Associations between serotonin transporter gene (SLC6A4) methylation and clinical characteristics and cortical thickness in children with ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene-environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD. METHOD: In 102 children with ADHD (age 6-15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated. RESULTS: A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temporal regions. CONCLUSIONS: Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.

Association between phthalates and externalizing behaviors and cortical thickness in children with attention deficit hyperactivity disorder.

BACKGROUND: Previous studies have implicated the relationship between environmental phthalate exposure and attention deficit hyperactivity disorder (ADHD) symptoms of childhood, but no studies have been conducted in children who have a confirmed diagnosis of ADHD obtained through meticulous diagnostic testing. We aimed to determine whether phthalate metabolites in urine would be higher in children with ADHD than in those without ADHD and would correlate with symptom severity and cortical thickness in ADHD children. METHOD: A cross-sectional examination of urine phthalate metabolite concentrations was performed; scores for ADHD symptoms, externalizing problems, and continuous performance tests were obtained from 180 children with ADHD, and brain-imaging data were obtained from 115 participants. For the control group, children without ADHD (N = 438) were recruited. Correlations between phthalate metabolite concentrations and clinical measures and brain cortical thickness were investigated. RESULTS: Concentrations of phthalate metabolites, particularly the di(2-ethylhexyl) phthalate (DEHP) metabolite, were significantly higher in boys with ADHD than in boys without ADHD. Concentrations of the di-n-butyl phthalate (DBP) metabolite were significantly higher in the combined or hyperactive-impulsive subtypes compared to the inattentive subtype, and the metabolite was positively correlated with the severity of externalizing symptoms. Concentrations of the DEHP metabolite were negatively correlated with cortical thickness in the right middle and superior temporal gyri. CONCLUSIONS: The results of this study suggest an association between phthalate concentrations and both the diagnosis and symptom severity of ADHD. Imaging findings suggest a negative impact of phthalates on regional cortical maturation in children with ADHD.

Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time.

Intra-individual variability in response time has been proposed as an important endophenotype for attention deficit hyperactivity disorder (ADHD). Here we asked whether intra-individual variability is predicted by common variation in catecholamine genes and whether it mediates the relationship between these gene variants and self-reported ADHD symptoms. A total of 402 non-clinical Australian adults of European descent completed a battery of five cognitive tasks and the Conners' Adult ADHD Rating Scale. Exclusion criteria included the presence of major psychiatric or neurologic illnesses and substance dependency. A total of 21 subjects were excluded due to incomplete data or poor quality cognitive or genotyping data. The final sample comprised 381 subjects (201 males; mean age=21.2 years, s.d.=5.1 years). Principal components analysis on variability measures yielded two factors (response selection variability vs selective attention variability). Association of these factors with catecholamine gene variants was tested using single-step linear regressions, with multiple comparisons controlled using permutation analysis. The response selection variability factor was associated with two ADRA2A single-nucleotide polymorphisms (SNPs) (rs1800544, rs602618), p corrected=0.004, 0.012, respectively, whereas the selective attention variability factor was associated with a TH SNP (rs3842727), p corrected=0.024. A bootstrapping analysis indicated that the response selection variability factor mediated the relationship between the ADRA2A SNP rs1800544 and self-reported ADHD symptoms. Thus this study finds evidence that DNA variation in the ADRA2A gene may be causally related to ADHD-like behaviors, in part through its influence on intra-individual variability. Evidence was also found for a novel association between a TH gene variant and intra-individual variability.

Anxiety and attention shifting in professional baseball players.

