Search

Objective Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has become an important cause of community-onset urinary tract infections. We aimed to evaluate the efficacy of non-carbapenem antibiotics for acute pyelonephritis (APN) due to ESBL-producing E. coli. Methods We conducted a retrospective cohort study of patients with community-onset APN due to ESBL-producing E. coli at a single centre in Korea from 2007 to 2013. Outcomes included both microbiological and clinical failure. To adjust for non-random assignment of antibiotics, the propensity score method of inverse probability of treatment weighting and a multivariable analysis using Cox proportional hazards modelling were employed to estimate the efficacy of non-carbapenem antibiotics as compared with carbapenems. Results Of 152 eligible patients, 85 (55.9%) received carbapenems and 67 (44.1%) received non-carbapenems. Non-carbapenem antibiotics used in this cohort included aminoglycosides (n = 30), β-lactam/β-lactamase inhibitors (n = 13), fluoroquinolones (n = 12) and trimethoprim/sulfamethoxazole (n = 5). Microbiological failure was observed in 16 patients receiving carbapenems (16/83, 19.3%) versus 4 patients receiving non-carbapenem (4/67, 6.0%). After weighting, the risk of microbiological failure was similar between the two groups [weighted hazard ratio (HR) 0.99; 95% CI 0.31–3.19]. In a multivariable regression analysis combined with weights, the estimate did not change (weighted adjusted HR 0.96; 95% CI 0.41–2.27). The clinical failure rate was also similar in the two groups (weighted HR 1.05; 95% CI 0.24–4.62). Conclusions These results suggest that non-carbapenem antibiotics were as effective as carbapenems as definitive therapy for treating community-onset APN caused by ESBL-producing E. coli if they are active in vitro. [ABSTRACT FROM PUBLISHER]

Objectives The optimal duration of antibiotic therapy for uncomplicated Gram-negative bacteraemia remains undefined. Our objective was to compare clinical outcomes of receiving short (7–10 days) versus prolonged (>10 days) durations of antibiotic therapy for children with uncomplicated Gram-negative bacteraemia. Methods We conducted a retrospective cohort study of children with uncomplicated Gram-negative bacteraemia at The Johns Hopkins Hospital between 2002 and 2012. We estimated the risk of bacteraemic relapse among children who received short versus prolonged durations of antibiotic therapy using 1 : 1 nearest neighbour propensity score matching without replacement prior to performing regression analysis. Results There were 170 matched pairs that were well balanced on baseline covariates. The median duration of therapy in the short and prolonged courses was 10 days (IQR 10–10) and 14 days (IQR 14–17), respectively. The 30 day mortality was similar between the groups (OR 1.12; 95% CI 0.96–1.21). A prolonged duration of antibiotic therapy did not reduce the relapse risk compared with shorter durations (adjusted hazard ratio 0.67; 95% CI 0.35–1.27). Similarly, each additional day of antibiotic therapy was not protective against relapse risk (adjusted hazard ratio 0.99 per additional day; 95% CI 0.92–1.03). There was a trend towards an increased subsequent risk of candidaemia in children receiving longer treatment durations (hazard ratio 2.44; 95% CI 0.97–6.19). Conclusions Antibiotic treatment for more than 10 days for uncomplicated bacteraemia in children does not reduce the risk of microbiological relapse compared with shorter-course therapy, but may be associated with an increased risk of candidaemia. Our findings need to be confirmed in a larger, prospective study. [ABSTRACT FROM PUBLISHER]

Background. The local peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) have been extensively described. However, the systemic effects of prolonged prescription of these solutions are unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF on systemic inflammation and endothelial dysfunction markers in peritoneal dialysis (PD) patients. Methods. This is a multicenter, open labeled, randomized controlled trial including one hundred fifty-two patients initiating continuous ambulatory peritoneal dialysis for end-stage renal disease from seven centers in Korea. Participants were randomly allocated to conventional PDF (Stay safe®; Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance®; Fresenius Medical Care) and were followed for 1 year. Primary outcome variable was the inflammation and endothelial dysfunction index (IEDI), a composite score derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C-reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF), peritoneal membrane transport characteristics, ultrafiltration volume and nutritional parameters were measured as secondary outcome variables. Results. Of 152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low-GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to the conventional group; hs-CRP was not different between groups. Peritoneal transport characteristics, RRF, nutritional parameters, incidence of peritonitis and death-censored technique survival were not different between groups. Conclusion. Neutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients. [ABSTRACT FROM PUBLISHER]

