Clinical characteristics, management and outcome of patients with invasive candidiasis hospitalized in Internal Medicine Units: findings from a registry by the Italian Scientific Society FADOI.

PURPOSE: Invasive candidiasis (IC) is a challenging clinical condition, burdened by relevant mortality and morbidity. There is limited knowledge on the occurrence and management of IC in Internal Medicine Units (IMUs). Aim of this study was to provide real-world data on this topic. METHODS: Consecutive objectively diagnosed cases of IC were collected in this prospective registry, which involved 18 IMUs in Italy. Patients were followed-up to 90 days from the diagnosis of candidemia. RESULTS: A total of 111 patients were observed (median age 78, IQR 67-83) for an overall incidence of infection of 1.89 cases/1000 hospital admissions. Candida albicans was the most frequent isolated species (62%), followed by Candida parapsilosis (17%) and Candida glabrata (13%). Echinocandins and fluconazole were used as initial therapy in 56.8 and 43.2% of patients, respectively. Antifungal therapy was started within 24 h in 18.9% of patients, in 40.6% in the period 1-3 days, and in 40.5% of patients more than 3 days after blood cultures. Death rate was 19.8% at 30 days and 40.5% at 90 days. At multivariable analysis concomitant bacteremia (i.e. polymicrobial sepsis), and fluconazole as the initial therapy were associated with an increased risk of death at 90 days. CONCLUSIONS: The incidence of IC is not negligible, and our registry confirmed that these patients have a relevant mortality rate at 90 days. Concomitant bacteremia, featuring polymicrobial sepsis, and starting antifungal treatment with fluconazole instead of echinocandins independently increase the risk of death. Efforts are needed to improve the awareness and management of IC in IMUs.

Successful Antifungal Combination Therapy and Surgical Approach for Aspergillus fumigatus Suppurative Thyroiditis Associated with Thyrotoxicosis and Review of Published Reports.

In immunocompromised patients, Aspergillus infections are important causes of morbidity and mortality. We describe a patient with cryoglobulinemic vasculitis who developed disseminated invasive aspergillosis with thyrotoxicosis caused by Aspergillus fumigatus. The diagnosis was based upon radiological, microbiological and pathological findings. The patient was treated successfully with voriconazole and caspofungin treatment followed by total thyroidectomy. We provide an overview of published reports on Aspergillus thyroiditis with an emphasis on therapeutic approaches.

Interference of confounding factors on the use of (1,3)-beta-D-glucan in the diagnosis of invasive candidiasis in the intensive care unit.

Invasive fungal infections (IFIs) are an increasing problem in intensive care units (ICUs), and conventional diagnostic methods are not always reliable or timely enough to deliver appropriate antimicrobial therapy. The dosage of fungal antigens in serum is a promising diagnostic technique, but several confounding factors, such as treatment with immunoglobulins (Ig), albumin, or antifungals, could interfere with the correct interpretation of the (1,3)-beta-D-glucan (BG) assay. This study assessed the reliability of the BG assay and the influence of timing and dosage of major confounding factors on circulating levels of IFI biomarkers. 267 ICU patients who underwent a BG assay were retrospectively studied. The timing and dosage of albumin, use of azole treatment, and infusions of intravenous IgG, red blood cells, concentrated platelets, and frozen plasma were analyzed to find possible correlations with the BG results. The sensitivity and specificity of the BG assay were calculated. The BG test in serum showed high sensitivity (82.9 %) but low specificity (56.7 %). The optimal cut-off for the test was 95.9 pg/mL. The mean BG level in proven invasive candidiasis was around 400 pg/mL. The only factor that was found to significantly confound (p < 0.05) the diagnostic performance of the BG assay was the administration of more than 30 g of albumin within 2 days prior to BG testing. The BG assay remains a useful diagnostic test in ICU patients and the levels of BG are useful in evaluating the positive predictive value of this biomarker. The only confounding factor in our study was the use of albumin.

Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series.

