Prospective study in critically ill non-neutropenic patients: diagnostic potential of (1,3)-ß-D-glucan assay and circulating galactomannan for the diagnosis of invasive fungal disease.

Diagnosis of invasive fungal disease (IFD) in patients under intensive care is challenging. Circulating biomarkers, (1,3)-ß-D-glucan (BG) and galactomannan (GM), were prospectively assessed in 98 critically ill patients at risk of IFD. There were 11 cases of invasive aspergillosis (IA; 4 proven and 7 probable), 9 cases of proven invasive candidiasis (IC), 1 case of mixed proven IC and probable IA, 1 case of proven zygomycosis, and 1 case of mixed mycelial proven IFD. In all IA cases there was no significant difference when the area under the receiver operating characteristic curve (AUC) of GM (0.873 [95%CI, 0.75-0.99]) and BG (0.856 [95% CI, 0.71-0.99]) were compared (p = 0.871). The AUC for BG in IC and for the rest of the IFD cases was 0.605 (95% CI, 0.39-0.82) and 0.768 (95% CI, 0.63-0.90) respectively. Positive BG (40%) predated blood culture (n = 3) and abdominal pus (n = 1) a mean of 3.25 days before Candida was grown. In patients with IFD caused by molds, BG appeared a mean of 5.65 days before culture results. For the diagnosis of patients at risk of IC, BG has shown a high NPV (94.5%), with positive results also predating blood cultures in 30% of patients. In conclusion, early BG results permit a timely initiation of antifungal therapy in patients at risk of IFD.

A prospective comparison of galactomannan in bronchoalveolar lavage fluid for the diagnosis of pulmonary invasive aspergillosis in medical patients under intensive care: comparison with the diagnostic performance of galactomannan and of (1→ 3)-ß-d-glucan chromogenic assay in serum samples.

Diagnosis of fungal pneumonia (FP) in critically ill patients is challenging. Circulating biomarkers for the diagnosis of FP have limitations and the combination of different assays in serum samples and directly from the target organ may further improve the diagnosis of FP. We prospectively assessed the diagnostic utility of paired galactomannan (GM) in bronchoalveolar lavage fluid (BAL) and serum GM and (1→3)-ß-D-glucan (BG) assays in critically ill patients at risk of FP. Patients with FP were classified according to European Organisation for Research and Treatment of Cancer-Mycoses Study Group criteria, with modifications. Out of 847 admissions, 51 patients were eligible. There were nine invasive aspergillosis (IA) cases (four proven, five probable), three proven Pneumocysitis jirovecii pneumonia (PJP) cases and one mixed FP case (probable IA and proven PJP). The diagnostic accuracy as given by the area under the receiver operating characteristic curve in IA cases (proven and probable) for GM in BAL was 0.98 (95% CI, 0.94-1.00), whilst for GM and BG in serum it was 0.85 (95% CI, 0.74-0.96) and 0.815 (95% CI, 0.66-0.96), respectively. For IA cases (proven and probable) AUC for GM in BAL was significantly higher than GM and BG in serum (p 0.025 and p 0.032, respectively). In one of four proven and one of six probable IA cases, GM in serum remained negative, whereas GM in BAL was positive. In patients with IA, GM (90%) and BG (80%) appeared a mean of 4.3 days (range, 1-10 days) before Aspergillus was cultured. GM detection in BAL appears to improve the diagnosis of IA in critical patients.

[Mortality and survival in a cohort of 1,115 HIV-infected patients (1989-97)]. / Estudio de la mortalidad y supervivencia en una cohorte de 1,115 pacientes con infección VIH (1989-97).

