Effects of Local Nasal Immunotherapy with FIP-fve Peptide and Denatured Tyrophagus putrescentiae for Storage Mite-Induced Airway Inflammation.

Allergic diseases are affecting public health and have increased over the last decade. Sensitization to mite allergens is a considerable trigger for allergy development. Storage mite-Tyrophagus putrescentiae shows great significance of allergenic potential and clinical relevance. The fungal immunomodulatory peptide FIP-fve has been reported to possess immunomodulatory activity. We aimed to determine whether T. putrescentiae-induced sensitization and airway inflammation in mice could be downregulated by FIP-fve in conjunction with denatured T. putrescentiae (FIP-fve and DN-Tp). Immune responses and physiologic variations in immunoglobulins, leukocyte subpopulations, cytokine productions, pulmonary function, lung pathology, cytokines in CD4+ and Treg cells were evaluated after local nasal immunotherapy (LNIT). After the LNIT with FIP-fve and DN-Tp, levels of specific IgE, IgG1, and IgG2a in the sera and IgA in the bronchoalveolar lavage fluid (BALF) were significantly reduced. Infiltrations of inflammatory leukocytes (eosinophils, neutrophils, and lymphocytes) in the airway decreased significantly. Production of proinflammatory cytokines (IL-5, IL-13, IL-17F and IL-23) and chemokine (IL-8) were significantly reduced, and Th1-cytokine (IL-12) increased in the airway BALF after LNIT. Pulmonary functions of Penh values were significantly decreased after the methacholine challenge, which resulted in a reduction of airway hypersensitivity after LNIT. Bronchus pathology showed a reduction of inflammatory cell infiltration and epithelium damage after LNIT. The IL-4+/CD4+ T cells could be downregulated and the IFN-γ+/CD4+ T cells upregulated. The Treg-related immunity of IL-10 and Foxp3 expressions in CD4+CD25+ cells were both upregulated after LNIT. In conclusion, LNIT with FIP-fve and DN-Tp had an anti-inflammatory effect on mite-induced airway inflammations and possesses potential as an immunomodulatory therapy agent for allergic airway diseases.

How Cryptococcus interacts with the blood-brain barrier.

Cryptococcus demonstrates predilection for invasion of the brain, but the mechanism by which Cryptococcus crosses the blood-brain barrier (BBB) to cause brain invasion is largely unknown. In order for Cryptococcus to cross the BBB, there must be a way to either cross human brain microvascular endothelial cells, which are the main constitute of the BBB, or go in between tight junctions. Recent evidence of human brain microvascular endothelial cell responses to transcellular brain invasions includes membrane rearrangements, intracellular signaling pathways and cytoskeletal activations. Several Cryptococcal genes related to the traversal of BBB have been identified, including CPS1, ITR1a, ITR3c, PLB1, MPR1, FNX1 and RUB1. In addition, Cryptococcus neoformans-derived microvesicles may contribute to cryptococcal brain invasion. Paracellularly, Cryptococcus may traverse across BBB using either routes utilizing plasmin, ammonia or macrophages in a Trojan horse mechanism.

Clinical characteristics of children and adults hospitalized for influenza virus infection.

BACKGROUND/PURPOSE: Influenza infection has different clinical presentations and outcomes in children and adults, and bacterial coinfection is associated with significantly higher morbidity and mortality. This study compared the clinical features in children and adults hospitalized for influenza virus infection and the role of concomitant bacteremia. METHODS: A retrospective observational cohort study was conducted by a review of medical records of all consecutive patients admitted for influenza infection between April 1, 2009 and February 28, 2011. RESULTS: Of the 1203 patients, 76.2% were children, and ranged in age from 1 month to 99 years, with a mortality of 3.1% for adults; no children died. Pneumonia, acute respiratory distress syndrome, acute respiratory failure, septic shock, and cardiovascular complications were more common in adults. Bacteremia was more common in adults than in children (3.5% vs. 0.4%). C-reactive protein (CRP) > 4 mg/dL and a longer hospital stay occurred more often in children with bacteremia than in the group without bacteremia. In adults with bacteremia, acute respiratory failure, septic shock, and cardiovascular complications were more common, with a mortality of 50% versus 1.4% compared with those without bacteremia, and thrombocytopenia and increased CRP were independent risk factors. Using receiver operating characteristic analysis, CRP ≥ 14 mg/dL had a sensitivity of 90.0% and a specificity of 80.0%. CONCLUSION: Influenza infection in adults is associated with increased risk of complications, bacteremia, and mortality compared with that in children. Bacteremia in adults with influenza is associated with increased complications and mortality; thrombocytopenia and elevated CRP levels could identify those at risk.

