Search

Background The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. Methods We conducted a 10-year (2005–2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus–negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. Results Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0–10.4; P Conclusions Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

BackgroundAnnual incidence of active tuberculosis (TB) cases has plateaued in the US from 2013-2015. Most cases are from reactivation of latent tuberculosis infection (LTBI). A likely contributor is suboptimal LTBI treatment completion rates in subjects at high risk of developing active TB. It is unknown whether these patients are adequately identified and treated under current standard of care.MethodsIn this study, we sought to retrospectively assess the utility of an online risk calculator (tstin3d.com) in determining probability of LTBI and defining the characteristics and treatment outcomes of Low: 0-Results51(41%), 46 (37%) and 28 (22%) subjects were in Low, Intermediate and High risk groups respectively. Tstin3d.com was useful in determining the probability of LTBI in tuberculin skin test positive US born subjects. Of 114 subjects with available treatment information, overall completion rate was 61% and rates of completion in Low (60%), Intermediate (63%) and High (57%) risk groups were equivalent. 75% subjects in the 3HP group completed treatment compared to 58% in the INH group. Provider documentation of important clinical risk factors was often incomplete. Logistic regression analysis showed no clear trends of treatment completion being associated with assessment of a risk factor.ConclusionThese findings suggest tstin3d.com could be utilized in the US setting for risk stratification of patients with LTBI and select treatment based on risk. Current standard of care practice leads to subjects in all groups finishing treatment at equivalent rates.

It is unknown whether patients with LTBI at high vs. low risk of developing active TB are currently adequately identified and treated in the US. In this study our objective was 1) To retrospectively apply the online calculator (tstin3d.com) to determine the probability of having LTBI and assign cumulative risk of progression. 2) Measure treatment outcomes in subjects with Low: 0

The diagnosis of acute infection with human immunodeficiency virus (HIV) presents a challenge for the primary care provider. We present a case of early HIV infection and discuss the limitations of the currently established diagnostic algorithm for HIV infection. We conclude that alternative diagnostic testing for human immunodeficiency virus type 1 (HIV-1) RNA is warranted in certain clinical settings. Appropriate, early diagnosis of HIV infection may improve the patient's outcome and provide additional public health benefits by reducing transmission of disease.

Two hemophiliacs infected with human immunodeficiency virus (HIV) presented with hematochezia secondary to gastrointestinal involvement with Histoplasmosis capsulatum. In one patient who was already receiving fluconazole, the diagnosis was obscured. Both patients responded to amphotericin B followed by intraconazole, with no recurrence of bleeding. © 1994 Wiley-Liss, Inc.

A cross-sectional epidemiology study evaluated the role of sexual activity and sexually transmitted diseases (STDs) in the transmission of hepatitis G virus (HGV/GBV-C) and other hepatitis virus infections in 944 subjects. There was a statistically significant higher prevalence of HGV/GBV-C, hepatitis B virus, and hepatitis C virus exposure in the STD clinic group (i.e., subjects who were currently seeking treatment for an STD) compared with the group who never had received treatment for an STD. In a comparison of the subjects with an STD versus those without an STD, the prevalence of HGV/GBV-C was 11.3% versus 4.9%, on the basis of polymerase chain reaction (PCR) results alone, and 36.6% versus 8.8%, when results of PCR and enzyme-linked immunosorbent assay were combined. Sexual activity and, possibly, the presence of an STD increases the risk of HGB/GBV-C transmission.

Severe acute hemolytic anemia developed in a woman following treatment with multiple antibiotics for possible postpartum uterine infection. On admission, the hemoglobin was 5 g per dL (50 g/L), the reticulocytes were 35 percent (0.350), the direct antiglobulin test was strongly positive for IgG and C3d (mixed fields), and the indirect antiglobulin test was negative. Serologic studies revealed antibody to cefotetan that reacted by both the immune complex and the drug adsorption mechanisms. Before the diagnosis of cefotetan-related immune hemolysis was made, all medications had been discontinued, and the patient received 4 units of red cells and a short course of adrenocorticosteroids. Recovery was prompt and complete.

A 36-year-old woman with gallbladder disease had an incidental finding of asymptomatic cavitary lung infection with Blastomyces dermatitidis. No treatment was given initially, and 2 months later she presented with vertebral osteomyelitis, paraspinal abscess, and spinal cord compression due to dissemination of the fungus. The patient recovered following surgical debridement and treatment with 1 g of amphotericin B, followed by itraconazole 400 mg QD for 6 months. In spite of previous reports of the self limiting nature of primary pulmonary blastomycosis in the normal host, antifungal therapy may be needed in cases that do not resolve spontaneously within a short period of time, or if transient immunosuppression may be anticipated as may occur following surgery or after acquisition of other infections.

A laboratory-derived mutant of Candida albicans B311 (L) and a clinical isolate (C) of C. albicans, both lacking membrane ergosterol, were less susceptible to amphotericin B (AmB)-induced cell membrane permeability to K+ and lethality than was the wild-type laboratory strain (B311) which contained ergosterol. The resistance of L and C to AmB-induced killing was much greater than the level of resistance to AmB-induced cell membrane permeability. L and C were also less susceptible to killing by H2O2 than was B311, and when treated with menadione, they each produced less H2O2 than did B311. In addition, their levels of catalase activity were 3.8-fold (L) and 2-fold (C) higher than that of B311. The ergosterol deficiency in L and C probably impaired AmB binding to the cells, thereby lowering AmB effectiveness as measured by both cell membrane permeability and killing. Resistance of strains L and C to oxidation-dependent damage likely contributed to a diminished response to AmB-induced lethality.

Amphotericin B (AmB) is known to bind to ergosterol in fungal cell membranes, but the precise mechanism of its toxicity to cells is as yet poorly understood. AmB autooxidizes, and it is possible that its antifungal effects could result from oxidative damage. Exposure of protoplasts of Candida albicans to AmB under hypoxic conditions reduced protoplast lysis by as much as 80% compared with incubations in air. Protoplasts were protected from AmB-induced lysis by exogenous catalase and/or superoxide dismutase (SOD). Whole cells of C. albicans were protected by exogenous catalase from AmB-induced leakage of [3H]leucine and from killing by AmB. Cells grown on medium inducing high levels of endogenous catalase were resistant to AmB-induced growth inhibition. In contrast, AmB-induced K+ leakage was not hindered under hypoxic conditions or in the presence of catalase or SOD. Thus the lethal and lytic effects of AmB on C. albicans cells and protoplasts, but not prelethal AmB-induced K+ leakage, are mediated by oxidative damage.

Candida albicans cells were exposed to equal concentrations of amphotericin B (AmB) administered either as a single large dose or as repeated small doses. Toxicity to C. albicans cells was less pronounced when AmB was administered in fractionated doses. Increased catalase activity in C. albicans cells was induced after exposure to fractionated doses of AmB; this increase may have contributed to the greater resistance of cells to AmB used according to this schedule.