Inappropriate Empirical Antimicrobial Therapy Research Articles

Guidance of empirical antimicrobial therapy by surveillance cultures in high-risk neutropenic patients: a retrospective cohort study

BackgroundIn neutropenic patients, bloodstream infections (BSI) significantly contribute to morbidity and mortality. Appropriate empirical antibiotic therapy (EAT) of BSI is essential, at the same time overconsumption of very broad-spectrum antibiotics should be avoided. We investigated: (1) whether surveillance cultures can predict BSI with third-generation cephalosporin –resistant Enterobacterales and Pseudomonas aeruginosa (3GC-R), (2) the effect of inappropriate empirical antimicrobial therapy (IEAT) on clinical outcome and (3) the potential reduction of carbapenem use when using surveillance cultures to guide therapy.MethodsRetrospective study of adult patients with haematological malignancies with febrile episodes during chemotherapy-induced high-risk neutropenia in whom surveillance cultures were collected weekly. IEAT was defined as the absence of in vitro susceptibility of blood-isolates to the administered EAT. Clinical outcome (ICU admission and death) was evaluated within 30 days.ResultsA total of 673 febrile episodes occurred among 372 high-risk neutropenic patients. BSI was present in 20.1% (135/673), of which 25.9% (35/135) were due to Enterobacterales and P. aeruginosa. Of these, 17/35 were 3GC-R and 70.6% (12/17) were preceded by 3GC-R colonization. Negative predictive value of surveillance cultures for 3GC-R BSI was 99.1%. IEAT due to (3GC-R) BSI was not significantly associated with clinical outcome. Using surveillance cultures to guide EAT could potentially reduce carbapenem use by 82.8%, when compared to standard EAT with carbapenem.ConclusionsThis retrospective analysis shows that in patients with high-risk neutropenia, surveillance cultures can potentially reduce the use of carbapenems with infrequent IEAT for 3GC-R BSI and no negative impact on clinical outcome.

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

IntroductionBloodstream 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.MethodsWe 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.ResultsWe 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 (I2 = 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 (I2 < 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.ConclusionAlthough 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 Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42021270274.

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

BackgroundStudies 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.MethodsIn 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.ResultsEach 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.ConclusionFor 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.

The epidemiology of bloodstream infection contributing to mortality: the difference between community-acquired, healthcare-associated, and hospital-acquired infections

BackgroundThe epidemiology of bloodstream infection (BSI) is well-established; however, little is known about the contribution of different pathogens to mortality. To understand true burden of BSI, pathogens contributing to mortality were investigated and compared according to where the BSI was acquired.MethodsData from deceased patients in two teaching hospitals in the Republic of Korea were collected. BSI contributing mortality was defined as BSI within 2-weeks before death. Cases were grouped by acquisition sites: community-acquired (CA)-, healthcare-associated (HCA)-, and hospital-acquired (HA)-BSI. Drug resistance, BSI focus, and appropriateness of empirical antimicrobial therapy were also compared.ResultsAmong 1849 deceased patients in the hospitals, 280 (15.1%) patients experienced BSI within 2-weeks before death. In all, 71, 53, and 156 patients in the CA-, HCA-, and HA-BSI groups, respectively, with 316 total isolated pathogens were analyzed. The three most common pathogens were Klebsiella pneumoniae (17.1%), Escherichia coli (16.4%), and Staphylococcus aureus (11.4%). While K. pneumoniae and E. coli were the most common pathogens in CA- and HCA-BSI, Acinetobacter baumannii and Candida species were in HA-BSI. 26.3% (41/156) of patients experienced breakthrough HCA-BSI during administration of carbapenem and/or vancomycin. The proportion of central venous catheter-related infection (0%, 3.4% and 28.3%), carbapenem resistant-Gram negative bacilli (0%, 6.9% and 21.9%), and inappropriate empirical antimicrobial therapy (21.1%, 37.7% and 51.9%; all P < 0.001) were more frequently observed in HA-BSI.ConclusionThe epidemiology of BSI related to mortality had unique characteristics according to the acquisition site. Given the epidemiology of HA-BSI, infection control and antibiotics stewardship programs should be emphasized.

Is qSOFA Suitable for Early Diagnosis of Sepsis Among Bacteremia Patients in Emergency Departments? Time for a Reappraisal of Sepsis-3 Criteria.