PURPOSE: Chronic pulmonary aspergillosis (CPA) is a rare disease that primarily affects subjects with moderate immunodepression and/or structural alterations in the lung. METHODS: Data for patients with probable CPA were collected over 24 months. Patients with probable CPA received oral voriconazole, and clinical, laboratory and radiological follow-up was performed at 3, 6 and 12 months. RESULTS: 21 patients (mean age 52.4 years) were evaluated. Factors predisposing to CPA were tuberculosis (n = 8), chronic obstructive pulmonary disease (n = 7), corticosteroids (n = 14), chemo- or radio-therapy (n = 6), tracheostomy or endotracheal prosthesis (n = 5), smoking (n = 4), asthma (n = 3), and chronic liver disease (n = 3). Sputum or bronchial aspirate cultures were positive for Aspergillus spp. in 14 cases (66.6 %). (1,3)-ß-D-glucan on serum was positive in 16 cases (76.2 %). Excavated pulmonary thickening was evident in 14 patients (66.6 %) and in 9 of these cases (64.2 %) aspergilloma was present. [(18)F]2-fluoro-2-deoxy-D-glucose-PET-CT was positive in 13/15 patients, and simple aspergilloma was diagnosed after surgical excision in one of the negative cases. All patients were treated with oral voriconazole. Therapy was discontinued due to skin toxicity (n = 3), liver toxicity (n = 2) and severe mental disorder (n = 1). At 12 months' follow-up, nine patients (42.9 %) were considered cured or improved. Seven patients (33.3 %) died during follow-up, mainly due to underlying disease. CONCLUSIONS: A reasonable proportion of patients achieved cure or improvement with voriconazole, but 28.5 % of treated patients had to discontinue therapy because of toxicity. The high mortality makes it difficult to fully assess the real efficacy of voriconazole and to establish the correct duration of therapy.

SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients.

PURPOSE: We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs). METHODS: Prospective surveillance (2009-2011) of proven and probable FFIs was implemented in 23 Italian hospitals. RESULTS: Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs. The most frequent infection was invasive aspergillosis (76.1 % for HAEs, 56.3 % for non-HAEs), and the localization was principally pulmonary (83.2 % for HAEs, 74.8 % for non-HAEs). Neutropenia was a risk factor for 89.4 % HAEs; the main underlying condition was corticosteroid treatment (52.9 %) for non-HAEs. The distribution of proven and probable FFIs was different in the two groups: proven FFIs occurred more frequently in non-HAEs, whereas probable FFIs were correlated with the HAEs. The sensitivity of the galactomannan assay was higher for HAEs than for non-HAEs (95.3 vs. 48.1 %). The overall mortality rate was 44.2 % among the HAEs and 35.3 % among the non-HAEs. The etiology influenced the patient outcomes: mucormycosis was associated with a high mortality rate (57.1 % for HAEs, 77.8 % for non-HAEs). CONCLUSIONS: The epidemiological and clinical data for FFIs were not identical in the HAEs and non-HAEs. The differences should be considered to improve the management of FFIs according to the patients' setting.

Prevalence of Strongyloides stercoralis infection among HIV-positive immigrants attending two Italian hospitals, from 2000 to 2009.

In patients with Strongyloides stercoralis infection, a dysregulation of host immunity can lead to hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), characterized by high fatality rate. HS has been reported in HIV-positive patients following use of corticosteroids or during immune reconstitution inflammatory syndrome (IRIS). A retrospective study was conducted to estimate the prevalence of S. stercoralis infection among HIV-positive immigrants, attending two Italian hospitals. From January 2000 to August 2009, 138 HIV-positive immigrants were systematically screened for strongyloidiasis, as a part of their routine care, with an indirect immunofluorescent antibody test (IFAT) developed at the Centre for Tropical Diseases, Sacro Cuore Hospital of Negrar, Verona. The majority were also submitted to stool examination. Fifteen (11%) resulted infected by S. stercoralis, of whom four (27%) had a negative serology (diagnosis made with stool examination). A higher eosinophil count (0·94 versus 0·24×10(9)/l, P<0·01) and more frequent gastrointestinal and cutaneous symptoms (odds ratio: 4·8 and 5·8, respectively) were found in patients with strongyloidiasis compared with controls. The IFAT is more sensitive than direct parasitological methods. The proportion of false negative results was higher than expected based on the theoretical test sensitivity. Considering the high prevalence detected and the apparent, lower sensitivity of serology, we propose a systematic screening for Strongyloides infection, with both serology and stool culture, for all HIV-positive immigrants coming from endemic areas.

