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Over 14 years 41 patients were diagnosed as having pulmonary cryptococcosis. Cryptococcus neoformans remained localized to the lung in 12 cases and disseminated in the remaining 29. Thirty-four patients were compromised hosts. Disseminated disease developed in 28 of these 34, and four of these 28 patients with disseminated disease presented with concomitant pulmonary and meningeal infections. In all the remaining 24 central nervous system involvement developed 2 to 20 weeks after the finding of an abnormal chest roentgenogram. Seven patients were normal hosts, and in six of these cases disease remained localized to the lung. Four important conclusions were drawn from this study: pulmonary cryptococcosis is rarely considered in the differential diagnosis of an abnormal chest roentgenogram, thereby leading to missed diagnoses and therapeutic errors; the natural history of untreated pulmonary cryptococcosis in compromised hosts is extrapulmonic dissemination; compromised hosts with pulmonary cryptococcosis should receive antifungal therapy because of a high propensity for dissemination; and normal hosts in whom dissemination has been excluded generally do not need antifungal therapy. [ABSTRACT FROM AUTHOR]

One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter, prospective, randomized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy. Among 91 patients who met preestablished criteria for randomization, cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks. The estimated relapse rate for the four-week regimen was higher--27 as compared with 16 percent--whereas the incidence of toxic effects for the two regimens was similar--44 as compared with 43 percent. Among 23 transplant recipients, 4 of 5 treated for four weeks relapsed, leading to the decision to treat the rest of the group for six weeks. Only 3 of the 18 treated for six weeks relapsed. In a third group of 80 patients, the protocol was not followed during the initial four weeks, and these patients were not randomized. Thirty-eight died or relapsed. Multifactorial analysis of pretreatment factors for all 194 patients identified three significant predictors (P less than 0.05) of a favorable response: headache as a symptom, normal mental status, and a cerebrospinal fluid white-cell count above 20 per cubic millimeter. These and other findings in this study are consistent with the view that the four-week regimen should be reserved for patients who have meningitis without neurologic complications, underlying disease, or immunosuppressive therapy; a pretreatment cerebrospinal fluid white-cell count above 20 per cubic millimeter and a serum cryptococcal antigen titer below 1:32; and at four weeks of therapy, a negative cerebrospinal fluid India ink preparation and serum and cerebrospinal fluid cryptococcal-antigen titers below 1:8. Patients who do not meet these criteria should receive at least six weeks of therapy. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant (MDR) Gram-negative bacterial pathogens, often resistant to more than one class of antibiotics including carbapenems and aminoglycosides, pose serious threats in healthcare settings worldwide. A 2015 White House task force issued guidelines to combat antibiotic-resistant strains in the United States, which the Center for Diseases Center has termed "nightmare bacteria". MDR pathogens cause at least two million illnesses and 23,000 deaths annually in the U.S. MDR A. baumannii (MDR-Ab) cause 10% of hospital-acquired infections (HAI) with 70% patient mortality. A mini-outbreak of carbapenem-resistant (CR)MDR-Ab (CR-MDR-Ab) occurred during