Background: For early recognition of patients with sepsis, quick Sequential Organ Failure Assessment (qSOFA) was proposed by Sepsis-3 criteria as initial sepsis identification outside of intensive care units. However, the new definition has subsequently led to controversy and prompted much discussion for delayed treatment efforts. We aimed to validate Sepsis-3 criteria on bacteremia patients by investigating prognostic impacts of inappropriate administration of empirical antimicrobial therapy (EAT) and delayed source control (SC) compared to Sepsis-2 criteria.Methods: In the multicenter cohort of adults with community-onset bacteremia in emergency departments (EDs), adverse effects of delayed treatment efforts on 30-day mortality were examined in septic and non-septic patients by fulfilling the Sepsis-2 or Sepsis-3 criteria using the Cox regression model after adjusting independent determinants of mortality.Results: Of the 3,898 total adults, septic patients accounted for 92.8% (3,619 patients) by Sepsis-2 criteria (i.e., SIRS criteria). Using Sepsis-3 criteria, 1,827 (46.9%) patients were diagnosed with early sepsis (i.e., initial qSOFA scores ≥ 2) in EDs and 2,622 (67.3%) with sepsis during hospitalization (i.e., increased SOFA scores of ≥ 2 from ED arrival). The prognostic impacts of inappropriate EAT or delayed SC (for complicated bacteremia) were both significant in septic patients with fulfilling the Sepsis-2 or Sepsis-3 (i.e., SOFA) criteria, respectively. Meanwhile, these delayed treatment efforts trivially impact prognoses of non-septic patients recognized by the Sepsis-2 or Sepsis-3 (i.e., SOFA) definitions. Notably, prognostic effects of inappropriate EAT or delayed SC were disclosed for septic patients in EDs, specifically those with qSOFA scores of ≥ 2, and prognostic impacts of delayed treatment efforts remained significant for patients initially recognized early as being non-septic (i.e., initial qSOFA scores of <2).Conclusions: For patients with community-onset bacteremia, inappropriate EAT and delayed SC might result in unfavorable outcomes of patients early identified as being non-septic on ED arrival based on the qSOFA scores (by Sepsis-3 criteria). Accordingly, a more prudent diagnosis of sepsis adopted among bacteremia patients in the ED is necessary.

Clinical and bacterial characteristics of Pseudomonas aeruginosa affecting the outcome of patients with bacteraemic pneumonia

Few studies have assessed the clinical and bacterial characteristics of Pseudomonas aeruginosa (PA) bacteraemic pneumonia (BP) episodes. This study analysed all non-duplicate PA-BP episodes from a tertiary hospital in 2013–2017. Epidemiology, clinical data, antimicrobial therapy and outcomes were recorded. Whole-genome sequencing was performed on PA blood isolates. The impact on early and late overall mortality of host, antimicrobial treatment and pathogen factors was assessed by multivariate logistic regression analysis. Of 55 PA-BP episodes, 32 (58.2%) were caused by extensively drug-resistant (XDR) PA. ST175 (32.7%) and ST235 (25.5%) were the most frequent high-risk clones. β-Lactamases/carbapenemases were detected in 29 isolates, including blaVIM-2 (27.2%) and blaGES type (25.5%) [blaGES-5 (20.0%), blaGES-1 (3.6%) and blaGES-20 (1.8%)]. The most prevalent O-antigen serotypes were O4 (34.5%) and O11 (30.9%). Overall, an extensive virulome was identified in all isolates. Early mortality (56.4%) was independently associated with severe neutropenia (aOR = 4.64, 95% CI 1.11–19.33; P = 0.035) and inappropriate empirical antimicrobial therapy (aOR = 5.71, 95% CI 1.41–22.98; P = 0.014). Additionally, late mortality (67.3%) was influenced by septic shock (aOR = 8.85, 95% CI 2.00–39.16; P = 0.004) and XDR phenotype (aOR = 5.46, 95% CI 1.25–23.85; P = 0.024). Moreover, specific genetic backgrounds [ST235, blaGES, gyrA (T83I), parC (S87L), exoU and O11 serotype] showed significant differences in patient outcomes. Our results confirm the high mortality associated with PA-BP. Besides relevant clinical characteristics and inappropriate empirical therapy, bacteria-specific genetics factors, such as XDR phenotype, adversely affect the outcome of PA-BP.

