amphotericin-b and Acquired-Immunodeficiency-Syndrome

Autochthonous leishmaniasis cases have been increasing continuously in Thailand over the years. We report multiple presentations of leishmaniasis in a 47-year-old patient with HIV/AIDS from Chiang Rai Province, northern Thailand. Physical examination showed multiple ulcerated papules, nodules, and plaques in a sporotrichoid distribution. Firm mucosal nodules on the hard palate and nasal opening, hepatosplenomegaly, and bilateral inguinal lymphadenopathy were found. Histopathological examination of the biopsies revealed an inflammatory infiltrate containing intramacrophage amastigotes compatible with Leishmania infection. In addition, Leishmania promastigotes were isolated successfully from the palatal biopsy and assigned the code MHOM/TH/2022/CULE6. Using internal transcribed spacer 1 polymerase chain reaction and sequence analysis, the causative parasite was identified as Leishmania martiniquensis. A definitive diagnosis of multiform leishmaniasis with disseminated cutaneous, mucocutaneous, and visceral involvement was established. The patient was administered intravenous amphotericin B 1 mg/kg/d for 2 weeks, followed by oral itraconazole 400 mg daily. At the 2-month follow-up, the cutaneous and mucosal lesions had improved significantly. To our knowledge, this is the first report of mucocutaneous involvement caused by L. martiniquensis in an immunocompromised patient with HIV/AIDS. In addition, we provide a literature review of leishmaniasis cases, reported formally in Thailand, resulting from this autochthonous parasite.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Humans; Leishmania; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Middle Aged; Thailand

We report here a case of disseminated Emergomyces pasteurianus infection from India in a patient with AIDS. The patient presented with weight loss, dyspnoea and multiple non-tender skin lesions over face, neck and chest over 3 months. The case was diagnosed by microscopy, histopathology of sample and isolation of fungus from skin lesion, breast nodule, bone marrow and sputum. The identification of the isolates was confirmed by sequencing internal transcribed spacer region of rDNA, beta-tubulin, actin and intein PRP8. The patient responded well to intravenous amphotericin B deoxycholate followed by itraconazole therapy.

Topics: Acquired Immunodeficiency Syndrome; Actins; Adult; Amphotericin B; Antifungal Agents; Deoxycholic Acid; DNA, Intergenic; DNA, Ribosomal; Drug Combinations; Female; Humans; India; Inteins; Itraconazole; Mycoses; Onygenales; Tubulin

Although antiretroviral therapy (ART) has greatly improved the prognosis of acquired immunodeficiency syndrome (AIDS) patients globally, opportunistic infections (OIs) are still common in Chinese AIDS patients, especially cryptococcosis.. We described here two Chinese AIDS patients with cryptococcal infections. Case one was a fifty-year-old male. At admission, he was conscious and oriented, with papulonodular and umbilicated skin lesions, some with ulceration and central necrosis resembling molluscum contagiosum. The overall impression reminded us of talaromycosis: we therefore initiated empirical treatment with amphotericin B, even though the case history of this patient did not support such a diagnosis. On the second day of infusion, the patient complained of intermittent headache, but the brain CT revealed no abnormalities. On the third day, a lumbar puncture was performed. The cerebral spinal fluid (CSF) was turbid, with slightly increased pressure. India ink staining was positive, but the cryptococcus antigen latex agglutination test (CrAgLAT: IMMY, USA) was negative. Two days later, the blood culture showed a growth of Cryptococcus neoformans, and the same result came from the skin culture. We added fluconazole to the patient's treatment, but unfortunately, he died three days later. Case two was a sixty-four-year-old female patient with mild fever, productive cough, dyspnea upon movement, and swelling in both lower limbs. The patient was empirically put on cotrimoxazole per os and moxifloxacin by infusion. A bronchofibroscopy was conducted with a fungal culture, showing growth of Cryptococcus laurentii colonies. Amphotericin B was started thereafter but discontinued three days later in favor of fluconazole 400 mg/d due to worsening renal function. The patient became afebrile after 72 h of treatment with considerable improvement of other comorbidities and was finally discharged with continuing oral antifungal therapy.. Our cases illustrate that cryptococcal disease is an important consideration when treating immunocompromised individuals such as AIDS patients. Life threatening meningitis or meningoencephalitis caused by C. neoformansmay still common in these populations and can vary greatly in clinical presentations, especially with regard to skin lesions. Pulmonary cryptococcosis caused by C. laurentii is rare, but should also be considered in certain contexts. Guidelines for its earlier diagnosis, treatment and prophylaxis are needed.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Amphotericin B; Antifungal Agents; Antigens, Fungal; China; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Humans; Male; Meningitis; Middle Aged; Opportunistic Infections; Treatment Outcome

Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths. Areas covered: Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotsericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent. Expert commentary: Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antigens, Fungal; Asymptomatic Diseases; Cost-Benefit Analysis; Cryptococcus neoformans; Developing Countries; Drug Administration Schedule; Fluconazole; Humans; Mass Screening; Meningitis, Cryptococcal; Sertraline

Disseminated histoplasmosis in South America is associated with AIDS in 70-90 % of cases. It is visceral and cutaneous, compromising the oral, pharynx, and laryngeal mucous membranes. The involvement of the nasal mucosa is unusual. Two patients with perforation of the nasal septum as the only sign of their disease were clinically and histopathologically diagnosed as leishmaniasis. The revision of the biopsies and the culture of nasal discharge secretions showed that the pathogens seen were not amastigotes but Histoplasma capsulatum. Other mycotic lesions were not detected, nor there was history of cutaneous leishmaniasis. The leishmanin skin test, available only for the male patient, was negative. The PCR and immunofluorescence antibody titers for Leishmania were negative in both patients. They were HIV positive; in the male, his CD4+ T cell count was 60/mm(3) and in the female 133/mm(3). The nasal ulcer was the only manifestation of histoplasmosis and the first of AIDS in both patients. The male patient recovered with amphotericin B and itraconazole treatment. The female has improved with itraconazole. Both patients received antiretroviral treatment. Nasal mucous membrane ulcers should include histoplasmosis among the differential diagnosis. In conclusion, two patients had perforation of their nasal septum as the only manifestation of histoplasmosis, a diagnosis confirmed by nasal mucosa biopsy and by culture of H. capsulatum, findings which demonstrated that both patients had AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Female; Histoplasma; Histoplasmosis; Humans; Itraconazole; Male; Nasal Septal Perforation; South America

Cryptococcal meningitis (CM) remains a major cause of morbidity and mortality among immunocompromised patients, especially in areas of high HIV prevalence, although it can also cause disease in the apparently immunocompetent. Improving the management of HIV-associated CM is important to ensure that patients can survive to benefit from increasing access to ART. In this review we focus on recent advances in prevention, diagnosis, and treatment of CM.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antihypertensive Agents; Developing Countries; Female; Fluconazole; Humans; Immunocompromised Host; Intracranial Hypertension; Male; Meningitis, Cryptococcal; Prevalence

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antigens, Fungal; Biopsy; Chronic Disease; Female; Histoplasma; Histoplasmosis; Humans; Lip Diseases; Mouth Mucosa; Staining and Labeling; Ulcer

Disseminated histoplasmosis is a disease with a high case-fatality rate, especially in patients with the acquired immunodeficiency syndrome (AIDS). The disease can occur in various sites, such as the lungs, eyes, oral cavity, larynx, nervous system, gastrointestinal tract and, more rarely, the nasal sinus region. It is a cosmopolitan mycosis with a high prevalence in Brazil. Nasal manifestation of the disease is rare, with only three cases reported in the literature, but it is part of the differential diagnosis for other granulomatous diseases, such as Wegener's granulomatosis, tegumentary leishmaniasis and nasal lymphoma. The authors of this study present a literature review and report a case of nasal histoplasmosis in a patient with AIDS. No record of such an aggressive presentation has been reported previously in the literature.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Female; Histoplasmosis; Humans; Injections, Intravenous; Nose Deformities, Acquired; Nose Diseases; Treatment Outcome

Two cases of Histoplasma meningitis are presented, illustrating the difficulty in diagnosis and treatment. The first case occurred in a patient with acquired immunodeficiency syndrome as a relapse of disseminated histoplasmosis and resolved after prolonged treatment and ongoing antiretroviral therapy. The second case occurred in a cardiac allograft recipient as meningitis and focal brain lesions that responded to liposomal amphotericin B, but the patient died shortly after therapy was completed. Unfortunately, there are no prospective studies addressing the diagnosis and management of patients with histoplasmosis of the central nervous system from which to provide evidence-based guidelines for care. In the absence of such data, an approach will be presented on the basis of our experience and opinions.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Amphotericin B; Antifungal Agents; Female; Fluconazole; Histoplasmosis; Humans; Immunocompromised Host; Male; Meningitis, Fungal; Mycological Typing Techniques; Sensitivity and Specificity

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Cryptococcosis; Humans; Male; Oral Ulcer; Palate; Scalp; Skin Diseases, Infectious

Immune reconstitution inflammatory syndromes (IRIS) in patients with AIDS are characterized by atypical manifestations of opportunistic pathogens in patients experiencing improvement in CD4 cell counts following receipt of highly active anti-retroviral therapy (HAART). We report four cases of IRIS due to Cryptococcus neoformans in three patients and review the literature of cryptococcal IRIS in AIDS (an additional 21 episodes). The IRIS presentation was lymphadenitis in all three patients; one patient also had meningeal IRIS. Combining our patients with the literature review revealed the following IRIS presentations: lymphadenitis (n=14), central nervous system (CNS) IRIS (n=10): meningitis in six and mass lesions in four, and pulmonary cavities (n=1). The median CD4 count of cases at the time of initial cryptococcal diagnosis and prior to the start of HAART was 25 cells/microl and the median HIV viral load was 439,053 copies/ml. At time of presentation of the IRIS, the median CD4 count had increased by 197 cells/microl. The median time from initial cryptococcal diagnosis and the start of HAART to the IRIS was 11 months (range 7 weeks to 3 years) and 7 months (range <2 weeks to 22 months), respectively. Patients with CNS IRIS tended to have shorter intervals from initiation of HAART to presentation compared to patients with lymphadenitis: median 3.5 months compared to 7 months. In 24 of 25 cases, the clinical manifestations of the IRIS resolved (range: days to months). Only four patients were given anti-inflammatory medications: corticosteroids in two and non-steroidal anti-inflammatory drugs in two, thus precluding assessment of efficacy. Patients with cryptococcal disease who initiate HAART are at risk for cryptococcal IRIS.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cryptococcus neoformans; Female; Fluconazole; Humans; Lymphadenitis; Male; Meningitis, Cryptococcal

The high frequency of oropharyngeal candidiasis in immunocompromised patients has led many institutions to develop protocols to guide the use of antifungal agents in the treatment of this opportunistic infection. However, few specific recommendations have been made for directing the management of oropharyngeal candidiasis in patients infected with HIV. To meet this need, a panel of experts representing a variety of disciplines met to formulate a consensus and devise a treatment strategy for clinical application. Among other recommendations, the algorithm calls for use of a topical agent for the treatment of initial and recurring oropharyngeal candidiasis in HIV-infected patients, provided there is no esophageal involvement, patients' CD4+ lymphocyte cell count is >50 cells/mm3, and they are currently receiving or expected to receive effective antiretroviral treatment. For episodes of oropharyngeal candidiasis with concurrent esophageal involvement or where patients have a CD4+ cell count of <50 cells/mm3, are not receiving or anticipating highly active antiretroviral therapy (HAART), and have a high viral load, the algorithm suggests a systemic oral azole as the more appropriate treatment choice. Acute treatment of all oropharyngeal candidiasis episodes is preferred. Chronic suppressive antifungal treatment is to be avoided in recognition of the potential for the development of drug-resistant infection.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; AIDS-Related Opportunistic Infections; Algorithms; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Candidiasis; Candidiasis, Oral; Clotrimazole; Dosage Forms; Esophagitis; Humans; Imidazoles; Viral Load

The deep mycoses are uncommon infections, usually acquired from the inhalation or ingestion of fungal spores, sometimes from the soil in areas of endemicity, such as in the Americas and south-east Asia, or from decaying vegetable matter. They are also seen in immunocompromised persons and, increasingly, in HIV-infected persons. Respiratory involvement is frequent, with granuloma formation, and mucocutaneous involvement may be seen. Oral lesions of the deep mycoses are typically chronic but non-specific, though nodular or ulcerative appearances are common. Person-to-person transmission is rare. In HIV disease, the most common orofacial involvement of deep mycoses has been in histoplasmosis, cryptococcosis, aspergillosis and zygomycosis. Diagnosis is usually confirmed by lesional biopsy although culture may also be valuable. Treatment is with amphotericin or an azole.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Azoles; Cryptococcosis; Female; Histoplasmosis; HIV Infections; Humans; Lung Diseases, Fungal; Male; Middle Aged; Mouth Diseases; Mucormycosis; Mycoses; Sinusitis

The epidemiological, clinical and biological features of associated visceral leishmaniasis/human immunodeficiency virus infection are examined on the basis of a literature review of 239 published cases. The co-infection is principally located in Southern Europe, mainly in Spain, France and Italy. The study of restricted cohorts of patients showed that co-infection occurs in about 2 to 7% of AIDS patients. A part from the classical symptoms of visceral leishmaniasis, atypical or unusual symptoms (cutaneous, digestive or pulmonary) are described in about 10% of the cases. The parasite is occasionally found in blood and normal skin. Visceral leishmaniasis is frequently associated with other opportunistic diseases. Nine different zymodemes of Leishmania infantum, including two new ones, have been isolated from co-infected patients. There have also been a few cases of tegumentary leishmaniasis associated with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antimony; Female; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Leishmaniasis, Visceral; Male

From 1983 to 1991 only isolated cases of aspergillosis in AIDS patients were reported; since 1991, an increasing number of cases have been reported suggesting a recent emergence of this fungal infection. Aspergillosis occurs about 10 to 25 months after AIDS diagnosis in patients with CD4 below 50/mm3. Neutropenia and/or steroid therapy, which are known as predisposing factors in aspergillosis, are noticed in about one half of the patients. Previous pulmonary infection, especially pneumocystosis, are very common. Clinical signs are typical of an invasive pulmonary aspergillosis: constant fever, cough, dyspnea, frequent thoracic pains and haemoptysis. Radiologic signs frequently indicate an interstitial infiltration. Nodular and cavitating lesions, pleural effusions, thoracic lymph node enlargement are often present. Diagnosis procedures are realised on bronchoalveolar lavage by direct examination, culture and antigen detection. Aspergillus fumigatus is the most usually species detected. Post-mortem diagnosis is frequent. Invasive bronchial aspergillosis, localised infections (aspergilloma, otitis, sinusitis) or disseminated infections (nervous system, heart, kidney, lymph nodes, thyroid) are also described. Prognosis is poor even with treatment (amphotericin B or itraconazole). An earlier diagnosis and treatment of the bronchial colonization could probably improve this prognosis.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Humans; Itraconazole; Lung Diseases, Fungal

In patients with AIDS with cryptococcosis, prompt diagnosis is essential. Poor results with conventional therapy (amphotericin-5FC) have led to exploration of the azoles. Both fluconazole and itraconazole have given good short-term results with less toxicity. However, cure is achieved far less often than in other compromised hosts. Fluconazole is also useful to prevent relapse after successful initial amphotericin therapy, particularly from genitourinary foci. In both histoplasmosis and aspergillosis, itraconazole has produced impressive therapeutic results, and in histoplasmosis, secondary prophylaxis as well. In coccidioidomycosis results thus far have not been better than conventional amphotericin therapy, especially in initial treatment.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Coccidioidomycosis; Cryptococcosis; Drug Therapy, Combination; Fluconazole; Histoplasmosis; Humans; Itraconazole; Meningitis, Cryptococcal

Coccidioidomycosis is usually acquired by inhalation of Coccidioides immitis in certain areas of the Western Hemisphere. However, the disease may occur far away in individuals who have visited or lived in, then departed from, the endemic areas. The disease which can affect normal and immunocompromised individuals, has many manifestations resembling those of many diseases. The diagnosis is usually not difficult and can be accomplished by histopathological, cultural, and serological methods. Therapy can be surgical and/or medical. The latter can make use of parenteral amphotericin B and its lipid-complex, or the azoles ketoconazole, fluconazole, and itraconazole. However coccidioidal meningitis, coccidioidal arthritis, and acute coccidioidal respiratory insufficiency pose significant challenges to the available therapy.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Coccidioidomycosis; Dermatomycoses; Drug Interactions; Drug Therapy, Combination; Humans; Surgical Procedures, Operative

Histoplasmosis is an infection caused by the dimorphic fungus, Histoplasma capsulatum. The initial site of entry is usually the lung, but dissemination to skin occurs in some patients, particularly those with human immunodeficiency virus (HIV) infection in whom it is part of a widespread infection. The organisms have to be distinguished from other yeasts in skin such as Cryptococcus neoformans and small forms of Blastomyces dermatitidis.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Dermatomycoses; Histoplasmosis; Humans; Lung Diseases, Fungal

The treatment of infectious complications in the cancer patient has evolved as a consequence of the developments in cancer chemotherapy, which significantly impair immune function. Broad-spectrum, single-agent antibiotics have replaced more cumbersome multidrug regimens for empiric coverage of fever and neutropenia in many institutions. The use of new, potent oral antibiotics may be a next step toward further simplifications. Several new antivirals have come into clinical use in the past decade, and reports of viral resistance to the standard agent, acyclovir, have come forth. Increasing experience with new (and older) antifungal and antiparasitic agents has given a better understanding of the use of these drugs for both prophylaxis and treatment. This overview includes a critical appraisal of the attributes and limitations of current antibiotics, antivirals, antifungals, and antiparasitic agents for the immunocompromised host.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Azoles; Aztreonam; Cephalosporins; Fluoroquinolones; Foscarnet; Ganciclovir; Humans; Imipenem; Immunocompromised Host; Infections; Neoplasms; Pneumonia, Pneumocystis; Vancomycin

Systemic fungal infections are an important cause of morbidity and mortality among immunocompromised patients. New antifungal agents, such as triazoles, are now available, and the place of in vitro tests has to be discussed. It has been shown that interlaboratory reproducibility of in vitro susceptibility tests against fungi was low, due to the lack of standardization. Recently, the NCCLS defined conditions permitting a good interlaboratory reproducibility. However, the predictive value of in vitro susceptibility tests on the therapeutic outcome remain to be demonstrated, and is now under investigation. At the present time, susceptibility testing can be useful: in patients treated by amphotericin B for a severe fungal infection and who do not improve under therapy; to detect resistance to 5-fluorocytosine; to compare the sensitivity to triazoles before and after treatment, in case of therapeutic failure. Serum levels monitoring is useful to prevent the toxicity due to 5-fluorocytosine and to control the digestive absorption of triazoles, especially the lipophilic compound itraconazole.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; In Vitro Techniques; Itraconazole; Ketoconazole; Opportunistic Infections

Treatment of cryptococcal meningitis in patients with AIDS with amphotericin B plus flucytosine is associated with a failure rate of 20%-30%. In the absence of chronic suppressive therapy, 40%-60% of patients develop recurrent disease. Recent comparative studies have evaluated fluconazole, a new triazole antifungal agent. In primary therapy, fluconazole is associated with response rates of 35%-60%, which are equivalent to those seen with amphotericin B alone. However, a smaller study suggested that amphotericin B plus flucytosine was superior to fluconazole alone. Both studies identified risk factors associated with a poor outcome; these factors include lethargy or obtundation at presentation, a high titer of cryptococcal antigen titer in the cerebrospinal fluid, and a low leukocyte count in the cerebrospinal fluid. Fluconazole is highly effective in suppressing relapses of cryptococcal meningitis. Itraconazole has been investigated less extensively in the treatment of cryptococcosis but offers promise. Future studies need to address alternative approaches to the management of acute cryptococcal disease and primary prophylaxis for cryptococcal infection in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Animals; Fluconazole; Flucytosine; Humans; Meningitis, Cryptococcal

Cryptococcosis is currently the most common life threatening mycoses found in patients with the acquired immunodeficiency syndrome (AIDS). Extrapulmonary involvement is most frequently seen, especially in the central nervous system and skin. Clinical findings are non-specific, even in patients with meningitis. Threshold for diagnosis of this infection should be low, with serum cryptococcal antigens, blood, urine and sputum cultures for Cryptococcus neoformans performed in febrile AIDS patients. Lumbar puncture should also be performed if unexplained headaches are included in a patient's complaints. There is currently no consensus for the most appropriate treatment strategy and the role of oral azoles versus amphotericin B or amphotericin B with flucytosine remains a serious question in need of further controlled studies. Patients eligible for multicentered trials should be encouraged to participate. Therapy for others should be individualized. This review will address some of these issues.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Fluconazole; Flucytosine; Humans

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Dermatomycoses; Diagnosis, Differential; Fluconazole; Humans; Injections, Spinal; Meningitis; Molluscum Contagiosum; Opportunistic Infections; Prognosis

Cryptococcosis is the most common life-threatening mycosis with AIDS. The combination therapy based on amphotericin B and flucytosine is furthermore the therapy of first choice, even after introduction of fluconazole. With a therapy maintained over a period of 6 weeks the combination is nearly always successful; a shorter treatment period leads to minor treatment success. Since no elimination of the pathogen is possible in cryptococcosis with AIDS a permanent relapse prevention is necessary. In this prevention strategy fluconazole is highly effective and at present the drug of first choice; it is as effective as amphotericin B. An additional advantage is the possibility of oral application.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans

Human immunodeficiency virus (HIV) carrier patients experience several secondary effects with drugs, being mainly skin reactions and myelosuppression. Owing to this, close observation of patients is necessary with regard to therapeutic and prophylactic schedules. In this paper, we describe the secondary effects of zidovudine in 60 patients of groups III and IV from CDC. The main toxicity was found in bone marrow; with anemia in 50% and leukopenia in 53% of patients. Finally, the more frequent secondary effects of therapy for opportunist infections are analysed. A guide for identifying the drugs' secondary effects is also included, based on our experience and on a wide range of literature reviews.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antitubercular Agents; Drug-Related Side Effects and Adverse Reactions; Ganciclovir; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Product Surveillance, Postmarketing; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Amphotericin B (Fungizone) remains the cornerstone of antifungal therapy because of its broad-spectrum fungicidal activity and rapid onset of action. Ketoconazole (Nizoral) and the new triazoles are welcome additions to the therapeutic armamentarium but do not replace amphotericin B. Adverse side effects of amphotericin B treatment are usually manageable and often preventable. Careful attention to detail reduces immediate toxicity and allows completion of the desired therapeutic course without an undue risk of permanent nephrotoxicity.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Humans; Ketoconazole; Mycoses; Risk Factors

