Antibiotic Combination to Effectively Postpone or Inhibit the In Vitro Induction and Selection of Levofloxacin-Resistant Mutants in Elizabethkingia anophelis.

Fluoroquinolones are potentially active against Elizabethkingia anophelis. Rapidly increased minimum inhibitory concentrations (MICs) and emerging point mutations in the quinolone resistance-determining regions (QRDRs) following exposure to fluoroquinolones have been reported in E. anophelis. We aimed to investigate point mutations in QRDRs through exposure to levofloxacin (1 × MIC) combinations with different concentrations (0.5× and 1 × MIC) of minocycline, rifampin, cefoperazone/sulbactam, or sulfamethoxazole/trimethoprim in comparison with exposure to levofloxacin alone. Of the four E. anophelis isolates that were clinically collected, lower MICs of levofloxacin were disclosed in cycle 2 and 3 of induction and selection in all levofloxacin combination groups other than levofloxacin alone (all p = 0.04). Overall, no mutations were discovered in parC and parE throughout the multicycles inducted by levofloxacin and all its combinations. Regarding the vastly increased MICs, the second point mutations in gyrA and/or gyrB in one isolate (strain no. 1) occurred in cycle 2 following exposure to levofloxacin plus 0.5 × MIC minocycline, but they were delayed appearing in cycle 5 following exposure to levofloxacin plus 1 × MIC minocycline. Similarly, the second point mutation in gyrA and/or gyrB occurred in another isolate (strain no. 3) in cycle 4 following exposure to levofloxacin plus 0.5 × MIC sulfamethoxazole/trimethoprim, but no mutation following exposure to levofloxacin plus 1 × MIC sulfamethoxazole/trimethoprim was disclosed. In conclusion, the rapid selection of E. anophelis mutants with high MICs after levofloxacin exposure could be effectively delayed or postponed by antimicrobial combination with other in vitro active antibiotics.

Comparison of Outpatient Department-Referred and Self-Referred Patients in the Emergency Department.

BACKGROUND: Patients present to emergency departments (EDs) from a variety of backgrounds, which may help inform decision making. OBJECTIVE: This study investigated the clinical characteristics and outcomes of outpatient department (OPD)-referred patients and self-referred patients in the ED. METHODS: We selected nontrauma ED adult patients from a tertiary teaching hospital in Taiwan between August 1, 2020, and October 31, 2020. The acuity levels were determined by dichotomizing the triage classification scores. After propensity score matching, we compared the hospitalization, mortality, and length of ED stay of OPD-referred and self-referred patients. We categorized the patients into "emergency" or "urgent" subgroups according to their triage information and then analyzed the effects of different severity levels. Statistical significance was set at p < 0.05. RESULTS: A total of 564 OPD-referred and 11,959 self-referred patients were included. After propensity score matching, the OPD-referred patients (n = 564), compared with self-referred patients (n = 564), had a higher admission rate (49.8% vs. 28.9%; p < 0.001; odds ratio [OR] 2.44). Among the emergency subgroup patients, there was no significant difference between OPD-referred patients (n = 131) and self-referred patients (n = 138) regarding the admission rate (p = 0.257) or the mortality rate (p = 0.253). Among the urgent subgroup patients, OPD-referred patients (n = 433), compared with self-referred patients (n = 426), had a significantly higher admission rate (46.0% vs. 20.2%; p < 0.001; OR 3.36), but not mortality rate (2.1% vs. 0.5%; p = 0.064). Regarding the length of ED stay, OPD-referred and self-referred patients had a significant difference only in the "urgent and discharged" subgroup (5.8 vs. 2.3 h; p < 0.001). CONCLUSIONS: OPD-referred ED patients might have more severe and complex conditions and need comprehensive care management.

Comprehensive Factors for Predicting the Complications of Diabetes Mellitus: A Systematic Review.

