Histoplasmosis and penicilliosis: Comparison of clinical features, laboratory findings and outcome

SummaryIntroductionHistoplasmosis and penicilliosis are infections caused by the dimorphic fungi, Histoplasma capsulatum and Penicillium marneffei, respectively. The aim of this study was to compare the clinical presentation, laboratory and radiologic findings and outcome of these infections at Srinagarind Hospital, Khon Kaen, Thailand.MethodsThe medical records of patients who had positive cultures for Histoplasma capsulatum and Penicillium marneffei during 1996–2002 were reviewed. The data were compared and analyzed by the Chi-square and Fisher's exact tests.ResultsThere were 32 and 36 medical records of patients with H. capsulatum and P. marneffei infection, respectively, available for review. The most common underlying disease of patients with histoplasmosis and penicilliosis was acquired immunodeficiency syndrome (AIDS), which accounted for 90.6% and 91.7%, respectively. The most common clinical findings in both infections were fever, weight loss, cough, anemia, lymphadenopathy, hepatomegaly and splenomegaly. Frequencies of skin lesions were not statistically different between either group (P=0.20). Laboratory findings were similar between the two infections, except hyperbilirubinemia, which was more common in the penicilliosis group (P=0.02). There were similar abnormal X-ray findings in both groups with interstitial infiltration the most common abnormality.ConclusionsHistoplasmosis and penicilliosis had similar clinical presentations, laboratory findings and chest X-ray abnormalities. Itraconazole is recommended as secondary prophylaxis in HIV-infected patients who have histoplasmosis or penicilliosis

Histoplasmosis and penicilliosis: Comparison of clinical features, laboratory findings and outcome

SummaryIntroductionHistoplasmosis and penicilliosis are infections caused by the dimorphic fungi, Histoplasma capsulatum and Penicillium marneffei, respectively. The aim of this study was to compare the clinical presentation, laboratory and radiologic findings and outcome of these infections at Srinagarind Hospital, Khon Kaen, Thailand.MethodsThe medical records of patients who had positive cultures for Histoplasma capsulatum and Penicillium marneffei during 1996–2002 were reviewed. The data were compared and analyzed by the Chi-square and Fisher's exact tests.ResultsThere were 32 and 36 medical records of patients with H. capsulatum and P. marneffei infection, respectively, available for review. The most common underlying disease of patients with histoplasmosis and penicilliosis was acquired immunodeficiency syndrome (AIDS), which accounted for 90.6% and 91.7%, respectively. The most common clinical findings in both infections were fever, weight loss, cough, anemia, lymphadenopathy, hepatomegaly and splenomegaly. Frequencies of skin lesions were not statistically different between either group (P=0.20). Laboratory findings were similar between the two infections, except hyperbilirubinemia, which was more common in the penicilliosis group (P=0.02). There were similar abnormal X-ray findings in both groups with interstitial infiltration the most common abnormality.ConclusionsHistoplasmosis and penicilliosis had similar clinical presentations, laboratory findings and chest X-ray abnormalities. Itraconazole is recommended as secondary prophylaxis in HIV-infected patients who have histoplasmosis or penicilliosis

Clinical perspectives on human genetic screening to prevent nevirapine toxicity

Nevirapine is one of the most extensively prescribed antiretroviral drugs worldwide. However, a concern is increased risk for severe toxicity when antiretroviral-naive individuals with higher CD4 T-cell counts initiate nevirapine-containing regimens. Several genetic variants are associated with nevirapine toxicities. The authors used data from a previous study to anticipate potential consequences of genetic screening to prevent nevirapine adverse events. That study enrolled cohorts of African, Asian and European descent in 11 countries, including 276 patients who had experienced severe cutaneous and/or hepatic adverse events with nevirapine-containing regimens and 587 matched nevirapine-tolerant controls. Associations were identified with HLA-Cw*04, HLA-B*35, HLA-DRB*01 and CYP2B6 516G>T (rs3745274); however, positive predictive values for these genetic markers were low, and most nevirapine-associated adverse events occurred in patients without these markers. Unless better genetic predictors are identified, nevirapine toxicity is best avoided by continuing to follow current prescribing guidelines that are based largely on CD4 T-cell criteria

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials

Item does not contain fulltextObjectives: To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non- albicans Candida species. Methods: Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; ClinicalTrials.gov). In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200 mg on day 1, followed by 100 mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5-10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for >/=14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population. Results: In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%-80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin. Conclusions: These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population

