1% of EP recurred within 24h. Most cases were accompanied by marked accumulation of eosinophils in peripheral (41 cases) and/or bronchoalveolar lavage fluid (27 cases). The main radiological features were pulmonary infiltration, ground glass opacity or consolidation in CT/CXR. All patients had symptom resolution after discontinuation of daptomycin except for one patient died due to the progression of the primary disease, the median time to symptoms relief was 3 days. Corticosteroids have been shown to help symptoms relief in some cases (59.6%). ConclusionDaptomycin-induced eosinophilic pneumonia is a rare and serious complication. Physicians should consider eosinophilic pneumonia as a differential diagnosis when receiving daptomycin therapy, particularly in elderly male patients.

Factors Associated with Daptomycin-Induced Eosinophilic Pneumonia.

The risk factors for eosinophilic pneumonia (EP) remain unclear. We investigate the characteristics of patients with daptomycin (DAP)-induced EP and conducted a retrospective observational study. A total of 450 patients aged ≥ 18 years who received DAP (25 DAP with EP, 425 DAP without EP) were included. The median duration from the first DAP administration to EP onset was 18.0 days. Definite, probable, and possible DAP-induced EP were diagnosed in 0, 9, and 16 patients, respectively. The median age (DAP with EP, 72.0 years; DAP without EP, 64.0 years), DAP dosage/body weight (BW) (9.00 vs. 7.50 mg/kg), blood eosinophil count (cells/μL) (419 vs. 96), and the percentage of hemodialyzed patients (40.0% vs. 13.4%) were significantly higher in patients with EP than in patients without EP in the univariate analysis. In separate multivariate logistic regression analyses, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.00–1.05), DAP dosage/BW (OR, 1.61; 95% CI, 1.25–2.07), and hemodialysis (OR, 4.42; 95% CI, 1.86–10.5) were significantly associated with DAP-induced EP. Clinicians may need to consider the potential factors associated with EP, especially in older patients, patients on hemodialysis, or patients who receive > 9.00 mg/kg of DAP.

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.

Daptomycin-induced eosinophilic pneumonia: Are there any risk factors?

ObjectivesDaptomycin is a widely used antibiotic. Rhabdomyolysis related to daptomycin is one of the adverse effects of treatment, justifying the need for regular monitoring of muscle enzymes throughout treatment. Daptomycin may also lead to eosinophilic pneumonia. However, risk factors for this adverse reaction have not been identified and do not permit targeting of at-risk populations who could benefit from appropriate monitoring. Patients and methodsLiterature was reviewed for cases of daptomycin-induced eosinophilic pneumonia (DIEP), which that were compared to cases of patients without this adverse effect. ResultsFifty patients with DIEP and 54 controls were identified. Age, sex, and treatment dose are not associated with the occurrence of DIEP. A high dose of daptomycin is not associated with an early onset of DIEP. About one third of patients with eosinophilic lung disease have diabetes or renal impairment. ConclusionsFurther studies may help to identify additional factors.

Daptomycin-induced Eosinophilic Pneumonia and a Review of the Published Literature

A 53-year-old man was admitted to the hospital with a diagnosis of cellulitis and osteomyelitis. Twenty-four days after the initiation of daptomycin and sulbactam/ampicillin, he developed a fever and pulmonary infiltration. Bronchoalveolar lavage revealed a high number of eosinophils, while an intracutaneous test revealed positivity for daptomycin. The patient improved after discontinuing antimicrobial therapy. The plasma daptomycin minimum concentration (Cmin) was elevated (27.4 μg/mL), but plasma protein binding of daptomycin was low (87.8%). Although the pathophysiology of eosinophilic pneumonia remains unclear, antigenic stimulation due to daptomycin accumulation in the alveoli may have caused continuous immune activation.

Daptomycin-Induced Eosinophilic Pneumonia in Renal Dysfunction

Daptomycin-Induced Eosinophilic Pneumonia in Renal Dysfunction

Daptomycin-induced eosinophilic pneumonia

Daptomycin-induced eosinophilic pneumonia

Daptomycin-Induced Eosinophilic Pneumonia Treated With Intravenous Corticosteroids

Objective: To describe 2 cases of drug-induced eosinophilic pneumonia in patients with variable exposure to daptomycin. Report: In our first case, a 77-year-old male was transferred to our facility for hypoxic respiratory failure, which occurred 1 day after completing a course of daptomycin. There was high clinical suspicion for daptomycin-induced eosinophilic pneumonia, thus the patient was started on intravenous methylprednisolone 40 mg every 6 hours. Within 72 hours, he was liberated from mechanical ventilation, as he experienced dramatic clinical improvement in regard to his oxygenation and radiographs. Approximately 6 weeks after case 1, a second case of eosinophilic pneumonia related to daptomycin was diagnosed. This case occurred in a 74-year-old female who developed respiratory failure requiring noninvasive positive pressure ventilation 72 hours after initiation of a second course of daptomycin. She was treated with methylprednisolone 60 mg every 6 hours and avoided the need for endotracheal intubation and mechanical ventilation. Conclusion: Since this potentially life-threatening adverse effect of daptomycin appears more common than previously reported, clinicians should have a high level of suspicion in any patient with recent daptomycin exposure who presents with pulmonary symptoms. In many cases, this process is highly responsive to prompt initiation of corticosteroid therapy.

Daptomycin-Induced Eosinophilic Pneumonia

SESSION TYPE: ILD Cases I

A rare cause of pulmonary infiltrates one should be aware of: a case of daptomycin-induced acute eosinophilic pneumonia

We report a 69-year-old patient who developed fever and dyspnea 3weeks after the initiation of daptomycin therapy for spondylodiscitis with lumbar epidural and bilateral psoas abscesses due to ampicillin- and high-level-gentamicin-resistant Enterococcus faecium. There was profound hypoxia and the chest X-ray showed extensive patchy infiltrates bilaterally. A bronchoalveolar lavage revealed 30% eosinophils and results of microbiological studies were normal. Daptomycin-induced eosinophilic pneumonia was diagnosed and the patient rapidly improved after the discontinuation of daptomycin and a brief course of prednisone. Increased attention must be paid to this rare but serious side effect of daptomycin.