Chih Chia Hsieh

Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: Impact of revised CLSI breakpoints

Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n=409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR)=19.96; P<0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR=13.91; P<0.001); bacteraemia because of pneumonia (OR=5.45; P=0.007); de-escalation after empirical therapy (OR=0.28; P=0.03); and isolates with a CTX MIC≤1mg/L (OR=0.17; P=0.02). Of note, isolates with a CTX MIC≤8mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ=1.00; P=0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC≤1mg/L.

Propensity score-matched analysis comparing the therapeutic efficacies of cefazolin and extended-spectrum cephalosporins as appropriate empirical therapy in adults with community-onset Escherichia coli, Klebsiella spp. and Proteus mirabilis bacteraemia

In this study, the therapeutic efficacy of cefazolin was compared with that of extended-spectrum cephalosporins (ESCs) (cefotaxime, ceftriaxone and ceftazidime) as appropriate empirical therapy in adults with community-onset monomicrobial bacteraemia caused by Escherichia coli, Klebsiella spp. or Proteus mirabilis (EKP). Compared with cefazolin-treated patients (n = 135), significantly higher proportions of patients in the ESC treatment group (n = 456) had critical illness at bacteraemia onset (Pitt bacteraemia score ≥4) and fatal co-morbidities (McCabe classification). Of the 591 patients, 121 from each group were matched using propensity score matching (PSM) based on the following independent predictors of 28-day mortality: fatal co-morbidities (McCabe classification); Pitt bacteraemia score ≥4 at bacteraemia onset; initial syndrome of septic shock; and bacteraemia due to pneumonia. After appropriate PSM, no significant differences were observed in the early clinical failure rate (10.7% vs. 7.4%; P = 0.37), the proportion of critical illness (Pitt bacteraemia score ≥4) (0% vs. 0%; P = 1.00) and defervescence (52.6% vs. 42.6%; P = 0.13) on Day 3 between the cefazolin and ESC treatment groups. Similarly, no significant differences were observed in the mean of time to defervescence (4.1 days vs. 4.9 days; P = 0.15), late clinical failure rate (18.2% vs. 10.7%; P = 0.10) and 28-day crude mortality rate (0.8% vs. 3.3%; P = 0.37) between the two groups. These data suggest that the efficacy of cefazolin is similar to that of ESCs when used as appropriate empirical antimicrobial treatment for community-onset EKP bacteraemia.

Clinical Benefit of Appropriate Empirical Fluoroquinolone Therapy for Adults with Community-Onset Bacteremia in Comparison with Third-Generation-Cephalosporin Therapy

ABSTRACT Both fluoroquinolones (FQs) and third-generation cephalosporins (3rd-GCs) are commonly prescribed to treat bloodstream infections, but comparative efficacies between them were rarely studied. Demographics and clinical characteristics of 733 adults with polymicrobial or monomicrobial community-onset bacteremia empirically treated by an appropriate FQ (n = 87) or 3rd-GC (n = 646) were compared. A critical illness (respectively, 8.0% versus 19.0%; P = 0.01), an initial syndrome with severe sepsis (33.3% versus 50.3%; P = 0.003), or a fatal outcome at 28 days (4.6% versus 10.5%; P = 0.08) was less common in the FQ group. A total of 645 (88.0%) patients were febrile at initial presentation, and the FQ group with (FQ group versus 3rd-GC group, respectively, 7.6 days versus 12.0 days; P = 0.04) and without (3.8 days versus 5.4 days; P = 0.001) a critical illness had a shorter time to defervescence than the 3rd-GC group. By the propensity scores, 87 patients with appropriate FQ therapy were matched with 435 treated by 3rd-GC therapy at a ratio of 1:5, and there were no significant differences in terms of bacteremia severity, comorbidity severity, major comorbidities, causative microorganisms, and bacteremia sources between groups. Moreover, crude mortality rates at 28 days (FQ group versus 3rd-GC group, respectively, 4.6% versus 7.8%; P = 0.29) did not differ significantly. However, the time to defervescence was shorter in the FQ group (4.2 ± 3.6 versus 6.2 ± 7.6 days; P < 0.001). Conclusively in the adults with community-onset bacteremia, appropriate empirical FQ therapy was related to shorter time to defervescence than with 3rd-GC therapy, at least for those without a critical illness.

