Deep-seated fungal infections in immunocompromised patients in iran

During the last two decades or so, the incidence of fungal infections has increased dramatically. Deep- seated mycoses are creating serious problems for clinicians working with certain populations of patients, such as those with cancer, the immunocompromised, and physiologically compromised.A study of fungal isolated for identification of deep fungal infections, risk factors and etiologic agents in immunocompromised patients was carried out in the section of Medical Mycology, Pasteur Institute of Iran from 1994 to 2001. Seventy one immunosuppressed patients with deep fungal infection were retrospectively analyzed for etiology and risk factors. They had one or more predisposing factors to disseminated fungal infections. Diagnosis was established by demonstration of fungus in direct and cultural examinations. Candida spp. were isolated in 70.4% (39.4% C. albicans and 30.9% non-albincans), and Aspergillus spp. were isolated in 14.1% of cases. The most frequent risk factors were hematologic malignancy (ALL, lymphoma, Hodgkin, multiple myeloma) and diabetes mellitus. This study suggests that in immunocompromised patients, fungal infections especially in saprophytic infections, background evaluation and clinical features, correspondence of clinical symptoms and laboratory examinations should be considered and investigation of other factors which created the infection will lead us to a clear picture of patients' situation.     

The role of itraconazole in preventing and treating systemic fungal infections in immunocompromised patients

The increasing use of immunosuppressive chemotherapy and allogeneic transplants for haematological malignancies has increased the number of patients at risk of systemic fungal infections (SFIs). A number of antifungal agents are now available. This paper reports the deliberations of an expert panel that considered the role of itraconazole. It concluded that itraconazole has an important role in the prophylaxis and treatment of SFIs whether proven or not.     

Respiratory infections in immunocompromised patients

HIV disease has been dramatically reduced in the developed world by the introduction of highly active antiretroviral therapy, with implications that prophylactic therapy against opportunistic infections may be stopped; however, tuberculosis is an escalating problem in the HIV-infected and HIV-noninfected populations worldwide. Compliance with effective treatment regimens, especially through directly observed therapy, remains the cornerstone of tuberculosis control strategies. Although tuberculosis prophylaxis is of benefit for tuberculin skin reactors with HIV in the developed world, several reservations are voiced about this approach in resource-poor settings. Recent advances in technology, particularly in antigen-specific systems, have revolutionized the understanding of HIV immunology and helped to elucidate the mechanisms of pathogenesis in diseases such as cytomegalovirus. In bone marrow transplantation and solid-organ transplantation patients, quantitative polymerase chain reaction (PCR) to predict cytomegalovirus disease is an important advance, and patients who undergo bone marrow transplantation, CT scanning has proven useful in the diagnosis of pulmonary aspergillosis.     

Invasive fungal infections associated with prior respiratory viral infections in immunocompromised hosts

Background

Increased risk of invasive pulmonary aspergillosis after influenza infection has been reported; however data are limited.

Purpose

To describe Invasive fungal infections (IFI) associated with preceding respiratory viral infection at a large referral center.

Methods

We reviewed all IFI cases among patients with positive influenza and/or RSV nasopharyngeal/lower respiratory tract PCR from October 2015 to December 2016. Cases of pulmonary IFI were classified as possible, probable, and definite based on EORTC-MSG definitions.

Results

We identified 8 cases (4 influenza, 4 RSV); 3 with probable Aspergillosis, 1 possible Aspergillosis, 1 probable Histoplasmosis, 1 probable Mucormycosis, and 2 possible IFI (consistent clinical and imaging findings). Half of our patients were men with a mean age of 64 years (SD 8) and median Charlson Comorbidity Score of 3.5 (IQR 3-7). Most common risk factors were stem cell transplant (75%) and neutropenia (62.5%). Four patients were on antifungal prophylaxis at presentation. All patients received anti-viral therapy with oseltamivir/ribavirin and 50% received empiric antibiotics. Median duration from onset of viral infection to diagnosis of IFI was 8.5 days (IQR 2.5-14) and 75% were diagnosed during the same admission. All received antifungal therapy; 62.5% required ICU care, and 37.5% died during index hospitalization.

Conclusions

Our study supports earlier observations describing IFI following respiratory viral infection in immunocompromised hosts. Secondary IFI occurred in 1.4% of our cohort and most occurred during the index admission. IFI following viral illness is associated with high mortality and early detection and therapy may improve outcomes.