Microbiological, epidemiological, and clinical characteristics and outcomes of patients with cryptococcosis in Taiwan, 1997-2010.

BACKGROUND: Among members of Cryptococcus neoformans- Cryptococcus gattii species complex, C. neoformans is distributed worldwide whereas C. gattii is considered to be more prevalent in the subtropics and tropics including Taiwan. This nationwide study was undertaken to determine the distribution of genotypes, clinical characteristics and outcomes of 219 patients with proven cryptococcosis at 20 hospitals representative of all geographic areas in Taiwan during 1997-2010. METHODS AND FINDINGS: Of 219 isolates analyzed, C. neoformans accounted for 210 isolates (95.9%); nine isolates were C. gattii (4.1%). The predominant genotype was VNI (206 isolates). The other genotypes included VNII (4 isolates), VGI (3 isolates) and VGII (6 isolates). Antifungal minimal inhibition concentrations higher than epidemiologic cutoff values (ECVs) were found in nine VNI isolates (7 for amphotericin B). HIV infection was the most common underlying condition (54/219, 24.6%). Among HIV-negative patients, liver diseases (HBV carrier or cirrhosis) were common (30.2%) and 15.4% did not have any underlying condition. Meningoencephalitis was the most common presentation (58.9%), followed by pulmonary infection (19.6%) and "others" (predominantly cryptococcemia) (18.7%). The independent risk factors for 10-week mortality, by multivariate analysis, were cirrhosis of liver (P = 0.014) and CSF cryptococcal antigen titer ≥ 512 (P = 0.020). All except one of 54 HIV-infected patients were infected by VNI genotype (98.1%). Of the 13 isolates of genotypes other than VNI, 12 (92.3%) were isolated from HIV-negative patients. HIV-infected patients compared to HIV-negative patients were more likely to have meningoencephalitis and serum cryptococcal antigen ≥ 1:512. Patients infected with C. gattii compared to C. neoformans were younger, more likely to have meningoencephalitis (100% vs. 57%), reside in Central Taiwan (56% vs. 31%), and higher 10-week crude mortality (44.4% vs. 22.2%). CONCLUSIONS: Cryptococcus neoformans in Taiwan, more prevalent than C. gatii, has a predominant VNI genotype. Isolates with antifungal MIC higher than ECVs were rare.

Lemierre's syndrome in a patient with habitual toothpick usage.

Lemierre's syndrome is characterized by septic thrombophlebitis of the internal jugular vein that is complicated by metastatic infections. The disease usually presents after oropharyngeal infection. In rare cases, odontogenic infection has been implicated as culprit. Here, we report a case of Lemierre's syndrome that most likely developed secondary to toothpick usage. The patient had an uneventful recovery after the timely administration of the appropriate antibiotics.

Disseminated zygomycosis caused by Cunninghamella bertholletiae in patient with hematological malignancy and review of published case reports.

Cunninghamella bertholletiae is an unusual opportunistic pathogen belonging to the class Zygomycetes, order Mucorales, and the family Cunninghamellaceae. It has been identified with increased frequency in immunocompromised patients, especially those with hematological malignancy. Clinical infection by this fungus is almost always devastating. We report a fatal case of disseminated zygomycosis due to Cunninghamella bertholletiae in an acute myeloid leukemia patient without chemotherapy. We also reviewed the cases of Cunninghamella bertholletiae infection reported in these 20 years. These cases highlight the high mortality rate and rapid progression associated with this opportunistic fungal infection in immunocompromised patients.

Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.

