Hung Chin Tsai

Eosinophilic meningitis caused by Angiostrongylus cantonensis: Report of 17 cases

PURPOSEnTo 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.nnnSUBJECTS AND METHODSnWe 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.nnnRESULTSnWe 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%]), Brudzinskis 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.nnnCONCLUSIONnEosinophilic meningitis caused by A. cantonensis should be considered in patients who have headache or central nervous system manifestations after eating raw snails.

Predictors of Septic Metastatic Infection and Mortality among Patients with Klebsiella pneumoniae Liver Abscess

BACKGROUNDnPrimary liver abscess caused by Klebsiella pneumoniae is an infection that is emerging worldwide and that is associated with severe morbidity and considerable mortality.nnnMETHODSnA retrospective analysis of 110 episodes of primary liver abscess caused by K. pneumoniae that required hospitalization during 2001-2002 was conducted to identify predictors of metastatic infection, mortality, and the efficacy of first-generation cephalosporins and percutaneous drainage. The potential role of Klebsiella rmpA and magA genes was also evaluated.nnnRESULTSnThe study included 59 men and 51 women, with a mean age of 61.8 years. Diabetes was noted in 67 patients (60.9%). Metastatic infection occurred in 17 patients (15.5%), with meningitis accounting for 11 patients (64.7%) and endophthalmitis accounting for 4 patients (23.5%). The overall mortality rate was 10.0% (11 patients). Most of the severe complications occurred within the first 3 days after hospital admission. Ninety-two patients (83.6%) received treatment with cefazolin for >3 days. Four patients (4.3%) of the group who received cefazolin had metastatic infection, 1 patient (1.1%) experienced septic shock, and 3 (3.3%) experienced acute respiratory failure. Five (5.4%) of those 92 patients died. Multivariable analysis revealed that rmpA (odds ratio [OR], 28.85), Acute Physiologic and Chronic Health Evaluation (APACHE) II score >or=20 (OR, 8.08), and septic shock (OR, 4.33) were statistically significant predictors of metastatic infection. Metastatic infection (OR, 6.73), severity of disease (APACHE II score >or=16; OR, 11.82), septic shock (OR, 8.30), acute respiratory failure (OR, 69.92), and gas formation revealed on imaging (OR, 13.26) predicted mortality. Pigtail drainage protected against both metastatic infection (OR, 0.25) and mortality (OR, 0.14).nnnCONCLUSIONnManagement of primary liver abscess caused by K. pneumoniae with use of first-generation cephalosporins and percutaneous drainage was associated with low rates of mortality, metastatic infection, and complications. These rates are comparable to those reported for third-generation cephalosporins.

Comparison of the interferon- gamma release assay and the tuberculin skin test for contact investigation of tuberculosis in BCG-vaccinated health care workers.

Health care workers are at increased risk of Mycobacterium tuberculosis infection. The tuberculin skin test (TST) is frequently false positive in BCG-vaccinated health care workers. QuantiFERON-TB GOLD (QFT-G) is a sensitive and specific interferon-γ release assay unaffected by BCG vaccination. This study compared TST and QFT-G in the diagnosis of latent TB infection in BCG-vaccinated health care workers. 39 health care workers exposed to a smear-positive TB patient were enrolled. Initial TST was positive in 33 (84.6%) cases, but only 4 (10.2%) cases using QFT-G. TST conversion occurred in 2/6 (33.3%), compared to 4/32(12.5%), cases using QFT-G. A higher proportion of QFT converters was associated with intimate contact, although not reaching statistical significance. Face-to-face contact >1 h was significantly associated with QFT-G conversion ≥0.7 IU/ml (OR 8.63, 95%CI 1.08–69.07, p=0.04). Agreement between TST and QFT-G was 18.0%, (κ: −0.03). Concordance between TST and QFT (≥0.35 IU/ml) conversion was 40.0%(κ=−0.40), and 60.0%(κ=0.00) if QFT ≥0.7 IU/ml was used. Agreement increased with increasing TST cut-offs. TST is not useful in contact investigation among BCG-vaccinated health care workers, in an area with intermediate burden of TB. QFT may provide additional information for the diagnosis and strategic management of preventive treatment of LTBI in BCG-vaccinated health care workers in a country with intermediate burden of TB.

