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We obtained nine Klebsiella pneumoniae isolates successively isolated from a single patient. Four pairs (M1–M4 and NM1–NM4) obtained simultaneously from the same site showed different colony types, mucoid and non-mucoid, while the final isolate (M5) was isolated alone from the blood and showed a mucoid phenotype. The whole genome of isolate M5 was sequenced de novo using the PacBio RSII system, while the others were sequenced with an Illumina Hiseq4000 and mapped to the genome sequences of M5. To identify insertions or deletions in the cps locus, we amplified and sequenced cps locus genes. We identified insertion sequence (IS) elements in several genes of the cps locus or one amino acid substitution in WcaJ in all non-mucoid isolates. Five additional amino acid alterations in RpsJ, LolE, Lon-2, PpsE, and a hypothetical protein were detected in some mucoid and non-mucoid isolates. Based on the genome data and cps locus sequences, the mucoid phenotype may have been lost or converted into the non-mucoid phenotype because of the insertion of IS elements or amino acid alterations at this locus. We inferred a within-host evolutionary scenario, in which non-mucoid variants emerged repeatedly from mucoid isolates, but may be short-lived because of their low fitness. [ABSTRACT FROM AUTHOR]

Abstract Recently, we have identified an extensively drug-resistant (XDR) Streptococcus pneumoniae serotype 15A isolate from a patient with bacterial meningitis. It belonged to sequence type 8279 (ST8279), a clone identified as XDR serotype 11A isolated in South Korea. We obtained and compared the genome sequences of an XDR 15A and an XDR 11A isolate. The genomes of two XDR isolates were highly identical, except for the capsular polysaccharide (cps) locus and another small region. Capsular switching from 11A to 15A may have occurred via recombination of the cps locus. The emergence of a new XDR clone via capsular switching would be a great concern for public health and in clinical settings. [ABSTRACT FROM AUTHOR]

• Rooms of patients with Middle East respiratory syndrome (MERS) were disinfected. • Environmental disinfection was performed after the 2015 Korean MERS outbreak. • Sodium hypochlorite and hydrogen peroxide vapor were used. • Vancomycin-resistant Enterococcus significantly decreased for 2 months. • Other multidrug-resistant organisms did not decrease. Environmental disinfection with sodium hypochlorite and hydrogen peroxide vapor was performed after a hospital-associated outbreak of Middle East respiratory syndrome. Although only 11% of total beds were disinfected, the isolation and vancomycin-resistance rates of Enterococcus spp significantly decreased for 2 months, whereas other multidrug-resistant organisms did not. [ABSTRACT FROM AUTHOR]

Objectives: Invasive fungal infections (IFIs) cause significant morbidity and mortality among recipients of hematopoietic stem cell transplantation (HSCT). Although fluconazole is used widely as an antifungal prophylactic agent in these patients, it is not reliably effective against mold infection including invasive aspergillosis. Micafungin provides antifungal activity against Candida and Aspergillus species, and previous studies have demonstrated its efficacy when used as a prophylactic agent for fungal infection in neutropenic patients. Here, we evaluated and compared the incidence of proven or probable IFIs after antifungal prophylaxis using micafungin or fluconazole.Methods: This was a prospective, single-center, phase II study involving adult patients who received allogeneic or autologous HSCT. Patients were randomly assigned to micafungin or fluconazole arms in a ratio of 2:1, and the treatment was initiated within 24 h of HSCT and maintained for up to 21 days. The primary end point was the incidence of proven or probable IFIs during the 100 days after HSCT. The secondary end points were the incidence rates of possible, proven, or probable IFIs, need to change the antifungal agent before engraftment, IFI-related mortality, and survival within 100 days after transplantation.Results: Between March 2010 and May 2015, a total of 257 patients were enrolled. After exclusion of seven patients who did not receive at least one dose of a study treatment, 250 patients (micafungin, n = 165; fluconazole, n = 85) were included in the analysis of clinical efficacy. The median age was 47 years (range, 20-64). Allogeneic and autologous transplantations were performed in 56.0% (n = 140) and 44.0% (n = 110) of the patients, respectively. Baseline characteristics were well balanced between the two groups. Overall, the incidence of proven and probable IFIs within 100 days of HSCT was 7.6% (n = 19). The percentages of patients who experienced proven or probable IFIs did not differ significantly between the micafungin and fluconazole groups: 7.3% and 8.2%, respectively (p = 0.786). Thirteen patients in the micafungin arm (7.9%) and eight patients in the fluconazole arm (9.4%) needed a change in antifungal agent before engraftment (p = 0.824). Mortality within 100 days after HSCT did not differ significantly between groups: 9.1% vs 12.9% in the micafungin and fluconazole arms, respectively (p = 0.345).Conclusion: Micafungin is comparable to fluconazole for the prevention of IFIs in HSCT recipients. [ABSTRACT FROM AUTHOR]

