High prevalence of latent tuberculosis infection in patients in end-stage renal disease on hemodialysis: Comparison of QuantiFERON-TB GOLD, ELISPOT, and tuberculin skin test.

BACKGROUND: Individuals with end-stage renal disease (ESRD) are 10- to 25-fold more likely than immunocompetent people to develop active tuberculosis (TB) and are candidates for being treated for latent TB infection (LTBI). However, diagnosis using the tuberculin skin test (TST) is doubly difficult due to cutaneous anergy and cross-reactions with Bacille-Calmette-Guérin (BCG) vaccination. MATERIALS AND METHODS: This was a prospective, doublematched, cohort study in which 32 ESRD patients and 32 age-matched, healthy controls were enrolled. The TST and two new interferon-gamma blood tests, QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB (ELISPOT), were performed. The subjects were followed up 2 years for active TB disease. ELISPOT was done in ESRD patients only. RESULTS: Compared to the healthy controls, a high prevalence of LTBI was found in the ESRD patients by TST (62.5%, 95% confidence interval [CI] 43.7-78.9), QFT-G (40.0%, 95% CI 22.7-59.4), and ELISPOT (46.9%, 95% CI 29.1-65.3). Agreement was moderate (kappa [kappa] = 0.53) for QFT-G and ELISPOT but only slight between TST and QFT-G (kappa = 0.25) and fair between TST and ELISPOT (kappa = 0.32). ESRD (p = 0.03) and diabetes mellitus (p = 0.04) were significant risk factors for QFT-G positivity on the multivariable analysis. The overall rate of active TB was 1.66 cases per 100 person-years (pys), with the rate higher in patients with ESRD (3.53 per 100 pys) and those with positive (3.40 per 100 pys) and indeterminate QFT results (30.16 per 100 pys), although the difference was not statistically significant. Sensitivity, specificity, and positive and negative predictive values of QFT-G for active TB was 100%, 62.1%, 8.3% and 100%. CONCLUSION: This pilot study is the first to compare QFT-G, ELISPOT, and TST in ESRD patients on hemodialysis and demonstrates a high prevalence of LTBI in this population. In our study, the QFT-G was the more accurate method for identifying those truly infected with Mycobacterium tuberculosis, even in BCG-vaccinated individuals.

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.

Once daily isepamicin treatment in complicated urinary tract infections.

Isepamicin is a new aminoglycoside, derived from gentamicin B, which is more stable than other aminoglycosides against inactivating enzymes, and is less nephrotoxic. We evaluated the efficacy and safety of a once daily isepamicin in the treatment of complicated urinary tract infections (UTIs), as compared with amikacin. During the period May, 1997, to January, 1998, a total of 52 patients with similar demographic and baseline characteristics were enrolled into a prospective, randomized, open-label, single-center trial at the Veterans General Hospital-Kaohsiung. Eleven patients were excluded for protocol violation. The remaining 41 patients were included in the efficacy analysis. Study subjects included 16 men and 25 women, with a mean age of 57.9 (range 18-95) years. Clinical improvement was noted in 100% of patients in both the isepamicin and amikacin group. No statistically significant difference was observed between the 2 groups in regard to the rapidity of defervescence, relief of dysuria and urinary frequency, and clearance of bacteriuria and pyuria. Bacteriological cure rates were 89.4% for the isepamicin group and 100% for the amikacin group. Fifteen of 25 subjects who received isepamicin and 16 of 27 subjects who received amikacin had an adverse effect, all of which were considered to be mild except for one in the amikacin group, who had an adverse event of moderate severity (vomiting). Seven (3 isepamicin and 4 amikacin) adverse events were considered probably or possibly related to the study drug, which included eosinophilia (2 isepamicin), liver function impairment (1 isepamicin, 2 amikacin), renal function impairment (1 amikacin) and flushed face (1 amikacin). However, none of the patients had a life-threatening or severe adverse event that required discontinuation of the drug. These results show that once daily administration of isepamicin is as effective and safe as amikacin in treatment of complicated UTIs.

[Septicemic melioidosis in Southern Taiwan: a case report].