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Male; Mycoses; Urologic Diseases

Histoplasmosis is a serious opportunistic infection in patients with AIDS, often representing the first manifestation of the syndrome. Most infections occurring within the endemic region are caused by exogenous exposure, while those occurring in nonendemic areas may represent endogenous reactivation of latent foci of infection or exogenous exposure to microfoci located within those nonendemic regions. However, prospective investigations are needed to prove the mode of acquisition. The infection usually begins in the lungs even though the chest roentgenogram may be normal. Clinical findings are nonspecific; most patients present with symptoms of fever and weight loss of at least 1 month's duration. When untreated, many cases eventually develop severe clinical manifestations resembling septicemia. Chest roentgenograms, when abnormal, show interstitial or reticulonodular infiltrates. Many cases have been initially misdiagnosed as disseminated mycobacterial infection or Pneumocystis carinii pneumonia. Patients are often concurrently infected with other opportunistic pathogens, supporting the need for a careful search for co-infections. Useful diagnostic tests include serologic tests for anti-H. capsulatum antibodies and HPA, silver stains of tissue sections or body fluids, and cultures using fungal media from blood, bone marrow, bronchoalveolar lavage fluid, and other tissues or body fluids suspected to be infected on clinical grounds. Treatment with amphotericin B is highly effective, reversing the clinical manifestations of infection in at least 80% of cases. However, nearly all patients relapse within 1 year after completing courses of amphotericin B of 35 mg/kg or more, supporting the use of maintenance treatment to prevent recurrence. Relapse rates are lower (9 to 19%) in patients receiving maintenance therapy with amphotericin B given at doses of about 50 mg weekly or biweekly than with ketoconazole (50-60%), but controlled trials comparing different maintenance regimens have not been conducted. Until results of such trials become available, our current approach is to administer an induction phase of 15 mg/kg of amphotericin B given over 4 to 6 weeks, followed by maintenance therapy with 50 to 100 mg of amphotericin B given once or twice weekly, or biweekly. If results of a prospective National Institutes of Allergy and Infectious Disease study of itraconazole maintenance therapy document its effectiveness, alternatives to amphotericin B may be reasonab

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Diagnosis, Differential; Histoplasmosis; Humans; Pneumonia, Pneumocystis

Cryptococcosis is the most common, deep-seated fungal infection in AIDS patients, and cryptococcal meningitis is the most frequently observed syndrome. AIDS patients with cryptococcal meningitis usually have an indolent presentation and nonspecific findings on physical examination. Routine laboratory tests are of little assistance in diagnosing cryptococcal meningitis. Cerebrospinal fluid (CSF) white blood cell counts tend to be low, and glucose and protein levels are nonspecific. Serum cryptococcal antigen (CRAG) is a sensitive test for cryptococcal meningitis, and CSF CRAG is usually also positive. Definitive diagnosis is made by culture of the CSF. Therapy of cryptococcal meningitis is changing to antifungal agents that are easy to administer as outpatient therapy. Amphotericin B continues to be the primary antifungal used in initial treatment of cryptococcal meningitis; addition of flucytosine is of no benefit. Recent data suggest oral fluconazole is effective as primary therapy, and may be superior to amphotericin B as maintenance therapy. Maintenance therapy decreases the incidence of relapse and increases survival.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Humans; Meningitis; Recurrence

Cryptococcus neoformans has become an increasingly important pathogen. Cryptococcosis is an important cause of morbidity and mortality in immunocompromised hosts and is the second most common fungal infection complicating AIDS. In recent years, research has focused on the host defenses against Cryptococcus and has led to an improved understanding of the capsular virulence of the organism, the mechanisms of T-cell defenses, and the role of phagocytic cells in the fungistasis and killing of cryptocci. Amphotericin B with or without flucytosine has clearly improved treatment of cryptococcosis, but therapy is associated with significant toxicity. Current investigation is focused on the triazoles, which may offer improved therapy for cryptococcosis. In this report, we review recent developments in the understanding of the host defenses against Cryptococcocus and discuss current recommendations for the management of cryptococcosis.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Humans; Immune Tolerance; Prognosis; Triazoles; Virulence

C. albicans and its related species have become major nosocomial causes of morbidity and mortality in the immunocompromised and in other severely ill patients. Diagnosis of the severe forms of the disease remains difficult and depends on the basis of a composite of clinical findings. Treatment for most forms of severe Candida infections remains amphotericin B despite its toxicities. Until more effective prevention of the disease becomes feasible, Candida infections are likely to increase in frequency as major iatrogenic problems.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Candidiasis; Humans; Immune Tolerance; Opportunistic Infections

Cutaneous cryptococcosis occurs in 10 to 15% of patients with cryptococcosis. Because the cutaneous crytpococcosis may precede clinical signs of central nervous system disease, early recognition may lead to more successful outcomes. This article reviews the mycology, epidemiology, pathology, clinical manifestations, and treatment of this disease, focusing primarily on the cutaneous aspects.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Biopsy; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Drug Therapy, Combination; Flucytosine; Humans; Immune Tolerance

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Histoplasmosis; Humans; Immune Tolerance; Immunity, Cellular; Mycoses; Opportunistic Infections

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antimony; Antiviral Agents; Humans; Oligopeptides; Peptide T; Suramin; Thymidine; Tungsten; Tungsten Compounds; Zidovudine

Systemic mycosis due to Penicillium marneffei is described in a man infected with human immunodeficiency virus and who had travelled in S.W. China. He responded completely to treatment with amphotericin B and a prolonged course of ketoconazole. Problems of diagnosis are discussed and all previously reported cases reviewed.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Humans; Ketoconazole; Male; Middle Aged; Mycoses; Penicillium

Systemic fungal infections are life-threatening diseases that are occurring with increasing frequency, especially in immunocompromised patients. Advances in the treatment of systemic fungal infections have been achieved through better understanding of two classic antifungal drugs, amphotericin B and flucytosine, and through the recent development of several antifungal azole derivatives. The purpose of this paper is to review the recent advances in pharmacology, toxicology, formulation and clinical trials of antifungal agents for the treatment of systemic mycoses.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Drug Resistance, Microbial; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Itraconazole; Ketoconazole; Miconazole; Mycoses; Triazoles

The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken.. In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio. A particular dose was not tested in Stage 2 if there were significant predetermined safety or efficacy concerns. In Stage-2, the 1200mg dose was excluded per protocol because of increased mortality, and participants were randomised to 1600mg, 2000mg FCZ or AMB in a 1:1:1 ratio.. One hundred and sixty eight participants were enrolled with 48, 50, and 48 in the AMB, 1600mg and 2000mg cohorts. The Kaplan Meier proportion for mortality (90% CI) at 10 and 24 weeks for AMB was 17% (10, 29) and 24% (15, 37), compared to 20% (12, 32) and 30% (20, 43) for 1600mg, and 33% (23, 46) and 38% (27, 51) for 2000mg/day FCZ. With the exception of a higher incidence of gastrointestinal side effects in the 2000mg cohort, both induction doses of FCZ were safe and well tolerated. There were no life-threatening changes in electrocardiogram QTc which were similar across all doses of FCZ and AMB. The median (IQR) change in log10 cryptoccal colony forming units (CFU) from week 0 to week 2 was -8(-4.1,-1.9) for AMB; -2.5(-4.0, -1.4) for 1600mg FCZ and -8 (-3.2, -1.0) for 2000mg FCZ. The proportion (90% CI) CSF CM negative at 10 weeks was 81%(71,90) for AMB; 56%(45,69) for 1600mg FCZ and 60%(49,73) for 2000mg FCZ.. Induction phase weight and renal-adjusted doses of 1600mg and 2000mg/day FCZ for CM were safe and well tolerated except for increased GI side effects in the 2000mg/day dose, and had similar times to achieve CSF sterilization, but took significantly longer than AMB. The WHO recommended 1200mg FCZ was associated with a high mortality. While not statistically significant, mortality was numerically lower in the AMB compared to 1600mg and 2000mg FCZ These data make a case for a phase 3 study of higher doses of FZC.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal; Treatment Outcome

Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens.. Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14.. A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82).. One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

Topics: Acquired Immunodeficiency Syndrome; Antifungal Agents; Drug-Related Side Effects and Adverse Reactions; Histoplasmosis; HIV; Humans; Prospective Studies

Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome-related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered.. We assessed survival at 26 weeks among 177 human immunodeficiency virus-infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole.. The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P=0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P=0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P=0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P=0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups.. Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. (Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152.).

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Antifungal Agents; Cause of Death; Cerebrospinal Fluid Otorrhea; Drug Administration Schedule; Female; Humans; Leukocyte Count; Male; Meningitis, Cryptococcal; South Africa; Survival Analysis; Uganda

Cryptococcal meningitis in Africa is associated with up to 70% mortality at 3 months and 500 000 deaths annually. We examined strategies to improve on fluconazole (FLU) monotherapy: addition of flucytosine (5-FC) and/or addition of short-course amphotericin B (AmB).. In step 1, previously reported, patients were randomized to receive FLU 1200 mg per day with or without 5-FC 100 mg/kg per day for 14 days. In step 2, 43 patients were similarly randomized, with addition of AmB 1 mg/kg per day for 7 days to both arms. After 2 weeks, patients received FLU monotherapy and were followed to 10 weeks. The primary endpoint was rate of clearance of infection (early fungicidal activity, EFA). Secondary endpoints related to safety and mortality.. Forty patients (25% with Glasgow Coma Scale <15) were analyzed. EFA for the triple combination arm was greater than that for AmB-FLU: -0.50 ± 0.15 log CFU/day vs. -0.38 ± 0.19 log colony forming units per day (P=0.03); and greater than that for step 1 with FLU-5-FC (-0.28 ± 0.17) or FLU alone (-0.11 ± 0.09). Combined analysis across steps revealed that addition of 5-FC and AmB had significant, independent additive effects on EFA, with trends toward fewer early deaths with addition of 5-FC (4/41 vs. 11/39, P = 0.05) and fewer deaths overall with addition of AmB (13/39 vs. 20/40, P = 0.1).. Addition of 5-FC and short-course AmB to high-dose FLU significantly enhanced EFA and may be associated with favorable trends in survival. Both these strategies should be tested in a larger phase III study.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Humans; Malawi; Male; Meningitis, Cryptococcal; Middle Aged; Treatment Outcome; Young Adult

Clearance of Histoplasma antigen has been used as a marker for response to treatment of progressive disseminated histoplasmosis (PDH) in patients with AIDS. Advancements in Histoplasma antigen detection permit accurate quantification of antigen concentration. We compared the clearance of antigenemia and antigenuria during effective treatment of PDH. Urine and serum specimens were serially collected from patients with AIDS who were successfully treated for PDH as part of two prospective clinical trials. Samples were stored frozen until they were tested in the quantitative Histoplasma antigen enzyme immunoassay. The kinetics of antigen clearance during the first 12 weeks of therapy were assessed in urine and serum during treatment with liposomal or deoxycholate amphotericin B followed by itraconazole and, in a separate analysis, in patients receiving only itraconazole. Latent class growth analysis was performed to define patterns of antigen clearance over time. In patients receiving amphotericin B, antigen levels declined the most during the first 2 weeks of treatment and antigenemia decreased more rapidly than antigenuria (5.90 ng/ml per week versus 4.21 ng/ml per week, respectively; P = 0.09). Mean reductions of antigen levels from baseline at weeks 2 and 12 were greater in sera than in urine: 11.26 ng/ml versus 7.65 ng/ml (P = 0.0948) and 18.52 ng/ml versus 14.64 ng/ml (P = 0.0440), respectively. In patients who received itraconazole alone, most of the decline in antigenuria occurred later during treatment and was overall slower than that seen with amphotericin B (P < 0.0001). Results of latent class growth modeling showed two distinct trajectories for each parameter. With effective therapy, Histoplasma antigenemia decreases more rapidly than antigenuria, providing a more sensitive early laboratory marker for response to treatment. Antigenuria declines earlier with amphotericin B than with itraconazole.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Antigens, Fungal; Drug Monitoring; Histoplasmosis; Humans; Immunoenzyme Techniques; Itraconazole

Amphotericin B treatment in cryptococcosis requires daily hospital visits or admission. Its toxicities and hospital costs have been concerned. Short course amphotericin B regimen warrants to be evaluated.. To compare the safety and efficacy of one-week (AmB1) with two-week (AmB2) amphotericin B both followed by fluconazole.. 57 AIDS with cryptococcal meningitis were randomly assigned to either AmB1 or AmB2. Microbiological and clinical clearances were the outcomes of the study.. The treatment success at 6 weeks was 63.3% in AmB1 and 70.4% in AmB2 (p = 0.574). Clinical assessment at week 10 and renal toxicities were not significantly different between both regimens. Mortality rate was 14% however, 75% of deaths were in AmB2.. AmB1 was comparably effective and safe as the standard AmB2 regimen in the treatment of AIDS related cryptococcal meningitis. It can be an alternative regimen to lower hospital based care and improve cost effective for source limiting health care centers.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluconazole; Humans; Male; Meningitis, Cryptococcal; Prospective Studies; Thailand; Time Factors

To evaluate the safety, tolerance and pharmacokinetics of a new formulation of amphotericin B (AmB; CAS 1397-89-3) 18 AIDS patients treated for different kinds of mycoses were studied: oropharingeal and/or esophageal azole-resistant candidiasis (9), CNS cryptococcosis (7) or aspergillosis (2). Amphotericin B daily dose was infused in 100 ml of a lipid emulsion. The patients aged from 26 to 54 years with body weight ranging from 42 to 89 kg. Blood samples were collected at fixed intervals and plasma stored at -20 degrees C until tested by a specific HPLC assay. The individual kinetic analysis of plasma drug levels was performed by a two-compartment open model. The data were analyzed using P-Pharm, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The effect of a variety of demographic factors on clearance and volume of distribution was investigated. The clearance and the apparent volume of distribution were, respectively, (mean +/- SD): 0.037 +/- 0.015 l/h/kg and 0.45 +/- 0.32 l/kg. The interindividual variability in AmB clearance and volume of distribution was modelled with proportional error with an estimated coefficient of variation of 40.6% and 70.9%, respectively. Clinical and biological tolerance was very good and no patient experience infusion-related adverse effects or hematologic and hepatic toxicity; a moderate renal failure occurred in only one patient.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Chromatography, High Pressure Liquid; Drug Delivery Systems; Female; Humans; Infusions, Intravenous; Lipids; Male; Middle Aged; Mycoses

To determine the safety and efficacy of liposomal amphotericin B (AmBisome) in the primary treatment of AIDS-associated cryptococcosis.. A Phase II, multicentre, European, non-comparative, open study to assess the use of AmBisome in 23 patients (26 enrolments) with cryptococcosis. Dose requirements, mycological response and toxicity were documented.. Hospital-based HIV units.. Twenty-three HIV-1-seropositive patients.. Drug toxicity, assessed in 25 enrolments, was well-tolerated with little renal, hepatic or haematological toxicity. Eighteen out of 23 (78%) enrolments responded clinically. Nineteen enrolments had cryptococcal meningitis: sterilization of spinal fluid was achieved in 12 out of the 18 (67%) who were mycologically evaluable. Fourteen out of the 19 (74%) responded clinically.. AmBisome is well-tolerated and may be an effective formulation in the treatment of cryptococcosis.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Body Fluids; Cryptococcosis; Cryptococcus neoformans; Drug Carriers; HIV-1; Humans; Leukocyte Count; Life Tables; Liposomes; Male; Meningitis, Cryptococcal; Middle Aged; Survival Analysis

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Anemia; Erythropoietin; Histoplasmosis; Humans; Recombinant Proteins; Zidovudine

We conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment.. The trial was a prospective, randomized, and non-blinded study.. The study was performed at an academic centre for AIDS, Amsterdam, The Netherlands.. Twenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis, randomized between 5 February 1987 and 1 January 1990, were included for analysis.. Oral itraconazole (200 mg twice daily), versus amphotericin B (0.3 mg/kg daily) intravenously plus oral flucytosine (150 mg/kg daily) was administered for 6 weeks followed by maintenance therapy with oral itraconazole (200 mg daily) to all patients.. Outcome measures were a complete or partial response, recrudescence and relapse.. A complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine (P = 0.009). A partial response was observed in seven out of the 14 patients assigned to itraconazole. During maintenance therapy, recrudescence (n = 6) or relapse (n = 1) occurred in seven out of the 12 patients initially assigned to itraconazole, whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine (P = 0.22); recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks (P = 0.003).. Itraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Flucytosine; Humans; Itraconazole; Ketoconazole; Male; Meningitis, Cryptococcal; Middle Aged; Opportunistic Infections; Prospective Studies; Survival Analysis

After primary treatment for cryptococcal meningitis, patients with the acquired immunodeficiency syndrome (AIDS) require some form of continued suppressive therapy to prevent relapse.. We conducted a multicenter, randomized trial that compared fluconazole (200 mg per day given orally) with amphotericin B (1 mg per kilogram of body weight per week given intravenously) in patients with AIDS who had completed primary therapy for cryptococcal meningitis with amphotericin B (greater than or equal to 15 mg per kilogram). To be eligible, patients had to have at least two negative cultures of cerebrospinal fluid immediately before randomization. The primary end point was relapse of cryptococcal disease as confirmed by biopsy or culture.. Of 218 patients initially enrolled, 119 were assigned to fluconazole and 99 to amphotericin B. Twenty-three patients were found not to have met the entry criteria; six other patients assigned to amphotericin B did not receive it and were lost to follow-up. Of the remaining 189 patients, after a median follow-up of 286 days 14 of 78 receiving amphotericin B (18 percent) and 2 of 111 assigned to fluconazole (2 percent) had relapses of symptomatic cryptococcal disease (P less than 0.001 by Fisher's exact test). There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001). Serious drug-related toxicity was more frequent in the amphotericin B group (P = 0.02), as were bacterial infections (P = 0.004) and bacteremia (P = 0.002).. Fluconazole taken by mouth is superior to weekly intravenous therapy with amphotericin B to prevent relapse in patients with AIDS-associated cryptococcal meningitis after primary treatment with amphotericin B.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Amphotericin B; Female; Fluconazole; Follow-Up Studies; Humans; Injections, Intravenous; Male; Meningitis, Cryptococcal; Middle Aged; Multivariate Analysis; Recurrence

Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease.. In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period.. Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001).. Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Aged; Amphotericin B; Female; Fluconazole; Humans; Injections, Intravenous; Male; Meningitis, Cryptococcal; Middle Aged; Random Allocation; Treatment Outcome

To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis.. Patients were randomly assigned to oral fluconazole, 400 mg/d, for 10 weeks or to amphotericin B, 0.7 mg/kg body weight daily for 1 week, then three times weekly for 9 weeks combined with flucytosine, 150 mg/kg d, in four divided doses.. Los Angeles County-University of Southern California Medical Center.. Between 15 February and 7 December 1988, 42 patients had evidence of their first episode of cryptococcal meningitis, of whom 21 participated in the trial. All patients enrolled were men with the acquired immunodeficiency syndrome (AIDS) except one woman who was receiving prednisone therapy and was excluded from the final analysis.. Of 14 patients with AIDS assigned to fluconazole, 8 (57%; 95% CI, 29% to 82%) failed; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy (0%; CI, 0% to 46%) (Fisher exact test, P = 0.04). The mean duration of positive cerebrospinal fluid cultures was 40.6 +/- 5.4 days in patients receiving fluconazole and 15.6 +/- 6.6 days in patients receiving amphotericin B plus flucytosine (Mann-Whitney test, P = 0.02). Overall, 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died (Fisher exact test, P = 0.27).. Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Male; Meningitis; Opportunistic Infections; Prospective Studies; Randomized Controlled Trials as Topic

Because of the increasing numbers of patients with acquired immunodeficiency syndrome (AIDS) who will require treatment for cryptococcosis and because of the problems associated with long-term administration of intravenous amphotericin B, an alternative therapeutic approach in the form of an efficacious and easily administered oral antifungal drug would be of great benefit. Fluconazole, a new triazole antifungal agent, represents such an alternative. We therefore conducted an open, non-randomized trial of oral fluconazole as maintenance suppressive therapy of disseminated cryptococcosis in patients with AIDS.. Twenty patients with AIDS, 19 of whom had cryptococcal meningitis, were studied. Patients were followed for up to 21 months. All patients received amphotericin B as primary therapy, from 20 to 257 days prior to entry (500 to 5,080 mg total dose). Eight also received flucytosine. After administration of amphotericin B for acute disseminated cryptococcosis, and prior to initiation of fluconazole therapy, Cryptococcus neoformans was isolated from the cerebrospinal fluid (CSF) in two patients and from the blood in one patient. Fluconazole was given once daily, in doses of 50 to 200 mg/day.. Following initiation of fluconazole, results of CSF and blood cultures continued to be negative, except for the CSF culture in one patient who had a relapse in the 32nd week of therapy. Fluconazole therapy has been successfully continued in nine patients, for a median of 11 months (nine to 21 months). Seven patients died; five had no evidence of active cryptococcosis at the time of death. Two patients had a relapse, although the CSF culture showed growth of the fungus in only one patient. One patient was lost to follow-up after five months of therapy and one was unevaluable. Fluconazole had to be discontinued in only one patient in whom thrombocytopenia developed, and then resolved when the drug was stopped.. We conclude that oral fluconazole represents a significant advance in the management of cryptococcal meningitis and should be useful in the long-term suppressive therapy of this opportunistic infection in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Antigens, Fungal; Clinical Trials as Topic; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Humans; Male; Triazoles

