Severity of illness scoring systems in patients with bacteraemic pneumococcal pneumonia: implications for the intensive care unit care.

Severity of illness scoring systems are useful for decisions on the management of patients with community-acquired pneumonia (CAP), including assessing the need for intensified therapy and monitoring, or for intensive care unit (ICU) admission. We compared the accuracy of the Pneumonia Severity Index (PSI), the CURB-65 and CRB-65 score, the modified-American Thoracic Society score (ATS), the IDSA/ATS guidelines and the Pitt Bacteraemia score (PBS) in evaluating severity of illness in 766 patients with bacteraemic pneumococcal pneumonia. We evaluated the sensitivity and specificity, the positive predictive value (PPV) and the negative predictive value (NPV) and the accuracy of the classification in predicting 14-day mortality. The PSI and the IDSA/ATS guidelines were the most sensitive whereas the PBS and modified-ATS scoring systems were the most specific in predicting mortality. The NPV was comparable for all four scoring systems (all above 90%), but the PPV was highest for PBS (54.2%) and lowest for PSI (23.2%). The predictive accuracy and discriminating power as measured by the receiver-operating characteristic (ROC) curve was highest for the PBS. Both the modified-ATS and the PBS scoring systems identified those patients who might benefit most from intensified care and monitoring. The PBS and modified-ATS proved superior to the IDSA/ATS guidelines, CURB-65 and CRB-65 with respect to their specificity and PPV. The low PPV of the PSI rendered it not usable as a parameter for decision-making in severely-ill patients with pneumococcal bacteraemia.

Clinicopathological features and prognosis of drug rash with eosinophilia and systemic symptoms: a study of 30 cases in Taiwan.

BACKGROUND: Drug rash with eosinophilia and systemic symptoms (DRESS), a group of non-blistering severe cutaneous adverse drug reactions (SCADRs), is characterized by skin rash and multiorgan involvement. Details of this reaction have not been reported in the literature so far. AIM: We investigate clinical and pathological features and prognosis of DRESS and hope this study will provide data concerning this disorder in Taiwan. METHODS: From January 2001 to June 2006, a total of 30 patients, diagnosed with DRESS, were enrolled and evaluated for demographic characteristics, pathological findings, complications and outcome. RESULTS: Patient ages ranged from 13 to 78, with an equal sex ratio. The most common offending drug was allopurinol followed by carbamazepine. Pathologic changes observed were lichenoid dermatitis, erythema multiforme, pseudolymphoma and vasculitis. Impairment of liver and renal functions and blood dyscrasia were frequent complications. Active infection or reactivation of HHV-6 was observed in 7 of 11 patients studied serologically. Two patients developed type 1 diabetes mellitus. The mortality rate was 10% (3 of 30). CONCLUSIONS: DRESS is a heterogeneous group of life-threatening conditions. The leading drug in DRESS in Taiwan is allopurinol. High eosinophil count and multiple underlying diseases are poor prognostic factors in patients with DRESS.

Association of serotypes of Streptococcus pneumoniae with disease severity and outcome in adults: an international study.

BACKGROUND: The introduction of conjugate pneumococcal vaccination for children has reduced the burden of invasive disease due to pneumococcal conjugate vaccine (PCV) types (i.e., serotypes 9V, 14, 6B, 18C, 23F, 19F, and 4) in adults. As nonvaccine serotypes become predominant causes of invasive disease among adults, it is necessary to evaluate the disease severity and mortality associated with infection due to nonvaccine serotypes, compared with PCV serotypes, in adults. METHODS: The association of pneumococcal serotype and host-related variables with disease severity and mortality was statistically examined (with multivariable analysis) in 796 prospectively enrolled, hospitalized adult patients with bacteremia due to Streptococcus pneumoniae. RESULTS: In multivariate analyses of risk in patients with invasive pneumococcal disease, older age (age, > or = 65 years; P = .004), underlying chronic disease (P = .025), immunosuppression (P = .035), and severity of disease (P < .001) were significantly associated with mortality; no association was found between nosocomial infection with invasive serotypes 1, 5, and 7 and mortality. The risk factors meningitis (P = .001), suppurative lung complications (P < or = .001), and preexisting lung disease (P = .051) were significantly associated with disease severity, independent of infecting serotype. No differences were seen in disease severity or associated mortality among patients infected with PCV serotypes, compared with patients infected with nonvaccine serotypes. CONCLUSIONS: Our data support the notion that host factors are more important than isolate serotype in determining the severity and outcome of invasive pneumococcal disease and that these outcomes are unlikely to change in association with nonvaccine serotype infection in the post-conjugate vaccine era.