Risk factors and mortality associated with multi-drug-resistant Gram-negative bacterial infection in adult patients following abdominal surgery

Multi-drug-resistant (MDR) Gram-negative bacterial (GNB) infection remains a significant cause of morbidity and mortality among surgical patients. The objective of this study was to recognize the risk factors for MDR GNB infection in patients following abdominal surgery, and determine the predictors independently associated with death. From 2010 to 2017, a retrospective cohort study was conducted among patients with abdominal surgery admitted to the surgical intensive care unit (ICU). Patients with GNB infection were included for analyses. In total, 364 patients experienced GNB infection following abdominal surgery. Of these, 117 (32.1%) were MDR GNB infection. Of 133 MDR GNB isolates, the most common isolate was Escherichia coli (45.1%). Patients with MDR GNB infection had significantly longer ventilator-days and hospital stay, as well as higher 30-day and in-hospital mortality compared with non-MDR GNB patients. Multi-variable analysis showed that longer length of pre-ICU stay, surgical re-exploration, receipt of group 2 carbapenems (e.g. imipenem, meropenem and doripenem) and fluoroquinolones, and higher total bilirubin were independent risk factors for the acquisition of MDR GNB infection. Predictors for 30-day mortality among patients with MDR GNB infection were chronic kidney disease, receipt of group 2 carbapenems and inappropriate empirical antimicrobial therapy. This study provides important information about the risk factors for MDR GNB infection and 30-day mortality among patients following abdominal surgery.

Short-Term Effects of Appropriate Empirical Antimicrobial Treatment with Ceftolozane/Tazobactam in a Swine Model of Nosocomial Pneumonia.

The rising frequency of multidrug-resistant and extensively drug-resistant (MDR/XDR) pathogens is making more frequent the inappropriate empirical antimicrobial therapy (IEAT) in nosocomial pneumonia, which is associated with increased mortality. We aim to determine the short-term benefits of appropriate empirical antimicrobial treatment (AEAT) with ceftolozane/tazobactam (C/T) compared with IEAT with piperacillin/tazobactam (TZP) in MDR Pseudomonas aeruginosa pneumonia. Twenty-one pigs with pneumonia caused by an XDR P. aeruginosa strain (susceptible to C/T but resistant to TZP) were ventilated for up to 72 h. Twenty-four hours after bacterial challenge, animals were randomized to receive 2-day treatment with either intravenous saline (untreated) or 25 to 50 mg of C/T per kg body weight (AEAT) or 200 to 225 mg of TZP per kg (IEAT) every 8 h. The primary outcome was the P. aeruginosa burden in lung tissue and the histopathology injury. P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage (BAL) fluid, the development of antibiotic resistance, and inflammatory markers were secondary outcomes. Overall, P. aeruginosa lung burden was 5.30 (range, 4.00 to 6.30), 4.04 (3.64 to 4.51), and 4.04 (3.05 to 4.88) log10CFU/g in the untreated, AEAT, and IEAT groups, respectively (P = 0.299), without histopathological differences (P = 0.556). In contrast, in tracheal secretions (P < 0.001) and BAL fluid (P = 0.002), bactericidal efficacy was higher in the AEAT group. An increased MIC to TZP was found in 3 animals, while resistance to C/T did not develop. Interleukin-1β (IL-1β) was significantly downregulated by AEAT in comparison to other groups (P = 0.031). In a mechanically ventilated swine model of XDR P. aeruginosa pneumonia, appropriate initial treatment with C/T decreased respiratory secretions' bacterial burden, prevented development of resistance, achieved the pharmacodynamic target, and may have reduced systemic inflammation. However, after only 2 days of treatment, P. aeruginosa tissue concentrations were moderately affected.