Background: After the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea, prediction of pneumonia development and progression to respiratory failure was emphasized in control of MERS outbreak.Methods: MERS-CoV infected patients who were managed in a tertiary care center during the 2015 Korean MERS outbreak were reviewed. To analyze predictive factors for pneumonia development and progression to respiratory failure, we evaluated clinical variables measured within three days from symptom onset.Results: A total of 45 patients were included in the study: 13 patients (28.9%) did not develop pneumonia, 19 developed pneumonia without respiratory failure (42.2%), and 13 progressed to respiratory failures (28.9%). The identified predictive factors for pneumonia development included age ≥45 years, fever ≥37.5 °C, thrombocytopenia, lymphopenia, CRP ≥ 2 mg/dL, and a threshold cycle value of PCR less than 28.5. For respiratory failure, the indicators included male, hypertension, low albumin concentration, thrombocytopenia, lymphopenia, and CRP ≥ 4 mg/dL (all P < 0.05). With ≥ two predictive factors for pneumonia development, 100% of patients developed pneumonia. Patients lacking the predictive factors did not progress to respiratory failure.Conclusion: For successful control of MERS outbreak, MERS-CoV infected patients with ≥ two predictive factors should be intensively managed from the initial presentation. [ABSTRACT FROM AUTHOR]

Objectives: The galactomannan (GM) test is a useful method for early diagnosis of invasive aspergillosis. Recently, multiple myeloma has newly been suggested to be related to false-positive results of GM. We performed a case-control study to validate this finding.Methods: Electronic medical records were reviewed for patients admitted March through June 2014. Patients with false-positive GM results were selected as cases and those with negatives as controls. To verify the results of the four-month analysis, additional analysis was performed in multiple myeloma patients over a three-year period.Results: There were 30 false-positive and 316 negative cases during the four-month period. Among the factors evaluated, multiple myeloma was the only significant factor in the adjusted analysis (OR = 3.59, CI 1.28-10.04). In the three-year analysis of 145 multiple myeloma patients, 25.5% showed false-positive results, which was 3 times higher than overall. GM false-positivity was not related to serum monoclonal protein level or type of immunoglobulin. GM optical density indexes (ODIs) in all false positives were lower than 3.0.Conclusions: Multiple myeloma was a major cause of GM false-positivity in adult cancer patients. GM was false-positive in 25.5% of multiple myeloma patients with GM ODIs lower than 3.0. [ABSTRACT FROM AUTHOR]

