Empirical use of fluoroquinolones may delay the initiation of appropriate therapy for tuberculosis (TB). This study aimed to evaluate the impact of empirical fluoroquinolone use on the survival of patients with pulmonary TB that mimicked severe community-acquired pneumonia (CAP) requiring intensive care.
Patients aged >18 years with culture-confirmed pulmonary TB who presented as severe CAP and were admitted to the ICU were divided into fluoroquinolone (FQ) and nonfluoroquinolone (non-FQ) groups based on the type of empirical antibiotics used. Those patients with previous anti-TB treatment or those who died within 3 days of hospitalization were excluded. The primary end point was 100-day survival.
Of the 77 patients identified, 43 (56%) were in the FQ group and 34 (44%) were in the non-FQ group. The two groups had no statistically significant difference in co-morbidities (95% vs. 97%, P > 0.99) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores (21.2 ± 7.1 vs. 22.5 ± 7.5, P = 0.46) on ICU admission. Overall, 91% and 82% of patients in the FQ and non-FQ groups, respectively, had sputum examinations for TB within 1 week of admission (P = 0.46), and results were positive in 7% and 15% (P = 0.47), respectively. For both groups, 29% received appropriate anti-TB therapy within 2 weeks after ICU admission. The 100-day mortality rate was 40% and 68% for the FQ and non-FQ groups, respectively (P = 0.02). By Cox regression analysis, APACHE score <20, no bacteremia during the ICU stay, and empirical fluoroquinolone use were independently associated with survival.
Empirical use of fluoroquinolones may improve the survival of ICU patients admitted for pulmonary TB mimicking severe CAP.
Outbreaks of sexually transmitted hepatitis C virus (HCV) infections have been recently reported in HIV-infected men who have sex with men (MSM) in Europe, Australia, and North America. Little is known concerning whether this also occurs in other Asia-Pacific countries. Between 1994 and 2010, a prospective observational cohort study was performed to assess the incidence of recent HCV seroconversion in 892 HIV-infected patients (731 MSM and 161 heterosexuals) who were not injecting drug users. A nested case-control study was conducted to identify associated factors with recent HCV seroconversion, and phylogenetic analysis was performed using NS5B sequences amplified from seroconverters. During a total followup duration of 4,270 person-years (PY), 30 patients (3.36%) had HCV seroconversion, with an overall incidence rate of 7.03 per 1,000 PY. The rate increased from 0 in 1994 to 2000 and 2.29 in 2001 to 2005 to 10.13 per 1,000 PY in 2006 to 2010 (P < 0.05). After adjustment for age and HIV transmission route, recent syphilis remained an independent factor associated with HCV seroconversion (odds ratio, 7.731; 95% confidence interval, 3.131 to 19.086; P < 0.01). In a nested case-control study, seroconverters had higher aminotranferase levels and were more likely to have CD4 ≥ 200 cells/μl and recent syphilis than nonseroconverters (P < 0.05). Among the 21 patients with HCV viremia, phylogenetic analysis revealed 7 HCV transmission clusters or pairs (4 within genotype 1b, 2 within genotype 2a, and 1 within genotype 3a). The incidence of HCV seroconversion that is associated with recent syphilis is increasing among HIV-infected patients in Taiwan.
This case-control study aimed to characterize the factors associated with amebiasis, defined as presence of anti-Entamoeba histolytica antibody titers of ≧ 128 by indirect hemagglutination assay, among persons seeking voluntary counseling and testing (VCT) for human immunodeficiency virus (HIV) infection. Between April 2006 and September 2009, 57 of 4,802 persons (1.2%) seeking VCT services were seropositive for E. histolytica infection. Compared with 228 seronegative controls, case subjects were older (odds ratio [OR] for per 1-year increase, 1.098; 95% confidence interval [CI], 1.036, 1.165), less likely to hold bachelor degree or higher (OR, 0.359; 95% CI, 0.152, 0.846), and were more likely to be men who have sex with men (MSM) (OR, 8.382; 95% CI, 2.050, 34.266) and have oral-anal sex (OR, 4.016; 95% CI, 1.711, 9.427) in multiple logistic regression analysis. The MSM, fecal-oral contamination, lower educational achievement, and older age were associated with increased risk for amebiasis among persons seeking VCT for HIV infection.
