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According to the new definition of septic shock, vasopressor therapy and hyperlactatemia are essential for diagnosis. However, there is controversy regarding the cutoff value for lactate, and prognostic factors in patients with septic shock and hypolactatemia. This study evaluated the prognostic significance of the cutoff value for lactate level in septic shock patients.

The purpose of our study was to investigate the timing of continuous renal replacement therapy (CRRT) application, based on the interval between the start of early goal-directed therapy (EGDT) and CRRT initiation, to ascertain whether the timing was an independent predictor of mortality in patients with septic acute kidney injury (AKI).

A sudden increase in vancomycin-resistant enterococci (VRE) infections was noted in 1998 in a tertiary care hospital in Korea. All of the VRE isolated in 1998 in the hospital were VanA type and most were multidrugresistant Enterococcus faecium. The increase in VRE was probably due to the increased use of oral vancomycin to treat Clostridium difficileinfections and clonal as well as horizontal spread. More restricted oral vancomycin use and stricter infection control measures are required to achieve a better control of the spread of VRE.

Objective.To compare the characteristics and risk factors for surgical site infections (SSIs) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in a nationwide survey, using shared case detection and recording systems.Design.Retrospective cohort study.Setting.Twenty-six hospitals participating in the Korean Nosocomial Infections Surveillance System (KONIS).Patients.From 2006 to 2009, all patients undergoing THA and TKA in KONIS were enrolled.Results.SSI occurred in 161 (2.35%) of 6,848 cases (3,422 THAs and 3,426 TKAs). Pooled mean SSI rates were 1.69% and 2.82% for THA and TKA, respectively. Of the cases we examined, 42 (26%) were superficial-incisional SSIs and 119 (74%) were “severe” SSIs; of the latter, 24 (15%) were deep-incisional SSIs and 95 (59%) were organ/space SSIs. In multivariate analysis, a duration of preoperative hospital stay of greater than 3 days was a risk factor for total SSI after both THA and TKA. Diabetes mellitus, revision surgery, prolonged duration of surgery (above the 75th percentile), and the need for surgery due to trauma were independent risk factors for total and severe SSI after THA, while male sex and an operating room without artificial ventilation were independent risk factors for total and severe SSI after TKA. A large volume of surgeries (more than 10 procedures per month) protected against total and severe SSI, but only in patients who underwent TKA.Conclusions.Risk factors for SSI after arthroplasty differ according to the site of the arthroplasty. Therefore, clinicians should take into account the site of arthroplasty in the analysis of SSI and the development of strategies for reducing SSI.

Red blood cell distribution width (RDW) is known to be a predictor of severe morbidity and mortality in some chronic diseases such as congestive heart failure. However, to our knowledge, little is known about RDW as a predictor of mortality in patients with Gram-negative bacteremia, a major nosocomial cause of intra-abdominal infections, urinary tract infections, and primary bacteremia. Therefore, we investigated whether RDW is an independent predictor of mortality in patients with Gram-negative bacteremia. Clinical characteristics, laboratory parameters, and outcomes of 161 patients with Gram-negative bacteremia from November 2010 to March 2011 diagnosed at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea, were retrospectively analyzed. The main outcome measure was 28-day all-cause mortality. The 28-day mortality rate was significantly higher in the increased RDW group compared with the normal RDW group (P< 0.001). According to multivariate Cox proportional hazard analysis, RDW levels at the onset of bacteremia (per 1 increase, P= 0.036), the Charlson index (per 1-point increase, P< 0.001), and the Sequential Organ Failure Assessment score (per 1-point increase, P= 0.001) were independent risk factors for 28-day mortality. Moreover, the nonsurvivor group had significantly higher RDW levels 72 h after the onset of bacteremia than did the survivor group (P= 0.001). In addition, the area under the curve of RDW at the onset of bacteremia, the 72-h RDW, and the Sequential Organ Failure Assessment score for 28-day mortality were 0.764 (P= 0.001), 0.802 (P< 0.001), and 0.703 (P= 0.008), respectively. Red blood cell distribution width at the onset of bacteremia was an independent predictor of mortality in patients with Gram-negative bacteremia. Also, 72-h RDW could be a predictor for all-cause mortality in patients with Gram-negative bacteremia.