The simultaneous occurrence of cerebral toxoplasmosis and cryptococcosis is rare. The infections continue to be treated with sulfadiazine and amphotericin-B-based regimens (preferred therapy), respectively. Both these drugs are linked to some serious adverse drug reactions (ADRs). We report such a unique instance of both; the CNS co-infections and adverse drug reactions to the preferred therapy.. A 44-year-old Asian-Indian female was diagnosed with cerebral toxoplasmosis, impending cryptococcal meningoencephalitis, and acquired immune deficiency syndrome (AIDS). The preferred therapy of opportunistic CNS co-infections commenced. Within a week, she had an occurrence of fall in hemoglobin concentrations (11.3 g/dL to 5.6 g/dL; grade IV), reticulocytosis (1% to 3.2%), and indirect hyperbilirubinemia (0.5 mg/dL to 2.8 mg/dL; grade IV) after sulfadiazine administration. The drug was discontinued and the patient was treated with hematocrit transfusions. After amphotericin-B deoxycholate (AmBd) administration, the patient developed hypokalemia (serum potassium; 4.5 mmol/L to 2.7 mmol/L) and increased serum creatinine (1.0 to 2.2 mg/dL; stage-I) levels. Hence, AmBd was discontinued and potassium correction was given. The patient got diagnosed with sulfadiazine induced hemolytic anemia and AmBd induced acute renal failure. He was switched to alternative therapy regimens for the treatment of cerebral toxoplasmosis and cryptococcosis. Radiological investigations were followed up to confirm the clinical outcomes of alternative therapy. Complete recovery from the ADRs and opportunistic infections was observed.. The preferred therapy regimens for toxoplasmosis and cryptococcosis are accompanied by potential adverse drug reactions, thus continuous monitoring is vital, especially in the initial phases of therapy. Discontinuation of the treatment should be the preliminary intervention in the management. Having said that, alternative therapy regimens had an optimal clinical response in the present case.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Coinfection; Cryptococcosis; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Potassium; Sulfadiazine; Toxoplasmosis, Cerebral

Cryptococcal meningitis (CM) is a life-threatening disease that primarily affects patients with human immunodeficiency virus (HIV). Antifungal therapy with antiretroviral treatment (ART) usually leads to the clinical remission of CM; however, in some cases, these treatments exacerbate intracranial inflammation because of paradoxical inflammatory reaction or immune reconstitution inflammatory syndrome (IRIS). Here we report two CM cases that presented atypical clinical courses attributed to paradoxical inflammatory reactions. The first case was a 43-year-old man with headache and vertigo diagnosed with CM and HIV. The patient's CM not only was refractory to the antifungal combination therapy of liposomal amphotericin B (L-AMB) and fluconazole (FLCZ) but suddenly worsened because of a paradoxical inflammatory reaction after 18 days of treatment. He passed away from brain herniation on day 23. The second case was a 43-year-old man diagnosed with CM and HIV. After receiving antifungal therapy and ART, the patient's status was stable for more than 3 years with undetectable HIV-RNA. He suddenly presented with brain inflammation and was diagnosed with IRIS due to CM (CM-IRIS). His brain lesions were migratory and refractory to various antifungal therapies such as L-AMB, FLCZ, flucytosine, and intrathecal amphotericin B. Although the cryptococcal antigen in the patient's cerebrospinal fluid gradually diminished after continuous antifungal therapies, his cognitive function declined, and right hemiparesis persisted. These two cases of CM presented atypical clinical courses, presumably because of paradoxical inflammatory reactions. It should be noted that the onset of CM-IRIS may not necessarily depend on the timing of ART initiation.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antifungal Agents; Fluconazole; HIV; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Inflammation; Male; Meningitis, Cryptococcal

Disseminated talaromycosis caused by Talaromyces marneffei is a life-threatening opportunistic infection. Although amphotericin B deoxycholate (dAmB) remains the first-line induction treatment, voriconazole can also be used. However, no clinical trials have compared dAmB and voriconazole in the administration of talaromycosis. We retrospectively evaluated the efficacy and safety of voriconazole or dAmB as induction therapy for talaromycosis in HIV-infected patients. We enrolled HIV-infected patients with a confirmed Talaromyces marneffei infection who received intravenous dAmB (0.6 to 0.7 mg/kg daily for 2 weeks) or voriconazole (6 mg/kg every 12 h on day 1 and 4 mg/kg every 12 h afterward) as induction therapy, followed by oral itraconazole as consolidation and maintenance therapy. Drug efficacy was evaluated based on response rate. Drug safety was evaluated based on the occurrence of adverse events. In total, 58 patients who received voriconazole and 82 who received dAmB were enrolled from two hospitals. The voriconazole and dAmB treatment groups had similar response rates at the primary and follow-up efficacy evaluations. However, the durations of induction antifungal therapy and hospital stay were shorter for patients in the voriconazole group than in the dAmB group. Few adverse reactions occurred in either the voriconazole or dAmB group. Our retrospective study indicated that voriconazole is an effective and safe induction antifungal drug for HIV-associated disseminated talaromycosis. The duration of induction treatment with voriconazole was shorter, indicating its potential as a better choice in clinical practice. The duration of voriconazole induction therapy is 11 to 13 days.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Humans; Induction Chemotherapy; Mycoses; Retrospective Studies; Talaromyces; Voriconazole

Clinical worsening or new manifestation of cryptococcal disease following initiation of anti-retroviral therapy (ART) in an HIV patient is a hallmark of cryptococcal immune reconstitution inflammatory syndrome (C-IRIS). However, it can be difficult to distinguish IRIS from worsening or new infection. Here, we present a case of severe C-IRIS involving multiple cerebellar, spinal, and intradural abscesses and spinal arachnoiditis 7 months after ART initiation in an AIDS patient with uncertain prior ART compliance. He had multiple prior episodes of cryptococcal meningitis with complications necessitating ventriculoperitoneal shunt placement and was on suppressive fluconazole when he developed worsening brain manifestations. He received empiric anti-cryptococcal re-induction without improvement. All cerebrospinal fluid cultures remained sterile, with negative

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Anti-Inflammatory Agents; Anti-Retroviral Agents; Antifungal Agents; Arachnoid; Arachnoiditis; Biopsy; Brain; Brain Abscess; Brain Edema; Cerebellar Diseases; Empyema, Subdural; Fluconazole; Flucytosine; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Magnetic Resonance Imaging; Male; Meningitis, Cryptococcal; Middle Aged; Prednisone; Recurrence

Histoplasmosis is a systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum, with disseminated histoplasmosis (HD) being one of its clinical forms. As a consequence of the HIV-AIDS pandemic, HD has become prevalent not only in regions that are recognized as endemic but also in areas not considered endemic, such as Europe and Asia. Its clinical manifestations are varied and mimic several infectious diseases, mainly tuberculosis. In endemic areas, it is the first manifestation of AIDS in 50 to 70% of patients. The diagnosis of histoplasmosis is difficult and HD can lead to death if not diagnosed early and if proper treatment is not instituted. The present report presents a patient with a recent diagnosis of HIV-AIDS, in treatment for miliary tuberculosis, who was diagnosed with disseminated histoplasmosis because of his dermatological manifestations.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Critical Illness; Dermatomycoses; Histoplasma; Histoplasmosis; Humans; Itraconazole; Male; Tuberculosis, Miliary; Young Adult

Visceral leishmaniasis (VL) is becoming endemic in São Paulo state, in the southeastern region of Brazil. Unusual manifestations with non-specific signs and symptoms may make diagnosis difficult and delay treatment, increasing the risk of severity and death, particularly in new endemic areas. There are few studies on patients with these characteristics in Brazil. We describe a case series of unusual manifestations of VL in children and its spatial dispersion in the western region of São Paulo state.. From 2009 to 2014, five clinical cases involving children treated in the Regional Hospital of Presidente Prudente (RH) were selected. Two patients had multiple relapses requiring liposomal amphotericin B; one patient had VL-cytomegalovirus-dengue co-infection and liver injury; one patient was diagnosed with X-linked agammaglobulinemia, a primary immunodeficiency; and one patient was diagnosed with VL-human immunodeficiency virus/acquired immunodeficiency syndrome (VL-HIV/AIDS) co-infection. Primary or secondary immunodeficiencies were found in four children, and associated viral infections were found in three children. Three patients were referred from other hospitals to RH. With regard to the geographic spread of VL, more cases were found in the northern area, in the epicenter of the infection where the first cases were registered, flowing south; a spatial-temporal occurrence was found.. Primary and secondary immunodeficiencies and viral co-infectious should be considered among unusual manifestations of VL, especially in those with multiple relapses. Spatial-temporal occurrence was found. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices to stem the tide of the epidemic.

Topics: Acquired Immunodeficiency Syndrome; Agammaglobulinemia; Amphotericin B; Animals; Antiprotozoal Agents; Brazil; Child; Child, Preschool; Coinfection; Cytomegalovirus Infections; Dogs; Female; Genetic Diseases, X-Linked; Humans; Immunologic Deficiency Syndromes; Infant; Leishmaniasis, Visceral; Male

Opportunistic infections, while well studied in the AIDS population, continue to have variable and surprising presentations. Here, we present a case of disseminated histoplasmosis with disseminated nontuberculous mycobacterial infection in a 50 year old man with long standing AIDS living in a non-endemic area.. Patient presented with a constellation of symptoms, and imaging of the chest showed a pulmonary mass with cavitation, multiple nodules, and ground glass opacities. Further investigations revealed granulomatous lung nodules and fungemia consistent with Histoplasma capsulatum, and coinfection with disseminated nontuberculous mycobateria in a nonendemic area.. Immunocompromised patients risk co-inhabitation by multiple infectious organisms. Some of these organisms may preside in the host for years prior to reactivation. Clinicians in non endemic areas should therefore be careful to not overlook specific organisms based on a lack of a recent travel history. Physicians in nonendemic areas should become more familiar with the clinical findings and diagnostic approach of infectious such as Histoplasmosis, to ensure earlier recognition and treatment in immunocompromised individuals.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Azithromycin; Bacteremia; California; Emtricitabine; Ethambutol; Fungemia; Heterocyclic Compounds, 3-Ring; Histoplasmosis; Humans; Lung; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Oxazines; Piperazines; Pyridones; Rifabutin; Tenofovir; Tomography, X-Ray Computed

Cutaneous fungal infections include onychomycosis, an infection of the nail that affects both healthy and immunocompromised patients. This study investigated the in vitro hydrolytic enzymes production, adhesion and biofilm formation capacity of Candida parapsilosis complex species and Kodamaea ohmeri isolates from onychomycoses of HIV/AIDS patients and also established the antifungal sensitivity profiles of these isolates. Onychomycosis in HIV/AIDS patients showed a high prevalence of emerging yeasts, among which C. parapsilosis complex species and K. ohmeri were the most frequent. Three C. parapsilosis sensu stricto and two C. orthopsilosis isolates were resistant to amphotericin B and 83% of isolates were resistant to terbinafine. All three different species evaluated were proteinase and hemolysin producers. All isolates adhered to stainless steel and siliconized latex surfaces, and carbohydrates intensified adhesion of all isolates. Isolates adhered to keratinous nail and 50% formed biofilms with strong intensity. In multispecies or polymicrobial biofilms, C. albicans and Staphylococcus aureus regulated the biofilm formation of the analyzed species, decreasing the number of their cells in biofilms. The isolation of emerging yeast species from onychomycosis which are great producers of hydrolytic enzymes and with high adhesion and biofilm formation capacity is a result that should be considered relevant in clinical practice. In addition, half of the isolates was resistant to at least one of the tested antifungals. Taken together these data corroborate the infectious capacity and viability of these isolates under favorable conditions.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Biofilms; Candida parapsilosis; DNA, Fungal; Drug Resistance, Fungal; Female; HIV; Humans; Latex; Male; Microbial Sensitivity Tests; Middle Aged; Onychomycosis; Saccharomycetales; Stainless Steel; Terbinafine; Virulence; Young Adult

Topics: Acquired Immunodeficiency Syndrome; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Bone Marrow; Fungemia; Histoplasma; Histoplasmosis; HIV; Humans; Itraconazole; Male; Viral Load

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.

Topics: Acquired Immunodeficiency Syndrome; Age Factors; Amphotericin B; Antibodies, Fungal; Antigens, Fungal; Brain; Central Nervous System Fungal Infections; Female; Histoplasmosis; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Spinal Cord

The treatment of cryptococcosis is hampered by inefficacy or intolerance to the recommended antifungal agents. A patient diagnosed with AIDS had multiple relapses of cryptococcal infection, which became refractory to antifungal agents during the course of therapy. During the follow-up, the patient developed renal toxicity due to amphotericin B use and non-susceptibility of isolated Cryptococcus neoformans to fluconazole was detected. Thereafter, antifungal treatment was performed exclusively with liposomal amphotericin B, reaching a cumulative dose of 19,180 mg over 46 months. The final relapse of cryptococcosis occurred during the maintenance phase with liposomal formulation in a once-weekly dose. Measurement of the minimum serum concentrations of amphotericin B, determined sequentially before and after this relapse, suggested the importance of monitoring drug levels when the liposomal formulation is used for a long period.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Drug Resistance, Fungal; Fluconazole; Humans; Male; Meningitis, Cryptococcal; Recurrence; Serum; Treatment Outcome

Diagnosis of central nervous system cryptococcosis relies on a spectrum of methods but has improved with lateral flow diagnostic assays that detect capsular polysaccharide antigens of Cryptococcus. Here, we present the case of an HIV-infected African-American man with cryptococcal meningoencephalitis caused by a strain producing little or no capsule.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Antigens, Fungal; Cryptococcus neoformans; Flucytosine; Fungal Capsules; Fungal Polysaccharides; Humans; Male; Meningitis, Cryptococcal; Meningoencephalitis

In patients with acquired immunodeficiency syndrome (AIDS), advanced immunosuppression is associated with atypical presentation of dermatological conditions. Our patient presented with a single crusted plaque over the lower lip and large tender cervical lymphadenopathy. The enzyme-linked immunosorbent assay for human immunodeficiency virus was found to be positive, and his CD4+ lymphocyte cell count was 4 cells/mm

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Biopsy; CD4 Lymphocyte Count; Deoxycholic Acid; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Histoplasma; Histoplasmosis; Humans; Itraconazole; Lymph Nodes; Lymphoma, Non-Hodgkin; Male; Treatment Outcome

Although with a lower incidence than in other geographic areas, leishmaniasis is also endemic on the European Mediterranean coast. However, there are few studies on the clinical features of cutaneous lesions of leishmaniasis in Europe. Our objective was to review the clinical features of cutaneous leishmanial lesions in our European Mediterranean population in the last 30 years and compare the clinical features of immunosuppressed and nonimmunosuppressed patients.. The clinical features of cutaneous lesions of leishmaniasis diagnosed between 1987 and 2016 at Bellvitge Hospital in Barcelona, Spain, were retrospectively analyzed.. Cutaneous lesions of leishmaniasis were diagnosed in 68 patients (40 male and 28 female, mean age 53.60 years, SD 19.68). Thirteen patients were immunosuppressed because of acquired immune deficiency syndrome (AIDS) (7), renal transplantation (1), lymphoma (1), and anti-TNF agents (4). Our immunosuppressed patients had more lesions (3.33 vs. 1.80, P = 0.021), with greater maximum diameter (33.00 vs. 13.33 mm, P = 0.001), and their lesions were more frequently disseminated (P = 0.008). Visceral leishmaniasis was observed only in immunosuppressed patients. Patients treated with anti-TNF drugs developed unusually large skin lesions with crusted, eroded surfaces and without a tendency to spontaneous remission.. With the widespread use of anti-TNF agents, an increase in severe forms of leishmaniasis can be expected. The development of persistent, crusted, or eroded erythematous-brownish plaques in patients treated with anti-TNF drugs who live or had traveled to endemic areas of Leishmania infection warrants consideration of a diagnosis of cutaneous leishmaniasis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Factors; Aged; Amphotericin B; Antiprotozoal Agents; Female; Humans; Immunocompromised Host; Kidney Transplantation; Leishmaniasis, Cutaneous; Male; Mediterranean Region; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Retrospective Studies; Severity of Illness Index; Tertiary Care Centers; Tumor Necrosis Factor-alpha

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Fever; Humans; Itraconazole; Lymphohistiocytosis, Hemophagocytic; Male; Pancytopenia; Splenomegaly

Candida albicans is the common cause of some infectious diseases such as vaginal candidiasis or candidemia. Due to the emergence of drug resistant isolates of C. albicans, finding a new anti-Candida agent is a new strategy for current treatments. This study evaluated the anti-candidal activity of Satureja khuzistanica ethanol extract against clinical isolates of C. albicans. S. khuzistanica ethanol extract from aerial parts of plant at full flowering stage was evaluated against 30 clinical isolates and two ATCC reference strains of C. albicans by disc diffusion and micro-broth dilution assay. Also, in this study we evaluated the synergistic effects of amphotericin B, clotrimazole and ketoconazole with S. khuzistanica ethanol extract. The means of MIC and MFC of S. khuzistanica ethanol extract against clinical isolates were 299.4 and 722.6 (μg/mL), respectively. S. khuzistanica ethanol extract increased the anti-candidal effect of amphotericin B and ketoconazole, while it had no synergistic effect on clotrimazole against clinical isolates of C. albicans. Therefore, S. khuzistanica ethanol extract can be introduced as a new source of anti-candidal agent against clinical isolates of C. albicans.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Clotrimazole; Diabetes Complications; Drug Interactions; Female; Humans; Ketoconazole; Male; Microbial Sensitivity Tests; Plant Components, Aerial; Plant Extracts; Satureja; Vagina

Refractory and relapsing crytocococcosis in acquired immune deficiency syndrome (AIDS) patients have a poor prognosis. The risk factors for this complicated infection course were evaluated by comparing refractory and/or relapsing cryptococcosis in human immunodeficiency virus-coinfected patients (cohort 1) with another group of AIDS patients who adequately responded to antifungals (cohort 2). Except for one isolate of Cryptococcus gattii from a cohort 2 case, all other isolates were identified as Cryptococcus neoformans var. grubii, sex type α, genotype VNI, including Cryptococcus reisolated from the relapse or in the refractory state. No differences were observed with respect to Cryptococcus capsule size and in the melanin and phospholipase production. The cohort 1 patients presented higher prevalence of cryptococcemia, cerebral dissemination, chronic liver disease, and leucopenia, and have increased death rate. Apparently, the refractory and/or relapsing cryptococcosis in the AIDS patients were more related to the host and the extent of the infection than to the fungal characteristics.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Coinfection; Cryptococcosis; Cryptococcus; Deoxycholic Acid; Drug Combinations; Female; Genotype; Humans; Male; Virulence Factors

Haemophagocytic lymphohistiocytosis is an uncommon syndrome that results from an uncontrolled activation of macrophages and lymphocytes resulting in the compromise of multiple organs that is potentially fatal without timely treatment. It can be hereditary or a secondary result of infectious processes, neoplasms or autoimmune conditions. We present the case of a patient with HIV/AIDS who developed hemophagocytic lymphohistiocytosis as well as disseminated intravascular coagulation associated with histoplasmosis and who was successfully treated with amphotericin B, steroids and transitory dialytic support.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Disseminated Intravascular Coagulation; Histoplasmosis; Humans; Lymphohistiocytosis, Hemophagocytic

Disseminated histoplasmosis is an invasive fungal infection documented in patients with impaired cellular immunity coming from endemic areas (America, Asia, Africa). We report two cases of disseminated histoplasmosis in AIDS patients paradigmatic of the multifaceted nature of the disease, which may be an expression either of an advanced state of immunosuppression or the immune reconstitution inflammatory syndrome (IRIS).

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Brazil; Deoxycholic Acid; Diagnosis, Differential; Drug Combinations; Female; Hepatitis B, Chronic; Hepatitis D, Chronic; Histoplasmosis; Homosexuality, Male; Humans; Immunocompromised Host; Invasive Fungal Infections; Italy; Male; Risk Factors; Thailand; Treatment Outcome; Voriconazole

Up to now, over 200 patients with paracoccidioidomycosis (PCM) associated to HIV infection have already been reported; however, the central nervous system involvement in this coinfection was rarely reported. This paper presents a 35-year-old Brazilian male AIDS patient who developed pulmonary PCM successfully treated with itraconazole. At the antiretroviral therapy starting, he had 32 CD4(+) T cells baseline count and high viral load levels. After 9 months, he presented severe fungal meningoencephalitis diagnosed by sublenticular enhanced nodular lesion at computerized tomography and magnetic resonance brain imaging and a positive Paracoccidiodes brasiliensis smear and culture from cerebrospinal fluid. At the time, a sixfold increase in CD4(+) T cell count and undetectable viral load level were evidenced. The patient received amphotericin B during 1 year presenting slow but progressive clinical improvement, and he is currently asymptomatic and without neurological disabilities. To our knowledge, this is the second case report of a patient with neuroparacoccidioidomycosis associated to HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Brazil; CD4-Positive T-Lymphocytes; Central Nervous System Fungal Infections; Humans; Itraconazole; Lymphocyte Count; Male; Meningoencephalitis; Paracoccidioides; Paracoccidioidomycosis; Tomography, X-Ray Computed; Viral Load

Topics: Abdominal Pain; Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Anti-HIV Agents; Histoplasma; Histoplasmosis; Humans; Ileal Diseases; Ileocecal Valve; Infusions, Intravenous; Intestinal Fistula; Itraconazole; Male; Opportunistic Infections; Rare Diseases; Risk Assessment; Treatment Outcome

We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci, from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient. Our review of literature identified this coinfection as unusual presentation. Opportunistic infections associated with HIV infection are increasingly recognized. It may occur at an early stage of HIV-infection. Whereas concurrent opportunistic infections may occur, coexisting Pneumocystis jiroveci pneumonia (PCP) and disseminated cryptococcosis with cryptococcal pneumonia is uncommon. The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours and over two-thirds of patients have at least one respiratory episode during the course of their disease. Pneumonia is the leading HIV-associated infection. We present the case of a man who presented dual Pneumocystis jiroveci and cryptococcal pneumonia in a patient with HIV. Definitive diagnosis of PCP and Cryptococcus requires demonstration of these organisms in pulmonary tissues or fluid. In patients with < 200/microliter CD4-lymphocytes, a bronchoalveolar lavage should be performed. This patient was successfully treated with amphotericin B and trimethoprim sulfamethoxazole. After 1 week the patient showed clinical and radiologic improvement and was discharged 3 weeks later.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Bronchoalveolar Lavage Fluid; Coinfection; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Microscopy; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality in patients with AIDS. A retrospective analysis of records of HIV-infected individuals registered in the Immunodeficiency Clinic of a tertiary care hospital and research institute was carried out. Records of 6900 HIV-infected individuals who were enrolled in the clinic between January 2002 and March 2011 were analyzed. Records of 6900 HIV-infected individuals were screened. Ninety-one were diagnosed with cryptococcal meningitis (1.32%). In 68 individuals cryptococcal meningitis was the presenting illness. Nine patients developed meningitis within 6 months of starting antiretroviral treatment (ART). Six patients were receiving ART for more than 6 months at the time of diagnosis. The remaining eight patients were not on ART at the time of development of meningitis. The mean baseline CD4 count of patients was 77.7 ± 61 (range, 4-259, n=91) cells/mm(3). Seventy-four patients had a CD4 value of less than 100 at the time of diagnosis of cryptococcal meningitis. Eleven of these ninety-one patients had a relapse of cryptococcal meningitis while receiving a maintenance dose of fluconazole. During follow-up 37 died, two were lost to follow-up, while 52 patients were on regular ART. Mortality due to cryptococcal meningitis amounted to 0.54% (37/6900). There was no correlation between survival and duration of ART at the time of cryptomeningitis (Pearsons χ(2)=0.241, p=0.884). There was a significant difference in the CD4 counts of the HIV-infected individuals who died with cryptomeningitis and those who survived (Pearson's χ(2)=9.1, df=4, p=0.05). The frequency of cryptococcal meningitis was 1.32%. Cryptococcal meningitis leads to high mortality in HIV patients. Management of cryptococcal infection remains a key facet of AIDS care in India.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Distribution; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; Fluconazole; Follow-Up Studies; Humans; India; Male; Medical Records; Meningitis, Cryptococcal; Middle Aged; Retrospective Studies; Sex Distribution; Young Adult

