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Background Ceftazidime–avibactam (CAV) was US FDA-approved for complicated intra-abdominal/urinary tract infections in 2015, and for hospital-acquired/ventilator-associated pneumonia in 2018. However, little is known about its real-world use. Methods Encounters of inpatients receiving CAV at academic hospitals in the VizientTM Clinical Resource Manager were identified (CAV encounters). CAV administered for ≤2 consecutive days during an encounter or any duration of CAV within 2 days of admission (excluding acute care hospital transfers) was considered empiric therapy. Targeted therapy was defined as ≥4 consecutive days or death within 2 days of therapy; empiric and targeted therapy cohorts were mutually inclusive. CAV-encounter characteristics, use patterns and Infectious Disease (ID) consultation were examined. Quarterly hospital uptake of CAV and % change in CAV encounter prevalence (using Poisson regression) were calculated. Results From January 2015 to December 2017, 20,590 CAV doses occurred in 2,128 encounters among 1,652 patients. Mean duration of therapy was 8 ± 7.9 days (range 1–86); overall mortality was 24%. The number of hospitals prescribing CAV increased from 5 to 92/168 and quarterly prevalence of CAV encounters increased from 5/10,000 hospitalizations in 2015q1 to 9.8 in 2017q4 (% change=2.1[0.7–3.6] %/quarter; (P = 0.004). Therapy was empiric in 904 (42%) encounters and targeted in 1,472 (69%); 63% of empiric CAV was initiated within 2 days of admission. CAV was initiated in the ICU in 862 (40.5%) encounters. Infection site was coded as respiratory in 34%, urinary in 26% and abdominal in 16% of encounters. Within 31 hospitals reporting consultant specialty, 29% of targeted therapy occurred without ID consultation. For targeted therapy encounters, CAV monotherapy occurred in 841 (57%) and combination therapy in 631 (43%) encounters, which most often included aminoglycosides, colistin or tigecycline. Mortality was 22% in the monotherapy and 25% in the combination therapy group (P = 0.08). Conclusion CAV use across US academic medical centers has increased modestly over 3 years. More than 40% of CAV prescriptions appear to be empiric and targeted therapy often occurs without ID consultation at academic centers. Disclosures All authors: No reported disclosures.

Background Tick-borne diseases are increasing in incidence in the United States; however, limited data exist on regional trends of associated hospitalizations. Using a nationally distributed dataset of US hospital-based medical records, we aimed to assess trends in incidence of hospitalizations from tick-borne disease by geographic region. Methods Data were examined from 156 US hospitals from 2009 to 2014 to identify hospitalizations with tick-borne disease. Cases were described and Poisson regression used to estimate the annual percent change (APC) and associated 95% confidence intervals (CI) in incidence by region over time. Results Overall, 2,543 hospitalized patients with tick-borne disease were identified (average annual incidence = 28.4 cases/100,000 hospitalized persons), including 1,613 (63%) with Lyme disease, 379 (15%) tick-borne fever, 293 (12%) ehrlichiosis, 93 (4%) babesiosis, 43 (2%) rickettsiosis, and 122 (4%) multiple tick-related diagnoses. Tick-borne diseases varied significantly by region, with Lyme disease more frequent in those residing in the Northeast (68%) than the South (57%) or West (42%) and tick-borne fever more common in the West (28%) vs. the South (18%), Midwest (14%), and Northeast (13%) (P < 0.0001). Significant increases in tick-borne disease hospitalizations were identified across nearly all US regions, ranging from 15% per year in the South (95% CI=8–24%) to 45% per year in the West (34–58%), with the exception of the Northeast, where incidence declined by 6% per year (0.04–11%). Lyme disease hospitalizations showed similar trends, with the greatest increase in the South (APC = 53%, 95% CI = 33–76%) and a decrease in the Northeast (APC = 13%; 3%–23%). Hospitalizations with tick-borne fever increased in the Midwest (APC = 49%; 8–206%) and Northeast (APC = 18%; 4–34%); with ehrlichiosisincreased in the West (APC = 231%; 75–306%); and with babesiosis increased in the South (APC = 50%; 12–201%) and the Midwest (APC = 21%; 5–39%). Conclusion Incidence of hospitalizations from tick-borne disease is increasing throughout much of the nation, except in the Northeast where decreases in Lyme disease were observed. While hospitalizations with tick-borne diseases remain rare, the increases noted are substantial and may reflect rising incidence of these diseases within the represented states. Disclosures All authors: No reported disclosures.

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, P0.05) and M. abscessus cases (51%; odds ratio = 0.5, P0.01) 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 (P0.01).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.

Poor adherence to diagnosis and treatment guidelines for nontuberculous mycobacterial lung disease in EU and Japan http://ow.ly/EVYl306vVcN

Highest hospitalization rates were for men ≥65 years of age, and rates decreased during 2005−2012., Invasive candidiasis is a major nosocomial fungal disease in the United States associated with high rates of illness and death. We analyzed inpatient hospitalization records from the Healthcare Cost and Utilization Project to estimate incidence of invasive candidiasis–associated hospitalizations in the United States. We extracted data for 33 states for 2002–2012 by using codes from the International Classification of Diseases, 9th Revision, Clinical Modification, for invasive candidiasis; we excluded neonatal cases. The overall age-adjusted average annual rate was 5.3 hospitalizations/100,000 population. Highest risk was for adults >65 years of age, particularly men. Median length of hospitalization was 21 days; 22% of patients died during hospitalization. Median unadjusted associated cost for inpatient care was $46,684. Age-adjusted annual rates decreased during 2005–2012 for men (annual change –3.9%) and women (annual change –4.5%) and across nearly all age groups. We report a high mortality rate and decreasing incidence of hospitalizations for this disease.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE mutations. It classically presents with chronic mucocutaneous candidiasis and autoimmunity that primarily targets endocrine tissues; hypoparathyroidism and adrenal insufficiency are most common. Developing any two of these classic triad manifestations establishes the diagnosis. Although widely recognized in Europe, where nonendocrine autoimmune manifestations are uncommon, APECED is less defined in patients from the Western Hemisphere. We enrolled 35 consecutive American APECED patients (33 from the US) in a prospective observational natural history study and systematically examined their genetic, clinical, autoantibody, and immunological characteristics. Most patients were compound heterozygous; the most common AIRE mutation was c.967_979del13. All but one patient had anti–IFN-ω autoantibodies, including 4 of 5 patients without biallelic AIRE mutations. Urticarial eruption, hepatitis, gastritis, intestinal dysfunction, pneumonitis, and Sjögren’s-like syndrome, uncommon entities in European APECED cohorts, affected 40%–80% of American cases. Development of a classic diagnostic dyad was delayed at mean 7.38 years. Eighty percent of patients developed a median of 3 non-triad manifestations before a diagnostic dyad. Only 20% of patients had their first two manifestations among the classic triad. Urticarial eruption, intestinal dysfunction, and enamel hypoplasia were prominent among early manifestations. Patients exhibited expanded peripheral CD4+ T cells and CD21loCD38lo B lymphocytes. In summary, American APECED patients develop a diverse syndrome, with dramatic enrichment in organ-specific nonendocrine manifestations starting early in life, compared with European patients. Incorporation of these new manifestations into American diagnostic criteria would accelerate diagnosis by approximately 4 years and potentially prevent life-threatening endocrine complications.

