Search

Interferon (IFN)-γ is crucial for normal immune surveillance and exhibits immunomodulatory, antimicrobial, and anticancer activity. Patients with nontuberculous mycobacteria (NTM) infection commonly express high levels of anti-IFN-γ autoantibodies (autoAbs) and suffer from recurrent infections due to adult-onset immunodeficiency with defects in IFN-γ immune surveillance. In this study, we developed the methods for determination of anti-IFN-γ autoAbs and then characterized their neutralizing activity in patients with NTM infection. A modified sandwich ELISA-based colorimetric assay followed by immunoblot analysis detected the presence of autoAbs in three out of five serum samples. Serum levels of IFN-γ were decreased. Synthetic peptide binding assay showed variable patterns of epitope recognition in patients positive for anti-IFN-γ autoAbs. Functional tests confirmed that patient serum blocked IFN-γ-activated STAT1 activation and IRF1 transactivation. Furthermore, IFN-γ-regulated inflammation, chemokine production and cytokine production were also blocked. These results provide potentially useful methods to assay anti-IFN-γ autoAbs and to characterize the effects of neutralizing autoAbs on IFN-γ signaling and bioactivity.

The interferon- (IFN-) γ expression is elicited in response to microbial infections and activates immune surveillance by antimicrobial immune elements to induce microbial killing. Patients with adult-onset immunodeficiency who suffer from recurrent infections with microbes, particularly nontuberculous mycobacteria (NTM), commonly display genetic defects in IFN-γ signaling as well as the generation of anti-IFN-γ autoantibodies (autoAbs). Because IFN-γ is an activator of macrophage differentiation and a proinflammatory activator of innate immunity, the blockade effects of the autoAbs present in NTM patient serum on IFN-γ are hypothesized to regulate the antimicrobial function of macrophages. In the presence of patient serum, IFN-γ-induced type 1 macrophage (M1) differentiation was inhibited in PMA-stimulated human monocytic THP-1 cells. Treatment with patient serum significantly blocked the production of proinflammatory factors, including cytokines/chemokines and reactive oxygen/nitrogen species, by M1 macrophages. Importantly, IFN-γ-facilitated phagocytosis and degradation of heat-killed mycobacterium were decreased by cotreatment with patient serum. These results show the blockade activity of anti-IFN-γ autoAbs on IFN-γ-mediated antimicrobial immunity in macrophages.

From June to September 2011, a total of 305 ertapenem-nonsusceptible Enterobacteriaceae isolates (MICs of ertapenem ≥ 1 μg/ml) were collected from 11 hospitals in different parts of Taiwan. The MICs of 12 antimicrobial agents against these isolates were determined using the broth microdilution method, and genes for carbapenemases were detected using PCR. Genotypes of isolates possessing carbapenemase genes were identified by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. The ertapenem-nonsusceptible Enterobacteriaceae isolates included Klebsiella pneumoniae ( n = 219), Escherichia coli ( n = 64), Enterobacter cloacae ( n = 15), and other species ( n = 7). Seven (2.3%) of the ertapenem-nonsusceptible Enterobacteriaceae isolates exhibited colistin MICs of >4 μg/ml, and 24 (7.9%) were not susceptible to tigecycline (MICs > 2 μg/ml). A total of 29 (9.5%) isolates carried genes encoding carbapenemases, namely, K. pneumoniae carbapenemase-2 (KPC-2) in 16 (7.3%) isolates of K. pneumoniae (KPC-2-KP) and IMP-8 in 5 (2.3%) isolates of K. pneumoniae , 5 (33.3%) isolates of E. cloacae , 1 isolate of E. coli , 1 isolate of Klebsiella oxytoca , and one isolate of Citrobacter freundii . The 16 KPC-2-KP isolates were isolated from patients at four different hospitals in northern Taiwan. All 16 of the KPC-2-KP isolates were susceptible to amikacin and colistin and had a similar pulsotype (pulsotype 1) and the same sequence type (sequence type 11). Infections due to KPC-2-KP mainly occurred in severely ill patients in the intensive care unit ( n = 14, 88%). Four patients with infections due to KPC-2-KP died within 14 days of hospitalization. The findings are the first to demonstrate intrahospital and interhospital dissemination of KPC-2-KP in northern Taiwan.

Among the 219 vancomycin-resistant Enterococcus faecium isolates collected in 20 Taiwanese hospitals from 2006 to 2010, all were susceptible to linezolid and daptomycin, and 98.6% were susceptible to tigecycline. There was a shift toward higher tigecycline MIC values (MIC 90 s) from 2006-2007 (0.06 μg/ml) to 2008–2010 (0.12 μg/ml). The MIC 90 s of daptomycin and linezolid remained stationary. Although pulsotypes among the isolates from the 20 hospitals varied, intrahospital spreading of several clones was identified in 13 hospitals.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli ( n = 602), ESBL-producing Klebsiella pneumoniae ( n = 736), and Acinetobacter baumannii ( n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC 90 values of tigecycline against MRSA, VRE, ESBL-producing E. coli , ESBL-producing K. pneumoniae , and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 μg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii . Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were E. coli . For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

Accurately differentiating tuberculous pleurisy from lung cancer is important for disease management but difficult using conventional laboratory methods. This study assessed the value of adenosine deaminase (ADA) and interferon gamma (IFN-γ) for differentiating the two conditions in a region of Taiwan with a high prevalence of tuberculosis. The study population comprised patients with lymphocytic exudative pleural effusions: tuberculous (n=24) and malignant (n=42). Mean levels of ADA and IFN-γ in pleural fluid, measured with commercial standardized kits, were significantly higher for tuberculous than for malignant pleurisy (p

Summary Objective The aim of this study was to assess the clinical significance of serological profiles suggestive of chronic Q fever after acute infection. Methods A prospective follow-up study consisting of two separate cohorts was conducted to monitor the serological evolution of Q fever. The first cohort comprised subjects with acute Q fever diagnosed in 2004–2007 and the second enrolled subjects whose infection occurred in 2009. The indirect immunofluorescence assay was used for serological monitoring, with serum PCR testing added for subjects whose serological profiles revealed high titers of anti-phase I IgG≥800, titers suggestive of chronic Q fever. Results In the first cohort of 92 persons, seventeen (18%) subjects had serological profiles suggestive of chronic Q fever (titers of anti-phase I IgG: 1280–5120, median: 1280) after a median follow-up period of 606.5 days. After a further follow-up (median period: 592 days) exclusively for those seventeen subjects, serological resolution with fourfold decrease of titers of anti-phase I IgG was noted in five of them. In the second cohort, only one (4%) of the twenty-eight subjects had high levels of anti-phase I IgG 180 days after acute infection. All the eighteen subjects with high levels of anti-phase I IgG were asymptomatic and had negative serum PCR testing. The different prevalence of subjects with high titers of anti-phase I IgG in the two cohorts was associated with duration of follow-up period ( P Conclusions Subjects with high titers of anti-phase I IgG≥800 was not uncommon and might not be detected until more than six months after acute Q fever infection. Asymptomatic subjects with high levels of anti-phase I IgG alone should not be treated as chronic Q fever and might not need continued serological monitoring in the absence of predisposing factors to chronic Q fever.