We compared the epidemiology of laboratory-confirmed paediatric cryptococcal disease with adult-onset disease in the South African population.. The study was an active, prospective, population-based, laboratory-based surveillance in South Africa. We compared cases of paediatric cryptococcosis (<15 years) with cases of adult-onset cryptococcosis that were reported to the surveillance programme between 1 January 2005 and 31 December 2007. The case definition was based on a positive India ink test, cryptococcal antigen test or cryptococcal culture. Clinical case data were obtained at enhanced surveillance sites.. Of 16,192 incident episodes of cryptococcosis in South Africa, 361 (2%) episodes occurred among children. In 2007, incidence was one and 19 cases per 100,000 persons in the general paediatric and adult populations and was 47 and 120 cases per 100,000 persons for HIV-infected children and adults, respectively. Among children, a bimodal peak in incidence was evident in the less than 1-year age group and in the 5 age group. Most children (64%) and adults (63%) were severely immunocompromised (CD4 T-lymphocyte cell count < 50 cells/μl) at the time of diagnosis. On multivariable analysis, children were significantly more likely than adults to be male, diagnosed on blood culture, infected with Cryptococcus gattii, treated with amphotericin B and admitted for a longer stay in hospital.. This series of 361 cases of paediatric cryptococcosis is by far the largest described to date. The diagnosis of cryptococcosis should be considered in the paediatric HIV-infected population, especially among those who are severely immunocompromised.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Age Distribution; Age of Onset; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Child; Child, Preschool; Cryptococcosis; Cryptococcus gattii; Female; Humans; Immunocompromised Host; Incidence; Infant; Infant, Newborn; Length of Stay; Male; Population Surveillance; Prospective Studies; Sex Distribution; South Africa; Treatment Outcome

Topics: Abdominal Pain; Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Cerebrospinal Fluid; Constipation; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Headache; Humans; Male; Microscopy; Viral Load

Penicillium marneffei (P. marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involvement. However, no cases of P. marneffei infection with chylous ascites have been reported thus far. In this report, we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with amphotericin B for 3 mo, while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo. P. marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with P. marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Alkynes; Amphotericin B; Anti-Retroviral Agents; Antifungal Agents; Benzoxazines; Chylous Ascites; Cyclopropanes; Diagnosis, Differential; Humans; Male; Middle Aged; Mycoses; Penicillium; Pyrimidines; Sepsis; Triazoles; Voriconazole

Abstract. Coinfection with tuberculosis in some countries occurs in 8-15% of human immunodeficiency virus (HIV) -infected patients who have histoplasmosis. This coinfection interferes with prompt diagnosis, and treatment is difficult because of drug interactions. We retrospectively reviewed the cases of 14 HIV-infected patients who had concomitant tuberculosis and histoplasmosis. The most frequent clinical manifestations were weight loss (85.7%), asthenia (78.5%), and fever (64.2%). The diagnosis of histoplasmosis was made primarily by histopathology (71.4%), and the diagnosis of tuberculosis was made by means of direct microscopic examination (71.4%). Death occurred in two patients, and relapse of both infections occurred in one patient. Moxifloxacin was substituted for rifampicin in six patients, with good outcomes noted for both infections. The clinical presentation does not readily identify acquired immunodeficiency syndrome (AIDS) patients who have tuberculosis and histoplasmosis. The use of a fluoroquinolone as an alternative agent in place of rifampicin for tuberculosis allows effective therapy with itraconazole for histoplasmosis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Coinfection; Deoxycholic Acid; Drug Combinations; Female; Histoplasmosis; Humans; Itraconazole; Male; Middle Aged; Retrospective Studies; Risk Factors; Tuberculosis

Human immunodeficiency virus (HIV) infection can cause a broad spectrum of clinical manifestations, ranging from an asymptomatic carrier state to severe immunodeficiency. The most common renal lesion, HIV-associated nephropathy (HIVAN), is a sclerosing glomerulopathy. However, potentially reversible causes of renal disease in HIV-infected patients should also be considered. We describe two cases of patients with acquired immune-deficiency syndrome (AIDS) who presented with rapidly progressive renal failure but were found to have reversible etiologies. The first case was found to have syphilis and the second, disseminated histoplasmosis; their renal injury resolved after initiation of a third-generation cephalosporin antibiotic and amphotericin B, respectively.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Associated Nephropathy; Amphotericin B; Biopsy; Ceftriaxone; Histoplasmosis; Humans; Kidney; Male; Neurosyphilis

Cryptococcal skin infection in persons with AIDS has been demonstrated. We describe a patient with nasal and facial infection with cryptococci after traumatic injury with battery acid.

Topics: Acids; Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Automobiles; Burns, Chemical; Cryptococcosis; Cryptococcus neoformans; Facial Injuries; Fluconazole; HIV-1; Humans; Immunocompromised Host; Male; Medication Adherence; Meningoencephalitis; Middle Aged; Recurrence

Sporotrichosis is a fungal disease usually restricted to the cutaneous and lymphatic systems. Visceral involvement is unusual. To date, only 21 cases of sporotrichosis meningitis have been reported, some of these associated with immunosuppression. According to the reported cases, difficulty establishing the correct diagnosis is almost the rule which, undoubtedly, is associated with a worse prognosis. In this report, two HIV infected patients are described who developed meningitis due to Sporothrix schenckii associated with immune reconstitution inflammatory syndrome. This is the first report of sporotrichosis meningitis associated with immune reconstitution inflammatory syndrome in AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Brain; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Meningitis, Bacterial; Sporothrix; Sporotrichosis; Tomography, X-Ray Computed

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Amphotericin B; Bone Marrow Cells; Fatal Outcome; Female; Histoplasma; Histoplasmosis; Humans; Leukocytes

Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well-conducted treatment of liposomal amphotericin B.

Topics: Acquired Immunodeficiency Syndrome; Aged; Amphotericin B; Fatal Outcome; HIV Infections; Humans; Kidney; Leishmania infantum; Leishmaniasis, Visceral; Male; Nephritis, Interstitial; Spain; Tunisia

Despite the advent of new antifungal agents, coccidioidal meningitis (CM) remains a difficult-to-treat condition with significant morbidity and mortality. In this study we directly compare the clinical presentation and management of patients with Coccidioides immitis meningitis in the azole era (after 1980) to that of a cohort of patients from the pre-azole era. We reviewed 30 CM cases seen at 3 Los Angeles hospitals between the years 1993 to 2008 ("2008 cohort") and compared them to 31 patients ("1980 cohort") described by Bouza et al in a previous study. The demographics and clinical presentation of patients in the 2008 cohort were similar to those of the 1980 cohort except for a higher incidence of Hispanic patients (2008: 53% vs. 1980: 6%) and a greater percentage of patients with underlying, predisposing clinical conditions (2008: 66% vs. 1980: 32%). Ten patients in the 2008 cohort had human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), a condition not reported in the earlier study. Laboratory findings were similar between the 2 groups except for a lower incidence of peripheral leukocytosis and eosinophilia in the 2008 group.There were marked differences in drug treatment between the 2 eras. In the 2008 cohort, 29 patients received fluconazole therapy: 13 were treated with fluconazole monotherapy, and 16 received a combination of fluconazole and intravenous amphotericin B. Although almost all patients (29/31) in the 1980 cohort received intrathecal amphotericin B, only 3 patients in the 2008 study received amphotericin B via this route. With respect to complications of CM, a similar percentage of patients in each cohort developed complications such as stroke and hydrocephalus. The 2008 cohort (40%) had similar mortality compared to patients in the 1980 study (39%); survivors in both groups experienced significant impairment of activities of daily living. Although recommended as first-line therapy for CM, azole-based therapies are not curative and do not necessarily prevent complications associated with the disease.CM remains a serious illness with a high rate of morbidity and mortality. Immunocompromised individuals, especially those with HIV/AIDS, are at special risk for CM and represent a greater share of the overall population with this condition. Despite the clear advantages of azole treatment in CM, new therapeutic approaches are needed to provide definitive cure and to reduce the need for long-term suppressive therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Coccidioides; Coccidioidomycosis; Enzyme-Linked Immunosorbent Assay; Female; Fluconazole; Humans; Hydrocephalus; Male; Meningitis; Middle Aged; Radiography, Thoracic; Young Adult

Neuromeningeal cryptococcosis occurs mainly in immunodepressed patients and especially AIDS patients. The purpose of this study was to determine the clinical and prognostic features of this severe brain infection.. This retrospective study was carried out on HIV-infected patients hospitalized for cryptococcal meningitis in the internal medicine unit of a military hospital in Libreville, Gabon from January 1, 2006 to November 31, 2009.. Eleven cases of cryptococcosis were identified among a total of 290 cases of AIDS. Mean patient age was 39 years. The main clinical manifestation was headache that was either isolated or associated with other cerebral signs. In all cases, cerebrospinal fluid analysis demonstrated a clear aseptic aspect with direct examination after addition of India ink showing the presence of encapsulated yeast cells identified as cryptococcus. The patient was treated with amphotericin B and fluconazole. The mortality rate was 81.8% (9/11 cases).. Since the manifestations of cryptococcosis during clinical AIDS are non-specific, systematic screening is recommended in AIDS patients. Early treatment could reduce mortality.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Female; Fluconazole; Humans; Immunocompromised Host; Male; Meningitis, Cryptococcal; Middle Aged; Retrospective Studies; Young Adult

Histoplasma polysaccharide antigen testing is used routinely to diagnose histoplasmosis. At least 3 antigen tests are commercially available. Controversy exists about the relative accuracy of these tests. We report 2 patients with AIDS and culture-confirmed Histoplasma capsulatum meningitis from whom discrepant Histoplasma polysaccharide antigen results were obtained from different laboratories and discuss the potential clinical implications of these results.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Antigens, Fungal; Diagnostic Errors; Histoplasma; Histoplasmosis; Humans; Immunoenzyme Techniques; Laboratories; Male; Meningitis, Fungal; Polysaccharides; Reproducibility of Results; Sensitivity and Specificity

A prospective multicenter study of cryptococcal immune reconstitution inflammatory syndrome (IRIS) was conducted as a substudy of the Bacteriology and Mycology Study Group 3-01. Of 101 AIDS patients with cryptococcal meningitis who received highly active antiretroviral therapy (HAART), 13 experienced cryptococcal IRIS. No association between the timing of HAART initiation and the diagnosis of IRIS was identified. Increased baseline serum cryptococcal antigen (CrAg) titer was a risk factor for cryptococcal IRIS.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antigens, Fungal; Antiretroviral Therapy, Highly Active; Clinical Trials, Phase II as Topic; Fluconazole; Humans; Immune Reconstitution Inflammatory Syndrome; Immunocompromised Host; Incidence; Kaplan-Meier Estimate; Logistic Models; Meningitis, Cryptococcal; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Time Factors

To describe the incidence of renal dysfunction, hypokalaemia and hypomagnesaemia in AIDS patients with cryptococcal meningitis and on amphotericin B treatment. Secondary objective was to determine all-cause mortality in the same group.. Prospective, observational study.. Kenyatta National Hospital (KNH), Nairobi, Kenya.. Seventy consecutive patients with AIDS and cryptococcal meningitis on amphotericin B.. About 58.6% of the patients had at least 100% rise in the creatinine level. Thirty eight point six per cent of patients experienced a rise in serum creatinine of at least 50%. Ninty three per cent of the patients developed hypokalaemia and 80% had hypomagnesaemia at trough magnesium level. Only 54.3% of patients completed the intended 14-day treatment. Thirty point five per cent of patients died within the two week follow-up period.. The incidences of amphotericin B associated nephrotoxicity, hypokalemia and hypomagnesaemia were high in this studied population.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Creatinine; Female; Humans; Kenya; Kidney Diseases; Male; Meningitis, Cryptococcal; Middle Aged; Prospective Studies

To describe the mycologic and clinical outcomes and factors associated with failure in Peruvian patients with AIDS-associated cryptococcal meningitis (CM) treated with amphotericin B deoxycholate (Amph B) followed by fluconazole.. Patients were treated with intravenous Amph B 0.7 mg/kg/day for 2 or 3 weeks followed by oral fluconazole 400mg/day for 7 or 8 weeks. Clinical and laboratory evaluations including cerebrospinal fluid (CSF) studies were performed at baseline and at weeks 2 and 10.. The CSF cultures were negative in 25% and 68% of 47 patients at weeks 2 and 10, respectively. In the univariate analysis, baseline low body mass index (BMI), hyponatremia, low serum albumin, positive blood culture and CSF antigen titers >or=1024 were associated with a positive CSF culture at week 2. Baseline positive urine culture, positive blood culture, any positive extraneural culture and CSF opening pressure at week 2 >or=300 mm H2O were associated with a positive CSF culture at week 10. In the multivariate analysis no association was found.. Therapy with Amph B and fluconazole, combined with aggressive management of elevated intracranial pressure (ICP), results in low CSF sterilization rates at week 2 and acceptable CSF sterilization rates at week 10 when compared with other series.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Blood; Cerebrospinal Fluid; Cryptococcus; Female; Fluconazole; Humans; Intracranial Pressure; Male; Meningitis, Cryptococcal; Peru; Risk Factors; Treatment Outcome; Urine

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Anti-Bacterial Agents; Cochlear Nerve; Cryptococcus neoformans; Drug Therapy, Combination; Flucytosine; Headache; Hearing Loss, Bilateral; Humans; Male; Meningitis, Cryptococcal; Reflex, Acoustic; Temporal Bone

We describe a case of primary cutaneous Absidia corymbifera infection in an AIDS patient with renal complications. The Sensititre YeastOne panel was adopted to determine antifungal susceptibility and liposomial amphotericin B was used which initially produced a significant clinical response.

Topics: Absidia; Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Female; Humans; Injections, Intravenous; Kidney Diseases; Leg Injuries; Mucormycosis; Soft Tissue Infections

A unique occurrence of two subsequent episodes of HIV-associated Cryptococcus neoformans followed by C. laurentii meningoencephalitis (successfully cured with fluconazole after demonstrated amphotericin B resistance) is presented and discussed. The available literature reported only two cases of HIV-associated C. laurentii infection to date, while a concurrent infection by C. neoformans and C. laurentii has been reported only once in a patient without HIV disease. The absence of prior descriptions of documented central nervous system infection by C. laurentii in non-HIV-infected patients is emphasized as well as the unpredictable in vitro and in vivo antifungal susceptibility of this non-neoformans Cryptococcus spp., and its apparent prevalence in hospitalized patients who received prior antifungal treatments. All epidemiologic, diagnostic, clinical, and therapeutic implications are discussed on the basis of the evolving characteristics of opportunism in the era of highly active antiretroviral therapy (HAART).

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Cryptococcus; Drug Resistance, Fungal; Humans; Male; Meningitis, Cryptococcal

Drug reactions are commonly present in the skin; however, their frequency in our setting is unknown.. A 10-month prospective cohort study including all hospitalized patients was designed. Those with adverse cutaneous drug reactions (ACDR) were clinically identified.. Thirty five drug reactions (prevalence of 0.7%) were seen among 4785 (2713 females, 2072 males) discharged patients. According to Begaud's imputability criteria, the reactions were most likely attributed to a drug in 4.87%, likely in 41.46% and possible in 53.65%. The most commonly seen dermatoses were morbilliform rash 51.2%, urticaria 12.2% and erythema multiforme 4.9%. Drugs most frequently associated with ACDR were amoxicillin clavulanate (8), amphotericin B (2) and metamizole (4). Expressed as risk by 1000 day-doses (Dd: the risk a patient has of developing an ACDR after receiving 1 day of treatment with the drug): amoxicillin clavulanate Dd 7.7, amphotericin B Dd 4.8 and metamizole Dd 3.7. Immunosuppressed patients were most frequently affected. Notably, patients with systemic lupus erythematosus (SLE) had a 4.68 higher risk (CI 95% 1.794-12.186 p <0.001) of developing an ACDR. AIDS patients showed a risk of 8.68 (CI 95% 2.18-33.19 p <0.001). Non-Hodgkin's lymphoma patients also had an increased risk of developing an ACDR. Six of the 35 identified cases were patients who had been hospitalized due to a severe drug reaction (1.3/1000 patients); one died from complications directly related to the ACDR, representing a 16.6% mortality rate among those admitted for an ACDR and 0.02% among the global mortality.. We have a low prevalence of drug reactions compared to data reported in the literature. Pharmacovigilance with special attention to immunosuppressed SLE or AIDS patients is stressed.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Amphotericin B; Clavulanic Acid; Cohort Studies; Dipyrone; Drug Eruptions; Female; Hospitalization; Humans; Immune Tolerance; Lupus Erythematosus, Systemic; Lymphoma, Non-Hodgkin; Male; Mexico; Middle Aged; Prevalence; Prospective Studies

The objective was to prospectively assess the efficacy and safety of caspofungin as salvage therapy for invasive aspergillosis in patients enrolled in the caspofungin compassionate-use study.. Forty-eight patients with invasive Aspergillus infections (36 with pulmonary infection, 12 with extrapulmonary or disseminated infection) were enrolled in this study. All patients were refractory to or intolerant of intravenous amphotericin B or a lipid amphotericin formulation(s). Efficacy was assessed at end of intravenous caspofungin therapy based on the clinical (symptom/sign and radiographic) response.. Underlying diseases included hematological malignancy (69%), organ transplant (8%), and AIDS (6%). Forty-three (90%) patients were refractory to prior antifungal treatment, including 25 patients refractory to multiple agents. Sixteen (33%) were neutropenic at study entry. Following caspofungin therapy, a favorable response was noted in 44% (20/45) of the patients, including nine (20%) and 11 (24%) patients with complete and partial responses, respectively. Caspofungin was generally well tolerated one serious drug-related adverse event was reported.. In this study, caspofungin was an effective alternative for patients with refractory Aspergillus infections.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Child; Drug Therapy, Combination; Echinocandins; Female; Humans; Itraconazole; Lipopeptides; Male; Middle Aged; Opportunistic Infections; Organ Transplantation; Peptides, Cyclic; Salvage Therapy

The risks associated with implanting a cerebrospinal fluid (CSF) shunt in immunocompromised patients with ongoing CSF infection have historically discouraged surgeons from implanting CSF shunts in patients with HIV and cryptococcal meningitis. However, this patient population often requires frequent lumbar punctures to manage elevated intracranial pressure (ICP) secondary to cryptococcal infection. To date, only 7 cases of ventriculoperitoneal (VP) shunting for the treatment of intracranial hypertension in patients with HIV-associated cryptococcal meningitis have been reported. Few of these reports have included outcomes more than 3 months postsurgery. It remains unclear if VP shunts are an effective long-term treatment of intracranial hypertension in this patient population.. Two patients with HIV/AIDS (CD4 counts of 8 and 81 cells/mm(3)) presented with altered mental status, visual changes, florid cryptococcal meningitis, and elevated ICP (>500 mm CSF) without evidence of hydrocephalus on computed tomography scan. Both patients experienced rapid reversal of symptoms with external lumbar CSF drainage, and remained lumbar drain-dependent after 2 weeks of amphotericin B and flucytosine therapy. Despite evidence of unresolved cryptococcal meningitis, each patient underwent implantation of a VP shunt without complication and was discharged on lifetime fluconazole therapy. They remained asymptomatic at 12 and 16 months after surgery without evidence of shunt infection or malfunction.. Patients with intracranial hypertension and HIV-associated cryptococcal meningitis who cannot tolerate cessation of external lumbar CSF drainage or frequent lumbar punctures may be considered for VP shunt placement despite severe immunosuppression and persistent CSF cryptococcal infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Humans; Immunocompromised Host; Intracranial Hypertension; Lateral Ventricles; Meningitis, Cryptococcal; Middle Aged; Neurosurgical Procedures; Tomography, X-Ray Computed; Treatment Outcome; Ventriculoperitoneal Shunt

Leishmaniasis is emerging as a common and serious opportunistic disease for patients with HIV infection. Almost all cases of HIV-Leishmania coinfection have been described in Mediterranean countries and they occur with various clinical presentations, ranging from typical visceral forms to asymptomatic or atypical cases, including cutaneous and mucocutaneous leishmaniasis. Pentavalent antimony compounds have been the mainstays of antileishmanial therapy for half a century and new lipid formulations of amphotericin B seem reliable, but the most effective treatment remains unknown. We describe a patient who was HIV infected and an intravenous drug user, with an unusual disseminated cutaneous leishmaniasis, after an initial visceral disease and after a 13-month maintenance treatment with liposomal amphotericin. The severe concurrent immunosuppression probably played an essential role in leading to this atypical cutaneous form, characterized by diffuse, nonulcerated, nonscabby maculopapular lesions.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Humans; Leishmaniasis, Diffuse Cutaneous; Leishmaniasis, Visceral; Male

Pentavalent antimonial drugs are habitually the first choice for treating leishmaniasis, although they possess well-known toxicity and may present some therapeutic failure. Lipid formulations of amphotericin B (LFAB) have been increasingly used for treating several types of leishmaniasis. However, the administration of such lipid formulations specifically to patients with cutaneous leishmaniasis (CL) is still rare, including immunocompromised patients to whom standard treatments are more frequently contraindicated. We describe here two cases of immunocompromised patients with CL, one of them with AIDS, representing the first case of AIDS and CL co-infection treated with LFAB described in the literature. The patient achieved therapeutic success with a total 1.500 mg dose of amphotericin B colloidal dispersion. The other had diabetes mellitus as well as kidney failure and was under dialysis, having obtained the healing of lesion with a total dose of 600 mg of liposomal amphotericin B. Thus, the authors suggest that LFAB can represent a safe, efficient and less toxic therapeutic alternative to pentavalent antimonials, as well as to the so-called second line drugs, pentamidine and amphotericin B deoxycholate.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antiprotozoal Agents; Drug Combinations; Humans; Immunocompromised Host; Kidney Failure, Chronic; Leishmaniasis, Cutaneous; Liposomes; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols

