Ji Ye Jung

Risk factors for multi-drug resistant Acinetobacter baumannii bacteremia in patients with colonization in the intensive care unit

BackgroundEpidemic outbreaks of multi-drug resistant (MDR) Acinetobacter baumannii (AB) in intensive care units (ICUs) are increasing. The incidence of MDR AB bacteremia, which develops as a result of colonization, is increasing through widespread dissemination of the pathogen, and further colonization. We sought to determine risk factors for MDR AB bacteremia in patients colonized with MDR AB in the ICU.MethodsWe conducted a retrospective, observational study of 200 patients colonized with MDR AB in the ICU at Severance Hospital, South Korea during the outbreak period between January 2008 and December 2009.ResultsOf the 200 patients colonized with MDR AB, 108 developed MDR AB bacteremia, and 92 did not. APACHE II scores were higher in bacteremic than non-bacteremic patients at the time of ICU admission and colonization (24.0 vs. 21.6; P = 0.035, 22.9 vs. 16.8; P < 0.001, respectively). There was no difference between the two groups in the duration of time from ICU admission to colonization (7.1 vs. 7.2 days; P = 0.923), but the duration of time at risk was shorter in bacteremic patients (12.1 vs. 6.0 days; P = 0.016). A recent invasive procedure was a significant risk factor for development of bacteremia (odds ratio = 3.85; 95% CI 1.45-10.24; P = 0.007). Multivariate analysis indicated infection and respiratory failure at the time of ICU admission, maintenance of mechanical ventilation, maintenance of endotracheal tube instead of switching to a tracheostomy, recent central venous catheter insertion, bacteremia caused by other microorganism after colonization by MDR AB, and prior antimicrobial therapy, were significant risk factors for MDR AB bacteremia.ConclusionsPatients in the ICU, colonized with MDR AB, should be considered for minimizing invasive procedures and early removal of the invasive devices to prevent development of MDR AB bacteremia.

Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis

BackgroundThe immature granulocyte count has been reported to be a marker of infection and sepsis. The difference in leukocyte subfractions (delta neutrophil index, DNI) in ADVIA 2120 reflects the fraction of circulating immature granulocytes in the blood. This study evaluated the clinical utility of DNI as a severity and prediction marker in critically ill patients with sepsis.MethodsOne hundred and three patients admitted to the medical intensive care unit with sepsis were studied. DNI (the difference in leukocyte subfractions identified by myeloperoxidase and nuclear lobularity channels) was determined using a specific blood cell analyzer.ResultsForty four patients (42.7%) were diagnosed with severe sepsis/septic shock. Overt disseminated intravascular coagulation (DIC) occurred in 40 (38.8%). DNI was significantly higher in patients with severe sepsis/septic shock and overt DIC than in patients without (p < 0.05). DNI correlated with DIC score (r = 0.54, p < 0.001). We observed a monotonic increase in the proportion of overt DIC and severe sepsis/septic shock associated with increasing quartiles of DNI (p < 0.001). A DNI value > 6.5% was a better indicator of severe sepsis/septic shock than C-reactive protein, lactate, white blood cell count, and absolute neutrophil count (sensitivity, 81.3%; specificity, 91.0%; positive predictive value, 88.6%; and negative predictive value, 84.7%). In 36 (82%) of the 44 patients with severe sepsis/septic shock, DNI values were already elevated up to 12 hours before the onset of organ/circulatory failure.ConclusionsDNI may be used as a marker of disease severity in critically ill patients with sepsis. High levels of DNI may help to identify patients with an impending risk of developing severe sepsis/septic shock.

Performance of the tuberculin skin test and interferon-γ release assay for detection of tuberculosis infection in immunocompromised patients in a BCG-vaccinated population

BackgroundInterferon-γ release assay (IGRA) may improve diagnostic accuracy for latent tuberculosis infection (LTBI). This study compared the performance of the tuberculin skin test (TST) with that of IGRA for the diagnosis of LTBI in immunocompromised patients in an intermediate TB burden country where BCG vaccination is mandatory.MethodsWe conducted a retrospective observational study of patients given the TST and an IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT), at Severance Hospital, a tertiary hospital in South Korea, from December 2006 to May 2009.ResultsOf 211 patients who underwent TST and QFT-IT testing, 117 (55%) were classified as immunocompromised. Significantly fewer immunocompromised than immunocompetent patients had positive TST results (10.3% vs. 27.7%, p 0.001), whereas the percentage of positive QFT-IT results was comparable for both groups (21.4% vs. 25.5%). However, indeterminate QFT-IT results were more frequent in immunocompromised than immunocompetent patients (21.4% vs. 9.6%, p 0.021). Agreement between the TST and QFT-IT was fair for the immunocompromised group (κ = 0.38), but moderate agreement was observed for the immunocompetent group (κ = 0.57). Indeterminate QFT-IT results were associated with anaemia, lymphocytopenia, hypoproteinemia, and hypoalbuminemia.ConclusionIn immunocompromised patients, the QFT-IT may be more sensitive than the TST for detection of LTBI, but it resulted in a considerable proportion of indeterminate results. Therefore, both tests may maximise the efficacy of screening for LTBI in immunocompromised patients.