Based on the work of both Eysenck and Nideffer, we hypothesized that higher ranking players (HRP) would have lower competitive anxiety and more flexible attention-shifting, compared to lower ranking players (LRP). In addition, different patterns of attention (low anxiety and flexible attention) would be represented by a different pattern of brain activity within the temporal lobe and dorsolateral prefrontal cortex. In accordance with the rookie draft ranking, the players were classified into 2 groups: HRP (top 30% of those selected in the draft) vs. LRP (bottom 30% of those selected in the draft). For assessment of executive function, a computerized version of the Wisconsin Card-sorting Test (WCST) was used. Brain activity was assessed using 1.5-Tesla functional magnetic resonance imaging. In response to scenes depicting baseball errors, HRP showed increased activation in the left cingulate cortex and decreased activation in right middle temporal gyrus, compared to LRP. In response to the simplified WCST in the scanner, HRP showed increased activation in left superior frontal cortex (DLPFC), compared to LRP. The present results suggest that HRP may demonstrate elevated cingulate activation and lower temporal cortex activation in response to scenes depicting baseball errors.

Association between urine cotinine levels, continuous performance test variables, and attention deficit hyperactivity disorder and learning disability symptoms in school-aged children.

BACKGROUND: We examined the cross-sectional relationship between environmental tobacco smoke exposure, continuous performance test (CPT) measures, and attention deficit hyperactivity disorder (ADHD) or learning disability symptoms in school-aged children. METHOD: In total, 989 children (526 boys, mean age 9.1 ± 0.7 years), recruited from five South Korean cities participated in this study. We used urine cotinine as a biomarker for environmental tobacco smoke exposure, and obtained the children's scores on a CPT. Parents completed the Korean versions of the ADHD rating scale-IV (ADHD-RS) and learning disability evaluation scale (LDES). Using generalized linear mixed model (GLMM), we assessed the associations between urine cotinine concentrations, neuropsychological variables, and symptoms of ADHD and learning disabilities. Additionally, we conducted structural equation models to explore the effects' pathways. RESULTS: After adjusting for a range of relevant covariates, GLMM showed urinary cotinine levels were significantly and positively associated with CPT scores on omission errors, commission errors, response time, and response time variability, and with parent- and teacher-rated ADHD-RS scores. In addition, urine cotinine levels were negatively associated with LDES scores on spelling and mathematical calculations. The structural equation model revealed that CPT variables mediated the association between urine cotinine levels and parental reports of symptoms of ADHD and learning disabilities. CONCLUSIONS: Our data indicate that environmental exposure to tobacco smoke is associated with ADHD and learning disabilities in children, and that impairments in attention and inhibitory control probably mediate the effect.

No significant association between the alpha-2A-adrenergic receptor gene and treatment response in combined or inattentive subtypes of attention-deficit hyperactivity disorder.

INTRODUCTION: Given the shortage of pharmacogenetic studies on treatment response according to subtype of attention-deficit hyperactivity disorder (ADHD), we investigated the associations between the MspI and DraI polymorphisms of the alpha-2 A-adrenergic receptor gene (ADRA2A) and treatment response to methylphenidate according to subtype of ADHD. METHODS: We enrolled 115 medication-naïve children with ADHD into an open label 8-week trial of methylphenidate. The participants were genotyped and evaluated using the Clinical -Global Impression (CGI), ADHD rating scale, and Continuous Performance Test (CPT) pre- and post-treatment. RESULTS: There was no statistically significant association between the MspI or DraI genotypes and the relative frequency of CGI-improvement (CGI-I) 1 or 2 status among any of the groups (all types of ADHD, ADHD-C, or ADHD-I). However, among the children with ADHD-C, those subjects with the C/C genotype at the ADRA2A DraI polymorphism tended to have a CGI-I 1 or 2 status post-treatment (OR=4.45, p=0.045). DISCUSSION: The results of this study do not support the association between the the MspI or DraI genotypes and treatment response to methylphenidate in ADHD. However, our results -suggest that subtypes might influence pharmacogenetic results in ADHD.·available online at http://www.thieme-connect.de/ejournals/toc/pharmaco.

Parental perceived benefits of OROS-methylphenidate treatment for the child with attention-deficit/hyperactivity disorder and for parents themselves.