Clinical features and impact of empirical therapy in cirrhotic adults with community-onset bacteremia

OBJECTIVES The objectives were to investigate the clinical characteristics of community-onset bacteremia in cirrhotic adults visiting the emergency department (ED), as well as the clinical impact of empirical antibiotics on their outcome. METHODS Cirrhotic adults with community-onset bacteremia who visited the ED from January 2005 to December 2009 were included retrospectively. Clinical data and outcome were collected from the medical chart. The in vitro susceptibility was measured by the broth microdilution method. RESULTS Of the 246 bacteremic episodes in cirrhotic patients, the major sources of bacteremia included intraabdominal infections (111, 45.1%), primary bacteremia (43, 17.5%), urinary tract infection (39, 15.9%), and soft tissue infection (22, 8.9%). Of the 258 bacteremic pathogens identified, Escherichia coli (83 isolates, 33.7%) and Klebsiella pneumoniae (61, 23.6%) were the most common microorganisms. In the multivariate analysis, delayed appropriate antibiotic therapy (>72 hours; odds ratio [OR], 4.29; P=.003), serum creatinine greater than 1.5 mg/dL at the ED (OR, 3.12; P=.005), severe sepsis (OR, 3.61; P=.01), Pittsburgh bacteremia score of at least 4 (OR, 2.66; P=.04), bacteremia due to pneumonia (OR, 5.44; P=.02), and a comorbidity of diabetes mellitus (OR, 3.54; P=.004) were independently associated with the 28-day mortality. CONCLUSIONS Focusing on cirrhotic adults with community-onset bacteremia, we emphasized that the cirrhosis severity is one of the critical factors when choosing empirical antimicrobial therapy and that the strategy of empirical therapy is warranted for cirrhotic adults with severe decompensation (Childs C group). For critically ill patients, especially in those with Childs C group, only piperacillin/tazobactam, ertapenem, or imipenem treatment was warranted because of susceptibility rate of greater than 90%.

Applications of a rapid and sensitive dengue DUO rapid immunochromatographic test kit as a diagnostic strategy during a dengue type 2 Epidemic in an Urban City

Dengue infection is a major health problem in tropical and subtropical countries. A prospective observational study in a university-affiliated hospital was conducted between August 2015 and September 2015. Patients who visited the emergency department (ED) with a presentation of any symptoms of dengue were eligible for the dengue non-structural protein 1 (NS1), IgM/IgG rapid immunochromatographic tests and real-time polymerase chain reaction (RT-PCR) to evaluate the performance of the rapid tests. Considering the RT-PCR as the gold standard for the dengue diagnosis, the ideal primary results of sensitivity (80–100%), specificity (60–84%), positive predicted value(75%-95%), and negative predicted value (70–100%) suggested that the NS1-based test with or without a combination of IgM and IgG tests have good diagnostic performances in detecting dengue infections, even in the afebrile or elderly populations.

Comparing the therapeutic efficacies of third-generation cephalosporins and broader-spectrum β-lactams as appropriate empirical therapy in adults with community-onset monomicrobial Enterobacteriaceae bacteraemia: a propensity score matched analysis

In this study, the therapeutic efficacy of third-generation cephalosporins (3GCs) was compared with that of broader-spectrum β-lactams (BSBLs) [fourth-generation cephalosporins (4GCs) and carbapenems] as empirical therapy in adults with community-onset monomicrobial Enterobacteriaceae bacteraemia. Compared with those in the 3GC group (n = 477), a significantly higher proportion of patients in the BSBL group (n = 141) had initial presentation with severe sepsis or septic shock, critical illness (Pitt bacteraemia score ≥4) at bacteraemia onset and fatal co-morbidities (McCabe classification). For propensity score matching, 318 of the 477 patients in the 3GC group were matched with 106 patients in the BSBL group with the closest propensity scores on the basis of five independent predictors of 28-day mortality. After appropriate matching, no significant differences were observed in major baseline characteristics between the 3GC and BSBL groups in terms of causative micro-organism, bacteraemia severity, major source of bacteraemia, major co-morbidities and severity of co-morbidity. Consequently, the early clinical failure rate (12.9% vs. 12.3%; P = 0.87), bacteraemia severity (Pitt bacteraemia score ≥4; 4.6% vs. 8.2%; P = 0.17) at Day 3, and 3-day (3.8% vs. 7.5%; P = 0.11) and 28-day (13.2% vs. 17.0%; P = 0.33) crude mortality rates between the two groups were similar. These data suggest that the efficacy of 3GCs is similar to that of 4GCs or carbapenems when used as empirical antimicrobial therapy for community-onset Enterobacteriaceae bacteraemia.

Predicting abscesses in adults with community-onset monomicrobial Enterobacteriaceae bacteremia: microorganisms matters

Enterobacteriaceae is a leading pathogen of community-onset bacteremia. This study aims to establish a predictive scoring algorithm to identify adults with community-onset Enterobacteriaceae bacteremia who are at risk for abscesses. Of the total 1262 adults, 152 (12.0%) with abscess occurrence were noted. The 6 risk factors significantly associated with abscess occurrence-liver cirrhosis, diabetes mellitus, thrombocytopenia and high C-reactive protein (>100 mg/L) at bacteremic onset, delayed defervescence, and bacteremia-causing Klebsiella pneumoniae-were each assigned +1 point to form the scoring algorithm. In contrast, the elderly, fatal comorbidity (McCabe classification), and bacteremia-causing Escherichia coli were each assigned -1 point, owing to their negative associations with abscess occurrence. Using the proposed scoring algorithm, a cut-off value of +1 yielded a high sensitivity (85.5%) and an acceptable specificity (60.4%). Although the proposed predictive model needs further validation, this simple scoring algorithm may be useful for the early identification of abscesses by clinicians.