Healthcare-associated pneumonia among hospitalized patients in a Korean tertiary hospital

BackgroundHealthcare-associated pneumonia (HCAP) has more similarities to nosocomial pneumonia than to community-acquired pneumonia (CAP). However, there have only been a few epidemiological studies of HCAP in South Korea. We aimed to determine the differences between HCAP and CAP in terms of clinical features, pathogens, and outcomes, and to clarify approaches for initial antibiotic management.MethodsWe conducted a retrospective, observational study of 527 patients with HCAP or CAP who were hospitalized at Severance Hospital in South Korea between January and December 2008.ResultsOf these patients, 231 (43.8%) had HCAP, and 296 (56.2%) had CAP. Potentially drug-resistant (PDR) bacteria were more frequently isolated in HCAP than CAP (12.6% vs. 4.7%; P = 0.001), especially in the low-risk group of the PSI classes (41.2% vs. 13.9%; P = 0.027). In-hospital mortality was higher for HCAP than CAP patients (28.1% vs. 10.8%, P < 0.001), especially in the low-risk group of PSI classes (16.4% vs. 3.1%; P = 0.001). Moreover, tube feeding and prior hospitalization with antibiotic treatment within 90 days of pneumonia onset were significant risk factors for PDR pathogens, with odds ratios of 14.94 (95% CI 4.62-48.31; P < 0.001) and 2.68 (95% CI 1.32-5.46; P = 0.007), respectively.ConclusionsFor HCAP patients with different backgrounds, various pathogens and antibiotic resistance of should be considered, and careful selection of patients requiring broad-spectrum antibiotics is important when physicians start initial antibiotic treatments.

The drug susceptibility profile and inducible resistance to macrolides of Mycobacterium abscessus and Mycobacterium massiliense in Korea

We conducted drug susceptibility testing (DST) against various antimicrobial agents, including new candidate drugs, and investigated the relationship between inducible resistance (IR) to macrolides and erm(41) gene in Mycobacterium abscessus complex. Sixty-two isolates of M. abscessus complex from 2 tertiary care hospitals in South Korea were tested against 10 antimicrobial agents. Thirty-five isolates were M. abscessus, and 27 were Mycobacterium massiliense. Amikacin, moxifloxacin, linezolid, clofazimine, and tigecycline were active against most isolates and cefoxitin and ciprofloxacin against moderate number of isolates. M. massiliense remained susceptible to macrolides; in contrast, M. abscessus became highly resistant on day 14 after incubation. DST pattern did not differ between clarithromycin and azithromycin. IR to clarithromycin was correlated with erm(41) genotype in M. abscessus. Variations in susceptibility to antimicrobial agents within species and the difference in DST patterns between M. abscessus and M. massiliense suggest that DST and identification of M. abscessus complex are significant before treatment.

Poor prediction of potentially drug-resistant pathogens using current criteria of health care-associated pneumonia

BACKGROUND Health care-associated pneumonia (HCAP) includes a broad range of patients having frequent or chronic contact with health care systems. However, the relationship between current defining criteria for HCAP and the risk of potentially drug-resistant (PDR) pathogens is controversial. METHODS We retrospectively evaluated patients admitted to Severance Hospital in South Korea with culture-positive pneumonia from January 2008 to December 2009. We analyzed the associations between risk factors for HCAP and infection with PDR pathogens, and developed a new scoring system to predict infection with PDR pathogens. RESULTS Among 339 patients, PDR pathogens were observed in 122 (36.0%). PDR pathogens were more common in HCAP than community-acquired pneumonia (CAP) (48.5% versus 23.8%, P<0.001). In a logistic regression, prior hospitalization within 90 days of pneumonia (OR=2.51, P=0.003), recent treatment with antimicrobials (OR=2.35, P=0.039), and nasogastric tube feeding (OR=15.28, P<0.001) were independently associated with PDR pathogens. For the prediction of PDR pathogens, the sensitivity and specificity of current HCAP criteria were 66.4% and 60.4%, respectively, and 68.0% and 67.3%, respectively, for the new scoring system. Moreover, the new scoring system showed better diagnostic accuracy than current HCAP criteria (area under curve=0.711 versus 0.634, P<0.001). CONCLUSIONS The current HCAP criteria are poor predictors of PDR pathogens and all patients with HCAP should not be empirically treated for these pathogens. To avoid excessive antibiotic use, individual risk stratification approaches should be considered.

