Usefulness of corticosteroid therapy during chronic disseminated candidiasis: case reports and literature review.

OBJECTIVES: Chronic disseminated candidiasis (CDC) is a disseminated fungal infection that is frequently seen in patients undergoing intensive treatment of haematological malignancies. The first signs of CDC appear during neutrophil recovery. Clinical and physiopathological characteristics of CDC suggest it belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome (IRIS). We report five cases of CDC treated with antifungal therapy and adjuvant corticosteroids to decrease the exacerbated inflammatory response. METHODS: We conducted a retrospective study in the Haematology Department of the University Hospital of Tours, France. The five reported cases were treated for CDC with antifungal therapy and adjuvant corticosteroids. RESULTS: Of the five cases of CDC, one was proven and four were possible, according to the 2008 European Organization for Research and Treatment of Cancer (EORTC) classification. All patients were being treated for acute leukaemia. In all cases, symptoms disappeared 2.8 days (range, 1-7) after the beginning of adjunctive corticosteroid therapy. Corticosteroids were administered on average for 146 days (range, 4 weeks-1 year) and antifungal therapy was administered for the duration of chemotherapy consolidation. There was no exacerbation of CDC symptoms during the next round of chemotherapy or bone marrow transplantation. One patient died from relapse of leukaemia. CONCLUSIONS: Within the framework of IRIS, adjuvant corticosteroid therapy could rapidly improve CDC symptoms and allow continued chemotherapy without delay and without compromising the haematological prognosis.

[Lyme borreliosis: census of adult patients hospitalized in Indre-et-Loire (France), from the Hospital Discharge Data (1999-2006)]. / Borréliose de Lyme: recensement des cas adultes hospitalisés en Indre-et-Loire, à partir du PMSI (1999-2006).

BACKGROUND: To describe the clinical forms and epidemiology of Lyme borreliosis, in French adult patients hospitalized in Indre-et-Loire (Centre region). METHODS: Patients were recruited from standardized discharge summaries collected in the hospital database. All adult patients, hospitalized in public hospitals of the Indre-et-Loire administrative district, over a period of 8 years (1999-2006), who satisfied the European diagnostic criteria of Lyme borreliosis, were included. RESULTS: Encoding of Lyme borreliosis had a poor positive predictive value (65%). Forty-seven adult patients presented with the 50 following clinical forms: erythema migrans (n=5), neuroborreliosis (n=32), knee single-joint arthritis (n=4), acrodermatitis chronica atrophicans (n=3), carditis (n=2), ocular borreliosis (n=2), miscellaneous (n=2). Three patients had a combination of two different clinical forms. Meningoradiculitis was the most frequent neurologic manifestation. When a cranial nerve was involved, it was constantly the facial nerve, and mainly bilaterally. Few patients in our study had erythema migrans: these patients are usually treated in a general medicine setting. Although the incidence in the Centre region was lower than in some other regions of France and Europe, the clinical spectrum of the disseminated forms was similar. CONCLUSION: This cohort illustrates the diversity of clinical manifestations of Lyme borreliosis in hospitalized patients, particularly at disseminated and late stages as well as the complexity of its diagnosis and its epidemiological surveillance.

Optimal duration of antibiotic therapy in vertebral osteomyelitis.

OBJECTIVES: To compare the risk of relapse of vertebral osteomyelitis (VO), according to the duration of antibiotic therapy (< or =6 weeks versus >6 weeks). METHODS: We performed a 10-year retrospective study to assess the risk of VO relapse and to verify that this risk was not enhanced in patients who received 6 weeks of antibiotic therapy (Group 1) as compared with those who received a longer treatment (Group 2). VO was diagnosed based on clinical manifestations, magnetic resonance imaging and/or computed tomography findings, and isolation of a pyogenic organism in blood cultures and/or a discovertebral biopsy. Relapse was diagnosed based on isolation of the same organism in blood cultures and/or a discovertebral biopsy. Outcome was evaluated 6 months post-treatment and in December 2004. RESULTS: Group 1 included 36 patients (mean age, 58 +/- 15 years) and Group 2 included 84 patients (mean age, 67 +/- 15 years) (P = 0.003). Clinical data and microorganisms were comparable in the 2 groups. In the first 6 months, 6 (5%) patients died (Group 1, n = 2; Group 2, n = 4), and 5 (4%) in Group 2 relapsed, 2 with recurrent VO and 3 with recurrent bacteremia. In 2004, 91 patients were evaluated (mean follow-up, 40.6 +/- 31 months): 77 (85%) were cured, 13 (14%) died (Group 1, n = 3; Group 2, n = 10), 1 had VO due to a different microorganism (Group 2), and no long-term relapses occurred. CONCLUSION: Our results suggest that antibiotic therapy of VO could be safely shortened to 6 weeks without enhancing the risk of relapse.