Given the shortage of studies on parental perceived benefits of OROS-methylphenidate treatment in Asian populations, we assessed parental response to OROS-methylphenidate treatment of Korean children with attention-deficit/hyperactivity disorder (ADHD), in relation to children's academic performance and behavioral symptoms as well as parental rearing stress and depressive symptoms.We enrolled 132 medication-naïve children with ADHD into a multicenter, open-label, 12-week trial of OROS-MPH. The outcome measures were the ADHD rating scale-IV (ADHD-RS), the comprehensive attention test and academic performance rating scale, and the clinical global impression (CGI)-severity/improvement instrument (for the children) and Beck depression inventory and parenting stress index (for their parents).We found parent-perceived improvements in children's ADHD-related behavioral symptoms and academic function and their parents' depressive symptoms and parenting stress. Investigator-rated ADHD symptoms and subjects' neuropsychological function were also improved (p<0.001).Parents of Korean children with ADHD perceive that OROS-methylphenidate treatment improves their children's academic function and behavior as well as their own child-rearing stress and emotional state. These findings must be interpreted with caution, due to a non-comparative open-label trial.

Clinical implication of extended-spectrum cephalosporin nonsusceptibility in Streptococcus pneumoniae meningitis.

The clinical implication of extended-spectrum cephalosporin (ESC) resistance has been unclear in patients with Streptococcus pneumoniae meningitis (SPM). We collected the clinical data of 120 patients with SPM in 12 hospitals of the Republic of Korea. The clinical characteristics and outcomes of 23 ESC-nonsusceptible SPM episodes were compared to those of 97 ESC-susceptible episodes. Hospital acquisition, presence of other foci of pneumococcal infection, septic shock at initial presentation, or concomitant bacteremia were more commonly observed in ESC-nonsusceptible than ESC-susceptible SPM. Empiric antimicrobial therapy with vancomycin and ESC combination was very common in both groups. Although there was a tendency towards higher early fatality in ESC-nonsusceptible SPM (3-day mortality; 17.4 % vs. 4.4 %, p = 0.05), in-hospital mortality (26.1 % vs. 20.9 %, p = 0.59) and median length of hospital stay (20 days vs. 24 days, p = 0.34) did not differ between ESC-nonsusceptible and ESC-susceptible SPM.

Transcriptional profiling of SHR/NCrl prefrontal cortex shows hyperactivity-associated genes responsive to amphetamine challenge.

Several studies suggest a strong genetic component of attention-deficit/hyperactivity disorder (ADHD), a complex neurodevelopmental disorder characterized by inappropriate levels of hyperactivity, impulsivity and inattention. Determining specific genetic risk variants for each symptom dimension of ADHD may aid in the identification of the biological risk factors of the disorder. In this study, we explored the potential genetic underpinnings of the hyperactive phenotype of ADHD. To this end, we examined differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of SHR/NCrl, an animal model of ADHD, compared with its genetic control, the Wistar Kyoto (WKY/NCrl) rat and the Wistar rat, strain used to represent the 'normal' heterogeneous population. Relative to WKY/NCrl and Wistar controls, SHR/NCrl showed hyperactivity in the open-field test. Treatment with the ADHD drug, amphetamine (AMPH) reduced hyperactivity in SHR/NCrl. Meanwhile, AMPH increased locomotor activity in WKY/NCrl and Wistar rats. Gene expression analysis found 21 common upregulated and 36 downregulated genes in the PFC of drug-naive SHR/NCrl when compared with WKY/NCrl and Wistar rats. Of these DEGs, expression levels of two genes, Atxn7 and Per2, which are involved in transcription and circadian rhythm, respectively, were downregulated following AMPH treatment in SHR/NCrl. Quantitative real-time-polymerase chain reaction analyses verified expression patterns of these genes in the PFC of drug-naïve and AMPH-treated SHR/NCrl. The present findings indicate genetic risk variants that may be associated with the hyperactive phenotype in ADHD. Further studies are warranted to establish the roles of Atxn7 and Per2 in mediating hyperactivity.

Surveillance of the Middle East respiratory syndrome (MERS) coronavirus (CoV) infection in healthcare workers after contact with confirmed MERS patients: incidence and risk factors of MERS-CoV seropositivity.

Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.

Clinical implications of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae bacteraemia.

To identify the clinical implications of extended-spectrum beta-lactamase (ESBL) production, 162 cases of Klebsiella pneumoniae bacteraemia in 154 adults were analysed. Of these cases, 44 (27.2%) were ESBL-producing (ESBLKP). Common sources of ESBLKP bacteraemia included primary bacteraemia (34.1%) and biliary infection (29.5%). The placement of a biliary drainage catheter, nosocomial acquisition, and prior antibiotic therapy were independently associated with ESBL production in multivariate analysis. More cases of ESBLKP than non-ESBLKP received inappropriate antibiotic therapy before culture results were reported (54.5 vs. 3.4%; P = 0.001). In 19 cases of ESBLKP, no significant difference in mortality was observed between patients who received appropriate empiric antibiotic therapy and those who did not (26.3 vs. 20.8%; P = 0.67). The mean length of hospital stay after the onset of bacteraemia was longer in the cases of ESBLKP than in the cases of non-ESBLKP (39.6 vs. 23.9 days; P = 0.008). Directly related mortality was not significantly different between the cases of ESBLKP and the cases of non-ESBLKP (23.3 vs. 20.0%; P = 0.65). None of the patients with biliary infection due to ESBLKP died (0/12; P = 0.03). In conclusion, ESBL production was not significantly associated with death but it had a considerable impact on patients with K. pneumoniae bacteraemia.

Methylphenidate increased regional cerebral blood flow in subjects with attention deficit/hyperactivity disorder.

The regional cerebral blood flow (rCBF) responses to methylphenidate (MPH) treatment were examined in children with attention deficit/hyperactivity disorder (ADHD). Thirty-two male children, diagnosed with ADHD by the DSM-IV diagnostic criteria, other behavioral assessment scales and neuropsychological battery, were studied using 99mTc-HMPAO-single photon emission computed tomography (SPECT). Subjects were studied before and after MPH treatment. First, using an image subtraction method, we obtained a NDR parametric image of each patient and found increased cerebral blood flow in the frontal lobes, caudate nuclei and thalamic areas after treatment. When the changes in SPECT and clinical response were compared, the matching rate, sensitivity and specificity between them were found to be 77.1, 80.0 and 79.2%, respectively. Second, three transaxial brain slices delineating anatomically defined regions of interest (ROI) at 20, 40, and 60mm above the orbitomeatal line (OML) were used, with the average number of counts for each region of interest normalized to the area of the cerebellar maximal uptake. The left and right prefrontal areas, and caudate and thalamic areas showed significant increases in rCBF after MPH treatment. These findings suggested MPH could affect the function of the fronto-striato-thalamic circuit, which is known as the pathophysiologic site of ADHD and could be used to correct the underlying brain dysfunction of ADHD.

A study on knowledge and attitude toward brain death and organ retrieval among health care professionals in Korea.

PURPOSE: The practice of retrieving vital organs from brain-dead donors is legally and medically accepted in Korea, but health care professionals' beliefs and opinions regarding these matters have not been sufficiently explored. The purpose of this study was to evaluate the knowledge and attitudes of health care professionals to the concepts of brain death and organ retrieval. METHODS: Data were collected using a 41-item questionnaire during a week in June 2011. Sixty-one doctors and 109 nurses from five hospitals with more than 2000 beds in Seoul, Korea, participated in the survey. The data was analyzed using SPSS version 17.0 (SPSS Inc. Chicago, Illinois, USA). RESULTS: There were statistically significant differences in the scores on knowledge according to marital status (P = .001) education level (P = .019), whether the participants were informed about organ donation from a brain-dead donor (P = .002), and the participant's experience managing potential brain-dead patients (P = .037). There were statistically significant differences in the scores on the attitude according to gender (P < .001), age (P < .001), marital status (P < .001), education level (P = .003), job position (P < .001), and the participant's experience referring brain-dead patients to the hospital-based organ procurement organization (P = .001). Significantly, attitude's positively correlated with knowledge about brain-dead organ donation (P < .001). CONCLUSION: Compared with previous studies, the knowledge and attitudes of health care professionals' regarding brain death and organ retrieval were not improved. There are passive attitudes to brain death and organ retrieval. More research must be performed to promote knowledge and understanding toward brain death and organ retrieval among health care professionals.