Setting Tertiary referral center, National Institutes of Health (NIH), USA. Objective To estimate the mortality rate and its correlates among persons with pulmonary non-tuberculous mycobacteria (PNTM) disease. Design A retrospective review of 106 patients who were treated at the NIH Clinical Center and met American Thoracic Society/Infectious Diseases Society of America criteria for PNTM. Eligible patients were aged ⩾18 years and did not have cystic fibrosis or human immunodeficiency virus (HIV) infection. Results Of 106 patients followed for a median of 4.9 years, 27 (25%) died during follow-up, for a mortality rate of 4.2 per 100 person-years. The population was predominantly female (88%) and White (88%), with infrequent comorbidities. Fibrocavitary disease (adjusted hazard ratio [aHR] 3.3, 95% confidence interval [CI] 1.3-8.3) and pulmonary hypertension (aHR 2.1, 95%CI 0.9-5.1) were associated with a significantly elevated risk of mortality in survival analysis. Conclusions PNTM remains a serious public health concern, with a consistently elevated mortality rate across multiple populations. Significant risk factors for death include fibrocavitary disease and pulmonary hypertension. Further research is needed to more specifically identify clinical and microbiologic factors that jointly influence disease outcome.

Background. The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. Methods. All blood samples from suspected Ebola virus–infected patients admitted to the Medecins Sans Frontieres ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus–infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. Results. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus–infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Conclusions. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.

Prevalence of pulmonary nontuberculous mycobacterial (PNTM) disease varies by geographic region, yet the factors driving these differences remain largely unknown.To identify spatial clusters of PNTM disease at the county level and to describe environmental and sociodemographic factors predictive of disease.PNTM cases identified from a nationally representative sample of Medicare Part B beneficiaries from 1997 to 2007 were geocoded by county and state of residence. County-level PNTM case counts and Medicare population data were then uploaded into SaTScan to identify significant spatial clusters and low-risk areas of disease. High-risk and low-risk counties were then compared to identify significant sociodemographic and environmental differences.We identified seven significant (P0.05) clusters of PNTM cases. These high-risk areas encompassed 55 counties in 8 states, including parts of California, Florida, Hawaii, Louisiana, New York, Oklahoma, Pennsylvania, and Wisconsin. Five low-risk areas were also identified, which encompassed 746 counties in 23 states, mostly in the Midwest. Counties in high-risk areas were significantly larger, had greater population densities, and higher education and income levels than low-risk counties. High-risk counties also had higher mean daily potential evapotranspiration levels and percentages covered by surface water, and were more likely to have greater copper and sodium levels in the soil, although lower manganese levels.Specific environmental factors related to soil and water exposure appear to increase the risk of PNTM infection. Still, given that environmental sources of NTM are ubiquitous and PNTM disease is rare, both host susceptibility and environmental factors must be considered in explaining disease development.

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.

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.

Since 2003, two communities in eastern Arizona have experienced a sustained outbreak of Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, associated with transmission by Rhipicephalus sanguineus, the brown dog tick; 70 human cases, including eight deaths, were reported from these communities during 2003 through 2008. In both of the affected communities, antibodies to spotted fever group rickettsiae (SFGR) were present in dogs before the notice of the first human cases, suggesting that dogs may serve as useful sentinels for human risk of RMSF in this region. During 2005 and 2006, an exploratory serosurvey was conducted among stray and relinquished dogs presenting to animal control facilities in eastern Arizona located outside the area where human cases had been reported. Antibodies to SFGR were detected in 5.7% (14 of 247) dogs assessed outside the RMSF outbreak area. Animal shelters located in counties that either included or shared large borders with the outbreak area were significantly more likely to have seropositive dogs than facilities in more geographically separated counties (P = 0.01). In addition, stray dogs were significantly more likely to be antibody-positive than relinquished animals (P = 0.01), suggesting that control of stray dog populations should be considered as a means of limiting SFGR transmission in this region. The findings from this study may be extrapolated to suggest that the current risk for human RMSF infection may extend beyond the noted outbreak area. Heightened surveillance for human disease is needed in the region.

Background Nontuberculous Mycobacterial Lung Disease (NTMLD) is a chronic, debilitating, and progressive disease. This study evaluates all-cause mortality in patients with NTMLD in the US Medicare. Methods Patients (n = 43,394) were identified from the Medicare database (excluding Part C) based on physician claims for NTMLD on ≥2 separate occasions ≥30 days apart between 2007 and 2015. About 12% patients were Results Mean age was 74 (±10) years and 68% were female in both NTMLD and control cohorts. Mean Charlson comorbidity index (CCI) was 2.9 (standard deviation ±2.6) in NTMLD vs. 1.3 (±1.9) in control cohort. In Medicare members ≥65 years, mean age was 76 (±7) years and 70% were female. Mean CCI was 2.8 (±2.5) in NTMLD cohort vs. 1.4 (±2.0) in control cohort. In Medicare members Conclusion Among US Medicare enrollees, NTMLD was associated with a 35% increased risk of mortality overall. Disclosures T. Marras, Insmed Incorporated: Investigator, Consulting fee and Research grant. Horizon Pharmaceuticals: Consultant, Consulting fee. Red Hill: Consultant, Consulting fee. AstraZeneca: CME, Speaker honorarium. Q. Zhang, Insmed Incorporated: Employee, Salary. G. Eagle, Insmed Incorporated: Employee, Salary. P. Wang, Insmed Incorporated: Employee, Salary. R. Zhang, Insmed Incorporated: Consultant, Consulting fee. E. Chou, Insmed Incorporated: Employee, Salary. K. L. Winthrop, Insmed Incorporated: Consultant and Scientific Advisor, Consulting fee and Research grant.

