Risk factors for incident diabetes mellitus among HIV-infected patients receiving combination antiretroviral therapy in Taiwan: a case-control study.

OBJECTIVES: Recent studies suggest that patients with HIV infection are at increased risk for incident diabetes mellitus (DM). We investigated the incidence and risk factors of DM among HIV-infected patients receiving combination antiretroviral therapy (CART) in Taiwan. METHODS: Incident cases of DM were identified among HIV-infected patients at the National Taiwan University Hospital between 1993 and 2006. A retrospective case-control study was conducted after matching cases with controls for sex, age at HIV diagnosis, year of HIV diagnosis, mode of HIV transmission and baseline CD4 lymphocyte count. A multivariate analysis was performed to identify risk factors for incident DM among HIV-infected patients. RESULTS: In 824 HIV-infected patients eligible for analysis, 50 cases of incident DM were diagnosed, resulting in an incidence of 13.1 cases per 1000 person-years of follow-up. In total, 100 matched controls were identified. Risk factors for incident DM were a family history of DM [odds ratio (OR) 2.656; 95% confidence interval (CI) 1.209-5.834], exposure to zidovudine (OR 3.168; 95% CI 1.159-8.661) and current use of protease inhibitors (OR 2.528; 95% CI 1.186-5.389). CONCLUSIONS: Incident DM was associated with a family history of DM, exposure to zidovudine and current use of protease inhibitors in HIV-infected patients receiving CART in Taiwan.

Aetiology of cavitary lung lesions in patients with HIV infection.

BACKGROUND: Although many studies have been carried out on pulmonary diseases in HIV-infected patients, studies specifically investigating the aetiologies of cavitary lung lesions are rare. METHODS: HIV-infected patients enrolled in a cohort study who presented with cavitary lung lesions by radiography were identified between June 1994 and March 2008. Medical records and radiological and microbiological data for these patients were retrospectively reviewed using a standardized case collection form. RESULTS: During the 14-year study period, 73 episodes of cavitary lung lesions were diagnosed in 66 of 1790 (3.7%) HIV-infected patients. At the diagnosis of cavitary lung lesions, the median CD4 count was 25 cells/microL (range 1-575 cells/microL). Eighty-one pathogens were considered causative, with fungi being the most common aetiology (42.0%), followed by bacteria (29.6%) and mycobacteria (25.9%). Of the fungal pneumonias, 19 (55.9%) were caused by Penicillium marneffei, 11 (32.4%) by Cryptococcus neoformans, two (5.9%) by Pneumocystis jirovecii, and two (5.9%) by Aspergillus species. During the study period, 11 of 205 patients (5.4%) who were diagnosed as having tuberculosis presented with cavitary lung lesions, compared with 19 of 36 patients (52.8%) with penicilliosis and 11 of 64 patients (17.2%) with cryptococcosis (P<0.0001). The median CD4 count of patients with cavitary lung lesions resulting from tuberculosis (115 cells/microL) was significantly higher than that of patients with cavitary lung lesions resulting from penicilliosis (4 cells/microL) and cryptococcosis (29.5 cells/microL). CONCLUSIONS: Our findings suggest that invasive infections attributable to endemic fungi were the leading cause of cavitary lung lesions among patients in the late stage of HIV infection, and were more common than infections attributable to bacteria and mycobacteria.

Generic velpatasvir plus sofosbuvir for hepatitis C virus infection in patients with or without human immunodeficiency virus coinfection.