In studying the epidemiology of parvovirus 4 (PARV4) in Taiwan, we detected DNA in plasma of 3 mothers and their newborns with hydrops. In 1 additional case, only the mother had PARV4 DNA. Our findings demonstrate that PARV4 can be transmitted through the placenta.
viruses; parvovirus B19V; parvovirus 4; hydrops; vertical transmission; infants; dispatch
An outbreak of human immunodeficiency virus (HIV) infection occurred among injecting drug users (IDU) in Taiwan between 2003 and 2006, when an extremely high prevalence of hepatitis C virus (HCV) infection was also detected. To determine whether clusters of hepatitis D virus (HDV) infection occurred in this outbreak, 4 groups of subjects were studied: group 1, HIV-infected IDU (n = 904); group 2, HIV-infected non-IDU (n = 880); group 3, HIV-uninfected IDU (n = 211); and group 4, HIV-uninfected non-IDU (n = 1,928). The seroprevalence of hepatitis B virus (HBV) was 19.8%, 18.4%, 17.1%, and 6.7%, and HDV seroprevalence among HBV carriers was 75.4%, 9.3%, 66.7%, and 2.3%, for groups 1, 2, 3, and 4, respectively. Ninety-nine of 151 (65.6%) HDV-seropositive IDU had HDV viremia: 5 were infected with HDV genotype I, 41 with genotype II, 51 with genotype IV, and 2 with genotypes II and IV. In the phylogenetic analysis, only one cluster of 4 strains within the HDV genotype II was identified. Among patients with HCV viremia, a unique cluster within genotype 1a was observed; yet, patients within this cluster did not overlap with those observed in the HDV phylogenetic analysis. In summary, although IDU had a significantly higher HDV seroprevalence, molecular epidemiologic investigations did not support that HDV was introduced at the same time as HCV among IDU.
Although access to highly active antiretroviral therapy (HAART) has prolonged survival and improved life quality, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support in intensive care units (ICU). This study aimed to describe the etiology and analyze the prognostic factors of HIV-infected Taiwanese patients in the HAART era.
Medical records of all HIV-infected adults who were admitted to ICU at a university hospital in Taiwan from 2001 to 2010 were reviewed to record information on patient demographics, receipt of HAART, and reason for ICU admission. Factors associated with hospital mortality were analyzed.
During the 10-year study period, there were 145 ICU admissions for 135 patients, with respiratory failure being the most common cause (44.4%), followed by sepsis (33.3%) and neurological disease (11.9%). Receipt of HAART was not associated with survival. However, CD4 count was independently predictive of hospital mortality (adjusted odds ratio [AOR], per-10 cells/mm3 decrease, 1.036; 95% confidence interval [CI], 1.003 to 1.069). Admission diagnosis of sepsis was independently associated with hospital mortality (AOR, 2.91; 95% CI, 1.11 to 7.62). A hospital-to-ICU interval of more than 24 hours and serum albumin level (per 1-g/dl decrease) were associated with increased hospital mortality, but did not reach statistical significance in multivariable analysis.
Respiratory failure was the leading cause of ICU admissions among HIV-infected patients in Taiwan. Outcome during the ICU stay was associated with CD4 count and the diagnosis of sepsis, but was not associated with HAART in this study.
Among 234 isolates comprising 26 different Candida species colonizing the oropharynx of 181 (54.3% of 399 surveyed) HIV-infected outpatients, 27 (11.7%) were fluconazole resistant. Antibacterial treatment was associated with increased rates of yeast colonization, while antiretroviral therapy and pneumococcal vaccination protected patients from yeast colonization.
In 2008, an outbreak of human trichinosis associated with ingestion of raw soft-shelled turtles was identified and investigated in Taiwan. The data suggested that patients were likely infected with Trichinella papuae.
Trichinella; trichinosis; zoonoses; parasites; soft-shelled turtles; Taiwan; dispatch
Tipranavir (TPV) is a recently approved nonpeptidic protease inhibitor (PI) of HIV-1 and has been indicated for those infected with PIs-resistant HIV-1. However, in clinical practice, whether the HIV-1 from the patients with virological failure to the regimens containing first-line PIs remains susceptible to TPV/r may be questionable.
To assess the resistance levels to TPV of HIV-1 from patients with treatment failure to first-line PIs, patients who experienced virological failure were tested for genotypic resistance of HIV-1 since August 2006 in National Taiwan University Hospital. Patients were enrolled for this analysis if their failed regimens contained > 12 weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group, respectively), but were excluded if they experienced both or other PIs. The levels of genotypic resistance to TPV/r were determined by TPV mutation score.
Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group were enrolled. The TPV mutation scores in subjects in LPV/r group were significantly higher than these in ATV group (median, 3 vs 1, P = 0.007). 95.2% subjects in ATV group and only 45% subjects in LPV/r group had an estimated maximal virological response to TPV/r (P < 0.001). The resistance levels to TPV/r correlated with the duration of exposure to first-line PIs, whether in ATV or LPV/r group.
