Thein Myint

Histoplasmosis After Solid Organ Transplant

BACKGROUND To improve our understanding of risk factors, management, diagnosis, and outcomes associated with histoplasmosis after solid organ transplant (SOT), we report a large series of histoplasmosis occurring after SOT. METHODS All cases of histoplasmosis in SOT recipients diagnosed between 1 January 2003 and 31 December 2010 at 24 institutions were identified. Demographic, clinical, and laboratory data were collected. RESULTS One hundred fifty-two cases were identified: kidney (51%), liver (16%), kidney/pancreas (14%), heart (9%), lung (5%), pancreas (2%), and other (2%). The median time from transplant to diagnosis was 27 months, but 34% were diagnosed in the first year after transplant. Twenty-eight percent of patients had severe disease (requiring intensive care unit admission); 81% had disseminated disease. Urine Histoplasma antigen detection was the most sensitive diagnostic method, positive in 132 of 142 patients (93%). An amphotericin formulation was administered initially to 73% of patients for a median duration of 2 weeks; step-down therapy with an azole was continued for a median duration of 12 months. Ten percent of patients died due to histoplasmosis with 72% of deaths occurring in the first month after diagnosis; older age and severe disease were risk factors for death from histoplasmosis. Relapse occurred in 6% of patients. CONCLUSIONS Although late cases occur, the first year after SOT is the period of highest risk for histoplasmosis. In patients who survive the first month after diagnosis, treatment with an amphotericin formulation followed by an azole for 12 months is usually successful, with only rare relapse.

Histoplasmosis Complicating Tumor Necrosis Factor–α Blocker Therapy: A Retrospective Analysis of 98 Cases

BACKGROUND Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Histoplasmosis in Patients With Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS): Multicenter Study of Outcomes and Factors Associated With Relapse

AbstractAlthough discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis.Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91–55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL.Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.

Temporal Trends, Clinical Characteristics, and Outcomes of Histoplasmosis in a Tertiary Care Center in Kentucky, 2000 to 2009

The impact of highly active antiretroviral therapy (HAART) on the epidemiology of AIDS-associated histoplasmosis in the past decade is poorly defined. Among 100 patients with histoplasmosis in an endemic region between 2000 and 2009, 42 patients were immunocompetent, 32 were infected with HIV, and 26 were non-HIV-immunocompromised patients. The percentage with HIV decreased 67% in 2000-2001 to 18% in 2008-2009 (P = .004), while the proportion of non-HIV immunocompromised patients increased, 8% to 41% (P = .14). Histoplasma antigen was the most sensitive test (73%), whereas potassium hydroxide examination of clinical specimens was the least sensitive test (33%) in all 3 groups. Bronchoalveloar fluid culture (74%) had the highest yield among the cultures. The relapse rate was higher in HIV-infected patients compared to the other 2 groups (P = .04). The epidemiology of histoplasmosis in our endemic area has changed during the era of HAART. Organ transplantation and increasing use of immunosuppressive agents for chronic inflammatory conditions in non-HIV patients now account for most of the cases of histoplasmosis.

Respiratory Muscle Paralysis Associated With Colistin, Polymyxin B, and Muscle Relaxants Drugs A Case Report

Polymyxins B and E (colistin) exert a bactericidal effect on the gram-negative bacterial cell wall, causing permeability changes in the cytoplasmic membrane, leading to cell death. Their use was substantially decreased in clinical practice from the 1970s to 2000s due to their significant nephrotoxicity and neurotoxicity compared to the newly introduced antibiotics. The increasing prevalence of multidrug-resistant gram-negative bacteria infections in this century has led to an upsurge in the use of these “older” drugs. Respiratory paralysis caused by neuromuscular blockage associated with the use of polymyxin B and E was reported mostly in literature published in the 1960s to 1970s with a few reports after 2000. In addition, such a reaction might be enhanced by the presence of other classes of drugs. We report a case of polymyxin B and E–induced apnea in a patient receiving “muscle relaxants.”