BACKGROUND: A mouse brain transmigration assessment (MBTA) was created to investigate the central nervous system (CNS) pathogenesis of cryptococcal meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Two cryptococcal mutants were identified from a pool of 109 pre-selected mutants that were signature-tagged with the nourseothricin acetyltransferase (NAT) resistance cassette. These two mutants displayed abnormal transmigration into the central nervous system. One mutant displaying decreased transmigration contains a null mutation in the putative FNX1 gene, whereas the other mutant possessing a null mutation in the putative RUB1 gene exhibited increased transmigration into the brain. Two macrophage adhesion-defective mutants in the pool, 12F1 and 3C9, showed reduced phagocytosis by macrophages, but displayed no defects in CNS entry suggesting that transit within macrophages (the "Trojan horse" model of CNS entry) is not the primary mechanism for C. neoformans migration into the CNS in this MBTA. CONCLUSIONS/SIGNIFICANCE: This research design provides a new strategy for genetic impact studies on how Cryptococcus passes through the blood-brain barrier (BBB), and the specific isolated mutants in this assay support a transcellular mechanism of CNS entry.

Hyaluronic acid receptor CD44 deficiency is associated with decreased Cryptococcus neoformans brain infection.

Cryptococcus neoformans is a pathogenic yeast that can invade the brain and cause meningoencephalitis. Our previous in vitro studies suggested that the interaction between C. neoformans hyaluronic acid and human brain endothelial CD44 could be the initial step of brain invasion. In this report, we used a CD44 knock-out (KO or CD44(-/-)) mouse model to explore the importance of CD44 in C. neoformans brain invasion. Our results showed that C. neoformans-infected CD44 KO mice survived longer than the infected wild-type mice. Consistent with our in vitro results, the brain and cerebrospinal fluid fungal burden was reduced in CD44-deficient mice. Histopathological studies showed smaller and fewer cystic lesions in the brains of CD44 KO mice. Interestingly, the cystic lesions contained C. neoformans cells embedded within their polysaccharide capsule and were surrounded by host glial cells. We also found that a secondary hyaluronic acid receptor, RHAMM (receptor of hyaluronan-mediated motility), was present in the CD44 KO mice. Importantly, our studies demonstrated an in vivo blocking effect of simvastatin. These results suggest that the CD44 and RHAMM receptors function on membrane lipid rafts during invasion and that simvastatin may have a potential therapeutic role in C. neoformans infections of the brain.

Cutaneous hyalohyphomycosis caused by Paecilomyces lilacinus successfully treated by oral voriconazole and nystatin packing.

Paecilomyces lilacinus causes multiple diseases in humans, especially in immunocompromised patients. Cutaneous infections are the second most commonly encountered circumstance. We describe a woman with liver cirrhosis with hemorrhagic, bullous, ulcerative leg lesions caused by Paecilomyces lilacinus. The lesions improved after treatment with oral voriconazole and topical nystatin powder. We also reviewed previously reported cases of cutaneous P. lilacinus infection that were treated by oral voriconazole.

Strategies to manage antifungal drug resistance.

INTRODUCTION: Invasive fungal infections continue to cause significant morbidity and mortality in immunocompromised hosts. From more than half a million deaths from cryptococcosis in sub-Saharan Africa to an unchanging death rate from invasive candidiasis, despite three antifungal classes of drugs, insights into better strategies to reduce therapeutic failures or resistance are needed. AREAS COVERED: This review examines the issues around antifungal drug resistance from both a basic description of the failures and how they are detected to the variety of issues that need to be addressed to help prevent failures for successful management. The reader will gain an understanding of the clinical complexities in this patient population for management of invasive fungal infections. Throughout the review, principles of management are given along with some specific clinical examples to illustrate the issues and frame the knowledge base. From this discussion it is hoped that the clinician can use the insights provided to manage individual patients and find links to the evidence-based material that support its conclusions. Also, this review specifically identifies the limitations of present management and directs clinicians to gather additional information and provide even better treatment strategies. EXPERT OPINION: Invasive fungal infections are life-threatening complications of serious underlying diseases. Their management can be complicated by both direct and clinical drug resistance and by understanding these possibilities and correcting them; most patients can be successfully managed with present antifungal drugs if the underlying diseases can be controlled.

Comparison of the clinical manifestations of infective endocarditis between elderly and young patients - a 3-year study.