Background While 50% of invasive candidiasis (IC) has historically been caused by C. albicans, the changing epidemiology and rise in drug-resistant Candida necessitates understanding the contribution of specific Candida species to IC. To date, species and site-specific trends in IC have not been reported on a large scale using US clinical data. Methods Using the Cerner Health Facts electronic health record (EHR) dataset, inpatient hospitalizations with any Candida spp. isolated from blood or a sterile site (SS) (abdominal or other) were identified from 2009 to 2015. Patient characteristics were described by species. Significant relationships (P ≤ 0.05) were assessed using chi-squared or exact binomial tests. Annual percent change in IC incidence by site and species were assessed via Poisson regression. Results Overall, 19,310 Candida isolates from 10,313 patients were identified. Of these, 46% of isolates were C. albicans, 22% C. glabrata, 14% C. parapsilosis, 7% C. tropicalis, and 11% other/unspeciated; no C. auris infections were identified. The overall incidence of IC was 99 cases/100,000 patients. Compared with C. albicans, isolation of other species was 35% more frequent from blood, and 43% and 30% less frequent from non-blood abdominal and non-abdominal SSs, respectively (Table 1). Total IC increased by 1% (95% CI = 0.2–2%) annually; while abdominal and SS IC significantly increased by 6% (4–8%) and 11% (9–13%) per year, respectively, candidemia decreased significantly by 4.5% (3–6%) annually. Among C. albicansinfections candidemia decreased by 6.5% (5–8%) annually, while abdominal (5%, 3–8%) and other SS infections (10%, 7–13%) increased (Figure 1). Candidemia incidence remained unchanged for the other species. SS infections increased for every species, and abdominal infections increased for all but C. parapsilosis (Figure 2). Conclusion In this first large-scale study on trends in IC using US hospital EHR data, the species distribution of IC isolates varied between blood and non-blood SSs. The incidence of candidemia is decreasing, but not for potentially drug-resistant species such as C. glabrata, which continue to pose treatment challenges. This work was supported in part by the Division of Intramural Research, NIAID, NIH Disclosures All authors: No reported disclosures.

Background In Gram-negative bacteremia (GNB), administrative data suggest that “difficult-to-treat resistance” (DTR; i.e., co-resistance to all first-line antibiotics) increases mortality. However, adequate risk-adjustment for severity of illness (SOI) may require granular laboratory and physiologic data. Methods Adult inpatients with GNB were identified from electronic health records (EHRs) of 140 hospitals in the Cerner Healthfacts database between 2009 and 2015. Mortality from DTR (intermediate/resistant in vitro to β-lactams including carbapenems and fluoroquinolones) was compared with GNB phenotypes susceptible to at least one first-line agent, but otherwise resistant to carbapenems (CR), extended-spectrum cephalosporins (ECR), or fluoroquinolones (FQR) per US Centers for Disease Control and Prevention surveillance definitions. Relative risk of mortality was adjusted (aRR) for age, sex, baseline Sequential Organ Failure Assessment (SOFA) score, Elixhauser comorbidity index, GNB source, taxon, hospital vs. community onset, year, and hospital region, bed capacity, and urban and teaching status using Poisson regression. Results Of 25,448 unique GNB encounters, 207 (1%) met DTR criteria. DTR patients were 2-fold more likely to receive intravenous colistin and 5-fold more likely to receive tigecycline compared with CR cases susceptible to ≥1 first-line agent. Crude mortality varied considerably by taxon and resistance phenotype, but resistance per se was associated with only a minority of overall deaths (DTR = 3% of deaths; any of the four resistance phenotypes = 28% of deaths; Figure 1). Inclusion of EHR-derived, baseline SOFA scores in SOI adjustments decreased aRR effect estimates; nonetheless, all resistance phenotypes still significantly increased mortality (Figure 2A). Among resistance phenotypes, aRR of mortality was similar for DTR vs. CR (aRR = 1.18; 95% CI, 0.91–1.54; P = 0.2), but higher for DTR vs. ECR (aRR = 1.26 [1.01–1.58]; P = 0.04), and DTR vs. FQR (aRR = 1.36 [1.08–1.70]; P = 0.008), respectively (Figure 2B). Conclusion DTR is associated with nonsurvival and greater use of reserve antibiotics in GNB, but adds little to the risk of death associated with CR. The impact of resistance on survival is attenuated but still present even after risk adjustment using granular clinical data. Disclosures All authors: No reported disclosures.

Rocky Mountain spotted fever (RMSF) occurs throughout much of the United States, ranging in clinical severity from moderate to fatal infection. Yet, little is known about possible differences among severity levels across geographic locations. To identify significant spatial clusters of severe and non-severe disease, RMSF cases reported to Centers for Disease Control and Prevention (CDC) were geocoded by county and classified by severity level. The statistical software program SaTScan was used to detect significant spatial clusters. Of 4,533 RMSF cases reported, 1,089 hospitalizations (168 with complications) and 23 deaths occurred. Significant clusters of 6 deaths (P = 0.05, RR = 11.4) and 19 hospitalizations with complications (P = 0.02, RR = 3.45) were detected in southwestern Tennessee. Two geographic areas were identified in north-central North Carolina with unusually low rates of severity (P = 0.001, RR = 0.62 and P = 0.001, RR = 0.45, respectively). Of all hospitalizations, 20% were clustered in central Oklahoma (P = 0.02, RR = 1.43). Significant geographic differences in severity were observed, suggesting that biologic and/or anthropogenic factors may be impacting RMSF epidemiology in the United States.

A total of 2,121 small mammals in California were assessed for Anaplasma phagocytophilum from 2006 through 2008. Odds ratios were >1 for 4 sciurids species and dusky-footed woodrats. High seroprevalence was observed in northern sites. Ten tick species were identified. Heavily infested rodent species included meadow voles, woodrats, deer mice, and redwood chipmunks.

