Outcome of intravenous azithromycin therapy in patients with complicated scrub typhus compared with that of doxycycline therapy using propensity-matched analysis.

There are no well-matched, controlled studies comparing azithromycin with doxycycline for the treatment of complicated scrub typhus. A retrospective propensity score-matched case-control study was performed for patients who presented with complicated scrub typhus and were treated with doxycycline or azithromycin between 2001 and 2011. Data on comorbidities, clinical manifestations, laboratory studies, treatments, and outcomes were extracted for analysis. The clinical characteristics and outcomes of the azithromycin-treated group (n=73) were compared to those of the doxycycline-treated group (n=108). Of 181 patients, 73 from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment success and survival rates were not significantly different (89% [65/73 patients] versus 96% [70/73 patients] and 96% [70/73 patients] versus 96% [70/73 patients], respectively [P>0.05]). No difference was observed in the time to defervescence or length of hospital stay between the two groups (P>0.05). In complicated scrub typhus patients (n=181), multivariate analysis showed that only APACHE II score was an independent risk factor for mortality (95% confidence interval, 1.11 to 1.56; P<0.001). Our data suggest that outcomes of azithromycin therapy are comparable to those of doxycycline therapy in patients with complicated scrub typhus.

Inappropriateness of quinolone in scrub typhus treatment due to gyrA mutation in Orientia tsutsugamushi Boryong strain.

The use of quinolone for treatment of rickettsial diseases remains controversial. Recent clinical studies suggest that quinolone is not as effective as others in patients with rickettsial diseases including scrub typhus, although the mechanism is not well understood. In this study, we evaluated the mutation in gyrA associated with quinolone resistance. We prospectively enrolled scrub typhus patients, collected blood samples and clinical data from October, 2010 to November, 2011. Among the 21 patients enrolled, one initially received ciprofloxacin for 3 days but was switched to doxycycline due to clinical deterioration. We obtained the gyrA gene of Orientia tsutsugamushi from 21 samples (20 Boryong strain, 1 Kato strain) and sequenced the quinolone resistance-determining region. All of 21 samples had the Ser83Leu mutation in the gyrA gene, which is known to be associated with quinolone resistance. This suggests that quinolones may be avoided for the treatment of serious scrub typhus.

Predictive Value of Procalcitonin for Bacterial Infection after Transarterial Chemoembolization or Radiofrequency Ablation for Hepatocellular Carcinoma.

This prospective observational study aimed at investigating the role of procalcitonin (PCT) in diagnosing bacterial infection and guiding antibiotic therapy for hepatocellular carcinoma (HCC) patients with fever after transarterial chemoembolization (TACE) and/or radiofrequency ablation (RFA). Ninety-seven cases (84 patients) were enrolled. Serum PCT, C-reactive protein (CRP), and white blood cell (WBC) counts were measured on the day of fever onset (day 0) and days 1, 3, 5, and 7 of fever. Empirical antibiotics were initiated only if PCT was ≥0.5 ng/mL or specific infection foci were suspected. An infectious cause was found in nine cases. PCT on day 0 of fever was significantly higher in patients with bacterial infection than in those without infection (P = 0.035). The area under the receiver operating characteristic curve for PCT was 0.715 (95% confidence interval, 0.538-0.892) and was higher than that for CRP (0.598 (0.368-0.828)) or WBC counts (0.502 (0.307-0.697)). In patients undergoing TACE and/or RFA, a significantly lower number of antibiotics were prescribed during the study period than during the prestudy period (P < 0.001). In conclusion, PCT might be a biomarker for diagnosing infection and guiding antibiotic treatment to reduce unnecessary antibiotic use in patients with fever after TACE and/or RFA.

Plant cell culture strategies for the production of natural products.

Plants have evolved a vast chemical cornucopia to support their sessile lifestyles. Man has exploited this natural resource since Neolithic times and currently plant-derived chemicals are exploited for a myriad of applications. However, plant sources of most high-value natural products (NPs) are not domesticated and therefore their production cannot be undertaken on an agricultural scale. Further, these plant species are often slow growing, their populations limiting, the concentration of the target molecule highly variable and routinely present at extremely low concentrations. Plant cell and organ culture constitutes a sustainable, controllable and environmentally friendly tool for the industrial production of plant NPs. Further, advances in cell line selection, biotransformation, product secretion, cell permeabilisation, extraction and scale-up, among others, are driving increases in plant NP yields. However, there remain significant obstacles to the commercial synthesis of high-value chemicals from these sources. The relatively recent isolation, culturing and characterisation of cambial meristematic cells (CMCs), provides an emerging platform to circumvent many of these potential difficulties. [BMB Reports 2016; 49(3): 149-158].