BACKGROUND AND PURPOSE: Infective endocarditis (IE) is associated with high morbidity and mortality. This study investigated the clinical manifestations and outcomes of IE and compared them between old and young patients. METHODS: In this retrospective study, data for patients with IE who were treated from November 1, 2003 to October 30, 2006 were collected. Patients were identified as having IE if they met the modified Duke criteria for definitive IE. RESULTS: Seventy two patients were included. The most common symptoms were fever (81%) and dyspnea (50%). Fifty four patients (75%) had culture-positive IE. Staphylococcus aureus (35%) was the most common organism isolated, followed by Streptococcus spp. (26%). Vegetations were detected in 60 patients (83%): mitral valve (MV; 40%), aortic valve (AV; 24%), tricuspid valve (TV; 14%), MV and AV (4%), and pulmonary valve (1%). Thirty nine patients (54%) had embolic complications - 26 older patients (79%) and 13 younger patients (33%). Twenty two patients (31%) died in hospital. There were significant differences in clinical features between older and younger patients. Diabetes mellitus (p

High prevalence rate of multidrug resistance among nosocomial pathogens in the respiratory care center of a tertiary hospital.

BACKGROUND AND PURPOSE: There is an increasing need for respiratory care centers (RCCs) for patients who require prolonged mechanical ventilation after intensive care unit (ICU) stay. Nosocomial infections occur at a high rate in ICUs, but there have been few studies of nosocomial infections in RCCs in Taiwan. METHODS: The infection rates, sources, and pathogens of nosocomial infections in the RCC of a tertiary hospital were retrospectively analyzed from January 2001 to December 2002. Nosocomial infections were defined in accordance with the recommendations of the Centers for Disease Control in the United States. RESULTS: There were 398 nosocomial infections in 265 patients (1.5 episodes for each patient). The incidence density of nosocomial infection was 27.3%. The mean age +/- standard deviation of patients was 74.5 +/- 12.8 years. The mean duration of infection from the day of patient transfer to the RCC was 13 days (range, 2-78 days). Urinary tract infection was most common (53.8%), followed by bloodstream infection (31.2%), skin and soft tissue infection (6.0%), and lower respiratory tract infection (5.5%). 481 strains of microorganisms were isolated, 12.8% of which were Staphylococcus aureus (all methicillin-resistant), 11.1% were Klebsiella pneumoniae (69.1% of which were the extended spectrum beta-lactamase [ESBL] phenotype), and 10.6% were Escherichia coli (31.4% of which were the ESBL phenotype). CONCLUSIONS: The infection incidence density in the RCC was similar to previous findings for ICUs during the same period. However, there were differences in the distribution of sites and pathogens. Multiple drug resistance rates were high.

Clinical experiences of pulmonary and bloodstream nocardiosis in two tertiary care hospitals in northern Taiwan, 2000-2004.

BACKGROUND AND PURPOSE: Nocardia is an uncommon pathogen in humans, and most patients with nocardiosis are immunocompromised, with variable etiologies. To understand the incidence, clinical characteristics, treatment and outcome of pulmonary and bloodstream nocardiosis, we conducted a retrospective study in two tertiary care hospitals in northern Taiwan. METHODS: We reviewed laboratory culture reports and clinical records of 29 adult patients with lower respiratory tract or bloodstream nocardiosis (21 and 8 patients, respectively) in two tertiary care hospitals, over a period of 5 years. The risk factors, clinical manifestations, response to therapy, outcome and recurrence rate were compared between these two groups. RESULTS: The most common underlying conditions in pulmonary nocardiosis were chronic lung disease and long-term steroid usage. For nocardemia, underlying malignancy and steroid administration are common. Fourteen of 21 patients with pulmonary nocardiosis ever transferred to an intensive care unit and 9 of them had concomitant infection. In patients with and without coexisting isolates during hospital course, the mean days from admission to specific therapy for nocardiosis were 26.4 and 11.9 days, respectively. Patients with nocardemia showed great variation in clinical manifestations and disease severity; central venous catheter implantation was noted in 6 of them. Only one patient with nocardemia had documented recurrence. Twenty four patients were treated with antimicrobials (trimethoprim-sulfamethoxazole, 83%; imipenem or meropenem, 25%). Treatment failure occurred in 7 of 20 patients treated with trimethoprim-sulfamethoxazole alone or in combination. CONCLUSIONS: Pulmonary or disseminated nocardiosis is rare but may be fatal as an opportunistic infection in an immunocompromised host with chronic lung disease, underlying malignancy or long-term steroid usage. The significance of primary nocardemia needs careful evaluation. Concomitant infection was the probable predisposing factor for intensive care unit admission for pulmonary nocardiosis in our study (p=0.019) and might obscure the isolation of nocardiae organisms and delay effective treatment. For critical patients with nocardiae infection, initial therapy with a combination antimicrobial regimen is recommended.

