Protectin DX promotes the inflammatory resolution via activating COX-2/L-PGDS-PGD2 and DP1 receptor in acute respiratory distress syndrome.

PURPOSE: Acute respiratory distress syndrome (ARDS) is characterized by uncontrollable inflammation. Cyclooxygenase-2(COX-2) and its metabolite prostaglandins are known to promote the inflammatory resolution of ARDS. Recently, a newly discovered endogenous lipid mediator, Protectin DX (PDX), was also shown to mediate the resolution of inflammation. However, the regulatory of PDX on the pro-resolving COX-2 in ARDS remains unknown. MATERIAL AND METHODS: PDX (5 µg/kg) was injected into rats intravenously 12 h after the lipopolysaccharide (LPS, 3 mg/kg) challenge. Primary rat lung fibroblasts were incubated with LPS (1 µg/ml) and/or PDX (100 nM). Lung pathological changes examined using H&E staining. Protein levels of COX-2, PGDS and PGES were evaluated using western blot. Inflammatory cytokines were tested by qPCR, and the concentration of prostaglandins measured by using ELISA. RESULTS: Our study revealed that, COX-2 and L-PGDS has biphasic activation characteristics that LPS could induce induced by LPS both in vivo and in vitro.. The secondary peak of COX-2, L-PGDS-PGD2 promoted the inflammatory resolution in ARDS model with the DP1 receptor being activated and PDX up-regulated the inflammatory resolutionvia enhancing the secondary peak of COX-2/L-PGDS-PGD2 and activating the DP1 receptor. CONCLUSION: PDX promoted the resolution of inflammation of ARDS model via enhancing the expression of secondary peak of COX-2/L-PGDS-PGD2 and activating the DP1 receptor. PDX shows promising therapeutic potential in the clinical management of ARDS.

Research on biological detoxification of Chinese medicine containing aristolochic acid A by ten microorganisms / 中国中药杂志

This paper was aim to screen microorganisms with attenualed efficiency for Chinese medicine containing aristolochic acid A by liquid-state fermentation. Twelve Chinese medicine were detected by UPLC and aristolochic acid A was only founded in four species of Aristolochia, those were Caulis Aristolochiae Manshuriensis, Aristolochiae Radix, Aistolochia Contorta Bunge and Herba Aristolochiae Mollissima,but not in the others. With the four Chinese medicine containing aristolochic acid A as raw material, ten microorganisms were tested, and the content of aristolochic acid A was detected by UPLC. The results showed that one microorganism can decrease content of aristolochic acid A in all those four Chinese medicine.

Successful treatment of Aerococcus viridans endocarditis in a patient allergic to penicillin.

Aerococcus viridans is a rare human pathogen that occasionally causes endocarditis. Most of the reported cases of endocarditis have been treated with penicillin. Here we describe a patient who was allergic to penicillin and was successfully treated with cefotaxime.

High-dose daptomycin and fosfomycin treatment of a patient with endocarditis caused by daptomycin-nonsusceptible Staphylococcus aureus: case report.

BACKGROUND: Emergence of daptomycin-nonsusceptible (DNS) Staphylococcus aureus is a dreadful problem in the treatment of endocarditis. Few current therapeutic agents are effective for treating infections caused by DNS S. aureus. CASE PRESENTATION: We describe the emergence of DNS S. aureus. in a patient with implantable cardioverter-defibrillator (ICD) device -related endocarditis who was priorily treated with daptomycin. Metastatic dissemination as osteomyelitis further complicated the management of endocarditis. The dilemma was successfully managed by surgical removal of the ICD device and combination antimicrobial therapy with high-dose daptomycin and fosfomycin. CONCLUSIONS: Surgical removal of intracardiac devices remains an important adjunctive measure in the treatment of endocarditis. Our case suggests that combination therapy is more favorable than single-agent therapy for infections caused by DNS S. aureus.

Prognostic factors of candidemia among nonneutropenic adults with total parenteral nutrition.

