Manuela Piazza

Body habitus changes and metabolic alterations in protease inhibitor-naive HIV-1-infected patients treated with two nucleoside reverse transcriptase inhibitors.

&NA; Background: Cross‐sectional and retrospective surveys suggest that nucleoside reverse transcriptase inhibitors (NRTIs) contribute to the metabolic and morphologic alterations observed in patients on antiretroviral therapy (ART). Objectives: To assess the risk of developing body habitus changes (BHCs) and metabolic abnormalities in protease inhibitor (PI)‐naive HIV‐1‐infected patients treated with two NRTIs, and the risk associated with each of these drugs. Design: Prospective cohort study. Patients and Methods: The BHCs occurring in 335 patients treated with two NRTIs were evaluated every 3 months. The laboratory tests included determination of CD4 cell counts and the measurement of HIV RNA, serum glucose, cholesterol, and triglyceride levels. Cox proportional hazard models were used to describe the factors associated with the development of BHCs. Results: During a median exposure of 747.5 days, 46 patients (13.7%) developed BHCs: nine fat accumulation alone, 12 fat loss alone, and 25 combined fat loss and accumulation in different body regions. Fat loss alone occurred after a significantly longer median duration of treatment than the other two forms (p = .004). The risk of developing any BHC was significantly higher in female patients (p < .0001). Fat loss was the prevalent alteration in males. Hypertriglyceridemia was observed in 76 patients (22.7%), hypercholesterolemia in 35 (10.5%), and hyperglycemia in 48 (14.3%). The adjusted risk of developing hypertriglyceridemia was higher in the stavudinetreated patients (p = .04) and in those who had previously received ART (p = .02). The only independent factor associated with the development of hypercholesterolemia was to be ART experienced at baseline (p = .02), whereas age was associated with the development of hyperglycemia (p = .0096). Conclusions: Treatment with NRTIs may be responsible for the same morphologic alterations as those observed in patients treated with PIs. Moreover, altered triglyceride levels are also frequently observed. The different timing of presentation and gender distribution of BHCs suggest that multiple pathogenetic mechanisms are involved.

Role of PCR in Diagnosis and Prognosis of Visceral Leishmaniasis in Patients Coinfected with Human Immunodeficiency Virus Type 1

ABSTRACT A group of 76 consecutive human immunodeficiency virus (HIV)-positive patients with fever of unknown origin (n = 52) or fever associated with pulmonary diseases was evaluated in order to assess the usefulness of PCR with peripheral blood in the diagnosis and follow-up of visceral leishmaniasis. We identified 10 cases of visceral leishmaniasis among the 52 patients with fever of unknown origin. At the time of diagnosis, all were parasitemic by PCR with peripheral blood. During follow-up, a progressive decline in parasitemia was observed under therapy, and all patients became PCR negative after a median of 5 weeks (range, 6 to 21 weeks). However, in eight of nine patients monitored for a median period of 88 weeks (range, 33 to 110 weeks), visceral leishmaniasis relapsed, with positive results by PCR with peripheral blood reappearing 1 to 2 weeks before the clinical onset of disease. Eight Leishmania infantum and two Leishmania donovani infections were identified by PCR-restriction fragment length polymorphism analysis. PCR with peripheral blood is a reliable method for diagnosis of visceral leishmaniasis in HIV-infected patients. During follow-up, it substantially reduces the need for traditional invasive tests to assess parasitological response, while a positive PCR result is predictive of clinical relapse.

Prospective observational study of fever in hospitalized returning travelers and migrants from tropical areas, 1997-2001.

BACKGROUND An estimated 50 million people each year from industrialized countries visit tropical areas: 3% to 11% of these travelers report a febrile illness on their return. We conducted a 5-year prospective observational study on the causes of fever in patients admitted to a university teaching hospital after returning from the tropics. METHODS We enrolled in this study all consecutive patients admitted to the Division of Infectious Diseases of the University of Milan, Italy, between January 1997 and December 2001 presenting with fever (oral temperature > or =37.5 degrees C) and a history of travel to a tropical country in the previous 6 months. RESULTS Seven percent (147/2,074) of all hospital admissions in the study period were due to fever in travelers and migrants returning from the tropics. Malaria accounted for 47.6 % of all admissions (70/147), followed by presumed self-limiting viral infections (12%). Pretravel screening and vaccination strategies could have prevented a considerable number of hospitalizations (e.g., hepatitis A and typhoid fever). The most useful investigations were blood examination and PCR for malaria, which gave positive results in 65% of cases in which they were performed. CONCLUSIONS During a 5-year period, the number of patients returning from tropical areas who were admitted with fever to a university hospital in northern Italy remained stable; malaria was the most frequent diagnosis, and should be considered in any febrile patient returning from the tropics. With the exception of hepatitis A and dengue fever infections, in a real-world setting serology is of modest utility and is probably overused.