Mechanical bowel strangulation mimicking mesenteric vasculitis in a systemic lupus erythematosus patient.

A case of systemic lupus erythematosus with jaundice and vague abdominal pain which did not respond to steroid pulse therapy is presented. Noninvasive examinations and imaging studies showed ileus. Two weeks later, an emergency laparotomy was performed because of severe refractory abdominal pain and hemodynamic decompensation. An ischemic part of the terminal ileum was resected. It was pathologically determined to be ischemic bowel disease because of mechanical strangulation resulting from adhesion band, but without evidence of vasculitis, atherosclerotic change, or thrombosis. After intensive postoperative care, the patient gradually recovered. This unusual case shows that nonlupus-related mechanical strangulation should be considered in the differential diagnosis of acute abdomen in lupus patients, particularly in those who have received steroid therapy or have a history of previous abdominal operation.

Fournier's gangrene: ten-year experience in a medical center in northern Taiwan.

BACKGROUND AND PURPOSE: Fournier's gangrene is a life-threatening infection. The mortality is still high despite the rapid advancement of modern intensive care and surgical technique. In this study, we present our institution's recent experience with a large series of patients with Fournier's gangrene. METHODS: A retrospective chart review was performed including 44 consecutive patients with Fournier's gangrene over a 10-year period. RESULTS: The 44 cases comprised 39 males and 5 females, with a mean age of 55.5 years. The mean duration of hospitalization was 27.9 days. Overall mortality was 22.7%. Diabetes mellitus, hypertension, chronic liver disease, liver cirrhosis and chronic renal insufficiency were the 5 leading predisposing factors. Liver cirrhosis was highly related to mortality (p=0.009). The etiologic origin of the gangrene was colorectal, urological and dermatological in 52.3%, 25.0%, and 11.4% of patients, respectively. The most common isolated pathogens were Escherichia coli, Bacteroides fragilis, Klebsiella pneumoniae, Enterococcus spp., and Proteus mirabilis. There were a total of 74 debridements. Other related surgical procedures were reconstruction surgery (n = 18), colostomy (2), cystostomy (1), vasectomy (1), orchiectomy (1) and penectomy (1). Major complications of Fournier's gangrene, including respiratory failure, renal failure, septic shock, hepatic failure and disseminated intravascular coagulopathy, were significantly to mortality (p<0.05). CONCLUSIONS: Early diagnosis, intensive medical care (aggressive resuscitation and broad-spectrum antibiotics), and prompt and repeated surgical intervention are the mainstays of treatment. Liver cirrhosis in particular is a poor prognostic factor. Reconstructive surgery should also be a consideration once the acute condition has improved. Patients with comorbid condition, serious infection, and major complications should be treated carefully and aggressively.

Cefotaxime-resistant Citrobacter freundii in isolates from blood in a tertiary teaching hospital in Northern Taiwan.

From January 2002 to December 2003, 12 patients in a tertiary teaching hospital in northern Taiwan had bloodstream infections caused by Citrobacter freundii. Seven of the 12 isolates were resistant to cefotaxime. Using polymerase chain reaction and DNA sequencing, 3 of the 7 cefotaxime-resistant C. freundii isolates were found to carry extended-spectrum beta-lactamase (ESBL). AmpC beta-lactamase genes were also detected in all strains of C. freundii. All strains of C. freundii with MICs >or=4 mg/L for cefepime were positive for ESBL. Rather than performing PCR on all cefotaxime-resistant C. freundii isolates, assessment of the MIC for cefepime might be a practical way to choose between treatment with cefepime or with carbapenems.

Treatment of pan-drug resistant Acinetobacter baumannii.

