Chin Chung Tseng

Handgrip strength is an independent predictor of renal outcomes in patients with chronic kidney diseases

BACKGROUND In dialysis patients, protein-energy wasting (PEW) is associated with high mortality, and some indicators of PEW, such as serum albumin value, subjective global assessment (SGA) score and handgrip strength (HGS), may predict mortality. However, whether PEW is associated with poor renal outcomes and whether the indicators of PEW can predict renal outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD-ND) is still unclear. METHODS We enrolled 128 clinically stable patients with CKD-ND and followed up for 33.8 ± 9.2 months. Baseline characteristics, echocardiographic information, laboratory data, HGS, SGA scores, anthropometric parameters, bioimpedance analyses and other indicators of PEW were examined in relation to the risk of reaching renal composite end points of pre-dialysis mortality or dialysis-dependent end-stage renal disease. RESULTS Twenty-six patients reached composite renal end points. Multivariate Cox regression analyses showed that HGS was an independent predictor of renal outcome in patients with CKD-ND of Stages 1-5 [CKD(1-5), hazard ratio (HR) = 0.90, P = 0.004] or advanced CKD-ND of Stages 3b [defined as estimated glomerular filtration rate (eGFR) of 30-44 mL/min/1.73 m(2)] to 5 (CKD(3b-5), HR = 0.91, P = 0.031), but not serum albumin, SGA score or other indicators of PEW. When the cutoffs were set at 24.65 kg in men with CKD(1-5), 20.15 kg in men with CKD(3b-5) and 10.15 kg in women with CKD(1-5) or CKD(3b-5), which were deduced from receiver-operating characteristics analyses, patients with lower HGS had significantly poor renal outcomes in Kaplan-Meier survival analyses in all subgroups and higher HR for reaching renal end points in multivariate Cox regression analyses in all subgroups except for women with CKD(3b-5), whose HR had marginal significance (HR = 3.78, P = 0.068) after adjusting for age and eGFR. CONCLUSIONS This is the first study demonstrating that HGS is an independent predictor of composite renal outcomes in CKD-ND patients. HGS can be incorporated to clinical practice for assessing nutrition status and renal prognosis in patients with CKD-ND.

Loss of Outer Membrane Protein C in Escherichia coli Contributes to Both Antibiotic Resistance and Escaping Antibody-Dependent Bactericidal Activity

ABSTRACT Outer membrane proteins (OMPs) serve as the permeability channels for nutrients, toxins, and antibiotics. In Escherichia coli, OmpA has been shown to be involved in bacterial virulence, and OmpC is related to multidrug resistance. However, it is unclear whether OmpC also has a role in the virulence of E. coli. The aims of this study were to characterize the role of OmpC in antimicrobial resistance and bacterial virulence in E. coli. The ompC deletion mutant showed significantly decreased susceptibility to carbapenems and cefepime. To investigate the survival of E. coli exposed to the innate immune system, a human blood bactericidal assay showed that the ompC mutant increased survival in blood and serum but not in complement-inactivated serum. These effects were also demonstrated in the natural selection of OmpC mutants. Also, C1q interacted with E. coli through a complex of antibodies bound to OmpC as a major target. Bacterial survival was increased in the wild-type strain in a dose-dependent manner by adding free recombinant OmpC protein or anti-C1q antibody to human serum. These results demonstrated that the interaction of OmpC-specific antibody and C1q was the key step in initiating the antibody-dependent classical pathway for the clearance of OmpC-expressing E. coli. Anti-OmpC antibody was detected in human sera, indicating that OmpC is an immunogen. These data indicate that the loss of OmpC in E. coli is resistant to not only antibiotics, but also the serum bactericidal effect, which is mediated from the C1q and anti-OmpC antibody-dependent classical pathway.

The Role of Bacterial Virulence and Host Factors in Patients with Escherichia coli Bacteremia Who Have Acute Cholangitis or Upper Urinary Tract Infection

We studied the pathogenic role of host and Escherichia coli virulence factors in the development of E. coli bacteremia in patients with acute cholangitis (AC) or upper urinary tract infection (UTI). Isolates recovered from 75 adult patients consecutively admitted to the hospital with E. coli bacteremia caused by AC (n=24) or upper UTI (n=51) were evaluated, as were 30 fecal strains isolated from healthy control individuals. Virulence genes of E. coli were detected by polymerase chain reaction analysis, including papG genes (classes I-III), sfa/foc, fimH, afa, hlyA, cnf1, and iutA. Our results show that biliary tract obstruction and urinary tract obstruction are important host factors for the development of E. coli bacteremia in patients with AC and upper UTI, respectively. With regard to E. coli virulence factors, the papG class II gene might play a more important role in the development of E. coli bacteremia in patients with upper UTI than in those with AC.

Adult-onset minimal change disease among Taiwanese: clinical features, therapeutic response, and prognosis.