Background Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) are the 2 most common tick-borne infectious diseases in Korea. Every year, an increasing number of cases are reported, which is a public health concern. Therefore, we aimed to investigate the prevalence of SFTS–scrub typhus coinfection in patients with SFTS. Methods Clinical samples were collected from 129 patients with SFTS. One-step reverse-transcription polymerase chain reaction (PCR) was performed to identify the SFTS virus (SFTSV), and real-time PCR followed by nested PCR was performed to detect the Orientia tsutsugamushi gene for scrub typhus. Phylogenetic analysis was conducted to confirm the evolutionary relationships among different species. Results Among 129 SFTS cases, 2 patients with SFTSV were positive for O. tsutsugamushi with a prevalence of coinfection of 1.6% (95% confidence interval,.001–.06). Phylogenetic analysis confirmed these as O. tsutsugamushi strain Boryong. Conclusions Our study found that 1.6% of patients were coinfected with SFTS and scrub typhus infection. We believe that this information will add a new dimension to clinical diagnosis, which should be considered for better public health management. Further research is needed to better understand the ecological transmission dynamics and geographical distribution of SFTSV and O. tsutsugamushi in endemic countries. [ABSTRACT FROM AUTHOR]

Background Increasing prevalence of mupirocin-resistant Staphylococcus aureus have been reported, and chlorhexidine resistance has become an issue. This study aimed to investigate the prevalence of mupirocin and chlorhexidine resistance in both colonized and infection causing Staphylococcus aureus in children, and find factors associated with increased virulence. Methods S taphylococcus aureus, isolated from children <18 years old admitted at a single center, were collected prospectively from August 2017 to July 2018. The isolates underwent multilocus sequence typing and were screened for genes causing chlorhexidine resistance (qac A/B), quaternary ammonium resistance (smr), mupirocin resistance (ileS mutation, Mup A, Mup B), and Pantone Valentine Leucocidin (pvl) toxin. Results During the study period, a total of 49 non-duplicate isolates were included, of which 69.4% (n = 34) were Methicillin-resistant Staphylococcus aureus (MRSA). Of the colonizers (n = 25), the most common sequence type was ST 72 (68.0%), whereas among pathogens (n = 24), ST 72 (29.2%) and ST 89 (29.2%) were most prevalent. Pathogens in this study caused abscess formation (n = 3), sepsis (n = 4), and skin infections such as cellulitis and omphalitis (n = 17). Mupirocin resistance was found in 16.0% among colonizers vs. 45.8% among pathogens (P = 0.023). High-level mupirocin resistance was more common (n = 3/25, 12.0%) than low-level mupirocin resistance (n = 1/25, 4.0%) in colonizers, whereas, pathogens had similar rates of low-level (25.0%) and high-level (n = 20.8%) mupirocin resistance. PVL toxin gene was more frequently found in colonizers than pathogens (64.0% vs. 33.3%, P = 0.032), and all isolates had quaternary ammonium resistance genes. Chlorhexidine resistance gene was found in only 3 MRSA isolates colonized in the nares of preterm infants. All were SCCmec type 4, however, two were ST 72, spa type t1054, which had high -level mupirocin resistance and PVL toxin gene. Conclusion A PVL toxin gene-positive MRSA which had genes causing mupirocin and chlorhexidine resistance were found in the nasal carriages of preterm infants. These stains may cause failure of MRSA eradication in hospital settings, using conventional methods of nasal mupirocin application and chlorhexidine bathing. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background. We investigated whether ex vivo mesothelial cells found in peritoneal dialysis (PD) effluents were representative of the in vivo epithelial-to-mesenchymal transition (EMT) in peritoneal membrane. Methods. Thirty-six male Sprague–Dawley rats were equally divided into three groups: Group C (control), no PD; Group D, infused with 4.25% Dianeal and Group P, infused with 4.25% Physioneal. PD infusions (25 mL) were given twice daily for 8 weeks. The in vivo study included morphometric analyses performed on the peritoneal membranes of tissue specimens obtained at the end of the study. The ex vivo study included peritoneal mesothelial cells collected from PD effluent and cultured to confluence. Cells were scored with light microscopy. Results. PD for 8 weeks induced significant EMT. The in vivo expression of EMT markers (α-smooth muscle actin:E-cadherin ratio, matrix metalloproteinase-2 and Snail) was higher in Group D than in Group P. However, ex vivo EMT marker expression was similar in cells derived from Groups D and P. A significant correlation was observed among in vivo EMT markers. Moreover, the ex vivo cell score increased with time on PD. However, changes in the ex vivo cell score did not correlated with changes in the in vivo EMT marker expression. Furthermore, we found no correlation between ex vivo and in vivo cells in the expression of EMT markers. Conclusions. In this animal study, ex vivo findings did not reflect the in vivo EMT changes in the peritoneum. It may be necessary to improve the current methodology for ex vivo studies. [ABSTRACT FROM AUTHOR]