a 2009-2010H1N1epidemic at Carilion Medical Center (CMC) in Virginia, U.S; three of the nine patients died. To develop effective strategies for prevention, control and treatment of MDR infections, we are performing whole genome analysis of the clinical isolates of CR-MDR-Ab. Methods & Materials: To date, we have analyzed 68 Ab clinical isolates, including five CR-MDR-Ab outbreak strains. We have sequenced and analyzed whole genomes of the following MDRAb isolates: an isolate from outbreak patients (CMC-MDR-Ab4); a carbapenem-sensitive isolate (CMC-MDR-Ab59); and a CR-MDR-Ab (CMC-MDR-Ab66) isolate from sporadic cases. The sequencing was performed on the PacBioRSII platform. Results: The CR CMC-MDR-Ab strains were found to carry two plasmids, pCMCVTAb1 and pCMCVTAb2. The latter is conjugative type and carried two transposons: Tn2008-like, containing a beta-lactamase gene (blaOXA23) and conferring CR, and a TnaphA6 element causing aminoglycoside resistance and further reducing treatment choices. Their chromosomes carried five bla genes and an aphA1 gene. A PCR analysis based upon the resistant determinants showed that all outbreak isolates (100%) carried pCMCVTAb2 containing the two transposons. Fourteen of the remaining 63 isolates (22.22%) carried pCMCVTAb2 and of these, six (42.85%) carried Tn2008-like, and two (14.28%) carried TnaphA6. These differences are statistically significant using Fisher's exact, two-tailed p = 0.0011, p = 0.0445 and p = 0.0018. Conclusion: The results suggested that pCMCVTAb2 was responsible for the CR-MDR outbreak. A PCR analysis based on the antibiotic-resistant genes of pCMCVTAb2 could be used for rapid identification of CR-MDR-Ab strains, thereby helping to prevent the spread and providing guidance for identification and treatment of hospitalized patients with CR-MDR-Ab infections. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the metabolic profile, routes of elimination, and total recovery of amprenavir and its metabolites after a single oral dose of [14C]-amprenavir. Six healthy male subjects each received a single oral 630 mg dose of amprenavir containing 95.76 microCi of [14C]-amprenavir in this Phase I mass balance study. The metabolic disposition of amprenavir was determined through analyses of radiocarbon in whole blood, plasma, urine, and stool samples, collected for a period of 10 to 17 days postdosing. Cerebral spinal fluid (CSF) sampling was conducted on day 1. The ratio of unchanged amprenavir AUC0-->infinity to plasma radiocarbon was 27%, suggesting that most of the radiocarbon was metabolites. The median total recovery of the administered dose of radiocarbon was 89% (range: 66%-93%), with 75% (range: 56%-80%) recovered in the feces and 14% (range: 10%-17%) in the urine. Most of the recovered radiocarbon in the feces and urine was excreted within 240 and 48 hours postdose, respectively. Of the 75% of the radiocarbon dose recovered in the feces, 62% was identified as a metabolite resulting from dioxidation of the tetrahydrofuran ring (GW549445X) and 32% as a metabolite resulting from subsequent oxidation of the p-aniline sulfonate group (GW549444X). Unchanged amprenavir was below the limit of quantitation in feces and urine. Therefore, approximately 94% of the dose excreted in the feces was accounted for by these two metabolites. Concentrations of radiocarbon in the CSF were below the limit of quantitation in 5 of 6 subjects sampled. In summary, oral amprenavir is extensively metabolized in humans, with concentrations of unchanged drug below the limits of quantitation in urine and feces. The majority (75%) of administered radiocarbon was excreted in feces.