The objective of this study was to investigate the role of sulbactam in the treatment of pan-drug resistant Acinetobacter baumannii (PDRAB). We studied 89 patients with PDRAB infection treated with different antibiotic regimens. Group A (n = 39) were treated with carbapenem with sulbactam and group B (n = 30) with second and third generation cephalosporins, antipseudomonas penicillins, or fluoroquinolones with aminoglycosides. We also studied the MICs for 48 PDRAB strains by using antimicrobial agents with and without sulbactam. The clinical outcomes of the 2 groups did not differ significantly, either in terms of resolution of infection (25/59, 42% in group A vs 12/30, 40% in group B) or survival (35/59, 59% vs 17/30, 57%). However, the MICs indicated that 16 of the 48 strains were sensitive to imipenem/sulbactam, compared with only 2 of the 48 to imipenem alone. The addition of sulbactam thus reversed the response in 30% (14/46) of strains initially resistant or only intermediate sensitive to imipenem. The MICs for meropenem/sulbactam were in the sensitive range for 8 of 48 strains compared to only 3 of the meropenem alone, indicating an 11% (5/45) reversal rate when sulbactam was added to meropenem. For the 38 isolates initially resistant to both carbapenems alone, imipenem/sulbactam reversed the resistance in 16% (6/38), while meropenem/sulbactam did so in only 3% (1/38). Thus, the carbapenem-sulbactam combinations did not clearly improve clinical outcome, but they did demonstrate lower MICs for the PDRAB strains tested. It may be that aggressive, early treatment of A. baumannii infections with these agents might prevent the emergence of PDRAB strains.

Severe acute respiratory syndrome in a medical center in Taipei.

From April 18 to May 31, 2003, 46 patients with probable severe acute respiratory syndrome were admitted to the negative-pressure isolation rooms of Mackay Memorial Hospital in Taipei, Taiwan. Their demographic, clinical, laboratory, and radiologic characteristics and clinical outcomes were analyzed. There were 15 males and 31 females, in this cohort, 13 of whom were healthcare workers. The latter included 6 hospital staff and 7 medical personnel transferred from other hospitals. The most common symptoms were fever (100%, 46/46), cough (72%, 33/46), shortness of breath (46%, 21/46), and diarrhea (39%, 18/46). Other common findings were lymphopenia (57%, 26/46), thrombocytopenia (39%, 18/46), elevated lactate dehydrogenase (63%, 29/46), and elevated creatine kinase (24%, 11/46). A total of 7 patients (15%) required mechanical ventilation, and 8 (17%) died. Advanced age was an independent significant risk factor for death. Fever followed by rapidly progressive respiratory compromise led to significant morbidity and mortality in this cohort.

Association of HLA class I with severe acute respiratory syndrome coronavirus infection.

BACKGROUND: The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection. METHODS: HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis. RESULTS: Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279). CONCLUSIONS: Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.

Brain abscess: clinical analysis of 53 cases.

Fifty-three cases of brain abscess were treated at Mackay Memorial Hospital from January 1991 through December 2001. The ages ranged from 2 weeks to 84 years, with a peak at 40 to 50 years (11/53, 21%). The male to female ratio was 1.8:1 (34 males, 19 females). The most common presenting symptoms were fever (30/53, 57%), headache (29/53, 55%), and changed mental status (24/53, 45%). The duration of symptoms before hospitalization ranged from several hours to 2 months. A shorter duration of symptoms was associated with poor outcome. The common predisposing factors were otic infection (10/53, 19%), penetrating head trauma and neurosurgery (10/53, 19%), and bacterial endocarditis (5/53, 9%). The leading underlying diseases were diabetes mellitus (12/53, 23%) and/or liver cirrhosis (6/53, 11%), and both were independently associated with increased risk of mortality. Computed tomographic scanning and magnetic resonance imaging facilitated early diagnosis and proper management. Surgical intervention was used together with antibiotics in 33 (62%) of 53 patients in whom the average abscesses diameter was 3.75 cm (range, 2-6 cm). The remaining 20 (38%) patients whose average abscesses diameter was 2.3 cm (range, 1-3.5 cm) were treated with antibiotics only. Culture of material drained from abscesses isolated 27 microorganisms from 19 (58%) of the 33 patients, 81% (22/27) of which were aerobic and 19% (5/27) anaerobic bacteria. The most common pathogen was alpha-hemolytic Streptococcus spp. (6/27, 22%). Most of the patients with Klebsiella pneumoniae isolated from brain abscess, cerebrospinal fluid, and blood cultures were diabetic. A high mortality rate (9/20, 45%) was found in patients with medical treatment. A high index of suspicion is needed for the early diagnosis of brain abscess, particularly in patients with predisposing factors. In this series, early diagnosis using computed tomography and/or magnetic resonance scanning, optimal timing of surgery, and appropriate use of antibiotics were associated with improved outcome.