BACKGROUND: This article focuses on extracting a standard feature set for predicting the complications of diabetes mellitus by systematically reviewing the literature. It is conducted and reported by following the guidelines of PRISMA, a well-known systematic review and meta-analysis method. The research articles included in this study are extracted using the search engine "Web of Science" over eight years. The most common complications of diabetes, diabetic neuropathy, retinopathy, nephropathy, and cardiovascular diseases are considered in the study. METHOD: The features used to predict the complications are identified and categorised by scrutinising the standards of electronic health records. RESULT: Overall, 102 research articles have been reviewed, resulting in 59 frequent features being identified. Nineteen attributes are recognised as a standard in all four considered complications, which are age, gender, ethnicity, weight, height, BMI, smoking history, HbA1c, SBP, eGFR, DBP, HDL, LDL, total cholesterol, triglyceride, use of insulin, duration of diabetes, family history of CVD, and diabetes. The existence of a well-accepted and updated feature set for health analytics models to predict the complications of diabetes mellitus is a vital and contemporary requirement. A widely accepted feature set is beneficial for benchmarking the risk factors of complications of diabetes. CONCLUSION: This study is a thorough literature review to provide a clear state of the art for academicians, clinicians, and other stakeholders regarding the risk factors and their importance.

In Vitro and In Vivo Antimicrobial Activities of Vancomycin and Rifampin against Elizabethkingia anophelis.

Elizabethkingia anophelis has emerged as a critical human pathogen, and a number of isolated reports have described the successful treatment of Elizabethkingia infections with vancomycin, a drug that is typically used to target Gram-positive bacteria. This study employed in vitro broth microdilution checkerboard and time-kill assays, as well as in vivo zebrafish animal models to evaluate the individual and combination antimicrobial effects of vancomycin and rifampin against E. anophelis. The minimum inhibitory concentration ranges of vancomycin and rifampin against 167 isolates of E. anophelis were 16-256 mg/L and 0.06-128 mg/L, respectively. The checkerboard assay results revealed a synergistic effect between vancomycin and rifampin in 16.8% (28/167) of the isolates. Time-kill assays were implemented for 66 isolates, and the two-drug combination had a synergistic interaction in 57 (86.4%) isolates. In vivo zebrafish studies revealed that treatment with vancomycin monotherapy, rifampin monotherapy, or vancomycin-rifampin combination therapy yielded a higher survival rate than the control group treatment with 0.9% saline. The results of this study support the use of vancomycin to treat E. anophelis infections.

Predictive models for short-term mortality and length of hospital stay among adults with community-onset bacteraemia before and during the COVID-19 pandemic: application of early data dynamics.

BACKGROUND: The development of scoring systems to predict the short-term mortality and the length of hospital stay (LOS) in patients with bacteraemia is essential to improve the quality of care and reduce the occupancy variance in the hospital bed. METHODS: Adults hospitalised with community-onset bacteraemia in the coronavirus disease 2019 (COVID-19) and pre-COVID-19 eras were captured as the validation and derivation cohorts in the multicentre study, respectively. Model I incorporated all variables available on day 0, Model II incorporated all variables available on day 3, and Models III, IV, and V incorporated the variables that changed from day 0 to day 3. This study adopted the statistical and machine learning (ML) methods to jointly determine the prediction performance of these models in two study cohorts. RESULTS: A total of 3,639 (81.4%) and 834 (18.6%) patients were included in the derivation and validation cohorts, respectively. Model IV achieved the best performance in predicting 30-day mortality in both cohorts. The most frequently identified variables incorporated into Model IV were deteriorated consciousness from day 0 to day 3 and deteriorated respiration from day 0 to day 3. Model V achieved the best performance in predicting LOS in both cohorts. The most frequently identified variables in Model V were deteriorated consciousness from day 0 to day 3, a body temperature ≤ 36.0 °C or ≥ 39.0 °C on day 3, and a diagnosis of complicated bacteraemia. CONCLUSIONS: For hospitalised adults with community-onset bacteraemia, clinical variables that dynamically changed from day 0 to day 3 were crucial in predicting the short-term mortality and LOS.

