Cheng Len Sy

In vitro activities of linezolid against clinical isolates of Mycobacterium tuberculosis complex isolated in Taiwan over 10 years.

ABSTRACT Significant increases in the MIC90s of linezolid in multidrug-resistant Mycobacterium tuberculosis isolates were seen between the baseline period of 2001 to 2003 (0.5 μg/ml) and 2004 (2 μg/ml). The MICs were 4 μg/ml in three strains. Both fluoroquinolones (except levofloxacin) and kanamycin were found to have statistically significant degrees of concordance with linezolid.

Clinical manifestations of eosinophilic meningitis caused by Angiostrongylus cantonensis: 18 years’ experience in a medical center in southern Taiwan

BACKGROUND With the improvement of public health, eosinophilic meningitis associated with Angiostrongylus cantonensis infection is now seldom reported in Taiwan. Eosinophilic meningitis typically occurred sporadically in children. This study aims to analyze the clinical manifestations and change in the contemporary epidemiology of eosinophilic meningitis in Taiwan. METHODS This is a retrospective study of patients diagnosed with eosinophilic meningitis at Kaohsiung Veterans General Hospital, from December 1991 to September 2009. The demographic characteristics, clinical presentations, laboratory data, radiographic imaging, and treatment and clinical outcome were analyzed. A PubMed search with the keywords of eosinophilic meningitis, A cantonensis, and Taiwan was performed to retrieve cases of eosinophilic meningitis caused by A cantonensis since 1960. RESULTS Thirty-seven patients were diagnosed to have eosinophilic meningitis during a period of 18 years. The median age was 32 years (range, 2-80 years). Ninety five percent (35/37) of the patients were adults. The median incubation period was 10.5 days (range, 3-80 days). Most of the patients presented with headache (29, 78%), fever (25, 68%), and 11(30%) had hyperesthesia. Patients with hyperesthesia had longer incubation period (55 vs. 7 days, p=0.004), lower serum immunoglobulin E levels (127.5 vs. 1295 IU/mL, p<0.001), and longer duration between symptom onset and spinal taps (14 vs. 5 days, p=0.011). Three patients presented initially with lymphocytic meningitis, and eosinophilia only appeared on a second lumbar puncture. Magnetic resonance imaging of the brain disclosed leptomeningeal enhancement (17/26, 65%) and increased signal intensity (10/26, 38%) on T2-weighted and fluid-attenuated inversion recovery images. There were eight relapses and two patients died. No sequela was noted except in one 2-year-old toddler, who had weakness of both lower limbs. CONCLUSIONS The epidemiology of eosinophilic meningitis has changed during the past two decades in Taiwan and occurs mainly in adults in the setting of outbreaks. Hyperesthesia; repeated lumbar puncture in cases with lymphocytic meningitis of uncertain cause; and a detailed history, including food consumption, are important to establish an accurate diagnosis.

Rapid emergence of oseltamivir resistance.