Follicular dendritic cells (FDCs) trap Ags and retain them in their native state for many months. Shortly after infection, HIV particles are trapped on FDCs and can be observed until the follicular network is destroyed. We sought to determine whether FDCs could maintain trapped virus in an infectious state for long periods of time. Because virus replication would replenish the HIV reservoir and thus falsely prolong recovery of infectious virus, we used a nonpermissive murine model to examine maintenance of HIV infectivity in vivo. We also examined human FDCs in vitro to determine whether they could maintain HIV infectivity. FDC-trapped virus remained infectious in vivo at all time points examined over a 9-mo period. Remarkably, as few as 100 FDCs were sufficient to transmit infection throughout the 9-mo period. Human FDCs maintained HIV infectivity for at least 25 days in vitro, whereas virus without FDCs lost infectivity after only a few days. These data indicate that HIV retained on FDCs can be long lived even in the absence of viral replication and suggest that FDCs stabilize and protect HIV, thus providing a long-term reservoir of infectious virus. These trapped stores of HIV may be replenished with replicating virus that persists even under highly active antiretroviral therapy and would likely be capable of causing infection on cessation of drug therapy.

Background: Although trimethoprim-sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent., Methods: We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months., Results: Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P<0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001)., Conclusions: Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

In summary, we have described a patient with AIDS and a previously unreported cause of biliary tract obstruction. The incidence of cryptococcal visceral lymphadenitis in patients with AIDS and disseminated cryptococcosis is unknown, but, if present, is probably clinically silent in most instances. However, in the differential diagnosis of abdominal pain and cholestasis in such patients, one should consider major biliary duct obstruction due to cryptococcal lymphadenitis.

Herpes zoster has recently been reported in young patients with risk factors for AIDS. In high-risk patients under age 55, herpes may be the first manifestation of AIDS or AIDS-related complex. Dissemination of zoster does not appear to be greatly increased in this group, but corticosteroid therapy should be withheld.

Hemophilus influenzae, usually pathogenic in the pediatric population, caused septicemia and peritonitis in the cirrhotic adult described here. Susceptibility to this unusual adult pathogen was perhaps related to liver disease or corticosteroid treatment. This organism has not previously been associated with the syndrome of spontaneous bacterial peritonitis in an adult.

Four new antifungal agents were compared in vitro with miconazole and ketoconazole. The agents were BAY n 7133 and ICI 153,066, two orally active triazoles, and bifonazole (BAY h 4502) and Ro 14-4767/002, both topical agents. While all four were found to be broad spectrum antifungal agents they also demonstrated certain gaps in their spectra. In general, Ro 14-4767/002 was the most active agent tested whereas bifonazole and BAY n 7133 were the least active. Noteworthy activities included that of Ro 14-4767/002 against Candida albicans, the dermatophytes and Sporothrix schenckii and that of ICI 153,066 against Torulopsis glabrata.

Zygomycosis of the basal ganglia should be recognized as a syndrome in intravenous drug users associated with a culture-negative cellular CSF, fever, lethargy, and lesions apparent on contrast-enhanced CT scans of the head. The infection is most likely the result of intravenous inoculation of fungal spores. This entity is different from the rhinocerebral zygomycosis seen with diabetes mellitus and other diseases. In the rhinocerebral form, there are external signs of the disease with involvement of the orbit, paranasal sinuses, and palate. In these drug users, infection was directed to areas deep within the brain.

Blastomycosis is the infection caused by the dimorphic fungus Blastomyces dermatitidis. The fungus was believed to be limited in distribution to North America but is found in Africa and northern South America, too. The exact natural habitat of B. dermatitidis is still uncertain with only rare reported isolation of the fungus from the environment. The inability to recover the organism from nature along with the absence of both a reliable skin test antigen and a sensitive serological test have significantly restricted our understanding of the epidemiology and the full clinical spectrum of blastomycosis. An accidental laboratory infection and several common source epidemics have enabled us to recognize that blastomycosis may be a self-limited pulmonary infection. Endogenous reactivation and opportunistic infections have been newly appreciated as clinical presentations of blastomycosis. This report will review blastomycosis with particular emphasis on these recent developments.

The treatment of most fungal infections is difficult, at best. Antifungal therapy is complicated by the development of resistant organisms and by the toxicity of many agents. Ketoconazole, an orally active imidazole derivative, has been approved by the Food and Drug Administration for the treatment of candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. At present, there is very little peer review literature on ketoconazole's effectiveness for several of its approved indications. Gastrointestinal side effects account for the majority of reported adverse reactions; however, preliminary evidence suggests that higher dosages of ketoconazole may decrease adrenal steroidogenesis. Currently, ketoconazole 200-400 mg/d is recommended; the duration of therapy remains to be firmly established. Until well-designed clinical trials are completed and ketoconazole's effectiveness is compared to that of established antifungal agents, its use should be limited.

This is a literature review of 361 opportunistic fungal infections caused by the Zygomycetes. The clinical and laboratory diagnosis, pathogenesis, management, treatment, and outcome of infection are discussed. The Zygomycetes are a group of opportunistic fungi (orders Mucorales and Entomophthorales) which cause severe infections which may be fatal. Early clinical recognition, prompt diagnostic procedures, control of underlying disease and treatment with high doses of amphotericin B and aggressive surgery increases survival in an otherwise lethal infection.