The patient was a 56 year-old man, a resident of Hen-Tsueng Township in Ping-Tung County. He worked as a ranger at Ken-Ting Farm in southern Taiwan, and had been to Thailand for sight-seeing 5 years ago. He came to our outpatient department about one month prior to hospitalization for intermittent fever of one week duration. At that time, complete blood count was within normal limits and a chest roentgenogram was unremarkable. He was given erythromycin without showing any clinical improvement. Two days prior to admission, he noted pain in the left hip. The next day, severe dyspnea developed suddenly and chest x-ray film revealed bilateral nodular lesions. Physical examination on hospitalization revealed an acutely ill and jaundiced male with a temperature of 37.4 degrees C, blood pressure: 110/47 mmHg, pulse rate: 137/min, and respiratory rate: 26/min. There were rales in both lungs, but no lymphadenopathy or organ enlargement. Laboratory study showed WBC: 1,470/mm(3), platelet count: 47,000/mm(3), blood sugar: 226 mg/dL, mildly elevated transaminases and bilirubin, and BUN: 69 mg/dL, Cr: 4.3 mg/dL. Arterial blood gas analysis indicated an acute metabolic acidosis with PaO2 of 32 mmHg. Despite the initial impression of melioidosis and administration of ceftazidime plus gentamicin, his condition rapidly deteriorated and expired 18 hours after admission. Two sets of blood cultures grew Burkholderia pseudomallei. Melioidosis has been called a great imitator of diseases and culture results are frequently misinterpreted. The mortality is high even with suggested therapy with ceftazidime, cotrimoxazole, amoxicillin-clavulanate, chloramphenicol, and/or tetracycline. There has been a total of 10 cases reported in southern Taiwan and 2 of them were clearly indigenous. Melioidosis should be included in the reportable diseases, and its prevalence in Taiwan also should be investigated.

Clinical characteristics of emphysematous pyelonephritis.

A total of 21 patients (20 women and one man) with emphysematous pyelonephritis (EPN), treated in the Kaohsiung Veterans General Hospital during the period from 1991 through 1999 were included in this study. All of the patients were diabetic. The most common symptoms or signs were fever/chills (80%) and costovertebral angle knocking pain (71%). Diagnosis was confirmed by the presence of gas in the parenchyma or paranephric space on plain X-ray of the abdomen or computed tomography. The left kidney (11 cases, 52%) was more frequently affected than the right one (nine cases, 43%), and both kidneys were involved in one case. Obstruction of the corresponding renoureteral unit was found in 19% of the patients, and renal or ureteral stone was found in 23% of the patients. One third of the patients had type I EPN, and two-thirds had type II EPN. Escherichia coli was the most commonly isolated organism, accounting for 61%, 76%, and 47% of isolates from blood, urine, and aspirated pus culture respectively. Prompt control of blood sugar was begun and intravenous antibiotics were given. Drainage was performed in 71% of the patients, and two persons required nephrectomy because of poor control of the infection or complications. Overall survival was 72%. Emphysematous pyelonephritis is a rare, life-threatening, suppurative infection of the renal parenchyma and perirenaL tissues. For successful management of EPN, appropriate medical treatment should be initiated, and immediate nephrectomy or drainage should not be delayed.

An outbreak of meningitis caused by Angiostrongylus cantonensis in Kaohsiung.

Eight Thai laborers developed meningitis after eating raw snails (Ampullarium canaliculatus) during the period from September 27 to October 6, 1998. The diagnosis of Angiostrongylus cantonensis infection was established in all patients by serologic studies of serum and cerebral spinal fluid (CSF). Clinical manifestations included meningitis, radiculitis and cranial nerve palsy. Symptoms included fever, headache, orbital pain, gastrointestinal upset, hyperesthesia, muscle weakness, skin rash and diplopia. Laboratory abnormalities included peripheral eosinophilia, CSF eosinophilia, transient elevation of liver enzymes and creatinine phosphokinase, elevation of IgE. No space occupying lesions were detected by magnetic resonance imaging of the brain. None of the patients developed severe sequelae during the 6-month follow-up except for occasional headache in one patient. This report also provides evidence that third stage larvae were present in the intermediate host, A. canaliculatus, which the laborers had eaten.

Comparative study of the efficacy and safety of valaciclovir versus acyclovir in the treatment of herpes zoster.