     

Dermatologic manifestations of infections in immunocompromised patients

Thirty-one immunocompromised patients (22 renal allograft recipients, 5 patients receiving chronic corticosteroid therapy, and 4 patients undergoing chemotherapy for acute leukemia) with significant dermatologic infection, excluding typical cellulitis and herpesvirus infections, were retrospectively identified over a 12-year period. Of these 31 patients, 15 (48%) had infection restricted to their skin, 6 (19%) appeared to have primary cutaneous infection that spread hematogenously to other parts of the body, 2 (6%) had infections of adjoining nasal tissue that spread to contiguous skin, and 8 (26%) appeared to have disseminated systemic infection that spread to the skin. In six of the eight patients with apparent secondary skin involvement, the development of the cutaneous lesion was the first clinical indication of disseminated infection. Eleven immunocompromised patients (35%) with bacterial infection of the skin or subcutaneous tissue were identified. These patients could be divided into three categories: leukemic patients with bacteremic gram-negative infection metastasizing to the skin (3 cases), renal transplant recipients with recurrent staphylococcal infection on and around the elbow ("transplant elbow") or streptococcal sepsis from a site of cellulitis (5 cases), and immunocompromised patients with opportunistic bacterial infection due to Nocardia asteroides or atypical mycobacteria (3 cases). Seventeen immunocompromised patients (55%) with fungal infection of the skin or subcutaneous tissue were identified. These included 12 patients with opportunistic fungal infection (Cryptococcus neoformans, 4 cases; Aspergillus species, 3 cases; Paecilomyces, 2 cases; Rhizopus species, 2 cases; and Candida tropicalis, 1 case) and 5 patients with extensive, confluent cutaneous dermatophyte infections. One patient with protothecosis and two patients with extensive papillomavirus infection were identified. Of these latter two cases, one had his immunosuppression discontinued, with clearing of his extensive warts; the other had confluent warts of the face and neck that subsequently underwent malignant degeneration to squamous cell carcinoma while chronic immunosuppressive therapy was continued.(ABSTRACT TRUNCATED AT 400 WORDS)     

Caspofungin as first line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies

Invasive Fungal Infections (IFI) remain a severe and major complication among patients with hematologic diseases, but the recent availability of new antifungal agents (echinocandins and new azoles) have improved the chance of cure. Caspofungin (Cancidas-Merck) is a large lipopeptide molecule able to inhibit the enzyme complex 1,3-d-glucan synthetase; this action specifically damages the fungal cell wall. Caspofungin (CAS) is active, in vitro and in vivo, against most Candida species and Aspergillus species. We report on our experience with this drug as first-line therapy for proven or probable pulmonary IFI in immunocompromised patients with hematologic malignancies. Thirty-two consecutive patients (20 males and 12 females, with a median age of 52 yr) have been treated with CAS (27 acute leukemias, 1 chronic leukemia, 3 lymphomas and 1 multiple myeloma). Sixteen patients (50%) had a relapsed or resistant hematologic disease, while 12 patients were in complete remission and 4 were at onset of disease; 8/32 (25%) developed IFI after a hematopoietic stem cell transplant (HSCT) procedure. Seven out of 32 patients (22%) had a proven pulmonary IFI (7/7 Aspergillosis) and 25 (78%) had a probable IFI with pulmonary localization as defined according to international consensus. Thirty-one patients (97%) had less than 1000 granulocytes/mL at onset of infection and at the start of CAS therapy. The CAS was given at the dose of 70 mg on day 1, followed by 50 mg/day. Median duration of CAS therapy was 20 d (range 8-64); all the 31 neutropenic patients received concomitant granulocyte colony-stimulating factor (G-CSF). The overall response rate was 56% (18/32) with 12/18 complete responses and 6/18 partial responses; two patients (6%) had a stable disease. Twelve out of 32 (38%) did not respond and seven died of mycotic infection. Univariate analysis showed that granulocytes recovery (>500/mL vs. <500/mL) and status of hematologic disease (remission/onset vs. refractory/relapsed) were significantly associated to favourable outcome. No clinical adverse events (AE) were reported and only a grades I and II transient increase of serum alkaline phosphatase and/or transaminases occurred in 4/32 (12%) patients. After CAS therapy six non-responders and six cases with a partial or stable response were rescued with voriconazole. Two out of six patients (33%) in the former group and 6/6 (100%) in the latter obtained a complete resolution of IFI. Our experience suggests an efficacy of CAS, in combination with G-CSF, as first-line treatment of proven or probable IFI with pulmonary localization. The drug was well tolerated and there were no significant hepatic AE even in patients receiving CAS with cyclosporine after a HSCT. A significant proportion of non-responders or partial responders to CAS can be rescued with a subsequent voriconazole-based therapy.     

Management of viral infections in immunocompromised cancer patients

Immunocompromised cancer patients are at elevated risk for serious viral disease. The introduction into clinical use of potent antiviral agents and of rapid diagnostic tests resulted in the development of efficient management strategies for infections due to herpes simplex virus, varicellazoster virus, and cytomegalovirus. The emergence of herpesvirus resistance to acyclovir, ganciclovir, cidofovir, or foscarnet represents an important challenge. The new neuraminidase inhibitors zanamivir and oseltamivir are efficacious in the treatment of influenza in otherwise healthy adults, and need to be investigated among immunodeficient patients with malignancy. Preliminary data on pleconaril, a first broad-spectrum anti-picornaviral compound, are promising.     