Cross-resistance from first-line PIs may impede the effectiveness of TPV/r-containing salvage therapy. TPV/r should be used cautiously for patients with virological failure to LPV/r especially long duration of exposure.
Among 345 persons who underwent indirect hemagglutination (IHA) serological assays and assays of specific amebic antigens in their stool samples, 24 of 36 (66.7%) who were seropositive for Entamoeba histolytica had intestinal amebiasis as determined by antigen assays compared with 2 of 309 (0.2%) who were seronegative (odds ratio, 307; 95% confidence interval, 64.9 to 1,451). The estimated cost to detect a case of intestinal amebiasis by serology followed by antigen assays ($52) could be reduced by 74.3% and 69.9%, respectively, compared with the costs of the concurrent use of both assays ($202) and the antigen assays alone ($173). Our finding suggests that IHA assays followed by specific-amebic-antigen assays can be cost-effective in the diagnosis of intestinal amebiasis among persons with or without human immunodeficiency virus infection who are at risk for E. histolytica infection.
Invasive amebiasis is an emerging parasitic disorder in Taiwan, especially in patients diagnosed with human immunodeficiency virus (HIV) infection. Thirty-three Taiwanese subjects with amebic liver abscess (ALA) were examined and a possible correlation between ALA and HIV infection was investigated.
Among ALA patients, the proportion of HIV-positive individuals increased during the study period. ALA was the first major clinical presentation in 54% of HIV patients with ALA. Overall, 58% (14/24) of HIV-infected patients had a CD4+ count > 200 cells/μL and 82.1% (23/28) had no concurrent opportunistic infection or other evidence of HIV infection. There was no marked difference in clinical characteristics between HIV-positive and HIV-negative ALA patients except the level of leukocytosis.
While the clinical characteristics described herein cannot be used to determine whether ALA patients have HIV infection, routine HIV testing is recommended in patients with ALA, even in the absence of HIV symptoms.
Incidence of Entamoeba histolytica infection and clinical manifestations and treatment response of invasive amebiasis (IA) in HIV-infected patients have rarely been investigated before.
At the National Taiwan University Hospital, medical records of HIV-infected patients who received a diagnosis of IA between 1994 and 2005 were reviewed. The incidence of amebiasis was investigated in serial blood and stool samples from 670 and 264 HIV-infected patients, respectively, using serological and specific amebic antigen assays. DNA extracted from stool samples containing E. histolytica were analyzed by PCR, sequenced, and compared. Sixty-four (5.8%) of 1,109 HIV-infected patients had 67 episodes of IA, and 89.1% of them were men having sex with men (MSM). The CD4 count at diagnosis of IA was significantly higher than that of the whole cohort (215 cells/µL vs. 96 cells/µL). Forty episodes (59.7%) were liver abscesses, 52 (77.6%) colitis, and 25 (37.3%) both liver abscesses and colitis. Fever resolved after 3.5 days of metronidazole therapy (range, 1–11 days). None of the patients died. The incidence of E. histolytica infection in MSM was higher than that in other risk groups assessed by serological assays (1.99 per 100 person-years [PY] vs. 0 per 100 PY; p<0.0001) and amebic antigen assays (3.16 per 100 PY vs. 0.68 per 100 PY; p = 0.12). In multiple logistic regression analysis, only MSM was significantly associated with acquisition of E. histolytica infection (adjusted odds ratio, 14.809; p = 0.01). Clustering of E. histolytica isolates by sequencing analyses from geographically-unrelated patients suggested person-to-person transmission.
HIV-infected MSM were at significantly higher risk of amebiasis than patients from other risk groups. Despite immunosuppression, amebic liver abscesses and colitis responded favorably to treatment.
Entamoeba histolytica, morphologically identical to but genetically different from E. dispar and E. moshkovskii, is the causative agent of amebiasis. Recently there have been reports of increased risk for amebiasis among men who have sex with men (MSM) due to oral-anal sexual contact in several developed countries. In this longitudinal follow-up study, the incidence of amebiasis was determined among HIV-infected patients using serological and specific amebic antigen assays. DNA extracted from stool samples containing E. histolytica were analyzed by PCR, sequenced, and compared. Clinical manifestations and treatment response of invasive amebiasis in HIV-infected patients were reviewed. The results demonstrated that HIV-infected MSM were at significantly higher risk of amebiasis than patients from other risk groups. Clustering of E. histolytica isolates by sequencing analyses from geographically unrelated patients suggested person-to-person transmission. Despite immunosuppression, amebic liver abscesses and colitis responded favorably to metronidazole therapy. It is important to investigate in areas of high incidence of both amebiasis and HIV (sub-Saharan Africa) how generalizable these findings are.