Kidney donation after cardiac death in Korea.

Organ donation after cardiac death (DCD) has been suggested due to the shortage of allografts in Korea. We investigated the outcomes of 446 deceased donor kidney transplant recipients in our center between September 1, 1995, and December 31, 2009. Twenty-four (5.4%) of those patients received DCD kidney grafts. The DCD group had a long intensive care unit stay, frequent inotropics use (such as norepinephrine and dopamine), low mean blood pressure and estimated glomerular filtration rate, and high serum creatinine and deceased donor scores compared to the standard criteria donor (SCD) group and the expanded criteria donor (ECD) group. Mean true warm ischemic time of the DCD group was 59.7 minutes based on asystole time. The DCD group had a long hospital stay after transplantation, but there was no statistically significant difference in delayed graft function and primary nonfunction. Serum creatinine levels at 3 months after transplantation in the ECD and DCD group were significantly higher than the SCD group (P < .001) but lower in the DCD group than in the ECD group at 6 months and 9 months (P < .001 and P = .004) posttransplantation. There were no statistically significant differences in serum creatinine levels or in the graft survival rates between groups at 12 months (P = .160 and P = .737). The use of DCD attracted Korean surgeons because DCD allografts are equivalent to a heart-beating donor. Donors who die during the evaluation of brain death should not be abandoned for procurement, and we need to try to harvest allografts after cardiac death (type 4 DCD) to expand donor pools.

Is it safe to use a kidney from an expanded criteria donor?

BACKGROUND: The use of expanded criteria donor (ECD) kidneys has been encouraged to enlarge the donor pools due to the shortage of donors. However, a major concern with ECD kidneys is poor long-term graft survival. The objective of this study was to determine whether ECD kidneys had a negative impact on graft survival. METHODS: We analyzed all deceased donor renal transplantations at our center from September 1995 to December 2009. RESULTS: ECD donors show characteristics, such as comparatively older age, a history of hypertension and diabetes, the use of norepinephrine, high serum creatinine levels and deceased donor scores, and decreased albumin levels and estimated glomerular filtration rates. However, the occurrence of delayed graft function and primary nonfunction among ECD grafts was comparable to those of standard criteria donor (SCD) grafts. Graft survival was not significantly different between the two groups. Only serum creatinine levels at 3, 6, and 9 months after transplantation were lower in the ECD than the SCD group. Multivariate analysis identified longer hospital stay after transplantation, delayed graft function, and acute rejection episodes as independent predictors of poor graft survival. CONCLUSION: Graft survival of ECD kidney was comparable to that of SCD kidneys. We observed that donor factors prior to procurement were not risk factors for graft failure.

Kidneys from deceased donors with oliguria are feasible for kidney transplantation.

BACKGROUND: Since kidneys from deceased donors with oliguria have not been widely used, compared their outcomes with those in recipients of kidneys without oliguria at the time of organ procurement. METHODS: We reviewed the deceased donors and kidney recipients between January 1999 and December 2009, all of whom were defined as standard criteria donors (SCD). RESULTS: The group included 26 recipients whose terminal serum creatinine level (P < .001), estimated glomerular filtration rates (P < .001), and deceased donor scores (P < .001) were higher than those of the control group. Delayed graft function (P = .044) occurred more often among recipients with donor kidneys with oliguria than those without oliguria, and their hospitalization period was longer (P = .012). The serum creatinine levels in both groups were comparable posttransplantation; there was no significant difference in graft survivals. CONCLUSION: Deceased donors with oliguria at organ procurement appeared to be poor predictors of outcomes in the early posttransplantation period. Kidneys from deceased donors with oliguria should not be discarded for transplantation. The present study suggested that it is acceptable to use kidneys from selected deceased donors with oliguria.