There are some racial differences in the prevalence and prognosis of idiopathic nephrotic syndrome; however, reports about minimal change disease (MCD) in Chinese were rare. We retrospectively analyzed 123 Chinese adults with idiopathic nephrotic syndrome, who received percutaneous renal biopsy in our institution within the last 10 years. In total, 46 patients (37.4%) were compatible with the pathological diagnosis of MCD. The male to female ratio was 1.2:1. The mean age of onset was 30.9 years, and 80% of the patients with MCD were less than 40 years. The mean daily proteinuria was 10.2 g, and serum albumin was 1.8 mg/dl. Azotemia occurred in 16 (35%) of 46 cases; hypertension, 13%; and microscopic hematuria, 13%. High selectivity index for proteinuria (SI <0.1) was noted in 12 (39%) of 31 cases; and high IgE level was found in 83.7% of the study subjects, although only one case had allergic history. Complete remission in 36 MCD patients treated with corticosteroid was achieved by 42% (15/36), 80% (29/36), and 94% (34/36) within 4, 8, and 12 weeks, respectively. The time interval to remission was similar between the younger group (<40 years old, 1.7 months) and older group (>40 years old, 1.6 months). Nineteen (56%) of 34 cases with steroid response did not relapse, and the other cases (44%) had a mean relapse rate of 1.5 times per patient within a period of 45 months. The age of onset in MCD cases was not significantly correlated with steroid-responsive rate, and the time interval to remission. However, a tendency existed between the onset in the young age and the sequentially relapsing rate (p = 0.06). Two cases with primary steroid resistance and 5 cases with frequent relapse or steroid dependence responded well to intravenous pulse therapy of cyclophosphamide, except one refractory case. No thrombotic episode was ever noted in our group. Regarding infectious complications, primary peritonitis occurred in one, pneumonia in one, and cellulitis in 6 cases during active nephrotic stage. Two mortality cases, one with E. coli-related necrotizing fasciitis and one from pneumonia, were noted. In brief, compared with children, adult patients with MCD had lesser high selectivity index for proteinuria, the same steroid-responsive rate (94%), but slower response, and significantly lesser relapsing rate. The intravenous pulse therapy of cyclophosphamide may be an alternative regimen for adult patients with steroid resistance or dependency. In addition, the Asian adult-onset MCD had younger age, male predominance, and lesser relapsing rate in comparison to those of the Western population.

Decreased predominance of papG class II allele in Escherichia coli strains isolated from adults with acute pyelonephritis and urinary tract abnormalities.

PURPOSE We compared the genotypes of fimbriae or adhesions of Escherichia coli causing acute pyelonephritis in adults with and without urinary tract abnormalities. MATERIALS AND METHODS We studied a total of 92 E. coli strains isolated from 54 patients with acute pyelonephritis and a normal urinary tract, and 38 with urinary tract abnormalities. Of those with urinary tract abnormalities 13 with moderate to severe hydronephrosis were also considered a separate group for the purpose of analysis. The genes of 7 known fimbriae or adhesins of E. coli were detected by the polymerase chain reaction, including the papG class I to III alleles (PapG adhesins of P-fimbriae), sfa/foc (S-/F1C-fimbriae), fimH (type 1 fimbriae), and afa (afimbrial adhesin). Virulence genes associated with APN were identified by comparing the prevalence of each of these 7 genes in E. coli strains from 54 patients with acute pyelonephritis with a normal urinary tract to the prevalence in the strains from 37 patients with acute cystitis using univariate and multivariate analysis. Differences in the prevalence of the genes associated with acute pyelonephritis and the incidence of underlying illness were then compared in the 3 acute pyelonephritis groups. RESULTS On univariate and multivariate analysis the papG class II allele was the only virulence gene associated with acute pyelonephritis (p <0.0001 and 0.001, respectively). No significant difference was noted in the prevalence of underlying medical disease in the 3 acute pyelonephritis groups. The papG class II allele was significantly less predominant in E. coli strains isolated from acute pyelonephritis cases with versus without urinary tract abnormalities (76% versus 93%, p = 0.03). The incidence of the papG class II allele in patients with urinary tract abnormalities and moderate to severe hydronephrosis was less than in those without urinary tract abnormalities (69% versus 93%, p = 0.04). CONCLUSIONS Our results imply that the papG class II allele has an important role in E. coli infection in patients with acute pyelonephritis and a normal urinary tract, while urinary tract abnormalities and/or obstruction may permit ascending infection of E. coli strains with lower adhesive ability.