Effectiveness of outpatient geriatric evaluation and management intervention on survival and nursing home admission: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The benefit of inpatient comprehensive geriatric assessment on patient survival and function has been demonstrated among frail older patients. However, the influence of outpatient geriatric evaluation and management (GEM) on clinical outcomes remains debated. This study aimed to update the research evidence detailing the effect of outpatient GEM on survival and nursing-home admission through a comparison with conventional care. METHODS: Cochrane Library, EMBASE, and MEDLINE databases were searched up to January 29th, 2022, to identify randomized controlled trials (RCTs) including older people over age 55 that compared outpatient GEM with conventional care on mortality (primary outcome) and nursing-home admission (secondary outcome) during a follow-up period of 12 to 36 months. RESULTS: Nineteen reports from 11 studies that recruited 7,993 participants (mean age 70-83) were included. Overall, outpatient GEM significantly reduced mortality (risk ratio (RR) = 0.87, 95% confidence interval (CI) = 0.77-0.99, I2 = 12%). For the subgroup analysis categorized by different follow-up periods, its prognostic benefit was only disclosed for 24-month mortality (RR = 0.68, 95% CI = 0.51-0.91, I2 = 0%), but not for 12- or 15 to 18-month mortality. Furthermore, outpatient GEM had significantly trivial effects on nursing-home admission during the follow-up period of 12 or 24 months (RR = 0.91, 95% CI = 0.74-1.12, I2 = 0%). CONCLUSIONS: Outpatient GEM led by a geriatrician with a multidisciplinary team improved overall survival, specifically during the 24-month follow-up period. This trivial effect was demonstrated in rates of nursing-home admission. Future research on outpatient GEM involving a larger cohort is warranted to corroborate our findings.

Association of Single Nucleotide Polymorphisms in Nucleotide-Binding Domain Leucine-Rich Repeat Protein 1 with Clostridioides difficile Colonization or Infection.

Introduction: Nucleotide-binding domain leucine-rich repeat protein (NLRP) is critical in the inflammasome-activation pathway, which is important for host survival and the clearance of Clostridioides difficile. Therefore, the influence of NLRP1 polymorphisms on C. difficile colonization (CdC) or infection (CDI) was analyzed. Materials and Methods: A prospective cohort study consisted of hospitalized adults was conducted from January 2011 to January 2013. Single nucleotide polymorphisms (SNPs) of NLRP1, including rs12150220, rs2670660, rs6502867, rs878329, rs8182352, rs3744717, and rs11078571, were incorporating in analyses. The episodes of CdC and CDI were the primary and secondary outcome, respectively. Results: Of the total of 509 eligible patients, 376 (73.9%) had neither CdC nor CDI, 104 (21.8%) had CdC without developing CDI, and 29 (4.3%) developed CDI during the study period. Through multivariate analyses, comorbid diabetes mellitus (adjusted odds ratio [AOR] 1.59, P=0.04) and CC genotype in NLRP1 rs3744717 (AOR 1.70, P=0.02) were recognized as the risk factor of CdC. After adjusting the independent predictors of CDI, in terms of comorbid diabetes mellitus (AOR 3.18, P=0.005) and prior exposure to ceftazidime/ceftriaxone (AOR 2.87, P=0.04) or proton pump inhibitors (AOR 3.86, P=0.001), patients with CC+GC genotype in NLRP1, rs878329 (AOR 2.39, P=0.03) remained a higher risk of CDI. Conclusion: For hospitalized adults, the association of CC genotype in NLRP1 rs3744717 and CdC as well as the CC+GC genotype in NLRP1 rs878329 and CDI was respectively evidenced. We believed the prompt identification of patients having specific genotype in NLRP1 would prevent and improve the quality of care in CDI.

Risk Factors and Clinical Impact of Carbapenem-Resistant Enterobacterales Coinfections Among Hospitalized Patients with Clostridioides difficile Infection.

Introduction: The risk factors and clinical impact of carbapenem-resistant Enterobacterales (CRE) coinfection among hospitalized patients with Clostridioides difficile infection (CDI) were analyzed in this study. Materials and Methods: A clinical study was performed at the medical wards of Tainan Hospital, Ministry of Health and Welfare in southern Taiwan. Patients with CDI between January 2013 and April 2020 were included. Results: Among 238 patients included for analysis, 22 (9.2%) patients developed CRE coinfections within 14 days before or after the onset of CDI. CDI patients with CRE coinfection had longer hospitalization stays (103.0 ± 97.0 days vs 42.5 ± 109.6 days, P = 0.01) than those without CRE coinfection. In the multivariate analysis, age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.10, P = 0.02) was independently associated with CRE coinfection. In contrast, underlying old stroke (OR 0.15, 95% CI 0.03-0.70, P = 0.02) was negatively linked to CRE coinfection. Conclusion: Among patients with CDI, CRE coinfections were associated with prolonged hospitalization for CDI. Age was an independent risk factor for CRE coinfection among patients with CDI.