BACKGROUND: Immediate removal of central venous catheters (CVCs) is not possible in patients with candidemia requiring total parenteral nutrition (TPN). This study analyzed the possible prognostic factors for survival time after onset of candidemia among nonneutropenic adults requiring TPN. METHODS: We conducted a retrospective analysis from September 2003 to August 2005. RESULTS: A total of 59 nonneutropenic adults with candidemia and requiring TPN were identified retrospectively. All Candida isolates were susceptible to flucytosine and amphotericin B. With the exception of one C glabrata isolate, all other isolates were susceptible to fluconazole and itraconazole. The only predictor of 30-day survival rate after onset of candidemia identified in our analysis was an Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 23 points or less. Adults with higher APACHE II scores, who did not have their CVCs changed, did not receive antifungal treatment, or who had thrombocytopenia had shorter survival times after the onset of candidemia. CONCLUSIONS: APACHE II scores, thrombocytopenia, antifungal agents, and CVCs changes are associated with survival time in nonneutropenic adults requiring TPN after the onset of candidemia.

Clinical and microbiological characteristics of Chryseobacterium indologenes bacteremia.

BACKGROUND/PURPOSE: Reports detailing bacteremia caused by Chryseobacterium indologenes remain limited, with most cases reported in Taiwan. The clinical significance of C. indologenes has not been fully established. This retrospective study investigated the clinical features and antimicrobial susceptibility of C. indologenes bacteremia. METHODS: Patients with C. indologenes bacteremia were identified at a medical center/teaching hospital in northern Taiwan between January 1, 2004 and January 31, 2008. Clinical features and the antimicrobial susceptibilities of these patients were analyzed. RESULTS: Sixteen isolates of C. indologenes from 16 episodes in 16 patients were identified, with all patients having underlying diseases. Two patients (12.5%) had polymicrobial bacteremia. The portal of bacteremia was not determined in most cases. Other clinical syndromes included catheter-related bacteremia, urinary tract infection and peritonitis. The majority of patients had undergone invasive procedures. Other associated conditions included immunosuppression, neutropenia and prolonged use of antibiotics. Only three patients were treated with appropriate antibiotics according to minimum inhibitory concentrations. The susceptibilities of isolates to trimethoprim-sulfamethoxazole (75.0%), levofloxacin (62.5%), piperacillin-tazobactam (50.0%), ciprofloxacin (43.75%) and cefepime (12.5%) were variable and the bacteremia-related mortality rate was 6.25%. CONCLUSION: C. indologenes isolates are resistant to multiple antibiotics, with newer fluoroquinolones and trimethoprim-sulfamethoxazole possibly representing the most appropriate antimicrobial agents to treat infections caused by this pathogen. However, the pathogenicity and factors of virulence for C. indologenes remain unclear, with our study revealing favorable outcomes of C. indologenes bacteremia. Epidemiological surveillance of this organism in Taiwan and extensive worldwide surveillance programs are required.

Clinical characteristics and predictors of mortality in patients with Enterobacter aerogenes bacteremia.

BACKGROUND AND PURPOSE: Enterobacter aerogenes is increasingly encountered in nosocomial infections. This study aimed to clarify the clinical characteristics and to identify the predictors of mortality in patients with E. aerogenes bacteremia. METHODS: From March 2001 to April 2007, all patients with positive blood cultures for E. aerogenes at Taipei Veterans General Hospital, Taipei, Taiwan, were enrolled in this retrospective study. The medical records were reviewed for clinical and laboratory data. RESULTS: Eighty eight patients were included, 9 (10.2%) of whom died of E. aerogenes bacteremia. Most of the patients had comorbidities. Seventy nine patients (89.8%) had nosocomial infections, and 43 patients (48.9%) had polymicrobial infections. Eighty four patients (95.5%) presented with fever. Empirical antimicrobial therapy was administered for 80 patients (90.9%), but was appropriate for only 55 patients (62.5%). Of the 9 patients who died, 8 had polymicrobial infection, 5 of whom had nosocomial pneumonia, and 6 did not receive appropriate antimicrobial therapy. Multivariate analysis indicated that high Acute Physiology and Chronic Health Evaluation (APACHE) II score (>16) [odds ratio (OR), 16.569; 95% confidence interval (CI), 1.24-221.24; p = 0.034] and strains not susceptible to extended-spectrum cephalosporins (OR, 9.21; 95% CI, 1.02-83.04; p = 0.048) were independent risk factors for mortality. CONCLUSIONS: The severity of E. aerogenes bacteremia, reflected by high APACHE II score and isolation of strains with no susceptibility to extended-spectrum cephalosporins, were independent risk factors for mortality. Patients with severe illness and isolates resistant to extended-spectrum cephalosporins should be treated with more potent antimicrobial agents.