Objective.To evaluate the risk factors for surgical site infection (SSI) after gastric surgery in patients in Korea.Design.A nationwide prospective multicenter study.Setting.Twenty university-affiliated hospitals in Korea.Methods.The Korean Nosocomial Infections Surveillance System (KONIS), a Web-based system, was developed. Patients in 20 Korean hospitals from 2007 to 2009 were prospectively monitored for SSI for up to 30 days after gastric surgery. Demographic data, hospital characteristics, and potential perioperative risk factors were collected and analyzed, using multivariate logistic regression models.Results.Of the 4,238 case patients monitored, 64.9% (2,752) were male, and mean age (±SD) was 58.8 (±12.3) years. The SSI rates were 2.92, 6.45, and 10.87 per 100 operations for the National Nosocomial Infections Surveillance system risk index categories of 0, 1, and 2 or 3, respectively. The majority (69.4%) of the SSIs observed were organ or space SSIs. The most frequently isolated microorganisms were Staphylococcus aureusand Klebsiella pneumoniae. Male sex (odds ratio [OR], 1.67 [95% confidence interval (CI), 1.09–2.58]), increased operation time (1.20 [1.07–1.34] per 1-hour increase), reoperation (7.27 [3.68–14.38]), combined multiple procedures (1.79 [1.13–2.83]), prophylactic administration of the first antibiotic dose after skin incision (3.00 [1.09–8.23]), and prolonged duration (≥7 days) of surgical antibiotic prophylaxis (SAP; 2.70 [1.26–5.64]) were independently associated with increased risk of SSI.Conclusions.Male sex, inappropriate SAP, and operation-related variables are independent risk factors for SSI after gastric surgery.

The plasma level of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) has been shown to be helpful in identifying critically ill patients with infection. However, it remains unknown whether it can be used to predict prognosis in patients with severe sepsis. This study investigated whether various inflammatory mediators, including sTREM-1, could be used as reliable markers to predict the prognosis of patients receiving early goal-directed therapy (EGDT). We prospectively enrolled patients 18 years or older with severe sepsis from April 2009 to May 2010 at a 2,000-bed university hospital. Patients were eligible if the initial resuscitation according to EGDT protocol was immediately performed at the emergency department. Plasma sTREM-1, C-reactive protein, and procalcitonin concentrations were measured on days 0, 3, 7, and 14. Soluble TREM-1 concentrations were significantly higher at admission and pre-EGDT in nonsurvivors (n = 16) than in survivors (n = 47) (514.1 pgmL interquartile range, 412.7–1,749.5 pgmL vs. 182.4 pgmL interquartile range, 54.3–327.0 pgmL; P= 0.001). Procalcitonin and C-reactive protein levels did not significantly differ, whereas central venous oxygen saturation and lactate levels at admission were significantly different between the two groups. The only sTREM-1 level remained significantly higher in nonsurvivors until death. On multivariate regression analysis, log(sTREM-1) (P= 0.028), central venous oxygen saturation (P= 0.022), and Simplified Acute Physiology Score II (P= 0.048) values at admission were independently significant. These results suggest that plasma sTREM-1 level at admission could be used as a marker to identify patients with a poor prognosis despite complete initial resuscitation in severe sepsis.

Objective.To describe the incidence of recovery of both vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus(MRSA) from culture of a single clinical specimen, to describe the clinical characteristics of patients from whom these specimens were recovered, and to identify the risk factors of these patients.Design.A retrospective cohort and case-control study.Setting.A tertiary care university hospital and referral center in Seoul, Korea.Methods.We identified 61 case patients for whom a single clinical specimen yielded both VRE and MRSA on culture, and 122 control patients for whom any clinical specimen yielded only VRE on culture. The control patients were selected by matching 2 :1 with the case patients for age, sex, and first date of sampling that led to isolation of VRE or both VRE and MRSA among 1,536 VRE-colonized patients from January 1, 2003, through December 31, 2006. To identify patient risk factors for the recovery of both VRE and MRSA in a single clinical specimen, we performed univariate comparisons between the 2 groups and then multivariate logistic regression analysis.Results.The incidence of recovery of both VRE and MRSA from culture of a single clinical specimen was 3.97% (for 61 of 1,536 VRE-colonized patients) over 4 years. Among these 82 single clinical specimens, the most common type was wound specimens (26.8%), followed by lower respiratory tract specimens (18.3%), urine specimens (17.1%), and catheter tips (15.9%). Of the 61 case patients, 14 (23.0%) had 2 or more single clinical specimens that yielded both VRE and MRSA on culture, and the longest interval from the first sampling that yielded both organisms to the last sampling that yielded both was 174 days. Independent patient risk factors for the presence of both VRE and MRSA in a single clinical specimen were chronic renal disease (odds ratio [OR], 7.00; P= .012), urinary catheterization (OR, 3.36; P= .026), and longer total cumulative duration of hospital stay within the previous year (OR, 1.03; P< .001).Conclusion.We confirmed that the recovery of VRE and MRSA from a single clinical specimen occurs continually. Because prolonged cell-to-cell contact can facilitate transfer of vanA,close observation and surveillance for vancomycin-resistant S. aureus, especially among patients with risk factors for the recovery of both VRE and MRSA from a single clinical specimen, should be continued.

Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. Recent studies have shown that the VEGF levels increase in several cell types, for example, macrophages and smooth muscle cells after LPS stimulation, suggesting that it is important in the initiation and development of sepsis. In particular, LPS-regulated contractility in lung pericytes may play an important role in mediating pulmonary microvascular fluid hemodynamics during sepsis. This study investigated the production of VEGF by rat lung pericytes in response to LPS. LPS was found to enhance VEGF mRNA expression in a concentration-dependent manner peaking 2 h after stimulation in pericytes. Vascular endothelial growth factor protein levels in conditioned medium and in cell lysate also increased on increasing LPS and peaked after 24 to 48 h. LPS also significantly augmented iNOS expression in lung pericytes within 6 h. However, iNOS mRNA induction occurred later than LPS-induced VEGF mRNA increases. Interestingly, attempted inhibition with nuclear factor-B or tyrosine kinase did not suppress LPS-induced augmented VEGF mRNA expression in lung pericytes, although both inhibitors markedly inhibited LPS-induced iNOS mRNA expression. SB203580, a p38 MAP kinase inhibitor, repressed LPS-induced VEGF mRNA expression. Furthermore, LPS stimulated a rapid and sustained phosphorylation of p38 MAP kinase. These results show that pericytes produce VEGF in response to LPS stimulation, and that this may be partly mediated by the p38 MAP kinase pathway. More research should be done to establish the regulation of capillary hemodynamics and identify mechanisms of their regulation.

Pathogens pose a significant threat to humans, animals, and plants. Consequently, a considerable effort has been devoted to developing rapid, convenient, and accurate assays for the detection of these unfavorable organisms. Recently, DNA-microarray based technology is receiving much attention as a powerful tool for pathogen detection. After the target gene is first selected for the unique identification of microorganisms, species-specific probes are designed through bioinformatic analysis of the sequences, which uses the information present in the databases. DNA samples, which were obtained from reference and/or clinical isolates, are properly processed and hybridized with species-specific probes that are immobilized on the surface of the microarray for fluorescent detection. In this study, we review the methods and strategies for the development of DNA microarray for pathogen detection, with the focus on probe design.

Abstract:  A sudden increase in vancomycin-resistant enterococci (VRE) infections was noted in 1998 in a tertiary care hospital in Korea. All of the VRE isolated in 1998 in the hospital were VanA type and most were multidrug-resistant Enterococcus faecium. The increase in VRE was probably due to the increased use of oral vancomycin to treat Clostridium difficile infections and clonal as well as horizontal spread. More restricted oral vancomycin use and stricter infection control measures are required to achieve a better control of the spread of VRE.

Carbapenem-resistant Acinetobacter spp. used to be rare, but are increasingly isolated in Korea. Among 28 isolates of imipenem-resistant Acinetobacter spp. found in a Korean hospital in 1998 and 1999, 14 produced metallo-beta-lactamases. The bla(VIM-2) gene was detected, by PCR, in 11 and two isolates of Acinetobacter baumannii and Acinetobacter genomospecies 3, respectively, and bla(IMP-1) in one isolate of A. baumannii. The MICs of imipenem for the isolates were 8-32 mg/L. PFGE analysis of SmaI-digested genomic DNA gave identical patterns in eight of 11 bla(VIM-2)-positive A. baumannii isolates from respiratory specimens of ICU patients. The bla(VIM-2) gene cassettes in the isolates are identical to those from Pseudomonas aeruginosa isolates in Europe, but are inserted into new class I integrons In105 and In106. The attC site of the last cassette of the array in In106 is interrupted by the insertion of a putative class II intron. This is the first report of VIM-2 beta-lactamase-producing A. baumannii and Acinetobacter genomospecies 3. Production of the VIM-2 enzyme presents an emerging threat of carbapenem resistance among Acinetobacter spp. in Korea.