Predicting Bacteremia among Septic Patients Based on ED Information by Machine Learning Methods: A Comparative Study.

INTRODUCTION: Bacteremia is a common but life-threatening infectious disease. However, a well-defined rule to assess patient risk of bacteremia and the urgency of blood culture is lacking. The aim of this study is to establish a predictive model for bacteremia in septic patients using available big data in the emergency department (ED) through logistic regression and other machine learning (ML) methods. MATERIAL AND METHODS: We conducted a retrospective cohort study at the ED of National Cheng Kung University Hospital in Taiwan from January 2015 to December 2019. ED adults (≥18 years old) with systemic inflammatory response syndrome and receiving blood cultures during the ED stay were included. Models I and II were established based on logistic regression, both of which were derived from support vector machine (SVM) and random forest (RF). Net reclassification index was used to determine which model was superior. RESULTS: During the study period, 437,969 patients visited the study ED, and 40,395 patients were enrolled. Patients diagnosed with bacteremia accounted for 7.7% of the cohort. The area under the receiver operating curve (AUROC) in models I and II was 0.729 (95% CI, 0.718-0.740) and 0.731 (95% CI, 0.721-0.742), with Akaike information criterion (AIC) of 16,840 and 16,803, respectively. The performance of model II was superior to that of model I. The AUROC values of models III and IV in the validation dataset were 0.730 (95% CI, 0.713-0.747) and 0.705 (0.688-0.722), respectively. There is no statistical evidence to support that the performance of the model created with logistic regression is superior to those created by SVM and RF. DISCUSSION: The advantage of the SVM or RF model is that the prediction model is more elastic and not limited to a linear relationship. The advantage of the LR model is that it is easy to explain the influence of the independent variable on the response variable. These models could help medical staff identify high-risk patients and prevent unnecessary antibiotic use. The performance of SVM and RF was not inferior to that of logistic regression. CONCLUSIONS: We established models that provide discrimination in predicting bacteremia among patients with sepsis. The reported results could inspire researchers to adopt ML in their development of prediction algorithms.

A brief on new waves of monkeypox and vaccines and antiviral drugs for monkeypox.

Monkeypox virus (MPXV), genetic closely linked to the notorious variola (smallpox) virus, currently causes several clusters and outbreaks in the areas outside Africa and is noted to be phylogenetically related to the West African clade. To prepare for the upsurge of the cases of monkeypox in the Europe and North America, two vaccines, Jynneos® in the U.S. (Imvamune® in Canada or Imvanex® in the Europe) and ACAM2000® (Acambis, Inc.) initially developed in the smallpox eradication program, can provide protective immunity to monkeypox, and their production and availability are rapidly scaled up in the response to the emerging threat. So far, these two vaccines are recommended for people at a high risk for monkeypox, instead of universal vaccination. Tecovirimat, an inhibitor of extracellular virus formation, and brincidofovir, a lipid conjugate of cidofovir, both are in vitro and in vivo active against MPXV, and are suggested for immunocompromised persons, who are at risk to develop severe diseases. However, current general consensus in the response to the monkeypox outbreak among public health systems is early identification and isolation of infected patients to prevent its spread.

Impacts of Corticosteroid Therapy at Acute Stage of Hospital-Onset Clostridioides difficile Infections.