Different clinical presentation of community-onset bacteremia among neutropenic adults in the ED

OBJECTIVES To analyze the differences in clinical presentation and characteristics of community-onset bacteremia between neutropenic and nonneutropenic adults visiting the emergency department. METHODS A case-control study with a ratio of 1:2 was conducted retrospectively over a 6-year period. Demographic characteristics, microorganisms, severity of illness, and clinical outcomes determined from medical records were analyzed. RESULTS In total, 116 neutropenic adults (case patients) and 232 nonneutropenic adults (control patients) were examined. Significant differences in the source of bacteremia, susceptibility, and species of bacteremia-causing organisms between the case patients and control patients were observed by univariate analyses. Significantly more patients presenting with an initial syndrome of severe sepsis or septic shock at the emergency department, having high Pittsburgh bacteremia scores (≥4 points) or having severe comorbidities (McCabe classification), and high 28-day mortality rates were discovered in the case group, compared with the control group. Of note, Pseudomonas aeruginosa (32/137 [23.4%] vs 8/272 [2.9%], P < .001) was more often isolated from the case patients. In a further analysis using a multivariate regression to demonstrate the independent predictors of P aeruginosa infection, patients with neutropenia remained as an independent risk factors (odds ratio, 7.48; P < .001). CONCLUSIONS This study demonstrated obvious differences of community-onset bacteremia in severity, the distribution of microorganisms, and susceptibility between neutropenic and nonneutropenic patients. Antipseudomonas therapy was empirically suggested for neutropenic patients with community-onset bacteremia and reducing the need for a glycopeptide.

A simple scoring algorithm predicting extendedspectrum b-lactamase producers in adults with community-onset monomicrobial Enterobacteriaceae bacteremia

Abstract The incidence of community-onset bacteremia caused by extended-spectrum-&bgr;-lactamase (ESBL) producers is increasing. The adverse effects of ESBL production on patient outcome have been recognized and this antimicrobial resistance has significant implications in the delay of appropriate therapy. However, a simple scoring algorithm that can easily, inexpensively, and accurately be applied to clinical settings was lacking. Thus, we established a predictive scoring algorithm for identifying patients at the risk of ESBL-producer infections among patients with community-onset monomicrobial Enterobacteriaceae bacteremia (CoMEB). In a retrospective cohort, multicenter study, adults with CoMEB in the emergency department (ED) were recruited during January 2008 to December 2013. ESBL producers were determined based on ESBL phenotype. Clinical information was obtained from chart records. Of the total 1141 adults with CoMEB, 65 (5.7%) caused by ESBL producers were identified. Four independent multivariate predictors of ESBL-producer bacteremia with high odds ratios (ORs)—recent antimicrobial use (OR, 15.29), recent invasive procedures (OR, 12.33), nursing home residents (OR, 27.77), and frequent ED user (OR, 9.98)—were each assigned +1 point to obtain the CoMEB-ESBL score. Using the proposed scoring algorithm, a cut-off value of +2 yielded a high sensitivity (84.6%) and an acceptable specificity (92.5%); the area under the receiver operating characteristic curve was 0.92. In conclusion, this simple scoring algorithm can be used to identify CoMEB patients with a high ESBL-producer infection risk. Of note, frequent ED user was firstly demonstrated to be a crucial predictor in predicting ESBL-producer infections. ED clinicians should consider adequate empirical therapy with coverage of these pathogens for patients with risk factors.

Impact of delayed admission to intensive care units on patients with acute respiratory failure

Background/Purpose: To determine the impact of delayed admission to the intensive care unit (ICU) on the clinical outcomes of patients with acute respiratory failure (ARF) in the emergency department (ED). Methods: This retrospective cohort study included non‐traumatic adult patients with ARF and mechanical ventilation support in the ED of a tertiary university hospital in Taiwan from January 1, 2013, to August 31, 2013. Clinical data were extracted from chart records. The primary and secondary outcome measures were a prolonged hospital stay (>30 days) and the in‐hospital crude mortality within 90 days, respectively. Results: For 267 eligible patients (age range 21.0‐98.0 years, mean 70.5 ± 15.1 years; male 184, 68.9%), multivariate analysis was used to determine the significant adverse effects of an ED stay >1.0 hour on in‐hospital crude mortality (odds ratio 2.19, P < .05), which was thus defined as delayed ICU admission. In‐hospital mortality significantly differed between patients with delayed ICU admission and those without delayed admission, as revealed by the Kaplan‐Meier survival curves (P < .05). Moreover, a linear‐by‐linear correlation was observed between the length of ICU waiting time in the ED and the lengths of total hospital stay (r = 0.152, P < .05), ICU stay (r = 0.148, P < .05), and ventilator support (r = 0.222, P < .05). Conclusions: For patients with ARF who required mechanical ventilation support and intensive care, a delayed ICU admission more than 1.0 hour is a strong determinant of mortality and is associated with a longer ICU stay and a longer need for ventilation.