Disseminated xanthogranulomas associated with adult T-cell leukaemia/lymphoma: a case report and review the association of haematologic malignancies.

Xanthogranuloma (XG) is rarely observed in adults and has been reported to be associated with chronic myelogenous leukaemia (CML) and/or neurofibromatosis type 1 (NF1). A 68-year-old woman with adult T-cell leukaemia/lymphoma (ATLL) gradually developed disseminated XGs over the 3 years since disease onset. Histopathological examination of a skin biopsy revealed the presence of histiocytes in the dermis with a few Touton giant cells admixed with lymphoid cells. The lesions of XGs persisted despite chemotherapy with prednisolone and chlorambucil for her ATLL. This is the first report of disseminated XGs associated with ATLL. The association of disseminated XGs with haematologic malignancies was reviewed and the possible pathogenesis of this association will be discussed.

Prolonged fever and pyuria: a urinary tract infection presentation of incomplete Kawasaki disease.

UNLABELLED: We report two patients with incomplete Kawasaki disease that presented as apparent urinary tract infection. Persistent fever and pyuria were the initial presentation without concomitant signs suggestive of Kawasaki disease; thus the patients were treated as urinary tract infection. Fever persisted despite antibiotic treatment. Diagnostic criteria of Kawasaki disease were not fulfilled for these two patients, yet aneurysmal dilatation of the coronary artery was noted 10 and 18 d, respectively, after the onset of fever. The diagnosis of incomplete Kawasaki disease was assigned when the coronary artery abnormality was detected. Fever subsided within 24 h of administration of intravenous immunoglobulin. CONCLUSION: This report highlights the potentially misleading presentation of fever and pyuria as the sole initial manifestation of incomplete Kawasaki disease. Echocardiography is indicated to detect coronary artery abnormality when fever persists in such patients after adequate antibiotic treatment and thorough urological evaluation.

Helicobacter pylori inhibits activity of cdc2 kinase and delays G2/M to G1 progression in gastric adenocarcinoma cell line.

BACKGROUND: Helicobacter pylori is a bacterial pathogen strongly associated with ulcer diseases and gastric cancer. The bacterial-induced alteration of cell-cycle control in host cells may play a role in the pathogenetic mechanisms. The aims of this study were to define the effect of H. pylori on the G2/M to G1 transition in a gastric cell line. METHODS: Cultured gastric cells, AGS, were synchronized in the S/early G2 phase and treated with intact H. pylori. The cell-cycle distribution of AGS cells was determined by flow cytometry. The activity of cdc2 kinase, as well as of some parameters that affect the kinase activity, was also examined. RESULTS: H. pylori delays cell-cycle progression at the G2/M phase in AGS cells. The G2/M delay was associated with reduced activity of cdc2 kinase. Both down-regulation of cell-cycle regulators (p34cdc2, cyclin B1 and cdc25C) and decreased association between p34cdc2 and cyclin B1 were found to be associated with the activity of cdc2 kinase abated after the H. pylori infection. In addition, the H. pylori-induced G2/M delay required direct contact between the bacteria and host cells. CONCLUSIONS: H. pylori inhibits G2/M to G1 progression and causes a reduction of cell division in gastric epithelial cells.