Prognostic factors and clinical features of non-typhoid Salmonella bacteremia in adults.

BACKGROUND: Infections caused by non-typhoid Salmonella (NTS) have increased, and the increasing incidence of multidrug-resistant NTS bacteremia in adult patients has also been noted. This study aimed to investigate the clinical and microbiological characteristics of NTS bacteremia. METHODS: A total of 71 episodes of NTS bacteremia among 65 patients were identified between 2004 and 2006. Clinical characteristics were collected from medical records. The agar dilution method described by the Clinical and Laboratory Standards Institute was used to determine the in vitro activities of each antibiotic. Multiple logistic regression analysis was used to evaluate the relationship between patient characteristics and all other covariates studied for prognosis. RESULTS: Salmonella enteritidis was isolated in 30 cases (42.3%), Salmonella typhimurium in 22 (31.0%), and Salmonella choleraesuis in 19 (26.7%). Thirty-two (45.1%) isolates of 71 NTS bacteremias were susceptible to chloramphenicol, 37 (52.1%) to ampicillin, 47 (66.2%) to trimethoprim/sulfamethoxazole (TMP/SMX), 56 (78.9%) to moxifloxacin, 57 (80.3%) to ciprofloxacin and levofloxacin, and 71 (100%) to ceftriaxone. The crude 30-day mortality rate was 19.7%. In multiple logistic regression analysis, the following variables were independent and significant predictors of mortality: coma (odds ratio, 12.03) and inadequate antibiotic treatment (odds ratio, 6.63). CONCLUSION: S. enteritidis was the most frequently isolated serotype. High resistance rates of NTS to some readily available antimicrobials (ampicillin, chloramphenicol, TMP/SMX, fluoroquinolones) were found. Patients with the factor of coma or inadequate antibiotic treatment had poor prognosis.

Clinical and microbiological analysis of Elizabethkingia meningoseptica bacteremia in adult patients in Taiwan.

A limited number of reports have documented bacteremia caused by Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) in adults. Most cases have occurred in Taiwan. This study investigated the clinical features and risk factors for mortality from E. meningoseptica bacteremia and the antimicrobial susceptibilities of the isolates. Patients with E. meningoseptica bacteremia were retrospectively analyzed at a medical center/teaching hospital in northern Taiwan over a 3-y period. We analyzed clinical features and outcomes of patients and antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results of the isolates. 28 patients had nosocomial bacteremia and 4 patients had healthcare associated bacteremia. The isolates exhibited variable susceptibilities to levofloxacin, ciprofloxacin, piperacillin-tazobactam, tigecycline, and trimethoprim-sulfamethoxazole. PFGE demonstrated that most isolates were epidemiologically unrelated. The 28-d mortality rate was 41%. Multivariate analysis indicated that shock and use of inappropriate antibiotics were independent risk factors for mortality. In conclusion, nosocomial bloodstream infection due to E. meningoseptica is an increasing problem in Taiwan. Our study indicates that patients with E. meningoseptica bacteremia face poor prognoses, with shock and use of inappropriate antibiotics as the main risk factors for mortality. Further clinical study is needed to establish the optimal therapy for E. meningoseptica bacteremia.

In vitro activities of piperacillin or cefoperazone alone and in combination with beta-lactamase inhibitors against gram-negative bacilli.

