Impact of reduced vancomycin susceptibility on the therapeutic outcome of MRSA bloodstream infections

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine whether clinical outcome of patients with methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) bacteraemia was correlated with vancomycin susceptibility of the corresponding strains.</p> <p>Methods</p> <p>A retrospective study on MRSA bacteraemia was performed at a teaching hospital between January 1998 and October 2005 by linking vancomycin susceptibility profiles of patients' isolates with hospitalization data.</p> <p>Results</p> <p>A total of 20 out of 209 MRSA bacteraemia patients were treated with vancomycin for at least 5 days with adequate trough levels, and fulfilled the study's inclusion and exclusion criteria. Twenty-two <it>S. aureus </it>isolates from these patients' blood cultures were identified as MRSA, including two <it>hetero</it>-VISA from separate patients and two VISA with vancomycin MIC of 4 mg/L from one patient. Between patients who showed 'good' vancomycin response and patients who did not, there was a significant difference (p < 0.01) in their corresponding MRSAs' vancomycin susceptibility expressed by 'area under curve' (AUC) of population analysis. Significant correlations were found between AUC and initial vancomycin therapeutic response parameters of 'days till afebrile' (<it>r </it>= 0.828, p < 0.01) and 'days till CRP ≦ 30% of maximum' (<it>r </it>= 0.627, p < 0.01)</p> <p>Conclusion</p> <p>Our study results caution healthcare personnel that early consideration should be given to cases with a poor vancomycin treatment response that could signify the involvement of MRSA with reduced susceptibility to vancomycin.</p

Intestinal carriage of methicillin-resistant Staphylococcus aureus in nasal MRSA carriers hospitalized in the neonatal intensive care unit

BACKGROUND: The current data regarding the correlation between the methicillin-resistant Staphylococcus aureus (MRSA) clones carried in the nasal cavity and digestive tract are inadequate. METHODS: MRSA strains were isolated from both the feces and nasal swabs of 21 nasal-MRSA carriers ranging from 10 to 104 days of age treated at the neonatal intensive care units of two hospitals. The molecular epidemiological characteristics of the isolates were determined: multilocus sequence types, spa-types, staphylococcal cassette chromosome mec (SCCmec) types, carriage of four exotoxin genes, and genes contained in commercially available kit. RESULTS: The feces of all nasal carriers contained MRSA at levels ranging from 4.0 × 10(2) to 2.8 × 10(8) colony forming units/g feces. The MRSA clones isolated from the feces and the nasal swabs of each patient were the same. Four MRSA clones, clonal complex (CC) 8-SCCmec IVl, CC8-SCCmec IVb, CC1-SCCmec IVa and CC5-SCCmec IIa were identified from 21 patients. All CC8-SCCmec IVl strains and one of three CC5-SCCmec IIa strains carried the toxic shock syndrome toxin gene. CONCLUSIONS: The feces of tested MRSA carriers contained the same MRSA clones as the nasal isolates in considerable amounts, suggesting that more careful attention should be paid for the handling of excrement in the case of newborn babies or infants than that of adults

Antimicrobial Resistance of Breakthrough-Urinary Tract Infections in Children under Antimicrobial Prophylaxis

Antimicrobial prophylaxis using cefaclor or trimethoprim-sulfamethoxazole (co-trimoxazole) is recommended for children with vesicoureteral reflex (VUR) to prevent recurrent urinary tract infection (UTI). This retrospective study was performed by reviewing the data of children ≥5 years of age treated for recurrent UTI in six hospitals from 2010 to 2015. The criteria for UTI diagnosis is fever (≥38°C) and positive results in urine culture (>104 colony-forming units/ml in midstream or withdrawn urine specimens). In total, 41 children were reviewed, and 31 children had recurrent UTI without antimicrobial prophylaxis and 10 had breakthrough (BT)-UTI treated with prophylaxis using cefaclor or co-trimoxazole. In the cases of BT-UTI treated with prophylaxis, 5 children received cefaclor and 5 received co-trimoxazole. We collected data on pathogens, antimicrobial resistance, and antimicrobial agents chosen for the empirical treatment of recurrent UTI. We also evaluated the validity of empirical therapy for recurrent UTI in this study. Various pathogens were found in children who received prophylaxis with cefaclor. The rate of empirical antimicrobial agents that were inappropriate based on antimicrobial susceptibility tests was higher in children who received prophylaxis with cefaclor (60.0%) than in those who received no prophylaxis (25.9%) or prophylaxis with co-trimoxazole (20.0%). Prophylaxis with cefaclor was found to be a risk factor for inappropriate empirical treatment in BT-UTI cases. The results suggest that the choice of empirical antimicrobial agents in BT-UTI cases should be carefully considered before treatment with prophylaxis. To encourage the adequate use of antimicrobial agents, we recommend prophylaxis with co-trimoxazole to prevent recurrent UTI

Efficacy of bacterial ribosomal RNA-targeted reverse transcription-quantitative PCR for detecting neonatal sepsis: a case control study