Prolonged hospitalisation for immigrants and high risk patients with positive smear pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) occurring in immigrants and resistance to drugs are major problems for TB control in Western countries. Directly observed therapy (DOT) reduces disease transmission, but this approach may have poor results among illegal immigrants. Our aim was to evaluate a prolonged hospitalisation programme to improve early outcome of TB treatment in high risk patients. METHODS: All the consecutive adult patients with sputum smear-positive pulmonary TB admitted to 2 Italian referral TB Centres were evaluated. Hospital-based DOT was provided to high risk patients up-to smear conversion. Demographic, microbiological and clinical conditions, as potential factors associated with confirmed smear conversion at 60 and 90 days of anti-tuberculous therapy were evaluated. RESULTS: 122 patients were studied, 45.9% of them were immigrants (20% illegal) from high-prevalence TB countries. HIV testing was negative in all cases. Twelve patients had M. tuberculosis resistant to > or = 1 first-line anti-tuberculous agents. The rate of defaulting from TB treatment was 73%. Sputum smear became negative in 84.4% cases after 60 days and 933% cases after 90 days. At such time, smear conversion rates were similar among different high risk subgroups such as illegal immigrants (95.9%), legal foreign-born (92.5%) and Italian persons (94.8%). Persistent sputum smear positivity was independently correlated with the extent of pulmonary lesions at 60 (p < 0.0001) and 90 days (p = 0.038) of hospital-based DOT. CONCLUSIONS: These findings suggest that prolonged hospitalisation for illegal immigrants and high risk TB patients, may positively influence the early outcome of TB treatment despite of drug resistance and legal status.

Mirtazapine in an HIV-1 infected patient with progressive multifocal leukoencephalopathy.

We describe the clinical course of an HIV-infected patient with progressive multifocal leukoencephalopathy who took mirtazapine for his depression. After six months of therapy the clinical symptoms had not worsened and the neuroradiological image of the brain was unchanged. Further studies are necessary to determine the effect of serotonin receptor antagonist in treating PML associated to HIV.

Ideal microbiological and pharmacological characteristics of a quality antimicrobial agent: comparing original and generic molecules.

This article critically evaluates the main in vitro and in vivo studies published which compare generic with the original molecules, both those administered orally and parenterally. The authors indicate that caution should be used in assuming bioequivalence of the generic drug with its clinical efficacy in clinical practice. In fact, mild differences in the content of the active ingredient, less relevant in healthy volunteers, may have an impact in the actual population, which is heterogeneous for age, sex, weight, concomitant risk factors and severity of the underlying disease, as in critically ill patients, with consequences for the patient and ecosystem. Nowadays the requirements for authorization to commercialize a generic antimicrobial agent are focused on demonstration of bioequivalence to the original molecule, with a range variability of +/-20%. However this kind of trial is not sufficient to predict the actual profile in clinical practice, particularly in critically ill patients. Thus while generics can represent an opportunity for physicians, patients and healthcare systems the regulatory procedures do not seem exhaustive, and it is probably necessary to define an ad hoc technical standard of quality before their commercialization and to perform adequate clinical trials regarding efficacy and safety of the "equivalent molecule", especially for drugs used in critically ill patients.

Hyperacute unilateral gonococcal endophthalmitis in an HIV-infected man without genital infection.

PURPOSE: To demonstrate the necessity of obtaining an accurate history from patients presenting abnormal evolution of ophthalmologic diseases. METHODS: A 42-year-old patient, denying any previous ocular or systemic morbidity, presented with an unusual severe and hyperacute gonococcal endophthalmitis with corneal abscess but no concurrent genitourinary infection. Only after a further interview did the patient reveal his human immunodeficiency virus status and a previous diagnosis of acquired immunodeficiency syndrome. RESULTS: Adequate topical and intravenous antibiotic treatment and surgery led to salvage of the eye. CONCLUSIONS: An accurate history should be obtained by patients with an abnormal course of an ophthalmologic disease, focusing on immunologic deficiencies that can cause extremely serious ophthalmologic complications with ensuing risk of visual impairment or ocular loss (bulbar enucleation).

Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a ß-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.

Secular trends in nosocomial candidaemia in non-neutropenic patients in an Italian tertiary hospital.

