Association of Antibiotic Treatment With Outcomes in Patients Hospitalized for an Asthma Exacerbation Treated With Systemic Corticosteroids

Stefan, Mihaela; Shieh, Meng Shiou; Spitzer, Kerry A.; Pekow, Penelope S.; Krishnan, Jerry A.; Au, David H.; Lindenauer, Peter K.

doi:10.1001/jamainternmed.2018.5394

Cited by 31 publications

(43 citation statements)

References 23 publications

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“…As a result, antibiotics are overprescribed-nearly half of the individuals in this study were given antibiotics, despite only a handful being adjudicated as having bacterial infection. This impacts antibiotic stewardship efforts as well as patient outcomes; a recent study reported longer admissions and higher cost of stay in asthmatics treated with antibiotics [31]. Gene expression approaches, once translated onto a clinically useful platform, could help abate empiric prescribing practices, mitigate antibiotic resistance, and improve patient care.…”

Section: Discussionmentioning

confidence: 99%

A host gene expression approach for identifying triggers of asthma exacerbations

et al. 2019

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Rationale Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable personalized asthma treatment and mitigate antibiotic overuse. Objectives To explore the performance of validated peripheral blood gene expression signatures in discriminating bacterial, viral, and noninfectious triggers in subjects with asthma exacerbations. Methods Subjects with suspected asthma exacerbations of various etiologies were retrospectively selected for peripheral blood gene expression analysis from a pool of subjects previously enrolled in emergency departments with acute respiratory illness. RT-PCR quantified 87 gene targets, selected from microarray-based studies, followed by logistic regression modeling to define bacterial, viral, or noninfectious class. The model-predicted class was compared to clinical adjudication and procalcitonin. Results Of 46 subjects enrolled, 7 were clinically adjudicated as bacterial, 18 as viral, and 21 as noninfectious. Model prediction was congruent with clinical adjudication in 15/18 viral and 13/21 noninfectious cases, but only 1/7 bacterial cases. None of the adjudicated bacterial cases had confirmatory microbiology; the precise etiology in this group was uncertain. Procalcitonin classified only one subject in the cohort as bacterial. 47.8% of subjects received antibiotics. Conclusions Our model classified asthma exacerbations by the underlying bacterial, viral, and noninfectious host response. Compared to clinical adjudication, the majority of discordances occurred in the bacterial group, due to either imperfect adjudication or model misclassification. Bacterial infection was identified infrequently by all classification schemes, but nearly half of subjects were prescribed antibiotics. A gene expression-based approach may offer useful diagnostic information in this population and guide appropriate antibiotic use.

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Section: Discussionmentioning

confidence: 99%

A host gene expression approach for identifying triggers of asthma exacerbations

et al. 2019

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“…As respiratory infections are a wellknown risk factor for exacerbations and worsening of inflammatory airway diseases, a vicious circle may emerge with increased risk of infections due to corticosteroid therapy and further worsening of the disease triggered by infections [21, 22 • ]. An overuse of antimicrobial agents in patients with chronic inflammatory airway diseases is also common and may result in unnecessary or prolonged hospital stays, higher costs, and increased risk of treatment failure [23]. Furthermore, data from animal models suggest that antimicrobial-induced reductions in microbiome diversity are related to impaired immune function and higher mortality following viral infection [24, 25 •• ].…”

Section: Unmet Needs In Chronic Inflammatory Airway Diseasesmentioning

confidence: 99%

Immunoactive preparations and regulatory responses in the respiratory tract: potential for clinical application in chronic inflammatory airway diseases

Feleszko

Rossi

Krenke

et al. 2020

Expert Review of Respiratory Medicine

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Introduction: The prevalence of chronic inflammatory airway diseases is rising. Their treatment with corticosteroids increases infection risk, while overuse of antimicrobial agents may increase morbidity and antimicrobial resistance. Nonspecific immunomodulatory compounds alter immune responses to both infectious and atopic challenges. These compounds may offer an alternative approach for symptom reduction and prophylaxis against both infections and exacerbations in chronic inflammatory airway disease. Areas covered: We assessed the available data on the efficacy of nonspecific immunomodulators including bacterial lysates, synthetic compounds, and vaccines in chronic rhinosinusitis (CRS); allergic and non-allergic rhinitis; chronic obstructive pulmonary disease (COPD), and asthma. A search of PubMed was carried out using the 'Clinical Trials' filter for each condition and immunomodulatory product detailed below, where available, data from meta-analyses were reported. Expert opinion: Pre-clinical data has revealed a coherent mechanistic path of action for oral immunomodulators on the respiratory immune system, principally via the gut-lung immune axis. In patients with asthma, allergic rhinitis, CRS, and COPD immunomodulatory therapy reduces symptoms, exacerbations, hospitalizations, and drug consumption. However, data are heterogeneous, and study quality remains limited. A lack of high-quality recent trials remains the major unmet research need in the field. ARTICLE HISTORY

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“…3,4 Additionally, a large retrospective observational study of nearly 20,0 0 0 patients hospitalised with an exacerbation suggests that antibiotic use does not improve outcome and is associated with higher costs. 5 Professional societies strongly discourage the use of antibiotics in asthma exacerbation through national guidelines 6,7 but despite this antibiotic use in adults hospitalised with exacerbation of asthma remains very common. [8][9][10] Patients hospitalised with exacerbation of COPD are also routinely treated with antibiotics despite viruses being frequently implicated in their aetiology 12 and a lack of high quality evidence for benefit in patients with non-life threatening exacerbations.…”

Section: Introductionmentioning

confidence: 99%

Impact of point-of-care testing for respiratory viruses on antibiotic use in adults with exacerbation of airways disease

Brendish

Mills

Ewings

et al. 2019

Journal of Infection

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s u m m a r yBackground: The ResPOC study demonstrated that syndromic molecular point-of-care testing (POCT) for respiratory viruses was associated with early discontinuation of unnecessary antibiotics compared to routine clinical care. Subgroup analysis suggests these changes occur predominantly in patients with exacerbation of airways disease. Use of molecular POCT for respiratory viruses is becoming widespread but there is a lack of evidence to inform the choice between multiplex syndromic panels versus POCT for influenza only. Materials/methods: We evaluated patients from the ResPOC study with exacerbation of asthma or COPD who were treated with antibiotics. The duration of antibiotics and proportion with early discontinuation were compared between patients testing positive and negative for viruses by POCT, and controls. Patients testing positive for viruses by POCT were compared according to virus types. Results: 118 patient with exacerbation of airways disease received antibiotics in the POCT group and 111 in the control group. In the POCT group 49/118 (42%) patients tested positive for viruses. Of those testing positive for viruses 17/49 (35%) had early discontinuation of antibiotics versus 9/69 (13%) testing negative and 7/111 (6%) of controls, p < 0.0 0 01. Of those positive for viruses by POCT 10/49 (20%) were positive for influenza, 21/49 (43%) for rhinovirus and 18/49 (37%) for other viruses. The proportion with early discontinuation of antibiotics was not different between the virus types ( p = 0.34). Conclusions: This data suggests that syndromic molecular POCT for respiratory viruses should be favoured over POCT for influenza alone in adults with exacerbation of airways disease.

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Association of Antibiotic Treatment With Outcomes in Patients Hospitalized for an Asthma Exacerbation Treated With Systemic Corticosteroids

Cited by 31 publications

References 23 publications

A host gene expression approach for identifying triggers of asthma exacerbations

A host gene expression approach for identifying triggers of asthma exacerbations

Immunoactive preparations and regulatory responses in the respiratory tract: potential for clinical application in chronic inflammatory airway diseases

Impact of point-of-care testing for respiratory viruses on antibiotic use in adults with exacerbation of airways disease

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