290. Impact of follow up blood cultures on outcomes of patients with gram-negative bloodstream infections

BackgroundImportance of follow up blood cultures (FUBC) for Staphylococcus aureus bloodstream infections (BSI) is well known, but the role of FUBC in gram-negative BSI remains controversial. This retrospective cohort study examined the association between obtaining FUBC and mortality in patients with gram-negative BSI.MethodsAdults with first episodes of community-onset monomicrobial BSI due to gram-negative bacilli hospitalized at Prisma Health-Midlands hospitals in Columbia, South Carolina, USA from January 1, 2010 to June 30, 2015 were identified. Patients who died or were discharged from hospital within 72 hours of collection of index blood culture were excluded to minimize impact of survival and selection biases on results, respectively. FUBC were defined as repeat blood cultures obtained between 24 and 96 hours from initial positive blood culture. Cox proportional hazards regression model was used to examine association between obtaining FUBC and 28-day all-cause mortality.ResultsAmong 766 patients with gram-negative BSI, 219 (28.6%) had FUBC obtained and 15 of 219 (6.8%) FUBC were persistently positive. Overall, median age was 67 years, 438 (57%) were women, 457 (60%) had urinary source of infection, and 426 (56%) had BSI due to Escherichia coli. Mortality was significantly lower in patients who had FUBC obtained than in those who did not have FUBC (6.3% vs. 11.7%, log-rank p=0.03). Obtaining FUBC was independently associated with reduced mortality (hazards ratio [HR] 0.49, 95%CI: 0.25–0.90) after adjustments for age (HR 1.35 per decade, 95% CI: 1.13–1.61), cancer (HR 5.90, 95% CI: 3.53–9.84), Pitt bacteremia score (HR 1.38 per point, 95% CI: 1.26–1.50), and inappropriate empirical antimicrobial therapy (HR 2.37, 95% CI: 1.17–4.39).ConclusionObtaining FUBC was associated with improved survival in hospitalized patients with gram-negative BSI. These observations are consistent with the results of recent publications from Italy and North Carolina supporting utilization of FUBC in the management of gram-negative BSI.DisclosuresJulie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)TRC Healthcare (Speaker’s Bureau)

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

BackgroundStaphylococcus 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. MethodsIn 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. ResultsA 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). ConclusionsFor 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.

1309. The Impact of Clinical Practice Guideline Using Educational Intervention for Improvement of Diabetic Foot Infections Treatment Outcomes

BackgroundDiabetic foot infections (DFIs) are important cause of lower-extremity amputation. The inappropriate empirical antimicrobial therapy for DFI was associated with amputation. We created the Clinical Practice Guideline (CPG) of empirical antimicrobial (ATB) therapy for in-patients with DFIs. The primary outcome of present study was to evaluate the intervention using educate and training the surgeons to adhere with CPG. The secondary outcome was the decreasing of unfavorable outcome (amputations).MethodsA prospective study of CPG implementation for treatment in adult in-patients who had DFIs was conducted at surgical and orthopedics wards. The CPG was developed by the investigator team based on the data from our previous study (submitted to publish). CPG was presented monthly to train the orthopedic and vascular surgeons for 1 year. The empirical ATB regimens were prescribed by the responsible surgeon who was trained to use CPG. Demographics data, wound characteristics, microbiological data, ATB therapy, and clinical outcome were recorded. The appropriate empirical ATB treatment was determined by investigators weather CPG matched or microbiological matched. The adherence to CPG, the appropriate empirical ATB, and the unfavorable outcome were analyzed. All data were reported by descriptive and inferential statistics.ResultsA total of 85 DFIs patients were enrolled. The patients received the appropriate empirical ATB matched to CPG and matched to microbiological data, were 87% and 67%, respectively. The unfavorable outcome was 26% while previously was 72.4% (submitted to publish data) before CPG implementation. The independent factors associated with unfavorable outcomes were (1) an inappropriate ATB and (2) infections with drug-resistant pathogens (adjusted relative ratio; aRR 2.98; 95% CI: 1.36–6.55, P = 0.007 and aRR 1.90; 95% CI: 1.05–3.43, P = 0.034, respectively).ConclusionThe current study demonstrated that mothly training of CPG resulting in the high adherence (87%) of CPG use and resulting in high rate of appropriate empirical ATB. Educational intervention insisted the responsible physician for administration the appropriate ATB with the improvement of unfavorable outcome in DFIs.Disclosures All authors: No reported disclosures.

Clinical manifestations, molecular characteristics, antimicrobial susceptibility patterns and contributions of target gene mutation to fluoroquinolone resistance in Elizabethkingia anophelis.

