Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better.

BACKGROUND: Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia. METHODS: The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model. RESULTS: Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness. CONCLUSIONS: Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.

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.

Incidence and co-infection with COVID-19 of dengue during the COVID-19 pandemic.

The co-infection of dengue and COVID-19 has been regarded as a public health issue for dengue-endemic countries during the COVID-19 pandemic. Travel restrictions might decrease the chance of mosquitoes biting and, thus, reduce the risk of dengue transmission. However, the spread of dengue was reported to increase with the policies of lockdowns and social distancing in specific areas due to delayed interventions in dengue transmission. Of cases experiencing dengue and COVID-19 co-infection, most recovered after receiving supportive care and/or steroid therapy. However, some episodes of severe or fatal diseases in specific individuals, such as pregnant women, have been reported, and the clinical course of this co-infection is unrecognized or unpredictable. Accordingly, it is crucial to promptly identify predictors of developing severe viral diseases among co-infection patients.

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.

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.

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.

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.

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.

Antimicrobial escalation is not beneficial for Gram-negative bacteremia in adults who remained critically ill after appropriate empirical therapy.

To study whether antimicrobial escalation is beneficial for the outcome of bacteremia patients receiving appropriate but less responsive antimicrobials as empirical therapy, adults with community-onset Gram-negative bacteremia and remained the critical illness after appropriate empirical therapy with third-generation cephalosporins were retrospective enrolled. Clinical outcomes included incidental nosocomial infections, breakthrough bacteremia, and in-hospital crude mortality were compared between patients receiving escalation and non-escalation therapy, after propensity-score (PS) matching at a ratio of 1:3 using independent predictors of 30-day mortality recognized by the multivariate regression model. Initially, the higher proportion of fatal comorbidities (McCabe classification) and 30-day mortality rates was exhibited in the escalation group (51 patients), compared to the non-escalation group (de-escalation, 81; non-switch, 95). After appropriate PS-matching, similar proportions of clinical variables between the escalation (45 patients) and no-escalation (135) groups, in terms of patient demographics, bacteremia severity at onset, severity and types of comorbidities, and bacteremia sources, were observed. Consequently, poorer clinical outcomes, such as the higher rate of incidental nosocomial infections and in-hospital crude mortality as well as the longer length of intravenous antimicrobial administration and hospitalization, were statistically evidenced in the escalation group, compared to the non-escalation group. Conclusively, for patients exhibiting poor responses to appropriate empirical therapy, antimicrobial escalation did not significantly result in improved outcomes; otherwise, clinicians should pay more attention to the strategy of supportive care or adequate control of septic complication.

Differential effects of inappropriate empirical antibiotic therapy in adults with community-onset gram-positive and gram-negative aerobe bacteremia.

Bacteremia is associated with high morbidity and mortality, which contribute substantially to health care costs. A beneficial influence of appropriate empirical antimicrobial therapy (EAT) on patient outcome is evidenced; However, the evidence highlighting a comparison of clinical manifestations and of the effects of inappropriate EAT between Gram-positive and Gram-negative bacteremia is insufficient. In a retrospective 6-year cohort study, the total 2053 adults (Gram-positive, 566; Gram-negative 1487) presenting with community-onset monomicrobial aerobes bacteremia were recruited. Inappropriate EAT was defined as the first dose of an appropriate antimicrobial agent not being administered within the first 24 h after blood cultures were drawn. Although the bacteremia severity (a Pitt bacteremia score) at onset, comorbidity severity (the McCabe-Johnson classification), and 28-day mortality rate were similar in the two groups. Furthermore, after adjustment of independent predictors of 28-day mortality respectively recognized by the multivariate regression model in Gram-negative and Gram-positive groups, the Kaplan-Meier curve and Cox regression analysis revealed a significant difference (adjust odds ratio [AOR], 2.68; P < 0.001) between appropriate and inappropriate EAT in the Gram-negative group, but not in the Gram-positive group (AOR, 1.54; P = 0.06). Conclusively, patients with Gram-positive and Gram-negative bacteremia exhibited the similar presentation in bacteremia severity, but a greater impact of inappropriate EAT on survival of patients with Gram-negative aerobe bacteremia was evidenced.

Differential impacts of inappropriate empirical therapy on ED patients with Staphylococcus aureus and streptococci bacteremia.