Objectives Although pyogenic vertebral osteomyelitis (PVO) with no identified microorganism is treated empirically, the clinical outcome is not well understood. Methods We conducted a retrospective review of patients with PVO at a tertiary-care hospital from 2000 through 2012. The study compared clinical features and outcomes of microbiologically confirmed (M-PVO) with clinically diagnosed PVO (C-PVO). Results Of 151 patients with PVO, 75 (49.7%) had M-PVO. Compared to patients with M-PVO, patients with C-PVO had fewer underlying medical conditions. In addition, they presented less frequently with fever, high acute-phase reactants levels, and paraspinal abscess. The rate of treatment failure tended to be lower in the C-PVO group [9.2% (7/76) vs. 17.3% (13/75); p = 0.157]. The overall relapse rate was 6.6% and did not differ significantly between groups; notably this rate was higher in patients who received antibiotics for ≤6 weeks [18.8% (3/16)] and ≤8 weeks [12.1% (4/33)]. The independent risk factors for treatment failure were higher CRP levels [odds ratio (OR) = 1.087; 95% confidence interval (CI): 1.025–1.153; p = 0.005] and fever ≥37.8°C (OR = 8.556; 95% CI: 2.273–32.207; p = 0.002). Conclusions Patients with C-PVO had less systemic inflammatory response and a more favorable outcome compared to M-PVO. Prolonged antibiotic therapy, for at least 8 weeks, might be required for C-PVO, as well as for M-PVO until better outcomes are assured. [ABSTRACT FROM AUTHOR]

Summary: Objective: This study was performed to identify risk factors for the development of bacteremic pneumonia and to evaluate the impact of bacteremia on the outcome of pneumococcal pneumonia. Methods: Using a database from a surveillance study of community-acquired pneumococcal pneumonia, we compared data of the bacteremic group with that of the non-bacteremic group. Results: Among 981 adult patients with pneumococcal pneumonia, 114 (11.6%) patients who had documented pneumococcal bacteremia were classified into the bacteremic group. In a multivariable analysis, use of immunosuppressant drugs, younger age (<65 years), and DM were independent risk factors associated with the development of bacteremic pneumonia among patients with pneumococcal pneumonia (all P < 0.05). The mortality rate was significantly higher in the bacteremic group than in the non-bacteremic group (28.6% vs. 8.5%; P < 0.001). The multivariable analysis revealed that concomitant bacteremia was one of the significant risk factors associated with mortality (OR, 2.57; 95% CI, 1.24–5.29), along with cerebrovascular disease and presentation with septic shock (all P < 0.05). Conclusions: Bacteremia was a common finding in pneumococcal pneumonia and was associated with a higher mortality rate. Several clinical variables may be useful for predicting bacteremic pneumonia among patients with pneumococcal pneumonia. [ABSTRACT FROM AUTHOR]

Abstract: The identification of clinical characteristics that could identify patients at high risk for Pseudomonas aeruginosa or Acinetobacter baumannii bacteremia would aid clinicians in the appropriate management of these life-threatening conditions, especially in patients admitted to the emergency department (ED) with community-onset infections. To determine clinical risk factors for P aeruginosa or A baumannii bacteremia in patients with community-onset gram-negative bacteremia (GNB), a post hoc analysis of a nationwide bacteremia surveillance database including patients with microbiologically documented GNB was performed. Ninety-six patients with P aeruginosa or A baumannii bacteremia were compared with 1230 patients with Escherichia coli or Klebsiella pneumoniae bacteremia. A solid tumor or hematologic malignancy was more likely to be associated with P aeruginosa or A baumannii bacteremia, whereas concurrent neurologic disease was less frequently seen. In regards to the site of infection, pneumonia was more common in P aeruginosa or A baumannii bacteremia, whereas a urinary tract infection was less frequently seen. Factors associated with P aeruginosa or A baumannii bacteremia in multivariate analysis included pneumonia (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.86-6.99), hematologic malignancy (OR, 2.71; 95% CI, 1.26-5.84), male sex (OR, 2.17; 95% CI, 1.31-3.58), solid tumor (OR, 1.89; 95% CI, 1.15-3.12), and health-care–associated infection (OR, 1.88; 95% CI, 1.48-2.41). Our data suggest that an initial empirical antimicrobial coverage of P aeruginosa or A baumannii bacteremia should be seriously considered in patients with pneumonia, a hematologic malignancy, solid tumor, or health-care–associated infection, when GNB is suspected, even in community-onset infections. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This study was performed to evaluate clinical features of community-onset Enterobacter bacteremia and determine the risk factors for Enterobacter bacteremia among patients admitted to the emergency department. Methods: A post hoc analysis of a nationwide surveillance database of bacteremia was performed. A total of 53 patients with community-onset Enterobacter bacteremia were compared with 882 patients with Escherichia coli bacteremia. Results: As for the underlying disease, solid tumor was more likely common in Enterobacter bacteremia than in E coli bacteremia (39.6% [21/53] vs 19.7% [174/882], P < .001). Neutropenia, indwelling urinary catheter, and tube insertion were significantly more common in Enterobacter bacteremia than in E coli bacteremia (all Ps < .05). As for the site of infection, lung and abdomen were more likely common in Enterobacter bacteremia than in E coli bacteremia, whereas urinary tract was less likely frequent in Enterobacter bacteremia than in E coli bacteremia (all Ps < .05). In the multivariate analysis, pneumonia, tube insertion, solid tumor, and health care–associated infection were found to be significantly associated with Enterobacter bacteremia (all Ps < .05). Conclusions: Enterobacter species were important pathogens among community-onset gram-negative bacteremia, in association with health care–associated infections. Pneumonia, tube insertion, solid tumor, and health care–associated infections were found to be significantly associated with Enterobacter bacteremia. [Copyright &y& Elsevier]