Granulocytic anaplasmosis (GA) and monocytic ehrlichiosis (ME) are maintained in wild rodent reservoirs and tick vectors in the Republic of Korea. This study investigated the prevalence of 2 tick-borne pathogens, Anaplasma phagocytophilum and Ehrlichia chaffeensis, in wild rodents and ticks in central Korea to identify any significant associations with existing or changing climatic conditions. Specifically, the goal of this study was to develop simple models for the probability of occurrence of an epidemic of GA or ME as a function of climate in an area in a given year. Climatic data from 2 regions, Munsan and Dongducheon, Gyeonggi, in central Korea (between the Demilitarized Zone and Seoul, latitude between 37 degrees N-38 degrees N and longitude between 127 degrees E-128 degrees E), were analyzed with respect to the prevalence of GA and ME in Paju, Yoncheon, Pocheon, and Dongducheon for the period from 2001 to 2005. Rates of A. phagocytophilum and E. chaffeensis decreased as the total yearly precipitation levels and daily humidity increased, and as the daily mean sunshine hours decreased. Rates of A. phagocytophilum and E. chaffeensis from rodent ticks and rodents increased in the fall season. Linear regression analyses evaluating the numbers of positive samples by sample type found that rodent ticks were 6.64 times more likely to be actively infected with A. phagocytophilum than grass ticks or rodents, though the likelihood of any samples testing positive for this pathogen decreased by 0.17 as the annual mean level of precipitation increased by 1 mm. For E. chaffeensis, rodents were 15.67 times more likely to be infected than ticks. Logistic regression analyses evaluating each sample separately found that the odds of infection with A. phagocytophilum were nearly 5 times greater for rodents than ticks. In these analyses, precipitation was one potential factor to account for the prevalence of tickborne diseases.

A survey of wild rodents was performed in the Morro Bay area of central coastal California to determine serological and polymerase chain reaction (PCR) prevalence of Anaplasma phagocytophilum Dumler, Barbet, Bekker, Dasch, Palmer, Ray, Rikihisa, and Rurangirwa, Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt, and Brenner, Francisella tularensis McCoy, and Yersinia pestis Yersin; to describe the ectoparasitic fauna on important vector-borne disease hosts; and to determine whether pathogen exposure was associated with infestation by ectoparasites. We trapped 411 rodents from 10 species in 2004 and 2005. Anaplasma phagocytophilum exposure was detected in 11% of all wild rodents tested, with seropositive animals in eight species. Anaplasma phagocytophilum DNA was detected by PCR amplification in Neotoma fuscipes Baird and Reithrodontomys megalotis Baird (0.6% of all rodents). Yersinia spp. exposure was identified in 3.2% of all rodents tested, with highest detected exposure in peridomestic rodents, Mus musculus L. (20%), and Rattus rattus L. (50%). No individuals tested positive for the Y. pestis pla gene by PCR. In total, 338 fleas were identified from each of 10 rodent species examined. The most abundant flea was Malareus telchinus Rothschild. Relative density of flea infestation was highest on Spermophilus beecheyi Richardson and Microtus californicus Peale. Ticks recovered from trapped animals included Ixodes angustus Neumann, Ixodes pacificus CooleyKohls, Ixodes spinipalpis HadwenNuttall, and Dermacentor occidentalis Marx. Given the moderate climate and diversity of rodents and arthropods in the Morro Bay area, ongoing investigation of this region will be helpful in understanding disease maintenance cycles.

Yersinia pestis invaded the continental United States in 1900 and subsequently became established in wild rodent populations in several western states, traversing 2,250 km in approximately 40 years. However, the specific path of the eastward expansion of plague into the United States is poorly understood. We directly calculated velocities of disease spread and performed trend-surface analyses on spatio-temporally unique plague cases to clarify the route and speed of the initial spread of plague eastward. Velocities of disease spread were then analyzed using multiple linear regression models to identify environmental features that significantly impacted the rate of spread. Between one and three introductions of plague along the Pacific coast were observed, after which plague traveled from 45 to 87 km/year. In all regression models, the coast ranges of California were associated with slower spread, and the Southern Rockies were associated with a significant increase in the rate of disease spread. Additional climatic and environmental factors affecting the velocity of plague's spread varied among the models. Maps were developed to graphically represent the traveling waves of plague over the United States landscape. These analyses identify important large-scale trends regarding the eastward invasion of plague into the continental United States that can be used to better understand the historical spread of plague, as well as how to manage threats from new or re-emerging diseases that might operate under similar spatio-temporal dynamics.

Background. Lyme disease is the most common vector-borne disease in the United States. Some patients report persistent or intermittent subjective symptoms of mild to moderate intensity after antibiotic treatment for Lyme disease. We sought to evaluate trends in clinical and quality-of-life (QOL) measures in a cohort of patients with Lyme disease enrolled in a natural history study at the National Institutes of Health from 2001–2014. Methods. QOL was measured using the self-administered 36-item Short Form Health Survey (SF-36) during study follow-up. Primary outcomes included mean physical (PCS) and mental (MCS) health QOL composite scores and reporting long-term (≥2 years) symptoms, adjusted for Lyme disease stage and severity at diagnosis. Results. Overall, 101 patients with an average follow-up time of 3.9 years (range, 0.5–11.3 years) were included. At first visit, overall mean QOL scores were below the US population mean for both PCS (45.6 ± 10.4) and MCS (47.3 ± 11.5) but increased to just above the national average after 3 years of follow-up for both PCS (50.7 ± 9.6) and MCS (50.1 ± 10.0). Baseline QOL scores were lowest in those with late disease (P < 0.01) but also increased by the end of follow-up to national averages. In multivariate analysis, the only factors significantly associated with long-term symptoms or lower QOL scores were other comorbidities unrelated to Lyme disease. Conclusions. Comorbid conditions can play a role in the reporting of long-term symptoms and overall QOL of Lyme disease patients and should be considered in the evaluation of these patients. Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT00028080","term_id":"NCT00028080"}}NCT00028080.

State-specific case numbers and costs are critical for quantifying the burden of pulmonary nontuberculous mycobacterial disease in the United States.To estimate and project national and state annual cases of nontuberculous mycobacterial disease and associated direct medical costs.Available direct cost estimates of nontuberculous mycobacterial disease medical encounters were applied to nontuberculous mycobacterial disease prevalence estimates derived from Medicare beneficiary data (2003-2007). Prevalence was adjusted for International Classification of Diseases, 9th Revision, undercoding and the inclusion of persons younger than 65 years of age. U.S. Census Bureau data identified 2010 and 2014 population counts and 2012 primary insurance-type distribution. Medical costs were reported in constant 2014 dollars. Projected 2014 estimates were adjusted for population growth and assumed a previously published 8% annual growth rate of nontuberculous mycobacterial disease prevalence.In 2010, we estimated 86,244 national cases, totaling to $815 million, of which 87% were inpatient related ($709 million) and 13% were outpatient related ($106 million). Annual state estimates varied from 48 to 12,544 cases ($503,000-$111 million), with a median of 1,208 cases ($11.5 million). Oceanic coastline states and Gulf States comprised 70% of nontuberculous mycobacterial disease cases but 60% of the U.S. population. Medical encounters among individuals aged 65 years and older ($562 million) were twofold higher than those younger than 65 years of age ($253 million). Of all costs incurred, medications comprised 76% of nontuberculous mycobacterial disease expenditures. Projected 2014 estimates resulted in 181,037 national annual cases ($1.7 billion).For a relatively rare disease, the financial cost of nontuberculous mycobacterial disease is substantial, particularly among older adults. Better data on disease dynamics and more recent prevalence estimates will generate more robust estimates.