Background/Purpose Infective endocarditis caused by Staphylococcus lugdunensis is a rare disease. Since its first description in 1988, there have only been a few reports of this disease and the causative organism. These publications were primarily case reports and brief case series. We conducted a literature review to identify the nature of the disease and its risk factors. Methods We retrospectively reviewed the cases reported between 1988 and 2008 by searching the relevant literature using the keywords "endocarditis" and " Staphylococcus lugdunensis " in the Medline database. All cases included met the definition of the modified Duke criteria. Results For the period 1988-2008, 67 cases from 27 articles were reviewed. The mean age of individuals was 53.9 years. Left-sided valvular endocarditis represented 52 (82.5%) of cases and native-valve endocarditis was evident in 48 (78.7%) of cases. A large proportion (82%) of 50 S. lugdunensis strains were susceptible to penicillin. Valve replacement operations were performed in 42 (66.7%) patients and the mortality rate was 38.8%. Univariate analysis showed a higher mortality rate in patients aged more than 50 years, those treated before 1995, those treated with antibiotics alone, and those with growth not detected by echocar-diography. Medical treatment alone was the independent risk factor for mortality by multivariate analysis. Conclusion S. lugdunensis endocarditis led to substantial morbidity and mortality. Detailed microbiological identification, echocardiography evaluation, and valve replacement may improve the clinical outcome of individuals with S. lugdunensis endocarditis.

We conducted a multi-center, randomized, laboratory-blinded clinical trial in 185 healthy adults (60 years) and 107 elders (60 years) to examine the immunogenicity and safety of different doses of an inactivated, monovalent, non-adjuvanted, split vaccine against the 2009 pandemic influenza A (H1N1) virus. The 186 adults were assigned to three treatment groups, i.e., one 15 μg hemagglutination (HA) antigen dose, two 15 μg or 30 μg HA doses in 3 weeks apart, and the 107 elders were treated with two 15 μg or 30 μg doses in 3 weeks apart. Prior to the vaccination, 4.8% subjects had hemagglutination-inhibition (HAI) antibody titers of 1:40 or more. By day 21 post-vaccination of one dose of 15 μg HA, the seroprotective rate was 95.1% and 75.5% in subjects60 and65 years of age, respectively; by day 21 post the second 15 μg HA dose, the seroprotective rates were 93.2% and 73.1%, respectively. The seroprotective rates for recipients of 30 μg HA antigen by day 21 were 95.2% for subjects60 years and 81.1% for subjects65 years of age, that was boosted to 98.3% and 80.4%, respectively with a second dose of 30 μg HA antigen. No vaccine-related serious adverse events occurred. The data indicated a single 15 μg HA dose of the vaccine induced a protective immune response in most adults, including the elders60 years of age, and a booster dose at the third week did not render a higher level of antibody response.

We conducted a multi-center, randomized and laboratory-blinded clinical trial with subgroup analyses, involving adults aged greater than 60 years old (range 61-86 years old), to investigate the immunogenicity and the potential factors affecting the immune response of a monovalent, unadjuvanted, inactivated, split-virus vaccine. A total of 107 subjects were randomized to receive 15 and 30 microg of hemagglutinin antigen in a 1:1 ratio. The immunogenicity was detected through hemagglutination inhibition (HAI) test of serum obtained before and 3 weeks after vaccination. By 3 weeks after vaccination, HAI titer >or=1:40 was observed in 75.5% and 81.1% of participants receiving 15 and 30 microg of hemagglutinin antigen, respectively. Positive seroconversion was observed in 71.7% and 81.1% of recipients of the 15 and the 30 microg, respectively. The GMTs increased by a factor of 10.7 and 17.4 in the groups of 15 and 30 microg, respectively. This study indicated that one dose of 15 microg hemagglutinin antigen without adjuvant induced protective immune response in the majority of elderly. Multivariate logistic regression analyses showed that gender, age and diabetes were statistically significant factors affecting the seroprotection rate (p=0.04, 0.01 and 0.01, respectively) and seroconversion rate (p=0.01, 0.01 and 0.01, respectively).

Background/Purpose Mycobacterium avium complex (MAC) is frequently considered to be a contaminant or transient colonizer. To the best of our knowledge, there have been very few reports regarding the clinical significance of MAC isolates in respiratory specimens, and the associated disease spectrum in Taiwan. The purpose of this study was to investigate the clinical significance of MAC isolates in respiratory specimens. Methods We retrospectively reviewed the medical records of patients in a medical center in Southern Taiwan from whom MAC isolates were recovered from respiratory specimens, and analyzed their clinical features, chest imaging findings, treatment and prognosis. We also performed an antibiotic susceptibility test on our MAC isolates. Results The 64 isolates used in this study were recovered from April to October 2001 from respiratory specimens in 54 patients admitted to Kaohsiung Veterans General Hospital, Taiwan. According to the 2007 criteria of the American Thoracic Society, a total of 12 patients (22.2%) had clinically significant MAC pulmonary disease. Conclusion Despite the increased frequency of recovering MAC from respiratory specimens, most cases did not meet the criteria of American Thoracic Society for clinically significant nontuberculous pulmonary disease. The minimum inhibitory concentrations of drugs against these MAC isolates might help to guide treatment, but further studies should be done.

A total of 393 isolates of A. baumannii were collected from patients treated at 19 teaching hospitals in Taiwan. Minimum inhibitory concentrations (MICs) and inhibitory zone diameters for tigecycline were determined by the broth microdilution method and the disk diffusion method, respectively. The MIC results were interpreted using the US FDA tigecycline susceptibility breakpoints for Enterobacteriaceae (susceptible [S]or=2 microg/mL; intermediate [I] 4 microg/mL; resistant [R]or=8 microg/mL). The disk diffusion results were interpreted by criteria recommended by Jones et al. (Sor=16 mm; I 13-15 mm; Ror=12 mm) and also by those recommended by the US FDA for Enterobacteriaceae (Sor=19 mm; I 15-18 mm; Ror=14 mm). The percentages of susceptible, intermediate and resistant isolates determined by the broth microdilution method were 80.9%, 12.2%, and 6.9%, respectively. The rates of susceptible, intermediate and resistant isolates by the disk diffusion method using the criteria of Jones et al. were 88.3%, 9.9% and 1.8% and using the US FDA criteria were 44.0%, 51.7% and 4.3%. Using the criteria recommended by Jones et al., the total error rate of the disk diffusion method in comparison with the broth microdilution method was 14.2% (56/393). For routine susceptibility testing of tigecycline against A. baumannii the broth microdilution method, not the disk diffusion method, should be used due to the poor correlation of results between these two methods interpreted either by the Jones et al. or US FDA criteria.

SummaryBackgroundThe major sources of Legionnaires’ disease (LD) are the potable water systems of large buildings including hospitals, nursing homes, and hotels. Culturing the hospital water system for Legionella allows a preventive approach for hospital-acquired LD. However, hospital-acquired LD is rarely reported in Taiwan, and environmental cultures of Legionella in hospital water systems in Taiwan have never been systematically performed.ObjectiveThe objective of this study was to determine if Legionella is present in hospital water systems in Taiwan. Water quality analysis was also performed to determine if geographic differences in water quality result in different Legionella positivity rates.MethodThe water systems of 16 hospitals throughout Taiwan were tested for Legionella by culture. Standardized culture procedures were followed.ResultsLegionella pneumophila was isolated from 63% (10/16) of the hospital water systems; 19% (3/16) of the hospitals had an L. pneumophila positive rate greater than 30%. L. pneumophila serogroups 1 and 6 (strains that are most responsible for Legionella infections) were isolated from 80% (8/10) and 60% (6/10), respectively, of the hospitals that yielded L. pneumophila in their water distribution systems.ConclusionAs was shown in epidemiological studies in the USA and Spain, hospital-acquired legionellosis may be prevalent but underdiagnosed in Taiwan.

