The significance of seizures and other predictive factors during the acute illness for the long-term outcome after bacterial meningitis

SummaryBackgroundSeizures are important neurological complications of bacterial meningitis, but no information about its epidemiology and the outcomes of seizures after community-acquired bacterial meningitis (CABM) in an adult population have been reported.AimsTo determine the frequency, clinical relevance, subtypes of seizures during the acute phase of bacterial meningitis, and the long-term outcomes of seizure complicating adult CABM.MethodsIn this 12-year retrospective study, 117 adult patients were identified with culture-proven CABM. A comparison was made between the clinical data of the patients with and without seizures during hospitalization.ResultsThirty-one patients had seizures during CABM, accounting for 27% (31/117) of the episodes. The time interval between the onset of bacterial meningitis and the seizures was 1–21 days (mean, 4 days). Furthermore, 80% (25/31) of the episodes occurred within 24h of presentation. Ten patients who had seizures progressed to status epilepticus. At follow-up after completing treatment, 10 patients completely recovered and were seizure-free, 19 died of meningitis during the acute stage and the other two progressed to chronic epilepsy.ConclusionA log-rank test demonstrated that the long-term outcome of adult CABM with acute seizures produced worse outcomes than for those who had no seizures, though no difference was noted between focal and generalized seizures. None of our patients without seizures in the acute phase of bacterial meningitis developed late seizures during the follow-up periods. Poor outcome in this study may attribute to neurological complications such as seizure, hydrocephalus, infection itself, or a combination of complications

Fluoroquinolone therapy for bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae

AbstractBackground/PurposeFor extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infections, carbapenems are recommended as first line therapy, and clinical data on the therapeutic efficacy of fluoroquinolones (FQs) is limited. This study compares the efficacy of FQs and carbapenems for bloodstream infections caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae.MethodsBetween 2008 and 2010, adults with ESBL-producing E. coli or K. pneumoniae bacteremia at two medical centers were reviewed. Adults receiving definitive FQ or carbapenem therapy were compared in a propensity score-matched analysis, and 30-day mortality was the primary endpoint.ResultsA total of 299 patients were eligible. Patients receiving a FQ (n = 24), either ciprofloxacin or levofloxacin, had a lower 30-day mortality rate than those with carbapenem therapy (8.3%, 2/24 vs. 23.3%, 64/275; p = 0.12). Multivariate regression analysis revealed that a critical illness [Pitt bacteremia score ≥ 4 points; odds ratio (OR), 7.09; p < 0.001], rapidly fatal underlying disease (OR, 5.73; p < 0.001), and hospital-associated infection (OR, 2.57; p = 0.01) were independently associated with 30-day mortality. By contrast, FQ definitive therapy was a protective factor compared with carbapenems (OR, 0.18; p = 0.04). There were 72 matched cases with carbapenem therapy in a propensity score-matched analysis, and a difference in the 30-day mortality rate of two groups was noted (8.3% vs. 29.2%; p = 0.05).ConslusionFor ESBL-producing E. coli or K. pneumoniae bacteremia, ciprofloxacin or levofloxacin, if active in vitro, can be considered as a carbapenem-sparing alternative

Bacteremic pneumonia caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: Appropriateness of empirical treatment matters