BACKGROUND: Staphylococcus aureus (S. aureus) and streptococci are leading Gram-positive pathogens causing community-onset bacteremia. The comparisons of initial presentations and impacts of inappropriate empirical antimicrobial therapy (EAT) on clinical outcomes between the two pathogens are lacking. METHODS: In a 6-year cohort study, adult patients with community-onset monomicrobial S. aureus or streptococci bacteremia in the emergency department (ED) were studied. Clinical variables were collected retrospectively from medical records; the primary outcome was 4-week mortality after ED arrival. The Cox regression model was studied for effects of inappropriate EAT on 4-week mortality, after adjustment of independent predictors of 4-week mortality recognized by the multivariate regression model. RESULTS: A difference of clinical manifestations between S. aureus (291 patients) and streptococci (223) bacteremia was exhibited, in terms of bacteremia sources and comorbidity types, but bacteremia and comorbidity severity at ED arrival were similar. Furthermore, a longer period of the time-to-defervescence and hospitalization as well as more frequencies of septic metastasis were disclosed in S. aureus bacteremia, compared to streptococcal bacteremia. Of note, a significant impact (adjusted odds ratio [ORa], 2.23; 95% confidence interval [CI], 1.25-3.96) of inappropriate EAT on 4-week mortality was evidenced in S. aureus bacteremia, but not in streptococcal bacteremia (ORa, 2.88; 95% CI, 0.85-9.86). CONCLUSIONS: For adults having community-onset monomicrobial bacteremia, the similarity of bacteremia and comorbidity severity at ED arrivals were observed between causative microorganisms of S. aureus and streptococci, but a crucial impact of inappropriate EAT on short-term mortality was only observed in S. aureus.

Validation of MEDS score in predicting short-term mortality of adults with community-onset bacteremia.

BACKGROUND: The Mortality in Emergency Department Sepsis (MEDS) score can be used to stratify ED patients with suspected infections according to mortality risk. However, it has yet to be externally validated for patients having bloodstream infections. METHODS: We retrospectively computed clinical information for the MEDS score, Pitt bacteremia score (PBS), Charlson comorbidity index (CCI), and McCabe-Jackson comorbid classification (MJCC) for adults with community-onset bacteremia. The MEDS score was validated by the comparisons with the following scoring systems: the PBS, CCI, MJCC, PBS plus MJCC, and PBS plus CCI. We evaluated goodness-of-fit statistics and c-statistics as measures of model calibration and discrimination, respectively. RESULTS: Of 2328 adults, a good calibration for 28-day crude mortality was obtained only in the MEDS score and PBS plus MJCC; a higher c-statistic (0.870, P < 0.001) were achieved by the MEDS score, compared to the PBS, CCI MJCC, PBS plus MJCC, and PBS plus CCI. A high c-statistic was observed in two combinative scoring system: the PBS plus CCI (0.855, P < 0.001) and PBS plus MJCC (0.843, P < 0.001). According to the Kaplan-Meier curves, 28-day crude mortality significantly differed between patients with scores equal to or higher than selected cutoff values and those with scores lower than selected cutoff values: 10 in the MEDS score and 5 in the PBS plus MJCC, respectively. CONCLUSION: The MEDS score is an excellent predictor of short-term outcomes in patients with community-onset bacteremia because it provides estimates with higher calibration and discrimination than those of the other scoring systems.

Beneficial effects of early empirical administration of appropriate antimicrobials on survival and defervescence in adults with community-onset bacteremia.