We investigated in vitro activities of piperacillin or cefoperazone alone and in combination with beta-lactamase inhibitors against Gram-negative bacilli. Piperacillin/tazobactam 8:1 lowered resistance for Escherichia coli, Serratia marcescens, Enterobactaer cloacae, Klebsiella pneumoniae and imipenem-susceptible Acinetobacter baumannii. When piperacillin was combined with sulbactam 2:1 or 4:1, resistance against E. coli, S. marcescens, E. cloacae, extended spectrum beta-lactamase (ESBL)-K. pneumoniae and A. baumannii were reduced. MIC90 of cefoperazone against S. marcescens, E. cloacae, ESBL-K. pneumoniae and A. baumannii were >128 mg/L. Addition of sulbactam 1:1 or 2:1 enhanced antimicrobial activities. Addition of sulbactam to piperacillin or cefoperazone enhanced antimicrobial activities of GNB.

Invasive Haemophilus influenzae disease in adults in Taiwan.

BACKGROUND AND PURPOSE: Haemophilus influenzae is an important cause of invasive infection in infants and children, but it has been considered an uncommon cause of invasive disease in adults. We conducted a retrospective survey of invasive H. influenzae disease in adults in order to better understand the characteristics of clinical presentation and microbiology. METHODS: Patients older than 18 years with H. influenzae isolated from normally sterile sites, between July 1999 and June 2002 in a teaching hospital for adult patients were retrospectively analyzed. Data on demographics, clinical presentation, serotype, antibiotic susceptibility, and beta-lactamase production of H. influenzae isolates were analyzed. RESULTS: Fifteen patients were enrolled. The infectious diagnosis of invasive diseases comprised: pneumonia (5 patients), empyema (2), pelvic inflammatory disease (2), peritonitis (2), periorbital cellulitis with abscess formation (2), endophthalmitis (1) and primary bacteremia (1). Most patients were elderly with underlying illness. Of ten H. influenzae isolates available for analysis, two were serotype b and eight were nontypeable. Beta-lactamase production and ampicillin resistance were found in 6 H. influenzae isolates (5 nontypeable, and 1 type b). CONCLUSION: These data show H. influenzae disease in adults to be rare in Taiwan. Our limited number of cases suggest that nontypeable strains predominate in patients with invasive infection due to H. influenzae. Most patients had respiratory tract infections. Ampicillin resistance was found in more than one-half of H. influenzae isolates, and should be taken into consideration when antibiotics are prescribed on an empirical basis.

Adult candidemia at a medical center in northern Taiwan: a retrospective study.

BACKGROUND AND PURPOSE: Candidemia has been associated with a very high mortality. This study evaluated the predictors of candidemia-related mortality at a teaching hospital in northern Taiwan. METHODS: We conducted a retrospective analysis of adult patients with candidemia between September 2003 and May 2005. A stepwise logistic regression analysis was performed to determine the predictors of candidemia-associated mortality. All Candida isolates were identified to species by use of the ATB ID 32C kit and their susceptibilities to antifungal agents were tested by ATB Fungus 2 system. RESULTS: 179 episodes in 174 adult patients with candidemia were identified retrospectively. The predictors of mortality included duration of prior antibiotics >or=28 days, Acute Physiology and Chronic Health Evaluation (APACHE) II score >or=23 and retention of central venous catheters (CVCs). There was no statistically significant association between the time to the start of antifungal therapy and mortality from nosocomial candidemia. In addition, there was no significant association between the time to CVC removal and mortality after stratification by APACHE II score. CONCLUSIONS: Despite effective antifungal therapy after the onset of candidemia in more than half of the patients studied, mortality remained very high, especially in the groups with longer duration of prior antibiotic treatment, higher APACHE II score and CVC retention. Timing of CVC removal after onset of candidemia was not correlated with mortality.

Non-typhoidal Salmonella bacteremia in adults.

BACKGROUND AND PURPOSE: Very few studies have examined prognostic factors in adult patients with non-typhoidal Salmonella (NTS) bacteremia. The purpose of this study was to identify the prognostic factors of these patients. METHODS: A total of 79 episodes of NTS bacteremia were identified in 73 patients between January 2001 and December 2003. Susceptibilities to various antimicrobials were determined using disk-diffusion tests and National Committee for Clinical Laboratory Standards criteria. Multiple logistic regression was used to evaluate the relationship between patients' characteristics and covariates of mortality. RESULTS: There were only 5 episodes (6%) of gastroenteritis, two of which were due to Salmonella septicemia contracted abroad. Potentially predisposing factors were identifiable in 51 episodes (65%). Infections in 24 patients (30%) were due to serogroup B Salmonella and in 22 patients (28%), to serogroup C Salmonella. A logistic regression analysis selected two variables as independently influencing prognosis: coma (p=0.006) and septic shock (p=0.002). CONCLUSIONS: Thus, most adult patients with NTS bacteremia do not develop gastroenteritis. Patients in shock or coma have poor prognosis, and susceptibility to third-generation cephalosporins, cefepime, and carbapenem is high.