More than 20 species of fleas in California are implicated as potential vectors of Yersinia pestis. Extremely limited spatial data exist for plague vectors-a key component to understanding where the greatest risks for human, domestic animal, and wildlife health exist. This study increases the spatial data available for 13 potential plague vectors by using the ecological niche modeling system Genetic Algorithm for Rule-Set Production (GARP) to predict their respective distributions. Because the available sample sizes in our data set varied greatly from one species to another, we also performed an analysis of the robustness of GARP by using the data available for flea Oropsylla montana (Baker) to quantify the effects that sample size and the chosen explanatory variables have on the final species distribution map. GARP effectively modeled the distributions of 13 vector species. Furthermore, our analyses show that all of these modeled ranges are robust, with a sample size of six fleas or greater not significantly impacting the percentage of the in-state area where the flea was predicted to be found, or the testing accuracy of the model. The results of this study will help guide the sampling efforts of future studies focusing on plague vectors.

Background Discordance between in vitro susceptibility and empiric antibiotic therapy is inextricably linked to antibiotic resistance and decreased survival in bloodstream infections (BSI). However, its prevalence, patient- and hospital-level risk factors, and impact on outcome in a large cohort and across different pathogens remain unclear. Methods We examined in vitro susceptibility interpretations for bacterial BSI and corresponding antibiotic therapy among inpatient encounters across 156 hospitals from 2000 to 2014 in the Cerner Healthfacts database. Discordance was defined as nonsusceptibility to initial therapy administered from 2 days before pathogen isolation to 1 day before final susceptibility reporting. Discordance prevalence was compared across taxa; risk factors and its association with in-hospital mortality were evaluated by logistic regression. Adjusted odds ratios (aOR) were estimated for pathogen-, patient- and facility-level factors. Results Of 33,161 unique encounters with BSIs, 4,219 (13%) at 123 hospitals met criteria for discordant antibiotic therapy, ranging from 3% for pneumococci to 55% for E. faecium. Discordance was higher in recent years (2010–2014 vs. 2005–2009) and was associated with older age, lower baseline SOFA score, urinary (vs. abdominal) source and hospital-onset BSI, as well as ≥500-bed, Midwestern, non-teaching, and rural hospitals. Discordant antibiotic therapy increased the risk of death [aOR = 1.3 [95% CI 1.1–1.4]). Among Gram-negative taxa, discordant therapy increased risk of mortality associated with Enterobacteriaceae (aOR = 1.3 [1.0–1.6]) and non-fermenters (aOR = 1.7 [1.1–2.5]). Among Gram-positive taxa, risk of mortality from discordant therapy was significantly higher for S. aureus (aOR = 1.3 [1.1–1.6]) but unchanged for streptococcal or enterococcal BSIs. Conclusion The prevalence of discordant antibiotic therapy displayed extensive taxon-level variability and was associated with patient and institutional factors. Discordance detrimentally impacted survival in Gram-negative and S. aureus BSIs. Understanding reasons behind observed differences in discordance risk and their impact on outcomes could inform stewardship efforts and guidelines for empiric therapy in sepsis. Disclosures All authors: No reported disclosures.

Background Persons with cystic fibrosis (CF) are at increased risk for nontuberculous mycobacteria (NTM) lung infections, with a national annual prevalence of 13%. However, for CF patients in Hawaii, estimates are as high as 50%. Active duty military who have dependents with CF may be transferred to Hawaii as part of their service, potentially placing their dependent at increased risk for NTM. To better describe the epidemiology of NTM in a high-risk environment, we report prevalence and risk factors for CF patients living in Hawaii and seeking care at Tripler Army Medical Center (TAMC), the only CF center in Hawaii. Methods Data were extracted on CF patients treated at TAMC from 2010 to 2014, including sex, age, time residing in Hawaii, and culture results. NTM cases (≥ 1 positive culture) and non-cases (no positive cultures) were identified and prevalence estimated. Log-binomial regression was used to estimate adjusted relative risks (aRR) and 95% confidence intervals (CI) for risk factors. Results Of 43 CF patients, 17 (40%) had NTM isolated at least once; 11 (26%) had ≥2 positives. Annual prevalence averaged 30%. Overall, 13 (76%) cases had Mycobacterium abscessus, 5 (29%) M. avium complex (MAC), and 6 (35%) other rapid growers isolated; 9 (53%) had multiple species isolated. Mean time to first positive culture was 1.6 yrs (range: 0–7.1); only 2(11%) cases were positive at first culture. NTM cases were more frequently female (59%; P = 0.02) and older than non-cases (14.4 vs. 11.9 yrs; P < 0.0001). Among CF patients living in Hawaii for >6 years, 80% had NTM compared with only 19% of those in Hawaii for

Persons with cystic fibrosis (CF) are at greater risk of nontuberculous mycobacterial (NTM) infections than the general population. However, among patients with CF, geographic variation in prevalence is poorly understood.To describe the prevalence and screening practices of NTM among U.S. patients with CF.CF Patient Registry data from 2010-2011 were obtained to estimate the prevalence of NTM among patients with CF 12 years of age or older by state. Climatic data were also obtained and predictors of NTM infection analyzed using regression analysis. Geographic clustering and mycobacterial culture rates by state were also assessed.Among patients with CF 12 years of age or older, 58% had mycobacterial cultures; 14% were positive for NTM. Most states (n = 31) had a prevalence of 10-20%; seven states predominantly in the West and Southeast had a prevalence of 20% or greater, including Alaska, which cultured patients more frequently than any other state. Nearly 60% of positive cultures were for Mycobacterium avium complex, although this ranged by state, from 29% in Louisiana to 100% for Nebraska/Delaware. Significant (P0.002) spatial clustering of NTM was detected, centering in Wisconsin, Arizona, Florida, and Maryland. Higher saturated vapor pressure increased risk for NTM (odds ratio = 1.06; 95% confidence interval = 1.02-1.10). The proportion of patients cultured for mycobacteria varied greatly by state of residence (median = 46%; range = 9-73%).NTM prevalence varies significantly among patients with CF by geographic area, and is largely influenced by environmental factors. However, NTM culture practices vary greatly, with some high-prevalence states screening less than 25% annually. Routine screening for all patients with CF is needed for timely detection.