Summary: Objective: The purpose of this study was to evaluate clinical features and outcomes of bacteremia in patients with liver cirrhosis (LC) and determine whether underlying LC is an independent risk factor for mortality in a population of patients with different underlying diseases. Methods: From the database of nationwide surveillance studies for bacteremia, data regarding bacteremia in patients with LC were analyzed and compared with those in patients with other diseases. Results: A total of 195 patients with LC were compared with 1659 patients with other underlying diseases. As for the site of infection, intraabdominal infection was more frequent in the LC group (P < 0.001), while pneumonia, urinary tract bacteremia, and primary bacteremia were more prevalent in the other diseases group (all P < 0.05). Patients with LC were more likely to have Klebsiella pneumoniae bacteremia (20.1% vs. 14.3%, P = 0.018), but less likely to have coagulase-negative staphylococcal bacteremia (5.1% vs. 10.4%, P = 0.028). The 30-day mortality rate was significantly higher in the LC group compared to the other disease group (27.2% [53/195] vs. 20.3% [336/1659], P = 0.025). Multivariate analysis revealed underlying LC as a significant predictor for mortality (OR, 2.11; 95% CI, 1.43–3.13; P < 0.001), along with old age, nosocomial acquisition, pneumonia, severe sepsis, and a higher Pitt bacteremia score. Conclusions: The mortality rate of patients with LC was significantly higher than that of patients with other diseases when they developed bacteremia. Underlying LC was found to be one of the independent risk factors for mortality in patients with bacteremia. [ABSTRACT FROM AUTHOR]

Summary: Objectives: This study was performed to identify risk factors in Pseudomonas aeruginosa bacteremia among Gram-negative bacterial infections in non-neutropenic patients with solid tumor. Methods: A case–control study was performed to identify clinical predictors for P. aeruginosa bacteremia among non-neutropenic patients with Gram-negative bacteremia. Each case of P. aeruginosa bacteremia was matched to one or two controls with Escherichia coli, Klebsiella, Enterobacter or Citrobacter species in non-neutropenic patients with solid tumor. Results: Seventy-eight patients with P. aeruginosa bacteremia were compared with 98 control patients who had other Gram-negative bacteremias. The most common types of cancer were biliary tract cancer (49/176, 27.8%) and hepatocellular carcinoma (38/176, 21.6%), followed by gastric and bladder cancer. Factors associated with development of P. aeruginosa bacteremia were the presence of lung cancer, percutaneous tubes, nosocomial exposure, an invasive procedure and previous antimicrobial therapy (all P < 0.05). Independent risk factors for P. aeruginosa bacteremia included the presence of lung cancer and previous antimicrobial therapy. In the subgroup analysis including 90 patients with community-onset bacteremia, the previous use of antimicrobial agents and presence of bladder cancer were independent factors significantly associated with P. aeruginosa bacteremia. Conclusions: Underlying lung cancer and previous antimicrobial treatment were significantly associated with P. aeruginosa bacteremia in non-neutropenic patients with solid tumor. P. aeruginosa should be considered as a probable cause of Gram-negative bacteremia in this patient group. [ABSTRACT FROM AUTHOR]