To the Editor: The influenza A pandemic (H1N1) 2009 virus has spread globally since it first appeared in Mexico in April 2009. This third influenza pandemic since the Spanish influenza pandemic of 1918 (1) has caused at least 400,000 infections within 6 months; estimated mortality rate is 1.2% (2). Emergence of oseltamivir resistance in the pandemic (H1N1) 2009 virus is a rising challenge to global control of the pandemic. So far, 39 oseltamivir-resistant pandemic (H1N1) 2009 viruses have been reported worldwide (3). Among the 32 resistant strains reported in October 2009, a total of 13 (41%) were associated with postexposure chemoprophylaxis and 16 (50%) were from samples of patients receiving oseltamivir (3). We report rapid emergence of resistance (H275Y mutation) in a patient, 4 days after early treatment with standard doses of oseltamivir for pandemic (H1N1) 2009 pneumonia. On September 1, 2009, a 20-year-old man with mental retardation consulted the emergency department of Kaohsiung Veterans General Hospital after 1 day of fever, sore throat, and nonproductive cough. A rapid diagnostic antigen test (Quick Vue Influenza test; Quidel, San Diego, CA, USA) showed the man to be positive for influenza A. He was hospitalized for bilateral pneumonitis and treated with oseltamivir (75 mg 2×/day for 5 days), ampicillin/sulbactam, and erythromycin. However, a progressive increase in bilateral perihilar interstitial infiltration developed on the third day, accompanied by increasing dyspnea. Influenza A pandemic (H1N1) 2009 virus was isolated from the patient’s nasopharyngeal secretions on days 1 and 4 by using MDCK cells. After DNA sequence analysis of the neuraminidase gene, the mutation of H275Y was not found in the first isolate, but sequence analysis of the second isolate detected mixed populations (C/T) in the 823-nt position of the neuraminidase gene. Only a single pattern (T) was found from the cultured viruses, indicating a mixed quasispecies of oseltamivir-resistant and -susceptible viruses emerging after 4 days of oseltamivir treatment. The oseltamivir-resistant viruses become dominant in the cell culture–propagated viruses. Chan et al. reported a similar case in which the original clinical specimens contained a mixed population of variants, and oseltamivir-resistant viruses become dominant after the passage in MDCK cells (4). On his 9th day in the hospital, the patient was intubated because of acute respiratory distress syndrome (Figure) and given levofloxacin. Urine samples were negative for Pneumococcus and Legionella spp. antigens. The patient improved and was extubated on hospital day 16. Figure Radiograph (anteroposterior view) of patient with acute respiratory distress syndrome and oseltamivir-resistant pandemic (H1N1) 2009 virus. Paired serologic test results were negative for Mycoplasma pneumoniae and Legionella spp. antibody; however, immunoglobulin G for Chlamydia pneumoniae increased 4-fold. By 37 days after illness onset, clinical signs and symptoms resolved and bilateral lineoreticular infiltration was reduced. On August 8, 2009, Taiwan had the most devastating typhoon (Typhoon Morakot) in 50 years. The patient reported here had stayed in a typhoon evacuation camp for 1 week before his influenza signs and symptoms developed. Although 4 sporadic cases of pandemic (H1N1) 2009 infections were reported from the same camp, none of the isolated viruses harbored the H275Y mutation in the neuraminidase gene. No evidence of virus transmission was found among healthcare personnel, family members, and camp members who had been in close contact with the patient. Oseltamivir has been recommended by the US Centers for Disease Control and Prevention for the treatment of infection caused by pandemic (H1N1) 2009 virus (5). The first 2 cases of oseltamivir resistance of pandemic H1N1 (2009) virus were reported in August 2009 (6). For these cases, oseltamivir-resistant virus was isolated on days 11 and 23 after the initial isolation of oseltamivir-susceptible viruses, for each patient, respectively. In contrast, in the case reported here, resistance to oseltamivir developed rapidly, after only 4 days of treatment. In severe cases of pandemic (H1N1) 2009 infections, mortality rates are highest for patients who are pregnant, <2 years of age, or obese, or who have chronic lung disease (7). The patient reported here was previously healthy except for mental retardation; his body mass index was 23.9 kg/m2. Progression of pneumonia to acute respiratory distress syndrome occurred despite early initiation of the standard dose of oseltamivir, within 48 hours after illness onset and initial susceptibility of the virus. Clinical deterioration might have resulted from the rapid emergence of an oseltamivir-resistant pandemic (H1N1) 2009 virus with a H275Y mutation, which is known to confer a high level of oseltamivir resistance while retaining zanamivir susceptibility (8), or it might have resulted from co-infection with C. pneumoniae. A 4-month study found concurrent bacterial infections in 29% of fatal cases of pandemic (H1N1) 2009 virus (9). Oseltamivir resistance can emerge rapidly during treatment of pandemic (H1N1) virus infection. Healthcare providers should be aware that resistance may emerge in otherwise apparently healthy persons as early as day 4 of treatment with standard doses of oseltamivir.

Brain Magnetic Resonance Imaging Abnormalities in Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection

Angiostrongylus cantonensis is a parasite endemic in the Southeast Asian and Pacific regions. Humans are incidentally infected either by eating uncooked intermediate hosts or by consuming vegetables containing the living third-stage larvae. Reports on brain magnetic resonance imaging (MRI) findings and how they correlate with clinical features are limited in the literature. In this retrospective study, we investigated the brain MR features of eosinophilic meningitis caused by human infection with A. cantonensis. A detailed clinical study of 26 of these patients was conducted. The brain MRI findings were nonspecific, ranging from normal (n=1), leptomeningeal enhancement (n=21), hyperintense signal lesions (n=11) on T2-weighted MRI and nodular enhancing lesions in gadolinium-enhanced T1W1 (n=1). There was an association between the presence of brain MRI high signal intensities with peripheral eosinophilia (p=0.02), cerebrospinal fluid (CSF), eosinophil count ≥10%, and the presence of CSF antibodies to A. cantonensis (p=0.01). The patients with leptomeningeal enhancement in brain MRI tended to be younger and predominantly men (p=0.03). The time from onset of symptom to spinal tapping or brain MRI studies did not have an effect on the presence of brain MRI abnormalities. The brain MRI findings did not add any additional importance to the clinical evaluation of patients with eosinophilic meningitis in this series. Further studies are required to clarify the role of brain MRI in eosinophilic meningitis.