Rationale: Persons with cystic fibrosis are at high risk of pulmonary nontuberculous mycobacterial infection, with a national prevalence estimated at 13%. The risk of nontuberculous mycobacteria associated with specific environmental exposures, and the correlation with climatic conditions in this population has not been described. Objectives: To describe the association of pulmonary nontuberculous mycobacteria with individual exposures to water and soil aerosols, and the population associations of these infections with climatic factors. Methods: We conducted a nested case–control study within a cohort study of pulmonary nontuberculous mycobacteria prevalence at 21 geographically diverse national cystic fibrosis centers. Incident nontuberculous mycobacterial infection cases (at least one prior negative culture followed by one positive culture) were age- and sex-matched to culture-negative controls. Exposures to water and soil were assessed by administering a standardized questionnaire. Cohort prevalence at each of the 21 centers was correlated with climatic conditions in the same area through linear regression modeling. Measurements and Main Results: Overall, 48 cases and 85 control subjects were enrolled. Indoor swimming was associated with incident infection (adjusted odds ratio, 5.9, 95% confidence interval, 1.3–26.1), although only nine cases (19%) and five control subjects (6%) reported indoor swimming in the 4 months prior to infection. Exposure to showering and municipal water supply was common among both cases and control subjects: 77% of cases and 76% of control subjects reported showering at least daily. In linear regression, average annual atmospheric water vapor content was significantly predictive of center prevalence (P = 0.0019), with R2 = 0.40. Conclusions: Atmospheric conditions explain more of the variation in disease prevalence than individual behaviors. The risk of specific exposures may vary by geographic region due to differences in conditions favoring mycobacterial growth and survival. However, because exposure to these organisms is ubiquitous and behaviors are similar among persons with and without pulmonary nontuberculous mycobacteria, genetic susceptibility beyond cystic fibrosis is likely to be important for disease development. Common individual risk factors in high-risk populations remain to be identified.

Although excessive alcohol consumption is a recognized cause of morbidity and mortality, many studies have linked moderate alcohol consumption to improved cardiovascular health and a lower risk of Type 2 Diabetes (T2D). Self-reported alcohol and diet data used to generate these results suffer from measurement error due to recall bias. We estimate the effects of diet, alcohol, and lifestyle choices on the prevalence and incidence of cardiovascular disease and T2D among U.S. adults using a nationally representative cohort of households with scanner data representing their food-at-home, alcohol, and tobacco purchases from 2007-2010, and self-reported health surveys for the same study participants from 2010-2012. Multivariate regression models were used to identify significant associations among purchase data and lifestyle/demographic factors with disease prevalence in 2010, and with incidence of new disease from 2011-2012. After controlling for important confounders, respondents who purchased moderate levels of wine were 25% less likely than non-drinkers to report heart disease in 2010. However, no alcohol-related expenditure variables significantly affected the likelihood of reporting incident heart disease from 2011-2012. In contrast, many types of alcohol-related purchases were associated with a lower prevalence of T2D, and respondents who purchased the greatest volumes of wine or beer--but not liquor--were less likely to report being diagnosed with T2D in 2011-2012 than non-drinkers.