Refractory Clostridium difficile Infection Cured With Fecal Microbiota Transplantation in Vancomycin-Resistant Enterococcus Colonized Patient.

The rates and severity of Clostridium difficile infections, including pseudomembranous colitis, have increased markedly. However, there are few effective treatments for refractory or recurrent C. difficile infections and the outcomes are poor. Fecal microbiota transplantation is becoming increasingly accepted as an effective and safe intervention in patients with recurrent disease, likely due to the restoration of a disrupted microbiome. Cure rates of >90% are being consistently reported from multiple centers. We cured a case of severe refractory C. difficile infection with fecal microbiota transplantation in a patient colonized by vancomycin-resistant enterococcus.

Cambial meristematic cells: a platform for the production of plant natural products.

Plant cell culture constitutes a sustainable, controllable and environmentally friendly tool to produce natural products for the pharmaceutical, cosmetic and industrial biotechnology industries. However, there are significant obstacles to the commercial synthesis of high value chemicals from plant culture including low yields, performance instability, slow plant cell growth, industrial scale-up and downstream processing. Cambial meristematic cells constitute a platform to ameliorate many of these potential problems enabling the commercial production of high value chemicals.

Clinical impact of prophylactic antibiotic treatment for self-expandable metallic stent insertion in patients with malignant colorectal obstruction.

Purpose. The aim of this study was to determine the efficacy of prophylactic antibiotics (PA) for reducing the infectious complications and the potential risk factors responsible for the infectious complications after stent insertion for malignant colorectal obstruction. Methods. We performed a retrospective review of 224 patients who underwent self-expandable metallic stent (SEMS) insertion for malignant colorectal obstruction from May 2004 to December 2012. Results. There were 145 patients in the PA group and 79 in non-PA group. The CRP level in PA group was significantly higher than that in non-PA. Abdominal tenderness and mechanical ileus were significantly more frequent in PA group than those in non-PA. The frequency of post-SEMS insertion fever, systemic inflammatory response syndrome (SIRS), and bacteremia was not significantly different between PA and non-PA groups. In multivariate analysis, the CRP level was risk factor related to post-SEMS insertion SIRS. However, in propensity score matching analysis, there was no independent risk factor related to post-SEMS insertion fever, SIRS, and bacteremia. Conclusion. The use of PA in patients with malignant colorectal obstruction may be not effective to prevent the development of infectious complications after SEMS insertion.

Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation.

BACKGROUND/AIMS: BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. METHODS: Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. RESULTS: Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. CONCLUSIONS: Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.

Enhanced expression of B-subunit of Escherichia coli heat-labile enterotoxin in tobacco by optimization of coding sequence.

Escherichia coli heat-labile toxin (LT) is a potent mucosal immunogen and immunoadjuvant for coadministered antigens. We synthesized a gene encoding the B-subunit of LT (LTB) adapted to the coding sequence of tobacco plants and fused to the endoplasmic reticulum retention signal SEKDEL to enhance its level of expression in plants. The synthetic LTB gene was cloned into a plant expression vector adjacent to the CaMV 35S promoter and was introduced into tobacco by Agrobacterium-mediated transformation. The amount of LTB protein detected in transgenic tobacco leaves was 2.2% of the total soluble plant protein, which is approx 200-fold higher than in previous reports of native LTB gene expression in transgenic plants. Enzyme-linked immunosorbent assay indicated that plant-synthesized LTB protein bound specifically to GM1-ganglioside, suggesting that the LTB subunits formed active pentamers.

Differences in the clinical presentation and the frequency of complications between elderly and non-elderly scrub typhus patients.

Age can affect the clinical features and severity of infectious disorders, such as scrub typhus. We performed this study to examine differences between elderly and non-elderly scrub typhus patients, and to identify risk factors predictive of disease outcomes. This retrospective study included patients admitted to a tertiary hospital with scrub typhus between 2001 and 2011. A total of 615 patients were enrolled in this study, 328 of which were >65 years of age. Of the elderly patients, 46.0% (151/328) experienced at least one complication compared to only 23.0% (66/287) in younger patients. A linear trend was observed between age and complication rates (p=0.002). The most common complication in elderly patients was acute kidney injury (75, 22.9%). Treatment failure was reported in 10 elderly patients (3.0%) compared to one non-elderly patient (0.3%). Mental confusion and dyspnea of clinical manifestations at admission were common in elderly patients. Frequency of fever, rash, and eschar were similar in both groups. The following four factors were significantly associated with severe scrub typhus in elderly patients: (1) white blood cell (WBC) counts>10,000/mm(3) (OR=2.569, CI=1.298-5.086), (2) MDRD GFR<60mL/min (OR=3.525, CI=1.864-6.667), (3) albumin≤3.0g/dL (OR=4.976, CI=2.664-9.294), and (4) acute physiology and chronic health evaluation II (APACHE II) score>10 points (OR=3.304, CI=1.793-60.87). Complications and mortality were more common in elderly patients, often associated with delays in diagnosis and treatment.

