Showing papers by "John W. Baddley published in 2018"

Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial

Abstract: Importance The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. Objective To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. Design, Setting, and Participants A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. Interventions Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. Main Outcomes and Measures Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. Results Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, −6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, −3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, −1.8 days [95% CI, −3.1 to −0.6]). Conclusions and Relevance Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm. Trial Registration ClinicalTrials.gov Identifier:NCT01191840

Mapping Histoplasma capsulatum Exposure, United States.

Abstract: Maps of Histoplasma capsulatum infection prevalence were created 50 years ago; since then, the environment, climate, and anthropogenic land use have changed drastically. Recent outbreaks of acute disease in Montana and Nebraska, USA, suggest shifts in geographic distribution, necessitating updated prevalence maps. To create a weighted overlay geographic suitability model for Histoplasma, we used a geographic information system to combine satellite imagery integrating land cover use (70%), distance to water (20%), and soil pH (10%). We used logistic regression modeling to compare our map with state-level histoplasmosis incidence data from a 5% sample from the Centers for Medicare and Medicaid Services. When compared with the state-based Centers data, the predictive accuracy of the suitability score-predicted states with high and mid-to-high histoplasmosis incidence was moderate. Preferred soil environments for Histoplasma have migrated into the upper Missouri River basin. Suitability score mapping may be applicable to other geographically specific infectious vectors.

Pneumocystis and glucocorticoid use: to prophylax or not to prophylax (and when?); that is the question

Abstract: Pneumocystis jiroveci is an opportunistic fungus with the ability to cause lethal pneumonia in those with advanced immunosuppression.1 Fortunately, this outcome is preventable with prophylaxis. Unfortunately, however, deciding who is immunosuppressed enough to justify prophylaxis can be a confusing subject, particularly among rheumatology patients where immunosuppression waxes and wanes based on the use of immunosuppressive therapies and the contribution of the underlying inflammatory disease. Foggy notions persist regarding who is at risk, the level of absolute risk where the risk-benefit of using trimethoprim/sulfamethoxazole (TMP/SMX) or other prophylaxis is worthwhile, and when can prophylaxis be safely stopped.2 The article by Park et al published in the Annals of Rheumatic Diseases 3 sheds light on these important questions, such that a picture of how to approach this issue clinically might finally be more clear for the practicing rheumatologist. Given the difficulty studying these questions in a randomised controlled trial fashion, comparative effectiveness studies such as this one might provide the next best thing. In the article, the authors address the following questions: in patients starting high-dose glucocorticoids and taking them greater than 4 weeks, what is the risk of pneumocystic jiroveci pneumonia (PJP) (and the risk factors for it) and how does risk relate to dose? Further, they evaluate the efficacy of TMP/SMX prophylaxis. To answer these questions, they retrospectively identified an institutional cohort of rheumatology patients in Korea treated with ‘high-dose’ glucocorticoids (>30 mg/day) for 4 or more weeks. Within this cohort, they selected patients offered TMP/SMX prophylaxis and compared their incidence of PJP with the remainder of the group that did not receive prophylaxis. There were important underlying differences between the groups, as one might expect, and it was clear that the treating physicians had generally chosen to give TMP/SMX to those they had perceived at higher risk for …

Epidemiology of Histoplasmosis

Abstract: Histoplasma capsulatum is an environmental fungus that contributes significant morbidity and mortality throughout the globe, especially in immunocompromised hosts. This review presents current data on the understanding of histoplasmosis epidemiology, including changing incidence among geographic regions and patient populations with increased risk. Global cases are more frequently identified due to the HIV epidemic, an increasing number of immunocompromised patients, and improved diagnostic capabilities. The global distribution of histoplasmosis extends to several countries in Central and South America and the Caribbean, as well as southern and sub-Saharan Africa, India, China, and Southeast Asia. Cases are also seen throughout Europe and non-endemic regions of the USA often due to migration and travelers. The changing epidemiology of histoplasmosis underlines the importance of continued surveillance and reporting to better understand the regions which place patients at a higher risk for infection.

Vaccinations in Rheumatology

Abstract: Immunization against vaccine-preventable diseases has improved morbidity and mortality for a wide range of patient populations, including both children and adults with rheumatic diseases. While patients with rheumatic diseases are at increased risk for infections at baseline, the addition of immunosuppressive therapy amplifies this risk. Inactivated vaccines (e.g., influenza, pneumococcus) are generally safe, while many live vaccines (e.g., MMR, zoster) are contraindicated depending on the degree of immunosuppression (e.g., conventional DMARDs vs. TNF inhibitors). This chapter will provide vaccine-specific recommendations and summarize host immune response and vaccine safety and efficacy among patients with rheumatic diseases.

Two Cases and a Review of Graft-Versus-Host Disease and the Role of Hepatitis C Treatment in Liver Transplant Patients

Abstract: Graft-versus-host disease (GvHD) is a rare but fatal complication after solid organ transplantation arising in 1% to 2% of cases. We report 2 cases of GvHD after orthotopic liver transplantation. Both patients had a history of hepatitis C virus (HCV) infection prior to transplantation. Both cases presented between 1 and 4 months after transplantation with rash, pancytopenia, and/or diarrhea. Our second case also developed oral and ocular manifestations after liver transplantation, which are more commonly described after stem cell transplantation. Diagnosis in both cases was made by clinical presentation in conjunction with histopathology and flow cytometry. Both patients were treated by increasing immunosuppression with tacrolimus and high-dose steroids. Response to treatment differed based on the degree of pancytopenia. Our case report is distinguished by several factors such as the context of GvHD presentation and the role of HCV treatment. Diagnosis of GvHD is difficult and often delayed due to nonspecific presentation that overlaps with other conditions. Furthermore, the relation between HCV treatment and potential initiation of GvHD in solid organ transplant patients is unclear.