Elizabethkingia anophelis has recently emerged as a cause of life-threatening infections in humans. We aimed to investigate the clinical and molecular characteristics of E. anophelis. A clinical microbiology laboratory database was searched to identify patients with Elizabethkingia infections between 2005 and 2016. Isolates were re-identified and their species were confirmed using 16S rRNA gene sequencing. Patients with E. anophelis infections were included in this study. Clinical information, antimicrobial susceptibility and mutations in DNA gyrase and topoisomerase IV were analysed. A total of 67 patients were identified to have E. anophelis infections, including 47 men and 20 women, with a median age of 61 years. Comorbidity was identified in 85.1% of the patients. Among the 67 E. anophelis isolates, 40 (59.7%) were isolated from blood. The case fatality rate was 28.4%. Inappropriate empirical antimicrobial therapy was an independent risk factor for mortality (adjusted OR = 10.01; 95% CI = 1.20-83.76; P = 0.034). The isolates were 'not susceptible' to multiple antibiotics. All the isolates were susceptible to minocycline. Susceptibilities to ciprofloxacin and levofloxacin were 4.5% and 58.2%, respectively. Mutations in DNA gyrase subunit A were identified in 11 isolates that exhibited high-level fluoroquinolone resistance. Minocycline has the potential to be the drug of choice in patients with E. anophelis infections. Additional investigations are needed to determine the optimal antimicrobial agents to treat this life-threatening infection.

Evaluation of early antimicrobial therapy adaptation guided by the BetaLACTA\xae test: a case-control study

BackgroundRapid diagnostic tests detecting microbial resistance are needed for limiting the duration of inappropriateness of empirical antimicrobial therapy (EAT) in intensive care unit patients, besides reducing the use of broad-spectrum antibiotics. We hypothesized that the betaLACTA® test (BLT) could lead to early increase in the adequacy of antimicrobial therapy.MethodsThis was a case-control study. Sixty-one patients with BLT-guided adaptation of EAT were prospectively included, and then matched with 61 “controls” having similar infection characteristics (community or hospital-acquired, and source of infection), in whom EAT was conventionally adapted to antibiogram results. Endpoints were to compare the proportion of appropriate (primary endpoint) and optimal (secondary endpoint) antimicrobial therapies with each of the two strategies, once microbiological sample culture results were available.ResultsCharacteristics of patients, infections and EAT at inclusion were similar between groups. Nine early escalations of EAT occurred in the BLT-guided adaptation group, reaching 98% appropriateness vs. 77% in the conventional adaptation group (p < 0.01). The BLT reduced the time until escalation of an inappropriate EAT from 50.5 (48–73) to 27 (24–28) hours (p < 0.01). Seventeen early de-escalations occurred in the BLT-guided adaptation group, compared to one in the conventional adaptation group, reducing patients’ exposure to broad-spectrum beta-lactam such as carbapenems. In multivariate analysis, use of the BLT was strongly associated with early appropriate (OR = 18 (3.4–333.8), p = 0.006) and optimal (OR = 35.5 (9.6–231.9), p < 0.001) antimicrobial therapies. Safety parameters were similar between groups.ConclusionsOur study suggests that a BLT-guided adaptation strategy may allow early beta-lactam adaptation from the first 24 hours following the beginning of sepsis management.

Association between inappropriate empirical antimicrobial therapy and hospital length of stay in Gram-negative bloodstream infections: stratification by prognosis.

The potential benefit from appropriate empirical antimicrobial therapy in patients with favourable prognosis at initial presentation with Gram-negative bloodstream infection (BSI) remains unclear. This retrospective cohort study examined the impact of inappropriate empirical antimicrobial therapy on hospital length of stay (HLOS) following Gram-negative BSI after stratification by predicted prognosis using the BSI mortality risk score (BSIMRS). Hospitalized adults with first episodes of Gram-negative BSI from 1 January 2010 to 31 December 2013 at Palmetto Health Hospitals in Columbia, SC, USA were identified. Multivariate Cox proportional hazards regression was used to examine the association between inappropriate empirical antimicrobial therapy and HLOS overall and within each predefined BSIMRS category (<5 and ≥5). Among 830 unique patients with Gram-negative BSI, 469 and 361 had BSIMRS <5 and ≥5, respectively. Overall, the median age was 65 years, 448 (54%) were women, Escherichia coli (444; 53%) was the most common bloodstream isolate and 444 (53%) had a urinary source of infection. After adjustments in the multivariate model, BSIMRS (HR = 1.14 per point, 95% CI = 1.11-1.17, P < 0.001) and inappropriate empirical antimicrobial therapy (HR = 1.41, 95% CI = 1.07-1.91, P = 0.01) were independently associated with increased risk of remaining hospitalized following Gram-negative BSI. Median HLOS with appropriate and inappropriate empirical antimicrobial therapy was 7 and 10 days, respectively, in patients with BSIMRS <5 (P = 0.03) and 13 and 17 days, respectively, in those with BSIMRS ≥5 (P = 0.02). Inappropriate empirical antimicrobial therapy is associated with prolonged HLOS following Gram-negative BSI in patients with both good and guarded prognosis.