Background: Although hospital-acquired infections presumably may have a poorer prognosis than community-onset infections because of unanticipated antimicrobial resistance, little data are available on the clinical and microbiological characteristics of hospital-acquired versus community-onset urinary tract–related bacteremia cases. Methods: Data were collected from a nationwide database of surveillance for bacteremia. Data from patients with hospital-acquired urinary tract–related bacteremia were compared with those with community-onset bacteremia. Results: Of 398 patients with urinary tract–related bacteremia, 71 (17.8%) had hospital-acquired infection, and the remaining 327 (82.2%) had community-onset infection. Although Escherichia coli was the most common isolate identified, pathogens other than E coli were more frequently isolated in hospital-acquired infections than in community-onset infections (46.5% vs 19.3%). Among E coli isolates causing hospital-acquired infections, 26.3% (10 of 38) were resistant to extended-spectrum cephalosporins (ESCs), whereas among E coli isolates causing community-onset infections, only 6.1% (16 of 264) were ESC-resistant. Hospital-acquired infection had a significantly higher mortality rate than community-onset infection (21.1% [15 of 71] vs 8.3% [27 of 327]; P = .004). Multivariate analysis identified nosocomial acquisition as a significant independent risk factor for mortality, along with severe sepsis, underlying solid tumor, ESC resistance, and high Pitt bacteremia score (all P < .05). Conclusion: Hospital-acquired urinary tract–related bacteremia has a poorer prognosis than community-onset bacteremia. The ESC-resistant nature of gram-negative bacilli, which may be more common in nosocomial isolates than in community isolates, adversely affects the outcome of urinary tract–related bacteremia. [ABSTRACT FROM AUTHOR]

Background: Although hospital-acquired infections presumably may have a poorer prognosis than community-onset infections because of unanticipated antimicrobial resistance, little data are available on the clinical and microbiological characteristics of hospital-acquired versus community-onset urinary tract–related bacteremia cases. Methods: Data were collected from a nationwide database of surveillance for bacteremia. Data from patients with hospital-acquired urinary tract–related bacteremia were compared with those with community-onset bacteremia. Results: Of 398 patients with urinary tract–related bacteremia, 71 (17.8%) had hospital-acquired infection, and the remaining 327 (82.2%) had community-onset infection. Although Escherichia coli was the most common isolate identified, pathogens other than E coli were more frequently isolated in hospital-acquired infections than in community-onset infections (46.5% vs 19.3%). Among E coli isolates causing hospital-acquired infections, 26.3% (10 of 38) were resistant to extended-spectrum cephalosporins (ESCs), whereas among E coli isolates causing community-onset infections, only 6.1% (16 of 264) were ESC-resistant. Hospital-acquired infection had a significantly higher mortality rate than community-onset infection (21.1% [15 of 71] vs 8.3% [27 of 327]; P = .004). Multivariate analysis identified nosocomial acquisition as a significant independent risk factor for mortality, along with severe sepsis, underlying solid tumor, ESC resistance, and high Pitt bacteremia score (all P < .05). Conclusion: Hospital-acquired urinary tract–related bacteremia has a poorer prognosis than community-onset bacteremia. The ESC-resistant nature of gram-negative bacilli, which may be more common in nosocomial isolates than in community isolates, adversely affects the outcome of urinary tract–related bacteremia. [Copyright &y& Elsevier]