BACKGROUND: Bloodstream infections are associated with high morbidity and mortality, both of which contribute substantially to healthcare costs. The effects of early administration of appropriate antimicrobials on the prognosis and timing of defervescence of bacteremic patients remain under debate. METHODS: In a 6-year retrospective, multicenter cohort, adults with community-onset bacteremia at the emergency departments (EDs) were analyzed. The period from ED arrival to appropriate antimicrobial administration and that from appropriate antimicrobial administration to defervescence was regarded as the time-to-appropriate antibiotic (TtAa) and time-to-defervescence (TtD), respectively. The primary study outcome was 30-day mortality after ED arrival. The effects of TtAa on 30-day mortality and delayed defervescence were examined after adjustment for independent predictors of mortality, which were recognized by a multivariate regression analysis. RESULTS: Of the total 3194 patients, a TtAa-related trend in the 30-day crude (γ = 0.919, P = 0.01) and sepsis-related (γ = 0.909, P = 0.01) mortality rate was evidenced. Each hour of TtAa delay was associated with an average increase in the 30-day crude mortality rate of 0.3% (adjusted odds ratio [AOR], 1.003; P < 0.001) in the entire cohort and 0.4% (AOR, 1.004; P < 0.001) in critically ill patients, respectively, after adjustment of independent predictors of 30-day crude mortality. Of 2469 febrile patients, a TtAa-related trend in the TtD (γ = 0.965, P = 0.002) was exhibited. Each hour of TtAa delay was associated with an average 0.7% increase (AOR, 1.007; P < 0.001) in delayed defervescence (TtD of ≥ 7 days) after adjustment of independent determinants of delayed defervescence. Notably, the adverse impact of the inappropriateness of empirical antimicrobial therapy (TtAa > 24 h) on the TtD was noted, regardless of bacteremia severity, bacteremia sources, or causative microorganisms. CONCLUSIONS: The delay in the TtAa was associated with an increasing risk of delayed defervescence and 30-day mortality for adults with community-onset bacteremia, especially for critically ill patients. Thus, for severe bacteremia episodes, early administration of appropriate empirical antimicrobials should be recommended.

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 score ≥ 4) 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.

Age-Related Trends in Adults with Community-Onset Bacteremia.

To understand the epidemiological variation in bacteremia characteristics among differently aged populations, adults with community-onset bacteremia during a 6-year period were studied in a retrospective cohort. A total of 2,349 bacteremic patients were stratified into four age categories: young adults (18 to 44 years old; 196 patients; 8.3%), adults (45 to 64 years old; 707 patients; 30.1%), the elderly (65 to 84 years old; 1,098 patients; 46.7%), and the oldest old (≥85 years old; 348 patients; 14.8%). Age-related trends in critical illness (a Pitt bacteremia score of ≥4) at bacteremia onset, antibiotic-resistant pathogens (extended-spectrum ß-lactamase [ESBL]-producing Escherichia coli, Klebsiella species, and Proteus mirabilis [EKP]; methicillin-resistant Staphylococcus aureus [MRSA]; and levofloxacin nonsusceptible EKP), inappropriate empirical antibiotic therapy (EAT), and 4-week mortality rate were observed. Using a multivariate regression model, critical illness at bacteremia onset (adjusted odds ratio [AOR], 9.03; P < 0.001) and inappropriate EAT (AOR, 2.67; P < 0.001) were the two leading predictors of 4-week mortality. Moreover, ESBL-producing EKP (AOR, 12.94; P < 0.001), MRSA (AOR, 8.66; P < 0.001), and levofloxacin-nonsusceptible EKP (AOR, 4.27; P < 0.001) were linked to inappropriate EAT. In conclusion, among adults with community onset bacteremia, significant positive age-related trends were noted in antibiotic-resistant pathogens and bacteremia severity, which were related to the increasing incidence of inappropriate EAT and 4-week mortality with age. Thus, different empirical antimicrobial regimens should be considered for distinct age groups.

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

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.

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

BACKGROUND: Early 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. METHODS: In 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. RESULTS: Among 2349 patients, the mean (interquartile range) TtAa was 2.0 (<1 to 12) hours. All selected cutoffs of TtAa, ranging from 1 to 96 hours, were significantly associated with 28-day mortality (adjusted odds ratio (AOR), 0.54-0.65, all P < 0.001), 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 48 hours, as the lowest AOR was identified (0.54, P < 0.001). In subgroup analyses, the most evident TtAa cutoff (i.e., the lowest AOR) remained at 48 hours in mildly ill (PBS = 0; AOR 0.47; P = 0.04) and moderately ill (PBS = 1-3; AOR 0.55; P = 0.02) patients, but shifted to 1 hour in critically ill patients (PBS ≥4; AOR 0.56; P < 0.001). CONCLUSIONS: The 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 48 hours after non-critically ill patients arrive at the ED. As bacteremia severity increases, effective antimicrobial therapy should be empirically prescribed within 1 hour after critically ill patients arrive at the ED.

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.

Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates.

A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 µg/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P = 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.