BACKGROUND: Data are limited regarding the effectiveness and safety of generic velpatasvir plus sofosbuvir (VEL/SOF) for hepatitis C virus (HCV) in patients with or without human immunodeficiency virus (HIV) coinfection. AIM: To evaluate the effectiveness and safety of generic VEL/SOF-based therapy for HCV infection in patients with or without HIV coinfection in Taiwan. METHODS: Sixty-nine HIV/HCV-coinfected and 159 HCV-monoinfected patients receiving 12 weeks of generic VEL/SOF with or without ribavirin (RBV) for HCV were prospectively enrolled. The anti-viral responses and the adverse events (AEs) were compared between the two groups. The characteristics potentially related to sustained virological response 12 weeks off therapy (SVR12 ) were analysed. RESULTS: The SVR12 was achieved in 67 HIV/HCV-coinfected patients (97.1%; 95% CI: 90.0%-99.2%) and in 156 HCV-monoinfected patients (98.1%; 95% CI: 94.6%-99.4%) receiving VEL/SOF-based therapy, respectively. The SVR12 rates were comparable between HIV/HCV-coinfected and HCV-monoinfected patients, regardless of pre-specified baseline characteristics. One hundred twenty-two (53.5%) and seven (3.1%) patients had baseline resistance-associated substitutions (RASs) in HCV NS5A and NS5B regions, but the SVR12 rates were not affected by the presence or absence of RASs. One (1.4%) and five (3.1%) patients in the HIV/HCV-coinfected and HCV-monoinfected groups had serious AEs. No patient died or discontinued treatment due to AEs. The eGFR remained stable throughout the course of treatment in HIV/HCV-coinfected patients receiving anti-retroviral therapy containing tenofovir disoproxil fumarate (TDF). CONCLUSIONS: Generic VEL/SOF-based therapy is well-tolerated and provides comparably high SVR12 rates for HCV infection in patients with and without HIV coinfection.

PTEN and NDUFB8 aberrations in cervical cancer tissue.

Cervical cancer is one of the world's major health issues. Despite many studies in this field, the carcinogenetic events of malignant conversion in cervical tumours have not been significantly characterised. The first aim of this project was to investigate the mutation status of the tumour suppressor gene- Phosphatase and Tension Homolog (PTEN)--in cervical cancer tissue. The second aim of this study was the analysis in the same cervical cancer tissue for aberrations in the mitochondrial electron transport chain subunit gene NDUFB8, which is localised to the same chromosomal contig as PTEN. The third aim was the evaluation of the potential therapeutic anti-cancer drug 2,4-Thiazolidinediones (TZDs) and its affect in regulating the PTEN protein in a cervical cancer cell line (HeLa). To approach the aims, paraffin-embedded cancerous cervical tissue and non-cancerous cervical tissue were obtained. DNA recovered from those tissues was then used to investigate the putative genomic changes regarding the NDUFB8 gene utilising SYBR Green I Real-Time PCR. The PTEN gene was studied via Dual-Labelled probe Real-Time PCR. To investigate the protein expression change of the PTEN protein, HeLa cells were firstly treated with different concentrations of 2,4-Thiazolidinediones and the level of PTEN protein expression was then observed utilising standard protein assays. Results indicated that there were putative copy-number changes between the cancerous cervical tissue and non-cancerous cervical tissue, with regard to the PTEN locus. This implies a potential gain of the PTEN gene in cancerous cervical tissue. With regards to normal cervical tissue versus cancerous cervical tissue no significant melting temperature differences were observed with the SYBR Green I Real-Time PCR in respect to the NDUFB8 gene. A putative up-regulation of PTEN protein was observed in TZD treated HeLa cells.

Endemic fungal infections caused by Cryptococcus neoformans and Penicillium marneffei in patients infected with human immunodeficiency virus and treated with highly active anti-retroviral therapy.