Background. The body metabolism of patients with end-stage renal disease may be altered in response to long-term dialysis treatment. Moreover, the pattern of serum metabolites could change depending on the type of dialysis modality used. However, dialysis modality-dependent changes in serum metabolites are poorly understood. Our aim was to profile comprehensively serum metabolites by exploiting a novel method of 1H-NMR-based metabonomics and identify the differences in metabolite patterns in subjects receiving haemodialysis (HD) and peritoneal dialysis (PD).Methods. Anuric and non-diabetic HD patients were matched to PD patients for age, sex and dialysis duration. Accurate concentrations of serum metabolites were determined using the target-profiling procedure, and differences in the levels of metabolites were compared using multivariate analysis.Results. Principal Components Analysis score plots showed that the metabolic patterns could be discriminated by dialysis modalities. Hypoxanthine and inosine were present only with HD, whereas serum xanthine oxidase activity and uric acid levels were not different. In contrast, PD was associated with higher levels of lactate, glucose, maltose, pyruvate, succinate, alanine, and glutamate linked to glucose metabolism and the tri-carboxylic acid cycle. Maltose appeared only in patients using icodextrin solution for PD. Known uraemic retention solutes such as urea, creatinine, myo-inositol and trimethylamine-N-oxide were increased in both dialysis groups.Conclusions. Metabonomics shows apparent differences in the profiles of serum metabolites between HD and PD, which were influenced by dialysis-related processes. Inosine and hypoxanthine are present only in HD patients, which is likely to represent more hypoxic and oxidative stress. [ABSTRACT FROM AUTHOR]