A prospective etiologic study of community-acquired pneumonia in Taiwan

BACKGROUND AND PURPOSEnThe treatment of community-acquired pneumonia (CAP) is complicated by the growing threat of antimicrobial resistance and the tendency to rely on empirical therapy. This study investigated the etiologic agents of adult CAP in Taiwan and the susceptibility of Streptococcus pneumoniae isolates from these patients.nnnMETHODSnA collaborative group was established in the emergency department to conduct a prospective study of the etiology of adult CAP. The etiologic agent was determined by a combination of microscopic, culture, serologic and antigen detection methods. Pneumococcal susceptibility testing was performed to determine the extent of penicillin resistance.nnnRESULTSnA total of 100 consecutive cases of mild to moderate adult CAP prior to the severe acute respiratory syndrome epidemic were enrolled. The etiologic agent was determined in 72% of cases. The 5 most common causative pathogens were S. pneumoniae (26%), Mycoplasma pneumoniae (20%), Chlamydia pneumoniae (13%), Haemophilus influenzae (9%), and Klebsiella pneumoniae (5%). Atypical pathogens accounted for 40% of CAP. Bacteremic pneumonia was diagnosed in 6.2% of cases. Co-infections with 2 or more pathogens were found in 16% of the cases. Among the 20 isolates of S. pneumoniae, 85% (17/20) were susceptible to penicillin, 3 (15%) were intermediate, and none were resistant to penicillin.nnnCONCLUSIONnS. pneumoniae, M. pneumoniae and C. pneumoniae were the 3 leading causes of mild to moderate CAP in Taiwan. This study indicates that penicillin-resistant S. pneumoniae play a very limited role in this condition in adults.

Efficacy of point-of-entry copper–silver ionisation system in eradicating Legionella pneumophila in a tropical tertiary care hospital: implications for hospitals contaminated with Legionella in both hot and cold water

A medical centre in Southern Taiwan experienced an outbreak of nosocomial Legionnaires disease, with the water distribution system thought to be the source of the infection. Even after two superheats and flush, the rate of Legionella positivity in distal sites in hospital wards and intensive care units (ICUs) was 14% and 66%, respectively. Copper-silver ionisation was therefore implemented in an attempt to control Legionella colonisation in both hot- and cold-water systems. Environmental cultures and ion concentration testing were performed to evaluate the efficacy of ionisation. When the system was activated, no significant change in rate of Legionella positivity in the hospital wards (20% vs baseline of 30%) and ICUs (28% vs baseline of 34%) of the test buildings over a three-month period was found, although all Legionella positivity rates were below 30%, an arbitrary target for Legionnaires disease prevention. When ion concentrations were increased from month 4 to month 7, however, the rate of Legionella positivity decreased significantly to 5% (mean) in hospital wards (P=0.037) and 16% (mean) in ICUs (P=0.037). Legionella positivity was further reduced to 0% in hospital wards and 5% (mean) in ICUs while 50% sites were still positive for Legionella in a control building. Although Legionella was not completely eradicated during the study period, no culture- or urine-confirmed hospital-acquired Legionnaires disease was reported. Ionisation was effective in controlling Legionella for both hot and cold water, and may be an attractive alternative as a point-of-entry systematic disinfection solution for Legionella.

Antimicrobial Resistance of Rapidly Growing Mycobacteria in Western Taiwan: SMART Program 2002

BACKGROUND/PURPOSEnTo 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.nnnMETHODSnDuring 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).nnnRESULTSnNearly all of the RGM were susceptible to amikacin and ofloxacin (= 90%) and resistant to doxycycline (less than 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 les than 40% of the RGM isolates remained susceptible to imipenem (21-38%).nnnCONCLUSIONnThe 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.

Pyogenic Liver Abscess Caused by Burkhoderia pseudomallei in Taiwan

Pyogenic liver abscess in Taiwan is a well-known disease entity, commonly associated with a single pathogen, Klebsiella pneumoniae. Melioidosis is an endemic disease in Taiwan that can manifest as multiple abscesses in sites including the liver. We report three cases of liver abscesses caused by Burkholderia pseudomallei. The first patient was a 54-year-old diabetic woman, who presented with liver abscess and a left subphrenic abscess resulting from a ruptured splenic abscess, co-infected with K. pneumoniae and B. pseudomallei. The second patient, a 58-year-old diabetic man, developed bacteremic pneumonia over the left lower lung due to B. pseudomallei with acute respiratory distress syndrome, and relapsed 5 months later with bacteremic abscesses of the liver, spleen, prostate and osteomyelitis, due to lack of compliance with prescribed antibiotic therapy. The third patient was a 61-year-old diabetic man with a history of travel to Thailand, who presented with jaundice and fever of unknown origin. Liver and splenic abscesses due to B. pseudomallei were diagnosed. A high clinical alertness to patients travel history, underlying diseases, and the presence of concomitant splenic abscess is essential to early detection of the great mimicker, melioidosis. The treatment of choice is intravenous ceftazidime for at least 14 days or more. An adequate duration of maintenance oral therapy, with amoxicillin-clavulanate or trimethoprim-sulfamethoxazole for 12-20 weeks, is necessary to prevent relapse. Liver abscess in Taiwan is most commonly due to K. pneumoniae, but clinicians should keep in mind that this may be a presenting feature of melioidosis.