This study compared the clinical presentations of 58 episodes of cryptococcosis in 50 patients and 26 episodes of penicillosis in 25 patients infected with human immunodeficiency virus (HIV) between June 1994 and June 2004, and assessed the safety of discontinuation of secondary prophylaxis for endemic fungal infections in those patients responding to highly active anti-retroviral therapy (HAART). Neurological symptoms were seen more commonly in patients with cryptococcosis, whereas respiratory symptoms, lymphadenopathy, hepatomegaly and/or splenomegaly, and non-thrush-related oral presentations were seen more commonly in patients with penicillosis. Patients with penicillosis were more likely to have abnormal chest radiography results and radiographic presentations of interstitial lesions, cavitations, fibrotic lesions and mass lesions. At the end of the study, maintenance antifungal therapy had been discontinued in 27 patients with cryptococcosis and in 18 patients with penicillosis in whom the median CD4 count had increased to 186 cells/microL (range, 9-523 cells/microL) and 95 cells/microL (range, 15-359 cells/microL), respectively, after HAART. Only one episode of penicillosis recurred (a relapse rate of 1.72/100 person-years; 95% CI, 1.44-2.10/100 person-years) after a median follow-up duration of 35.3 months (range, 2.6-91.6 months). No relapses occurred in patients with cryptococcosis after a median follow-up duration of 22.3 months (range, 1-83.4 months). These findings suggest that there are differences in the clinical presentations between endemic cryptococcosis and penicillosis in patients with HIV infection, and that it is safe to discontinue secondary antifungal prophylaxis for cryptococcosis and penicillosis in patients responding to HAART.

Germline polymorphisms are potential metastasis risk and prognosis markers in breast cancer.

A number of theories have been proposed to account for the origins of metastasis, although none as yet have adequately explained all of its characteristics. With approximately 90% of cancer-related deaths due to the effects of disseminated tumors, improved understanding of this process is critical for reducing cancer-associated morbidity and mortality. Extensive research to investigate the molecular basis of this process has been conducted, and our lab has focused on the role of germline polymorphism in this complex process. Simple breeding experiments using a highly metastatic mouse model showed that germline polymorphisms significantly contribute to metastasis susceptibility. Genetic mapping studies revealed that a number of genomic regions are linked to metastasis susceptibility, including a metastasis modifier on mouse chromosome 19. Subsequent analysis identified Sipa1 as the most likely candidate for the observed linkage on Chr 19. Evaluation of SNPs in SIPA1 in a pilot association study in a human breast cancer cohort supported this possibility and demonstrated that SIPA1 polymorphisms are associated with various markers of poor prognosis including differential sentinel lymph node status. Taken together, these data suggest that germline polymorphism is an important modulating component in metastatic progression that needs to be investigated if we are to fully understand the metastatic process.

Prevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis in non-haemophiliac HIV-1-infected adults in Taiwan.

We assessed the seroprevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis (TE) in 844 non-haemophiliac HIV-infected patients in Taiwan between June 1994 and April 2003. Approximately 70% (69.3%) of them had a baseline CD4+ lymphocyte count of 200 x 10(6)/L or less, and more than 70% (73.9%) having initiated highly active antiretroviral therapy. The seroprevalence of T. gondii infection was 10.2%, which did not differ with sex,age,route of transmission, birth inside or outside of Taiwan, or CD4+ lymphocyte stratifications. After a median observation duration of 603 days (range, 1-3264 days), 10 (1.2%) patients developed 11 episodes of TE after a median interval of 30 days (range, 1-941 days) between enrolment and diagnosis of TE, with an incidence of 0.59 per 100 person-years (PY) (95% confidence interval, 0.56-0.63 per 100 PY). We concluded that the incidence of TE of HIV-infected patients in Taiwan was lower than that reported in western countries because of a lower seroprevalence of T. gondii infection and use of antimicrobial prophylaxis and antiretroviral therapy, although most of the patients were at the late stage of HIV infection.

Impact of chronic hepatitis C infection on outcomes of patients with an advanced stage of HIV-1 infection in an area of low prevalence of co-infection.