A retrospective study was performed in an Italian tertiary hospital to evaluate trends in candidaemia between 1992 and 2001, and to compare the characteristics of episodes of fungaemia between 1992--1997 and 1998--2001. In total, 370 episodes of candidaemia were identified, with an average incidence of 0.99 episodes/10 000 patient-days/year (range 0.49--1.29 episodes). On an annual trend basis, the overall incidence was essentially stable in surgical and medical wards, but decreased in intensive care units (ICUs) (p 0.0065). The average use of fluconazole was 37.9 g/10 000 patient-days/year (range 21.4--56.1 g), and did not change significantly during the 10-year period. Nearly two-thirds of patients were in ICUs at the onset of candidaemia, but none was neutropenic in either study period. Candida albicans remained the predominant species isolated (53.8% vs. 48.1%), followed by Candida parapsilosis, Candida glabrata and Candida tropicalis, the distribution of which did not change significantly. The 30-day crude mortality rate was essentially similar (44% vs. 35%) in both study periods. Thus the incidence of nosocomial candidaemia, although high in this institution, decreased among critically-ill patients during the 10-year period. This finding seemed to be related to an improvement in infection control practices, particularly regarding the prevention of intravascular catheter-related infections in ICUs. Although the overall use of fluconazole was considerable, no increase in azole-resistant non-albicans Candida spp. was detected.

Stereotactic brain biopsy in human immunodeficiency virus-infected patients.

OBJECTIVE: To evaluate prospectively the diagnostic efficacy and safety of stereotactic brain biopsy and its impact on treatment, outcome, and survival in human immunodeficiency virus-infected patients with focal brain lesions. METHODS: Computed tomography-guided stereotactic brain biopsy was performed in 26 patients, of whom 17 failed to respond to a 2- to 3-week anti- Toxoplasma regimen. Exclusion criteria for biopsy were overt acquired immunodeficiency syndrome for 2 years or longer, Karnofsky score less than 50, and severe coagulopathies. RESULTS: A definitive diagnosis was obtained in 24 patients (92%), of whom 12 (46%) had primary brain lymphoma, six (23%) had progressive multifocal leukoencephalopathy, and four (15%) had Toxoplasma encephalitis. Two thirds of contrast-enhancing lesions on computed tomography were lymphoma and three fourths of contrast-negative lesions were leukoencephalopathy. Three patients had biopsy-related cerebral hemorrhages (morbidity, 11.5%). Median follow-up and survival for the entire group were 24 weeks (range, 6 to 135 weeks). Twenty patients (77%) received specific therapy and 13 (50%) responded to treatment. Of 11 patients with lymphoma undergoing irradiation treatment (whole-brain radiotherapy in seven and gamma-knife treatment in four), nine (82%) had clinical and radiologic response, with a median survival of 34 weeks (range, 13 to 57 weeks). CONCLUSIONS: Stereotactic brain biopsy has high diagnostic efficacy and clinical benefit in carefully selected human immunodeficiency virus-infected patients. The procedure should be performed essentially in patients with contrast-enhancing lesions on computed tomography who have a high frequency of treatable cerebral diseases.

Neurological complications of HIV infection in pre-HAART and HAART era: a retrospective study.

The introduction of highly active anti-retroviral therapy (HAART) led to a radical change in the natural history of HIV infection and of the associated neurological opportunistic infections. However, the mortality of central nervous system (CNS) complications and opportunistic infections is still high in untreated HIV-infected individuals or in patients unaware of their HIV infection. We describe the outcome of HIV-infected patients followed at a single center for AIDS-related neurological syndromes in the 16 years following the introduction of HAART, and compare the findings with those in patients admitted up to 1996. We have conducted a retrospective study of patients with HIV infection or AIDS (based on WHO criteria and classified according to the 1993 CDC criteria) admitted during 20 years (January 1992 to March 2012) to the Infectious Diseases Unit of the University of Verona for the presence of focal or widespread CNS lesion on neuroimaging. Clinical history, CD4 cell count, HIV-RNA level, neurological examination, imaging, cerebrospinal fluid examination and eventual cerebral biopsy results were reviewed as well as the final neurological diagnosis and the treatment. The survival time from the clinical onset of the neurologic syndrome to death was calculated for each patient who died. A statistical analysis was performed comparing data collected up to and after 1996, i.e., before and after HAART introduction. Among 1043 patients with HIV infection or AIDS admitted to the Infectious Diseases Unit of the University of Verona between January 1992 and March 2012, 114 had a CNS lesion. The following diseases were observed: neurotoxoplasmosis (NT), progressive multifocal leukoencephalopathy), primary central nervous system lymphoma (PCNSL), the severe form of HIV-associated neurocognitive disorder, cryptococcal encephalitis (CE) and lesions of undetermined origin. The follow-up period was 4 weeks to 72 months both in the pre-HAART and HAART era. Cerebral lesions were detected in 53/243 patients (21.8%) in the pre-HAART era and in 61/801 patients (7.6%) in the HAART era (p < 0.001). Most patients who developed a neurological complication in the HAART period (40/59, 67.8%) were untreated or did not know to be HIV-infected; in particular, 27.9% of patients with a CNS lesion in the HAART era were unaware of their HIV infection vs 13.2% in the pre-HAART era (p < 0.05). Some patients were not virologically suppressed (14/59, 23.7%) or were immunological non-responders (undetectable viral load, with CD4 count <200 cells/µL; 4/59, 6.8%). Other statistically significant data were the mean age at the onset of neurological complications (32.6 ± 5.4 years in the pre-HAART, 40.3 ± 9.5 in the HAART group, p < 0.001) and the mean CD4 cell count at the onset of illness (median of 38 cells/µL (2-215) in the pre-HAART, 77 cells/µL (2-752) in the HAART group; p < 0.001). In the HAART era a reduction of PCNSL and NT was observed. Our results, while confirming a decrease in the incidence of opportunistic infections of the CNS in the HAART era, show that late presentation of patients with HIV infection remains an important issue in our catchment area.