Synergy, pharmacodynamics, and time-sequenced ultrastructural changes of the interaction between nikkomycin Z and the echinocandin FK463 against Aspergillus fumigatus.

We investigated the potential synergy between two cell wall-active agents, the echinocandin FK463 (FK) and the chitin synthase inhibitor nikkomycin Z (NZ), against 16 isolates of filamentous fungi. Susceptibility testing was performed with a broth macrodilution procedure by NCCLS methods. The median minimal effective concentration (MEC) of FK against all Aspergillus species was 0.25 microg/ml (range, 0.05 to 0.5 microg/ml). For Fusarium solani and Rhizopus oryzae, MECs of FK were >512 microg/ml. The median MEC of NZ against Aspergillus fumigatus was 32 microg/ml (range, 8 to 64 microg/ml), and that against R. oryzae was 0.5 microg/ml (range, 0.06 to 2 microg/ml); however, for the other Aspergillus species, as well as F. solani, MECs were >512 microg/ml. A checkerboard inhibitory assay demonstrated synergy against A. fumigatus (median fractional inhibitory concentration index = 0.312 [range, 0.15 to 0.475]). The effect was additive to indifferent against R. oryzae and indifferent against other Aspergillus spp. and F. solani. We further investigated the pharmacodynamics of hyphal damage by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and examined the time-sequenced changes in hyphal ultrastructure. Significant synergistic hyphal damage was demonstrated with the combination of NZ (2 to 32 microg/ml) and FK (0.03 to 0.5 microg/ml) over a wide range of concentrations (P < 0.001). The synergistic effect was most pronounced after 12 h of incubation and was sustained through 24 h. Time-sequenced light and electron microscopic studies demonstrated that structural alterations of hyphae were profound, with marked transformation of hyphae to blastospore-like structures, in the presence of FK plus NZ, while fungi treated with a single drug showed partial recovery at 24 h. The methods used in this study may be applicable to elucidating the activity and interaction of other cell wall-active agents. In summary, these two cell wall-targeted antifungal agents, FK and NZ, showed marked time-dependent in vitro synergistic activity against A. fumigatus.

Cryptococcus laurentii fungemia in a premature neonate.

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

Helicobacter pylori infection induced alteration of gene expression in human gastric cells.

BACKGROUND: Helicobacter pylori, a human pathogen responsible for many digestive disorders, induces complex changes in patterns of gene expression in infected tissues. cDNA expression arrays provide a useful tool for studying these complex phenomena. AIM: To identify genes that showed altered expression after H pylori infection of human gastric cells compared with uninfected controls. METHODS: The gastric adenocarcinoma cell line AGS was cocultivated with H pylori. Growth of infected cells was determined by trypan blue exclusion assay. Complementary DNA probes derived from H pylori treated and untreated cells were hybridised to two identical Atlas human cDNA expression arrays, and those genes with altered expression levels were identified. A real time quantitative reverse transcription-polymerase chain reaction assay was used to better define expression patterns of these genes in endoscopically gastric mucosal biopsies with and without H pylori infection. RESULTS: Over 24 hours, coincubation with H pylori inhibited AGS cell growth but did not cause a noticeable degree of cell death. H pylori treatment altered the pattern of gene expression in AGS cells. We identified 21 overexpressed genes and 17 suppressed genes from the cDNA expression arrays. The majority of genes were transcription factors such as c-jun, BTEB2, and ETR101. Other genes were involved in signal transduction pathways, such as MAP kinase, interleukin 5, and insulin-like growth factor. Genes involved in cell cycle regulation and differentiation, such as CDC25B and NM23-H2, were also identified. In patients with H pylori infection (n=20), there was a significant difference for ERCC3, Id-2, and NM23-H2 mRNA levels in infected gastric mucosa compared with uninfected gastric mucosa in patients without peptic diseases (n=20) (ERCC3 4.75 molecules/10(4) beta-actin mRNA molecules v 13.65, p<0.001; Id-2 16.1 v 23.4, p<0.05; NM23-H2 17.5 v 45.5, p<0.001). There was no significant difference between mRNA levels of c-jun and CDC25B in H pylori colonised gastric mucosa and uninfected mucosa. CONCLUSION: We demonstrated that H pylori infection caused alteration of gene expression in AGS cells. The differential hybridisation technique of Atlas human cDNA expression array is a useful method to identify host genes involved in pathogenic mechanisms in H pylori infection.