To ascertain whether hepatitis C (HCV) co-infection affects the progression of HIV infection, we initiated an eight-year prospective observational study at a university hospital in Taiwan where seroprevalences of HCV antibody and HIV antibody were low. Fifty-three (12.0%) consecutive non-haemophiliac HIV1-infected patients with HCV co-infection and 387 (88.0%) patients without HCV and hepatitis B co-infection were enrolled between June 1994 and June 2002 and observed until December 2002. Outcomes evaluated included the risk for acute hepatitis, hepatic decompensation, HIV disease progression and mortality, and changes of CD4+ count and plasma viral load (PVL) after initiation of highly active antiretroviral therapy (HAART) at the end of the study. The baseline CD4+ count, PVL and proportion of patients with AIDS-defining opportunistic illnesses (OI) at study entry were similar between patients with HCV co-infection and those without co-infection, but HCV-co-infected patients were older (39 versus 35 years, P = 0.01) and had a higher proportion of intravenous drug use (17.0% versus 0.8%, P < 0.001). After a total observation duration of 1137 patient-years (PY) (median, 791 days; range, 3-3053 days), the incidence of acute hepatitis in HCV-co-infected patients was 13.89 per 100 PY (95% confidence interval [CI], 13.31-14.49) and that in patients without co-infection was 6.39 per 100 PY (95% CI, 6.24-6.55 per 100 PY), with an adjusted odds ratio (OR) of 2.769 (95% CI, 1.652-4.640). At the end of the study, CD4+ count increased by 137 x 10(6) and 157 x 10(6)/L in patients with and without HCV co-infection, respectively, (P = 0.47). The proportions of achieving undetectable PVL (<400 copies/mL) after HAART was similar (76.7% versus 74.9%, P = 0.79). The adjusted OR for development of new AIDS-defining OI was 1.826 (95% CI, 0.738-4.522) in HCV-co-infected patients as compared with HCV- uninfected patients. The adjusted hazards ratio for death of HCV-co-infected patients when compared with those without co-infection was 0.781 (95% CI, 0.426-1.432). Our findings suggested that HCV co-infection was associated with a significantly higher risk for acute hepatitis in HIV-infected patients receiving antiretroviral therapy, but it had no adverse impact on virological, immunological and clinical responses to HAART and survival when compared with patients without HCV and HBV co-infection.

Dynamics of plasma cytokine levels in patients with advanced HIV infection and active tuberculosis: implications for early recognition of patients with poor response to anti-tuberculosis treatment.

OBJECTIVE: To examine whether the serial measurement of plasma cytokine levels can assist in the early recognition of AIDS/tuberculosis patients with poor response to anti-tuberculosis treatment. DESIGN: Longitudinal, prospective cohort study. SETTING: A university hospital, the largest centre for HIV/AIDS patients in Taiwan. METHODS: Between January 1997 and September 1998, 25 consecutive patients with advanced HIV infection and suspected tuberculosis were enrolled in the study. Plasma samples were obtained on day 1 (baseline), 3, 7 and 14 of anti-tuberculosis treatment and the levels of tumour necrosis factor-alpha (TNF-alpha) were measured. Patients were classified as either responders or non-responders according to the results of assessment of symptoms and follow-up cultures during the sixth and eighth week of anti-tuberculosis treatment. Thirty consecutive HIV-negative tuberculosis patients were also enrolled in the study. RESULTS: The data of a total of 16 AIDS patients (median CD4 cell count 16 x 10(6)/l; 12 responders and four non-responders) and 21 HIV-negative patients (16 responders and five non-responders), whose tuberculosis was culture-proven, were included for analysis. In responders, TNF-alpha levels declined remarkably within the first week of anti-tuberculosis treatment; however, the decline of TNF-alpha levels in non-responders was significantly less [the median ratio of TNF-alpha level on day 7 to that at baseline was 0.32 versus 0.85 (P < 0.001) in AIDS patients; 0.34 versus 0.80 (P = 0.001) in HIV-negative patients). The lack of a > or = 50% reduction in pre-treatment TNF-alpha levels during the first week of treatment was strongly associated with a poor response to anti-tuberculosis treatment (P = 0.001 in AIDS patients; P < 0.001 in HIV-negative patients). CONCLUSION: Serial measurement of plasma TNF-alpha levels may help to assess the response to anti-tuberculosis treatment in AIDS patients, in spite of very low CD4 cell counts. Failure of TNF-alpha levels to decline by > or = 50 % of pre-treatment levels in the first week of treatment may be an early surrogate marker of a poor response.