CLINICAL FEATURES OF TUBERCULOUS SEPTIC ARTHRITIS IN KHON KAEN, THAILAND: A 10-YEAR RETROSPECTIVE STUDY

Abstract. Tuberculous septic arthritis is difficult to diagnose. A retrospective analysis was done on patients over 15 years of age who attended Srinagarind Hospital, Khon Kaen, Thailand, between January 1, 1997 and December 31, 2006, whose synovial fluid culture was positive for Mycobacterium tuberculosis. The medical records of 77 patients were reviewed; one-third were in their sixth decade. Comorbid disease was found in 33 cases (42.9%), with systemic sclerosis being the most common (9 cases) followed by diabetes mellitus (5 cases) and chronic kidney disease (5 cases). Chronic monoarthritis was the most common presentation (34 cases) followed by acute monoarthritis (20 cases). More than half of the polyarticular involvements were disseminated tuberculosis. The knee was the most commonly affected joint (36.4%). Sixty percent had delayed diagnosis due to an incorrect diagnosis. Abnormal chest radiography and blood eosinophilia were found in 40 and 57.3% of cases, respectively. Synovial fluid and synovial tissue staining for acid-fast bacteria were positive in 30 and 40% of cases, respectively. A caseous granuloma was present in 57.5% of cases and non-specific synovitis in 12%. Sixtythree percent had bone erosions. Tuberculous septic arthritis should be considered in patients who present with acute or chronic monoarthritis, and who have an abnormal chest radiograph or eosinophilia. Polyarticular involvement was commonly related to having disseminated tuberculosis and may indicate systemic involvement of tuberculous infection

Nocardiosis at a London teaching hospital: Be aware and beware of what is rare

Aims To review all laboratory-confirmed cases of nocardiosis at a tertiary referral hospital over an extended period (2000–2018; 216 months) with regard to microbiological and epidemiological characteristics, risk factors, clinical management, morbidity and mortality. Methods The medical records and microbiological data of all laboratory-confirmed cases of nocardiosis, identified by culture (with reference laboratory confirmation) or identified in a reference laboratory only, were included and analysed retrospectively. Results 18 cases of nocardiosis were identified; 72% (n = 13) were male; all were UK resident. Median age at presentation was 56 years (range 6–83 years). Most had underlying pathology or risk factors including cancer in 39% (n = 7) and immunosuppression in 33% (n = 6). Alcohol and acid fast bacilli (AAFB) microscopy performed in 8/18 cases was negative. Routine 48-hour bacterial culture of 18 isolates was positive in 15; 3 culture-negative specimens were subsequently confirmed positive in a reference laboratory. Four patterns of clinical presentation were observed: cerebral 39% (n = 7), disseminated 28% (n = 5), pulmonary 17% (n = 3), and isolated cutaneous/articular (both n = 1). In addition one case of bacteraemia was noted. Nocardia farcinica accounted for half (n = 9) of all nocardia species identified. 55% (n = 10) required surgical intervention. One co-trimoxazole resistant isolate was identified. Morbidity and mortality were high: 78% (n = 14) required critical care. More than half of patients (55%; n = 10) died from refractory infection, including all of those with disseminated disease (n = 5). Conclusions Nocardia spp should never be regarded as a contaminant or commensal organism in clinical specimens. Correlation of clinical and radiology findings plus risk factors are imperative for nocardiosis to be considered in the differential diagnosis in order to guide appropriate laboratory processing of specimens. Although rare, recognition of nocardiosis is important because of its high mortality. Routine 48-hour bacterial culture does not always identify Nocardia spp and isolates should also be sent to a reference laboratory

Immunoassays Based on Penicillium marneffei Mp1p Derived from Pichia pastoris Expression System for Diagnosis of Penicilliosis