Novel penicillin-, cephalosporin-, and macrolide-resistant clones of Streptococcus pneumoniae serotypes 23F and 19F in Taiwan which differ from international epidemic clones.

A cluster (14 of 18) of Streptococcus pneumoniae serotype 23F isolates that were resistant to penicillin (PEN), cephalosporin, and macrolide was found in one day care center in Kaohsiung, Taiwan. We analyzed the 18 isolates by pulsed field gel electrophoresis (PFGE). All but one serotype 23F isolate demonstrated identical PFGE patterns, which were different from the established pattern of the internationally spread Spanish 23F clone. The three strains of serotype 19F also showed a uniform pattern. These data strongly suggest that two novel clones of PEN-, cephalosporin-, and macrolide-resistant S. pneumoniae serotypes 23F and 19F are present in Taiwan.

Esophageal candidiasis in pediatric acquired immunodeficiency syndrome: clinical manifestations and risk factors.

BACKGROUND: Little is known about the epidemiology and clinical features of esophageal candidiasis (EC) in pediatric AIDS. We therefore investigated the clinical presentation and risk factors of EC in a large prospectively monitored population of HIV-infected children at the National Cancer Institute. PATIENTS AND METHODS: We reviewed the records of all HIV-infected children (N = 448) followed between 1987 and 1995 for a history of esophageal candidiasis to characterize the epidemiology, clinical features, therapeutic interventions and outcome of esophageal candidiasis. To understand further the risk factors for EC in pediatric AIDS, we then performed a matched case-control analysis of 25 patients for whom control cases were available. RESULTS: There were 51 episodes of EC documented in 36 patients with 23 male and 13 female patients (0.2 to 17 years; median CD4, count 11/microl), representing a frequency of EC of 8.0%. Concurrent oropharyngeal candidiasis (OPC) was the most common clinical presentation of EC (94%); other signs and symptoms included odynophagia (80%), retrosternal pain (57%), fever (29%), nausea/vomiting (24%), drooling (12%), dehydration (12%), hoarseness (6%) and upper gastrointestinal bleeding (6%). The causative organism documented in 36 episodes (18 from OPC, 17 from endoscopic biopsy and 1 from autopsy) was Candida albicans in all cases. Patients received treatment for EC with amphotericin B (63%), fluconazole (29%), ketoconazole (4%) or itraconazole (1%). A clinical response was documented in all 45 evaluable episodes. In 6 other cases, EC was a final event without contributing to the cause of death. By a conditional logistic regression model for matched data, the best predictor of EC was the presence of prior OPC (P<0.0001), followed by CD4 count and CD4 percentage (P = 0.0002) and use of antibacterial antibiotics (P = 0.0013). The risks associated with low CD4 count were independent of that of prior OPC. CONCLUSION: EC in pediatric AIDS is a debilitating infection, which develops in the setting of prior OPC, low CD4 counts and previous antibiotics.

New drugs and novel targets for treatment of invasive fungal infections in patients with cancer.

Invasive fungal infections have emerged as important causes of morbidity and mortality in profoundly immunocompromised patients with cancer. Current treatment strategies for these infections are limited by antifungal resistance, toxicity, drug interactions, and expense. In order to overcome these limitations, new antifungal compounds are being developed, which may improve our therapeutic armamentarium for prevention and treatment of invasive mycoses in high-risk patients with neoplastic diseases.