Introduction: The influence of corticosteroid therapy before or after the onset of Clostridioides difficile infections (CDIs) on the clinical outcomes of adults with hospital-onset CDIs was investigated. Materials and Methods: A clinical study was conducted on the medical wards of a teaching hospital between January 2013 and April 2020. Adults (aged ≥ 20 years) with hospital-onset CDIs (ie, symptom onset at least 48 hours after hospitalization) were included. "Corticosteroid therapy during acute CDIs" was defined as the receipt of a corticosteroid at the prednisolone equivalent (PE) dose of ≥10 mg for at least 48 hours within one week after the CDI diagnosis. "Prior corticosteroid exposure" was defined as the receipt of a corticosteroid at the PE dose of ≥5 mg PE for at least 48 hours within one month before the CDI diagnosis. Results: Of the 243 adults with hospital-onset CDIs, patients (44, 18.1%) who received corticosteroid therapy during acute CDIs were more likely to have prior corticosteroid exposure (86.4% vs 11.9%, P <0.001) and CDI episodes in intensive care units (31.8% vs 10.8%, P =0.001). Of note, a crucial association between corticosteroid therapy during acute CDIs and CDI recurrence was evidenced (13.6% vs 1.5%, P =0.002). Prior corticosteroid exposure was not associated with favorable CDI outcomes in terms of successful treatment (78.3% vs 74.9%, P =0.89), in-hospital crude mortality (17.4% vs 24.0%, P =0.61), or CDI recurrence (4.3% vs 5.3%, P = 1.00). However, for 177 patients without prior corticosteroid exposure, corticosteroid therapy during acute CDIs was linked to a higher proportion of CDI recurrence (33.3% vs 5.3%, P =0.046). Conclusion: Corticosteroid therapy during acute CDIs might impact the recurrence of CDIs, particularly in those with a lack of prior corticosteroid exposure.

Effect of Intragenomic Sequence Heterogeneity among Multiple 16S rRNA Genes on Species Identification of Elizabethkingia.

Accurate identification of Elizabethkingia species mostly requires the use of molecular techniques, and 16S rRNA gene sequencing is generally considered the method of choice. In this study, we evaluated the effect of intraspecific diversity among the multiple copies of the 16S rRNA gene on the accuracy of species identification in the genus Elizabethkingia. Sequences of 16S rRNA genes obtained from the 32 complete whole-genome sequences of Elizabethkingia deposited in GenBank and from 218 clinical isolates collected from 5 hospitals in Taiwan were analyzed. Four or five copies of 16S rRNA were identified in the Elizabethkingia species with complete genome sequences. The dissimilarity among the copies of the16S rRNA gene was <1% in all Elizabethkingia strains. E. meningoseptica demonstrated a significantly higher rate of nucleotide variations in the 16S rRNA than did E. anophelis (P = 0.011). Nucleotide alterations occurred more frequently in regions V2 and V6 than in other hypervariable regions (P < 0.001). E. meningoseptica, E. anophelis, and E. argenteiflava strains were clustered distinctly in the phylogenetic tree inferred from 16S rRNA genes, and the intragenomic variation of gene sequences had no profound effect on the classification of taxa. However, E. miricola, E. bruuniana, E. ursingii, and E. occulta were grouped closely in the phylogenetic analysis, and the variation among the multiple copies of the 16S rRNA in one E. ursingii strain affected species classification. Other marker genes may be required to supplement the species classification of closely related taxa in the genus Elizabethkingia. IMPORTANCE Incorrect identification of bacterial species would influence the epidemiology and clinical analysis of patients infected with Elizabethkingia. The results of the present study suggest that 16S rRNA gene sequencing should not be considered the gold standard for the accurate identification of Elizabethkingia species.

Reappraisal of the clinical role of metronidazole therapy for Clostridioides difficile infection in Taiwan: A multicenter prospective study.

BACKGROUND/PURPOSE: Although metronidazole is not recommended to treat Clostridioides difficile infection (CDI) in Western countries, it was still to be recommended for the treatment of non-severe CDI among Taiwanese adults in 2020. This controversy in the clinical role of metronidazole therapy for CDI was examined in a prospective clinical study. METHODS: The study was conducted from January 2015 to December 2016 in three hospitals in Taiwan. Metronidazole treatment failure (MTF) was defined as the persistence of diarrhea after six days of treatment, medication modification (shifting to oral vancomycin), or death after five days of therapy. RESULTS: Overall, 325 patients receiving metronidazole for CDI were included. The overall MTF rate was 48.6% (158 patients). Leukocyte counts of >15,000 cells/mL in peripheral blood (odd ratio [OR] 1.81; P = 0.04) and congestive heart failure (OR 3.26; P = 0.02) were independently associated with MTF. The MTF rate for patients with leukocyte counts of ≤15,000 cells/mL and no congestive heart failure, leukocyte counts of >15,000 cells/mL and no congestive heart failure, leukocyte counts of ≤15,000 cells/mL and congestive heart failure, and leukocyte counts of >15,000 cells/mL and congestive heart failure were 44.2%, 51.8%, 73.3%, and 66.7%, respectively. Of note, patients who experienced MTF had a higher recurrence rate of CDI than those with metronidazole treatment success (13.9% vs. 6.0%, P = 0.02). CONCLUSION: For Taiwanese adults with CDI, the failure rate of metronidazole therapy approached 50%, which suggests the reappraisal of the therapeutic role of metronidazole therapy, especially for patients with leukocytosis or underlying congestive heart failure.