Invasive amoebiasis: an emerging parasitic disease in patients infected with HIV in an area endemic for amoebic infection.

OBJECTIVES: To describe the incidence and presentations of invasive amoebiasis (IA) in patients with HIV infection in an area endemic for amoebic infection and to assess the role of the indirect haemagglutination (IHA) assay in the diagnosis of IA in HIV-infected patients. DESIGN: Retrospective study of 18 cases of IA and HIV infection. SETTING: A university hospital, the largest centre for management of HIV-associated complications in Taiwan. METHODS: Medical, microbiological and histopathological records of 296 HIV-infected patients and serological data of IHA assay of 126 HIV-infected patients were reviewed to identify cases of IA from 23 June 1994 to 31 March 1999. An IHA titre > or = 1 : 128 was considered positive. Clinical characteristics of HIV-infected patients with IA and without IA were compared. RESULTS: Eighteen of the 296 patients (6.1%) with HIV infection were diagnosed with IA: 12 patients were diagnosed with definite IA and six with probable IA. The clinical manifestations included amoebic colitis (13 patients), amoebic liver abscess (nine), both colitis and abscess (four), and pleural effusion (two). IA was the initial presentation of HIV infection in nine patients. Co-infection with other enteric pathogens was diagnosed in six patients with IA. Compared with the 161 patients without IA who were newly diagnosed with HIV infection, the nine patients with IA had a higher median CD4+ lymphocyte count (202 x 10(6)/l versus 33 x 10(6)/l; P = 0.0017), were less likely to be diagnosed with AIDS (55.6% versus 85.4%; P = 0.039), and had fewer concurrent AIDS-defining illnesses (median number 0 versus 2; P = 0.003). Estimated mean survival duration was not significantly different between the two groups (597 days versus 611 days). Fourteen out of 126 patients (11.1%) had an IHA titre > or = 1 : 128. Of the 18 patients diagnosed with IA, 13 had a titre > or = 1 : 128. The sensitivity of IHA assay in the diagnosis of IA was 72.2% (13 out of 18) and the specificity was 99.1% (107 out of 108). The positive predictive value of IHA test for IA of this patient population was 92.9% (13 out of 14) whereas the negative predictive value was 95.5% (107 out of 112). CONCLUSION: IA is an increasingly important parasitic disease among patients with HIV infection in Taiwan. IHA assay has a good specificity and high negative predictive value in diagnosis of IA.

Clinical features and outcome in disseminated mycobacterial diseases in AIDS patients in Taiwan.

OBJECTIVE: To describe and compare the clinical features and outcome of disseminated tuberculosis (TB) and Mycobacterium avium complex (MAC) disease in AIDS patients. DESIGN: Prospective cohort study. SETTING: A 1800-bed university teaching hospital, the largest centre for HIV/AIDS patients in Taiwan. METHODS: From July 1994 through June 1997, a standardized protocol was used to record the demographic and clinical features in all hospitalized HIV-infected patients, and to perform routine studies and invasive procedures for diagnosis of disseminated mycobacterial diseases. To compare the survival, control patients were selected from the HIV-infected patients hospitalized in the same hospital during the same study period, and had similar age, sex, CD4+ cell counts and antiretroviral therapy regimens. RESULTS: A total of 22 cases of disseminated TB and 15 cases of disseminated MAC were identified. Disseminated TB and MAC occurred in patients with similarly low CD4+ cell counts (median, 23 versus 5 x 10(6)/l; P = 0.08). The clinical features favouring disseminated TB included night sweats, peripheral lymphadenopathy, acid-fast bacilli in sputum smears, chest radiographic findings of hilar enlargement, and lack of prior AIDS-defining illnesses. Hepatosplenomegaly, elevated serum alkaline phosphatase (more than twice the upper limit of normal), elevated serum gamma-glutamyl transpeptidase (more than three times the upper limit of normal), and leukopenia favoured disseminated MAC. The patients with disseminated TB survived much longer than patients with disseminated MAC (mean survival, 96 versus 22 weeks, P = 0.008) but had a similar outcome to control patients (P = 0.60). CONCLUSION: Disseminated TB and MAC are distinguishable by clinical features in AIDS patients with similar immunocompromised states. Those features may facilitate diagnosis and selection of specific therapeutic regimens. Disseminated TB was not associated with a shortened survival period in AIDS patients when they completed anti-TB treatment. In contrast, disseminated DMAC was associated with shortened survival despite treatment with potent regimens. These results may emphasize the importance of prophylaxis for MAC in this population.

