Chung Hsun Lee

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 (nu2009=u2009135), significantly higher proportions of patients in the ESC treatment group (nu2009=u2009456) 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%; Pu2009=u20090.37), the proportion of critical illness (Pitt bacteraemia score ≥4) (0% vs. 0%; Pu2009=u20091.00) and defervescence (52.6% vs. 42.6%; Pu2009=u20090.13) 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; Pu2009=u20090.15), late clinical failure rate (18.2% vs. 10.7%; Pu2009=u20090.10) and 28-day crude mortality rate (0.8% vs. 3.3%; Pu2009=u20090.37) 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.

Timing of appropriate empirical antimicrobial administration and outcome of adults with community-onset bacteremia

BackgroundEarly administration of appropriate antimicrobials has been correlated with a better prognosis in patients with bacteremia, but the optimum timing of early antibiotic administration as one of the resuscitation strategies for severe bacterial infections remains unclear.MethodsIn a retrospective cohort study, adults with community-onset bacteremia at the emergency department (ED) were analyzed. Effects of different cutoffs of time to appropriate antibiotic (TtAa) administration after arrival at the ED on 28-day mortality were examined, after adjustment for independent predictors of mortality identified by multivariate regression analysis.ResultsAmong 2349 patients, the mean (interquartile range) TtAa was 2.0 (<1 to 12) hours. All selected cutoffs of TtAa, ranging from 1 to 96xa0hours, were significantly associated with 28-day mortality (adjusted odds ratio (AOR), 0.54–0.65, all Pu2009<u20090.001), after adjustment of the following prognostic factors: fatal comorbidities (McCabe classification), critical illness (Pitt bacteremia score (PBS) ≥4) on arrival at the ED, polymicrobial bacteremia, extended-spectrum beta-lactamase-producer bacteremia, underlying malignancies or liver cirrhosis, and bacteremia caused by pneumonia or urinary tract infections. The adverse impact of TtAa on 28-day mortality was most evident at the cutoff of 48xa0hours, as the lowest AOR was identified (0.54, Pu2009<u20090.001). In subgroup analyses, the most evident TtAa cutoff (i.e., the lowest AOR) remained at 48xa0hours in mildly ill (PBSu2009=u20090; AOR 0.47; Pu2009=u20090.04) and moderately ill (PBSu2009=u20091–3; AOR 0.55; Pu2009=u20090.02) patients, but shifted to 1xa0hour in critically ill patients (PBS ≥4; AOR 0.56; Pu2009<u20090.001).ConclusionsThe time from triage to administration of appropriate antimicrobials is one of the primary determinants of mortality. The optimum timing of appropriate antimicrobial administration is the first 48xa0hours after non-critically ill patients arrive at the ED. As bacteremia severity increases, effective antimicrobial therapy should be empirically prescribed within 1xa0hour after critically ill patients arrive at the ED.

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.

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 (nu2009=u2009477), a significantly higher proportion of patients in the BSBL group (nu2009=u2009141) 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%; Pu2009=u20090.87), bacteraemia severity (Pitt bacteraemia score ≥4; 4.6% vs. 8.2%; Pu2009=u20090.17) at Day 3, and 3-day (3.8% vs. 7.5%; Pu2009=u20090.11) and 28-day (13.2% vs. 17.0%; Pu2009=u20090.33) 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.

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.

Propensity-matched analysis of the impact of extended-spectrum β-lactamase production on adults with community-onset Escherichia coli, Klebsiella species, and Proteus mirabilis bacteremia

BACKGROUNDnThe presence of extended-spectrum β-lactamase (ESBL) in Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) is of great microbiological and clinical importance. The study dealing with the direct impact of ESBL producers on the outcome of patients with community-onset bacteremia is lacking.nnnMETHODSnAdults with community-onset EKP bacteremia were recruited retrospectively during a 6-year period. ESBL producers were determined according to ESBL phenotype. ESBL patients were compared on a 1:2 basis with non-ESBL patients by using propensity-score matching (PSM) calculated based on independent predictors of 28-day mortality.nnnRESULTSnOf the 1141 eligible adult patients, 65 (5.7%) caused by ESBL producers. Significant differences between the two groups were discovered in the proportions of patients with critical illness (a Pitt bacteremia scorexa0≥xa04) at bacteremia onset, inappropriate empirical antibiotic therapy, bacteremia because of urosepsis and pneumonia, and several comorbidities. In a PSM analysis after controlling for six independent predictors-critical illness at bacteremia onset, underlying fatal comorbidities (McCabe classification), inappropriate empirical antibiotic therapy, comorbidities with liver cirrhosis, bacteremia because of urosepsis and pneumonia-a appropriate matching between two groups (ESBL group, 60 patients; non-ESBL group, 120) were observed in age, causative microorganism, bacteremia severity, major comorbidities, comorbidity severity, and major bacteremia source. Consequently, a strong relationship between ESBL producers and poor prognosis was highlighted.nnnCONCLUSIONSnThe adverse influence of ESBL producers on clinical outcomes was presented with respect to adults with community-onset EKP bacteremia. Establishing a predictive scoring algorithm for identifying patients at risk of ESBL-producer infections is crucial.