The clinical characteristics, carbapenem resistance, and outcome of Acinetobacter bacteremia according to genospecies.

BACKGROUND: Few clinical data are available on the relationship between genospecies and outcome of Acinetobacter bacteremia, and the results are inconsistent. We performed this study to evaluate the relationship between genospecies and the outcome of Acinetobacter bacteremia. METHODS: Clinical data from 180 patients who had Acinetobacter bacteremia from 2003 to 2010 were reviewed retrospectively. The genospecies were identified by rpoB gene sequence analysis. The clinical features and outcomes of 90 patients with A. baumannii bacteremia were compared to those of 90 patients with non-baumannii Acinetobacter bacteremia (60 with A. nosocomialis, 17 with Acinetobacter species "close to 13 TU", 11 with A. pittii, and two with A. calcoaceticus). RESULTS: A. baumannii bacteremia was associated with intensive care unit-onset, mechanical ventilation, pneumonia, carbapenem resistance, and higher APACHE II scores, compared to non-baumannii Acinetobacter bacteremia (P<0.05). In univariate analyses, age, pneumonia, multidrug resistance, carbapenem resistance, inappropriate empirical antibiotics, higher APACHE II scores, and A. baumannii genospecies were risk factors for mortality (P<0.05). Multivariate analysis revealed A. baumannii genospecies (OR, 3.60; 95% CI, 1.56-8.33), age, pneumonia, and higher APACHE II scores to be independent risk factors for mortality (P<0.05). CONCLUSION: A. baumannii genospecies was an independent risk factor for mortality in patients with Acinetobacter bacteremia. Our results emphasize the importance of correct species identification of Acinetobacter blood isolates.

Active surveillance of the trachea or throat for MRSA is more sensitive than nasal surveillance and a better predictor of MRSA infections among patients in intensive care.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of infection in the intensive care unit (ICU). Although surveillance culture for MRSA is recommended for ICU patients, no comparative study investigating the optimal sites and frequency of culture has been performed in this population. METHODS: A prospective observational cohort study was performed in an 18-bed emergency intensive care unit (EICU) in a tertiary teaching hospital. A total of 282 patients were included. Samples for MRSA detection were obtained at the time of admission, 48 h after admission, and then weekly thereafter. All subjects were routinely monitored for the development of MRSA infection during their stay in the ICU. RESULTS: MRSA colonization was detected in 129 (46%) patients over the course of the study. The sensitivity of MRSA surveillance culture was significantly higher in throat or tracheal aspirates (82%; 106/129) than in anterior nares (47%; 61/129) (P<0.001). The sensitivity of MRSA surveillance culture for subsequent MRSA infection and MRSA pneumonia was also higher in the throat/trachea (69 and 93%, respectively) than in the anterior nares (48 and 50%, respectively). The area under the curve for subsequent MRSA infection was higher in trachea/throat (0.675) than in the anterior nares (0.648); however, this difference was not significant (P>0.05). The area under the curve for MRSA pneumonia was significantly higher in trachea/throat (0.791; 95% CI, 0.739-0.837) than anterior nares (0.649; 95% CI, 0.590-0.705) (P = 0.044). CONCLUSION: MRSA colonization was more common in the trachea/throat than in the anterior nares in ICU patients. Cultures from throat or tracheal aspirates were more sensitive and predictive of subsequent MRSA pneumonia than cultures from the anterior nares in this population.

Clinical experience of raltegravir with abacavir/lamivudine or zidovudine/lamivudine in HIV-infected Korean adults.

The efficacy and safety of raltegravir (RAL) with tenofovir (TDF)/emtricitabine (FTC) have been well studied in human immunodeficiency virus (HIV)-infected patients. However, limited clinical data are available on the use of RAL with abacavir (ABC)/lamivudine (3TC) or zidovudine (ZDV)/3TC. We investigated HIV-1-infected Korean adults, including 13 antiretroviral-naïve patients and 15 antiretroviral-experienced patients, treated with RAL plus ABC/3TC or ZDV/3TC. Virological suppression was achieved in 12 of the 13 (92%) antiretroviral-naïve patients within 24 weeks and in all (100%) patients within 96 weeks. In 13 of the 15 treatment-experienced patients, ritonavir-boosted lopinavir (LPV/r) was replaced with RAL because of hyperlipidemia (n = 11) and diarrhea (n = 2). A significant decrease in median total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels was observed in these patients (P < 0.01, each). No adverse event related to RAL was observed in any of the 28 patients. The RAL plus ABC/3TC or ZDV/3TC regimens were effective and safe in antiretroviral-naïve Korean HIV-infected patients, and replacing LPV/r with RAL significantly improved lipid abnormalities in patients previously treated with regimens including LPV/r.