Antithyroid-drug-induced agranulocytosis complicated by life-threatening infections.

Agranulocytosis is a rare complication of antithyroid drugs, and the aetiologies of community-acquired, life-threatening infections in patients taking these drugs have not previously been systematically described. Of 5653 hyperthyroid patients treated with antithyroid drugs at National Taiwan University Hospital between January 1987 and December 1997, 13 (0.23%) developed agranulocytosis with life-threatening infections. The most common presentations were fever (92%) and sore throat (85%). Initial clinical diagnoses were acute pharyngitis (46%), acute tonsillitis (38%), pneumonia (15%) and urinary tract infection (8%). Positive blood cultures from six patients yielded Pseudomonas aeruginosa (3), Escherichia coli (1), Staphylococcus aureus (1), Capnocytophaga species (1). Two patients died of uncontrolled infection, thyroid storm and multiple organ failure. Cases of antithyroid-drug-induced agranulocytosis in the English language literature are reviewed; Gram-negative bacilli, including Klebsiella pneumoniae (4 patients) and P. aeruginosa (3), were the most common pathogens in clinical isolates. Our observation and review suggest that broad-spectrum antibiotics with anti-pseudomonal activity should be given to patients with antithyroid drug-induced agranulocytosis who present with severe infection.

Oral fusidic acid fails to eradicate methicillin-resistant Staphylococcus aureus colonization and results in emergence of fusidic acid-resistant strains.

Carriers of methicillin-resistant Staphylococcus aureus (MRSA) in hospital constitute a reservoir of infections and increase the risk of bacteremia and wound infection. In this prospective randomized trial, we tested the effectiveness of oral fusidic acid for eradication of MRSA colonization. From March 1997 through February 1998, patients with MRSA colonization in medical intensive care units in a large urban teaching hospital were randomly assigned to receive fusidic acid 500 mg q8h orally for 7 days or no anti-staphylococcal treatment. Twenty-three MRSA carriers were found during the study period and 16 were eligible for evaluation; six of them received fusidic acid. MRSA colonization was cleared in only two of the six patients with fusidic acid treatment, and later recurred in one of them. MRSA disappeared for 1, 2, 7, 7, and 8 weeks, respectively, in five of the 10 patients without treatment. MRSA persisted in the other five cases. Although all MRSA isolates found in the initial surveillance culture were susceptible to fusidic acid (MIC /= 256 microg/mL). Pulsed-field gel electrophoresis pattern analysis showed that the resistant strains were genetically identical to the susceptible strains isolated from the same patient before fusidic acid treatment, in both cases. However, genetically distinct strains colonized in the same individual during follow-up were found in four out of 16 cases. We conclude that oral fusidic acid alone is not suitable for eradication of MRSA colonization, and may lead to the emergence of resistant strains.

The role of tissue studies in facilitating early initiation of antimycobacterial treatment in AIDS patients with disseminated mycobacterial disease.