Expression of capsid [correction of caspid] protein VP1 for use as antigen for the diagnosis of enterovirus 71 infection.

To produce enterovirus 71 antigen for diagnostic purposes, the gene encoding the entire capsid protein VP1 was amplified by reverse transcription-polymerase chain reaction (RT-PCR), cloned and expressed in Escherichia coli as a poly-histidine fusion protein. Western blotting experiments with sera from patients with enterovirus 71 infection indicated that immunoglobulin G (IgG) and IgM antibodies bound to a single polypeptide VP1. According to these results, IgM anti-VP1 appeared in sera of patients with a symptomatic enterovirus 71 acute infection, whereas IgG anti-VP1 was present in sera of past infection. This finding suggests that detecting IgG and IgM immune responses against linear epitopes of recombinant VP1 is an effective means of determining the different phases of enterovirus 71 infection. In addition, sera containing coxsackie virus 16 (CA16) antibodies did not cross-react with the recombinant VP1 of enterovirus 71, despite the homology between VP1 proteins of both viruses. Comparison with reference PCR and neutralization assays showed these antibody tests to be appropriate for the serodiagnosis of enterovirus 71 infection.

Purification and characterization of neutral sphingomyelinase from Helicobacter pylori.

Phospholipase activities of human gastric bacterium, Helicobacter pylori, are regarded as the pathogenic factors owing to their actions on epithelial cell membranes. In this study, we purified and characterized neutral sphingomyelinase (N-SMase) from the superficial components of H. pylori strains for the first time. N-SMase was purified 2083-fold with an overall recovery of 37%. The purification steps included acid glycine extraction, ammonium sulfate precipitation, CM-Sepharose, Mono-Q, and Sephadex G-75 column chromatography. Approximate molecular mass for the native N-SMase was around 32 kDa. When N-omega-trinitrophenylaminolauryl sphingomyelin (TNPAL-SM) was used as a substrate, the purified enzyme exhibited a K(m) of 6.7 microM and a V(max) of 15.6 nmol of TNPAL-sphingosine/h/mg of protein at 37 degrees C in 50 mM phosphate-buffered saline, pH 7.4. N-SMase reaches optimal activity at pH 7.4 and has a pI of 7.15. The enzyme activity is magnesium dependent and specifically hydrolyzed sphingomyelin and phosphatidylethanolamine. The enzyme also exhibits hemolytic activity on human erythrocytes. According to Western blot analysis, a rabbit antiserum against purified N-SMase from H. pylori cross-reacted with SMase from Bacillus cereus. Sera from individuals with H. pylori infection but not uninfected ones recognizing the purified N-SMase indicated that it was produced in vivo. In enzyme-linked immunosorbent assays, the purified N-SMase used as an antigen was as effective as crude protein antigens in detecting human antibodies to H. pylori.

Mastoiditis: a disease often overlooked by pediatricians.

Although mastoiditis can be a life threatening disease, clinicians often overlook it because it is uncommon. We reviewed the presentation and management of all children younger than 15 years of age with the discharge diagnosis of mastoiditis in our hospital from January 1994 through December 1999. Nineteen patients that fulfilled the case definition were included. The most common clinical presentation in this series was fever. More specific findings, such as otorrhea, postauricular pain, swelling, and redness of mastoid could be found in less than half of these patients. Only two patients had characteristic physical findings, and mastoiditis was diagnosed in only three patients upon admission. Plain radiographic evidence of mastoiditis was usually not apparent early in the course. In this series, the majority of patients were diagnosed by computed tomography (CT) scans. The present study demonstrates that mastoiditis most commonly presents without a clearly diagnostic set of physical examination and laboratory findings. Mastoiditis should be considered in patients with otitis media or with fever of unknown origin (FUO). The empirical antibiotic treatment should cover organisms commonly found in acute otitis media (AOM), including Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis.

Applications of acute phase reactants in infectious diseases.