Acyclovir, a specific and selective inhibitor of the replication of Herpesviridae family, has well-documented efficacy and tolerability in the treatment of herpes zoster. Its limited oral bioavailability and short half-life, however, necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, could be rapidly converted to acyclovir after oral administration, resulting in a three- to five-fold increase in acyclovir bioavailability compared with oral acyclovir in humans. Valaciclovir allows less frequent dosing and maintains the safety profiles of the parent drug. During the period from October 1996 through May 1998, a randomized, prospective study was performed in the Kaohsiung Veterans General Hospital to compare the safety and efficacy of valaciclovir with acyclovir in the treatment of herpes zoster in Taiwanese patients. Patients presenting with herpes zoster within 72 h after the onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg valaciclovir three times daily for 7 days or acyclovir 800 mg five times daily for 7 days. Patients were followed up for 29 days beginning with the start of therapy. A total of 57 patients were enrolled and randomized to receive valaciclovir (n = 32) or acyclovir (n = 25). Five patients in the valaciclovir group and three in the acyclovir group did not complete the study. The intent-to-treat analysis (57 patients) showed that valaciclovir significantly accelerated the resolution of herpes zoster-associated pain compared with acyclovir; on day 29, the valaciclovir group was 23% superior to the acyclovir group. There was no clinically significant difference in the nature, frequency or severity of adverse events between these two groups, although one and three adverse events were reported in the acyclovir and valaciclovir group, respectively. Thus, we conclude that in the management of herpes zoster, valaciclovir accelerates the resolution of pain and offers a simpler dosing, and maintains the favorable safety profile of acyclovir.

Azithromycin in the treatment of pneumonia caused by Chlamydia pneumoniae: report of a case.

We report a 67-year-old male with pneumonia in which Chlamydia pneumoniae was identified by serologic studies as the causative agent. After initial treatment failure with amoxicillin + clavulanic acid, pneumonia was successfully treated with the administration of oral azithromycin, 500 mg per day, for three days. Azithromycin is a new macrolide which has a long half-life and superior action to erythromycin. It provides a new and alternative choice in the treatment of Chlamydia pneumoniae infection in the future.

Endogenous Escherichia coli endophthalmitis.

Metastatic bacterial endophthalmitis caused by Klebsiella pneumoniae is a unique but well-known phenomenon in Taiwan, where most cases occur in diabetic patients with pyogenic liver abscesses. However, endogenous Escherichia coli endophthalmitis is quite rare. The most common primary site of this infection is the urinary tract and the incidence of concurrent systemic infections, such as abscess formation and infective endocarditis, is high. This illness has a rapidly progressive clinical course associated with a poor prognosis for recovery of visual acuity. This is a report of a case of endogenous E. coli endophthalmitis originating from a renal abscess in a diabetic woman. Despite aggressive local and systemic treatment, evisceration was required to prevent the infection from spreading.

Comparison of the APACHE II and APACHE III scoring systems in patients with respiratory failure in a medical intensive care unit.

BACKGROUND AND PURPOSE: This retrospective study compared the capability of the Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scoring systems to predict outcome and determined the independent predictors of survival in these scoring systems for patients with respiratory failure in a medical intensive care unit (ICU). MATERIALS AND METHODS: Seven hundred and eight patients with respiratory failure admitted to the medical ICU throughout a 9-year period were studied. Patients with an ICU stay of less than 24 hours, patients under 12 years of age, and burn and surgery patients were excluded. APACHE scores were calculated at 24 hours after admission. Student's t-test was used to compare the total APACHE scores of survivor and non-survivor groups. Multivariate logistic regression analysis was used to determine which variables were predictors of mortality. The discriminative power of APACHE scores to predict in-hospital mortality was studied by the area under the receiver operating characteristic curves of the APACHE II and APACHE III systems, respectively. RESULTS: Both systems showed a significant association between higher scores and higher mortality. The APACHE II system under-predicted the actual hospital mortality rate. The APACHE III systems had a higher discriminative power (area 0.7462) than the APACHE II systems (area 0.6856; p < 0.05). The independent predictors of survival as assessed by APACHE II and III systems were respiratory rate, arterial oxygen pressure, oxygen gradient between alveoli and artery, serum creatinine concentration, and the presence of neurologic abnormalities. CONCLUSIONS: The APACHE III systems has greater discriminative power than the APACHE II systems for predicting in-hospital mortality. The variables of oxygenation, mean artery pressure, respiratory rate, serum creatinine concentration, and Glasgow Coma Scale play important roles in predicting survival for patients with respiratory failure.

Streptococcal toxic shock syndrome in southern Taiwan.

