Hsin-Yun Sun

Pneumonia Due to Pseudomonas aeruginosa: Part I: Epidemiology, Clinical Diagnosis, and Source

Pseudomonas aeruginosa is an uncommon cause of community-acquired pneumonia (CAP), but a common cause of hospital-acquired pneumonia. Controversies exist for diagnostic methods and antibiotic therapy. We review the epidemiology of CAP, including that in patients with HIV and also in hospital-acquired pneumonia, including ventilator-associated pneumonia (VAP) and bronchoscope-associated pneumonia. We performed a literature review of clinical studies involving P aeruginosa pneumonia with an emphasis on treatment and prevention. Pneumonia due to P aeruginosa occurs in several distinct syndromes: (1) CAP, usually in patients with chronic lung disease; (2) hospital-acquired pneumonia, usually occurring in the ICU; and (3) bacteremic P aeruginosa pneumonia, usually in the neutropenic host. Radiologic manifestations are nonspecific. Colonization with P aeruginosa in COPD and in hospitalized patients is a well established phenomenon such that treatment based on respiratory tract cultures may lead to overtreatment. We present circumstantial evidence that the incidence of P aeruginosa has been overestimated for hospital-acquired pneumonia and reflex administration of empirical antipseudomonal antibiotic therapy may be unnecessary. A diagnostic approach with BAL and protected specimen brush using quantitative cultures for patients with VAP led to a decrease in broad-spectrum antibiotic use and improved outcome. Endotracheal aspirate cultures with quantitative counts are commonly used, but validation is lacking. An empirical approach using the Clinical Pulmonary Infection Score is a pragmatic approach that minimizes antibiotic resistance and leads to decreased mortality in patients in the ICU. The source of the P aeruginosa may be endogenous (from respiratory or GI tract colonization) or exogenous from tap water in hospital-acquired pneumonia. The latter source is amenable to preventive measures.

Mucormycosis: its contemporary face and management strategies

Several countries have seen rising frequencies of mucormycosis among patients with haematological disorders, malignancies, or diabetes mellitus, and among transplant recipients. Growing numbers of immunocompromised hosts, widespread use of antifungal agents inactive against mucormycosis, or other unidentified factors, could be contributing to this situation. The predominant clinical manifestations of mucormycosis vary from host to host. Additionally, risk factors specific to different subgroups have been identified, such as leukaemia, allogeneic haemopoietic stem-cell transplant, voriconazole prophylaxis, diabetes, and malnutrition. We summarise the current state of knowledge of characteristics and risk factors and discuss topical developments in therapeutic methods and strategies in the management of mucormycosis.

Prevention of posttransplant cytomegalovirus disease and related outcomes with valganciclovir: a systematic review.

The precise impact of valganciclovir as preventive therapy for cytomegalovirus (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from studies using valganciclovir as preemptive therapy or prophylaxis for CMV in SOT recipients were synthesized for descriptive analysis. CMV disease occurred in 2.6% and 9.9% of the patients receiving valganciclovir as preemptive therapy and prophylaxis, respectively. Although the incidence of early‐onset (≤90 days posttransplant) CMV disease was only 0.8% and 1.2% in all patients and R–/D+ patients receiving valganciclovir prophylaxis, the incidence of late‐onset (>90 days posttransplant) CMV disease rose up to 8.9% and 17.7% in the prophylactic group, respectively. On the contrary, no patients developed late‐onset CMV disease in preemptive group. Both approaches with valganciclovir have successfully decreased CMV disease in SOT recipients. Late‐onset CMV disease is a complication observed uniquely with valganciclovir prophylaxis, particularly in R–/D+ patients, but not with preemptive therapy.