SETTING: The question of whether aggressive investigations are useful in diagnosis and initiation of treatment in AIDS patients with disseminated mycobacterial disease (DMD) is still under debate. OBJECTIVE: To define the role of tissue studies in facilitating early initiation of antimycobacterial treatment and in establishing diagnosis in AIDS patients with DMD. DESIGN: From July 1994 through June 1997, 167 AIDS cases with fever were evaluated by stepwise investigation using a standardized protocol. Data of DMD cases were analyzed to define the role of tissue studies. RESULTS: A total of 40 cases of culture-proven DMD were identified. Antimycobacterial treatment was initiated due to positive acid-fast bacilli smears of sputum in only five cases. In the remaining cases, positive pathologic findings from tissue biopsies (lymph node, bone marrow or liver) facilitated early initiation of treatment in 60% (21/35). In 50% of all cases (20/40), the diagnosis could not have been established if cultures of tissue biopsies had not been performed. Both the pathologic examinations and mycobacterial cultures from liver biopsies had positivity rates of more than 50% (53.8% and 69.2%, respectively). CONCLUSIONS: Tissue studies were useful in facilitating early initiation of treatment and establishing diagnosis at least in half of the AIDS cases with DMD. Liver biopsy is worthwhile if the cause of fever is not discovered using less invasive investigations.

In vitro activity of linezolid against clinical Gram-positive bacterial isolates from Taiwan: an area with a high prevalence of antibiotic resistance.

The prevalence of antibiotic-resistant bacteria in Taiwan is due to the heavy use of antimicrobial agents in both animal husbandry and clinical practice over the past decades. Minimum inhibitory concentrations (MICs) of linezolid were established for 371 clinical isolates of staphylococci, pneumococci, enterococci and group A streptococci from Taiwan. All isolates tested including those resistant to beta-lactams, erythromycin, vancomycin and quinupristin-dalfopristin were uniformly susceptible to linezolid, with MICs ranging from 0.125 to 2 mg/l. Our data support the observation that there is no cross-resistance between linezolid and other classes of antimicrobial substances.

Efficacy and safety of cefepime treatment in Chinese patients with severe bacterial infections: in comparison with ceftazidime treatment.

An open label, randomized comparative study was conducted to evaluate the safety and efficacy of cefepime, in comparison with ceftazidime, in the treatment of adult hospitalized Chinese patients with severe bacterial infections. Forty patients with severe infections including septicemia, urinary tract infection and bacterial pneumonia were randomly assigned to receive treatment with cefepime (2 g intravenously every 12 h) or ceftazidime (2 g intravenously every 8 h). The cefepime group (20 evaluable patients) and ceftazidime group (16 evaluable patients) were comparable with respect to age, sex, underlying diseases and distribution of infection type. In both groups urinary tract infection was the most common type of infection and Escherichia coli was the most common etiologic microorganism. The rates of satisfactory clinical response were similar in the cefepime and ceftazidime groups (95 versus 93.7%; 95% confidence interval: -0.14 - 0.17, P = 0.87). The bacteriological response rates of the cefepime and ceftazidime groups did not differ significantly (88.9 versus 85.7%; 95% confidence interval: -0.30 - 0.36, P = 0.85). Both cefepime and ceftazidime were well tolerated, with similar incidence of side effects. The results of this study suggest that cefepime is as safe and effective as ceftazidime for the treatment of serious infections in adult hospitalized Chinese patients.

Efficacy and adverse effects of higher dose amphotericin B monotherapy for cryptococcal meningitis in patients with advanced HIV infection.

Treatment with a low daily dose of amphotericin B (0.4 mg/kg) in AIDS patients with cryptococcal meningitis has been associated with low efficacy and high mortality. We report our successful clinical experiences on a higher daily dose of amphotericin B (0.8-1.0 mg/kg) monotherapy in treating cryptococcal meningitis from June 1994 to August 1997 in 13 cases of advanced HIV infection. Most of them (12/13) had at least one of several poor prognostic factors. The mean duration of amphotericin B administration was 26 days (range, 3 to 58 days). Both microbiologically and clinically successful rates of treatment at the end of amphotericin B therapy were high (85%, 11/13). The median duration of negative CSF culture post therapy was 17 days (range, 8 to 33 days). Bone marrow toxicities were; thrombocytopenia (46%) and significant anemia (92%) after a mean of 9 days of treatment. Both, impaired renal function and hypokalemia, were seen in 10 cases (77%), while elevation of amylase and lipase values were present in 6 cases (46%). Our report reveals that a higher daily dose of amphotericin B can achieve a high efficacy in treatment of cryptococcal meningitis in AIDS patients, even though most cases had poor prognostic factors and were in severe immunocompromised states. However, clinicians should monitor higher dose-related adverse effects carefully.