Psychiatric morbidity of second and third grade primary school children in Korea.

This study was undertaken to identify psychiatric morbidity among Korean second and third elementary school children using an objective diagnostic interview tool. Data from 5,118 (2,723 boys, 2,395 girls; mean age = 8.41 years (SD = 0.66)) second and third grade schoolchildren were drawn from 28 elementary schools. After initial screening assessments using the 28-item Child Problem-Behavior Screening Test for parents, 672 primary caregivers were subjected to secondary screening using the Korean version of the CBCL. Two hundred and seventy-one high-risk children selected according to the K-CBCL results, 138 (50.9%) children and their primary caregivers were interviewed using the Korean version of K-SADS-PL for objective DSM-IV psychiatric diagnoses. Sixty-four (46.4%) of the hundred and thirty eight children were determined to have at least one psychiatric disorder. More boys were diagnosed as psychiatric patients than girls (46 males, 18 females; OR = 2.21). The most frequently diagnosed disorder was ADHD (46/64; 71.9%), followed by tic disorder, anxiety disorders, mental retardation, oppositional defiant disorder, and separation anxiety disorder. Two or more comorbid psychiatric disorders were found in 22 (34.4%) of the 64 patients. The computed crude percentage of psychiatric patients in this study was 4.12%, which is similar to previously published data.

A high-strain-rate superplastic ceramic.

High-strain-rate superplasticity describes the ability of a material to sustain large plastic deformation in tension at high strain rates of the order of 10-2 to 10-1 s-1 and is of great technological interest for the shape-forming of engineering materials. High-strain-rate superplasticity has been observed in aluminium-based and magnesium-based alloys. But for ceramic materials, superplastic deformation has been restricted to low strain rates of the order of 10-5 to 10-4 s-1 for most oxides and nitrides with the presence of intergranular cavities leading to premature failure. Here we show that a composite ceramic material consisting of tetragonal zirconium oxide, magnesium aluminate spinel and alpha-alumina phases exhibits superplasticity at strain rates up to 1 s-1. The composite also exhibits a large tensile elongation, exceeding 1,050 per cent for a strain rate of 0.4 s-1. The tensile flow behaviour and deformed microstructure of the material indicate that superplasticity is due to a combination of limited grain growth in the constitutive phases and the intervention of dislocation-induced plasticity in the zirconium oxide phase. We suggest that the present results hold promise for the application of shape-forming technologies to ceramic materials.

Retrospective analysis of clinical and microbiological aspects of Klebsiella oxytoca bacteremia over a 10-year period.

From 1991 to 2000, 125 sporadic cases of Klebsiella oxytoca bacteremia were analyzed retrospectively to review clinical features and to identify the risk factors associated with resistance to extended-spectrum cephalosporins and fatal outcome. Bacteremia was acquired nosocomially in 52% of the patients. Almost all patients (97%) had an underlying disease, with biliary and pancreatic disease occurring most frequently (55%). The biliary tract was the most common site of infection (44%). Resistance to extended-spectrum cephalosporins was identified in 22 of the 125 (18%) Klebsiella oxytoca blood isolates and resistance to ciprofloxacin in 9 (7%). Only previous antibiotic therapy was strongly associated with resistance to extended-spectrum cephalosporins in patients with Klebsiella oxytoca bacteremia ( P=0.009). The mortality rate was 24% and was higher in patients infected with isolates resistant to extended-spectrum cephalosporins (41% vs. 20%; P=0.04). In multivariate analysis, fatal outcome was independently associated with septic shock, deteriorated mental status, polymicrobial bacteremia, and solid tumor. Surgical therapy had a protective effect (OR, 0.06; 95% CI, 0.005-0.7; P=0.03). In conclusion, Klebsiella oxytoca bacteremia was most commonly associated with biliary tract infection. Previous antibiotic therapy was strongly associated with resistance to extended-spectrum cephalosporins in patients with Klebsiella oxytoca bacteremia.