Mucormycosis in Organ and Stem Cell Transplant Recipients

Mucormycosis is a devastating invasive fungal disease whose incidence has increased during the past decade. Mucormycosis now represents a major threat in transplant recipients, accounting for 2% and 8% of invasive fungal infections in recent cohorts of solid-organ and allogeneic stem-cell transplant recipients, respectively. Mucormycosis most often occurs late, >3 months after transplantation, although cases occurring early have been observed, especially among liver transplant recipients and in cases of graft-transmitted infection. Recent guidelines have emphasized the direct examination of the involved fluid or tissue and culture from a sterile site as the most appropriate diagnostic strategy and the use of lipid formulations of amphotericin B and major surgery when feasible as the most appropriate first-line therapeutic strategy for mucormycosis in organ and stem cell transplant recipients.

Evolution of Hepatitis B Serological Markers in HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy

BACKGROUND Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). METHODS During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers. RESULTS After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively. CONCLUSIONS Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.

Characterisation of breakthrough invasive mycoses in echinocandin recipients: an evidence-based review

The echinocandins have emerged as important antifungal agents in the current era. Despite their potent antifungal activity, breakthrough invasive mycoses occur in echinocandin recipients, however their precise incidence and causative pathogens are not well delineated. This review shows that breakthrough mycoses occur in 2.4% of patients receiving echinocandins as prophylaxis and are predominantly due to non-albicans Candida spp. and less frequently to invasive aspergillosis. Candida isolates demonstrating reduced susceptibility occurred following prolonged exposure to the echinocandins, primarily in severely immunocompromised patients, and manifested as recurrent episodes of candidaemia or invasive candidiasis.

Immune reconstitution inflammatory syndrome in non-HIV immunocompromised patients.

Purpose of review In the era of highly active antiretroviral therapy, immune reconstitution inflammatory syndrome has become well recognized in the HIV-infected population. However, little is known about its occurrence in non-HIV immunocompromised hosts. The present review aims to propose the pathogenesis of immune reconstitution inflammatory syndrome, summarize its occurrence in immunocompromised patients without HIV infection, and suggest potential treatment options. Recent findings Immune reconstitution inflammatory syndrome is exuberant and dysregulated inflammatory responses to invading microorganisms. It manifests when an abrupt shift of host immunity from an anti-inflammatory and immunosuppressive status towards a pathogenic proinflammatory state occurs as a result of rapid decreases or removal of factors promoting immunosuppression or inhibiting inflammation. In addition to HIV-infected patients, immune reconstitution inflammatory syndrome has also been observed in solid organ transplant recipients, women during the postpartum period, neutropenic patients, and tumor necrosis factor antagonist recipients. Corticosteroids are the most commonly employed treatment, whereas other potential agents based on its pathogenesis deserve further investigation. Summary Non-HIV immunocompromised hosts develop immune reconstitution inflammatory syndrome when the sudden change in the dominant T helper responses to inflammation is not well balanced by anti-inflammatory responses. Judicious manipulation of host immunity and timely recognition of immune reconstitution inflammatory syndrome as we deal with the infections in these populations is critical to limit or avoid the harm by immune reconstitution inflammatory syndrome.

Cryptococcosis in Solid-Organ, Hematopoietic Stem Cell, and Tissue Transplant Recipients: Evidence-Based Evolving Trends

The impact of current transplantation practices on the characteristics of cryptococcosis in solid-organ transplant recipients is not well defined. The incidence of cryptococcal disease among solid-organ transplant recipients has remained unchanged; however, patients are less likely to present with central nervous system or disseminated disease and are more likely to have cryptococcosis limited to the lungs. Additionally, lipid formulations of amphotericin B are now used more frequently, whereas their use in combination with flucytosine has decreased. The overall mortality of cryptococcosis has significantly improved in the current era. Renal failure remains associated with poor outcome, whereas use of lipid formulations of amphotericin B is associated with a higher survival rate. Despite rare infectious complication, certain peculiar attributes of cryptococcal disease in hematopoietic stem cell recipients and tissue transplant recipients warrant recognition.