To quantitate cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase 9 (MMP-9) in adult patients with Klebsiella pneumoniae meningitis and to correlate levels of MMP-9 with parameters of intrathecal inflammation and analyze the kinetic changes of MMP-9. In a prospective cohort study, levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP-1) concentrations were measured in the CSF of six adult patients with meningitis and 11 controls. MMP-9 and TIMP-1 were detected in all of the six patients at presentation and follow up lumbar puncture. CSF levels of MMP-9 (6.71+/-7.29 ng/ml) and TIMP-1(454.3+/-242.9 ng/ml) were higher in patients than in the control group (0.07+/-0.11 ng/ml and 27.14+/-39.34 ng/ml, respectively). Levels of MMP-9 correlated with CSF concentrations of protein, cell count and lactate. Repeated lumbar punctures showed that levels of MMP-9 decrease during clinical recovery, although the levels of MMP-9 in the CSF are variable because of the small number of cases. The relative change in gelatin zymography is comparable to the changes of MMP-9 levels found in ELISA. MMP-9 levels in CSF may be a useful tool in follow-up in patients with K. pneumoniae meningitis.

Background/Purpose: To understand the resistance patterns of rapidly growing mycobacteria (RGM) in Taiwan, antimicrobial resistance of clinical isolates was determined as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. Methods: During the period from January 2002 to December 2003, clinical isolates were collected from eight hospitals located on the west side of Taiwan and one reference laboratory. Broth microdilution minimum inhibitory concentrations of 11 antimicrobial agents were determined for 312 clinical isolates of RGM, including the Mycobacterium fortuitum group (110 isolates), Mycobacterium abscessus group (168 isolates), and Mycobacterium chelonae group (34 isolates). Results: Nearly all of the RGM were susceptible to amikacin and ofloxacin (≥90%) and resistant to doxycycline (＜3% susceptible). Tobramycin showed similar in vitro activity against the M. fortuitum and M. chelonae (77%) groups, but was less active against the M. abscessus group (58%). Ciprofloxacin was active mainly against M. fortuitum (95%). Nearly all RGM were resistant to erythromycin and doxycycline. However, around half of the RGM isolates remained susceptible to minocycline (50-54%). Clarithromycin was active against the M. abscessus group (53% susceptible), with a high rate of resistance in the M. chelonae (38% susceptible) and M. fortuitum (15% susceptible) group. Cefoxitin was more active against the M. fortuitum group (65%) than the other two RGM (40-44%), and ＜40% of the RGM isolates remained susceptible to imipenem (21-38%). Conclusion: The resistance of RGM in Taiwan is not as high as previously reported (notably for tobramycin, ciprofloxacin and cefoxitin), but reduction in the susceptibility rates of clarithromycin and imipenem for the M. fortuitum and M. abscessus groups demonstrates the importance of in vitro susceptibility testing of clinically important isolates, as susceptibility may differ in different geographical areas, even regionally, and over time. [J Formos Med Assoc 2008; 107(4):281-287]

The results of long-term, follow-up studies show that the severity and frequency of acute exacerbation of chronic hepatitis B virus (HBV) are associated with the development of liver cirrhosis in chronic HBV infection. The aim of this study was to investigate the relationship between virological factors of HBV and the severity of acute exacerbation.Fifty-one chronic hepatitis B patients with symptomatic acute exacerbation without antiviral therapy were enrolled in the study. Genotype of HBV was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Precore (A1896) and basal core promoter (BCP) mutations (T1762A1764) were determined by PCR and direct sequencing.Thirty-nine patients had genotype B, 11 patients had genotype C, and 1 patient had an unclassified genotype. Thirty-two patients had precore mutation and 24 patients had BCP mutation. After adjusting for age, gender, aspartate aminotransferase (ASAT) level, albumin level, and platelet count by multiple logistic regression test, precore mutation had a protective effect on the occurrence of hepatic decompensation (p=0.046), and genotype and BCP mutations were not associated with the occurrence of hepatic decompensation.HBV precore mutation may confer less severe liver disease during acute exacerbation of chronic HBV. Genotype and BCP mutations did not have a significant association with the occurrence of hepatic decompensation.

We describe a patient with Mycobacterium marinum tenosynovitis associated with a fish spine injury acquired at a gambling fishing pond in southern Taiwan and identify the source of the infection. M. marinum was isolated from fishing ponds and underground water and wastewater at the site. The isolates shared the same pulsed-field gel electrophoresis pattern as the patient. M. marinum was not detected in 54 samples obtained from 27 fish. Mycobacterium gordonae was isolated from 24 samples collected from the fish. Mycobacterium abscessus was isolated from 3 fish samples (Lateolabrax japonicus 1 and Sciaenops ocellatus 2). M. abscessus and M. gordonae were isolated from all water samples. This investigation provides strong evidence that the predisposing factor for the M. marinum infection was with a fish spine injury acquired at a gambling fishing pond. The source of the infection was the contaminated pond water.

Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of vascular endothelial growth factor in eosinophilic meningitis, vascular endothelial growth factor was measured in the cerebrospinal fluid (CSF) and blood of 9 patients with eosinophilic meningitis in a cohort study. VEGFCSF was detected in 8 (90%) of 9 eosinophilic meningitis patients (range, 45-2190 pg/mL) at presentation. The mean VEGFCSF at presentation, 1 week, and 2 weeks after admission was 568 pg/mL, 751 pg/mL, and 1031 pg/mL, respectively. There was an association between VEGFCSF, CSF protein, white cell count, and eosinophil counts. The VEGFSERUM fluctuated during the 6-month follow-up period. These results indicate that vascular endothelial growth factor may be associated with blood-brain barrier disruption in patients with eosinophilic meningitis.

Nontuberculous mycobacterium (NTM) is one of the well-known causes of cervicofacial lymphadenopathy in children under 5 years of age. Children often present with a painless cervical mass that fails to respond to conventional antibiotics. They are often referred under the suspicion of a neoplasm or bacterial adenitis rather than NTM cervical lymphadenitis. The lack of systemic symptoms, modest or negative purified protein derivative test and absence of exposure to active tuberculosis are characteristics of NTM lymphadenitis. The diagnosis usually requires the isolation of pathogen or pathologic proof. Complete excision is the choice of treatment by the majority of authors in the literature. This not only enables rapid diagnosis but ensures the lowest recurrence rate. Medical management is sometimes successful when complete resection is impossible or refused. To our knowledge, the incidence of NTM cervical lymphadenitis in children is increasing throughout the world. However, such reports of children in Taiwan is lacking. Clinicians should suspect a possible nontuberculous mycobacterial infection when a cervical lump is found in a child.

The human immunodeficiency virus type 1 (HIV-1) epidemic in Taiwan is rapidly escalating because of an increasing number of injection drug users (IDUs). A molecular epidemiological study of HIV-1-infected IDUs in Taiwan was conducted from January 2004 to April 2005. Of the 131 HIV-1-positive specimens collected all contained detectable sequences including 105 from the C2-V3 region of env and 87 from the protease and reverse transcriptase genes of pol. Phylogenetic analysis of these sequences indicated that 128 individuals harbored CRF07_BC which resembles the dominant strains circulating among IDUs in China. Twenty-three individuals had a history of travel to the southwest provinces of China and shared needles or apparatuses there. This suggests that CRF07_BC might have been transmitted from China into Taiwan thereby causing an outbreak among IDUs in Taiwan. This is the first report in the English literature of the appearance of HIV-1 CRF07_BC in Taiwan. These provide information relevant to the development of antiviral therapy and vaccine in Taiwan and may assist public health workers in the prevention of HIV-1 spread. (authors)

Production of extended-spectrum β-lactamases and plasmid-mediated AmpC enzymes was investigated among 291 Escherichia coli and 282 Klebsiella pneumoniae isolates that showed decreased susceptibilities to extended-spectrum cephalosporins from seven Taiwanese medical centers. CTX-M-type and SHV-type enzymes were the most prevalent extended-spectrum β-lactamases. CMY-2-like and DHA-1-like β-lactamases were the most prevalent AmpC-type enzymes.