Cellular proviral HIV-DNA decline and viral isolation in naïve subjects with <5000 copies/ml of HIV-RNA and >500 x 10(6)/l CD4 cells treated with highly active antiretroviral therapy.

OBJECTIVE: To evaluate the decay rate of cellular proviral HIV-DNA and viral replication in patients receiving highly active antiretroviral therapy (HAART) in the very early phase of infection. METHODS: Thirty-four patients treated with HAART and retrospectively selected for progressive decline of plasma viraemia up to undetectable levels (< 20 copies/ml), were stratified according to CD4+ cell count and plasma viraemia at base line: > 500 x 10(6) cells/l with < 5000 copies/ml (group 1) or with > 5000 copies/ml (group 2), > 5000 copies/ml with 300-500 x 10(6) cells/l (group 3) or with < 300 x 10(6) cells/l (group 4). Plasma HIV-RNA and proviral HIV-DNA were analysed at baseline and after 1, 2, 3, 6, 9 and 12 months of treatment. RESULTS: After 1 year of treatment, a significant decrease of proviral DNA titre was observed in all patients and a decrease > 1 log was achieved in 24 of 29 subjects of the first three groups. The more pronounced decay of HIV-DNA (half-life 28 weeks) up to < 50 HIV-DNA copies/10(6) CD4+ cells was detected in patients of group 1. At the year's endpoint, five patients (four in group 1 and one in group 2) had < 20 HIV-DNA copies. However, HIV strains sensitive to antiretroviral drugs were isolated from peripheral lymphocytes of 16 out of 34 patients. CONCLUSION: In patients with undetectable plasma viraemia after 1 year of HAART, the highest reduction of proviral DNA up to < 50 copies/10(6) CD4+ cells was obtained only in subjects in the early asymptomatic phase of infection. Nevertheless, a replication-competent virus can be detected in all phases of antiretroviral therapy.

A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection.

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).

Transbronchial biopsy in the diagnosis of pulmonary infiltrates in immunocompromised patients.

Bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) frequently are performed in the investigation of immunocompromised patients with lung disorders. The risk-benefit ratio of TBB currently is debated, since several authors have found that the less invasive BAL may provide as much information as TBB, with the avoidance of some biopsy-related side effects. We retrospectively evaluated 157 instances of bronchoscopy carried out on 142 immunocompromised patients, with both BAL and TBB performed in every case. Immunosuppressant conditions were HIV infection (79), hematologic malignancies (36), and antirejection therapy in renal transplant recipients (27). Transbronchial biopsy provided a diagnostic yield significantly higher than that obtained by BAL in all categories investigated; diagnostic rates were 77.3% for TBB and 47.6% for BAL (p < 0.001) in patients with HIV infection, 55 and 20% (p < 0.001) in patients with hematologic malignancies, and 57.5 and 27.2% (p < 0.001) in renal transplant recipients. Looking at the whole series, the diagnostic rates of TBB and BAL were 67.5 and 36.3%, respectively (p < 0.001), with a total additional yield of 33% provided by TBB, while in only 2% of cases BAL gave rise to diagnostic information not achieved by TBB. Considering that side effects followed TBB at a negligible rate (2.5%), we believe that TBB should be routinely carried out in these patients once the diagnostic strategy has been oriented to bronchoscopy.