Cryptococcal meningitis (CM) causes significant morbidity and mortality globally; however, recent national trends have not been described. Incidence and trends for CM-associated hospitalizations in ...18 states were estimated using the Agency for Healthcare and Research Quality (AHRQ) State Inpatient Databases (SID) datasets for 1997 through 2009. We identified 30,840 hospitalizations coded for CM, of which 21.6% were among HIV-uninfected patients. CM in-hospital mortality was significant (12.4% for women and 10.8% for men) with a total of 3,440 deaths over the study period. Co-morbidities of CM coded at increased frequency in HIV-uninfected CM hospitalized populations included hydrocephalus and acute/chronic renal failure as well as possible predispositions including transplantation, combined T and B cell defects, Cushing's syndrome, liver disease and hypogammaglobulinemia. Median hospitalization costs were significant for CM and higher for HIV-uninfected patients (16,803.01 vs. 15,708.07; p<0.0001). Cryptococcal meningitis remains a disease with significant morbidity and mortality in the U.S. and the relative burden among persons without HIV infection is increasing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Population-based data have documented a worldwide increase in the prevalence of human nontuberculous mycobacterial (NTM) infections since 2000. Mycobacterium avium complex is predominant in North ...America and East Asia, whereas in regions within Europe, M kansasii, M xenopi, and M malmoense are more common. Host factors important to the current epidemiology of NTM pulmonary disease include thoracic skeletal abnormalities, rheumatoid arthritis, and use of immunomodulatory drugs. Clustering of disease within families suggests a heritable genetic predisposition to disease susceptibility. Warm, humid environments with high atmospheric vapor pressure contribute to population risk.
Persons with cystic fibrosis (CF) are at high risk of nontuberculous mycobacterial (NTM) infection, with treatment requiring prolonged multidrug regimens that include macrolides. Although macrolides, ...specifically azithromycin, are used in the management of patients with CF with chronic Pseudomonas, macrolide-resistant NTM infections are of growing concern.
To evaluate the relationship between chronic macrolide use and NTM infection among patients with CF included in the 2011 CF Patient Registry (CFPR).
We performed a nested case-control study: incident NTM cases were persons aged more than 5 years with at least one positive culture for NTM in 2011. Controls were persons with negative cultures in 2010 and 2011.
The 2011 CFPR included 27,112 patients; 5,403 (20%) were cultured for mycobacteria in 2010-2011 and met all inclusion criteria. Of these, 191 (4%) were NTM-positive in 2011 only (cases); 5,212 (96%) were NTM-negative in 2010 and 2011 (control subjects). Among the cases, 122 (64%) were culture-positive for Mycobacterium avium complex (MAC) and 69 (36%) for M. abscessus. Azithromycin use in 2010 was less frequently reported among MAC cases (57%; odds ratio = 0.7, P < 0.05) and M. abscessus cases (51%; odds ratio = 0.5, P < 0.01) than in control subjects (66%). Among adolescents and adults, patients with the greatest number of years on chronic macrolides were the least likely to develop incident NTM in 2011 (P < 0.01).
Patients with incident NTM infections from either MAC or M. abscessus were less likely to have had chronic azithromycin treatment in the past year. However, because macrolide monotherapy may lead to macrolide resistance, routine screening for NTM should be considered for persons with CF.
Background Bronchiectasis is a potentially serious condition characterized by permanent and abnormal widening of the airways, the prevalence of which is not well described. We sought to describe the ...trends, associated conditions, and risk factors for bronchiectasis among adults aged ≥ 65 years. Methods A 5% sample of the Medicare outpatient claims database was analyzed for bronchiectasis trends among beneficiaries aged ≥ 65 years from 2000 to 2007. Bronchiectasis was identified using International Classification of Diseases, Ninth Revision, Clinical Modification claim diagnosis codes for acquired bronchiectasis. Period prevalence was used to describe sex- and race/ethnicity-specific rates, and annual prevalence was used to describe trends and age-specific rates. We estimated trends using Poisson regression and odds of bronchiectasis using multivariate logistic regression. Results From 2000 to 2007, 22,296 people had at least one claim for bronchiectasis. The 8-year period prevalence of bronchiectasis was 1,106 cases per 100,000 people. Bronchiectasis increased by 8.7% per year. We identified an interaction between the number of thoracic CT scans and race/ethnicity; period prevalence varied by a greater degree by number of thoracic CT scans among Asians compared with whites or blacks. Among people with one CT scan, Asians had a 2.5- and 3.9-fold higher period prevalence compared with whites and blacks. Conclusions Bronchiectasis prevalence increased significantly from 2000 to 2007 in the Medicare outpatient setting and varied by age, sex, and race/ethnicity. This increase could be due to a true increase in the condition or an increased recognition of previously undiagnosed cases.