The elevation of acute phase reactants (APRs) is a nonspecific host response to infection, inflammation, and tissue injury. The major biologic function of APRs is to restore homeostasis and to improve survival. Measuring the alterations in APRs can be a useful clinical marker when an infection or inflammatory response is suspected. Serum levels of reactants like fibrinogen and complement proteins increase as part of the inflammatory response, but the increase is trivial and does not contribute to the differential diagnosis or the evaluation of therapeutic responsiveness. By contrast, C-reactive protein (CRP) concentrations increase markedly with acute invasive infections which parallel the severity of inflammation or tissue injury. This advantage makes CRP a useful marker for the presence of disease, response to therapy, and ultimate recovery.

Extremely high prevalence of nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae among children in Kaohsiung, Taiwan.

Resistance (intermediate and high) to penicillin among Streptococcus pneumoniae strains is an emerging problem worldwide. From 1995 to 1997, isolates of S. pneumoniae not susceptible to penicillin were seen with increasing frequency from blood, cerebrospinal fluid, pleural fluid, and middle ear fluid from pediatric patients at the Veterans General Hospital-Kaohsiung. To determine the prevalence of carriage of these penicillin-nonsusceptible S. pneumoniae isolates, we obtained nasopharyngeal swab specimens from 2,905 children (ages, 2 months to 7 years) attending day-care centers or kindergartens or seen in our outpatient clinic. S. pneumoniae was isolated from 611 children, and 584 strains were available for analysis. The oxacillin disc test was used as a screening test to evaluate penicillin susceptibility. The MICs of 11 antibiotics (penicillin, cefaclor, cefuroxime, ceftriaxone, cefotaxime, imipenem, chloramphenicol, clarithromycin, rifampin, vancomycin, and teicoplanin) were determined by the E-test. Only 169 (29%) of the strains were susceptible to penicillin; 175 (30%) strains were intermediately resistant and 240 (41%) were highly resistant. The isolates also demonstrated high rates of resistance to other beta-lactams (46% were resistant to cefaclor, 45% were resistant to cefuroxime, 45% were resistant to ceftriaxone, 31% were resistant to cefotaxime, and 46% were resistant to imipenem). The rate of resistance to macrolide antimicrobial agents was strikingly high; 95% of the isolates were not susceptible to clarithromycin. However, 97% were susceptible to rifampin and 100% were susceptible to the two glycopeptides (vancomycin and teicoplanin). While reports of penicillin-resistant S. pneumoniae increased worldwide through the 1980s, the high prevalence (71%) of resistance reported here is astonishing. Surveillance of nasopharyngeal swab specimen cultures may provide useful information on the prevalence of nonsusceptible strains causing invasive disease. Such information could be used to guide therapy of pneumococcal infections.

Coxsackievirus B1 infection in infants less than 2 months of age.

Most of the neonatal enteroviral infections reported in the literature are associated with Coxsackievirus B2-B5 and echovirus 9 and 11. We report a retrospective Coxsackievirus B1 (CB1) infection in infants less than 2 months of age. Seventeen patients had aseptic meningitis and 8 had systemic sepsis (multi-organ involvement including meningitis, impaired liver function, and abnormality in coagulation). The symptoms and signs were nonspecific and could not be distinguished with bacterial infection on clinical grounds. Virus isolation was mandatory for diagnosis. Impaired liver function and coagulation profiles were noted in patients with systemic sepsis, but not in patients with meningitis only. CSF examination showed some uncommon features of viral meningitis: predominance of polymorphonuclear cells (PMN) was noted in 62.5% of patients and hypoglycorrhachia in 64% of patients. The patients with only meningitis recovered completely without any sequela. One of the eight patients with systemic sepsis died with case fatality rate 12.5%. Physicians should be aware of the possibility of CB1 virus infection in young infants during prevalent seasons. Specimens should be sent for viral culture in patients with meningitis and sepsis to make a definite diagnosis.