A case of disseminated cryptococcosis caused by Cryptococcus neoformans var. grubii is presented in a male diabetic who had AIDS. The diagnosis was based upon the isolation and identification of the aetiological agent from a lymph-node biopsy, cerebrospinal fluid and sputum. The isolate formed spherical, encapsulated yeast cells, produced cherry-brown colonies on niger-seed agar, grew on canavanine-glycine-bromothymol blue (CGB) medium, changing its colour from greenish yellow to blue, and hydrolysed urea weakly in the presence of 100 microM EDTA. The strain was unable to assimilate D-proline and, serologically, it was untypable. The identity of the isolate as C. neoformans var. grubii, serotype A, possessing a mating-type allele A alpha, was confirmed by crossing with standard laboratory test strains and by performing PCR with the mating-type alpha allele-specific primer of the STE12 gene and with serotype (A and D)- and mating type (a and alpha)-specific primers of the STE20 gene. To the best of our knowledge, this is the first report of disseminated cryptococcosis in an AIDS patient caused by a canavanine-resistant strain of C. neoformans var. grubii, serotype A, possessing mating type allele A alpha; the strain is probably a hybrid. The report suggests that, in the absence of a clear-cut serotyping result, a positive CGB reaction alone is not sufficient for intervarietal discrimination and additional confirmatory evidence is required.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Canavanine; Cryptococcosis; Cryptococcus neoformans; Diabetes Mellitus; Drug Resistance, Fungal; Fatal Outcome; Fluconazole; Humans; Male; Middle Aged

Primary renal aspergillosis is a very rare complication of AIDS which usually have fatal outcome (53% of mortality). The immune status of the patient and the early and correct therapeutic approach are the main factors that predict disease advancement. The new antiretroviral therapies improve the CD4 cell count and permit to treat these patients as immuno-competent. The local approach with antifungal drugs instillations, percutaneous drainage combined with systemic antifungal therapy can increase the number of patients that may benefit from a conservative treatment. We report a case of a 44-year-old homosexual patient with AIDS since 1991 in stage IVc (CDC--Centers for Disease Control and Prevention) in antiretroviral treatment. In September 1999 he came because of left low back pain. Laboratory data showed leucocytosis. Urinalysis revealed the presence of white and red blood cells and a negative urine culture. The abdominal ultrasound examination, the intravenous pyelogram and finally the computerized tomography confirm the presence of solid material that occupied the renal pelvis and the middle and superior caliceal group of the left kidney associated with lymph nodes enlargement. An echo-guided needle aspiration allowed us to identify Aspergillus fumigatus. Local instillations with amfotericina B through a nephrostomy and systemic antifungal drugs resolved the urinary infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Humans; Injections; Kidney; Kidney Diseases; Male; Ultrasonography

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Drug Resistance, Fungal; Fluconazole; Humans; Male; Meningitis, Cryptococcal

To study the diagnosis and therapy of cryptococcal meningitis.. Retrospective review of the clinical features, treatment and outcome of 26 patients with cryptococcal meningitis from October 1981 to September 2001 at Peking Union Medical College Hospital.. The age of the patients ranged from 5 to 62 years (mean: 35.6 years), 12 were male and 14 were female. There were 16 patients with underlying diseases, 9 had systemic lupus erythematosus (SLE), 4 had human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS) and 3 had other diseases. 12 patients had contact with pigeons. The nonspecific clinical and laboratory findings in these patients led to misdiagnosis: as lupus encephalopathy in 6 cases and tuberculous meningitis in 5 cases. 23 of the 26 cases were positive of cryptococcus on cerebrospinal fluid (CSF) smear. 13 cases were positive on CSF culture, but latex coagulate test performed in 20 cases were all positive, 15 patients had high intracranial pressure (> 300 mm H(2)O), 9 patients with dilated ventricle received brain ventricular draining. Only 2 cases used fluconazole monotherapy. One patient only used amphotericin B. The rest of the patients were given amphotericin B in combination with flucytosine (12 patients) or fluconazole (5 cases), or flucytosine combined with fluconazole (6 cases). The mean dose of amphotericin B was 2.6 g, the highest dose of amphotericin B and liposomal amphotericin B was 10.05 g and 20 g, respectively. The outcome of the 26 cases showed that 17 were cured, 4 improved, 3 patients were died and 2 patients gave up any further treatment. From Oct. 1981 to Sep. 1996 we found only 9 cases, but in recent 5 years we found 17 cases.. The incidence of cryptococcal meningitis was increasing in the recent 5 years. The conditions associated with this disease include extensive broad spectrum antibiotics, immunosuppressive drugs or ligh-dose corticosteroids and increasing cases of HIV/AIDS. The early diagnosis and treatment of cryptococcal meningitis may reduce death rate. We still recommended amphotericin B plus flucytosine as the standard therapy for cryptococcal meningitis. Ventricular drainage and amphotericin B intraventricularly via an implanted tube into dilated ventricle could improve the clinical condition of serious cryptococcal meningitis and decrease the dosage of systemic use of amphotericin B, therefore, reduce the side-effects of the drugs.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Amphotericin B; Child; Cryptococcus; Drainage; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Humans; Lupus Erythematosus, Systemic; Male; Meningitis, Cryptococcal; Middle Aged; Retrospective Studies; Survival Rate; Treatment Outcome

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Animals; Antiretroviral Therapy, Highly Active; Humans; Immunocompromised Host; Leishmania major; Male; Syndrome; Uveitis

Topics: Acquired Immunodeficiency Syndrome; Adolescent; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Brain Diseases; Female; Histoplasma; Histoplasmosis; HIV-1; Humans; Itraconazole; Transfusion Reaction

We report on a case of cryptococcal intramedullary abscess, which occurred three years after a disseminated cryptococcosis and two years after a lymph node cryptococcal recurrence in a HIV-infected patient who exhibited a long-standing immune restoration. At the time of diagnosis, CD4(+) lymphocyte-count was 640x10(6)/l and HIV viral load was undetectable. Spinal involvement is rare during cryptococcosis of the central nervous system. As far as we are aware, there is only one case of proven intramedullary cryptococcal abscess reported in the literature and this case is then the second one. The significant and sustained increase in CD4 count following effective antiretroviral therapy was probably associated with only a partial immune restitution that did not allow to avoid the occurrence of the cryptococcal medullar abscess. Finally, this case raises the question of when to stop secondary prophylaxis of cryptococcal disease after increase in CD4 cell count under antiretroviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Brain Abscess; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Flucytosine; Humans; Male

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Dermatomycoses; Histoplasma; Histoplasmosis; Humans; Immunocompromised Host; Injections, Intravenous; Itraconazole; Male; Recurrence

Oropharyngeal candidiasis caused by various species of Candida is one of the most common infections in HIV seropositive or AIDS patients. Drug resistance among these yeasts is an increasing problem. We studied the frequency of resistance profile to fluconazole, itraconazole, ketoconazole, amphotericin B and terbinafine of 137 isolates of Candida sp. From HIV positive or AIDS patients with oropharyngeal candidiasis at Instituto de Inmunología, U.C.V. and the Hospital "Jose Ignacio Baldó", Caracas Venezuela, using the well diffusion susceptibility test (Magaldi et al.). We found that nearly 10% of C. albicans isolates were primarily fluconazole resistant, 45% of C. albicans isolates from patients with previous treatment were resistant to fluconazole, of which 93% showed cross-resistance to itraconazole, and even about 30% of C. tropicalis (n = 13) were resistant to fluconazole and/or itraconazole. To this respect, several recent reports have been described antifungal cross-resistance among azoles. Therefore, we consider that C. tropicalis should be added to the growing list of yeast in which antifungal drug resistance is common. This report could be useful for therapeutic aspect in AIDS patients with oral candidiasis.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Azoles; Candida albicans; Candidiasis; Drug Resistance, Microbial; HIV Seropositivity; Humans; Microbial Sensitivity Tests; Naphthalenes; Pharyngeal Diseases; Terbinafine

A wide spectrum of oral lesions has been associated with human immunodeficiency viral infection (HIV), or AIDS. This report describes the case of an HIV-infected patient who developed a case of disseminated sporotrichosis whose first clinical sign was the presence of orofacial lesions. A histopathological study of this patient's biopsy specimens taken from the oropharyngeal lesions revealed a number of rounded and/or oval free-spore forms of Sporothrix schenkii, the identification of which was corroborated by culturing skin lesion exudate on Sabouraud's glucose agar. To the best of our knowledge to date, this is the first time a case of the oral manifestation of sporotrichosis in association with HIV infection has been described in the dental literature.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Biopsy; Facial Dermatoses; Gingival Hyperplasia; HIV Infections; Humans; Male; Mouth Diseases; Oropharynx; Periodontal Diseases; Pharyngeal Diseases; Sporothrix; Sporotrichosis

To present a case of rhino-orbital mucormycosis in a patient with AIDS and neutropenia managed without exenteration.. Case report.. A 60-year-old African-American man with AIDS developed neutropenia that was probably secondary to antiretroviral therapy. He developed right rhino-orbital mucormycosis and was treated with right partial ethmoidectomy with debridement and liposomal amphotericin B. The infection was cured without need for orbital exenteration, although visual acuity in his right eye ultimately was no light perception.. Rhino-orbital mucormycosis is uncommon in patients with AIDS. When rhino-orbital mucormycosis occurs, patients require a careful search for an underlying metabolic derangement such as neutropenia. Treatment should be aggressive, but these patients may not require orbital exenteration.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Debridement; Eye Infections, Fungal; Humans; Leukocyte Count; Liposomes; Magnetic Resonance Imaging; Male; Middle Aged; Mucormycosis; Neutropenia; Orbital Diseases; Paranasal Sinus Diseases; Risk Factors; Visual Acuity

The in vitro activities of three antifungal drugs alone and in combination were evaluated against five isolates of Cryptococcus neoformans using time-kill curves (TKC). The isolates were from AIDS patients who had either died or had failed to show a clinical response during amphotericin B (AMB) treatment. AMB, fluconazole (FCZ) and flucytosine (5FC), and combinations of the drugs (AMB plus 5FC, AMB plus rifampicin (RIF) and FCZ plus 5FC), were evaluated. With all five isolates AMB did not show fungicidal activity; instead, a persistent or tolerant effect was observed. Combinations of AMB plus 5FC and AMB plus RIF showed a clear synergic effect, except for one isolate tested with AMB plus RIF. In contrast, the FCZ plus 5FC combination did not inhibit growth of any isolate.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Interactions; Drug Resistance, Microbial; Fluconazole; Flucytosine; Humans; Leprostatic Agents; Rifampin; Time Factors

Cryptococcus neoformans isolates that exhibited unusual patterns of resistance to fluconazole and voriconazole were isolated from seven isolates from two different geographical regions: one isolate from an Israeli non-AIDS patient and six serial isolates from an Italian AIDS patient who had suffered six recurrent episodes of cryptococcal meningitis. Each isolate produced cultures with heterogeneous compositions in which most of the cells were susceptible, but cells highly resistant to fluconazole (MICs, >/=64 microg/ml) were recovered at a variable frequency (7 x 10(-3) to 4.6 x 10(-2)). Evidence showed that this type of resistance is innate and is unrelated to drug exposure since the Israeli patient had never been treated with azoles or any other antimycotic agents. Analysis of clonal subpopulations of these two strains showed that they exhibited heterogeneous patterns of resistance. The number of subpopulations which grew on fluconazole or voriconazole agar declined progressively with increasing azole concentration without a sharp cutoff point. For the Italian serial isolates, the number of clonal populations resistant to fluconazole (64 microg/ml) and voriconazole (1 microg/ml) increased steadily, yielding the highest number for the isolate from the last episode. Attempts to purify a sensitive subpopulation failed, but clones highly resistant to fluconazole (100 microg/ml) and moderately resistant to voriconazole (1 microg/ml) always produced a homogeneous population of resistant cells. Upon maintenance on drug-free medium, however, the majority of the homogeneously resistant cells of these subclones lost their resistance and returned to the stable initial heteroresistant phenotype. The pattern of heteroresistance was not affected by the pH or osmolarity of the medium but was influenced by temperature. The resistance appeared to be suppressed at 35 degrees C and was completely abolished at 40 degrees C. Although heterogeneity in azole resistance among subpopulations of single isolates has been reported for Candida species, the transient changes in expression of resistance under different growth conditions reported here have not been observed in fungal pathogens.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Drug Resistance, Microbial; Fluconazole; Humans; Hydrogen-Ion Concentration; Itraconazole; Male; Meningitis, Fungal; Microbial Sensitivity Tests; Osmolar Concentration; Phenotype; Pyrimidines; Staining and Labeling; Temperature; Triazoles; Voriconazole

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Female; Fluconazole; Humans; Meningitis, Cryptococcal; Sporotrichosis

Amphotericin B susceptibility was measured by a flow cytometric membrane potential assay in Leishmania infantum promastigotes isolated from 11 immunocompetent children treated with liposomal amphotericin B and 19 HIV-infected young adults treated with intralipid amphotericin B. Susceptibility levels were measured by the 90% inhibitory concentrations (IC90) representing the concentrations of drug that induced a 90% decrease in membrane potential compared with the control culture. In immunocompetent children, treatment was fully effective whatever the susceptibility of isolates to amphotericin B. In immunocompromised adults, on the contrary, unresponsiveness and relapses could be observed in all cases and IC90 increased in the course of successive treatments: a decrease of amphotericin B susceptibility in both promastigote and amastigote forms could be observed in a patient who had six relapses. These results suggest that the success of amphotericin B treatment depends greatly on patient immunity status, and indicate that successive relapses could enhance emergence of amphotericin B resistant isolates. The results demonstrate that the flow cytometric membrane potential assay can be used as an easy and reliable tool for studying the evolution of interactions between amphotericin B and the parasite membrane during long-term treatments.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Animals; Antiprotozoal Agents; Child, Preschool; Drug Resistance; Fat Emulsions, Intravenous; Flow Cytometry; Humans; Immunocompetence; Immunocompromised Host; Infant; Leishmania infantum; Leishmaniasis, Visceral; Membrane Potentials; Monocytes

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Fatal Outcome; Humans; Male; Mastoiditis; Otitis Media with Effusion

Histoplasmosis has been little reported among HIV-infected children. We report a case of a 4-year old boy with AIDS who presented with disseminated histoplasmosis diagnosed by lung biopsy. The patient had a good clinical response to amphotericin B followed by itraconazole oral solution.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Amphotericin B; Antifungal Agents; Biopsy; Child, Preschool; Histoplasmosis; Humans; Itraconazole; Lung; Male; Radiography

In the era before protease inhibitors were available, the great majority of patients with AIDS died within five years of the diagnosis. This grim reputation may cause both physician and patient to give up hope prematurely when antiretroviral therapy fails. We report a patient who survived five years after the diagnosis of cryptococcal meningitis and AIDS. Although there are now combinations of antiretroviral drugs available that can delay disease progression and extend the lives of AIDS patients, these are associated with a significant failure rate. It is thus important to be aware of the potential to extend life in patients even when antiretroviral therapy is not effective.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Fatal Outcome; Fluconazole; HIV Antibodies; Humans; Male; Meningitis, Cryptococcal; Time Factors

Fluconazole resistance occurs in > 10% of cases of candidosis during the late stages of AIDS. We show here in two clinical isolates that resistance was caused by defective sterol delta5,6-desaturation. This altered the type of sterol accumulating under fluconazole treatment from 14alpha-methylergosta-8,24(28)-dien-3beta,6alpha -diol to 14alpha-methylfecosterol which is capable of supporting growth. A consequence of this mechanism of azole resistance is that an absence of ergosterol causes cross-resistance to the other major antifungal agent available, amphotericin B. The results also show that growth arrest after fluconazole treatment of C. albicans in clinical conditions is caused by 14alpha-methylergosta-8,24(28)-dien-3beta,6alpha -diol accumulation.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Candida albicans; Drug Resistance, Microbial; Female; Fluconazole; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Oxidoreductases; Sterols

Disseminated cryptococcosis is a major cause of morbidity and mortality in immunocompromised individuals, especially those with the acquired immunodeficiency syndrome (AIDS). Early diagnosis and treatment greatly improves the outcome, so clinical clues that lead to prompt diagnosis are important.. Three patients with AIDS in whom multifocal choroiditis and choroidal lesions were the initial signs of disseminated cryptococcosis were treated with systemic amphotericin B and flucytosine. All of the patients had a systemic work-up that included evaluation of the cerebral spinal fluid (CSF).. All three patients who were seen with the choroidal lesions as the presenting sign were noted to have either positive titers for cryptococcus or cultures that grew cryptococcus in the CSF. The choroidal lesions are presumed to be due to cryptococcus as no histopathologic or microscopic studies were available for ocular tissues. The choroidal lesions started to resolve one to three months after systemic treatment with amphotericin B and flucytosine.. Primary choroidal lesions in patients with AIDS may herald severe systemic disseminated disease. Funduscopic examination, however, may detect disseminated cryptococcal disease before other overt clinical manifestations, thereby allowing prompt institution of effective therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Choroiditis; Cryptococcosis; Flucytosine; Fluorescein Angiography; Humans; Male

During 1995, among 1105 HIV patients explored in our department, 64 presented a deep fungic infection (5.8%). The yeast was searched for in cerebrospinal fluid, blood, urine, and bronchoalveolar aspiration. Isolated germs were Cryptococcus neoformans (95%), Candida tropicalis (1 case), Saccharomyces cerevisiae (1 case) et Aspergillus fumigatus (1 case). Results of treatment with amphotericin B were: recovery (9%), clinical success (11%), out of sight (14%), letality (66%), relapse (23%) and side effects (19%). We emphasized diagnostical and therapeutical difficulties, and bad prognostic of mycoses in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Body Fluids; Candida; Candidiasis; Cote d'Ivoire; Cryptococcosis; Cryptococcus neoformans; Humans; Mycoses; Prognosis; Saccharomyces cerevisiae

Penicillium marneffei (PM) is a fungal pathogen that has become a common cause of opportunistic infection in HIV-infected patients in Southeast Asia and Southern China. Clinical features usually present as disseminated infection, reminiscent of disseminated infection with other endemic mycoses or of disseminated mycobacterial infection. Common symptoms involve fever, anemia, and weight loss. Clinical features of children with PM in HIV infection are identical to those seen in adults. Amphotericin B has become standard therapy followed by itraconazole once clinical resolution has been achieved.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Asia, Southeastern; CD4 Lymphocyte Count; Humans; Itraconazole; Mycoses; Penicillium

A case report of two HIV-infected men diagnosed with aspergillus sinusitis is provided. Despite aggressive treatment with antifungal agents, such as amphotericin B and itraconazole, the sinusitis would not resolve. Both protease inhibitor-naive patients were treated with the same antiretroviral regimen. Only one of the patients had a dramatic drop in viral load; the other patient succumbed to neurologic deficits and respiratory failure. Many patients who are using protease inhibitors continue to have good clinical status despite rising viral loads. The availability of antiretroviral therapy has changed the outlook for opportunistic infections, such as severe intestinal cryptosporidiosis, PML, and azole-resistant oral candidiasis. The key role in recovery is successful treatment with antiretroviral therapy to enable the body to fight such infections.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; CD4 Lymphocyte Count; Humans; Itraconazole; Male; Middle Aged; Sinusitis; Treatment Outcome; Viral Load

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Flucytosine; Humans; Male; Peritonitis

A rare case of mucormycosis of the upper limb in a patient with AIDS is described. The pathophysiology and natural history of the disease are described along with a classification of its clinical stages.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Amphotericin B; Amputation, Surgical; Antifungal Agents; Arm; Female; Humans; Mucormycosis; Treatment Failure

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Animals; Antifungal Agents; Antigens, Fungal; CD4 Lymphocyte Count; Cryptococcosis; Diagnosis, Differential; Disease Progression; Drug Resistance, Microbial; False Positive Reactions; Fluconazole; Humans; Latex Fixation Tests; Mice; Polysaccharides

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Biopsy; Brain; CD4 Lymphocyte Count; Diabetes Complications; Humans; Male; Mucormycosis; Nasopharynx; Pentamidine; Pneumonia, Pneumocystis

Due to intrinsic resistance Candida krusei is emerging as a systemic pathogen in AIDS patients undergoing fluconazole therapy, but acquired resistance to itraconazole has not been studied biochemically. We report here studies on the basis for azole resistance and sterol composition in C. krusei. An itraconazole-resistant isolate showed reduced susceptibility to azole drugs in in vitro growth inhibition studies. Accumulation of 14 alpha-methyl-3,6-diol under azole treatment was associated with growth arrest. In vitro ergosterol biosynthesis and type II binding studies suggested no alteration in the affinity to azole drugs of the target enzyme, the cytochrome P-450 sterol 14 alpha-demethylase, in the resistant isolate. Resistance was associated with a decreased intracellular content of drug in the resistant isolate.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cytochrome P-450 Enzyme System; Drug Resistance, Microbial; Humans; Itraconazole; Microsomes; Oxidoreductases; Spectrophotometry, Ultraviolet; Sterol 14-Demethylase; Sterols

Eighteen consecutive AIDS patients with a first episode of cryptococcal meningitis were enrolled in the study to evaluate the efficacy and tolerability of amphotericin B with or without flucytosine followed by fluconazole as primary therapy for cryptococcal meningitis in patients with AIDS. The treatment consisted of intravenous amphotericin B 0.6 mg/kg daily with or without flucytosine (150 mg/kg d in four divided doses) for 2 weeks which was then followed by oral fluconazole 400 mg daily for 8 weeks. After completion of primary therapy, all patients received a maintenance dose of oral fluconazole 200 mg daily. The primary therapy was successful in 17 (94%) of the 18 patients. The median length of time to the first negative cerebrospinal fluid culture for Cryptococcus neoformans in the 17 patients with successful treatment was 3 (range 2 to 6) weeks. No patient had to discontinue the treatment due to adverse drug reactions. During a mean observation period of 26.94 weeks, no relapse case was documented among the 17 patients. Our results indicate that this regimen as primary therapy for cryptococcal meningitis in AIDS patients is effective and well tolerated.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Humans; Male; Meningitis, Cryptococcal