Association Between Inappropriate Empirical Antimicrobial Therapy and Hospital Length of Stay in Gram-Negative Bloodstream Infections

Association Between Inappropriate Empirical Antimicrobial Therapy and Hospital Length of Stay in Gram-Negative Bloodstream Infections

Impact of fluoroquinolone resistance in Gram-negative bloodstream infections on healthcare utilization

There has been a concerning increase in fluoroquinolone resistance among Gram-negative bloodstream isolates. This retrospective cohort study examines the implications of fluoroquinolone resistance on use of healthcare resources in patients with Gram-negative bloodstream infections (BSI). Hospitalized adults with first episodes of community-onset Gram-negative BSI from 2010 to 2012 at Palmetto Health Hospitals in Columbia, SC, USA were identified. Multivariate linear regression was used to examine risk factors for prolonged hospital length of stay (HLOS) in survivors of Gram-negative BSI. Among 474 unique patients, 384 (81%) and 90 (19%) had BSI due to fluoroquinolone-susceptible (FQ-S) and fluoroquinolone non-susceptible (FQ-NS) Gram-negative bacilli, respectively. The FQ-NS bloodstream isolates, particularly Escherichia coli, were more likely than FQ-S isolates to be multi-drug resistant (56% versus 6%, p < 0.001). Compared with patients with BSI due to FQ-S bloodstream isolates, those with FQ-NS isolates were more likely to receive inappropriate empirical antimicrobial therapy (26% versus 3%, p < 0.001), have longer mean HLOS (11.6 versus 9.3 days, p 0.03) and treatment duration with intravenous antibiotics during hospitalization (9.1 versus 7.1 days, p 0.001), and use outpatient intravenous antibiotics at hospital discharge (15% versus 8%, p 0.05). After adjustments in the multivariate model, inappropriate empirical antimicrobial therapy was an independent risk factor for prolonged HLOS in survivors of Gram-negative BSI (parameter estimate 3.65 days, 95% CI 0.43–6.86). Multi-drug resistance among FQ-NS bloodstream isolates limits both empirical and definitive antimicrobial treatment options and poses excessive burdens on the healthcare system.

Stratification of the impact of inappropriate empirical antimicrobial therapy for Gram-negative bloodstream infections by predicted prognosis.

The bloodstream infection mortality risk score (BSIMRS) predicts the outcome of patients with Gram-negative bloodstream infections (BSI) with high discrimination. This retrospective cohort study examined the impact of inappropriate antimicrobial therapy on mortality in adult patients with Gram-negative BSI admitted to Palmetto Health Hospitals in Columbia, SC, USA, from 1 January 2011 to 31 December 2012 after stratification by predicted prognosis at initial presentation using BSIMRS. A multivariate Cox regression model was used to identify independent risk factors for 28-day mortality overall and within each predefined BSIMRS category (<5, 5 to 9, and ≥ 10). Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated from a predictive logistic regression model of mortality. Overall, 390 unique patients with first episodes of Gram-negative BSI were identified. The median age was 66 years, and 229 (59%) were women. There was significant association between inappropriate antimicrobial therapy and mortality in patients with BSIMRS of 5 to 9 (adjusted hazard ratio [aHR], 3.55; 95% confidence intervals [CI], 1.22 to 8.31; P = 0.02) and BSIMRS of ≥ 10 (aHR, 4.99; 95% CI, 1.09 to 22.87; P = 0.04) but not in those with BSIMRS of <5 (aHR, 3.34; 95% CI, 0.17 to 22.77; P = 0.34). RRR, ARR, and NNT were 0.25, 0.02, and 63 for BSIMRS of <5; 0.56, 0.32, and 3 for BSIMRS of 5 to 9; and 0.39, 0.39, and 3 for BSIMRS of ≥ 10, respectively. There is a significant benefit from appropriate antimicrobial therapy in patients with Gram-negative BSI with guarded (BSIMRS of 5 to 9) and poor (BSIMRS of ≥ 10) predicted prognosis. Survival difference remains unclear among those with good predicted prognosis (BSIMRS of <5) at initial presentation.

