by
Raymund Dantes;
Yi Mu;
Lauri A. Hicks;
Jessica Cohen;
Wendy Bamberg;
Zintars G. Beldavs;
Ghinwa Dumyati;
Monica Farley;
Stacy Holzbauer;
James Meek;
Erin Phipps;
Lucy Wilson;
Lisa G. Winston;
L. Clifford McDonald;
Fernanda C. Lessa
Background. Antibiotic use predisposes patients to Clostridium difficile infections (CDI), and approximately 32% of these infections are community-associated (CA) CDI. The population-level impact of antibiotic use on adult CA-CDI rates is not well described. Methods. We used 2011 active population- and laboratory-based surveillance data from 9 US geographic locations to identify adult CA-CDI cases, defined as C difficile-positive stool specimens (by toxin or molecular assay) collected from outpatients or from patients ≤3 days after hospital admission. All patients were surveillance area residents and aged ≥20 years with no positive test ≤8 weeks prior and no overnight stay in a healthcare facility ≤12 weeks prior. Outpatient oral antibiotic prescriptions dispensed in 2010 were obtained from the IMS Health Xponent database. Regression models examined the association between outpatient antibiotic prescribing and adult CA-CDI rates. Methods. Healthcare providers prescribed 5.2 million courses of antibiotics among adults in the surveillance population in 2010, for an average of 0.73 per person. Across surveillance sites, antibiotic prescription rates (0.50-0.88 prescriptions per capita) and unadjusted CA-CDI rates (40.7-139.3 cases per 100 000 persons) varied. In regression modeling, reducing antibiotic prescribing rates by 10% among persons ≥20 years old was associated with a 17% (95% confidence interval, 6.0%-26.3%; P = .032) decrease in CA-CDI rates after adjusting for age, gender, race, and type of diagnostic assay. Reductions in prescribing penicillins and amoxicillin/clavulanic acid were associated with the greatest decreases in CA-CDI rates. Conclusions and Relevance. Community-associated CDI prevention should include reducing unnecessary outpatient antibiotic use. A modest reduction of 10% in outpatient antibiotic prescribing can have a disproportionate impact on reducing CA-CDI rates.
by
Julie A. Womack;
Terrence E. Murphy;
Harini Bathulapalli;
Kathleen M. Akgun;
Cynthia Gibert;
Ken M. Kunisaki;
David Rimland;
Maria Rodriguez-Barradas;
H. Klar Yaggi;
Amy C. Justice;
Nancy S. Redeker
During the late phase of the Human Immunodeficiency Virus Type-1 (HIV-1) replication cycle, viral Gag proteins and the intact RNA genome are trafficked to specific sub-cellular membranes where virus assembly and budding occurs. Targeting to the plasma membranes of T cells and macrophages is mediated by interactions between the N-terminal matrix (MA) domain of Gag and cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P 2 ] molecules. However, in macrophages and dendritic cells, a subset of Gag proteins appears to be targeted to tetraspanin enriched viral compartments, a process that appears to be mediated by MA interactions with the Delta subunit of the cellular Adaptor Protein AP-3 (AP-3δ). We cloned, overexpressed and purified the protein interactive domain of AP-3δ and probed for MA binding by NMR. Unexpectedly, no evidence of binding was observed in these in vitro experiments, even at relatively high protein concentrations (200μM), suggesting that AP-3δ plays an alternative role in HIV-1 assembly.
Background: Men who have sex with men (MSM) in the United States experience an approximately 100-fold greater rate of primary and secondary (P&S) syphilis diagnoses compared with men who have sex with women only. As in the general population, racial/ethnic disparities in P&S syphilis diagnosis rates may exist among MSM, but MSM-specific P&S syphilis rates by race/ethnicity are unavailable. We enhanced a published modeling approach to estimate area-level MSM populations by race/ethnicity and provide the first estimates of P&S syphilis among black and white non-Hispanic MSM. Methods: We used data from the American Community Survey (ACS), published findings from the National Health and Nutrition Examination Survey (NHANES), and national syphilis surveillance data to estimate state-level rates of P&S syphilis diagnoses among MSM, overall and for black and white non-Hispanic MSM. We also used variability around ACS and NHANES estimates to calculate 95% confidence intervals for each rate. Results: Among 11,359 cases of P&S syphilis among MSM with known race/ethnicity in 2014, 72.5% were among white (40.3%) or black (32.2%) MSM. The national rate of P&S syphilis diagnosis was 168.4/100,000 for white MSM and 583.9/100,000 for black MSM. Regional rates for black MSM ranged from 602.0/100,000 (South) to 521.5/100,000 (Midwest) and were consistently higher than those for white MSM. Conclusions: Although white MSM accounted for more P&S syphilis diagnoses than black MSM in 2014, when evaluating diagnoses based on rate per 100,000, black MSM had consistently and markedly higher rates than white MSM, with the highest impacted states located in the US South.