Visceral leishmaniasis. Persistence of parasites in lymph nodes after clinical cure.

Visceral leishmaniasis (VL) is generally associated with severe immunodeficiency (AIDS; renal, liver, and heart transplantations; haemopoietic malignancies). More rarely it can be related to an immunotolerence status such as pregnancy. Various observations report the development of leishmaniasis several months or even years after exposure to the parasite. Relapses occur rarely in patients not known to be immunocompromised, but are common after incomplete treatment. They are frequent in patients with Leishmania/HIV co-infection. Asymptomatic phases and relapses suggest that parasite can exist in the tissues for a long time before and/or after clinical onset of the disease. The mechanisms of onset of clinical leishmaniasis following exposure and infestation are highly relevant to understanding the pathology of the disease. The survival of Leishmania parasite between infection and disease or after cure is a very important issue for clinicians and epidemiologists. We describe two cases of VL occurring in a patient with lymphoma and in a pregnant woman. In both cases, parasites remained present in the lymph nodes after clinical cure.

Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection.

Published data suggest that therapeutic drug monitoring of human immunodeficiency virus protease inhibitors would improve the management of antiretroviral therapy. The authors have developed a high-pressure liquid chromatographic assay allowing simultaneous determination of six protease inhibitors (ritonavir, saquinavir, indinavir, nelfinavir, amprenavir, and lopinavir), using carbamazepine as internal standard. Detection was based on a dual wavelength ultraviolet spectrophotometer and can be improved by the use of a photodiode array detector. Monitoring was performed 1 month after initiation of therapy or in instances of therapeutic failure, side effects, suspicion of noncompliance, drug interactions, or malabsorption. Trough concentrations were 0.15 to 13.6 mg/L for ritonavir, 0.06 to 9.7 mg/L for indinavir, 0.03 to 5.5 mg/L for saquinavir, and 0.15 to 4.15 mg/L for nelfinavir. Concentrations below the limit of quantification were observed in 63/438 (14%) of the patients. Target concentrations are not well established, and reported in vitro inhibitory concentrations may be of limited value. The authors therefore chose to compare observed concentrations with mean plasma concentrations reported in clinical trials. Observed saquinavir and indinavir concentrations were often below or close to these target concentrations, particularly when used as a single protease inhibitor. Concentration-controlled studies should now be used to select proper target concentrations for each protease inhibitor, either prescribed alone or in combination.

[Hepatitis B virus reactivation in patients infected with HIV]. / Reactivarea virusului hepatitei B la pacientii infectati cu HIV.

The authors study the reactivation of B hepatitis virus in three HIV infected patients, correlating the moment of reactivation of and the CD4 and CD8 lymphocytes. Prior to the B viral reactivation, the three patients were with Ac HBc IgG (+) in serum, assessing that the presence of AC HBc IgG is insufficient to prevent the reactivation and to consider a B hepatitis cured. In two patients, prior to the B virus reactivation, AgHBs was (-) in the serum. It is considered that the predominant hepatocytolysis mechanism is the viral one, in the stage of B virus reactivation in patients with AIDS, the cell immunity mechanism being depressed.

[Spontaneous reactivation of the hepatitis B virus?]. / Reactivarea spontana a virusului hepatitei B?

The authors present 4 cases of chronic AgHBs positive hepatitis, with reactivations of hepatitis B virus. The reactivations occurred spontaneously, as mentioned in references. The authors appreciate that the cause of B virus reactivation bases upon factors which modify the immune status of the host. Alcohol is one of these factors, not yet mentioned in references as cause of virus B reactivation. Are also presented data about the existence of virus B mutants, in the studied patients, which could play a role in the reactivation of chronic hepatitis B.