Etiology of community-onset monomicrobial bacteremic pneumonia and its clinical presentation and outcome: Klebsiella and Pseudomonas matters

To describe the difference of the clinical features, bacteremia severity, and outcome of patient with community-onset bacteremic pneumonia between Pseudomonas, Klebsiella, and other causative microorganisms, the total 278 adults with community-onset monomicrobial bacteremic pneumonia were studied in a retrospective cohort. Klebsiella (61 patients, 21.9%) and Pseudomonas (22, 7.9%) species was the leading and the fifth common pathogen, respectively. More patients having initial presentation with critical illness (a Pitt bacteremia scorexa0≥xa04) and a fatal comorbidity (McCabe classification) as well as a higher short- (30-day) or long-term (90-day) mortality rate was evidenced in patients infected with Klebsiella or Pseudomonas species, compared to other causative microorganisms. Compared to patients in the Klebsiella group, more frequencies of recent chemotherapy and an initial presentation of febrile neutropenia, and less proportions of diabetes mellitus were disclosed among those in the Pseudomonas group. Of importance, a significantly differential survival curve between Klebsiella or Pseudomonas species and other species during 30-day or 90-day period after bacteremia onset but a similarity of Pseudomonas and Klebsiella species was evidenced, using the Cox-regression after adjusting the independent predictors of 30-day mortality. Conclusively, of pathogens causing community-onset bacteremic pneumonia, Klebsiella and Pseudomonas species should be recognized as the highly virulent pathogens and resulted in poor short- and long-term prognoses.

Propensity score matched analysis comparing the clinical outcome of Klebsiella pneumoniae and Escherichia coli causing community-onset monomicrobial bacteremia

Abstract Bacteremia is a life-threatening condition that is associated with substantial healthcare costs. Escherichia coli and Klebsiella pneumoniae are the leading causes of community-onset gram-negative bacteremia. However, a comprehensive comparison between these pathogens involved in bacteremia episodes has yet to be reported. In this retrospective cohort study, adults with community-onset monomicrobial bacteremia caused by E coli or K pneumoniae were recruited in the emergency department of a medical center during a 6-year period, and the clinical variables were collected retrospectively from medical records. The complicated abscess occurrence was determined through imaging studies, according to the opinion of an infectious disease consultant. According to the independent predictors of 28-day mortality identified through multivariate regression analyses, patients in the E coli group were propensity score matched (PSM) in a 1:1 ratio to those in the K pneumoniae group. A total of 274 and 823 adults with K pneumoniae and E coli bacteremia were included in the present study. The K pneumoniae group had more patients with fatal comorbidities (McCabe classification), critical illness (Pitt bacteremia score ≥ 4) at bacteremia onset, and initial syndrome (e.g., severe sepsis and septic shock) as well as a higher crude mortality rate than did the E coli group. After appropriate matching, no significant differences were observed in the critical illness at bacteremia onset, initial syndrome, major comorbidities, and comorbidity severity of the 2 groups (E coli, nu200a=u200a242; K pneumoniae, nu200a=u200a242). Furthermore, despite similar 14- and 28-day crude mortality rates between the 2 PSM groups, more frequent abscess occurrences and a longer length of hospitalization were observed in the K pneumoniae group than in the E coli group. Conclusively, numerous clinical features at initial presentations varied between the E coli and K pneumoniae groups. Despite conducting a PSM analysis to control the differences in the baseline characteristics, a longer length of hospitalization and more frequent abscess occurrences were observed in the K pneumoniae group than in the E coli group.