A compassionate use protocol for AmBisome (liposomal amphotericin B) was announced by NeXstar Pharmaceuticals. Eligible patients include those immunosuppressed from bone marrow transplantation, active chemotherapy for cancer, or the administration of other immunosuppressive agents; AIDS patients; premature and newborn infants; or patients otherwise compromised.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Bone Marrow Transplantation; Clinical Protocols; Drug Carriers; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Liposomes; Mycoses

A 35-year-old man from Central America with a history of AIDS and numerous opportunistic infections presented with progressive neutropenia and thrombocytopenia despite having been stable for a period of 6 months. Cessation of antiviral medications did not stop his neutropenia, nor did use of folinic acid, G-CSF, or erythropoietin. The failure of these measures required repeated blood transfusions. Although the physical examination was relatively unremarkable, hematology and blood chemistries indicated that the patient needed urgent hospitalization due to fever and neutropenia. Neutropenia within HIV infection can be confusing, since it may be a result of the infection itself, an adverse effect of drug therapy, or from an opportunistic infection or malignancy. If the cause is not evident, it is wise to seek the etiology first rather than immediately use bone marrow stimulants, such as G-CSF. In this case, an infectious disease specialist made a diagnosis of disseminated histoplasmosis, after which the patient was treated with amphotericin B and released on itraconazole maintenance therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Erythropoietin; Fever; Granulocyte Colony-Stimulating Factor; Histoplasmosis; Humans; Male; Mucous Membrane; Neutropenia

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiprotozoal Agents; Antiviral Agents; Atovaquone; Candidiasis, Oral; Clindamycin; Clotrimazole; Cryptosporidiosis; Cytomegalovirus Infections; Dapsone; Didanosine; Drug Combinations; Drug Therapy, Combination; Fluconazole; Flucytosine; Folic Acid Antagonists; Foscarnet; Glucuronates; Herpes Simplex; Herpes Zoster; Humans; Isoniazid; Itraconazole; Ketoconazole; Lamivudine; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Nystatin; Pentamidine; Pneumocystis Infections; Pneumonia, Pneumocystis; Prednisone; Primaquine; Reverse Transcriptase Inhibitors; Stavudine; Syphilis; Toxoplasmosis; Trimetrexate; Tuberculosis; Zalcitabine; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Candidiasis; Candidiasis, Oral; Child, Preschool; Drug Resistance, Microbial; Esophageal Diseases; Female; Humans; Male; Middle Aged; Triazoles

Histoplasma capsulatum histoplasmosis occurs frequently in endemic areas and with the AIDS outbreak, it appears as an opportunistic fungus involved in disseminated disease. We report the clinical, biological and treatment features of seven cases diagnosed in the CISIH of the Eastern part of Paris. Clinically, four patients were suffering from pulmonary symptoms, in three cases digestive disorders and in three cutaneous lesions. In all cases, the mycologic diagnosis was necessary. Amphotericin B and itraconazole were used as treatment for five patients (two died before the diagnosis was completed). Among these five subjects, four died (death was attributed to histoplasmosis in only one case). These observations emphasize the importance of this infection in HIV-infected patients coming from endemic areas.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Female; Histoplasmosis; Humans; Itraconazole; Male; Recurrence; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Drug Resistance; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Meningitis, Cryptococcal

We report a young homosexual male with AIDS that presented a systemic Cryptococcus neoformans infection. He had skin, lymph node and colonic involvement but the central nervous system was spared. Treatment was started with amphotericin B, achieving a good remission of skin lesions. However, malaise and digestive symptoms did not abate and the patient died.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Humans; Itraconazole; Lymph Nodes; Male; Meningitis, Cryptococcal; Prognosis; Skin

Although the importance of Aspergillus in AIDS is now increasing, extra-pulmonary disease is still an unusual event, especially when a single localization occurs. A case of isolated renal aspergilloma in an AIDS patient is described. At onset, no recognized risk factors were present in our patient. An early surgical approach combined with antifungal chemotherapy (amphotericin B, Itraconazole) led to a good control of the disease, with no evidence of recrudescence at 8 months' follow-up.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Humans; Itraconazole; Kidney Diseases; Male

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Candida; Candidiasis, Oral; Female; Fluconazole; Fungemia; Humans; Recurrence; Zidovudine

Reports of thrush clinically refractory to azoles in AIDS patients are increasing with the more widespread use of these agents. We studied our own oral preparation of amphotericin B in the treatment of two AIDS patients who developed oral thrush due to Candida glabrata after prolonged fluconazole use. Improvement occurred in both in less than 1 week, with eventual clearing and absence of side effects. Oral amphotericin B may have advantages over alternatives for this increasing problem.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Amphotericin B; Candidiasis, Oral; Cost-Benefit Analysis; Drug Resistance, Microbial; Fluconazole; Humans; Male; Treatment Outcome

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antimony; Antiprotozoal Agents; Drug Resistance; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pentamidine; Substance Abuse, Intravenous

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.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Diagnosis, Differential; Fluconazole; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Hemophilia A; Histoplasmosis; Humans; Male; Middle Aged

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Humans; Lung Diseases, Fungal; Male

Two Cryptococcus neoformans strains isolated from an AIDS patient were investigated, a pretreatment isolate (CN1) and a second isolate (CN3) following failure of fluconazole and amphotericin B treatment. No difference in fluconazole sensitivity, but relative resistance to amphotericin B was observed for CN3. The sterol composition of CN3 indicated a defect in sterol delta 8-->7 isomerase in this strain and depletion of ergosterol, the major sterol of the CN1.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcus neoformans; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Mutation; Steroid Isomerases

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Animals; Drug Carriers; Humans; Leishmania infantum; Leishmaniasis, Visceral; Liposomes; Male; Recurrence

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Drug Therapy, Combination; Frontal Sinusitis; Humans; Itraconazole; Male; Maxillary Sinusitis

Eighty-six patients with laboratory evidence of human immunodeficiency virus infection presented to Chiang Mai University Hospital in Chiang Mai, Thailand, between 1 June 1990 and 30 June 1992 with systemic infection caused by the dimorphic fungus Penicillium marneffei. Thirty isolates of P. marneffei from clinical specimens from these patients were tested for their in vitro susceptibilities to amphotericin B, 5-fluorocytosine, miconazole, ketoconazole, itraconazole, and fluconazole. P. marneffei was highly susceptible to miconazole, itraconazole, ketoconazole, and 5-fluorocytosine. Amphotericin B showed intermediate antifungal activity, while fluconazole was the least active; some strains of the fungus were resistant to fluconazole. The clinical and microbiological responses correlated with the overall patterns of in vitro susceptibility to the azoles, whereas results with amphotericin B were more difficult to assess. Antibiotic failures of initial therapy occurred in 8 of 35 (22.8%) patients treated with amphotericin B, 3 of 12 (25%) patients treated with itraconazole, and 7 of 11 (63.6%) patients treated with fluconazole. Itraconazole or ketoconazole should be considered to be the drug of first choice in the treatment of mild to moderately severe P. marneffei infection. Parenteral therapy with amphotericin B may be required for seriously ill patients. Since at least 12 patients who responded to initial therapy relapsed within 6 months regardless of initial antifungal therapy, maintenance oral therapy with itraconazole or ketoconazole may be necessary.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Azoles; Flucytosine; Humans; Microbial Sensitivity Tests; Mycoses; Penicillium

The manifestations of histoplasmosis in 20 patients with the acquired immunodeficiency syndrome are presented. In this series, patients were treated with either itraconazole or fluconazole. Twelve patients received treatment with itraconazole at 400 mg/day, including two patients who had not responded to treatment with fluconazole at 100 mg/day. Of the responses, seven were classified as remissions (mean treatment duration of 24 months), two as improvements, and three as failures. Ten patients received fluconazole. Of the responses, three were classified as remissions (mean treatment duration of 12 months), one as improvement, and six as failures. Of the 10 patients treated with fluconazole, five received doses of 100 mg/day, and five were given doses of 400 or 800 mg/day. The differences in outcome among the five patients receiving the lower dose of fluconazole (one remission, one improvement, and three failures) and the five patients given the higher doses of fluconazole (two remissions and three failures) were negligible. One other patient showed signs of histoplasmosis while receiving fluconazole at 50 mg/day for treatment of thrush. Three failures (two treated with itraconazole and one with fluconazole) followed lapses in azole therapy because of associated conditions. Azole therapy was well tolerated. The treatment responses in this pilot series appear promising in comparison with those reported in the literature with amphotericin B or ketoconazole.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Amphotericin B; Antifungal Agents; Fluconazole; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Middle Aged; Retrospective Studies; Treatment Outcome

We studied the occurrence of ulcerative keratitis in five eyes of four patients who were examined at the University of Maryland Hospital ophthalmology clinic over a 12-month period. All were young women who were intravenous drug abusers, with no known predisposing factors for ulcerative keratitis. Two patients had acquired immunodeficiency syndrome (AIDS), one was human immunodeficiency virus (HIV)-positive, and the fourth refused HIV testing. One had a corneoscleral limbus to corneoscleral limbus keratitis; three had inferiorly located corneal ulcers (bilateral in one patient with AIDS). Corneal cultures disclosed Capnocytophaga species in the corneoscleral limbus to corneoscleral limbus keratitis. The remaining ulcers were polymicrobial; cultures of three grew Candida albicans, cultures of two grew alpha-hemolytic streptococci, cultures of two grew Staphylococcus aureus, and culture of one grew Pseudomonas aeruginosa. Treatment with topical fortified antibiotics and antifungal agents resulted in complete healing in all four inferiorly located ulcers. The corneal ulcer became perforated and the eye was eviscerated. Histopathologic analysis of the eviscerated specimen disclosed acute keratitis with necrosis and no microorganisms.

Topics: Acquired Immunodeficiency Syndrome; Administration, Topical; Adult; Amikacin; Amphotericin B; Candida albicans; Cefazolin; Ciprofloxacin; Corneal Ulcer; Female; Gentamicins; HIV Seropositivity; Humans; Miconazole; Pseudomonas aeruginosa; Staphylococcus aureus; Substance Abuse, Intravenous; Vancomycin; Visual Acuity

As medical interventions prolong the lives of patients with acquired immunodeficiency syndrome (AIDS), we have begun to observe multiple infections occurring simultaneously in a single patient. This report describes two central nervous system (CNS) infections, cryptococcal meningitis and cerebral toxoplasmosis, coexisting in a patient with AIDS. Although the treatment strategies for these CNS infections are generally established, often the physician must make management decisions based on clinical and statistical data and patient response to empiric trials of therapy rather than on the results of invasive diagnostic tests.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Humans; Male; Meningitis, Cryptococcal; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Cerebral

We present here three AIDS patients with disseminated cryptococcal infection and lung involvement. Two patients presented with respiratory symptoms and in the third one, pulmonary disease was only a radiologic finding. Chest X-ray films showed an interstitial pattern in two cases and pulmonary cavitation in one case. One patient has also simultaneous infection by P. carinii. Diagnosis was established by culture from bronchoalveolar lavage in all cases and also by non-induced sputum exam in two cases. All patients were treated with amphotericin B, with good clinical outcome, and without relapses under maintenance therapy with fluconazole. Cryptococcosis must be included in differential diagnosis of AIDS patients with diffuse interstitial lung infiltrates. The presence of C. neoformans in respiratory samples does not rule out the existence of other opportunistic infections, and therefore bronchoalveolar lavage is advisable.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Fluconazole; Humans; Incidence; Lung Diseases, Fungal; Male; Pulmonary Fibrosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Fluconazole; Humans; Meningitis, Cryptococcal

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Drug Carriers; Humans; Liposomes; Male; Middle Aged

The purpose of this study was to establish the effect of induction and maintenance treatment with amphotericin B on levels of Histoplasma capsulatum var. capsulatum polysaccharide antigen (HPA) in the urine and blood of patients with acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis.. This was a retrospective study of the effect of amphotericin B treatment on levels of HPA in the urine or serum from 70 patients with AIDS and disseminated histoplasmosis. All patients received initial intensive induction treatment with amphotericin B, and a subset continued to receive amphotericin B at less frequent intervals for maintenance therapy to prevent relapse. Treatment regimens varied in intensity and duration and specimens were obtained at irregular intervals. Urine and serum specimens were stored and retested for HPA in the same radioimmunoassay.. HPA levels in serum decreased by at least 2 units during induction therapy in all 19 (100%) patients with initial levels of greater than or equal to 2.6 units and reverted to negative in 40.9% of those with initial levels of greater than or equal to 1.0 unit. HPA in urine decreased by at least 2 units in 84.8% and reverted to negative in 17.3% of patients. During induction treatment, HPA cleared more rapidly from serum than from urine. During maintenance treatment, HPA levels in serum decreased by at least 2 units in 100% and became negative in 66.7%. HPA in urine decreased by at least 2 units in 54.5% and reverted to negative in 20.0%. Rates of clearance of HPA from the serum and urine were similar, 0.01 unit/week compared with -0.04 unit/week, respectively, but less than rates during induction treatment.. Successful therapy of histoplasmosis with amphotericin B is associated with reduction of HPA in body fluids. Periodic measurement of HPA levels offers a method for monitoring the response to therapy and for comparing new treatments for histoplasmosis.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antigens, Fungal; Histoplasma; Histoplasmosis; Humans; Least-Squares Analysis; Polysaccharides; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Drug Administration Schedule; Follow-Up Studies; Histoplasmosis; HIV-1; Humans

Cryptococcosis is more frequently observed since the appearance of the acquired immunodeficiency syndrome (AIDS). AIDS has modified the clinical and evolutive forms of the disease. This study reviews the changes produced in the infection from the context of AIDS.. The present is a retrospective study (1985-1990) including patients presenting: 1) a positive latex agglutination test (serum or spinal fluid) or 2) a Sabouraud culture positive for cryptococcus. Clinical histories were revised collecting clinical, radiologic, analytic, therapeutic and evolutive data.. Twenty-six patients (21 males) were included in the study. Twenty patients had the human immunodeficiency virus. The clinical picture was: 22 cases with cryptococcal meningitis (13 with hematogenous participation), 3 with pulmonary cryptococcosis and one with disseminated cryptococcosis without meningeal involvement. The patients with AIDS had: greater frequency of positive hemocultures, higher serologic titers and fewer with the meningeal syndrome. The number of T4 lymphocytes was lower than 150 elements/ml in AIDS patients. In 17 patients treatment with amphotericin B and 5-fluorocytosine was administered, 5 received amphotericin B and two fluconazole and two did not receive the above since they had not been diagnosed alive. There were 6 deaths and 10 relapses in 6 AIDS patients and none in the remaining patients.. The incidence of cryptococcosis has increased as a consequence of AIDS. In these patients the disease occurs in advanced stages of immunodeficiency and frequently in disseminated, severe and paucisymptomatic forms. Treatment is usually effective although a maintenance therapy is required to avoid relapse.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Aged, 80 and over; Amphotericin B; Antigens, Fungal; Cryptococcosis; Cryptococcus; Female; Flucytosine; Humans; Male; Middle Aged; Opportunistic Infections; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Fluconazole; Humans; Prognosis

The clinical course of cryptococcal meningitis in AIDS shows some important differences from the features of the illness in non-AIDS patients. Complications such as raised intracranial pressure and visual impairment that are recognised in non-AIDS patients may be less frequent in those with AIDS. Persistent intracranial hypertension should be managed actively to prevent visual impairment. In AIDS patients, in whom ventriculo-peritoneal shunts carry additional risks, acetazolamide can be used successfully to lower the CSF pressure and prevent visual loss.. 2 AIDS patients are described who had cryptococcal meningitis accompanied by increased intracranial pressure (ICP) and visual complications, a finding thought to be relatively rare in AIDS. Of the 2-6% of AIDS patients who develop cryptococcal meningitis, many have disseminated and recurrent infections. The 1st case was a 45-year old Ugandan woman who presented with stiff neck, and right VIth cranial nerve palsy. She was treated with amphotericin B and flucytosine with some improvement, but on the 9th day she awoke with headache, drowsiness, and total blindness, although no papilledema. Her CSF pressure was 40 cm H20. She recovered after a month of intravenous chemotherapy and acetazolamide, but remained blind. Her sudden blindness was thought to be due to bilateral optic nerve infarction. The 2nd case was a 32-year old male homosexual, admitted with headache, vomiting, confusion, and drowsiness. He had stiff neck, and a CSF of 40 cm containing Cryptococcus neoformans. He was given amphotericin B, flucytosine, and has CSF drained every other day. On day 21 papilledema was seen in the right eye, and acetazolamide was started to lower CSF pressure. This patient recovered without loss of vision. 3 published series of cryptococcus meningitis in AIDS patients remarked about the low incidence of raised ICP, while 1 reported 9 of 27 with neurological and ophthalmic complications. The visual complications and increased ICP in these patients was thought to be due to inflammatory arachnoiditis or direct cryptococcal infiltration.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Blindness; Cranial Nerve Diseases; Cryptococcus neoformans; Female; Flucytosine; Humans; Intracranial Pressure; Male; Meningitis, Cryptococcal; Middle Aged; Papilledema; Uganda

A retrospective analysis of 41 patients with cryptococcal meningitis and AIDS or neoplastic disease was done. Patients with AIDS were younger and predominantly male; they had a shorter duration of prior illness, higher initial serum cryptococcal antigen titers, and lower initial cerebrospinal fluid white blood cell counts than those with neoplastic disease. The median overall survival for patients with AIDS was 9 months compared with 2 months for those with neoplastic disease (P = .004). Seventy-eight percent of patients with AIDS and 43% of those with neoplastic disease were cured or improved 6 months after diagnosis (P = .039). Toxicity from amphotericin B and flucytosine was similar for both groups. One patient with AIDS relapsed. Multivariate predictors of survival included headache (P = .007) and an AIDS diagnosis (P = .009). Examination of outcomes for other opportunistic infections associated with AIDS and other immunosuppressive illness may distinguish prognostic features for different patient populations.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Female; Flucytosine; Follow-Up Studies; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Neoplasms; Opportunistic Infections; Prognosis; Retrospective Studies; Treatment Outcome

The nucleoside analogue azidothymidine (AZT) and the methyl ester of amphotericin B (AME) were assayed for antiviral effect on HIV infection singly and in combination. Both compounds were effective in inhibiting HIV infection of MT-4 cells. At concentrations where either compound alone had no significant effect on infection, the compounds in combination were potent inhibitors of HIV as evaluated by reduction in HIV antigen production and HIV induced cytopathic effect. These results indicate that a combination therapy employing compounds with different modes of action like AZT and AME may have synergistic antiviral properties. Amphotericin B itself significantly reduced HIV infectivity in vitro and should not be used as an antifungal agent in cultures intended to propagate HIV.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Cells, Cultured; Drug Synergism; Drug Therapy, Combination; HIV; HIV Infections; Humans; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adenosine Deaminase; Adult; Amphotericin B; Drug Therapy, Combination; Fluconazole; Humans; Male; Meningitis, Cryptococcal

We discuss 19 cases of infection due to Cryptococcus neoformans diagnosed in 438 AIDS patients admitted to our center (4%). Fourteen of them showed meningitis confirmed by culture of C. neoformans in CSF. Clinical features were rather unspecific and disorders in CSF parameters were non striking. The diagnostic techniques performed with best results were culture of C. neoformans and antigen determination, especially in serum. Survival probability at one year was 75%. Treatment response was good. Treatment with fluocytosine did not seem to provide additional benefits versus amphotericin alone, neither in respect to clinical evolution nor regarding survival probability at one year. Fluconazole has shown effectiveness in maintenance therapy, being not be possible to evaluate it as an acute phase therapy because the low number of cases in which it was studied. It is advisable to follow a suppressive treatment, having found a 10% relapse rate in patients following therapy and a 50% in those who interrupted it.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; HIV-1; Homosexuality; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Opportunistic Infections; Substance Abuse, Intravenous

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Fluconazole; Humans; Meningitis, Cryptococcal; Recurrence

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Azoles; Costs and Cost Analysis; Cryptococcosis; Humans; Rwanda

A 30-year-old, HIV-positive, man who had been repeatedly treated with amphotericin B for oral thrush, developed headaches, fever up to 38.5 degrees C, dizzy spells with falling tendency, as well as disorder of speech and word finding. Cerebrospinal fluid (CSF) contained 5700/3 cells, of which 90% were encapsulated yeast-fungus. Cryptococcal antigen titres were elevated both in serum (1:256) and CSF (1:1024), providing the diagnosis of cryptococcal meningitis. Intravenous treatment was started with amphotericin B, 0.3 mg/kg daily and flucytosine, 150 mg/kg daily. The clinical, microbiological and serological findings regressed after 4 weeks. After 8 weeks the creatinine concentration rose to 2.5 mg/dl. Because amphotericin B nephrotoxicity was suspected, further intravenous administration was stopped after a cumulative dosage of 2 g. He was placed on a prophylactic dosage of fluconazole, 100 mg by mouth twice daily. The cryptococcal antigen titre had fallen to normal within one year. The prophylactic regimen has been continued now for three years without recurrence or other fungal infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antigens, Bacterial; Cryptococcus; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Male; Meningitis, Cryptococcal; Opportunistic Infections; Recurrence; Time Factors; Zidovudine

Three patients with AIDS who had cryptococcal meningitis were treated with liposomal amphotericin B after unsuccessful treatment with fluconazole and conventional amphotericin B. One patient responded but relapsed nine weeks later; he responded to a second course of treatment but again relapsed and subsequently died. Another patient deteriorated despite an improvement in cryptococcal antigen titres. The third patient was found to have culture negative CSF and treatment was therefore stopped. None of the patients suffered any adverse effects and renal function improved in all after conventional amphotericin was stopped and liposomal amphotericin B commenced.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Creatinine; Drug Carriers; Humans; Liposomes; Male; Meningitis, Cryptococcal

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Candida albicans; Candidiasis; Humans; Male; Meningitis, Fungal

We report a case of Candida albicans meningitis in a male with human immunodeficiency virus (HIV) infection. This finding has seldom been reported, both in this group of patients and in those with other causes of immunosuppression or other underlying diseases. We discuss the clinical presentation and the features of cerebrospinal fluid, which showed only a mild inflammatory reaction as found in other fungal meningitis (basically cryptococcal) in AIDS patients. Finally, we emphasize the ineffectiveness of amphotericin therapy to achieve a complete microbiological cure and to prevent the relapse of meningitis in this patient. We also stress the need to make an early diagnosis in cases of fungal meningitis in patients with VIH infection, so that appropriate therapy is begun as soon as possible.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Candidiasis; Drug Therapy, Combination; Flucytosine; Humans; Immunocompromised Host; Ketoconazole; Male; Meningitis, Fungal