Summary Objective The resurgence of tuberculosis (TB) and the emergence of drug resistance of Mycobacterium tuberculosis (MTB) isolates are of great impact on public health. Methods Taiwanese data on disease burden of TB and anti-microbial resistance of MTB identified from Annual Reports of Centre for Disease Control, Department of Health, Taiwan and from peer-reviewed publications from MEDLINE (1995–2004). Results In Taiwan in 2002, the incidence (per 100 000 population) of tuberculosis was 74.6 and it was higher in aborigines (289.8) and in people living in mountainous regions (256.0). The mortality rate of tuberculosis in Taiwan in 2002 was 5.68 per 100 000 population. Susceptibility data summarized from 1990 to 2002 reports showed primary resistance ranged from 4.7 to 12% for isoniazid, 0.7 to 5.9% for rifampin, 1 to 6% for ethambutol, and 4 to 11% for streptomycin. The overall rates of multidrug-resistant tuberculosis (MDRTB) among new cases and previously treated cases were 1 to 3% and 15 to 46%, respectively. The increasing burden of patients with MDRTB infection, the persistent high rate of mortality, the lack of nationwide surveillance system using the standard methodology to determine the trends and current status of resistance, and the inadequate current TB control infrastructure and training to accomplish the tasks required to implement the directly observed treatment short-course (DOTS) strategy are having a great impact on public health in Taiwan. Conclusions High disease burden of TB and high resistance rates in MTB as well as inappropriateness of the current control infrastructure for TB services illustrate increasingly serious health problems from TB in Taiwan.

A laboratory-based surveillance network of 11 clinical virological laboratories for influenza viruses was established in Taiwan under the coordination of the Center for Disease Control and Prevention (CDC), Taiwan. From October 2000 to March 2004, 3,244 influenza viruses were isolated, including 1,969 influenza A and 1,275 influenza B viruses. The influenza infections usually occurred frequently in winter in the northern hemisphere. However, the influenza seasonality in Taiwan was not clear during the four seasons under investigation. For example, the influenza A viruses peaked during the winters of 2001, 2002, and 2003. However, some isolated peaks were also found in the summer and fall (June to November) of 2001 and 2002. An unusual peak of influenza B also occurred in the summer of 2002 (June to August). Phylogenetic analysis shows that influenza A isolates from the same year were often grouped together. However, influenza B isolates from the year 2002 clustered into different groups, and the data indicate that both B/Victoria/2/87-like and B/Yamagata/16/88-like lineages of influenza B viruses were cocirculating. Sequence comparison of epidemic strains versus vaccine strains shows that many vaccine-like Taiwanese strains were circulating at least 2 years before the vaccine strains were introduced. No clear seasonality of influenza reports in Taiwan occurred in contrast to other more continental regions.

The susceptibilities of nonduplicate isolates to six antifungal agents were determined for 391 blood isolates of seven Candida species, 70 clinical isolates (from blood or cerebrospinal fluid) of Cryptococcus neoformans , and 96 clinical isolates of four Aspergillus species, which were collected in seven different hospitals in Taiwan (as part of the 2003 program of the study group Surveillance of Multicenter Antimicrobial Resistance in Taiwan). All isolates of Candida species other than C. glabrata and C. krusei were susceptible to fluconazole. Among the 59 C. glabrata isolates, 16 (27%) were not susceptible to fluconazole, and all were dose-dependently susceptible or resistant to itraconazole. For three (5.1%) C. glabrata isolates, voriconazole MICs were 2 to 4 μg/ml, and for all other Candida species isolates, voriconazole MICs were ≤0.5 μg/ml. The proportions of isolates for which amphotericin B MICs were ≥2 μg/ml were 100% (3 isolates) for C. krusei , 11% (23 of 207 isolates) for Candida albicans , 3.0% (2 of 67 isolates) for Candida tropicalis , 20% (12 of 59 isolates) for C. glabrata , and 0% for both Candida parapsilosis and Candida lusitaniae . For three (4%) Cryptococcus neoformans isolates, fluconazole MICs were ≥16 μg/ml, and two (3%) isolates were not inhibited by 1 μg of amphotericin B/ml. For four (4.2%) of the Aspergillus isolates, itraconazole MICs were 8 μg/ml. Aspergillus flavus was less susceptible to amphotericin B, with the MICs at which 50% (1 μg/ml) and 90% (2 μg/ml) nsrsid417869\delrsid7301351 of isolates were inhibited being twofold greater than those for Aspergillus fumigatus and Aspergillus niger . All Aspergillus isolates were inhibited by ≤1 μg of voriconazole/ml, including isolates with increased resistance to amphotericin B and itraconazole. This study revealed the emergence in Taiwan of decreased susceptibilities of Candida species to amphotericin B and of C. neoformans to fluconazole and amphotericin B. Voriconazole was the most potent agent against the fungal isolates tested, including fluconazole- and amphotericin B-nonsusceptible strains.

Clinical features of 84 patients with V. vulnificus infection are analyzed and molecular features of isolates are described., Residents in Taiwan are often exposed to marine microorganisms through seafood and occupational exposure. The number of reported cases of infection attributable to this organism has increased since the first case was reported in 1985. The increasing number of cases may be caused by greater disease activity or improved recognition by clinicians or laboratory workers. We analyze a clinical-case series of 84 patients with Vibrio vulnificus infection from 1995 to 2000 and describe the molecular epidemiologic features of pathogens isolated from these patients. The spectrum of clinical manifestations and outcomes, options of antimicrobial therapy, and virulence mechanisms were investigated. Results of molecular typing of isolates from humans and marine environment in this country had a high genetic divergence among these isolates. Education and measures are needed to prevent this emerging disease.

The most common cause of eosinophilic meningitis is the rat lungworm Angiostrongylus cantonensis a parasite that is endemic in the southeast Asian and Pacific regions. Outbreaks of eosinophilic meningitis associated with drinking raw vegetable juice are rarely reported, even in regions of endemic infection. We performed a cohort study among Taiwanese with eosinophilic meningitis who drank raw vegetable juice within three months of the onset of the outbreak. Clinical manifestations, laboratory examinations, and outcomes were prospectively followed. Five native Taiwanese met the case definition of eosinophilic meningitis. Specific antibodies to A. cantonensis were detected in the serum of five of the patients and in the cerebrospinal fluid (CSF) of four of the patients. Central nervous system manifestations included headache (n = 5 [100%]), Brudzinski's sign/stiff neck (n = 5 [100%]), hyperesthesia/paresthesias (n = 5 [100%]), and cranial nerve palsy (n = 1 [20%]). Laboratory findings included peripheral (n = 5 [100%]) and CSF eosinophilia (n = 4 [80%]), transient increases in the white blood cell count (n = 1 [20%]), and in serum levels of creatine kinase (n = 1 [20%]). Meningeal enhancement, as well as high signal intensity, at the subcortical white matter on T2 weighted and fluid attenuated inversion recovery images were observed on magnetic resonance imaging in four patients. There were three episodes of relapse during treatment and all resolved with after a lumbar puncture and/or administration of steroids. At the 12-month follow up, all five patients had recovered without neurologic sequelae. Risk factors identification showed that consumption of raw vegetable juice was associated with illness (Pearson correlation test r = 0.867, P = 0.01). There was association between the presence of raw vegetable juice and CSF eosinophilia (Spearman's correlation test r = 0.816, P = 0.004).