Post operative fungal endopthalmitis due to Geotrichum candidum

Geotrichum species have been rarely reported as the cause of sepsis, disseminated infection in immunosuppressed patients. The patient we describe developed indolent endophthalmitis four months after her routine right eye cataract surgery. The intraoperative sample from right vitreous fluid grew Geotrichum candidum. The patient underwent vitrectomy, artificial lens explantation and intravitreal injection of amphotericin B followed by oral voriconazole. Despite these interventions, she underwent enucleation. This is the first published case of Geotrichum candidum endophthalmitis.

Rhodococcus equi pericarditis in a patient living with HIV/AIDS.

Introduction: Rhodococcus equi, previously called Corynebacterium equi, is known to cause pneumonia in foals and swine. Although it was known to cause infection rarely in humans, R equi infection in humans has increased with the advent of HIV and increased use of immunosuppressants. Case: We report a case of a 48-year-old male patient with newly diagnosed HIV/AIDS presenting with recurrent R equi bacteremia, pericardial effusion, and pericardial cyst. The infection was treated with drainage of the pericardial effusion and cyst and 2 weeks of intravenous vancomycin and 6 months of oral azithromycin and levofloxacin. Discussion: Rhodococcus equi causes pericarditis and pericardial effusion. It can be effectively treated with debridement, drainage, and a prolonged course of antibiotics. In vitro antibiotic susceptibility should be checked as resistance to antibiotics can develop, especially if drainage is inadequate.

Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment

Abstract Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment. A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment. Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment. While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid

Improvements in the immunologic tests performed on cerebrospinal fluid have increased the sensitivity and reduced the turnaround time for diagnosis of central nervous system histoplasmosis over prior antigen and antibody detection methods and culture.

Impact of an Antimicrobial Stewardship and Emergency Department Initiated Dalbavancin Guideline for Patients with Acute Bacterial Skin and Soft Tissue Infections

Abstract Background Acute bacterial skin and skin structure infections (ABSSI) are one of the most common reasons for patient hospitalization. These admissions may be solely for receipt of intravenous vancomycin due to concern for resistance to alternative agents or failure of oral therapy, providing a niche for long-acting agents like dalbavancin. The objective of this study was to evaluate patient outcomes following initiation of a dalbavancin guideline for ABSSI in the emergency department (ED). Methods This was a single-center, case series study evaluating adult patients with ABSSI from April 2016 to May 2017 who were screened for receipt of dalbavancin. Candidates were identified by a dalbavancin guideline implemented in the ED in April 2016 with hours from 7 am to 7 pm. Patients were assessed for inclusion by an ED pharmacist and physician. If the patient qualified for receipt of dalbavancin, the ED pharmacist contacted the Antimicrobial Stewardship Team (AST) for final approval. The guideline was revised in January 2017 to lessen restrictions. Patients were contacted via phone by an ED pharmacist for follow-up and the interaction documented in the electronic medical record. Patient data were collected using REDCap™. Results Overall, 22 patients (15 males/7 females) were evaluated for inclusion to receive dalbavancin. The average age of the patients was 38 years old, ranging from 21 to 61 years. Of these 22 patients, 7 received a single dalbavancin dose of 1,500 mg over 30 minutes for ABSSI (cellulitis {n = 5} and shooter’s abscess {n = 2}). The reasons for exclusion were: lack of systemic signs of infection (n = 5), risk of Gram-negative infection (n = 2), outside guideline time period (n = 2), required hospital support (n = 2), immunocompromised (n = 1), severe hepatic disease (n = 1), bacteremia (n = 1), and diabetic foot infection (n = 1). All patients received a follow-up visit (n = 4) or phone call from the ED pharmacist (n = 3). Only 1 patient required a later hospital admission due to further complications. Conclusion A multidisciplinary team approach to treating ABSSI in the ED was highly successful at our academic medical center. Further expansion of guideline hours should enhance the utilization of this guideline. Disclosures All authors: No reported disclosures.