Human foamy virus bel1 sequence in patients with autoimmune rheumatic diseases.

Since the association between human foamy virus (HFV) with rheumatic autoimmune diseases remains controversial, this study was designed to determine the relationship between HFV and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or progressive systemic sclerosis (PSS). The bel1 and Pol sequences of HFV were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) in plasma and by PCR in peripheral blood mononuclear cells (PBMC) from patients with SLE, RA, and PSS. Antibodies against Bel1 and Pol were assessed by enzyme-linked immunosorbent assay. Active HFV infections were detected by a Bel1-responsive indicator cell line. The bel1 sequence was detected in the plasma (SLE 59, RA 32, and PSS 63%) and PBMC (SLE 54, RA 71, and PSS 57%). However, active HFV infection existed only in patients with the bel1 sequence in both plasma and PBMC. In SLE patients, antibodies against Bel1 (7.1%) and Pol (4.5%) were also detected. The results suggest a possible association between HFV infection and these autoimmune rheumatic diseases.

Bacteremia in patients with hematological malignancies.

BACKGROUND: An appropriate regimen in the empirical therapy of neutropenic fever episodes must be individualized at each institution. Hospitals have different patterns of microbial isolates and antibiotic resistance that must be taken into account. The aim of this study was to investigate isolates of bacteremia and their antibiotic susceptibility in patients with hematological malignancies. METHODS: All positive blood cultures at a medical center in Taiwan between 1999 and 2002 from patients with hematological malignancies were evaluated. Eleven kinds of antibiotics were tested for antimicrobial activities. The risk factors for mortality were evaluated. RESULTS: Three hundred seventy-one episodes of bacteremia in 266 patients with hematological malignancies were recorded. Gram-negative bacilli (GNB) were still predominant and accounted for 78.2% of isolates, followed by gram-positive cocci for 20.8% of isolates, and anaerobes for 1% of isolates. Escherichia coli was the most common isolated organism accounting for 27.5% of GNB isolates. Other isolates included Klebsiella pneumoniae (19.3%), Pseudomonas aeruginosa (11%), and Enterobacter cloacae (10.1%). The most isolated microorganisms were susceptible to cefoperazone/sulbactam, piperacillin/tazobactam, cefepime or imipenem. Age, GNB microorganism and inadequate empirical antibiotics were risk factors. CONCLUSIONS: We suggest that cefoperazone/sulbactam, piperacillin/tazobactam, cefepime or imipenem is an ideal empirical therapy.

In vitro activities of beta-lactam antibiotics alone and in combination with sulbactam against Gram-negative bacteria.

The resistance rates of ampicillin/sulbactam 2:1 against imipenem-susceptible and -resistant Acinetobacter baumannii were 23.5 and 30%, respectively. Ceftazidime/sulbactam combination showed significant reduction of resistant rates against Enterobacter cloacae, A. baumannii, ESBL Klebsiella pneumoniae. MIC90 of cefoperazone against E. cloacae, Serratia marcescens, A. baumannii and ESBL K. pneumoniae were > 128 mg/l. Addition of sulbactam enhanced the antimicrobial activities significantly. When imipenem was combined with sulbactam, the resistant rates against imipenem-resistant A. baumanni were significantly reduced. Cefepime/sulbactam combination was active against imipenem-resistant A. baumanni. The resistance rates of aztreonam/sulbactam combination against E. cloacae, imipenem-sensitive and resistant A. baumannii, ESBL K. pneumoniae were lowered significantly. The cefotaxime/sulbactam combination showed a significant improvement of activities against E. cloacae, S. marcescens, A. baumannii and ESBL K. pneumoniae.