This report outlines our experience with streptococcal toxic shock syndrome (STSS) at the Veterans General Hospital-Kaohsiung during the period October 1990 to November 1993. Group A streptococci were isolated from blood or normally sterile tissue in association with hypotension and multi-organ failure in the eight cases studied. A primary focus of infection was identified in seven cases, including pneumonia (1), septic arthritis (1) and soft-tissue infections (5). The remaining patient suffered from hyperglycemic hyperosmolar non-ketotic coma and Group A streptococcal bacteremia, without an obvious focus of infection. There were four cases of bacteremia. Clinical complications included acute renal failure in all eight cases, disseminated intravascular coagulation in five cases, liver involvement in two cases, adult respiratory distress syndrome in one case and soft-tissue necrosis in five cases. All isolates were sensitive to penicillin, and most patients were treated with intravenous penicillin G, with or without other antibiotics (gentamicin or clindamycin). Of the six patients with soft-tissue infection, two underwent amputation of the infected limb, and one patient underwent sono-guided pigtail drainage of psoas muscle abscess. Three of the patients died. STSS may be uncommon in Taiwan, but it is not rare. Early recognition of STSS (facilitated by Gram stain and culture), prompt debridement and drainage, and adequate antibiotic treatment with penicillin or clindamycin, or both, are necessary for control of such lethal infections.

Melioidosis: two indigenous cases in Taiwan.

We report the first two indigenously acquired cases of melioidosis in Taiwan, diagnosed by positive culture and biochemically identified using the ID 32 GN system (BioMerieux Vitek Inc, Hazelwood, MO, USA). The first patient was a 75-year-old Chinese woman who had not travelled abroad since her arrival from mainland China (San-Tung province) 47 years ago. She presented with spontaneous bacterial peritonitis and hepatitis C-related liver cirrhosis with septic shock. Burkholderia pseudomallei (formerly Pseudomonas pseudomallei) was isolated from cultures of both blood and ascites fluid. The second patient, a 70-year-old Chinese man, presented with right lower lobar pneumonia complicated with empyema and septic shock. Blood cultures grew B. pseudomallei. Both patients had underlying diabetes mellitus; one also had liver cirrhosis and chronic renal failure, while the other had a renal stone. The first patient died of refractory septic shock prior to diagnosis. The second patient survived with the use of intravenous ceftazidime for 30 days, followed by oral amoxicillin-clavulanic acid for a further 3 months. These cases serve as a reminder to clinical physicians that melioidosis is now no longer exclusive to patients with a history of travel to endemic areas. A high index of clinical suspicion is required for early diagnosis and treatment in order to reduce the mortality and improve clinical outcome.

Legionnaires' disease in an immunocompetent young adult.

Infection with Legionella pneumophila (LP) is a rare cause of pneumonia in previously healthy young adults. Pleural effusion is relatively common in Legionnaires' disease but is usually clinically insignificant. Herein we describe an immunocompetent, 19-year-old female with LP respiratory infection that presented with pleural effusion and mild interstitial infiltrates in the lower lungs. She received 3 weeks' treatment with erythromycin and rifampin and recovered completely. Diagnosis was based on serology testing with a four-fold rise of the antibody titer in the acute and convalescent phase. Legionnaires' disease should be considered in the differential diagnosis of culture-negative pleural effusion in immunocompetent young adults.

Optimal treatment for asymptomatic neurosyphilis.

In the pre-penicillin era, patients with asymptomatic neurosyphilis (ANS) were more likely to develop long-term neurological sequelae than those patients with normal cerebrospinal fluid (CSF). Although benzathine penicillin G cannot achieve treponemicidal levels in the CSF, decreased rates of neurological complications of syphilis and non-treponemal titre serological responses are usually observed after treatment with this antibiotic. We here a homosexual man with ANS successfully treated with benzathine penicillin G. This case suggests that reconsideration on the necessity of a lumbar puncture in HIV-infected patients with ANS is warranted.

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 (p 0.032 and p <0.001, respectively). However, the CSF TIMP-4 levels were significantly lower in the meningitis groups compared with the control groups (p <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.

Reduced health provider delay and tuberculosis mortality due to an improved hospital programme.