Successful discontinuation of fluconazole as secondary prophylaxis for cryptococcosis in AIDS patients responding to highly active antiretroviral therapy.

Seven AIDS patients with disseminated cryptococcosis who had had immune reconstitution following highly active antiretroviral therapy (HAART) had discontinued their secondary antifungal prophylaxis to prevent relapse of Cryptococcus neoformans infection. The median CD4+ count was 236 cells/ micro L (range, 117-404 cells/ micro L; mean, 247 cells/ micro L) and the plasma viral loads were undetectable in five patients at discontinuation of antifungal prophylaxis. No relapse of cryptococcosis was detected in these patients after a median observation duration of nine months (range, 5.5-4.1 months, mean, 14.6 months) following discontinuation. Our data and review of the literature suggest that discontinuation of fluconazole prophylaxis is safe in patients with reconstitution of immunity following#10; initiation of HAART.

Fatal lactic acidosis associated with highly active antiretroviral therapy in patients with advanced human immunodeficiency virus infection in Taiwan.

Lactic acidosis (LA), a rare but life-threatening adverse effect associated with antiretroviral therapy, has been reported with an increasing frequency since the mid-1990s. From June 1994 to June 2002, a total of six patients, four males and two females with a median age of 43 years (range, 30 to 74 years), had been diagnosed with LA. The estimated incidence of LA was 5.1 per 1000 patient-years (PYs) on highly active antiretroviral therapy (HAART) (95% confidence interval [95% CI], 4.5-5.5 per 1000 PYs) and 4.4 per 1000 PY on nucleoside analogues (NAs) (95% CI, 3.9-4.7 per 1000 PYs). Their median body mass index at diagnosis of LA was 17.6 kg/m(2) (range 16.3 to 22.6 kg/m(2)). The median CD4+ lymphocyte count at the initial diagnosis of HIV infection and at the onset of LA was 38 cells/ micro L (range, 4 to 103 cells/ micro L) and 108 cells/ micro L (range, 79 to 224 cells/ micro L), respectively. The most common symptoms were nausea, vomiting, and dyspnoea. All of the patients had findings suggestive of NA-related mitochondrial toxicity, such as myositis, pancreatitis, fatty hepatitis, peripheral neuropathy or lipodystrophy. The prescribed NA related to LA were stavudine in six patients, lamivudine, five, and didanosine, one. Despite treatment, all patients died of persistent circulatory collapse following LA. The median duration from diagnosis to death was eight days (range, 4-17 days). Our report highlights that clinicians caring for patients with AIDS should be alerted to the potentially fatal LA associated with antiretroviral therapy when patients present with low body mass index, lipodystrophy, unexplained abdominal symptoms, dyspnoea, or elevated aminotransferases.

The simulation of hexavalent chromium formation under various incineration conditions.

The formation of hexavalent chromium Cr(VI) during waste incineration processes is of interested because its carcinogenic characteristic. The objective of this study is to simulate the formation of Cr(VI) species under various operating temperatures and input waste compositions during incineration by a thermodynamic model. The results show that the major hexavalent chromium species are CrO2Cl2(g) and CrO3(g). Chlorine and oxygen can increase the formation of Cr(VI) species; while hydrogen, sulfur, sodium, and calcium can inhibit. The input waste composition has greater effect on the formation of hexavalent chromium species than operating temperature.