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Confidence Intervals; Cryptococcosis; Fluconazole; Humans; Male; Meningitis; Prospective Studies; Prostatic Diseases; Recurrence

These patients demonstrate the difficulty in arriving at the diagnosis of disseminated histoplasmosis. The diagnosis in two of the three patients also served as the initial AIDS case-defining opportunistic infection. In each of these patients, the clinical presentations were atypical and in only one patient was a positive exposure history elicited. Recurrent bowel obstruction was the presenting complaint in the first patient and the diagnosis was made only on pathologic exam of the resected small bowel. The second patient's diagnosis was made on biopsy of the colon via colonoscopy. The third patient's diagnosis also eluded an extensive FUO workup; he was diagnosed by bone marrow culture and silver stain of a mediastinal lymph node biopsy, despite serial negative serologic tests for histoplasmosis. The first two patients had significant gastrointestinal disease which is a relatively unusual manifestation for disseminated histoplasmosis. The third patient illustrates the limited diagnostic usefulness of serologic testing in AIDS patients and the continued usefulness of bone marrow analysis in an FUO evaluation. In conclusion, these case presentations demonstrate that disseminated histoplasmosis in patients with HIV infection can present with unusual manifestations, outside of the typical endemic arca, without a positive exposure history or positive serologic test, and may be the initial AIDS case-defining opportunistic infection in these patients. Consequently, a disseminated histoplasmosis should be considered in all AIDS patients with perplexing clinical presentations.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Amphotericin B; Female; Histoplasma; Histoplasmosis; Humans; Ketoconazole; Male; Maryland; Middle Aged; Opportunistic Infections

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Humans; Liposomes; Male

Although amphotericin B (AB) is the primary therapeutic agent for cryptococcosis complicating the acquired immunodeficiency syndrome (AIDS), the total dose administered is extremely variable, and the end point of therapy has not been well defined. Since these patients require life-long suppressive therapy following the primary therapy, the definition of treatment "end point" becomes crucial. To delineate more effective treatment approaches, we reviewed the medical records of 48 patients with cryptococcosis complicating AIDS. Fever (81%) and headache (77%) were the predominant symptoms. A clinical response to AB (defervescence and resolution of symptoms) was noted in 46% of the febrile patients. The cumulative AB dose administered to the time of clinical response was variable (0.1-1.76 g), but was noted early in the majority of the patients (less than 0.4 g). Repeat fungal cultures from the initial positive site for Cryptococcus neoformans (CN), obtained after observation of the clinical response, were negative in 7/7 patients. Nosocomial bacterial infections were quite common and often complicated intravenous AB therapy. Bacteremias were documented in 10/14 febrile episodes occurring during AB therapy in the 22 patients with an initial clinical response. Bacteremias were identified in 6/21 patients who failed to defervesce with AB therapy. Staphylococcus aureus (N = 9) and Salmonella species (N = 2) were the most common pathogens causing bacteremia. An algorithm for the treatment of cryptococcosis complicating AIDS may shorten the duration of primary intravenous AB therapy. This might reduce secondary infectious complications and the costs of hospitalization.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Female; Humans; Male; Middle Aged; Opportunistic Infections

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Female; Humans; Latin America; Opportunistic Infections; Paracoccidioidomycosis

The extra demands placed upon health care resources by management of AIDS patients have increased the focus on cost implications of therapeutic alternatives. Cryptococcal meningitis is a common life-threatening infection in AIDS patients, usually treated with amphotericin B, often in combination with flucytosine. Administered intravenously, this therapy is associated with frequent and often severe side effects. Fluconazole is a new alternative which can be given orally once daily and has fewer such side effects. The purpose of this study was to examine the cost implications of these different therapies for both primary and maintenance treatment of cryptococcal meningitis. Comparison of these two therapies in recent clinical trials has indicated that fluconazole is at least as effective as amphotericin B, and therefore cost-minimisation analysis is an appropriate method to study the economic consequences of the alternative treatments. Patient management and resource-use information for both treatments was obtained using a modified Delphi technique with a panel of European physicians experienced in the treatment of this disease, and three models were developed to reflect the variability of practice evident among the panel members. U.K. health care costs were used to value these resources. The results indicated that, despite the higher cost of the drug itself, the costs associated with fluconazole were likely to be markedly less than those for amphotericin B for primary treatment, and similar or slightly cheaper for maintenance treatment. Over 1 year of treatment, the saving from the use of fluconazole would be in the range of 4000-14,000 pounds.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Amphotericin B; Costs and Cost Analysis; Cryptococcosis; Delphi Technique; Drug Therapy, Combination; Fluconazole; Flucytosine; Hospitalization; Humans; Infusions, Intravenous; Meningitis; Models, Theoretical; Surveys and Questionnaires

We have reported what we believe to be the first case of disseminated infection due to a multiply drug resistant strain of Nocardia asteroides in a patient with the acquired immunodeficiency syndrome and concomitant disseminated histoplasmosis. This strain of the organism fits a pattern of susceptibility that is rare among N asteroides isolates in general and has been called the type 5 pattern, described as a resistance to broad spectrum cephalosporins, ciprofloxacin, and all aminoglycosides except amikacin. The recognition of disease due to this group of organisms is especially important in patients with AIDS because sulfonamides, considered the drugs of choice for treatment of N asteroides infection, are associated with a high incidence of adverse effects in these patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Drug Resistance, Microbial; Histoplasmosis; Humans; Ketoconazole; Male; Nocardia asteroides; Nocardia Infections

To determine the spectrum of esophageal disease responsible for dysphagia/odynophagia in AIDS patients not responding to current oral antifungals, we studied 49 consecutive patients whose esophageal symptoms failed to improve after a minimum of 3 wk of therapy with oral ketoconazole or fluconazole. An esophageal candidiasis resistant to oral antifungals was the most frequent disease found (22 single infections and four mixed with viruses). Viral esophagitis was identified in 13 cases (eight herpes simplex virus and five cytomegalovirus), and an esophagitis of unknown origin was documented in two patients. Other causes of symptoms included peptic esophagitis (four cases), esophageal stenosis (two cases), and Kaposi's sarcoma of the esophagus (one patient). Most patients with esophageal opportunistic infection experienced prompt relief of symptoms and complete endoscopic resolution on the specific antifungal (amphotericin B or fluconazole iv) or antiviral (acyclovir or gancyclovir iv) therapy, with the exception of those with concomitant fungal and viral infection who responded poorly to treatment. We conclude that most AIDS patients with dysphagia/odynophagia who do not respond to oral antifungals have an opportunistic infection of the esophagus. Nevertheless, specific antifungal or antiviral therapy is worthwhile, because it will eradicate, at least temporarily, the causative pathogens in most such patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Drug Resistance, Microbial; Esophagitis; Female; Fluconazole; Ganciclovir; Humans; Infusions, Intravenous; Ketoconazole; Male; Opportunistic Infections; Prospective Studies; Treatment Outcome

Colonic histoplasmosis is a rare entity. There have been four previous reported cases within the population of patients with human immunodeficiency virus (HIV) infection. Because of the increasing incidence of HIV infection within regions where histoplasmosis is endemic, this condition may become more common. Gastrointestinal histoplasmosis has protean clinical manifestations, and symptoms are often nonspecific. Any patient with HIV infection who has unexplained GI symptoms should undergo evaluation for possible histoplasmosis. Aggressive long-term amphotericin B therapy has been effective in HIV patients with histoplasmosis. Resection or diversion of symptomatic colonic strictures caused by histoplasmosis may be necessary in addition to medical therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Colonic Diseases; Histoplasmosis; Humans; Intestinal Obstruction; Male; Middle Aged

We describe a patient with the acquired immunodeficiency syndrome who had persistent oral esophageal pseudomembranous candidiasis clinically refractory to nystatin, clotrimazole, and ketoconazole. In vitro resistance to clotrimazole was demonstrated as well. The patient received temporary relief with intravenous amphotericin B therapy, but this was associated with serious adverse effects, including transfusion-requiring anemia, azotemia, and severe thrombophlebitis. Despite two courses of intravenous amphotericin B therapy, the patient's highly symptomatic, recurrent oral and esophageal candidiasis continued. The patient was then treated with fluconazole and obtained immediate relief without associated adverse effects.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Candida albicans; Candidiasis, Oral; Clotrimazole; Deglutition Disorders; Drug Resistance, Microbial; Esophageal Diseases; Fluconazole; Humans; Ketoconazole; Male

Although cryptococcal meningitis is a frequent infection in patients with AIDS, papilledema is rarely reported. We have reported a case of profound papilledema associated with cryptococcal meningitis in a patient with AIDS. After treatment failure with amphotericin B, the patient was successfully treated with fluconazole, and the papilledema resolved.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Fluconazole; Humans; Male; Meningitis; Papilledema

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Carriers; Humans; Liposomes; Male; Meningitis

In a thirty-year-old patient with AIDS the diagnosis of disseminated histoplasmosis was established via biopsy and culture. The patient had grown up in Argentina, where histoplasmosis is endemic. He had not been in an endemic region during the last two years anteceding the manifestation of systemic histoplasmosis. Accordingly, in patients with a progressive immunodeficiency syndrome, reactivation of a former (possibly inapparent) infection with Histoplasma capsulatum must be considered. Therapy with Amphotericin B lead to a remarkable improvement of clinical, laboratory and sonographic findings. Due to the fact that total eradication of H. capsulatum from the infected host cannot be achieved with any known drug regimen, a life-long follow-up therapy was begun. The patient showed no signs of relapse after a follow-up of 7 months.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Histoplasmosis; Humans; Male

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Clindamycin; Communicable Diseases; Fluconazole; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

Cryptococcosis is a systemic fungal disease and meningeal or meningoencephalitis involvement is the most serious complication. This is a retrospective analysis of 80 patients admitted from December 1983 to October 1985 (30 cases) and June 1987 to December 1988 (50 cases) in hospital of Bujumbura, Burundi, Central Africa. All patients have an AIDS. Clinically, the meningeal and meningoencephalitis attack prevails in 87% cases. The diagnosis in our study is essentially based on the examination of the CRL. Before the new antifungals, the treatment involved the association of amphotericin B and 5-fluorocytosine, during 6 to 8 weeks. This treatment was badly tolerated and the second falls, when the therapy was stopped, were frequent. Presently, the fluconazole is the best treatment of this affection (ailment?): it enables maintenance therapy for a disease in which the risks of recurrence and reinfection by the environment are not negligible in Africa.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Amphotericin B; Burundi; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Male; Middle Aged; Retrospective Studies

The history of 29-year-old male from Surinam with antibodies to HIV-1 and long-lasting fever, lymphadenopathy, pain in the right upper abdomen and a granulomatous hepatitis is described. The patient suffered from disseminated histoplasmosis, a fungal disease rare in The Netherlands, which is the indicator disease for the diagnosis of AIDS (CDC-IVCI). It is stressed that in seropositive patients coming from endemic areas, including Surinam, the possibility of this disease should be considered.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Drug Therapy, Combination; Histoplasma; Histoplasmosis; Humans; Male; Zidovudine

Fungal infections have become one of the major causes of death among immunocompromised patients, particularly patients with AIDS. Accurate and quick diagnosis is difficult; therefore, empirical therapy is often necessary. This scenario is complicated by the fact that most antifungal agents are toxic at the doses used or relatively ineffective against deep-seated mycoses. Because the population of AIDS patients is increasing, physicians will be faced more often with the management of systemic fungal infections. Despite the current bleak prognosis for these patients, several new antigen detection tests are being developed and triazole agents are proving to be effective and less toxic than their predecessors. Many cases of systemic mycoses do result in mortality, but appropriate treatment can both prolong life and improve its quality.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Azoles; Candidiasis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Meningitis; Mycoses

Fluconazole, a novel triazole antifungal drug, holds promise as a significant advance in the management of human fungal diseases. This new drug can be both orally and parenterally administered and is reported to be less toxic than other antifungal agents. The Authors studied the in vitro susceptibility of yeasts isolated from AIDS patients to this antimycotic drug, in order to evaluate if fluconazole's MICs were comparable to those of amphotericin B. A sample of 200 yeast strains (100 C.albicans, 20 C.parapsilosis, 20 C.tropicalis, 8 C.guilliermondii, 6 C.krusei, 6 C.pseudotropicalis, 24 T.glabrata and 16 Cr.neoformans) was tested. The results show an average MIC for amphotericin B (MIC90: 3.12 micrograms/ml) ten-fold lower than for fluconazole (MIC90: 100 micrograms/ml). However, C.albicans and Cr.neoformans presented the same MIC value (3.12 micrograms/ml) both for fluconazole and for amphotericin B, suggesting that fluconazole could represent a valid alternative to amphotericin B in the treatment of fungal infections caused by these two agents.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Candida; Cryptococcus neoformans; Fluconazole; Humans; Microbial Sensitivity Tests; Mycoses; Yeasts

We report four cases of acute reversible renal failure in patients with acquired immune deficiency syndrome who received both amphotericin B (for systemic mycoses) and pentamidine isethionate (for Pneumocystis carinii pneumonia). The concurrent use of amphotericin B with either inhaled pentamidine or trimethoprim-sulfamethoxazole did not cause significant renal impairment.

Topics: Acquired Immunodeficiency Syndrome; Acute Kidney Injury; Adult; Amphotericin B; Drug Therapy, Combination; Female; Humans; Male; Mycoses; Pentamidine; Pneumonia, Pneumocystis

Two patients with acquired immune deficiency syndrome presented with headaches and fevers. A diagnosis of cryptococcal meningitis was made by lumbar puncture and elevated cryptococcal antigens. Complaints of decreased vision in both patients led to the diagnosis of optic disc edema and cryptococcal choroiditis with yellow-white choroidal infiltrates noted in both eyes of the two patients. Systemic treatment with amphotericin B and 5' flucytosine led to resolution of the choroidal infiltrates. Late visual acuity loss was believed to be secondary to optic atrophy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antigens, Fungal; Choroiditis; Cryptococcosis; Eye Infections, Fungal; Flucytosine; Fluorescein Angiography; Fundus Oculi; Humans; Male; Papilledema; Visual Acuity

Disseminated histoplasmosis was diagnosed in 36 (4%) of 980 patients with AIDS seen at Parkland Memorial Hospital in Dallas, Texas before September 30, 1989. Diagnostic sensitivity of blood culture plus examination of peripheral smear was 88%; sensitivity of bone marrow aspiration and blood culture was 80%. Median CD4 lymphocyte count at diagnosis was 33/cu mm. Median actuarial survival from the date histoplasmosis was diagnosed was 188 days. Thirteen (36%) of the 36 patients died before adequate antifungal therapy could be administered, while 13 survived long enough to receive 1,500 mg of amphotericin B; actuarial survival of the latter group from the date 1,500 mg of amphotericin B had been infused was 47% at 1 year. The substantial early mortality of AIDS-associated disseminated histoplasmosis and the modestly encouraging survival of those who were diagnosed in time to receive adequate therapy raise the issues of surveillance, prophylaxis, and empiric therapy for this infection in selected HIV-positive patients.

Topics: Acquired Immunodeficiency Syndrome; Actuarial Analysis; Adult; Amphotericin B; Cryptococcosis; Evaluation Studies as Topic; Female; Histoplasma; Histoplasmosis; Humans; Ketoconazole; Male; Middle Aged; Retrospective Studies; Texas; Time Factors

The AIDS epidemic has made previously uncommon infectious diseases and tumors commonplace in HIV-infected individuals. In this article we discuss specific cases of various infections and tumors of the sinonasal tract. Several of these diseases may be the presenting signs of HIV-seropositivity and AIDS. As a result, the clinician first to see such patients must be aware of the diagnosis of these diseases and tumors so that proper testing and treatment may ensue.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Anti-Bacterial Agents; HIV Seropositivity; Humans; Ketoconazole; Nasopharyngeal Diseases; Opportunistic Infections; Paranasal Sinus Diseases; Rifampin; Therapeutic Irrigation

Disseminated histoplasmosis is an increasingly important opportunistic infection in patients with the acquired immunodeficiency syndrome (AIDS). We report the first case of histoplasmosis as a cause of pleural effusion in a patient with AIDS. Recognition of the typical intracellular yeast on a Wright-Giemsa stained smear of the pleural fluid cells allowed prompt initiation of amphotericin B.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Histoplasma; Histoplasmosis; Humans; Male; Opportunistic Infections; Pleural Effusion

Multiple drug effect analyses with mismatched double-stranded RNA (mismatched dsRNA or Ampligen) as a core drug were performed to identify other agents and mechanisms through which mismatched dsRNA may potentiate effective therapeutic intervention in human immunodeficiency virus (HIV) infection. Antiviral activities were defined by a microtiter infection assay utilizing MT-2 cells as targets and HTLV-III-B produced in H9 cells as a virus source. The scope of agents tested included rIFN-alpha A, rIFN-beta Ser 17, and rIFN-gamma as cytokines; azidothymidine and phosphonoformate (Foscarnet) as inhibitors of reverse transcription; ribavirin as a putative inhibitor of proper HIV mRNA capping; amphotericin B as a lipophile; and castanospermine as a glycoprotein processing (glucosidase I) inhibitor. Separately, each drug demonstrated dose-dependent anti-HIV activity and, when used in combination with mismatched dsRNA, demonstrated synergism. Although mismatched dsRNA was synergistic with all three IFNs for anti-HIV activity in microtiter infection assays, it did not potentiate the transient inhibition of virus production observed for IFN in cultures of H9/HTLV-III-B cells. The results of these studies suggest that the pleiotropic activities of dsRNAs differ from those of IFN and may provide synergism in combination therapy with a wide range of antiviral drugs for the treatment of the acquired immunodeficiency syndrome (AIDS).

Topics: Acquired Immunodeficiency Syndrome; Alkaloids; Amphotericin B; Antiviral Agents; Drug Therapy, Combination; Foscarnet; HIV; Humans; In Vitro Techniques; Indolizines; Interferon beta-1a; Interferon beta-1b; Interferon Type I; Interferon-beta; Interferon-gamma; Interferons; Microbial Sensitivity Tests; Phosphonoacetic Acid; Recombinant Proteins; Ribavirin; RNA, Double-Stranded; Zidovudine

This report shows the potential of using a liposomal encapsulated preparation of amphotericin B (a polyene macrolide antibiotic) for the in vitro inhibition of HIV. There was no significant difference between the effective doses of the free form of drug when compared to the liposomal encapsulated preparation in inhibiting the growth of HIV. Virus expression was suppressed at a concentration of 5-10 micrograms/ml of the drugs. The liposomal preparation showed greatly reduced cytotoxicity in experiments using cultures of murine leukocytes. These results show the potential usefulness of liposomal encapsulated drugs in the treatment of patients with AIDS or AIDS related complex.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Animals; Antibodies, Viral; Cell Line, Transformed; Complement Fixation Tests; Dose-Response Relationship, Drug; Drug Carriers; Fluorescent Antibody Technique; HIV-1; Humans; Immunoglobulin G; Liposomes; Mice; RNA-Directed DNA Polymerase; Spleen; Virus Replication

Cryptococcosis and aspergillosis in immunocompromised patients are extremely difficult clinical conditions to manage and treatment with available antifungal drugs often fails. Itraconazole, R-51211, Janssen Pharmaceutica, a new orally absorbed triazole, is a possible alternative drug which is potentially effective and nontoxic. Preliminary experience with 28 patients, eight with cryptococcosis and 20 with aspergillosis, is reported. Of these patients, 16 were immunocompromised (seven with the acquired immune-deficiency syndrome (AIDS), five heart transplant recipients and four with leukaemia or lymphoma). Overall, results of treatment were good (18 in remission, four markedly improved, four moderately improved and two failed). Prevention of relapses of cryptococcosis was obtained in all patients with AIDS on long-term itraconazole monotherapy (3 mg/kg). Treatment of invasive aspergillosis required a higher dosage (about 5 mg/kg) and prolonged administration. Besides its efficacy this antifungal agent allowed outpatient management.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Cryptococcosis; Disease; Heart Transplantation; Humans; Immunosuppression Therapy; Itraconazole; Ketoconazole; Male; Neoplasms; Opportunistic Infections

To assess the frequency of persistent Cryptococcus neoformans infection in patients with the acquired immunodeficiency syndrome (AIDS) after receiving apparently adequate treatment for meningitis.. Blood, urine, and cerebrospinal fluid were cultured at the conclusion of primary therapy to assess the adequacy of treatment.. Outpatient clinics at three medical centers.. Patients had C. neoformans grown in culture from cerebrospinal fluid. Primary therapy consisted of either 2.0 g of amphotericin B alone; 6 weeks of combination therapy with flucytosine; or, if flucytosine was poorly tolerated, an adjusted minimum total amphotericin B dose. To meet criteria for adequate treatment of meningitis all patients had two sequential cerebrospinal fluid samples which were culture negative.. Nine of forty-one patients grew C. neoformans from urine after completion of primary treatment, but none had urinary symptoms. Fungi were visualized in expressed prostatic secretions in 4 of these patients. One patient refused further treatment and developed cryptococcemia within 5 weeks. Three patients received additional amphotericin B; all had persistent funguria without systemic relapse. Six patients received fluconazole; 4 became urine culture negative, and 2 had systemic relapse.. The persistence of urinary C. neoformans after adequate therapy for meningitis suggests that the urinary tract (probably the prostate) is a sequestered reservoir of infection from which systemic relapse may occur.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; Humans; Male; Meningitis; Prostatic Diseases; Recurrence; Triazoles; Urine

We present the first case of disseminated histoplasmosis in an AIDS patient in Europe, a 33-year-old Danish homosexual man, and recommend a detailed travel history in HIV-positive patients presenting with fever, weight loss and organomegaly. In Scandinavia disseminated histoplasmosis is rare but should be kept in mind as the disease is a major opportunistic infection in patients with AIDS. Treatment with amphotericin B followed by fluconazole was effective.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Denmark; Fluconazole; Histiocytes; Histoplasma; Histoplasmosis; Homosexuality; Humans; Immunity, Cellular; Male; Microscopy, Electron

This report is a description of two Ohio cases of acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis, with discussion of diagnosis and treatment of this combination. The patient in case 1 developed disseminated histoplasmosis as the first significant symptomatic medical condition of his life. The patient in case 2 presented with severe pharyngitis, but without signs or symptoms specific to the lungs. Amphotericin B alone does not eradicate histoplasmosis in an AIDS patient. The best therapy at present is a full course of amphotericin B followed by a lifetime regimen of ketoconazole to prevent relapse. Family physicians in the District of Columbia, Texas, Maryland, Louisiana, Missouri, Illinois, Arizona, and Puerto Rico should be particularly vigilant in looking for the combination of these two diseases.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Histoplasmosis; Humans; Ketoconazole; Male; Middle Aged