Detection of Circulating Galactomannan in Serum Samples for Diagnosis of Penicillium marneffei Infection and Cryptococcosis among Patients Infected with Human Immunodeficiency Virus

ABSTRACT Galactomannan (GM) is a heteropolysaccharide in the cell walls of most Aspergillus and Penicillium species. Cross-reactivity of Cryptococcus neoformans galactoxylomannan in an Aspergillus GM test has also been reported. In this study, we used a Platelia Aspergillus enzyme immunoassay kit (Bio-Rad) to test serum samples obtained from 48 human immunodeficiency virus (HIV)-infected patients (15 with penicilliosis [7 with fungemia alone, 4 with cavitary lung lesions alone, 3 with both fungemia and cavitary lung lesions, and 1 with disseminated disease], 22 with cryptococcosis [11 with fungemia alone, 5 with cavitary lung lesions, 3 with both, and 3 with meningitis alone], and 11 without any invasive fungal infection [control]) for GM levels. None of the patients had aspergillosis or concurrent use of piperacillin-tazobactam or amoxicillin-clavulanate. The median time between diagnosis of fungal infection and collection of serum samples was 0 days for penicilliosis and 1.5 days for cryptococcosis. Of patients with penicilliosis, cryptococcosis, and controls, 73.3%, 13.6%, and 9%, respectively, had GM optical density (OD) indices of >0.5 (P = 0.0001). GM OD indices were higher for penicilliosis (median OD index, 4.419; range, 0.158 to >20) than for cryptococcosis (median, 0.247; range, 0.112 to 3.849) cases (P < 0.001). Patients with fungemic penicilliosis had higher OD indices (median, 10.628; range, 0.401 to >20) than patients with nonfungemic penicilliosis (median, 0.378; range, 0.158 to 4.419) and patients with cryptococcemia (median, 0.231; range, 0.112 to 1.168) (P < 0.001). Of the 15 patients with cavitary lung lesions, those with penicilliosis had higher antigen levels (median OD index, 1.641; range, 0.247 to >20) than those with cryptococcosis (median, 0.227; range, 0.112 to 3.849) (P = 0.011). This study showed that the GM OD index was significantly elevated for HIV patients with penicilliosis. The use of the GM antigen assay may facilitate earlier diagnosis of Penicillium marneffei infection for HIV-infected patients in areas of endemicity.

Rhino-orbital-cerebral zygomycosis in solid organ transplant recipients

Background. Rhino-orbital-cerebral disease is a significant manifestation of zygomycosis in solid organ transplant (SOT) recipients. However, its characteristics and outcome are not well addressed. Methods. SOT recipients with zygomycosis as per the European Organization for Research and Treatment in Cancer and the Mycoses Study Group criteria in a cohort study at our centers published previously and those identified with a PubMed search from the 1950s to November 2009 were studied. Patients with mycosis involving the sinuses, orbits, or central nervous system (CNS) were included. Results. Patients comprised a total of 90 SOT recipients with rhino-orbital-cerebral zygomycosis, including 13 in our cohort and 77 in the literature. CNS disease occurred in 57% (51 of 90). Overall mortality was 52.3% (46 of 88), and the mortality in patients with CNS disease was 73.5% (36 of 49). In logistic regression analysis, older age (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.04–1.21, P=0.002) was associated with a higher mortality rate, whereas lipid formulations of amphotericin B compared with amphotericin B deoxycholate (OR 0.09, 95% CI 0.02–0.50, P=0.006) and surgery (OR 0.12, 95% CI 0.01–0.94, P=0.043) were independently associated with an improved survival even when controlled for CNS involvement and the era of diagnosis of disease. Conclusions. Rhino-orbital-cerebral zygomycosis, particularly CNS disease, is associated with substantial mortality rate in SOT recipients. Older age is a significant risk factor for mortality, whereas lipid formulations of amphotericin B and surgery improved outcomes.