BackgroundClinical information about bacteremic pneumonia caused by extended-spectrum beta-lactamase (ESBL)-producing organism is limited.MethodsA retrospective study was conducted at two medical centers in Taiwan. From May 2002 to August 2010, clinical information and outcome of adults with bacteremic pneumonia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae were analyzed. The primary outcome is the 30-day mortality.ResultsA total of 111 patients with bacteremic pneumonia caused by E. coli (37 patients, 33.3%) and K. pneumoniae (74, 66.7%) were identified. Their mean age was 69.2 years and 51.4% were male patients. Fifty-seven (51.3%) episodes were classified as hospital-acquired infections, 19 (17.1%) as health-care-associated infections, and four (3.6%) as community-acquired infections. Fifty-one (45.9%) patients received appropriate empiric antimicrobial therapy. The 30-day mortality rate was 40.5% (45 patients). In the multivariate analysis, several independent risk factors, including rapidly fatal underlying disease [odds ratio (OR), 5.75; 95% confidence interval (CI), 1.54–21.48; p = 0.009], severe sepsis (OR, 4.84; 95% CI, 1.55–15.14; p = 0.007), critical illness (OR, 4.28; 95% CI, 1.35–13.57; p = 0.013), and receipt of appropriate empirical therapy (OR, 0.19; 95% CI, 0.07–0.55; p = 0.002), were associated with 30-day mortality. The survival analysis consistently found that individuals with appropriate empiric therapy had a higher survival rate (log-rank test, p < 0.001).ConclusionESBL-producing bacteremic pneumonia, especially health-care-associated infections, often occurred in adults with comorbidities. Appropriate empirical therapy was associated with a favorable outcome

Low-cell-number, single-tube amplification (STA) of total RNA revealed transcriptome changes from pluripotency to endothelium

Table S1. Summary of the sequencing results. The alignments against the GRCh38 genome assembly (Aligned Reads) were counted for exon reads (exon) and transcript reads based on GENCODE v22. Intronic counts (intron) were defined by transcript counts minus exon ones. Nontranscript reads were used to obtain tRNA counts (tRNA) based on the tRNA database of GENCODE v22. Nontranscript and non-tRNA reads were used for counts on repetitive sequences (repeats) based on RepeatMasker. Those not belonging to any category were defined as unannotated reads (unannotated). The counting of exonic features was based on the “gene_type” attribute in GENCODE v22. The percentages of mature miRNA reads were defined by reads aligned exclusively to the mature “miRNA” feature divided by reads aligned to the “miRNA_primary_transcript” feature of miRBase v21. (DOCX 42 kb

Carbapenem-Resistant Enterobacteriaceae Infections: Taiwan Aspects

Carbapenem-resistant Enterobacteriaceae (CRE), a major resistance concern emerging during the last decade because of significantly compromising the efficacy of carbapenem agents, has currently become an important focus of infection control. Many investigations have shown a high association of CRE infections with high case-fatality rates. In Taiwan, a few surveys observed that a significant proportion (29–47%) of the CR-Klebsiella pneumoniae isolates harbored a plasmidic allele encoding K. pneumoniae carbapenemases (KPC, especially KPC-2). A significant increase in the number of oxacillinase (OXA)-48-like carbapenemases among CR-K. pneumoniae isolates was observed between 2012 and 2015. By striking contrast, isolates of CR-Escherichia coli and CR-Enterobacter species in Taiwan had a much lower percentage of carbapenemase production than CR-K. pneumoniae isolates. This differs from isolates found in China as well as in the India subcontinent. Apart from the hospital setting, CRE was also cultured from the inpatients from communities or long-term care facilities (LTCF). Therefore, implementation of regular CRE screening of LTCF residents, strict disinfectant use in nursing homes and hospital settings, and appropriate control of antibiotic prescriptions is suggested to alleviate the spread of clinical CRE isolates in Taiwan. Although there are some promising new antibiotics against CRE, such as ceftazidime-avibactam, meropenem-vaborbactam, aztreonam-avibactam and cefiderocol, these agents are not available in Taiwan currently. Therefore, in order to effectively decrease case-fatality rates among patients with the infections owing to carbapenemase-producing CRE isolates, combination antibiotic schemes, including colistin (or amikacin) and/or tigecycline in combination with an anti-pseudomonal carbapenem agent, remain the mainstay for treating clinical CRE infections

Clinical characteristics and therapeutic outcomes of nosocomial super-infection in adult bacterial meningitis