Summary: Objectives: As ciprofloxacin resistance rate of Escherichia coli causing urinary tract infections has been increasing, concern about inappropriate empirical therapy has been arisen. Methods: We performed a retrospective cohort study to determine the impact of discordant empirical antimicrobial therapy on outcome of community-acquired bacteremic acute pyelonephritis. Results: Among a total of 164 cases included, ciprofloxacin was empirically used in 80.5%. The most frequent etiologic organism was E. coli (92.1%), of which 20.5% was resistant to ciprofloxacin. Discordant empirical therapy was documented in 29 cases, which included 25 cases caused by ciprofloxacin-resistant E. coli. Discordant therapy resulted in lower early clinical response rate (34.5% vs. 82.2%; P < 0.001) and longer hospital stay (13.3 days vs. 8.7 days; P = 0.002) compared to concordant therapy. However, overall mortality and clinical cure rate did not differ between two groups. Multivariate analyses showed that worse early clinical response was associated with discordant empirical therapy (OR, 11.08; 95% CI, 4.37–28.07) and presentation with septic shock (OR, 8.52; 95% CI, 1.75–41.49). Longer hospital stay was also associated with discordant empirical therapy (OR, 2.47; 95% CI, 1.04–5.84). Conclusions: Discordant empirical therapy, mostly with ciprofloxacin, leads to worse early clinical response and longer hospital stay than concordant therapy in community-acquired bacteremic acute pyelonephritis, although it does not affect on overall mortality or clinical cure rate. [ABSTRACT FROM AUTHOR]

Summary: Background: The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). Methods: From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. Results: Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35–4.74), after adjustment for other variables predicting poor prognosis. Conclusions: Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB. [ABSTRACT FROM AUTHOR]

Summary: Objective: This study was conducted to identify the predictors of mortality and to evaluate the impact of methicillin resistance on outcome in patients with Staphylococcus aureus infection according to underlying conditions and type of infection. Methods: An observational cohort study including 4949 patients with S. aureus infection was conducted. We compared data from patients with MRSA infection with those with MSSA infection. Results: The 30-day mortality rate of MRSA group was significantly higher than that of MSSA group (15.6% vs. 6.2%, P < 0.001). However, MRSA infection was not found to be independent risk factor for mortality after adjusting for other variables (OR = 1.03, 95% CI = 0.80–1.32). When we analyzed patients with S. aureus bacteremia (n = 709), MRSA infection was found to be significantly associated with mortality in multivariate analysis (Adjusted OR = 1.69, 95% CI = 1.15–2.49). When the 30-day mortality rates were compared according to underlying diseases, the 30-day mortality rate of MRSA group was significantly higher than that of MSSA group in patients with malignancy or renal diseases. MRSA infection was also found to be one of the independent risk factors for mortality in patients with malignancy (adjusted OR = 1.69, 95% CI = 1.06–2.70) and in those with renal disease (adjusted OR = 1.70, 95% CI = 1.0–2.89), after adjustment for host variables. Conclusions: Methicillin resistance adversely affected the outcome of patients with S. aureus infection, in patients with cancer or renal disease and in those with S. aureus bacteremia, although MRSA infection was not found to be significantly associated with higher mortality in overall patient population. [ABSTRACT FROM AUTHOR]

Summary: Objectives: The purpose of this study was to evaluate the impact of inappropriate antimicrobial therapy on the outcome of patients with hospital-acquired pneumonia (HAP) caused by Acinetobacter baumannii. Methods: All cases of HAP caused by A. baumannii from January 2000 to March 2006 at the Samsung Medical Center (Seoul, Korea) were analyzed retrospectively. Results: A total of 116 patients with clinically significant Acinetobacter HAP were enrolled. Among the A. baumannii isolates, 60.3% showed multi-drug resistance (MDR), 16.4% were found to have imipenem resistance, and 15.5% had pan-drug resistance (PDR). The mean APACHE II score of the patients was 22.3 ± 7.9. The overall in-hospital and pneumonia-related mortality rates were 47.4% and 37.9%, respectively. The univariate analysis showed that the factors associated with pneumonia-related mortality were: MDR, PDR, high APACHE II score, inappropriate empirical antimicrobial therapy, and inappropriate definitive antimicrobial treatment (All p < 0.05). Among these, a high APACHE II score and inappropriate definitive antimicrobial therapy were found to be independent factors associated with a high mortality, after adjustment for other variables. Conclusions: The appropriate definitive antimicrobial therapy should be provided in patients with HAP caused by A. baumannii. [ABSTRACT FROM AUTHOR]