We evaluated the disk susceptibility data of 671 nontyphoid Salmonella isolates collected from different parts of Taiwan from March 2001 to August 2001 and 1,261 nontyphoid Salmonella isolates from the National Taiwan University Hospital from 1996 to 2001. Overall, ciprofloxacn resistance was found in 2.7% (18/671) of all nontyphoid Salmonella isolates, in 1.4% (5/347) of Salmonella enterica serotype Typhimurium and in 7.5% (8/107) in S. enterica serotype Choleraesuis nationwide. MICs of six newer fluoroquinolones were determined for the following isolates: 37 isolates of ciprofloxacin-resistant (human) S. enterica Typhimurium (N = 26) and Choleraesuis (N = 11), 10 isolates of ciprofloxacin-susceptible (MIC 0.12 μg/mL). Sequence analysis of the gryA, gyrB, parC, parE, and acrR genes, ciprofloxacin accumulation; and genotypes generated by pulsed-field gel electrophoresis with three restriction enzymes (SpeI, XbaI, and BlnI) were performed. All 26 S. enterica Typhimurium isolates from humans and pigs belonged to genotype I. For S. enterica Choleraesuis isolates, 91% (10/11) of human isolates and 54% (7/13) of swine isolates belonged to genotype B. These two genotypes isolates from humans all exhibited a high-level of resistance to ciprofloxacin (MIC 16–64 μg/mL). They had two-base substitutions in the gyrA gene at codons 83 (Ser83Phe) and 87 (Asp87Gly or Asp87Asn) and in the parC gene at codon 80 (Ser80Arg, Ser80Ile, or Ser84Lys). Our investigation documented that not only did these two S. enterica isolates have a high prevalence of ciprofloxacin resistance nationwide but also that some closely related ciprofloxacin-resistant strains are disseminated from pigs to humans.

This study evaluated the current status of antimicrobial resistance in clinical isolates of Streptococcus pyogenes in Taiwan as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. In 2001, 419 different isolates of S. pyogenes , including 275 from respiratory secretions, 87 from wound pus, and 31 from blood, were collected from nine hospitals in different parts of Taiwan. MICs of 23 antimicrobial agents were determined at a central location by the agar dilution method. All of the isolates were susceptible to penicillin (MIC at which 90% of the isolates were inhibited [MIC 90 ], ≤0.03 μg/ml), cefotaxime (MIC 90 , ≤0.03 μg/ml), cefepime (MIC 90 , 0.06 μg/ml), meropenem (MIC 90 , ≤0.03 μg/ml), moxifloxacin (MIC 90 , 0.25 μg/ml), vancomycin (MIC 90 , 0.5 μg/ml), and linezolid (MIC 90 , 1 μg/ml). Overall, 78% of isolates were not susceptible to erythromycin (54% were intermediate, and 24% were resistant), and 5% were not susceptible to clindamycin. Of the 101 erythromycin-resistant isolates, 80.2% exhibited the M phenotype ( mefA gene positive), 18.9% exhibited the cMLS (constitutive resistance to macrolides-lincosamides-streptogramin B [MLS]) phenotype ( ermB gene positive), and 1% exhibited the iMLS (inducible resistance to MLS) phenotype ( ermB gene positive). Fluoroquinolones (sitafloxacin > moxifloxacin > ciprofloxacin = levofloxacin = gatifloxacin > gemifloxacin) demonstrated potent activity against nearly all of the isolates of S. pyogenes tested. Thirty-two isolates (8%) were not susceptible to quinupristin-dalfopristin. Seventeen percent of isolates had telithromycin MICs of ≥1 μg/ml, and all of these isolates exhibited erythromycin MICs of ≥32 μg/ml. The high prevalence of resistance to telithromycin (which is not available in Taiwan) limits its potential use in the treatment of S. pyogenes infections, particularly in areas with high rates of macrolide resistance.

There is a high prevalence of β-lactam- and macrolide-resistant Streptococcus pneumoniae in Taiwan. To understand the in vitro susceptibilities of recent isolates of S. pneumoniae to fluoroquinolones and telithromycin (which is not available in Taiwan), the MICs of 23 antimicrobial agents for 936 clinical isolates of S. pneumoniae isolated from different parts of Taiwan from 2000 to 2001 were determined by the agar dilution method. Overall, 72% of isolates were not susceptible to penicillin (with 61% being intermediate and 11% being resistant) and 92% were resistant to erythromycin. Telithromycin MICs were ≥1 μg/ml for 16% of the isolates, and for 99% of these isolates the MICs of all macrolides tested were ≥256 μg/ml; all of these isolates had the constitutive macrolide-lincosamide-streptogramin B phenotype. Eighty-eight percent of the isolates were resistant to three or more classes of drugs. The ciprofloxacin MICs were ≥4 μg/ml for six (0.6%) isolates from five patients collected in 2000 and 2001, and the levofloxacin MICs were ≥8 μg/ml for five of these isolates. Seven isolates for which ciprofloxacin MICs were ≥4 μg/ml, including one isolate recovered in 1999, belonged to three serotypes (serotype 19F, five isolates; serotype 23A, one isolate; and serotype 23B, one isolate). The isolates from the six patients for which ciprofloxacin MICs were ≥4 μg/ml had different pulsed-field gel electrophoresis profiles and random amplified polymorphic DNA patterns, indicating that no clonal dissemination occurred over this time period. Despite the increased rate of fluoroquinolone use, the proportion of pneumococcal isolates for which ciprofloxacin MICs were elevated (≥4 μg/ml) remained low. However, the occurrence of telithromycin resistance is impressive and raises concerns for the future.

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis worldwide. Human infection occurs after ingestion of the worms in raw snails or fish that serve as intermediate hosts. Two outbreaks of central nervous system infection with A. cantonensis occurred in Kaoshiung, Taiwan, during 1998 and 1999 among Thai laborers who ate raw snails. A detailed clinical studies of 17 of these patients was conducted, including study of 13 patients who underwent magnetic resonance imaging (MRI) scans of the brain. The MRI scans revealed high signal intensities over the globus pallidus and cerebral peduncle on T1-weighted imaging, leptomeningeal enhancement, ventriculomegaly, and punctate areas of abnormal enhancement within the cerebral and cerebellar hemisphere on gadolinium-enhancing T1 imaging, and a hyperintense signal on T2-weighted images. There was a significant correlation between severity of headache, cerebrospinal fluid (CSF) pleocytosis, and CSF and blood eosinophilia with MRI signal intensity in T1-weighted imaging (P < 0.05). Eosinophilic meningitis produced by A. cantonensis needs to added to the list of causes of hyperintense basal ganglia lesions found on T1-weighted MRI scans in tropical countries.

Studies of the pathogenesis of dengue hemorrhagic fever (DHF), a potentially life-threatening disease, have revealed the importance of initial high levels of virus replication. However, the possible involvement of virus during the transition from fever to defervescence, a critical stage in determining the severity of disease, has not been appreciated. Using quantitative reverse transcription-polymerase chain reaction, we examined the levels of plasma dengue viral load during both fever and defervescence periods in patients from a DEN-3 outbreak in southern Taiwan in 1998. Higher levels of plasma dengue viral RNA were found in DHF patients than in DF patients. During defervescence, while the level of plasma dengue viral RNA was undetectable in most DF patients, it remains high in all DHF patients. Using a modified immunoprecipitation assay, we demonstrated for the first time that the plasma dengue viruses persisting during defervescence were in the immune complexes for most DHF patients. These findings suggest that continued active viral replication or delay in the clearance of viremia contributes to the pathogenesis of DHF. Moreover, high levels of plasma dengue viral RNA during defervescence may serve as a disease marker for DHF.