Microorganism Distributions and Antimicrobial Susceptibility in Community-Onset Bacteremia: A 6-Year Longitudinal Multicenter Cohort in Southern Taiwan.

Background: Prompt administration of appropriate antimicrobials has been correlated with improved prognoses in patients with bacteremia. Because the Clinical and Laboratory Standards Institute (CLSI) has numerously revised the interpretive criteria of susceptibility to numerous antimicrobials, the updated susceptibility is useful for empirical administration. Methods: In the multicenter retrospective cohort study consisting of adults with community-onset bacteremia in the emergency department (ED) during the period between January 2010 and December 2015, causative microorganisms were identified by the Vitek 2 system and prospectively collected. Antimicrobial susceptibility were respectively tested by the disk diffusion method for aerobes and the agar dilution method for anaerobes, in accordance with the contemporary CLSI criteria. Clinical information was retrospectively retrieved by reviewing the medical records. Results: Of the total 3,194 patients and 3,583 causative microorganisms, the leading source of bacteremia was the urinary tract infection (1,034 patients, 32.4%), and Escherichia coli accounted for the majority (1,332 isolates, 37.2%) of the total microorganisms. Overall, the lowest (58.2%) and highest (93.5%) susceptibility to cefazolin and piperacillin/tazobactam were, respectively, observed. In the leading five sources of bacteremia, in terms of the urinary tract infections, pneumonia, intraabdominal infections, skin and soft-tissue infections, and biliary tract infections, cefazolin or cefuroxime was only active against 49.3%-62.3% or 63.2%-74.1% of causative microorganisms, respectively. Notably, E. coli , Klebsiella species, and Proteus mirabilis (EKP) with the production of extended-spectrum beta-lactamases (ESBLs) accounted for 7.4% (142 isolates) of 1,908 EKP and 4.0% of all 3,583 microorganisms; and methicillin-resistant Staphylococcus aureus (MRSA) accounted for 37.7% (158 isolates) of S . aureus and 4.4% of all causative isolates. Conclusions: For adults with community-onset bacteremia, a low incidence (approximate 4%) of ESBL-producing EKP and MRSA among all causative microorganisms, but low susceptibility to cefazolin and cefuroxime were recognized. To achieve favorable prognoses by prompt administration of appropriate antimicrobials in EDs, our findings might offer useful information for the antimicrobial stewardship program.

Prognostic Effects of Delayed Administration of Appropriate Antimicrobials in Bacteraemic Adults Initially Presenting with Various Body Temperatures.

Purpose: To investigate the different impact of delayed administration of appropriate antimicrobial therapy (AAT) on short-term mortality of bacteraemia patients initially presenting with various body temperatures (BTs). Materials and Methods: A six-year, two-center cohort consisting of adults with community-onset bacteraemia in emergency departments (EDs) was retrospectively collected. Through the multivariable analyses, clinical impacts of delayed AAT, assessed by the time gap between the first dose of AAT and ED arrival, on 30-day mortality (primary outcomes) were respectively examined in the different groups of initial BTs (iBTs). Results: Of the 3171 adults, despite the similarities of delayed AAT in six iBT categories, hourly AAT delay was associated with an average increase in 30-day mortality rates of 0.24% in the group of iBT <36.0℃, 0.40% in the 36.0℃-36.9℃ group, 0.48% in the 37.0℃-37.9℃ group, 0.59% in the 38.0℃-38.9℃ group, 0.58% in the 39.0℃-39.9℃ group, and 0.71% in the ≥40.0℃ group, after respective adjusting independent predictors of mortality. Furthermore, for 589 patients who inappropriately received empirical antimicrobial treatment (ie, delayed AAT ≥ 24 hours), with a cutoff of 34.0℃, each 1℃ increase in iBTs was independently associated with an average increase in 30-day mortality rates of 42%. Conclusion: For adults with community-onset bacteraemia, the iBT-related differences in the prognostic impacts of delayed administration of appropriate antimicrobials might be evident.