To the Editor: Women over the age of 50 who lack antecedent structural lung damage have emerged as a growing population afflicted with pulmonary nontuberculous mycobacteria (PNTM) (1). A common body morphology among these women, who are often tall and lean with scoliosis, pectus excavatum (PE), and mitral valve prolapse (MVP), points to a possible genetic basis for susceptibility to PNTM (2, 3). Exploration of these traits in family members of patients with PNTM provides evidence for the hypothesis that genetic factors modify disease susceptibility. To date, a systematic analysis of a large cohort of patients with PNTM and their relatives has not been performed. We describe here a comprehensive review of families with PNTM designed to identify a familial phenotype of disease. Some of the results of this study have been previously reported in the form of an abstract (4). Methods Probands included in our study were adult patients who met diagnostic criteria for PNTM (5) and were enrolled in a natural history of mycobacterial disease protocol at the National Institutes of Health. Probands with other known underlying structural lung diseases or characterized immunodeficiency were excluded. Chart records for each proband were abstracted for demographic data, mycobacterial species identified, and the presence of bronchiectasis, scoliosis, MVP, and PE. Bronchiectasis was identified by chest computed tomography (CT) imaging, scoliosis by spinal X-rays, MVP by echocardiogram, and PE by computing a Haller index greater than 3.5 from chest CT imaging (6). All probands were contacted to construct family pedigrees extending to first- and second-degree relatives. Probands were asked to report the following in all members of the pedigree: current or past diagnosis of PNTM, bronchiectasis, MVP, scoliosis, and PE. When possible, consent was obtained from family members to interview them directly as well. The instrument used to ascertain these characteristics can be found in the online supplement. Summary statistics were performed in Excel (Microsoft Corporation, Redmond, WA). Results A total of 383 patients were enrolled in the natural history protocol, 274 of whom were excluded for the following reasons: 87 had an underlying immunodeficiency, 53 were enrolled relatives of patients, 44 had withdrawn from the study, 35 were already deceased, 24 had a known underlying structural lung disorder, 14 were unable to be contacted, 11 had tuberculosis, and 6 were pediatric patients (5 with isolated endobronchial mycobacterial lesions and 1 with pulmonary alveolar proteinosis). The remaining 109 probands included for analysis led to 2,285 first- and second-degree relatives with an average of 21 family members per proband. Seventy-two relatives consented to in-person interviews; the remainder of the relatives’ medical histories were ascertained via interview of the proband. Characteristics of the probands are listed in Table 1. The majority of probands were white females with an average age of 66.7 years. The most common mycobacterial species was Mycobacterium avium complex, followed by M. abscessus and M. fortuitum. Sixty-three (57.8%) patients had scoliosis, 15 (13.8%) had echocardiographic evidence of MVP, and 4 (3.7%) had radiographic evidence of PE by the Haller index. The proportion of probands featuring different combinations of these traits is shown in Figure 1a. TABLE 1. CHARACTERISTICS OF STUDY PROBANDS (N = 109) Figure 1. (a) The percentage of probands exhibiting different combinations of scoliosis, mitral valve prolapse (MVP), and pectus excavatum (PE) is shown. The largest proportions of probands exhibited either only scoliosis (45%) or none of the pertinent traits (39%). ... The proportion of probands reporting pertinent characteristics in at least one family member is displayed in Figure 1b. Of 109 probands, 14 (12.8%) reported having at least one other first- or second-degree relative diagnosed with PNTM. In addition, 13 (11.9%) probands reported bronchiectasis and 21 (19.2%) probands reported scoliosis in at least one relative. MVP was found in 7 (6.4%) families and PE in 6 (5.5%) families. Twenty-three relatives exhibited just scoliosis, 14 exhibited just MVP, and 12 exhibited just PE. Two relatives exhibited scoliosis and MVP together, and one relative exhibited MVP and PE together. Of the 14 families with more than one member with PNTM, 8 were sibling pairs, 4 were parent–child pairs, and 2 were aunt–niece pairs. Discussion To date, no systematic review of a large cohort has evaluated whether conditions previously ascribed to patients with PNTM, such as scoliosis, MVP, and PE, cluster among family members. The infrequency of these traits in large population-based epidemiologic studies suggests that they are much more prevalent among relatives of patients with PNTM than in the general population. Whereas studies of general pediatric populations demonstrate rates of scoliosis of between 0.5 and 3.2% (7–10), we observe here 21 (19.2%) families with at least one member with scoliosis. Comparisons with populations similar to patients with PNTM also suggest a higher rate. For example, an estimate of scoliosis in a population of patients with cystic fibrosis, who also carry higher risk for developing PNTM, only revealed a prevalence of 2.2% (11). Similarly, our observations exceed those found in a comparable cohort of postmenopausal women, where lumbar scoliosis was found in 12.9% (12). Estimates of MVP in the general population range from 2.4 to 2.7% (13, 14) whereas we observed 7 (6.4%) families with at least one affected relative. Even rarer conditions such as PE, affecting 0.12% in one autopsy series (15) and 0.49% in one pediatric screening study (16), were found in 6 (5.5%) families. Patients with primary ciliary dyskinesia, another structural lung disease associated with PNTM, may feature similar rates of PE compared with our population, with one study finding a 9% prevalence on CT scans (17). Although inherited syndromes of these traits certainly exist, how frequently these traits are expressed in first- and second-degree relatives of comparable populations remains unknown. The genetic underpinnings of this familial syndrome remain undetermined. The triad of scoliosis, MVP, and PE points strongly to a Marfan-like syndrome, although it should be noted that none of our probands met diagnostic criteria for Marfan syndrome. As a corollary to our findings, Marfan syndrome is known to be associated with bronchiectasis (18). Other connective tissue diseases, such as congenital contractural arachnodactyly, have been associated with PNTM infection (19). Involvement of the transforming growth factor-β pathway, alterations in which account for many connective tissue diseases, could potentially explain the marked similarities in body morphotype between the families in our cohort and the connective tissue disease population (20). Our study has several limitations, most notably that traits identified by probands and their family members need in-person verification. These findings, based on family member report, are subject to ascertainment bias; however, this bias is likely to underestimate the prevalence, particularly for mild forms of conditions such as scoliosis and MVP, which may not be apparent to individuals without full medical examinations. Second, the fact that PNTM is a disease largely affecting postmenopausal women makes the estimation of disease difficult for younger relatives who have not yet reached the “at-risk” age for disease onset. Longitudinal follow-up over decades will be necessary to determine the true degree of risk for family members. Moreover, the identification of PNTM, bronchiectasis, and associated traits is challenging in the oldest generations of pedigrees, many of whom are already deceased or may not have undergone diagnostic testing during their lifetimes. Despite the limitations intrinsic to using generations who are presymptomatic and those who may not have had adequate testing, at least some of these families show parent–child transmission, most consistent with dominant disease. It is also possible that there are recessive families in this cohort as well. Finally, the relative rarity of exhibiting all associated traits together in both the probands and the relatives raises the possibility that although they are clustered, these traits may not necessarily be inherited together. Further explorations of larger populations of patients with PNTM in addition to clarifying the inheritance pattern of these traits would better demonstrate whether a true syndrome of traits exists, rather than mere clustering. This study is the first to show a familial clustering of traits related to PNTM infections in otherwise unaffected relatives. The higher-than-expected prevalence of PNTM, bronchiectasis, scoliosis, MVP, and PE strongly supports a genetic basis for at least some cases of PNTM.

The 2007 American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) recommend that patients with pulmonary nontuberculous mycobacterial (PNTM) disease caused by Mycobacterium avium complex (MAC) or M. abscessus be treated with a macrolide-based multidrug antibiotic regimen until sputum culture negative for 1 year. After 6 years, the degree of adherence to recommended guidelines among physicians remains unknown.To describe antibiotic treatment practices among physicians treating patients with PNTM in the United States.A nationally representative sample of 1,286 U.S. physicians was contacted in December 2011 through January 2012; 582 of the responding physicians were treating patients with PNTM and were eligible to participate. Physicians were asked to extract medical record data on the last four patients they treated in the past year with PNTM disease from either MAC or M. abscessus. Treatment patterns were assessed for all patients by NTM species and physician specialty, and compared with the 2007 recommended ATS/IDSA guidelines.Questionnaires were completed by 349 physicians on 915 patients with PNTM, including 744 (81%) with MAC and 174 (19%) with M. abscessus; 3 patients were positive for both. Physicians treated 76 (44%) patients with M. abscessus and 411 (55%) patients with MAC. Only 13% of antibiotic regimens prescribed to patients with MAC met ATS/IDSA guidelines, 56% did not include a macrolide, and 16% were for macrolide monotherapy. Among patients with M. abscessus, 64% of regimens prescribed did not include a macrolide.Adherence to the 2007 ATS/IDSA guidelines for treating PNTM disease is poor. Across all physician specialties evaluated, suboptimal or potentially harmful antibiotic regimens were commonly prescribed.