Galactomannan (GM) is a heteropolysaccharide in the cell walls of most Aspergillus and Penicillium species. Cross-reactivity of Cryptococcus neoformans galactoxylomannan in an Aspergillus GM test has also been reported. In this study, we used a Platelia Aspergillus enzyme immunoassay kit (Bio-Rad) to test serum samples obtained from 48 human immunodeficiency virus (HIV)-infected patients (15 with penicilliosis [7 with fungemia alone, 4 with cavitary lung lesions alone, 3 with both fungemia and cavitary lung lesions, and 1 with disseminated disease], 22 with cryptococcosis [11 with fungemia alone, 5 with cavitary lung lesions, 3 with both, and 3 with meningitis alone], and 11 without any invasive fungal infection [control]) for GM levels. None of the patients had aspergillosis or concurrent use of piperacillin-tazobactam or amoxicillin-clavulanate. The median time between diagnosis of fungal infection and collection of serum samples was 0 days for penicilliosis and 1.5 days for cryptococcosis. Of patients with penicilliosis, cryptococcosis, and controls, 73.3%, 13.6%, and 9%, respectively, had GM optical density (OD) indices of >0.5 (P = 0.0001). GM OD indices were higher for penicilliosis (median OD index, 4.419; range, 0.158 to >20) than for cryptococcosis (median, 0.247; range, 0.112 to 3.849) cases (P < 0.001). Patients with fungemic penicilliosis had higher OD indices (median, 10.628; range, 0.401 to >20) than patients with nonfungemic penicilliosis (median, 0.378; range, 0.158 to 4.419) and patients with cryptococcemia (median, 0.231; range, 0.112 to 1.168) (P < 0.001). Of the 15 patients with cavitary lung lesions, those with penicilliosis had higher antigen levels (median OD index, 1.641; range, 0.247 to >20) than those with cryptococcosis (median, 0.227; range, 0.112 to 3.849) (P = 0.011). This study showed that the GM OD index was significantly elevated for HIV patients with penicilliosis. The use of the GM antigen assay may facilitate earlier diagnosis of Penicillium marneffei infection for HIV-infected patients in areas of endemicity.
Brain abscesses are occasionally associated with a dental source of infection. An unusual case of frontal lobe abscess in a nonimmunocompromised child infected with multidrug-resistant Capnocytophaga ochracea is described and confirms the pathogenic potential of this organism to cause human disease in the central nervous system.
Progressive cell-mediated immunodeficiency with decrease of CD4+ lymphocyte count to less than or equal to 200 cells/mm3 is a major risk factor for colonization with Candida species and development of candidiasis. Oropharyngeal candidiasis may occur in up to 90% of human immunodeficiency virus (HIV)-infected patients during the course of the disease. This study is to determine the effect of prolonged highly active antiretroviral therapy (HAART) on oropharyngeal colonization with Candida species and oral candidiasis.
A prospective, longitudinal follow-up study in HIV-infected patients receiving HAART.
The mean CD4+ count increased from 232.5 to 316 cells/mm3 and the proportion of patients whose CD4+ count less than 200 cells/mm3 decreased from 50.0% to 28.9% (p = 0.0003) in patients receiving HAART for at least 2 years. The prevalence of oral candidiasis decreased from 10.6% to 2.1% (p = 0.004). The decrease in Candida colonization was less impressive, falling from 57.8% to 46.5 % (p = 0.06). Of the 142 patients enrolled in at least two surveys, 48 (33.8%) remained colonized with Candida and 42 (29.6%) remained negative. In the remaining 52 patients, 34 switched from culture positive to negative, and an increase in CD4+ lymphocytes was noted in 91.2% of them. Among the 18 patients who switched from culture negative to positive, 61.1% also demonstrated an increase in CD4+ lymphocyte count (p = 0.01).
These findings indicate that HAART is highly effective in decreasing oral candidiasis in association with a rise in CD4+ lymphocyte counts, but only marginally effective in eliminating Candida from the oropharynx.
To understand the Candida colonization of human immunodeficiency virus (HIV)-infected outpatients in Taiwan, we have conducted a prospective cohort study of Candida colonization and its risk factors at the National Taiwan University Hospital from 1999 to 2002. More than 50% of the patients were colonized with Candida species, and 12% developed symptomatic candidiasis. Patients colonized with fluconazole-resistant strains of Candida species had a higher prevalence of candidiasis than those colonized with susceptible strains. Our analysis found that antibiotic treatment and lower CD4+ counts (<200 cells/mm3) increased the rate of oropharyngeal candidiasis in HIV-infected patients, while antiretroviral therapy protected patients from the development of candidiasis.