The cost‐effectiveness of the ProbeTec ET Direct TB assay (DTB) was compared with that of culture for detection of Mycobacterium tuberculosis complex in 361 acid‐fast stain‐positive respiratory specimens. The overall sensitivity, specificity, positive predictive value and negative predictive value of DTB were 97.7%, 86.6%, 87.2% and 97.6%, respectively. When clinical evaluation was added to DTB, the specificity and positive predictive value of DTB increased to 94.7% and 95.4%, respectively. Treatment costs of $133 521 would have been saved in this cohort if DTB, instead of culture results, had been used to eliminate ‘false‐positive' smear results.

Background Toxocariasis, which is predominantly caused by Toxocara canis (T. canis) infection, is a common zoonotic parasitosis worldwide; however, the status of toxocariasis endemicity in the Republic of the Marshall Islands (RMI) remains unknown. Methods A seroepidemiological investigation was conducted among 166 primary school children (PSC) aged 7–12 years from the capital area of the RMI. Western blots based the excretory-secretory antigens of larval T. canis (TcES) was employed, and children were considered seropositive if their serum reacted with TcES when diluted at a titer of 1:64. Information regarding demographic characteristics of and environmental risk factors affecting these children was collected using a structured questionnaire. A logistic regression model was applied to conduct a multivariate analysis. Results The overall seropositive rate of T. canis infection was 86.75% (144/166). In the univariate analysis, PSC who exhibited a history of feeding dogs at home (OR = 5.52, 95% CI = 1.15–26.61, p = 0.02) and whose parents were employed as nonskilled workers (OR = 2.86, 95% CI = 1.08–7.60, p = 0.03) demonstrated a statistically elevated risk of contracting T. canis infections. Cleaning dog huts with gloves might prevent infection, but yielded nonsignificant effects. The multivariate analysis indicated that parental occupation was the critical risk factor in this study because its effect remained significant after adjusting for other variables; by contrast, the effect of dog feeding became nonsignificant because of other potential confounding factors. No associations were observed among gender, age, consuming raw meat or vegetables, drinking unboiled water, cleaning dog huts with gloves, or touching soil. Conclusions This is the first serological investigation of T. canis infection among PSC in the RMI. The high seroprevalence indicates the commonness of T. canis transmission and possible human risk. The fundamental information that the present study provides regarding T. canis epidemiology can facilitate developing strategies for disease prevention and control.

Purpose To describe two outbreaks of Angiostrongylus cantonensis infection that occurred in Kaohsiung, Taiwan, during 1998 and 1999, and to characterize the source of the outbreaks and the clinical manifestations of the disease. Subjects and methods We performed a retrospective cohort study among Thai laborers with eosinophilic meningitis who ate raw snails ( Ampullarium canaliculatus ), as well as an environmental surveillance of larvae in snails. Results We enrolled 17 Thai laborers in whom severe headache and eosinophilia developed within 4 to 23 days after eating raw snails. Twelve (71%) developed eosinophilic meningitis. Third-stage larvae were found in the cerebrospinal fluids of 2 patients and in all 12 tested snails. Specific antibodies to A. cantonensis were detected in serum from 16 of the patients and in cerebrospinal fluid from 5 of the patients. Central nervous system manifestations included headache (n = 17 [100%]), fever (n = 11 [65%]), Brudzinski's sign/stiff neck (n = 11 [65%]), hyperesthesia (n = 3 [18%]), cranial nerve palsy (n = 2 [12%]), diplopia (n = 2 [12%]), and ataxia (n = 1 [6%]). Laboratory findings included peripheral eosinophilia (n = 15 [88%]) and cerebrospinal fluid eosinophilia (n = 12 [71%]); elevated immunoglobulin (Ig) E levels (n = 13 [100%]); and transient increases in white blood cell count (n = 7 [41%]) and in serum levels of creatine kinase (n = 7 [41%]), transaminase (n = 3 [18%]), and lactate dehydrogenase (n = 2 [12%]). The severity of illness and eosinophilia were correlated with the number of ingested snails. Meningeal and basal ganglion enhancement was noted on magnetic resonance imaging in several patients. Treatment with mebendazole combined with glucocorticosteroids appeared to shorten the course of the infection, but not the number of relapses. The eosinophil count fell to normal within 3 months, but IgE levels remained elevated for as long as 6 months. All patients recovered with minimal neurologic sequelae. Conclusion Eosinophilic meningitis caused by A. cantonensis should be considered in patients who have headache or central nervous system manifestations after eating raw snails.

Cryptococcus spp. other than Cryptococcus neoformans are generally considered nonpathogenic to humans. There are only 15 case reports of disease in humans caused by Cryptococcus laurentii infection. Underlying diseases and predisposing risk factors seem to play an important role in these cases. Our patient is the first case of an extremely low birth weight infant with C. laurentii fungemia reported in the English literature. In our case, the MIC of amphotericin B for C. laurentii was 0.25 to 1 μg/ml and the patient had a good outcome following the administration of amphotericin B at 10 mg/kg combined with central venous catheter removal. There will undoubtedly be an increasing occurrence of unusual fungal infections accompanying further advances in medicine. A high degree of suspicion and improvements in the techniques for culture and identification will contribute to the earlier diagnosis and treatment of unusual fungal infections.

Hepatocyte growth factor (HGF) is a member of the angiogenic growth factor family, which exerts a variety of effects on epithelial, endothelial, and neuronal cells by binding to the c-MET receptor tyrosine kinase. It was reported that HGF attenuates cerebral ischemia-induced increase in permeability of the blood-brain barrier (BBB) and decreases in expression of tight junction proteins in cerebral vessels of rats. Studies on the localization of the c-Met/HGF receptor in the rat brain and the interaction with HGF after brain injuries show that HGF plays an important role as a neurotrophic factor in the brain. To assess the role of HGF in patients with eosinophilic meningitis, a retrospective, cohort study was conducted to measure the dynamic changes of HGF in the cerebrospinal fluid (CSF) and blood of nine patients with eosinophilic meningitis. The mean HGF(CSF) at presentation, 1 week, 2 weeks, and 3 weeks after admission was 539 pg/mL, 540 pg/mL, 376 pg/mL, and 279 pg/mL, respectively. The mean level of HGF(CSF) at presentation (539 +/- 242 pg/mL) and 1 week after admission (540 +/- 213 pg/mL) was significantly higher than in controls (162 +/- 207 pg/mL)(P = 0.02 and P = 0.01, respectively). The CSF/blood ratio of HGF at presentation (0.61) was higher when compared with physiologic situations in uninfected individuals (0.51). The levels of HGF in CSF were not correlated with the amount of CSF cells or proteins. All patients recovered without neurologic sequelae. These results indicate that high concentrations of HGF in the CSF occur in eosinophilic meningitis, and may have a role in protecting against endothelial injury and reducing BBB dysfunction.