<p>Abstract</p> <p>Background</p> <p>Super-infection in adult bacterial meningitis (ABM) is a condition wherein the cerebrospinal fluid (CSF) grows new pathogen(s) during the therapeutic course of meningitis. It is an uncommon but clinically important condition rarely examined in literature.</p> <p>Methods</p> <p>Twenty-seven episodes of super-infection states in 21 ABM patients collected in a 9.5-year study period (January 2001 to June 2010) were evaluated. The clinical characteristics, implicated pathogens, results of antimicrobial susceptibility tests, and therapeutic outcomes were analyzed.</p> <p>Results</p> <p>Twenty-one patients (13 men, 8 women) aged 25-73 years (median, 45 years) had post-neurosurgical state as the preceding event and nosocomial infection. The post-neurosurgical states included spontaneous intracranial hemorrhage (ICH) with craniectomy or craniotomy with extra-ventricular drainage (EVD) or ventriculo-peritoneal shunt (VPS) in 10 patients, traumatic ICH with craniectomy or craniotomy with EVD or VPS in 6 patients, hydrocephalus s/p VPS in 2 patients, and one patient each with cerebral infarct s/p craniectomy with EVD, meningeal metastasis s/p Omaya implant, and head injury. All 21 patients had EVD and/or VP shunt and/or Omaya implant during the whole course of ABM. Recurrent fever was the most common presentation and the implicated bacterial pathogens were protean, many of which were antibiotic resistant. Most patients required adjustment of antibiotics after the pathogens were identified but even with antimicrobial therapy, 33.3% (7/21) died. Morbidity was also high among survivors.</p> <p>Conclusions</p> <p>Super-infection in ABM is usually seen in patients with preceding neurosurgical event, especially insertion of an external drainage device. Repeat CSF culture is mandatory for diagnostic confirmation because most of the implicated bacterial strains are non-susceptible to common antibiotics used. Unusual pathogens like anaerobic bacteria and fungi may also appear. Despite antimicrobial therapy, prognosis remains poor.</p

Genotype-phenotype correlation in Taiwanese children with diazoxide-unresponsive congenital hyperinsulinism

ObjectiveCongenital hyperinsulinism (CHI) is a group of clinically and genetically heterogeneous disorders characterized by dysregulated insulin secretion. The aim of the study was to elucidate genetic etiologies of Taiwanese children with the most severe diazoxide-unresponsive CHI and analyze their genotype-phenotype correlations.MethodsWe combined Sanger with whole exome sequencing (WES) to analyze CHI-related genes. The allele frequency of the most common variant was estimated by single-nucleotide polymorphism haplotype analysis. The functional effects of the ATP-sensitive potassium (KATP) channel variants were assessed using patch clamp recording and Western blot.ResultsNine of 13 (69%) patients with ten different pathogenic variants (7 in ABCC8, 2 in KCNJ11 and 1 in GCK) were identified by the combined sequencing. The variant ABCC8 p.T1042QfsX75 identified in three probands was located in a specific haplotype. Functional study revealed the human SUR1 (hSUR1)-L366F KATP channels failed to respond to intracellular MgADP and diazoxide while hSUR1-R797Q and hSUR1-R1393C KATP channels were defective in trafficking. One patient had a de novo dominant mutation in the GCK gene (p.I211F), and WES revealed mosaicism of this variant from another patient.ConclusionPathogenic variants in KATP channels are the most common underlying cause of diazoxide-unresponsive CHI in the Taiwanese cohort. The p.T1042QfsX75 variant in the ABCC8 gene is highly suggestive of a founder effect. The I211F mutation in the GCK gene and three rare SUR1 variants associated with defective gating (p.L366F) or traffic (p.R797Q and p.R1393C) KATP channels are also associated with the diazoxide-unresponsive phenotype

Oncologic impact of delay between diagnosis and radical nephroureterectomy

PurposeThis study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU).MethodsIn this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (&gt;90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan–Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression.ResultsOf the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166−3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137−3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival.ConclusionsFor patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival