Clinical Significance of Mucor in Airway Culture of Immunocompetent Patients With Chronic Lung Disease.

OBJECTIVES: Mucor within the airways of immunocompromised patients often signifies an invasive life-threatening infection. However, its significance in immunocompetent patients with chronic lung diseases is less clear. We aimed to assess the clinical implication of mucor in airway-secretion cultures of these patients. METHODS: A single-center retrospective cohort study was performed. Patients with cystic fibrosis (CF), primary ciliary dyskinesia (PCD) or non-CF/non-PCD bronchiectasis followed in our Pediatric Pulmonary Institute, with sputum or bronchoalveolar lavage cultures growing Mucorales molds in the years 2010-2022, were included. Demographic and clinical parameters such as body mass index and spirometry values (forced expiratory volume at 1 second) were collected and compared with values up to 12 months prior to and following the index (positive culture) visit. RESULTS: A total of 27 patients of whom 22 (82%) patients were with CF, 3 with PCD (11%) and 2 (7%) with non-CF/non-PCD bronchiectasis were included. Median age was 21.8 (14.9-32.1) years, with forced expiratory volume at 1 second of 62.8% ± 21.9% at the index visit. None of the patients developed disseminated disease, none had clinical or radiological evidence of fungal disease and none required antifungal therapy. Throughout the 12 months prior to and following the positive cultures, no significant changes were noted in body mass index, forced expiratory volume at 1 second, frequency of pulmonary exacerbations, days of hospitalization or days of antibiotic treatment. CONCLUSIONS: Evidence of mucor in airway cultures of immunocompetent patients with chronic lung disease does not necessarily signify clinical deterioration nor suggests invasive fungal disease. Larger, long-term prospective studies are required to obviate the need for a thorough evaluation in these patients.

Clinical significance and burden of carbapenem-resistant Enterobacterales (CRE) colonization acquisition in hospitalized patients.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) infections have a significant morbidity and mortality toll. The clinical significance and associated burden of CRE colonization rather than infection state are not frequently investigated. We aimed to assess the outcomes of CRE colonized patients compared to matched controls. METHODS: A secondary analysis of a 1:2 matched case-control study at a tertiary hospital in northern Israel (January-2014 to June-2017). Cases were adults who newly acquired CRE colonization during hospitalization. Controls were inpatients negatively screened for CRE, matched by age, hospitalization division and total days of hospitalization 90 days prior to screening. Our primary outcome was 1-year all-cause mortality. Secondary outcomes included 30-day mortality, diagnosis of any clinical infection, overall days of hospital stay and bloodstream infections all in 1-year follow-up. We estimated crude and propensity score weighted estimates for study outcomes. RESULTS: We included a total of 1019 patients: 340 CRE colonized and 679 non-colonized controls. After adjustment, CRE colonization was not associated with increased 1-year mortality (weighted OR 0.98, 95% CI 0.64-1.50, p = 0.936). CRE colonized patients had 1.7 times the odds of clinical infection of any cause (weighted odds ratio (OR) 1.65, 95% CI 1.06-2.56, p = 0.025). CRE colonized patients had increased length of hospital stay compared to controls (weighted OR 1.52, 95%CI 1.10-2.10, p < 0.001) among 1-year survivors. CONCLUSIONS: CRE colonization may not be independently associated with mortality but with higher risk of clinical infections and longer hospital stays. Infection prevention and antimicrobial stewardship are of utmost importance to prevent acquisition and infections in colonized patients.

Prevalence and Clinical Consequences of Colistin Heteroresistance and Evolution into Full Resistance in Carbapenem-Resistant Acinetobacter baumannii.

Colistin heteroresistance (HR) refers to a bacterial population comprised of several subpopulations with different levels of resistance to colistin. In this study, we discuss the classic form of HR, in which a resistant subpopulation exists within a predominantly susceptible population. We investigated the prevalence of colistin HR and its evolution into full resistance among 173 clinical carbapenem-resistant Acinetobacter baumannii isolates and examined the effect of HR on clinical outcomes. To determine HR, we performed population analysis profiling. Our results showed a high prevalence of HR (67.1%). To examine evolution of HR strains into full resistance, the HR strains were grown in colistin-containing broth, transferred onto colistin-containing plates, and colonies on these plates were transferred into colistin-free broth. Many of the HR strains (80.2%) evolved into full resistance, 17.2% reverted to HR, and 2.6% were borderline. We used logistic regression to compare 14-day clinical failure and 14-day mortality between patients infected by HR versus susceptible non-HR carbapenem-resistant A. baumannii. In the subgroup of patients with bacteremia, HR was significantly associated with 14-day mortality. IMPORTANCE To our knowledge, this is the first large-scale study to report on HR in Gram-negative bacteria. We described the prevalence of colistin HR in a large sample of carbapenem-resistant A. baumannii isolates, the evolution of many colistin HR isolates to a resistant phenotype following colistin exposure and withdrawal, and the clinical consequences of colistin HR. We found a high prevalence of HR among clinical carbapenem-resistant A. baumannii isolates; most evolved into a resistant phenotype following colistin exposure and withdrawal. In patients treated with colistin, evolution of HR A. baumannii into full resistance could lead to higher rates of treatment failure and contribute to the reservoir of colistin-resistant pathogens in health care settings.