The clinical and histopathological features and the therapeutic response of a pustular eruption occurring in a homosexual man with Acquired Immune Deficiency Syndrome (AIDS) is reported. The rare cutaneous presentation consisted of mostly circumscribed, tender, tense pustules, associated with erythema, confined to the face and neck. Biopsy of these lesions revealed intracellular round to oval bodies surrounded by a clear space, consistent with Histoplasma capsulatum. Prompt resolution was observed after initiation of amphotericin B therapy. Clinicians are alerted to the occurrence of exotic presentations of this entity and emphasis is given to the need for skin biopsy and culture to avoid delay in diagnosis and failure to initiate appropriate therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Histoplasmosis; Humans; Male; Opportunistic Infections

We reviewed the records of 106 patients with cryptococcal infections and the acquired immunodeficiency syndrome (AIDS) treated at San Francisco General Hospital. We examined four issues: the efficacy of treatment with amphotericin plus flucytosine as compared with amphotericin alone, the efficacy of suppressive therapy, the prognostic clinical characteristics, and the course of nonmeningeal cryptococcosis. In 48 of the 106 patients (45 percent), cryptococcosis was the first manifestation of AIDS. Among the 89 patients with cryptococcal meningitis confirmed by culture, survival did not differ significantly between those treated with amphotericin plus flucytosine (n = 49) and those treated with amphotericin alone (n = 40). Flucytosine had to be discontinued in over half the patients because of cytopenia. Long-term suppressive therapy with either ketoconazole or amphotericin was associated with improved survival, as compared with survival in the absence of suppressive therapy (median survival, greater than or equal to 238 vs. 141 days; P less than 0.004). The only clinical features independently associated with a shorter cumulative survival were hyponatremia and a positive culture for cryptococcus from an extrameningeal source. The 14 patients with nonmeningeal cryptococcosis had a median survival (187 days) and rate of relapse (20 percent) similar to those in the patients with meningitis (165 days and 17 percent, respectively). From this retrospective study of cryptococcal infections in patients with AIDS we conclude that the addition of flucytosine to amphotericin neither enhances survival nor prevents relapse, but long-term suppressive therapy appears to benefit these patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Flucytosine; Humans; Hyponatremia; Ketoconazole; Male; Meningitis; Middle Aged; Pancytopenia; Prognosis; Recurrence

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Humans; Meningitis

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Histoplasmosis; Humans; Injections, Intravenous; Male; Skin; Substance-Related Disorders

Progressive disseminated histoplasmosis (PDH) has now been described in acquired immunodeficiency syndrome (AIDS) patients from areas both endemic and nonendemic for histoplasmosis. We review the clinical presentation, diagnosis, and therapy of PDH in patients with AIDS by comparing 64 patients from our series collected retrospectively from Houston and the surrounding area with the case summaries of 61 patients reported in the medical literature. PDH occurred as the first manifestation of AIDS half of the time. Fever, weight loss, enlargement of the liver, spleen, or lymph nodes, and anemia were the most common clinical symptoms and signs. Pulmonary symptoms were less common. The chest roentgenogram showed diffuse interstitial infiltrates in slightly more than half of the patients. Bone marrow biopsy and culture, examination and culture of pulmonary tissue and secretions, and blood culture were the most common initial means of establishing a diagnosis. Ketoconazole alone was ineffective in the majority of cases. Patients treated with amphotericin B (AMB) in a dose of at least 30 mg/kg experienced a significantly longer period of follow-up than those treated with less AMB. However, relapses were observed in four of 16 patients (25%) receiving at least 30 mg/kg of AMB followed by ketoconazole suppression. It appears that long-term suppression with 50 to 100 mg of AMB weekly, after completion of initial therapy, has the best chance of maintaining a satisfactory functional status.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Biopsy; Histoplasma; Histoplasmosis; Humans; Ketoconazole; Lung; Radiography

Disseminated histoplasmosis is a serious and often rapidly progressive, opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), supporting the importance of rapid diagnostic tests. We investigated Histoplasma capsulatum polysaccharide antigen (HPA) detection, a promising new method for rapid diagnosis of histoplasmosis.. Sixty-one cases of disseminated histoplasmosis in patients with AIDS form the basis of this report. Control cases were patients with AIDS who had other opportunistic infections and whose cultures were negative for H. capsulatum. A slightly modified radioimmunoassay procedure was used to measure the levels of HPA in urine and blood specimens.. High levels of HPA were detected in the urine of 59 of 61 (96.7%) and the blood of 37 of 47 (78.7%) patients with AIDS complicated by disseminated histoplasmosis. Treatment with amphotericin B reduced levels of HPA in the urine in 19 of 21 (90.5%) and the serum of all 10 patients tested. HPA levels increased in the urine in all eight and in the serum in all five patients with culture-proven relapse.. In conclusion, HPA detection offers a rapid method for diagnosing disseminated histoplasmosis. Additional experience is required to establish the role of this test in monitoring the effects of treatment and in identifying relapse in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antigens, Fungal; Blood; Histoplasma; Histoplasmosis; Humans; Opportunistic Infections; Polysaccharides; Radioimmunoassay; Recurrence

To assess the efficacy and toxicity of long-term maintenance amphotericin B therapy in preventing relapses after treatment in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis.. Open, nonrandomized pilot study.. Three private, university-affiliated community hospitals.. We studied 22 consecutive patients with disseminated histoplasmosis and human immunodeficiency virus (HIV) infection. Sixteen patients completed the study, 5 patients died before completing the initial intensive phase of treatment, and 1 patient received a different treatment regimen.. Seven patients were treated with an initial intensive course of 1000 mg of amphotericin B, followed by weekly infusions of 50 to 80 mg until a cumulative dose of 2000 mg was attained; biweekly infusions of 50 to 80 mg were then continued indefinitely. Nine patients received an initial amphotericin B course of 2000 mg followed by weekly infusions of 80 mg.. Of the 7 patients in the 1000-mg intensive regimen group, 6 patients have survived without clinical or laboratory evidence of a histoplasmosis relapse, and 1 died of unrelated causes. Of the 9 patients in the 2000-mg intensive regimen group, 7 patients have survived, 1 patient died of a histoplasmosis relapse, and 1 patient died of other causes. Thus, 13 of 14 patients (93%) who did not die of other causes remained relapse-free. The median follow-up period was 14 months (range, 2 to 23 months). No apparent differences in outcome were observed between patients treated with weekly maintenance regimens and those treated with biweekly maintenance regimens. Sixty-three percent of patients developed intravascular device-related complications.. Long-term, intermittent maintenance amphotericin B therapy in HIV-infected patients with disseminated histoplasmosis is well tolerated and is highly effective in suppressing relapses after treatment.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Catheters, Indwelling; Drug Administration Schedule; Female; Histoplasmosis; Humans; Male; Middle Aged; Opportunistic Infections; Pilot Projects; Recurrence

The clinical course and response to therapy of seven patients with cryptococcosis and AIDS were reviewed. One patient was still in the primary stage of cryptococcosis in AIDS, i.e. the stage that is characterized by the sole cultural detection of Cryptococcus neoformans in the respiratory tract. The other six patients were in the secondary stage, where C. neoformans can be detected from the cerebrospinal fluid (CSF), blood, urine, faeces and other body sites. The main presenting features (headache, fever, nausea) were due to central nervous system involvement, although meningism and mental changes were rarely present, and CSF changes were very subtle. Treatment with amphotericin B and flucytosine was very effective, there being no more growth of fungi in cultures in most cases. Adverse reactions to the drugs used occurred frequently and consisted mainly of anaemia, hepatosis and fever. Diagnosis in the primary stage of cryptococcosis may improve the prognosis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male; Nervous System Diseases; Opportunistic Infections

Three cases are reported of patients with the Acquired Immune Deficiency Syndrome (AIDS) and cutaneous histoplasmosis. Their initial presentation was that of a generalised maculopapular rash. Two patients were bisexual males and the third was an unmarried female. The range of opportunistic infections seen in AIDS patients in Trinidad is mentioned and clinicians are alerted to the fact that in areas endemic for Histoplasma capsulatum maculopapular rash in patients with AIDS may suggest disseminated histoplasmosis. The value of skin biopsy is mentioned.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Biopsy; Dermatomycoses; Enzyme-Linked Immunosorbent Assay; Female; Histoplasmosis; Humans; Ketoconazole; Male; Middle Aged; Staining and Labeling; Trinidad and Tobago

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole; Humans; Male; Meningitis; Triazoles

We describe a patient who presented with cryptococcosis and the adult respiratory distress syndrome (ARDS) as the initial manifestation of the acquired immunodeficiency syndrome. This patient represents the first reported recovery from ARDS secondary to widespread cryptococcosis. He is currently doing well as an outpatient on maintenance therapy with amphotericin B and azidothymidine.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antiviral Agents; Cryptococcosis; Humans; Intubation, Intratracheal; Male; Radiography; Respiratory Distress Syndrome; Thymidine; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Opportunistic Infections

Cryptococcus neoformans strains from 26 individual patients with acquired immunodeficiency syndrome (AIDS) and three isolates from patients without AIDS were tested for their susceptibility to amphotericin B, flucytosine, ketoconazole, and miconazole nitrate. Ninety percent of the C neoformans isolates from patients with AIDS were inhibited by drug concentrations within achievable serum levels. The minimum fungicidal concentration of the four tested antifungal agents, however, exceeded obtainable cerebrospinal fluid levels.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Cryptococcus; Cryptococcus neoformans; Flucytosine; Humans; Ketoconazole; Miconazole; Microbial Sensitivity Tests

Progressive disseminated histoplasmosis is now diagnosed frequently in patients with the acquired immunodeficiency syndrome (AIDS) living in the central United States. Previous review articles of AIDS have failed to mention this infection. Herein, we describe 48 AIDS patients with progressive disseminated histoplasmosis in an effort to better understand the clinical presentation and diagnosis of the condition in this setting and to assess the efficacy of antifungal chemotherapy.. In the Houston metropolitan area, there were 66 cases of progressive disseminated histoplasmosis among 1,300 confirmed cases of AIDS from January 1983 to July 1987. Of AIDS patients in East Texas with histoplasmosis, 16 patients were available for follow-up by one of us, and the histories of 32 were obtained by examination of hospital charts and physician records.. Fever, weight loss, and splenomegaly were the most common presenting signs and symptoms, occurring in 81, 52, and 31 percent, respectively. One-third of the patients had hematologic abnormalities. Infiltrates on chest roentgenograms were observed in 52 percent. Progressive disseminated histoplasmosis was the initial manifestation of AIDS in almost three-fourths of our patients. Biopsy and culture of the bone marrow established the diagnosis of progressive disseminated histoplasmosis in 69 percent. Clinical or autopsy proof of relapse occurred in three patients despite an initial course of more than 2 g of amphotericin B chemotherapy followed by ketoconazole suppression.. Progressive disseminated histoplasmosis is often the first sign of immunodeficiency in patients with AIDS, and the diagnosis of this condition is most often established by bone marrow biopsy and culture. Because of the permanence of the immunodeficient state in these patients, progressive disseminated histoplasmosis is resistant to treatment.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Female; Histoplasmosis; Humans; Ketoconazole; Male; Middle Aged

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Flucytosine; Humans; Lung Diseases, Fungal; Male

Involvement of the central nervous system (CNS) by Histoplasma capsulatum is a rare event. It is usually not included in the differential diagnosis of CNS lesions in patients with acquired immunodeficiency syndrome (AIDS). Herein are described four patients with AIDS and progressive disseminated histoplasmosis who had CNS involvement. Histoplasmosis in the CNS may produce meningitis, single or multiple brain abscesses, and may present with either a clinical picture of obtundation or a deteriorating space-occupying CNS lesion. Three of the four patients were treated with amphotericin B and had initial clinical response, but ultimately, all experienced a relapse and died from their infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Central Nervous System Diseases; Histoplasmosis; Humans; Male

A widespread maculo-papular cutaneous rash appeared on a HIV-positive young bisexual Cambodian man. He was treated for Mycobacterium tuberculosis and Pneumocystis carinii infections. He had been residing in France for seven years. Histology showed, within the dermis, abundant extracellular and intramacrophagic yeast-like organisms suggestive of histoplasmosis. Cultured specimens produced a growth of colonies after three weeks on Sabouraud 4 p. 100 dextrose agar at 25 degrees C. Numerous macroconidia were found which made the species diagnosis of Histoplasma capsulatum possible. Despite initiation of therapy with amphotericin B the patient died. Cutaneous involvement with or without specific features is uncommon in disseminated histoplasmosis. The specific cutaneous lesions are protean. They rarely are the presenting sign of initial infection. Disseminated histoplasmosis has a poor prognosis in acquired immunodeficiency syndrome: amphotericin B is not curative. Maintenance suppressive therapy with ketoconazole has been recommended following amphotericin B completion, although break-through has been reported.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Biopsy; Dermatomycoses; Histoplasmosis; Humans; Male; Prognosis

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Drug Administration Schedule; Follow-Up Studies; Humans; Meningitis; Recurrence

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male

Of 27 patients with the acquired immunodeficiency syndrome (AIDS) in Tucson, Arizona, 7 had concurrent coccidioidomycosis. Early manifestations of infection in 6 patients included diffuse nodular pulmonary infiltrates and Coccidioides immitis in many extrathoracic sites. By comparison, a retrospective review of the cases of 300 patients hospitalized with coccidioidal infection identified only 13 patients without AIDS who had the same extent of infection, and only 3 of these patients had no immunosuppressing conditions. Antibodies for coccidioidal antigens at serum dilutions as high as 1:2048 were detected in 5 of the 7 patients with AIDS. Six had temporary responses to amphotericin B treatment, taken both alone and combined with ketoconazole, but all died within 14 months of their diagnosis of coccidioidomycosis. Because annual rates of coccidioidal infection in the Tucson area are 4% or less, the rate of 27% that we calculated, based on 7 patients having the infection during 26 years of risk for AIDS, suggests frequent reactivation of the infection or enhanced susceptibility to endemic exposure in persons with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Arizona; Coccidioidomycosis; Humans; Ketoconazole; Lung Diseases, Fungal; Male; Middle Aged; Retrospective Studies

Cryptococcus neoformans is a major pathogen in patients with acquired immune deficiency syndrome and was found to infect 13.3 percent of such patients seen at two medical centers. Serum cryptococcal antigen levels were as high as 1:2,000,000 and, despite therapy, often remained elevated. Antigen titers in the cerebrospinal fluid generally declined at an expected rate in the survivors. The significance of high antigen titers in the blood after a prolonged course of therapy with amphotericin B and 5-flucytosine is unknown.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans

In two AIDS patients (homosexual men) microscopical demonstration of Cryptococcus neoformans in samples obtained by puncture of the liver (n = 1) and additionally of the spleen (n = 1) led to the diagnosis of systemic cryptococcosis. Using the India ink method capsulated Cryptococcus neoformans cells could also be detected in cerebrospinal fluid (CSF) and urine. Concomitant culture of the fungus from tracheal secretion, CSF, urine and faeces confirmed the diagnosis of a disseminated infection; the identification and germ count of C. neoformans was achieved by means of the differential-selective medium Guizotia-abyssinica-creatinine agar. The C. neoformans antigen titres in serum and CSF corresponded to the stage of the mycosis as detected by microscopy and culture. After a six-week course of treatment with amphotericin B and flucytosine (Ancotil), the fungus could no longer be isolated from the materials examined in one patient. Mycological monitoring aiming at the detection of C. neoformans in the tracheal secretions by means of the mentioned differential-selective medium is therefore recommended as a prophylactic measure in AIDS patients and persons at risk.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male

Five patients with disseminated histoplasmosis are reviewed. Four of five had the acquired immune deficiency syndrome (AIDS) and one was receiving steroid therapy. All were immigrants to the United States from Puerto Rico, the Dominican Republic, or South America, and none had a history of travel to regions of the United States where Histoplasma is endemic. Histoplasma complement fixation titers to mycelial antigen were not demonstrable in three of three patients in whom they were measured. Of the four patients with AIDS, Histoplasma capsulatum was isolated from bone marrow aspirates in two patients and from lymph node and liver biopsy specimens in one patient each. One of the bone marrow specimens showed organisms on Gomori-methenamine silver stain. In the other three cases, results of staining were falsely negative and diagnosis awaited culture results weeks later. Amphotericin B therapy resulted in rapid clinical improvement in the three patients that were treated. Intravenous therapy was followed by treatment with oral ketoconazole. Follow-up has not been long enough to determine the ultimate efficacy of ketoconazole. Disseminated histoplasmosis should be considered in all patients from the Caribbean or South America with AIDS or who are receiving immunosuppressive therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Drug Therapy, Combination; Ethnicity; Female; Histoplasma; Histoplasmosis; Humans; Ketoconazole; Male; Middle Aged

Between 1 January 1981 and 1 December 1984, 34 of 396 patients with the acquired immunodeficiency syndrome (AIDS) developed cryptococcal infections. Twenty-six cases are reviewed. Twenty-two patients had brain or meningeal disease; the others had pulmonary disease (2 patients), pericarditis (1 patient), and antigenemia (1 patient). During treatment, 3 patients died of cryptococcosis and 3 died of other causes. Fifteen patients were followed for more than 6 weeks after treatment. Of 8 patients who received no additional amphotericin B, 4 had relapses and died of cryptococcosis within 6 months, 3 died of other causes, and 1 survived. Of 7 patients who received maintenance therapy with amphotericin B, none had relapses, 3 died of other causes, and 4 survived. Our data suggest that maintenance therapy with amphotericin may be needed to prevent relapse in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Brain Diseases; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Injections, Intravenous; Injections, Intraventricular; Male; Meningitis; Middle Aged; Prognosis; Recurrence; Retrospective Studies; Tomography, X-Ray Computed

The risk for AIDS patients from Cryptococcus neoformans is outlined on the basis of a case report on a 28-year old male patient whose disease was complicated by cryptococcosis. Beside the description of the diagnosis of cryptococcosis (demonstration of the agent and its antigen), epidemiological associations (habitat of Cr. neoformans in fecal matter of birds) and the clinically, mostly not recognized, route of infection via the lungs is stressed. The effective therapy with the combination of amphotericin B and 5-flucytosine, which also in this case has been successful is described from the clinical and microbiological angles. Finally, proposals for the prevention of Cr. neoformans infections in AIDS patients and for a special mycological surveillance directed at this fungus are made.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Male; Meningoencephalitis; Risk

This report describes the experience with disseminated histoplasmosis in seven of 15 patients with the acquired immune deficiency syndrome (AIDS) diagnosed in Indianapolis since 1981. Three were homosexual, two were intravenous drug addicts, one was the spouse of another patient with AIDS and disseminated histoplasmosis, and the seventh was a hemophiliac. Six had associated infections: candidiasis in three, Pneumocystis carinii pneumonia, recurrent mucocutaneous herpes simplex infection, and disseminated Mycobacterium avium infection in two each, and disseminated infection with an unidentified mycobacterium in one. Clinical diseases suggested sepsis in four. Histoplasma fungemia occurred in five, but the diagnosis was established first by visualization of organisms in blood or bone marrow in three. Results of Histoplasma serologic tests were positive in each. Three died before receiving 50 mg of amphotericin B, three had prompt improvement with amphotericin B, and one was treated with ketoconazole to prevent dissemination. However, two of the three patients treated with amphotericin B had relapses after a 35 mg/kg course, and the third died within a month following therapy. Disseminated histoplasmosis is a major opportunistic infection in patients with AIDS from endemic areas. AIDS should be strongly considered in otherwise healthy persons with disseminated histoplasmosis, especially if risk factors for AIDS are present. Amphotericin B is not curative in these patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Candidiasis; Female; Herpes Simplex; Histoplasmosis; Homosexuality; Humans; Ketoconazole; Male; Mycobacterium avium; Mycobacterium Infections; Pneumonia, Pneumocystis; Tuberculosis

The clinical course and response to therapy of 27 patients with cryptococcosis and the acquired immunodeficiency syndrome were reviewed. Cryptococcosis was the initial manifestation of the syndrome in 7 patients, and the initial opportunistic infection in an additional 7. Meningitis was the commonest clinical feature (18 patients). Blood cultures and serum cryptococcal antigen were frequently positive. In patients with meningitis, leukocyte count, protein level, and glucose level in cerebrospinal fluid were frequently normal; cerebrospinal fluid India ink test (82%), culture (100%), and cryptococcal antigen (100%) were usually positive. Only 10 of 24 patients had no evidence of clinical activity of cryptococcal infection after completion of therapy; 6 of these 10 had relapses shown by clinical findings or at autopsy. Standard courses of amphotericin B alone or combined with flucytosine were ineffective. Cryptococcosis in patients with the syndrome is a debilitating disease that does not respond to conventional therapy; earlier diagnosis or long-term suppressive therapy may improve the prognosis.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antibodies, Fungal; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Encephalitis; Flucytosine; Humans; Meningitis; Retrospective Studies; Serologic Tests

The acquired immune deficiency syndrome (AIDS) has reached epidemic proportions in the USA and the incidence of this potentially fatal viral infection is increasing rapidly in Australia. The loss of normal cellular immunity in affected individuals predisposes them to severe opportunistic infections and neoplasms, especially Kaposi's sarcoma. Both of these pathological processes may affect the eye, and ocular involvement with an opportunistic infection or malignancy may be the first clue to the presence of AIDS. We present here the first Australian report of a patient with AIDS presenting with ocular involvement. The case is discussed in relation to current concepts of AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Candidiasis, Oral; Cryptococcosis; Eyelid Neoplasms; Flucytosine; Humans; Male; Sarcoma, Kaposi; Vinblastine

Disseminated histoplasmosis developed in a previously healthy man as the initial manifestation of the acquired immune deficiency syndrome. Following apparently successful therapy with intravenous amphotericin B, he presented two months later with a subacute pneumonitis syndrome diagnosed by bronchoscopy as Pneumocystis carinii pneumonia. He showed response to intravenous trimethoprim/sulfamethoxazole with resolution of his symptoms and clearing of chest radiographic findings. While he was receiving antibiotics, oral candidiasis developed and has persisted for more than two months despite topical therapy and discontinuation of all antibiotics.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Candidiasis, Oral; Histoplasmosis; Humans; Lymphocytes; Male; Pneumonia; Pneumonia, Pneumocystis; Pseudomonas Infections

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Histoplasmosis; Humans; Immunity, Cellular