Prevalence and impact of extended-spectrum β-lactamase production on clinical outcomes in cancer patients with Enterobacter species bacteremia.

Background/AimsWe examined the prevalence of extended-spectrum β-lactamase (ESBL) production and the impact of ESBL on clinical outcomes in cancer patients with Enterobacter spp. bacteremia.MethodsUsing prospective cohort data on Enterobacter bacteremia obtained between January 2005 and November 2008 from a tertiary care center, the prevalence and clinical impact of ESBL production were evaluated.ResultsTwo-hundred and three episodes of Enterobacter spp. bacteremia were identified. Thirty-one blood isolates (15.3%, 31/203) scored positive by the double-disk synergy test. Among 17 isolates in which ESBL genes were detected by polymerase chain reaction and sequencing, CTX-M (n = 12), SHV-12 (n = 11), and TEM (n = 4) were the most prevalent ESBL types. Prior usage of antimicrobial agents (77.4% vs. 54.0%, p = 0.02) and inappropriate empirical antimicrobial therapy (22.6% vs. 3.0%, p < 0.001) were more commonly encountered in the ESBL-positive group than in the extended-spectrum cephalosporin-susceptible ESBL-negative group, respectively. Clinical outcomes did not differ significantly between the two groups (30-day mortality rate, 19.4% vs. 17.0%, p = 0.76; median length of hospital stay, 24.0 days vs. 30.5 days, p = 0.97). Initial presentation of severe sepsis/septic shock, pneumonia, and intra-abdominal infection were independently associated with 30-day mortality.ConclusionsThe prevalence of ESBL-producing isolates was 15.3% in cancer patients with Enterobacter bacteremia. Although inappropriate empirical therapy was more common in the ESBL-positive group, ESBL production was not associated with poorer outcomes.

Healthcare-associated, community-acquired and hospital-acquired bacteraemic urinary tract infections in hospitalized patients: a prospective multicentre cohort study in the era of antimicrobial resistance

AbstractThe clinical and microbiological characteristics of community-onset healthcare-associated (HCA) bacteraemia of urinary source are not well defined. We conducted a prospective cohort study at eight tertiary-care hospitals in Spain, from October 2010 to June 2011. All consecutive adult patients hospitalized with bacteraemic urinary tract infection (BUTI) were included. HCA-BUTI episodes were compared with community-acquired (CA) and hospital-acquired (HA) BUTI. A logistic regression analysis was performed to identify 30-day mortality risk factors. We included 667 episodes of BUTI (246 HCA, 279 CA and 142 HA). Differences between HCA-BUTI and CA-BUTI were female gender (40% vs 69%, p <0.001), McCabe score II–III (48% vs 14%, p <0.001), Pitt score ≥2 (40% vs 31%, p 0.03), isolation of extended spectrum β-lactamase-producing Enterobacteriaciae (13% vs 5%, p <0.001), median hospital stay (9 vs 7 days, p 0.03), inappropriate empirical antimicrobial therapy (21% vs 13%, p 0.02) and mortality (11.4% vs 3.9%, p 0.001). Pseudomonas aeruginosa was more frequently isolated in HA-BUTI (16%) than in HCA-BUTI (4%, p <0.001). Independent factors for mortality were age (OR 1.04; 95% CI 1.01–1.07), McCabe score II–III (OR 3.2; 95% CI 1.8–5.5), Pitt score ≥ 2 (OR 3.2 (1.8–5.5) and HA-BUTI OR 3.4 (1.2–9.0)). Patients with HCA-BUTI are a specific group with significant clinical and microbiological differences from patients with CA-BUTI, and some similarities with patients with HA-BUTI. Mortality was associated with patient condition, the severity of infection and hospital acquisition.