Effects of Inappropriate Administration of Empirical Antibiotics on Mortality in Adults With Bacteraemia: Systematic Review and Meta-Analysis.

Introduction: Bloodstream infections are associated with high mortality rates and contribute substantially to healthcare costs, but a consensus on the prognostic benefits of appropriate empirical antimicrobial therapy (EAT) for bacteraemia is lacking. Methods: We performed a systematic search of the PubMed, Cochrane Library, and Embase databases through July 2021. Studies comparing the mortality rates of patients receiving appropriate and inappropriate EAT were considered eligible. The quality of the included studies was assessed using Joanna Briggs Institute checklists. Results: We ultimately assessed 198 studies of 89,962 total patients. The pooled odds ratio (OR) for the prognostic impacts of inappropriate EAT was 2.06 (P < 0.001), and the funnel plot was symmetrically distributed. Among subgroups without between-study heterogeneity (I 2 = 0%), those of patients with severe sepsis and septic shock (OR, 2.14), Pitt bacteraemia scores of ≥4 (OR, 1.88), cirrhosis (OR, 2.56), older age (OR, 1.78), and community-onset/acquired Enterobacteriaceae bacteraemia infection (OR, 2.53) indicated a significant effect of inappropriate EAT on mortality. The pooled adjusted OR of 125 studies using multivariable analyses for the effects of inappropriate EAT on mortality was 2.02 (P < 0.001), and the subgroups with low heterogeneity (I 2 < 25%) exhibiting significant effects of inappropriate EAT were those of patients with vascular catheter infections (adjusted OR, 2.40), pneumonia (adjusted OR, 2.72), or Enterobacteriaceae bacteraemia (adjusted OR, 4.35). Notably, the pooled univariable and multivariable analyses were consistent in revealing the negligible impacts of inappropriate EAT on the subgroups of patients with urinary tract infections and Enterobacter bacteraemia. Conclusion: Although the current evidence is insufficient to demonstrate the benefits of prompt EAT in specific bacteraemic populations, we indicated that inappropriate EAT is associated with unfavorable mortality outcomes overall and in numerous subgroups. Prospective studies designed to test these specific populations are needed to ensure reliable conclusions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021270274.

Mutant Prevention Concentrations of Ciprofloxacin and Levofloxacin and Target Gene Mutations of Fluoroquinolones in Elizabethkingia anophelis.

Fluoroquinolones are potentially effective against Elizabethkingia anophelis. We investigated the MIC, mutant prevention concentration (MPC), and target gene mutations of fluoroquinolones in E. anophelis. Eighty-five E. anophelis isolates were collected from five hospitals in Taiwan. The MIC and MPC of ciprofloxacin and levofloxacin were examined for all E. anophelis except 17 isolates, in which ciprofloxacin MPC could not be determined due to drug precipitation caused by overly high drug concentration. Mutations in the quinolone resistance-determining regions of DNA gyrase (GyrA and GyrB) and topoisomerase IV (ParC and ParE) in the clinical isolates and fluoroquinolone-selected mutants were examined. Overall, 23.5% and 71.8% of the isolates tested were susceptible to ciprofloxacin and levofloxacin, respectively. The MPC50 of ciprofloxacin was 128 mg/L, and the MPC50 of levofloxacin was 51.2 mg/L. The MPC50/MIC50 ratio for ciprofloxacin was 64, whereas that for levofloxacin was 25.6. The coefficient of determination between the MPC and MIC for ciprofloxacin and levofloxacin was 0.72 and 0.56, respectively, in the linear regression analysis. Preexisting mutations in GyrA (S83I, S83R, and D87Y) were identified in 18 clinical isolates, all of which were resistant to both ciprofloxacin and levofloxacin. Additional amino acid substitutions in GyrA were identified in all ciprofloxacin- and levofloxacin-selected mutants. Furthermore, GyrB alterations (D431N or D431H) were found in nine levofloxacin-treated isolates. Given that maintaining the serum concentrations of fluoroquinolones above MPCs is impossible under presently recommended doses, the selection of mutant E. anophelis strains seems inevitable.