Urine Cotinine for Assessing Tobacco Smoke Exposure in Korean: Analysis of the Korea National Health and Nutrition Examination Survey (KNHANES)

Background The level of urine cotinine is an indicator of tobacco smoke exposure. The purpose of this study is to investigate urine cotinine for the purpose of assessing the smoking status of Korean smokers and non-smokers exposed to tobacco smoke. Methods The subjects were identified from the 2007-2009 and the 2010 data sets of the Korea National Health and Nutrition Examination Survey (KNHANES). They were assigned as non-smokers, current smokers and ex-smokers. Non-smokers were also divided into three subset groups according to the duration of smoke exposure. Each group was stratified by gender prior to analysis. Results The median value of urine cotinine in the male current smokers was 1,221.93 ng/mL which was the highest among all groups. The difference between levels of urine cotinine for male and the female groups was statistically significant (p<0.01). In the female group, passive smoke exposure groups reported higher urine cotinine levels than non-exposure groups (p=0.01). The cutoff point for the discrimination of current smokers from non-smokers was 95.6 ng/mL in males and 96.8 ng/mL in females. The sensitivity and specificity were 95.2% and 97.1%, respectively, in males, 96.1% and 96.5% in females. However, the determination of urine cotinine level was not useful in distinguishing between passive smoke exposure groups and non-exposure groups. Conclusion Urine cotinine concentration is a useful biomarker for discriminating non-smokers from current smokers. However, careful interpretation is necessary for assessing passive smoke exposure by urine cotinine concentration.

Phase II study with oxaliplatin and S-1 for patients with metastatic colorectal cancer

BACKGROUND To evaluate the efficacy and safety of the combination of oxaliplatin and S-1 (OS) in treating metastatic colorectal cancer. PATIENTS AND METHODS Eligible patients were those with measurable lesions, no previous history of chemotherapy (except adjuvant chemotherapy), an age of 18-70 years, and an Eastern Cooperative Oncology Group performance status of zero to two. Oxaliplatin 130 mg/m(2) was administered i.v. on day 1, and S-1 40 mg/m(2) b.i.d. was administered orally on days 1-14, every 3 weeks. RESULTS Forty-eight patients (median age, 56 years) were enrolled: 23 had colon cancer, seven rectosigmoid colon cancer; and 18 rectal cancer. Of the 48 patients, 31 were diagnosed with metastatic cancer and 17 had relapsed cancer after surgery, with adjuvant chemotherapy or chemoradiotherapy. In total, 413 cycles were administered (median 6 per patient; range 2-24). Toxicity was evaluated in 48 patient and response in 46. Major toxic effects were grade 3/4 thrombocytopenia (13%) and neutropenia (10%). The overall response rate was 54% [95% confidence interval (CI) 40% to 68%]. The median time to progression and median survival time were 8.5 (95% CI 6.2-10.9) months and 27.2 (95% CI 20.3-34.0) months, respectively. CONCLUSIONS These data indicate that the OS regimen is effective and well tolerated in patients with advanced colorectal cancer.

Efficacy of IP-10 as a biomarker for monitoring tuberculosis treatment.

OBJECTIVES IP-10 has been proposed as a promising alternative marker for the diagnosis of tuberculosis (TB). METHODS In this exploratory study, we assessed the levels of serum IP-10 and TB antigen-dependent IP-10 at the time of diagnosis and after completing treatment in 32 patients with active TB. RESULTS Significant changes in concentration between the time of diagnosis and the completion of therapy were observed for serum IP-10 (P < 0.001; median: 140.4 and 105.7 pg/ml, respectively) and TB antigen-dependent IP-10 (P = 0.002; median: 20,000 and 13,720 pg/ml, respectively). The proportion of TB antigen-dependent IP-10 responders did not change significantly between baseline and the completion of therapy (P = 0.35), whereas the proportion of serum IP-10 responders was significantly different (P = 0.001). CONCLUSIONS Serum IP-10 and TB antigen-dependent IP-10 responses to QFT-GIT antigens might be a useful biomarker for monitoring the efficacy of therapy in patients with active TB.

Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma

OBJECTIVES The aim of this study is to evaluate the prevalence and prognostic significance of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangement in never-smokers with surgically resected lung adenocarcinoma. METHODS We retrospectively analyzed 162 consecutive never-smokers who underwent curative resection for stage IB to IIIA lung adenocarcinoma at a single institution. We concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes, and investigated ALK rearrangements by fluorescence in situ hybridization assay. ROS1 rearrangement was also determined in all triple (EGFR/KRAS/ALK)-negative tumors. RESULTS Of 162 never smokers with lung adenocarcinoma, 14 (8.6%) and 5 (3.1%) had ALK and ROS1 rearrangements, respectively. Nineteen of the 74 (25.7%) EGFR and KRAS mutation-negative patients were fusion-positive (ALK or ROS1 fusion). Fusion-positive patients tended to have shorter median disease-free survival (DFS) than fusion-negative patients (28.0 vs. 33.9 months; p=0.128). In multivariate analysis, fusion-positive patients had significantly poorer DFS than fusion-negative patients after adjustment for age, sex, T stage, N stage, and adjuvant chemotherapy use (p=0.022; hazard ratio, 2.11; 95% confidence interval, 1.19-4.30). The first recurrence sites were not significantly different between fusion-positive and fusion-negative patients in this study. CONCLUSION This study shows significantly poorer DFS of ALK or ROS1 fusion-positive lung adenocarcinoma in never-smokers after curative surgery.