Abstract
Background
Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such ...difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic.
Methods
The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories.
Results
Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0.
Conclusion
Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.
Resistance to all first-line agents or difficult-to-treat resistance (DTR) was observed in 1% of gram-negative bacteremias. DTR was identified at half the hospitals; nearly 80% of patients with DTR received "reserve" agents. Mortality risk increased with decreasing active first-line categories.
Pulmonary nontuberculous mycobacteria (PNTM) are an important cause of morbidity among older adults in the United States, but national prevalence estimates are lacking.
To describe the prevalence and ...trends of PNTM disease among adults aged 65 years or older throughout the United States.
A nationally representative 5% sample of Medicare Part B beneficiaries was analyzed from 1997 to 2007. Demographic and medical claims data were compiled and prevalence estimates for PNTM and selected comorbidities were calculated and trends over time evaluated. Logistic regression was used to identify demographic and geographic factors associated with PNTM.
From 1997 to 2007, the annual prevalence significantly increased from 20 to 47 cases/100,000 persons, or 8.2% per year. The period prevalence was 112 cases/100,000 persons, although prevalence was twofold higher among Asians/Pacific Islanders than among whites (228 vs. 116 cases/100,000 persons). Western states had the highest period prevalence at 149 cases/100,000 persons, with Hawaii having the highest prevalence at 396 cases/100,000 persons, followed by southeastern states, which had a period prevalence of 131 cases/100,000 persons. PNTM cases had more comorbid conditions than noncases and were 40% more likely to die than noncases. Women were 1.4 times more likely to be a PNTM case than men. Relative to whites, Asians/Pacific Islanders were twice as likely to be a case, whereas blacks were half as likely.
The prevalence of PNTM is increasing across all regions of the United States and among both men and women. Significant racial/ethnic and geographic differences suggest important gene-environment interactions.
Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been reported and is of increasing concern. No standardized epidemiologic ...investigation tool has been published for healthcare-associated NTM outbreak investigations. This report describes the design of an ongoing observational study to standardize the approach to NTM outbreak investigation among pwCF.
This is a parallel multi-site study of pwCF within a single Center who have respiratory NTM isolates identified as being highly-similar. Participants have a history of positive airway cultures for NTM, receive care within a single Center, and have been identified as part of a possible outbreak based on genomic analysis of NTM isolates. Participants are enrolled in the study over a 3-year period. Primary endpoints are identification of a shared healthcare-associated encounter(s) among patients in a Center and identification of environmental isolates that are genetically highly-similar to respiratory isolates recovered from pwCF. Secondary endpoints include characterization of potential transmission modes and settings, as well as incidence and prevalence of healthcare-associated environmental NTM species/subspecies by geographical region.
We hypothesize that genetically highly-similar strains of NTM among pwCF cared for at the same Center may arise from healthcare sources including patient-to-patient transmission and/or acquisition from environmental sources. This novel study design will establish a standardized, evidence-based epidemiologic investigation tool for healthcare-associated NTM outbreak investigation within CF Care Centers, will broaden the scope of independent outbreak investigations and demonstrate the frequency and nature of healthcare-associated NTM transmission in CF Care Centers nationwide. Furthermore, it will provide valuable insights into modeling risk factors associated with healthcare-associated NTM transmission and better inform future infection prevention and control guidelines. This study will systematically characterize clinically-relevant NTM isolates of CF healthcare environmental dust and water biofilms and set the stage to describe the most common environmental sources within the healthcare setting harboring clinically-relevant NTM isolates.