BACKGROUND: Penicillium marneffei is a dimorphic fungus endemic in Southeast Asia. It can cause fatal penicilliosis in humans, particularly in HIV-infected people. Diagnosis of this infection is difficult because its clinical manifestations are not distinctive. Specialized laboratory tests are necessary to establish a definitive diagnosis for successful management. We have demonstrated previously that a cell wall mannoprotein Mp1p, abundant in P. marneffei, is a potential biomarker for diagnosis of P. marneffei infections. In the present study, we describe immunoassays based on Mp1p derived from the yeast Pichia pastoris expression system. METHODOLOGY/PRINCIPAL FINDINGS: We generated monoclonal antibodies (MAbs) and rabbit polyclonal antibodies (PAbs) against Mp1p expressed in P. pastoris. Subsequently, we developed two Mp1p antigen capture ELISAs which employed MAbs for both the capture and detecting antibodies (MAb-MAb pair) or PAbs and MAbs as the capture and detecting antibodies (PAbs-MAb pair) respectively. The two Mp1p antigen ELISAs detected Mp1p specifically in cultures of P. marneffei yeast phase at 37-40 degrees C and had no cross-reaction with other tested pathogenic fungi. The sensitivities and specificities of the two antigen assays were found to be 55% (11/20) and 99.6% (538/540) for MAb-MAb Mp1p ELISA, and 75% (15/20) and 99.4% (537/540) for PAbs-MAb Mp1p ELISA performed using 20 sera with culture-confirmed penicilliosis, and 540 control sera from 15 other mycosis patients and 525 healthy donors. Meanwhile, we also developed an anti-Mp1p IgG antibody ELISA with an evaluated sensitivity of 30% (6/20) and a specificity of 98.5% (532/540) using the same sera. Furthermore, combining the results of Mp1p antigen and antibody detection improved the sensitivity of diagnosis to 100% (20/20). CONCLUSIONS/SIGNIFICANCE: Simultaneous detection of antigen and antibody using the immunoassays based on Mp1p derived from P. pastoris greatly improves detection sensitivity. The procedures should be useful for the routine diagnosis of penicilliosis.published_or_final_versio

Serum albumin and osmolality inhibit Bdellovibrio bacteriovorus predation in human serum

We evaluated the bactericidal activity of Bdellovibrio bacteriovorus, strain HD100, within blood sera against bacterial strains commonly associated with bacteremic infections, including E. coli, Klebsiella pneumoniae and Salmonella enterica. Tests show that B. bacteriovorus HD100 is not susceptible to serum complement or its bactericidal activity. After a two hour exposure to human sera, the prey populations decreased 15- to 7,300-fold due to the serum complement activity while, in contrast, the B. bacteriovorus HD100 population showed a loss of only 33%. Dot blot analyses showed that this is not due to the absence of antibodies against this predator. Predation in human serum was inhibited, though, by both the osmolality and serum albumin. The activity of B. bacteriovorus HD100 showed a sharp transition between 200 and 250 mOsm/kg, and was progressively reduced as the osmolality increased. Serum albumin also acted to inhibit predation by binding to and coating the predatory cells. This was confirmed via dot blot analyses and confocal microscopy. The results from both the osmolality and serum albumin tests were incorporated into a numerical model describing bacterial predation of pathogens. In conclusion, both of these factors inhibit predation and, as such, they limit its effectiveness against pathogenic prey located within sera

High dose fluconazole in salvage therapy for HIV-uninfected cryptococcal meningitis.

BACKGROUND: The 2010 Infectious Diseases Society of America (IDSA) guidelines for management of cryptococcal diseases recommend high dose fluconazole (≥ 800 mg/day), either alone or with other antifungal drugs, as alternative anticryptococcal choices. But evidence for its use in the treatment of HIV-uninfected cryptococcal meningitis (CM) remains sparse. METHODS: A retrospective analysis of HIV-uninfected CM patients who received fluconazole 800 mg/day for salvage therapy from January 2011 to December 2016 at Huashan Hospital, Shanghai, China was performed. Efficacy and safety were assessed, and mortality and prognostic factors evaluated. RESULTS: A total of 44 patients were studied including 19 refractory to amphotericin B induction therapy, 8 refractory to fluconazole consolidation therapy (400 mg/d), and 17 intolerant of antifungal drugs. For salvage, 11 patients received triple therapy of high dose fluconazole, amphotericin B and flucytosine, 20 received dual therapy of high dose fluconazole and flucytosine, 13 received monotherapy of high dose fluconazole. Median duration of high dose fluconazole in salvage regimens was 136.5 days (range, 1-667 days). Clinical response rates were 72.1% (31/43) and 83.7% (36/43) when assessed at 2 weeks and the end of salvage therapy, respectively. Adverse events possibly related to high dose fluconazole occurred in 54.5% (24/44) of the patients, and all were mild or moderate. From the initiation of salvage therapy, 1-year all-cause mortality was 13.6% (6 of 44 patients) among the study population with no significant difference in refractory or intolerant patients. CONCLUSIONS: Adherence to guideline recommendations of high dose fluconazole, alone or in combination with other antifungals, was safe and often effective for salvage therapy of HIV-uninfected CM patients