Summary: Objective: Ciprofloxacin-resistant Escherichia coli is growing concern in clinical settings. In this study, we investigated the distribution of virulence determinants and phylogenetic groups among community-onset, ciprofloxacin-resistant E. coli isolates causing urinary tract infections (UTIs) in Korea. In addition, the evidence of clonal spread in the community was also examined. Methods: From November 2006 to August 2007, 543 community-onset E. coli isolates causing UTIs were collected as part of a multicenter surveillance study. In vitro susceptibility testing was performed using broth microdilution method. Distribution of virulence determinants and phylogenetic groupings were examined. In addition, multilocus sequence typing (MLST) analysis was performed. Results: In vitro antimicrobial susceptibility testing revealed that 154 isolates (28.4%) were ciprofloxacin-resistant. Of these, 129 ciprofloxacin-resistant E. coli isolates were further characterized. As a result of phylogenetic subgrouping, we found that phylogenetic subgroup D was the most predominant (46 isolates, 35.7%), followed by B2 (44 isolates, 34.1%), A (21 isolates, 16.3%), and B1 (18 isolates, 14.0%). MLST analysis showed 48 sequence types (STs). The most prevalent ST was ST131 (32 isolates, 24.8%), followed by ST393 (23 isolates, 17.8%). While all ST131 isolates belonged to phylogenetic subgroup B2, which is known to be a highly virulent, all ST393 isolates belonged to subgroup D. ST131 and ST393 showed different profiles of virulence factors; papA, papG allele III, and traT genes were significantly more prevalent in ST131 than in ST393 (p values, <0.001). Conclusions: Based on genotyping, it is suggested that epidemic and virulent ciprofloxacin-resistant E. coli clones such as ST131 and ST393 have disseminated in Korea. However, the diversity of CTX-M genes in ST131 isolates may indicate that ESBL genes have been acquired independently or several ESBL-producing, ciprofloxacin-resistant E. coli clones may have disseminated in the Korean community. [Copyright &y& Elsevier]

Summary: Objectives: Animal models have suggested that various cytokines and chemokines play an important role in host defense against Orientia tsutsugamushi, however, human data are limited. We investigated the kinetics of inflammatory responses in patients with scrub typhus receiving doxycycline. Methods: Amongst patients being treated for scrub typhus, serially collected sera were tested for TNF-α, IFN-γ, IL-2, IL-4, IL-5, and IL-10 by immunoassay. The mRNAs encoding TNF-α, IL-1β, IL-6, IL-8, IFN-γ, IL-12, IL-2, IL-4, IL-5, and IL-10 were measured by semiquantitative reverse transcription-PCR. Results: The concentrations of TNF-α, IFN-γ, and IL-10 of patients prior to doxycycline treatment were significantly higher than those of healthy volunteers. They decreased markedly within 24h after starting doxycycline. The mRNAs for IL-1β, TNF-α, IL-6, IFN-γ, and IL-10 were highly expressed. Expression of mRNAs for IL-1β, IFN-γ, and IL-10 decreased at day 2–7 of doxycycline treatment. Conclusions: Inflammatory cytokines including TNF-α, IL-1β, and IL-6 are markedly upregulated in patients with scrub typhus. Doxycycline treatment rapidly reduces the production of these cytokines, corresponding to the early defervescence after the start of the treatment. The profiles of T cell-derived cytokines in patients with scrub typhus do not follow typical Th1 or Th2 patterns. [Copyright &y& Elsevier]