ClinicalTrials.gov NCT04024423. Date of registry July 18, 2019.
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Increased awareness of nontuberculous mycobacterial pulmonary disease (NTM PD) has led to efforts to more fully describe the burden, epidemiological and clinical features, and cost of this condition ...in different populations globally. Approaches encompass various methodologies including surveillance, population-based studies, analysis of large linked datasets, surveys, laboratory-based convenience samples and combinations of these approaches. Surveillance has been defined as the “systematic collection, consolidation, and evaluation of morbidity and mortality reports, and… regular dissemination to all who need to know” 1. For NTM PD, notifiable condition reporting varies. In Queensland, Australia, notification of NTM infections is required; reporting is electronic and laboratory-based 2. In several states within the USA, NTM isolates or cases are listed as notifiable conditions 3, 4, although in Oregon, only extrapulmonary isolates are listed as notifiable 3. Although reporting might not be complete, and the system may have biases related to healthcare-seeking behaviour and physician awareness, these data are essential to elucidating the epidemiology of NTM PD 3.
Nontuberculous mycobacteria are an important cause of morbidity in the United States, although patient outcomes vary greatly by species. Currently, nationally representative data on the distribution ...of mycobacterial species from clinical isolates are limited.
Using a national hospitalization database capturing microbiologic data for nearly 6 million patient encounters, we describe the geographic distribution of, and patient demographic features associated with, clinical mycobacterial isolates in the United States.
Linked demographic and microbiologic data from the Premier Healthcare Database were extracted for all patient encounters from 2009 to 2013. Patients with at least one positive potentially pathogenic nontuberculous mycobacterial culture were identified as cases. The period prevalence was calculated, and patient-, encounter-, and hospital-level factors were analyzed. Regional differences in species distribution were analyzed; a subanalysis was conducted among patients with International Classification of Diseases, Ninth Revision, codes for pulmonary nontuberculous mycobacterial disease. Significant differences were assessed (P < 0.05).
Of 5,928,830 unique patients included during the 5-year study period, 7,812 (0.13%) had at least one positive nontuberculous mycobacterial culture. The mean age of cases was 64 years (range, <1-89 yr), and most were female (52%) and white (70%). Hospitals with cases were more often labeled "urban" (96%), "teaching" (56%), and had at least 500 beds (78%). Species distribution differed significantly by geographic area. Mycobacterium avium complex ranged from 61 to 91% of isolates and were most frequent in the South and Northeast regions; M. abscessus/M. chelonae ranged from 2 to 18% of isolates and were most frequent in the West; and other species, including M. fortuitum and M. kansasii, ranged from 7 to 26% and were also most frequent in the West.
Significant geographic variation exists in the distribution of nontuberculous mycobacterial species in the United States. Whereas M. avium complex was the most common species isolated in the South, M. abscessus/M. chelonae was proportionately higher in the West. Greater clinical awareness in regions with increased levels of harder-to-treat mycobacteria are needed, given differences in treatment options and implications for patient outcomes.
Olivier and Prevots discuss Gross and colleagues's report of a retrospective study, HALT-NTM (Healthcare-associated Links in Transmission of NTM; NCT04024423), that used whole-genome sequencing (WGS) ...and a systematic, evidence-based, standardized epidemiologic approach to investigate the potential for transmission versus environmental acquisition at the University of Colorado Adult CF Center. Core genome analysis identified 11 clusters comprising 27 subjects, with 4 of these clusters (2 Mycobacterium abscessus and 2 Mycobacterium avium) having overlapping opportunities for healthcare transmission. This study does make a significant contribution to the building literature seeking to address nontuberculous mycobacteria (NTM) transmission and acquisition. One of the most promising aspects is its planned extrapolation to other cystic fibrosis (CF) centers, which is already underway using a standardized study design. With increasing numbers of same-site clusters being evaluated in a similar fashion at multiple geographically dispersed centers with variations in infection control practices, additional data may help to clarify the validity of the findings in this study.
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