Clinical and Molecular Epidemiology of Infective Endocarditis in Intravenous Drug Users

Background: Infective endocarditis (IE) in intravenous drug users has been increasing in incidence. The major pathogen used to be methicillin‐susceptible Staphylococcus aureus, but resistant isolates have also been increasing. This study aimed to investigate the clinical characteristics of IE in intravenous drug users and to evaluate the molecular patterns of methicillin‐resistant S. aureus (MRSA) that cause IE in these drug users. Methods: A total of 37 episodes of IE in intravenous drug users hospitalized from 1980 to 2006 at a 1,250‐bed teaching hospital in Southern Taiwan were evaluated retrospectively. The genetic relatedness of S. aureus strains was assessed using pulsed‐field gel electrophoresis. Polymerase chain reaction was used to detect Panton‐Valentine leukocidin (PVL) and staphylococcal γ‐hemolysin (Hlg), and to determine the staphylococcal chromosomal cassette carrying the mecA methicillin‐resistant gene (SCCmec) type. Results: The patients had a mean ± standard deviation age of 31.5 ± 9.25 years, with a male predominance of 76%. Hepatitis C was present in all patients. Methicillin‐susceptible S. aureus accounted for 76% of infections, and the most common clinical symptoms were fever (97%) and embolic phenomenon (68%). There were 4 MRSA isolates, 3 of which were SCCmec type III. PVL and Hlg genes were found in 2 and 3 MRSA isolates, respectively. Eighty percent similarity was found among the MRSA isolates by pulsed‐field gel electrophoresis. Conclusion: Our results suggest that coinfection with hepatitis C was common in intravenous drug users with IE, and that molecular patterns of MRSA isolates had high similarity. SCCmec type III, which is usually hospital‐acquired, could have caused the community‐associated MRSA endocarditis in our patients.

Synergy of β-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods

ABSTRACT Modified disk diffusion (MDD) and checkerboard tests were employed to assess the synergy of combinations of vancomycin and β-lactam antibiotics for 59 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Mu50 (ATCC 700699). Bacterial inocula equivalent to 0.5 and 2.0 McFarland standard were inoculated on agar plates containing 0, 0.5, 1, and 2 μg/ml of vancomycin. Oxacillin-, cefazolin-, and cefoxitin-impregnated disks were applied to the surface, and the zones of inhibition were measured at 24 h. The CLSI-recommended checkerboard method was used as a reference to detect synergy. The MICs for vancomycin were determined using the Etest method, broth microdilution, and the Vitek 2 automated system. Synergy was observed with the checkerboard method in 51% to 60% of the isolates when vancomycin was combined with any β-lactam. The fractional inhibitory concentration indices were significantly lower in MRSA isolates with higher vancomycin MIC combinations (P < 0.05). The overall agreement between the MDD and checkerboard methods to detect synergy in MRSA isolates with bacterial inocula equivalent to McFarland standard 0.5 were 33.0% and 62.5% for oxacillin, 45.1% and 52.4% for cefazolin, and 43.1% and 52.4% for cefoxitin when combined with 0.5 and 2 μg/ml of vancomycin, respectively. Based on our study, the simple MDD method is not recommended as a replacement for the checkerboard method to detect synergy. However, it may serve as an initial screening method for the detection of potential synergy when it is not feasible to perform other labor-intensive synergy tests.

A nationwide covert observation study using a novel method for hand hygiene compliance in health care

HighlightsA novel covert observation method and reporting system was developed.The novel covert observation method is feasible for large‐scale observation.Overall hand hygiene compliance by covert observation is low in Taiwan.Hand hygiene compliance increases significantly with an increase in the number of indications within 1 hand hygiene opportunity. Background: Evaluation and feedback is a core hand hygiene (HH) improvement strategy. The covert observation method avoids observation bias inherent to the overt method. The aim of the study was to observe HH compliance by a novel covert method in a real‐world setting. Methods: We conducted a 2‐year, nationwide, prospective, observational study in teaching hospitals across Taiwan. Medical students and students who may have contact with patients in their careers were recruited as participants. A novel, shorthand notation method for covert observation was used. Observation results were reported through a study website. Results: There were a total of 25,379 HH opportunities covertly observed by 93 observers. Overall HH compliance was 32.0%. Health care workers had the highest HH compliance for indication 4 (42.6%), and the lowest for indication 5 (21.7%). Overall handrubbing percentage was high, reaching 83.6%. The HH compliance increased significantly with an increase in the number of indications within 1 HH opportunity (P < .001). Conclusions: The overall HH compliance by the covert observation method was low. An innovative shorthand notation method facilitated covert observation, and website reporting was demonstrated to be feasible for large‐scale observation.