Bacterial characteristics and glycemic control in diabetic patients with Escherichia coli urinary tract infection

BACKGROUND Patients with diabetes mellitus have an increased risk of infection. The roles of bacterial characteristics and glycemic control in diabetic patients with Escherichia coli infection have not been well investigated. The aims of this study were to examine the bacterial characteristics and glycemic control in diabetic patients with E. coli infections arising in the urinary tract. METHODS A total of 271 E. coli isolates were collected from urine and bloodstream. Phylogenetic groups, the presence of virulence genes, and antimicrobial susceptibility of E. coli isolates were determined. RESULTS There were few differences in E. coli bacterial characteristics between 190 diabetic and 81 nondiabetic patients. In diabetic patients with urosepsis, there was a higher hemoglobin A(1C) level, and the related E. coli strains had more neuA, papG II, afa and hlyA genes, and a lower prevalence of antimicrobial resistance to cephalosporins and fluoroquinolones than those with asymptomatic bacteriuria and urinary tract infection. Multivariate logistic regression analysis revealed that increased hemoglobin A(1C) and presence of papG II and afa genes were independent factors associated with development of urosepsis in diabetic patients. CONCLUSION This study demonstrated that more virulent E. coli isolates, especially with papG II and afa genes, and poorer glycemic control were important determinants for development of urosepsis in diabetic patients.

Clinical and Microbiological Characteristics of Community-Acquired Staphylococcus lugdunensis Infections in Southern Taiwan

ABSTRACT Most Staphylococcus lugdunensis strains (49/59, 83%) were related to clinical infections, were susceptible to most antimicrobial agents with an overall oxacillin-resistant rate of 5% (3/58), and carried relatively great genetic diversity. Community-acquired infections (41/49, 84%) were dominant, often developed in patients with comorbidity, and had rather benign clinical courses without mortality.

Early identification of microorganisms in blood culture prior to the detection of a positive signal in the BACTEC FX system using matrix-assisted laser desorption/ionization–time of flight mass spectrometry

BACKGROUND Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is a valuable method for rapid identification of blood stream infection (BSI) pathogens. Integration of MALDI-TOF MS and blood culture system can speed the identification of causative BSI microorganisms. MATERIALS AND METHODS We investigated the minimal microorganism concentrations of common BSI pathogens required for positive blood culture using BACTEC FX and for positive identification using MALDI-TOF MS. The time to detection with positive BACTEC FX and minimal incubation time with positive MALDI-TOF MS identification were determined for earlier identification of common BSI pathogens. RESULTS The minimal microorganism concentrations required for positive blood culture using BACTEC FX were >10(7)-10(8) colony forming units/mL for most of the BSI pathogens. The minimal microorganism concentrations required for identification using MALDI-TOF MS were > 10(7) colony forming units/mL. Using simulated BSI models, one can obtain enough bacterial concentration from blood culture bottles for successful identification of five common Gram-positive and Gram-negative bacteria using MALDI-TOF MS 1.7-2.3 hours earlier than the usual time to detection in blood culture systems. CONCLUSION This study provides an approach to earlier identification of BSI pathogens prior to the detection of a positive signal in the blood culture system using MALDI-TOF MS, compared to current methods. It can speed the time for identification of BSI pathogens and may have benefits of earlier therapy choice and on patient outcome.

Identification of Escherichia coli Genes Associated with Urinary Tract Infections

ABSTRACT Escherichia coli is the most common cause of urinary tract infections (UTIs). E. coli genes epidemiologically associated with UTIs are potentially valuable in developing strategies for treating and/or preventing such infections as well as differentiating uropathogenic E. coli from nonuropathogenic E. coli. To identify E. coli genes associated with UTIs in humans, we combined microarray-based and PCR-based analyses to investigate different E. coli source groups derived from feces of healthy humans and from patients with cystitis, pyelonephritis, or urosepsis. The cjrABC-senB gene cluster, sivH, sisA, sisB, eco274, and fbpB, were identified to be associated with UTIs. Of these, cjrABC-senB, sisA, sisB, and fbpB are known to be involved in urovirulence in the mouse model of ascending UTI. Our results provide evidence to support their roles as urovirulence factors in human UTIs. In addition, the newly identified UTI-associated genes were mainly found in members of phylogenetic groups B2 and/or D.

Urinary Macrophage Migration Inhibitory Factor Serves as a Potential Biomarker for Acute Kidney Injury in Patients with Acute Pyelonephritis

Conventional markers of kidney function that are familiar to clinicians, including the serum creatinine and blood urea nitrogen levels, are unable to reveal genuine injury to the kidney, and their use may delay treatment. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine, and the predictive role and pathogenic mechanism of MIF deregulation during kidney infections involving acute kidney injury (AKI) are not currently known. In this study, we showed that elevated urinary MIF levels accompanied the development of AKI during kidney infection in patients with acute pyelonephritis (APN). In addition to the MIF level, the urinary levels of interleukin (IL)-1β and kidney injury molecule (KIM)-1 were also upregulated and were positively correlated with the levels of urinary MIF. An elevated urinary MIF level, along with elevated IL-1β and KIM-1 levels, is speculated to be a potential biomarker for the presence of AKI in APN patients.