Background: Given high rates of HIV among men who have sex with men (MSM) in the United States, there is a need to more effectively leverage the health care system to bolster promotion of pre-exposure prophylaxis (PrEP) to at-risk MSM. Methods: Using data collected from a 2018 venue-based cross-sectional survey, we examined factors associated with health care-seeking behaviors, discussing PrEP with a provider, and barriers to PrEP uptake among MSM. Associations between outcomes and respondents' sociodemographic characteristics and sexual behaviors were assessed using log binomial regression. Results: Of 478 MSM, 247 (51%) were PrEP-naïve and HIV-negative. Although 85% of PrEP-naïve MSM reported visiting a health care provider in the past year, only 31% recalled having any provider discuss PrEP. The most frequently cited reasons for not taking PrEP were low perception of personal risk of acquiring HIV (37%) and not knowing enough about PrEP (35%). Those who saw a provider in the last year were less likely than those who did not to cite lack of knowledge as a barrier to use (prevalence rate, 0.66, 95% confidence interval, 0.45-0.96). Conclusions: Despite the majority of PrEP-naïve MSM interfacing with the health care system, recollection of discussing PrEP with providers was limited. Increased efforts to equip providers with the tools to discuss PrEP and address pressing concerns with at-risk individuals may help improve PrEP uptake among priority populations.
by
Parastu Kasaie;
Stephen A. Berry;
Maunank S. Shah;
Eli Rosenberg;
Karen W. Hoover;
Thomas L. Gift;
Harrell Chesson;
Jeff Pennington;
Danielle German;
Colin P. Flynn;
Chris Beyrer;
David W. Dowdy
Background Preexposure prophylaxis (PrEP) greatly reduces the risk of human immunodeficiency virus (HIV) acquisition, but its optimal delivery strategy remains uncertain. Clinics for sexually transmitted infections (STIs) can provide an efficient venue for PrEP delivery. Methods To quantify the added value of STI clinic-based PrEP delivery, we used an agent-based simulation of HIV transmission among men who have sex with men (MSM). We simulated the impact of PrEP delivery through STI clinics compared with PrEP delivery in other community-based settings. Our primary outcome was the projected 20-year reduction in HIV incidence among MSM. Results Assuming PrEP uptake and adherence of 60% each, evaluating STI clinic attendees and delivering PrEP to eligible MSM reduced HIV incidence by 16% [95% uncertainty range, 14%-18%] over 20 years, an impact that was 1.8 (1.7-2.0) times as great as that achieved by evaluating an equal number of MSM recruited from the community. Comparing strategies where an equal number of MSM received PrEP in each strategy (ie, evaluating more individuals for PrEP in the community-based strategy, because MSM attending STI clinics are more likely to be PrEP eligible), the reduction in HIV incidence under the STI clinic-based strategy was 1.3 (1.3-1.4) times as great as that of community-based delivery. Conclusions Delivering PrEP to MSM who attend STI clinics can improve efficiency and effectiveness. If high levels of adherence can be achieved in this population, STI clinics may be an important venue for PrEP implementation.
Background: In the outpatient setting, the majority of antibiotic prescriptions are for acute respiratory infections (ARIs), but most of these infections are viral and antibiotics are unnecessary. We analyzed provider-specific antibiotic prescribing in a group of outpatient clinics affiliated with an academic medical center to inform future interventions to minimize unnecessary antibiotic use. Methods: We conducted a cross-sectional study of patients who presented with an ARI to any of 15 The Emory Clinic (TEC) primary care clinic sites between October 2015 and September 2017. We performed multivariable logistic regression analysis to examine the impact of patient, provider, and clinic characteristics on antibiotic prescribing. We also compared provider-specific prescribing rates within and between clinic sites. Results: A total of 53.4% of the 9600 patient encounters with a diagnosis of ARI resulted in an antibiotic prescription. The odds of an encounter resulting in an antibiotic prescription were independently associated with patient characteristics of white race (adjusted odds ratio [aOR] = 1.59; 95% confidence interval [CI], 1.47-1.73), older age (aOR = 1.32, 95% CI = 1.20-1.46 for patients 51 to 64 years; aOR = 1.32, 95% CI = 1.20-1.46 for patients ≥65 years), and comorbid condition presence (aOR = 1.19; 95% CI, 1.09-1.30). Of the 109 providers, 13 (12%) had a rate significantly higher than predicted by modeling. Conclusions: Antibiotic prescribing for ARIs within TEC outpatient settings is higher than expected based on prescribing guidelines, with substantial variation in prescribing rates by site and provider. These data lay the foundation for quality improvement interventions to reduce unnecessary antibiotic prescribing.
Invasive group A Streptococcus (GAS) infections can be fatal and can occur in healthy children. A case-control study identified factors associated with pediatric disease. Case-patients were identified when Streptococcus pyogenes was isolated from a normally sterile site, and matched controls (≥2) were identified by using sequential-digit dialing. All participants were noninstitutionalized surveillance-area residents <18 years of age. Conditional regression identified factors associated with invasive disease: other children living in the home (odds ratio [OR] = 16.85, p = 0.0002) and new use of nonsteroidal antiinflammatory drugs (OR = 10.64, p = 0.005) were associated with increased risk. More rooms in the home (OR = 0.67, p = 0.03) and household member(s) with runny nose (OR = 0.09, p = 0.002) were associated with decreased risk. Among children, household-level characteristics that influence exposure to GAS most affect development of invasive disease.