Chlamydia (Chlamydophila) pneumoniae is an obligate intracellular bacterium commonly associated with both upper and lower respiratory tract infections including pharyngitis, bronchitis, and pneumonia. First described in 1986, C. pneumoniae infections generally consist of low-grade fever, prolonged cough, coryza, headache, myalgias, and laryngitis [1, 2]. Macrolides are a common first-line treatment; however, tetracyclines and fluoro-quinolones are also effective. Symptoms may resolve without antibiotics and asymptomatic infection can occur [3–5]. Chlamydia pneumoniae is endemic world-wide. Outbreaks occur periodically and without a clear seasonal pattern, primarily in close-contact settings among high-risk populations such as in long-term care facilities [6–8]. Chlamydia pneumoniae is frequently detected alongside other respiratory pathogens, making its role as a primary disease-causing pathogen unclear [9–11]. The diagnosis of C. pneumoniae infection is commonly made through commercially available serological assays, despite poor sensitivity and specificity due to high background seroprevalence and potential cross-reaction with other Chlamydia species [12]. More recently, real-time polymerase chain reaction (qPCR) assays are being used to identify C. pneumoniae from respiratory specimens that are highly sensitive and specific for acute C. pneumoniae infection but are unable to provide a retrospective diagnosis [13–15]. During November 2009–February 2010, an outbreak of pneumonia was identified in a male federal correctional institution in Texas. Symptoms included low-grade fever, dry cough, and body aches, and illness appeared to occur in previously healthy inmates. Four inmates were hospitalized. Sputum and blood cultures, sputum testing for acid-fast bacilli, and urine testing for Legionella and Histoplasma were negative. This report describes the outbreak’s laboratory and epidemiological investigation, and illustrates the challenges of implementing outbreak control interventions in this setting.

Background Nontuberculous mycobacteria (NTM) are associated with human lung disease, with 80% of cases caused by Mycobacterium avium complex (MAC). American Thoracic Society (ATS)-led treatment guidelines exist for MAC (macrolide/ethambutol/rifamycin), although studies suggest poor concordance with clinician practice. Using a national database of hospitalized patients with MAC isolated, we sought to characterize US treatment practices and trends. Methods Linked demographic and microbiologic data from PremierTM Healthcare Database were extracted for all inpatient encounters from 2009 to 2013. Patients with ≥1 positive MAC culture were identified as cases; concomitant pathogens were also identified. Antibiotics ordered within 3-months post-positive culture were evaluated. Regression models were used to estimate the relative risk (RR) for factors associated with receiving an ATS regimen or macrolide monotherapy. Results Of 3629 MAC cases, 2285 (63%) received an evaluated antibiotic regimen. Most (59%) were treated with a quinolone-based regimen, and 481 (21%) received an ATS regimen. Concordance with ATS guidelines improved over time from 12% in 2009 to 20% in 2013, peaking in 2012(23%). Concordance was highest at facilities in the South (24%) and lowest in the Midwest (13%). Regimens associated with macrolide resistance were given to 160 (7%) cases, including macrolide monotherapy (4%). Guideline concordance was 60% more likely in the South (RR: 1.6, P < 0.01) and 5-fold greater among those who received initial tuberculosis-specific therapy (isoniazid/pyrazinamide, RR: 4.7, P < 0.01). Cases in the Northeast (RR: 2.3, P = 0.02) and without co-infection (only MAC isolated) (RR: 1.7, P = 0.05) were more likely to receive macrolide monotherapy. Conclusion Prescribing concordance with ATS guidelines increased over time. However, regimens associated with macrolide-resistance are still ordered nationally. Clinicians managing hospitalized patients with suspected MAC infections should avoid use of regimens associated with macrolide resistance, which can result in worse clinical outcomes. This work was supported in part by the Division of Intramural Research, NIAID, NIH Figure 1. Treatment regimens prescribed among a national cohort of inpatients with MAC isolated by co-infection status. Disclosures All authors: No reported disclosures.

Marburg hemorrhagic fever was detected among 4 miners in Ibanda District, Uganda, from June through September, 2007. Infection was likely acquired through exposure to bats or bat secretions in a mine in Kamwenge District, Uganda, and possibly human-to-human transmission between some patients. We describe the epidemiologic investigation and the health education response.

Background In October 2007, a cluster of patients experiencing a novel polyradiculoneuropathy was identified at a pork abattoir (Plant A). Patients worked in the primary carcass processing area (warm room); the majority processed severed heads (head-table). An investigation was initiated to determine risk factors for illness. Methods and Results Symptoms of the reported patients were unlike previously described occupational associated illnesses. A case-control study was conducted at Plant A. A case was defined as evidence of symptoms of peripheral neuropathy and compatible electrodiagnostic testing in a pork abattoir worker. Two control groups were used - randomly selected non-ill warm-room workers (n = 49), and all non-ill head-table workers (n = 56). Consenting cases and controls were interviewed and blood and throat swabs were collected. The 26 largest U.S. pork abattoirs were surveyed to identify additional cases. Fifteen cases were identified at Plant A; illness onsets occurred during May 2004–November 2007. Median age was 32 years (range, 21–55 years). Cases were more likely than warm-room controls to have ever worked at the head-table (adjusted odds ratio [AOR], 6.6; 95% confidence interval [CI], 1.6–26.7), removed brains or removed muscle from the backs of heads (AOR, 10.3; 95% CI, 1.5–68.5), and worked within 0–10 feet of the brain removal operation (AOR, 9.9; 95% CI, 1.2–80.0). Associations remained when comparing head-table cases and head-table controls. Workers removed brains by using compressed air that liquefied brain and generated aerosolized droplets, exposing themselves and nearby workers. Eight additional cases were identified in the only two other abattoirs using this technique. The three abattoirs that used this technique have stopped brain removal, and no new cases have been reported after 24 months of follow up. Cases compared to controls had higher median interferon-gamma (IFNγ) levels (21.7 pg/ml; vs 14.8 pg/ml, P

In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28–52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005–December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.

This study aimed to describe the occurrence of Yersinia pestis, Rickettsia rickettsii, Anaplasma phagocytophilum, and ectoparasites in a wild rodent community in the eastern Sierra Nevada. From May to September 2006, rodents were live-trapped, examined for ectoparasites, and blood was collected. All rodents were serologically tested for antibodies to Y. pestis, R. rickettsii, and A. phagocytophilum; in addition, blood samples and ectoparasites were tested by PCR to detect the presence of these zoonotic agents. Overall, 89 rodents, 46 fleas, and four ticks were collected. Antibody prevalence rates observed for rodents were 14% for R. rickettsii or antigenically related spotted-fever group rickettsiae, and 8% for A. phagocytophilum. No samples were positive for antibodies to Y. pestis. Positive PCR results included one yellow-pine chipmunk for Y. pestis (CT=32.8), one golden-mantled ground squirrel for R. rickettsii (CT=33), and one flea found to be co-infected with both R. rickettsii (CT=17) and A. phagocytophilum (CT=36). The results of this study provide evidence of multiple zoonoses overlapping within a single, located rodent community.