Background Fluoroquinolone prophylaxis has been widely used in high-risk neutropenic patients with hematological malignancies, which may reduce bloodstream infection (BSI) and mortality. However, concerns about antibiotic resistance also exist. The aim of this study was to assess the impact of new institutional strategy of restricting fluoroquinolone prophylaxis and saving carbapenem, applied since October 2016. Fluoroquinolone prophylaxis was adopted only in remission induction chemotherapy, and carbapenems were saved until other antibiotics prove no effectiveness Methods We retrospectively reviewed all consecutive intensive chemotherapy episodes for acute leukemia from April 2016 to March 2017 at the Catholic Hematology Hospital. In addition, antibiotics consumption was assessed by calculating defined daily doses (DDDs) per 100 bed-days. Results Among 420 admissions during the study period, 201 and 219 admissions were identified before (period 1) and after (period 2) the strategy modification. Baseline characteristics including types of leukemia, chemotherapy, severity and duration of neutropenia were not different between the two periods.Development of febrile neutropenia (83.6% vs. 84.0%, P = 0.487), BSI (46.3% vs. 52.5%, P = 0.291), and septic shock (4.0% vs. 6.4%, P = 0.268) were not significantly different. Polymicrobial BSI increased significantly (7.1% vs. 20.0%, p = 0.012) in period 2. Quinolone resistance (97.8% vs. 43.6%, P < 0.001) and extended-spectrum β-lactamase producers (50% vs. 29.1%, P = 0.032) among Enterobacteriaceae were significantly reduced. Carbapenem-resistant Enterobacteriaceae was not isolated in period 2. Vancomycin resistance among enterococci (66.7% vs. 15%, P = 0.006) decreased. Consumption of ciprofloxacin (37.2 vs. 13.8) and carbapenem (22.3 vs. 16.8) decreased, while piperacillin/tazobactam consumption increased (5.2 vs. 13.0). BSI-related death (1.0% vs. 0.9%) was not increased. Conclusion Fluoroquinolone prophylaxis restriction and carbapenem saving strategies resulted in significant reduction of resistant bacterial BSIs, without increase in febrile neutropenia, BSI, septic shock, and BSI-related death. Antibiotics stewardship program can be tried in neutropenic patients, which may improve the ultimate outcome. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background National surveillance data should be validated to identify data quality issues. This study tested the validity of healthcare-associated infection (HAI) data in the Korean National Healthcare-associated Infections Surveillance System (KONIS), intensive care unit (ICU) module. Methods The validation process consisted of external (EV) and internal (IV) validation phases. For the 10 hospitals that were selected based on the HAI rate, among the 193 participating hospitals between July 2016 and June 2017, both EV and IV were performed. For the EV, the validation team reviewed 295 medical records of 60 patients with reported HAIs, including 20 urinary tract infections (UTIs), 27 bloodstream infections (BSIs), and 13 cases of pneumonia (PNEU), and 235 patients with no reported HAI during 1-day visits conducted in November and December 2017. The reviewer's diagnosis of HAI was regarded as the reference standard. IV was conducted by the staff of each hospital and evaluated whether UTI or BSI were present. Primary IV was performed for 279 patients who were subject to EV. Secondary IV was performed on 203 patients in another 11 selected participating hospitals that did not report HAIs to KONIS during the 1-year study period. Results In the EV, the diagnosis of UTI in the participating hospitals had a sensitivity of 72.0% and specificity of 99.3%. The sensitivity of BSI and PNEU was 63.2% and 70.6%, respectively, and specificity was 98.8% and 99.6%. The agreement (kappa) between the EV and primary IV was significant, with κ = 0.754 for UTI and κ = 0.674 for BSI. The results of the secondary IV showed that the hospitals that had no reports of HAI had few hospital beds and performed few blood or urine culture tests. In the secondary IV, eight UTIs and three BSIs were newly diagnosed in three hospitals, respectively. The reasons for not reporting the HAIs were presumed to be a lack of understanding of the surveillance standards and fear of the disadvantages of disclosing the HAI. Conclusion This study shows the need for ongoing validation and continuous training of surveillance personnel to maintain the accuracy of surveillance data. We also confirmed that IV can be used as an alternative monitoring method to examine validity and accuracy. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background SFTS and scrub typhus have similar clinical features and difficult to differentiate. Thus, a study to develop a scoring system to differentiate between two diseases in a clinical setting before the confirmation of laboratory results was reported by Kim et al. However, the statistical power could be low because of low numbers of cases (21 SFTS, 91 scrub typhus), our study analyzed by increasing the number of cases to overcome these limitations. Methods We retrospectively collected data from 183 SFTS and 178 scrub typhus patients who visited the 21 hospitals in South Korea between October, 2013 and November, 2017. The study protocol was approved by the IRB of each institution. SFTS was diagnosed through detection of SFTS viral RNA using RT–PCR. Scrub typhus was diagnosed either detection of 56-kDa antigen of O. tsutsugamushi using nested PCR or ≥ 4 fold rise in IgM or IgG titer using indirect IFA. Statistical analyses were performed by using SPSS and Medcalc. Results To differentiate SFTS from scrub typhus, we applied the scoring system proposed by Kim et al. After multivariable logistic regression, altered mental status, leukopenia, prolonged aPTT, and normal CRP(≤ 1.0 mg/dL) were significantly associated with SFTS compared with scrub typhus. Each variable was scored by 1 point, with a total score of 0–4 points, the optimal cutoff value was > 1 for the ROC curve. A score > 1 had 92% sensitivity, 96% specificity for diagnosis of SFTS, with a ROC AUC of 0.974. Because the sensitivity was less than 95%, we changed the normal CRP criteria to ≤ 3.0 mg/dL. The modified scoring system had 97% sensitivity, 96% specificity for diagnosis of SFTS, with an AUC of 0.983, and it showed a statistically higher accuracy than original scoring system (P = 0.0487). In this study, four factors for predicting SFTS were newly developed: leukopenia, prolonged aPTT, normal CRP (≤3.0 mg/dL), and elevated CK (>1,000 IU/L). Our study scoring system had 97% sensitivity, 98% specificity for diagnosis of SFTS, with an AUC of 0.992, and it showed a statistically higher accuracy than original scoring system (P = 0.0308). Conclusion In conclusion, we can easily differentiate SFTS from scrub typhus by using our scoring system of leukopenia, prolonged aPTT, normal CRP, and elevated CK in the endemic area. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]