Diagnostic use of serum ferritin levels to differentiate infectious and noninfectious diseases in patients with fever of unknown origin.

INTRODUCTION: In this study, we determined whether serum ferritin levels could be used to differentiate between fever of unknown origin (FUO) caused by infectious and noninfectious diseases. METHODS: FUO patients were hospitalized at Chonnam National University Hospital between January, 2005 and December, 2011. According to the final diagnoses, five causes were identified, including infectious diseases, hematologic diseases, noninfectious inflammatory diseases, miscellaneous and undiagnosed. RESULTS: Of the 77 patients, 11 were caused by infectious diseases, 13 by hematologic diseases, 20 by noninfectious inflammatory diseases, 8 by miscellaneous diseases, and 25 were undiagnosed. The median serum ferritin levels in infectious diseases was lower than those in hematologic diseases and (median (interquartile range) of 282.4 (149.0-951.8) ng/mL for the infectious disease group, 1818.2 (485.4-4789.5) ng/mL for the hematologic disease group, and 563.7 (399.6-1927.2) ng/mL for the noninfectious inflammatory disease group, p=0.048, Kruskal-Wallis test). By comparison using the Mann-Whitney test, statistically significant differences were found only between the infectious disease and hematologic disease groups (p=0.049) and between the infectious disease and groups (p=0.04). CONCLUSION: An optimal cutoff value of serum ferritin levels to predict FUO caused by a noninfectious disease (hematologic diseases, noninfectious inflammatory diseases) was established as 561 ng/mL.

Was 2009 Pandemic Influenza A (H1N1) Mild Among Pregnant Korean Women?

Clinical and laboratory data from Western countries suggest that pregnant women are at an increased risk for severe illness and complications associated with 2009 pandemic influenza A (H1N1). However, previous data among Korean women suggested a less severe outcome. In this study performed at a single referral center in Korea, rates of admission, pneumonia, intensive care unit admission, and death related to 2009 pandemic influenza A (H1N1) were significantly higher in 33 pregnant women than in 723 nonpregnant women of reproductive age (p<0.05 each). We report two cases of 2009 pandemic influenza A (H1N1) in pregnant Korean women who were admitted to the intensive care unit because of severe pneumonia that led to maternal and fetal death in one of the patients. This case series suggests that pregnant Korean women were also at increased risk of severe illness and complications during the 2009 pandemic influenza A (H1N1) outbreak.

Lemierre Syndrome Caused by Arcanobacterium haemolyticum Alone in a Healthy Man.

Arcanobacterium haemolyticum was isolated from the blood cultures of a previously healthy 37-year-old man who met all the criteria of Lemierre syndrome, including a primary oropharyngeal infection, evidence of thrombophlebitis of the internal jugular vein, and metastatic infections. To the best of our knowledge, this is the first case of Lemierre syndrome caused by A. haemolyticum in Korea and shows that A. haemolyticum alone can cause Lemierre syndrome.

Endovascular stent in traumatic thoracic aortic dissection.

Traumatic thoracic aortic injury is typically fatal. However, recent improvements in pre-hospital care and diagnostic modalities have resulted in an increased number of patients with traumatic aortic injury arriving alive at the hospital. Also, the morbidity and mortality associated with endovascular repair are significantly lower than with conventional open surgery in traumatic thoracic aorta injury. We experienced two cases of successful management of traumatic thoracic aortic dissection with endovascular stents caused by traffic accidents.

Expression of the B subunit of E. coli heat-labile enterotoxin in the chloroplasts of plants and its characterization.

Transgenic chloroplasts have become attractive systems for heterologous gene expressions because of unique advantages. Here, we report a feasibility study for producing the nontoxic B subunit of Escherichia coli heat-labile enterotoxin (LTB) via chloroplast transformation of tobacco. Stable site-specific integration of the LTB gene into chloroplast genome was confirmed by PCR and genomic Southern blot analysis in transformed plants. Immunoblot analysis indicated that plant-derived LTB protein was oligomeric, and dissociated after boiling. Pentameric LTB molecules were the dominant molecular species in LTB isolated from transgenic tobacco leaf tissues. The amount of LTB protein detected in transplastomic tobacco leaf was approximately 2.5% of the total soluble plant protein, approximately 250-fold higher than in plants generated via nuclear transformation. The GM1-ELISA binding assay indicated that chloroplast-synthesized LTB protein bound to GM1-ganglioside receptors. LTB protein with biochemical properties identical to native LTB protein in the chloroplast of edible plants opens the way for inexpensive, safe, and effective plant-based edible vaccines for humans and animals.