High rate of HIV-1 drug resistance in treatment failure patients in Taiwan, 2009–2014

Background Drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has been associated with loss of viral suppression measured by a rise in HIV-1 RNA levels, a decline in CD4 cell counts, persistence on a failing treatment regimen, and lack of adherence to combination antiretroviral therapy. Objectives This study aimed to monitor the prevalence and risk factors associated with drug resistance in Taiwan after failure of first-line therapy. Materials and methods Data from the Veterans General Hospital Surveillance and Monitor Network for the period 2009–2014 were analyzed. Plasma samples from patients diagnosed with virologic failure and an HIV-1 RNA viral load >1000 copies/mL were analyzed by the ViroSeq™ HIV-1 genotyping system for drug susceptibility. Hazard ratios (HRs) for drug resistance were calculated using a Cox proportional hazard model. Results From 2009 to 2014, 359 patients were tested for resistance. The median CD4 count and viral load (log) were 214 cells/μL (interquartile range [IQR]: 71–367) and 4.5 (IQR: 3.9–5.0), respectively. Subtype B HIV-1 strains were found in 90% of individuals. The resistance rate to any of the three classes of antiretroviral drugs (NRTI, NNRTI, and PI) was 75.5%. The percentage of NRTI, NNRTI, and PI resistance was 58.6%, 61.4%, and 11.4%, respectively. The risk factors for any class of drug resistance included age ≤35 years (adjusted HR: 2.30, CI: 1.48–3.56; p<0.0001), initial NNRTI-based antiretroviral regimens (adjusted HR: 1.70, CI: 1.10–2.63; p=0.018), and current NNRTI-based antiretroviral regimens when treatment failure occurs (odds ratio: 4.04, CI: 2.47–6.59; p<0.001). There was no association between HIV-1 subtype, viral load, and resistance. Conclusion This study demonstrated a high level of resistance to NRTI and NNRTI in patients with virologic failure to first-line antiretroviral therapy despite routine viral load monitoring. Educating younger men who have sex with men to maintain good adherence is crucial, as PI use is associated with lower possibility of drug resistance.

Isolation of dengue virus from the upper respiratory tract of four patients with dengue fever

Background Dengue fever is an important arboviral disease. The clinical manifestations vary from a mild non-specific febrile syndrome to severe life-threatening illness. The virus can usually be detected in the blood during the early stages of the disease. Dengue virus has also been found in isolated cases in the cerebrospinal fluid, urine, nasopharyngeal sections and saliva. In this report, we describe the isolation of dengue virus from the upper respiratory tract of four confirmed cases of dengue. Methods We reviewed all laboratory reports of the isolation of dengue virus from respiratory specimens at the clinical microbiology laboratory of the Kaohsiung Veterans General Hospital during 2007 to 2015. We then examined the medical records of the cases from whom the virus was isolated to determine their demographic characteristics, family contacts, clinical signs and symptoms, course of illness and laboratory findings. Results Dengue virus was identified in four patients from a nasopharyngeal or throat culture. Two were classified as group A dengue (dengue without warning signs), one as group B (dengue with warning signs) and one as group C (severe dengue). All had respiratory symptoms. Half had family members with similar respiratory symptoms during the period of their illnesses. All of the patients recovered uneventfully. Conclusions The isolation of dengue virus from respiratory specimens of patients with cough, rhinorrhea and nasal congestion, although rare, raises the possibility that the virus is capable of transmission by the aerosol route among close contacts. This concept is supported by studies that show that the virus can replicate in cultures of respiratory epithelium and can be transmitted through mucocutaneous exposure to blood from infected patients. However, current evidence is insufficient to prove the hypothesis of transmission through the respiratory route. Further studies will be needed to determine the frequency of respiratory colonization, viable virus titers in respiratory secretions and molecular genetic evidence of transmission among close contacts.

Emergence of a strain of methicillin-resistant Staphylococcus aureus with decreased susceptibility to vancomycin 7 months after treatment with glycopeptide antibiotics

This case report describes a methicillin-resistant Staphylococcus aureus isolated repeatedly from the blood of a patient with community-acquired endocarditis who developed a four-fold increase in the minimal inhibitory concentration of vancomycin and daptomycin 7 months after his last exposure to glycopeptide antibiotics. This is contrary to the expected situation in which antimicrobial resistance tends to decrease after a patient is no longer exposed to vancomycin.