Pyogenic liver abscess is an uncommon complication of intra-abdominal or biliary tract infection and is usually a polymicrobial infection associated with high mortality and high rates of relapse. However, over the past 15 years, we have observed a new clinical syndrome in Taiwan: liver abscesses caused by a single microorganism, Klebsiella pneumoniae. We reviewed 182 cases of pyogenic liver abscess during the period September 1990 to June 1996; 160 of these cases were caused by K. pneumoniae alone, and 22 were polymicrobial. When patients with K. pneumoniae liver abscess were compared with those who had polymicrobial liver abscess, we found higher incidences of diabetes or glucose intolerance (75% vs. 4.5%) and metastatic infections (11.9% vs. 0) and lower rates of intra-abdominal abnormalities (0.6% vs. 95.5%), mortality (11.3% vs. 41%), and relapse (4.4% vs. 41%) in the former group. Liver abscess caused by K. pneumoniae is a new clinical syndrome that has emerged as an important infectious complication in diabetic patients in Taiwan.

Cefpodoxime proxetil is a new orally administered prodrug which is absorbed and de-esterified by the intestinal mucosa to release the third-generation cephalosporin, cefpodoxime, and which is undergoing in vitro and in vivo evaluations. Using the standard agar dilution method, we compared the in vitro activity of this drug with other oral cephalosporins and quinolones against 637 recent clinical isolates from Kaohsiung Veterans General Hospital in Taiwan. Against Escherichia coli and Klebsiella pneumoniae, cefpodoxime showed excellent activity, inhibiting over 90% of these isolates at 1 mg/l. Like other oral drugs of its class, it had little activity against Pseudomonas aeruginosa and Acinetobacter spp. Against Haemophilus influenzae, irrespective of beta-lactamase production, its activity was similar to comparative drugs. Against methicillin-susceptible Staphylococcus aureus, cefpodoxime showed moderate activity, inhibiting 90% of these isolates at 4 mg/l, whereas it was inactive against methicillin-resistant S. aureus. However, all cephalosporins have shown little in vivo activity against methicillin-resistant S. aureus regardless of in vitro results. Cefpodoxime was inactive against Enterococcus spp. Against other streptococci, its activity was similar to other oral cephalosporins and quinolones tested. The results of this in vitro study indicated that oral administration of cefpodoxime should be an ideal agent in the empirical outpatient treatment for community-acquired cutaneous, respiratory and urinary tract infections.

Cefprozil is a new orally active cephalosporin which is undergoing in vitro and in vivo evaluations. Using the standard agar dilution method we compared the in vitro activity of this drug with other oral cephalosporins and ciprofloxacin against 637 recent clinical isolates from the Kaohsiung Veterans General Hospital, Taiwan. Against Escherichia coli and Klebsiella pneumoniae, cefprozil showed good activity, inhibiting over 80% of these isolates at 8 mg/l. Like other oral drugs of its class, it had little activity against Pseudomonas aeruginosa and Acinetobacter spp. Against Haemophilus influenzae, irrespective of beta-lactamase production, its activity was similar to comparable drugs. Against methicillin-susceptible Staphylococcus aureus, cefprozil showed high activity, inhibiting 90% of these isolates at 4 mg/l, whereas against methicillin-resistant S. aureus, its activity was higher than that of other oral cephalosporins tested and was similar to that of ciprofloxacin. Of enterococci tested, 57.7% were inhibited by 8 mg/l of cefprozil. Against beta-hemolytic streptococci, its activity was superior to all other drugs tested. The results of this in vitro study indicate that oral administration of cefprozil might be efficacious in the treatment of community-acquired cutaneous, respiratory and urinary tract infections.

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a worldwide surveillance program designed to longitudinally monitor the in vitro activity of antimicrobial agents against pathogens that cause intra-abdominal infections (IAIs). In this study, trends in antimicrobial resistance during the period 2006 to 2010 were analyzed at five tertiary-care hospitals in Taiwan. Enterobacteriaceae accounted for the majority (80.9%) of the 2417 Gram-negative isolates, and the two most common species were Escherichia coli (38.8%) and Klebsiella pneumoniae (23.5%). The rates of susceptibility of Enterobacteriaceae isolates to cephalosporins decreased during the study period. Although carbapenems, fluoroquinolones, piperacillin-tazobactam, and amikacin were active in vitro against more than 80% of the Enterobacteriaceae isolates, the activity of carbapenems declined during the study period. Extended-spectrum β-lactamase (ESBL) production in E. coli was steady, but that in K. pneumoniae decreased during the study period. The rate of ESBL-producing species was three-fold higher among patients with nosocomial IAIs than among patients with community-acquired IAIs. The majority of isolates from liver were K. pneumoniae (69%) and very few of those isolates were ESBL producers (0.9%). Pseudomonas aeruginosa (9.3%) and Acinetobacter baumannii (3.8%) were the two most common non-Enterobacteriaceae. P. aeruginosa showed improved susceptibility, whereas A. baumannii showed a rapid development of resistance during the study period. There was marked geographic variation in resistance patterns of the isolates obtained during the study period. Northern Taiwan had the highest rate of ESBL producers and the highest rate of ceftazidime resistance among P. aeruginosa isolates. Central Taiwan had the lowest rate of ESBL producers but the highest rates of carbapenem resistance among P. aeruginosa and A. baumannii isolates. Continuous monitoring and regular updates of epidemiological data are needed to guide appropriate empiric antimicrobial therapy.

We investigated the trend in resistance to carbapenems among isolates of Enterobacteriaceae that had been collected from patients with intra-abdominal infections at five medical centers in Taiwan from 2006 to 2010 and evaluated the correlation between resistance to carbapenems and consumption of said agents as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, the usage of ertapenem and that of total carbapenems (ertapenem, imipenem, and meropenem) increased significantly from 6.13 to 13.38 defined daily doses per 1000 patient-days for ertapenem and from 20.43 to 34.25 defined daily doses per 1000 patient-days for total carbapenems. The most common species were Escherichia coli (n = 1095), Klebsiella spp. (n = 663), and Enterobacter spp. (n = 202). The susceptibility of all isolates to ertapenem and to imipenem varied during the study period. For ertapenem, the rates of nonsusceptibility ranged from 3.5% to 10.3% and those for imipenem ranged from 3.5% to 10.7%. Although the use of carbapenems increased during the study period, there was no marked increase in resistance to carbapenems. Continuous monitoring of resistance trends is necessary so that antimicrobial prescription policies can be adjusted and infection control intervention programs can be implemented.

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is an international surveillance study designed to monitor resistance trends among aerobic and facultative Gram-negative bacilli (GNB) isolated from intra-abdominal infections. During 2003-2010, a total of 20710 GNB isolates were collected at medical centers in China, Hong Kong, Korea, New Zealand, and Taiwan. The susceptibility profiles of 2252 isolates of non-Enterobacteriaceae GNB were determined. At least 10 isolates of a given organism were required for that organism to be included in the analysis. Pseudomonas aeruginosa was the leading organism (49.2% of non-Enterobacteriaceae GNB), followed by Acinetobacter baumannii (21.5%), Aeromonas spp. (11.6%), and Stenotrophomonas maltophilia (9.1%). All the other species/genera made up less than 2%. The rates of susceptibility of the four major organisms were examined for two different time periods and according to whether the isolates had been obtained48 h after hospitalization or ≥ 48 h after hospital admission. P. aeruginosa, Aeromonas spp., and S. maltophilia showed sustained levels of susceptibility to several antimicrobial agents in the two time periods, whereas A. baumannii exhibited very high rates of resistance to most antimicrobial agents including imipenem. Nosocomial P. aeruginosa and A. baumannii were more resistant than community-acquired pathogens, although this was not the case for Aeromonas spp. and S. maltophilia. Worldwide and regional surveillance is necessary to guide empirical antimicrobial therapy for infections due to non-Enterobacteriaceae GNB.