Direct isotopic assessment of aerosolized pentamidine deposition: influence of nebuliser.

OBJECTIVES: The aim of the present study was to compare the efficiency of pulmonary deposition of pentamidine using the Respirgard II jet nebuliser or the Fison ultrasonic nebuliser with 99m technetium (99m Tc) labelled pentamidine in the current conditions of recommended treatment. The study was designed in three stages, to verify particle size distribution, to validate the isotope labelling, and to compare pulmonary deposition of pentamidine isethionate with the two nebulisers. METHODS: Count median aerodynamic diameter and mass median aerodynamic diameter were measured using the velocimetry technique and aerosol dispersion was calculated according to the standard deviation defined by the ratio of diameters between 84.3% and 50% of the total distribution. Stability of labelling was checked both in vitro, by radiochromatography, and in vivo, by the absence of free technetium thyroid fixation after intravenous injection of the preparation to a rat and inhalation by baboons. The direct isotopic technique was used to compare pulmonary deposition of 300 mg aerosolized 99m Tc labelled pentamidine isothionate with the two nebulisers in four HIV patients treated with primary prophylaxis. RESULTS: Count median aerodynamic diameter and mass median aerodynamic diameter (MMAD) were higher with Fisoneb than with Respirgard II. Nevertheless Fisoneb MMAD remained in the optimal range for peripheral deposition. In one patient, pentamidine lung burden was higher using the Respirgard II (13% of dose originally in nebuliser) when compared with the Fisoneb (10.2% of dose originally in nebuliser). A better result was obtained in the 3 other patients with Fisoneb (mean = 14.3%) compared with Respirgard II (mean = 3.8%). In all 4 patients gastric contamination was higher with Fisoneb (mean = 5.2%) as compared with Respirgard II (mean = 2.6%). Cough and bronchospasm were not observed with either device. CONCLUSION: This study showed that Fisoneb, a practical and cheap nebuliser which has proved to be effective in clinical studies when used for pentamidine nebulisation, leads to correct particle size distribution and pulmonary deposition of the drug. We believe that such studies to evaluate aerosol characteristics should be recommended for any kind of nebuliser.

[Scintigraphic assessment of pulmonary deposition of pentamidine administered by aerosol]. / Evaluation scintigraphique de la déposition pulmonaire de la pentamidine administrée en aérosol.

Isotopic techniques enable to determine the best conditions to aerosolize pentamidine as a preventive treatment of pneumocystis. An original labelling technique of pentamidine isethionate has led into a feasibility study of pentamidine scintigraphy in the monkey, and then to a clinical study. A tracer dose of 2 mg of pentamidine isethionate was diluted into 200 mg of pentamidine mesylate. An ultrasonic nebulizer (TV 6000) and a jet nebulizer (Venticis II) were first compared in four baboons. With the two nebulisers the curves of pulmonary kinetic activity showed a peak 10-15 minutes after the beginning of inhalation and then a plateau. With the ultrasonic TV6000 the pulmonary dose was on average 0.8 mg or 0.4% of the pentamidine aerosolized and the gastric contamination 3.1%. With the Venticis II compressed air apparatus the amount of pentamidine delivered to the deep lung was a mean of 4.2 mg or 2.1% of the aerosolized dose whereas the gastric contamination was only 0.5%. The delivery of the aerosol by the ultrasonic inhaler TV 6000 was then compared with two compressed air inhalers Venticis II and Respirgard II in four patients infected with HIV virus who were submitted to a preventative therapy against pneumocystis. With the ultrasonic TV 6000 the pulmonary dose was 0.8 mg or 0.3%-0.5% of the dose of pentamidine aerosolized and the digestive contamination was 3.1%. The performance of the two compressed air nebulizers Venticis II and Respirgard II were similar. The amount of pentamidine delivered to the deep lung was respectively 12 and 14 mg or 6 and 8% of the dose of pentamidine aerosolized and the digestive activity was 0.2%.(ABSTRACT TRUNCATED AT 250 WORDS)