Early detection of SARS-CoV in throat wash and saliva suggests that these specimens are ideal for SARS diagnosis.
The severe acute respiratory syndrome–associated coronavirus (SARS-CoV) is thought to be transmitted primarily through dispersal of droplets, but little is known about the load of SARS-CoV in oral droplets. We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 102 to 5.93 x 106 copies/mL) and saliva (7.08 x 103 to 6.38 x 108 copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. Immunofluorescence study showed replication of SARS-CoV in the cells derived from throat wash, demonstrating the possibility of developing a convenient antigen detection assay. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis.
severe acute respiratory syndrome; SARS; coronavirus; CoV; Taiwan; perspective
Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients.
Severe acute respiratory syndrome; healthcare workers; environmental contamination; real-time reverse transcriptase–polymerase chain reaction
We describe a 66-year-old woman with infective endocarditis due to Cardiobacterium hominis whose condition, complicated by severe aortic regurgitation and congestive heart failure, necessitated aortic valve replacement despite treatment with ceftriaxone followed by ciprofloxacin. The blood isolate of C. hominis produced β-lactamase and exhibited high-level resistance to penicillin (MIC, ≧256 μg/ml) and reduced susceptibility to vancomycin (MIC, 8 μg/ml).
Studies of macrolide resistance mutations and molecular typing using the newly proposed enhanced typing system for Treponema pallidum isolates obtained from HIV-infected patients in the Asia-Pacific region are scarce. Between September 2009 and December 2011, we conducted a survey to detect T. pallidum using a PCR assay using clinical specimens from patients with syphilis at six major designated hospitals for HIV care in Taiwan. The T. pallidum strains were genotyped by following the enhanced molecular typing methodology, which analyzed the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and the sequence of base pairs 131 to 215 in the tp0548 open reading frame of T. pallidum. Detection of A2058G and A2059G point mutations in the T. pallidum 23S rRNA was performed with the use of restriction fragment length polymorphism (RFLP). During the 2-year study period, 211 clinical specimens were obtained from 136 patients with syphilis. T. pallidum DNA was isolated from 105 (49.8%) of the specimens, with swab specimens obtained from chancres having the highest yield rate (63.2%), followed by plasma (49.4%), serum (35.7%), and cerebrospinal fluid or vitreous fluid (18.2%) specimens. Among the 40 fully typed specimens, 11 subtypes of T. pallidum were identified. Subtype 14f/f (18 isolates) was the most common isolates, followed by 14f/c (3), 14b/c (3), and 14k/f (3). Among the isolates examined for macrolide resistance, none had the A2058G or A2059G mutation. In conclusion, we found that type 14 f/f was the most common T. pallidum strain in this multicenter study on syphilis in Taiwan and that none of the isolates exhibited 23S rRNA mutations causing resistance to macrolides.
Risk of pneumocystosis after discontinuation of primary or secondary prophylaxis among HIV-infected patients before CD4 counts increase to ≧200 cells/μL (early discontinuation) after receiving highly active antiretroviral therapy (HAART) is rarely investigated.
Medical records of 660 HIV-infected patients with baseline CD4 counts <200 cells/μL who sought HIV care and received HAART at a university hospital in Taiwan between 1 April, 1997 and 30 September, 2007 were reviewed to assess the incidence rate of pneumocystosis after discontinuation of prophylaxis for pneumocystosis.
The incidence rate of pneumocystosis after HAART was 2.81 per 100 person-years among 521 patients who did not initiate prophylaxis or had early discontinuation of prophylaxis, which was significantly higher than the incidence rate of 0.45 per 100 person-years among 139 patients who continued prophylaxis until CD4 counts increased to ≧200 cells/μL (adjusted risk ratio, 5.32; 95% confidence interval, 1.18, 23.94). Among the 215 patients who had early discontinuation of prophylaxis after achievement of undetectable plasma HIV RNA load, the incidence rate of pneumocystosis was reduced to 0.31 per 100 person-years, which was similar to that of the patients who continued prophylaxis until CD4 counts increased to ≧200 cells/μL (adjusted risk ratio, 0.63; 95% confidence interval, 0.03, 14.89).
Compared with the risk of pneumocystosis among patients who continued prophylaxis until CD4 counts increased to ≧200 cells/μL after HAART, the risk was significantly higher among patients who discontinued prophylaxis when CD4 counts remained <200 cells/μL, while the risk could be reduced among patients who achieved undetectable plasma HIV RNA load after HAART.