The Role of Lumbar Puncture in the Management of Elevated Intracranial Pressure in Patients with AIDS-Associated Cryptococcal Meningitis

Aspergillosis 1/1 Astrocytoma/glioblastoma 3/3 2 (1–3) Bacterial meningitis — 7/10 CMV encephalitis — 49/54 CMV plus other OI 5/23 Cryptococcosis 6/45 2 (1–4) 67/263 Encephalopathy, unknown origin 6/7 1 (1–2) 36/41 Herpetic meningoencephalitis — 8/10 HIV encephalopathy — 74/87 HIV encephalopathy plus other OI 2/3 Primary brain lymphoma 15/16 1 (1–2) — PML 67/78 Syphilis — 11/14 Systemic non-Hodgkin’s lymphoma 3/6 2 (1–3) 1/3 Toxoplasmosis 74/91 3 (1–5) — Toxoplasmosis plus other OI 10/17 2 (1–4) Tuberculosis 3/7 3 (1–5) 20/25 Tuberculosis plus other OI 2/3 Total 121/193 349/614

Is it time to revise linezolid dose in elderly patients

Sir, No indications on dose adjustments for linezolid in elderly patients are actually given on the drug’s label sheet. Nevertheless, some evidence shows significant association between patients’ age and linezolid exposure [1, 2]. In particular, we have previously documented that old (70–79 yrs) and very old patients (≥80 yrs) have linezolid concentrations three times higher compared with younger adult patients. Here we aimed to extend these findings by describing the exposure of linezolid in elderly patients in which the dose was reduced guided by therapeutic drug monitoring (TDM). Patients included in the present study had to fulfill the following criteria: (a) age ≥70 yrs, (b) linezolid therapy at 600 mg b.i.d. for at least 3 days to ensure steady state conditions, (c) blood samples for TDM taken 12 h after the last drug intake (a timewindow of ±20min was considered acceptable). Patients taking drugs known to interfere with linezolid pharmacokinetics were excluded from the study. Plasma linezolid concentrations were determined using a validated high-performance liquid chromatographic method [2]. The therapeutic range for linezolid trough concentrations was set at 2–8 mg/L [3]. After the first TDM, patients with linezolid trough concentrations exceeding the upper therapeutic threshold underwent drug dose reduction, and a second TDM was carried out 4 to 6 days after the first assessment. Comparisons of the hematochemical and pharmacokinetic data between the first and the second TDM assessments were performed using t test analysis. All data were expressed as median [interquartile range, IQR], unless specified. Given the retrospective, observational nature of this research, no formal approval from the local ethics committee was required according to national legislation. Written informed patient consent for medical procedures/interventions performed as per clinical practice was collected by each center. Twenty patients fulfilling the inclusion criteria were identified. They were given linezolid for the treatment of hospitalacquired pneumonia (n = 6), osteomyelitis (n = 5), spondylodiscitis (n = 3), skin and skin structure infections (n = 3), bacteremia (n = 2), and urinary tract infection (n = 1). Patients had a median age of 79 yrs. (ranging from 70 to 92 yrs), equally distributed for sex (50% males), with normal renal function/mild renal dysfunction (median glomerular filtration rate estimated with the MDRD equation 62.8 [47.2–86.8] mL/min] and a Charlson index of 3 [2–4]. As shown in Fig. 1, at the first TDM, performed at a median of five [3–6] days after starting antibiotic therapy, all patients had linezolid trough concentrations exceeding the cutoff of 8.0 mg/L, resulting in median drug levels of 13.0 [11.9–16.0] mg/L. At this stage, patients had no or minor alterations in platelet count (242 [158–277] 10/μL), red blood cell count (RBC, 7.3 [5.7–8.5] 10/μL), and hemoglobin levels (Hb, 10.4 [9.7–11.6] g/dL). According to the TDM results, all patients underwent linezolid dose reduction (in 19 patients the dose was reduced to 300 mg b.i.d., and in the remaining, an obese patient, the dose was reduced to 450 mg b.i.d.), and a second TDM was performed 4.6 days after the first assessment. The dose reduction resulted in significant decrease in the linezolid trough concentrations (5.4 * Dario Cattaneo Dario.cattaneo@asst-fbf-sacco.it