This study examined the rates of susceptibility to third-generation cephalosporins and carbapenems among Enterobacteriaceae isolates that had been obtained from patients with intraabdominal infections in the Asia-Pacific region as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). Susceptibility profiles obtained using 2009 Clinical and Laboratory Standards Institute (CLSI) breakpoints were compared with those obtained using the 2011 CLSI breakpoints. From 2002 to 2010, Escherichia coli and Klebsiella pneumoniae together accounted for more than 60% of the 13714 Enterobacteriaceae isolates analyzed during the study period. Extended-spectrum β-lactamase (ESBL) producers comprised 28.2% of E. coli isolates and 22.1% of K. pneumoniae isolates in the Asia-Pacific region, with China (55.6% and 33.7%, respectively) and Thailand (43.1% and 40.7%, respectively) having the highest proportions of ESBL producers. Based on the 2011 CLSI criteria, 77.2% of the Enterobacteriaceae isolates, 40.4% of ESBL-producing E. coli, and 25.2% of ESBL-producing K. pneumoniae isolates were susceptible to ceftazidime. Carbapenems showed in vitro activity against >90% of Enterobacteriaceae isolates in all participating countries, except for ertapenem in South Korea (susceptibility rate 82.2%). Marked differences (>5%) in susceptibility of ESBL-producing E. coli and K. pneumoniae isolates to carbapenems were noted between the profiles obtained using the 2009 CLSI criteria and those using the 2011 CLSI criteria. Continuous monitoring of antimicrobial resistance is necessary in the Asia-Pacific region.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) ( n = 1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) ( n = 423), vancomycin-resistant enterococci (VRE) ( n = 219), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli ( n = 1,141), ESBL-producing Klebsiella pneumoniae ( n = 1,330), Acinetobacter baumannii ( n = 1,645), and Stenotrophomonas maltophilia ( n = 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC 90 , 0.03 μg/ml), and only one MRSA isolate (MIC 90 , 0.5 μg/ml) and three VRE isolates (MIC 90 , 0.125 μg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC 90 , 0.5 μg/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC 90 , 2 μg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate for A. baumannii (MIC 90 , 4 μg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii .

Chlamydia pneumoniae (TWAR) is a relatively newly discovered respiratory tract pathogen which was first isolated in Taiwan. In order to describe the seroepidemiology of C. pneumoniae in Taiwan, we evaluated 1,085 stored serum samples: 904 from patients, 97 from umbilical cord blood samples, and 84 from medical personnel at the Veterans General Hospital-Kaohsiung, between January 1 and April 30, 1991. Antibodies were determined by the use of a microimmunofluorescence test using elementary bodies of C. pneumoniae AR-39 as antigen. Sera were tested with screening titres of 16 and 512 for immunoglobulin G antibody. The antibody prevalence was found to be 23.1% in young children (6 months to 10 years old), rising to 66.7% in teenagers, and to 96.2% in older age groups. These rates were higher than any reported earlier. The progressively increasing rates of seropositivity found in older individuals indicated a surge of reinfection in these age groups. Only 5 cases were found with micro-IF IgG titres equal to or greater than 512. All were asymptomatic according to the hospital records. In addition to a high prevalence rate in Taiwan, the data also showed high infection rates in teenagers and elderly people.

Human parechovirus (HPeV) may cause various illnesses; however, technologists and clinicians often overlook it. This study, designed to detect HPeV in 3124 clinical specimens from 2849 patients between January and August 2007, presents the first report of HPeVs confirmed by RNA sequences in Taiwan. Reverse transcriptase polymerase chain reaction (RT-PCR) and phylogenetic tree analysis identified the isolates as HPeV1 (n = 5), HPeV3 (n = 1), and HPeV4 (n = 2) from 6 children. Although the prevalence is low, HPeVs do cause significant clinical manifestations in children. Phylogenetic analysis has separated the 8 HPeV1 strains as a new lineage from the prototype strain (L02971) in evolutionary transition. Clinicians and technologists should have a high index of suspicion and apply RT-PCR for identification when presented with slower Enterovirus-like cytopathic effect (CPE) in cell cultures and negative or equivocal results of staining with indirect immunofluorescence assay, particularly if the CPE is larger, smoother, and more refractive and relatively slow.

Early identification of tuberculosis in the clinical setting is of great importance in order for specific therapy to be swiftly initiated. MB REDOX (Heipha Diagnostika), a growth-based medium without radioactive materials, was evaluated and was compared to the BACTEC system for detection of mycobacteria, including the Mycobacterium tuberculosis complex and atypical mycobacteria. MB REDOX consists of a Kirchner medium enriched with growth-promoting additives, antibiotic compounds, and a redox indicator which can be monitored to detect growth of mycobacteria with the naked eye. MB REDOX only detects growth and cannot differentiate the M. tuberculosis complex ( M. tuberculosis , M. bovis , and M. africanum ) from other species of Mycobacterium . Therefore, PCR-restriction fragment length polymorphism analysis (PRA) was used in this investigation to identify to the species level organisms showing positive growth with MB REDOX. Our data demonstrate the usefulness of MB REDOX for the detection of mycobacteria in clinical specimens. The rate of detection of M. tuberculosis complex with MB REDOX (84.3%) was higher than that with the BACTEC system (68.6%). When combined with PRA for species identification, MB REDOX is easy to perform and is suited to most clinical laboratory settings for the detection and identification of mycobacteria.

Tigecycline In-vitro Surveillance in Taiwan (TIST), initiated in 2006, is a nationwide surveillance programme designed to monitor longitudinally the in-vitro activity of tigecycline against commonly encountered resistant bacteria. This study compared the in-vitro activity of tigecycline against clinical isolates of resistant Gram-negative bacteria determined by the broth microdilution and Etest methods. A total of 622 isolates were collected from patients treated at 20 teaching hospitals. Tigecycline had excellent in-vitro activity against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (N = 275) with MIC(90) 0.5 microg/mL and a 99.6% susceptibility rate, and also against ESBL-producing Klebsiella pneumoniae (N = 324) with MIC(90) 2 microg/mL and a 98.5% susceptibility rate. For ESBL-producing Proteus mirabilis (N = 15) the MIC(90) was 4 microg/mL with a 73.3% susceptibility rate. For ESBL-producing Klebsiella oxytoca (N = 8) the MIC(50) and MIC(90) were 0.5 and 1 microg/mL, respectively, with a 100% susceptibility rate. Limited agreement (

We performed susceptibility testing using the microdilution method to determine the in-vitro activity of tigecycline against 393 Acinetobacter baumannii clinical isolates collected in 2006 from 19 hospitals in Taiwan. Significant proportions of the isolates were resistant to imipenem (44%), ciprofloxacin (75%), amikacin (69%), sulbactam (34%) and all four antibiotics (22%), and susceptibility to tigecycline among these different resistant phenotypes of A. baumannii varied from 71% to 82%. The minimum inhibitory concentration (MIC) of tigecycline ranged from 0.6 to 16 microg/mL (MIC(50) 2 microg/mL; MIC(90) 4 microg/mL). The cumulative curve of tigecycline MICs showed that when the MIC cut-offs were set at 2 microg/mL and 4 microg/mL, 80.9% and 93.1% of the isolates were susceptible, respectively. As tigecycline will be used in the future for infections caused by multidrug-resistant A. baumannii because of limited antibiotic choice, and as resistance to tigecycline in A. baumannii isolates may develop following antibiotic exposure, continuous monitoring of the susceptibility of A. baumannii isolates to tigecycline is warranted.