Streptococcus Suis Meningitis with Ventriculoperitoneal Shunt Infection and Spondylodiscitis

Streptococcus suis is a zoonotic pathogen which causes meningitis, bacteremia, and endocarditis in pigs. Human infection is rare and often presents as meningitis with the sequela of permanent deafness and endocarditis. Previous cases were reported from pig-rearing countries such as Holland and Hong Kong. We report a 55-year-old bedridden man with S. suis meningitis complicated with ventriculoperitoneal shunt infection and lumbar spine spondylodiscitis. He presented with fever, delirium, neck stiffness, lower leg weakness and sudden onset hearing loss for several days. He was successfully treated with intravenous antibiotics, ventriculoperitoneal shunt replacement, lumbar spinal laminotomy and discectomy. Cerebrospinal fluid culture initially misidentified the organism as Streptococcus acidominimus, and S. suis was later identified by 16S rRNA sequencing. Misidentification of the microbiological findings may lead to a failure to correctly diagnose this disease. S. suis meningitis should be included in the differential diagnosis of patients with meningitis and sudden hearing loss.

Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis

The potential mechanisms for altered matrix metalloproteinase (MMP) or tissue inhibitors of matrix metalloproteinase (TIMP) function in patients with syphilis and HIV-1 co-infection (HIV-S) was unclear. To determine the expression of MMP-2, 9 and TIMP-1, 2, 4 in the serum and cerebrospinal fluid (CSF) of HIV-S patients, a total of 20 HIV-S patients and 8 controls were enrolled in a HIV-1 clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of MMP-2, 9, and TIMP-1, 2, 4 were determined by ELISA. Gelatin zymography was used to detect the expression of MMP-2 and MMP-9 in the CSF. Neurosyphilis was defined as a CSF white blood cell count ≥ 20 cells/μL or a reactive CSF Venereal Disease Research Laboratory (VDRL). All the patients with HIV-S were males. Most (85%) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ≥ 1:32. The median age was 35 years (IQR 30-43). The median CD4 T cell counts at the time of the diagnosis of syphilis were 270 cells/μL (IQR 96-484). Ten patients (50%) had neurosyphilis based on a reactive CSF VDRL test (n=8) or increased CSF white cell counts ≥ 20/μL (n=2). The concentrations of CSF MMP-9, TIMP-1, and TIMP-2 were significantly higher in patients with HIV-S than the controls (P<0.05). The CSF TIMP-4 concentrations were significantly lower in those with HIV-S (452 pg/ml) than controls (3101 pg/ml), P<0001. There were no significant differences in serum concentrations between the groups. The only finding that distinguished HIV-1 patients with from those without neurosyphilis is a significant higher expression of CSF MMP-9. In conclusion, the MMP/TIMP system was found to be dysregulated in patients with HIV-S regardless of whether they met the laboratory definition of neurosyphilis. The CSF level of MMP-9 was the only measure that distinguished those with or without neurosyphilis.

Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with meningitis

Meningitis is associated with an imbalance between matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of MMP (TIMPs). Serum and CSF were collected prospectively from all patients with meningitis between January 2008 and December 2008 to measure the concentrations of MMP/TIMP in those patients who underwent a lumbar puncture for a presumptive diagnosis of meningitis. A total of 199 patients were enrolled into the study. The concentrations of CSF MMP-9 and TIMP-1 were significantly higher in the meningitis group compared with the control group (pu20030.032 and pu2003<0.001, respectively). However, the CSF TIMP-4 levels were significantly lower in the meningitis groups compared with the control groups (pu2003<0.001). Patients with bacterial meningitis had higher CSF MMP-9 and TIMP-1 levels than those who had aseptic meningitis and controls. Patients with various infectious meningitis etiologies tended to have higher CSF MMP-9 expression by gelatin zymography when compared with the controls. In conclusion, MMP/TIMP system dysregulation was found in patients with meningitis, and CSF MMP and TIMP might act as novel indicators in patients with meningitis.