SETTING: A referral hospital in Kaohsiung, Taiwan. OBJECTIVE: To evaluate the impact of an in-hospital tuberculosis (TB) quality care programme initiated in May 2005 on health provider delay and outcome of newly diagnosed TB cases. DESIGN: Retrospective chart review of newly diagnosed TB cases presenting in 2002 and 2006. Health provider delay, clinical manifestations, management and outcome were recorded. RESULTS: Overall, 327 patients before (2002) and 262 patients after (2006) the programme began were enrolled. Patients were older men (mean age 65.9 years) and 23.4% (138/589) had diabetes; 84.4% had received anti-tuberculosis treatment. The programme shortened the time for doctors to order a chest X-ray (P < 0.01), and the reporting time for smear (P < 0.0001) and culture (P < 0.0001). On multivariable analysis, risk factors for attributable mortality included age >/=65 years (OR 4.4, 95%CI 1.8-10.9, P = 0.001) and liver cirrhosis (OR 4.3, 95%CI 1.1-16.6, P = 0.04). Treatment reduced mortality by 81% (OR 0.2, 95%CI 0.1-0.4, P < 0.001) and the programme halved overall mortality (OR 0.5, 95%CI 0.3-0.8, P = 0.01), and reduced attributable mortality by 62% (OR 0.4, 95%CI 0.2-0.8, P < 0.01). CONCLUSION: Intervention at the hospital level for quality control of TB care was instrumental in reducing health provider delay and led to a significant reduction in mortality.

Acute flaccid paralysis as an unusual presenting symptom of Japanese encephalitis: a case report and review of the literature.

Japanese encephalitis (JE) is an endemic disease in Taiwan. Acute JE virus infection characterized by acute flaccid paralysis in an adult has never been reported in Taiwan. We report a young adult man who received four doses of JEV (Nakayama strain) vaccination in childhood, but still developed acute JE virus infection, characterized with acute flaccid paralysis.He presented with fever, headache, progressive muscle weakness, and respiratory paralysis requiring mechanical ventilator. Deep tendon reflexes were decreased except for the Achilles reflex. After supportive care, he was weaned from the mechanical ventilator and at discharge 1 month later, his muscle power level and deep tendon reflexes recovered partially. The diagnosis of JE was based on the presence of anti-JE virus IgM in the CSF and seroconversion of IgM and IgG by the ELISA method. Electrophysiological findings were described. From the experience of this case, we caution that a history of vaccination for JE with the Nakayama strain may not provide a complete protection against natural infection in the community; and in Taiwan or any area where JE remains an endemic disease, Japanese virus encephalitis infection should be considered as a differential diagnosis in any adult presenting with acute flaccid paralysis.

Fever of unknown origin in Taiwan.

BACKGROUND: Fever of unknown origin (FUO) is a challenging problem worldwide. There was no prospective study of FUO in the past two decades in Taiwan. A prospective study was conducted. MATERIALS AND METHODS: The prospective study was undertaken from March 2001 to May 2002. All patients fulfilling the modified criteria for FUO, either admitted, referred or consulted in a medical center in southern Taiwan, were enrolled for analysis. RESULTS: A total of 94 cases met the criteria of FUO. The final diagnoses of FUO consisted of 54 infectious diseases (57.4%), 8 hematologic/neoplastic (8.5%), 7 noninfectious inflammatory (7.4%), 8 miscellaneous (8.5%) and 17 undiagnosed (18.1%) cases. The single most common cause of FUO was tuberculosis. Some infectious diseases, such as rickettsiosis and melioidosis, were rarely reported in western countries. Three patients with hemophagocytotic syndrome without ascertainable etiologies were present with FUO in this study. Between the patients with and those without a final diagnosis, the short-term survival (3 months) was compared by the Kaplan-Meier analysis, which revealed no difference. CONCLUSIONS: Mycobacteriosis is still the leading cause of FUO in Taiwan and it is important to identify this treatable disease from all causes of FUO. This study has showed geographical variation among the studies of FUO.

A method for quantification of the level of somatic embryogenesis among Norway spruce callus lines.

A method for quantitative determination of the level of somatic embryogenesis in Norway spruce embryogenic callus is described. Embryogenic callus was dispersed in liquid by agitation and plated in a thin layer of medium containing 0.6% low melting point agarose. The number of embedded somatic embryos per mg of callus ranged from 0.2 to 1.5 among 11 embryogenic callus lines surveyed. Each callus line was derived from an individual immature embryo explant. Further development occurred as somatic embryos grew out of the agarose layer. This method was useful for identifying highly embryogenic callus lines among phenotypically similar lines, and should be useful for quantitatively determining the effect of medium and growth regulator modifications on somatic embryo density and developmental capacity.