Clostridium butyricum therapy for mild-moderate Clostridioides difficile infection and the impact of diabetes mellitus.

The therapeutic effect of Clostridium butyricum for adults with Clostridioides difficile infection (CDI) was investigated. A retrospective study was conducted in medical wards of Tainan Hospital, Ministry of Health and Welfare, between January 2013 and April 2020. The disease severity of CDI was scored based on the Clinical Practice Guidelines of the IDSA/SHEA. Treatment success was defined as the resolution of diarrhea within six days of a therapeutic intervention without the need to modify the therapeutic regimen. In total, 241 patients developed CDI during hospitalization in the study period. The treatment success rates for the 99 patients with mild-moderate CDI among them were as follows: metronidazole, 69.4%; C. butyricum, 68.2%; metronidazole plus C. butyricum, 66.7%; and oral vancomycin, 66.7% (p=1.00). Patients with treatment success were less likely to have diabetes mellitus than those with treatment failure (38.2% vs. 61.3%, p=0.05). Patients treated with C. butyricum alone or in combination with metronidazole had shorter durations of diarrhea than those treated with metronidazole alone (3.1 ± 2.0 days or 3.5 ± 2.4 days vs. 4.2 ± 3.5 days; p=0.43 or 0.71), although the differences were not statistically significant. In conclusion, the treatment success rate of C. butyricum alone or in combination with metronidazole for patients with CDI was non inferior to that of metronidazole alone. The presence of diabetes mellitus in affected individuals is a risk factor for treatment failure.

Prognostic Effects of Inappropriate Empirical Antimicrobial Therapy in Adults With Community-Onset Bacteremia: Age Matters.

Background: Studies have reported the effects of delayed administration of appropriate antimicrobial therapy (AAT) on the short-term prognosis of patients with bloodstream infections; however, whether there is an age-related difference in these effects remains debated. Methods: In this 4-year multicenter case-control study, patients with community-onset bacteremia were retrospectively categorized into the "middle-aged" (45-64 years), "old" (65-74 years), and "very old" (≥75 years) groups. Two methods were adopted to investigate the prognostic effects of delayed AAT in each age group. First, its effects were, respectively, investigated, after adjustment for the independent predictors of 30-day mortality. Second, patients in each age group were matched by the closest propensity-score (PS), which was calculated by independent predictors of mortality; the survival curves and Pearson chi-square tests were adopted to disclose its effects in each PS-matching group. Results: Each hour of delayed AAT resulted in an average increase in the 30-day crude mortality rate of 0.2% (P = 0.03), 0.4% (P < 0.001), and 0.7% (P < 0.001) in middle-aged (968 patients), old (683), and very old (1,265) patients, after, respectively, adjusting the independent predictors of mortality in each group. After appropriate PS-matching, no significant proportion differences in patient demographics, bacteremia characteristics, severity of bacteremia and comorbidities, and 15-day or 30-day crude mortality rates were observed between three matched groups (582 patients in each group). However, significant differences in survival curves between patients with delayed AAT > 24 or >48 h and those without delayed administration were demonstrated in each age group. Furthermore, the odds ratios of 30-day mortality for delayed AAT > 24 or >48 h were 1.73 (P = 0.04) or 1.82 (P = 0.04), 1.84 (P = 0.03) or 1.95 (P = 0.02), and 1.87 (P = 0.02) or 2.34 (P = 0.003) in the middle-aged, old, and very old groups, respectively. Notably, the greatest prognostic impact of delayed AAT > 24 or >48 h in the very old group and the smallest impact in the middle-aged group were exhibited. Conclusion: For adults (aged ≥45 years) with community-onset bacteremia, the delayed AAT significantly impacts their short-term survival in varied age groups and the age-related differences in its prognostic impact might be evident.