Pulmonary infections due to Legionella in immunocompromised patients

At present, 11 different species of Legionella have been implicated in human disease. It has become apparent that disease caused by Legionella is acquired from a variety of environmental sources and that water is the factor that links many of them. Patients who are immunosuppressed, such as individuals receiving cancer chemotherapy or therapy designed to prevent organ rejection, are particularly susceptible to such environmental sources. It appears that intact cell-mediated immunity is more important in host defense than are adequate numbers of granulocytes or immunoglobulin concentrations. Diagnostic steps should be undertaken in all patients developing nosocomial pneumonia who present with a picture suspicious for this disorder. In the meantime, appropriate antimicrobial therapy with erythromycin and rifampin should be begun. If clusters of cases are detected in a hospital, immediate steps should be taken to attempt to isolate the organism from any aqueous environmental sources, and if found appropriate, steps taken. Awareness of the threat of legionnaires' disease must be maintained among clinicians and hospital epidemiologists because it is unlikely that the problem of nosocomial legionnaires' disease will disappear.     

Fungal infections in granulocytopenic and immunocompromised patients]

Opportunistic fungus infections in neutropenic immunocompromised patients have strikingly increased, especially with the improvement of antibiotic treatment. Their outcome is often fatal because of the difficulties in diagnosis and treatment. Therefore a rationale of surveillance diagnostics and empiric treatment in risk patients is necessary. In these patients a continuous weekly mycotic diagnosis of mouth, throat, faeces, urine, vagina, as well as of the blood is necessary. During an aggressive neutropenia-producing chemotherapy an antimycotic prophylaxis with the aim of reducing fungal colonization in the gastrointestinal tract (sometimes in the respiratory pathways, too) should be performed. Fever of unknown origin lasting longer than 4-5 days in spite of broad spectrum antibiotic treatment and/or positive diagnostic findings must lead to treating risk patients empirically using amphotericin B 1 mg/kg/d or a combination of amphotericin B 0.3-0.5 mg/kg/d together with flucytosin (Ancotil) 150 mg/kg/d. In case of a beginning candidiasis, patients can first be treated with fluconazol (Diflucan). The dose is 400 mg/d, later on 200 mg/d. It is pointed out that, much more often than usual, in risk patients with fever, atypical pneumonia, meningoencephalitis or other organ symptoms fungal infections should be taken into consideration. The most common opportunistic fungal diseases are presented and details concerning the different antimycotic drugs are given.     

Imaging in the diagnosis of infections in immunocompromised patients

Early use of CT and MRI helps to diagnose infection in immuno-compromised patients earlier and more precisely. Anti-fungal therapy can now be instituted in the knowledge that there is scan proven fungal disease and withheld when scans indicate other pathology. The optimal way to utilise these tests is described.     

Aggressive non-Hodgkin's lymphomas in immunocompromised homosexual males

During the period from 1981 through 1984, 14 immunocompromised homosexual males with intermediate or high-grade non-Hodgkin's lymphoma were seen at University of Texas M.D. Anderson Hospital and Tumor Institute. Six patients had diffuse large-cell lymphoma, seven had diffuse undifferentiated lymphoma, and one had unclassifiable lymphoma that suggested large-cell lymphoma. Eight patients had the acquired immunodeficiency syndrome (AIDS) and five had the AIDS-related complex. Kaposi's sarcoma was initially present in four patients and developed later in two others. The patients with diffuse large-cell lymphoma were characterized by more severely altered immune parameters, multicentric brain mass lesions, pretherapy opportunistic infections, lower performance status, poor response to therapy, and death in all within six months. The undifferentiated lymphoma group had preceding generalized reactive lymphadenopathy, less severe immune dysfunction, and excellent response to combination chemotherapy, with survival time greater than 19 months in three patients. Twelve of the patients had extranodal sites of lymphoma at presentation. There is a definite trend for the development of aggressive non-Hodgkin's lymphomas with unusual sites of extranodal involvement in immunocompromised homosexual males, with the potential for good tolerance to combination chemotherapy and improved survival in the subgroup without severe concomitant opportunistic infections.     

Improved outcomes associated with advances in therapy for invasive fungal infections in immunocompromised hosts

Invasive fungal infections cause substantial morbidity and mortality in immunocompromised hosts. The response rate to therapy, in particular for invasive aspergillosis and invasive mould infections, has been poor. Recently a number of techniques to facilitate early diagnosis of these infections, in parallel with the development of a number of antifungals with increased potency and lower toxicity, have raised optimism that outcomes for invasive fungal infection can be improved upon. The availability of lipid formulations of amphotericin B, azoles with extended spectrum against filamentous fungi and the development of a new class of antifungal agents, the echinocandins, presents the clinician with a range of therapeutic choices. Recent clinical trials have provided important insights into how these agents should be used. In particular, voriconazole has demonstrated superior efficacy to amphotericin B in the management of invasive aspergillosis, posaconazole has been shown to have significant efficacy in the prophylaxis of invasive fungal infection in high-risk individuals and a role in salvage therapy of invasive aspergillosis, caspofungin has demonstrated efficacy in salvage therapy of invasive aspergillosis, and each of the echinocandins show activity without significant toxicity in invasive candidiasis. Nevertheless, many therapeutic areas of uncertainty remain, including the role of combination therapy, and will provide the focus for future studies.