We investigated the phenotypic and genetic properties of metallo-beta-lactamase-producing Pseudomonas isolates collected at a tertiary-care hospital in Korea since 1995. The prevalence of imipenem resistance among Pseudomonas aeruginosa isolates reached 16% in 1997, when 9% of the resistant organisms were found to produce VIM-2 beta-lactamase, a class B enzyme previously found only in P. aeruginosa isolates from Europe. VIM-2-producing isolates of Pseudomonas putida were also detected. Resistance was transferable from both these species to P. aeruginosa PAO4089Rp by filter mating, although the resistance determinant could not be found on any detectable plasmid. Serotyping showed that many of the VIM-2-producing P. aeruginosa isolates belonged to serotypes O:11 and O:12, and pulsed-field gel electrophoresis of XbaI-digested genomic DNA revealed that many had identical profiles, whereas the P. putida isolates were diverse. Sequencing showed that the bla(VIM-2) genes resided as cassettes in class 1 integrons. In contrast to previous VIM-encoding integrons, the integron sequenced from a P. aeruginosa isolate had bla(VIM) located downstream of a variant of aacA4. bla(VIM) also lay in a class 1 integron in a representative P. putida strain, but the organization of this integron was different from that sequenced from the P. aeruginosa strain. In conclusion, the metallo-beta-lactamase produced by these imipenem-resistant Pseudomonas isolates was VIM-2, and the accumulation of producers reflected clonal dissemination as well as horizontal spread. Strict measures are required in order to control a further spread of resistance.

ABSTRACTWe investigated the phenotypic and genetic properties of metallo-β-lactamase-producing Pseudomonasisolates collected at a tertiary-care hospital in Korea since 1995. The prevalence of imipenem resistance among Pseudomonas aeruginosaisolates reached 16% in 1997, when 9% of the resistant organisms were found to produce VIM-2 β-lactamase, a class B enzyme previously found only in P. aeruginosaisolates from Europe. VIM-2-producing isolates of Pseudomonas putidawere also detected. Resistance was transferable from both these species to P. aeruginosaPAO4089Rp by filter mating, although the resistance determinant could not be found on any detectable plasmid. Serotyping showed that many of the VIM-2-producing P. aeruginosaisolates belonged to serotypes O:11 and O:12, and pulsed-field gel electrophoresis of XbaI-digested genomic DNA revealed that many had identical profiles, whereas the P. putidaisolates were diverse. Sequencing showed that the blaVIM-2genes resided as cassettes in class 1 integrons. In contrast to previous VIM-encoding integrons, the integron sequenced from a P. aeruginosaisolate had blaVIMlocated downstream of a variant of aacA4. blaVIMalso lay in a class 1 integron in a representative P. putidastrain, but the organization of this integron was different from that sequenced from the P. aeruginosastrain. In conclusion, the metallo-β-lactamase produced by these imipenem-resistant Pseudomonasisolates was VIM-2, and the accumulation of producers reflected clonal dissemination as well as horizontal spread. Strict measures are required in order to control a further spread of resistance.

ABSTRACTWe retrospectively analyzed the performance of the Architect HIV antigen/antibody (Ag/Ab) combination assay in a tertiary health care center with a situation of low HIV prevalence. The specificity and positive predictive value (PPV) were 99.78% and 31.21%, respectively. However, the specificity and PPV could increase to 99.99% and 89.70% using an arbitrary cutoff value.

We retrospectively analyzed the performance of the Architect HIV antigen/antibody (Ag/Ab) combination assay in a tertiary health care center with a situation of low HIV prevalence. The specificity and positive predictive value (PPV) were 99.78% and 31.21%, respectively. However, the specificity and PPV could increase to 99.99% and 89.70% using an arbitrary cutoff value.

Human cytomegalovirus (HCMV) establishes a lifelong chronic latent infection and often reactivates in immunocompromised patients. In addition, HCMV reactivates in patients with sepsis or other critical illnesses, particularly in patients with poor prognoses. However, the immunological characteristics of sepsis patients with HCMV reactivation have not been elucidated. In the present study, we examined T-cell responses in severe sepsis patients with and without HCMV reactivation. First, HCMV pp65-specific T-cell functions were assessed by intracellular cytokine staining (ICS) for IFN-γ, TNF-α, and MIP-1β and by CD107a staining. We analyzed the ICS data for each function individually and found no difference between the patient groups. However, the relative frequency of polyfunctional CD8+T cells was significantly decreased in sepsis patients with HCMV reactivation. Next, we examined programmed cell death protein 1 (PD-1) expression. It was significantly increased in the CD8+T-cell population in severe sepsis patients with HCMV reactivation, indicating CD8+T-cell exhaustion. Interestingly, the frequency of PD-1+cells in the CD8+T-cell population was inversely correlated with the relative frequency of polyfunctional CD8+T cells. Herein, we demonstrate that HCMV reactivation in severe sepsis patients is associated with PD-1 expression and impaired polyfunctionality of CD8+T cells.