<p>Abstract</p> <p>Background</p> <p>Neonatal sepsis is difficult to diagnose and pathogens cannot be detected from blood cultures in many cases. Development of a rapid and accurate method for detecting pathogens is thus essential. The main purpose of this study was to identify etiological agents in clinically diagnosed neonatal sepsis using bacterial ribosomal RNA-targeted reverse transcription-quantitative PCR (BrRNA-RT-qPCR) and to conduct comparisons with the results of conventional blood culture. Since BrRNA-RT-qPCR targets bacterial ribosomal RNA, detection rates using this approach may exceed those using conventional PCR.</p> <p>Methods</p> <p>Subjects comprised 36 patients with 39 episodes of suspected neonatal sepsis who underwent BrRNA-RT-qPCR and conventional blood culture to diagnose sepsis. Blood samples were collected aseptically for BrRNA-RT-qPCR and blood culture at the time of initial sepsis evaluation by arterial puncture. BrRNA-RT-qPCR and blood culture were undertaken using identical blood samples, and BrRNA-RT-qPCR was performed using 12 primer sets.</p> <p>Results</p> <p>Positive rate was significantly higher for BrRNA-RT-qPCR (15/39, 38.5%) than for blood culture (6/39, 15.4%; p = 0.0039). BrRNA-RT-qPCR was able to identify all pathogens detected by blood culture. Furthermore, this method detected pathogens from neonates with clinical sepsis in whom pathogens was not detected by culture methods.</p> <p>Conclusions</p> <p>This RT-PCR technique is useful for sensitive detection of pathogens causing neonatal sepsis, even in cases with negative results by blood culture.</p

A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer

Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, intratumor heterogeneity in colorectal precancerous lesions has been poorly studied. We perform multiregion whole-exome sequencing on ten early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we show that the early tumors accumulate a higher proportion of subclonal driver mutations than the advanced tumors, which is highlighted by subclonal mutations in KRAS and APC. We also demonstrate that variant allele frequencies of subclonal mutations tend to be higher in early tumors, suggesting that the subclonal mutations are subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression

Liver autophagy contributes to the maintenance of blood glucose and amino acid levels

Both anabolism and catabolism of the amino acids released by starvation-induced autophagy are essential for cell survival, but their actual metabolic contributions in adult animals are poorly understood. Herein, we report that, in mice, liver autophagy makes a significant contribution to the maintenance of blood glucose by converting amino acids to glucose via gluconeogenesis. Under a synchronous fasting-initiation regimen, autophagy was induced concomitantly with a fall in plasma insulin in the presence of stable glucagon levels, resulting in a robust amino acid release. In liver-specific autophagy (Atg7)-deficient mice, no amino acid release occurred and blood glucose levels continued to decrease in contrast to those of wild-type mice. Administration of serine (30 mg/animal) exerted a comparable effect, raising the blood glucose levels in both control wild-type and mutant mice under starvation. Thus, the absence of the amino acids that were released by autophagic proteolysis is a major reason for a decrease in blood glucose. Autophagic amino acid release in control wild-type livers was significantly suppressed by the prior administration of glucose, which elicited a prompt increase in plasma insulin levels. This indicates that insulin plays a dominant role over glucagon in controlling liver autophagy. These results are the first to show that liver-specific autophagy plays a role in blood glucose regulation

Bistable Multifunctionality and Switchable Strong Ferromagnetic-to-Antiferromagnetic Coupling in a One-Dimensional Rhodium(I)–Semiquinonato Complex

We present a comprehensive study of the synthesis, heat capacity, crystal structures, UV–vis−NIR and mid-IR spectra, DFT calculations, and magnetic and electrical properties of a one-dimensional (1D) rhodium­(I)–semiquinonato complex, [Rh­(3,6-DBSQ-4,5-(MeO)₂)­(CO)₂]_∞ (<b>3</b>), where 3,6-DBSQ-4,5-(MeO)₂^•– represents 3,6-di-<i>tert</i>-butyl-4,5-dimethoxy-1,2-benzosemiquinonato radical anion. The compound <b>3</b> comprises neutral 1D chains of complex molecules stacked in a staggered arrangement with short Rh–Rh distances of 3.0796(4) and 3.1045(4) Å at 226 K and exhibits unprecedented bistable multifunctionality with respect to its magnetic and conductive properties in the temperature range of 228–207 K. The observed bistability results from the thermal hysteresis across a first-order phase transition, and the transition accompanies the exchange of the interchain C–H···O hydrogen-bond partners between the semiquinonato ligands. The strong overlaps of the complex molecules lead to unusually strong ferromagnetic interactions in the low-temperature (LT) phase. Furthermore, the magnetic interactions in the 1D chain drastically change from strongly ferromagnetic in the LT phase to antiferromagnetic in the room-temperature (RT) phase with hysteresis. In addition, the compound <b>3</b> exhibits long-range antiferromagnetic ordering between the ferromagnetic chains and spontaneous magnetization because of spin canting (canted antiferromagnetism) at a transition temperature <i>T</i>_N of 14.2 K. The electrical conductivity of <b>3</b> at 300 K is 4.8 × 10^–4 S cm^–1, which is relatively high despite Rh not being in a mixed-valence state. The temperature dependence of electrical resistivity also exhibits a clear hysteresis across the first-order phase transition. Furthermore, the ferromagnetic LT phase can be easily stabilized up to RT by the application of a relatively weak applied pressure of 1.4 kbar, which reflects the bistable characteristics and demonstrates the simultaneous control of multifunctionality through external perturbation