BACKGROUND: To study survival and HIV/AIDS-related mortality from 1989 through 1997. To analyze the effect of antiretroviral treatment and prophylaxis against P. carinii pneumonia (PCP-prophylaxis). PATIENTS AND METHODS: We retrospectively studied a cohort of 1,115 HIV (+) outpatients (331 with AIDS-defining criteria) seen in our specific HIV hospital unit from January 1989 through May 1997. We analyzed the effect of different antiretroviral treatments on annual mortality rate. In survival studies we used Cox regression analysis to analyze survival over time as well as the effect of different opportunistic events, adherence and changes in treatment during follow up. RESULTS: Mortality rate was 13.7 per 100 person-years in 1994. It went down to 4.2 during the first half of 1997 (p=0.001). Mortality rate decreased depending on treatment received: 53% (CI 95=34-65%) with monotherapy, 68% (CI 95=38-84%) with bitherapy, 86% (CI 95=40-96%) with triple therapy, and 49% (CI =29-64%) with PCP-prophylaxis. Patients with more than 100 CD4 had an increasing survival over time (p=0.002). In AIDS patients good adherence to antiretroviral treatment and PCP-prophylaxis were associated with a lower risk of death (RR=0.88; CI 95=0.63-1.22 and RR=0.72; CI 95=0.55-0.95 respectively). CONCLUSIONS: In recent years PCP-prophylaxis and antiretroviral treatment (especially combined therapy) have contributed to a decrease in AIDS-related mortality. Adherence to treatments relates to risk of death and survival.

[Efficacy and safety of zidovudine in monotherapy in patients with HIV infection]. / Eficacia y tolerancia del tratamiento con zidovudina (ZDV) en monoterapia en pacientes con infección VIH.

BACKGROUND: To study the efficacy and the tolerance of the zidovudine (ZDV) in monotherapy for the treatment of a cohort of patients with HIV infection, most of them injection-drug users (IDU). METHODS: Retrospective study of a historic cohort of 350 patients, from January 1988 to December 1994. The clinic progression, the immunologic deterioriation and the survival after the ZDV administration were evaluated, like the toxicity of the drug. RESULTS: The estimated progression time to AIDS for the 25% of the cohort was 29 months for the initially asymptomatic patients and 22 months for the subjects who showed symptoms. After 26 months half of the patients showed CD4 cell counts less to 50% of the basals. The cumulative survival probability after a year was 99%, 97% and 85% for the groups A, B y C of the CDC classification, and 94%, 87% and 58% after two years for these groups. The predictive factors associated with the survival were the clinic and immunologic status, ESR, LDH, and beta 2-microglobulin levels at the beginning of the treatment. The 35% of the patients suffered adverse events, mainly hematologic effects, although they only forced to suspend the treatment in the 5% of the cases. The only predictive factor associated with the toxicity was a neutrophile count less than 1.500 cells/mm3 previous to the treatment (p < 0.001). CONCLUSION: The ZDV use in monotherapy in a cohort of patients majority IDU shows the same efficacy and safety as the treatment in other patients with HIV infection.

[Predictive factors of non-compliance with anti-tuberculosis treatment in patients infected with the human immunodeficiency virus]. / Factores predictivos del abandono del tratamiento antituberculoso en pacientes infectados por el virus de la inmunodeficiencia humana.

A study was conducted to know the rate of non-compliance of antituberculosis therapy among HIV-infected patients, the factors associated with non-compliance and the evolution of these patients. The therapy compliance in 276 tuberculous HIV infected patients diagnosed in two Madrid hospitals was analyzed. Fifty-one patients (18%) were not included in the analysis (6 died without therapy, 6 were lost and 39 died during therapy). Out of the 225 evaluable patients, 36 (16%, 95% CI, 11.6-21.6) did not comply with therapy. The only factor associated with a higher therapy non-compliance was the antecedent of drug use (20% of non-compliance; relative risk: 10, 95% CI, 1.4-71). Patients using drugs at tuberculosis diagnosis had higher risk for non-compliance (31%; RR, 3.1; 95% CI, 1.6-6.3). The incidence of tuberculosis reactivation after leaving therapy was 78.8/100 patient-years. Therapy non-compliance increased death risk associated with tuberculosis (RR, 9.8; 95% CI, 4.6-21). Programs for controlling antituberculous therapy should give priority to active drug users, as this is the group with the highest risk for non-compliance.

Infection of the central nervous system by Rhinocladiella atrovirens in a patient with acquired immunodeficiency syndrome.

A case of central nervous system invasion by Rhinocladiella atrovirens is described. The patient was an intravenous drug abuser suffering from acquired immunodeficiency syndrome.