Inappropriate Initial Antibiotic Therapy Research Articles

Impact of multidrug resistance on outcomes in hematologic cancer patients with bacterial bloodstream infections

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003–2007) to 39.7% (2018–2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum β-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

High mortality associated with inappropriate initial antibiotic therapy in hematological malignancies with Klebsiella pneumoniae bloodstream infections

Bloodstream infections caused by multidrug-resistant organisms such as Klebsiella pneumoniae are a significant challenge in managing hematological malignancies. This study aims to characterize the epidemiology of Klebsiella pneumoniae bloodstream infections specifically in patients with hematological malignancies, delineate the patterns of initial antibiotic therapy, assess the prevalence of resistant strains, identify risk factors for these resistant strains, and evaluate factors influencing patient outcomes. A retrospective analysis was conducted at a single center from January 2017 to December 2020, focusing on 182 patients with hematological malignancies who developed Klebsiella pneumoniae bloodstream infections. We compared the 30-day mortality rates between patients receiving appropriate and inappropriate antibiotic treatments, including the effectiveness of both single-drug and combination therapies. Kaplan–Meier survival analysis and multivariate logistic and Cox regression were used to identify factors influencing mortality risk. The 30-day all-cause mortality rate was 30.2% for all patients. The 30-day all-cause mortality rates were 77.2% and 8.8% in patients who received inappropriate initial treatment and appropriate initial treatment (p < 0.001). Inappropriate initial treatment significantly influenced mortality and was a key predictor of 30-day mortality, along with septic shock and previous intensive care unit (ICU) stays. Patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections exhibited more severe clinical symptoms compared to the CSKP group. The study demonstrates a significant association between empirical carbapenem administration and the escalating prevalence of CRKP and multidrug-resistant K. pneumoniae (MDR-KP) infections. Furthermore, the study identified inappropriate initial antibiotic therapy, septic shock, and ICU admission as independent risk factors for 30-day mortality.

Risk Factors for Recurrence of Community-Onset Urinary Tract Infections Caused by Extended-Spectrum Cephalosporin-Resistant Enterobacterales.

Extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) are an increasingly important cause of community-onset urinary tract infections (UTIs), including recurrent infections. We evaluated risk factors for recurrence among patients with community-onset ESCrE UTI. This retrospective cohort study included adults with community-onset ESCrE UTI in the Duke University Health System from April 2018 through December 2021. ESCrE UTI recurrence by the same species was assessed 14-180 days (ie, 6 months) after completion of antibiotic treatment. We evaluated the relationships between candidate risk factors and time to recurrence using Cox proportional hazards regression models. Among 1347 patients with community-onset ESCrE UTI, 202 (15.0%) experienced recurrent infection during the 6-month follow-up period. Independent risk factors for recurrence included neurogenic bladder (adjusted hazard ratio [aHR], 1.8 [95% confidence interval {CI}, 1.2-2.6]; P = .005), prior history of UTI (aHR, 2.4 [95% CI, 1.7-3.3]; P < .001), and fluoroquinolone nonsusceptibility of the index UTI (aHR, 1.5 [95% CI, 1.1-2.1]; P = .02). Klebsiella pneumoniae infection was associated with recurrence in univariate analysis (HR, 1.6 [95% CI, 1.1-2.1]; P = .007) but not multivariate analysis (aHR, 1.4 [95% CI, 1.0-1.9]; P = .06). Inappropriate initial or definitive antibiotic therapy was not predictive of ESCrE UTI recurrence. Recurrence of community-onset ESCrE UTI was common and associated with several patient and pathogen-level risk factors. Future studies should evaluate microbial risk factors for recurrence and improve the management of ESCrE UTI.

Determinants of Mortality for Ventilated Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia.

To determine if vHAP is an independent predictor of mortality among patients with nosocomial pneumonia. Single-center retrospective cohort study conducted at Barnes-Jewish Hospital, St. Louis, MO, between 2016 and 2019. Adult patients with a pneumonia discharge diagnosis were screened and patients diagnosed with vHAP and VAP were included. All patient data was extracted from the electronic health record. The primary outcome was 30-day all-cause mortality (ACM). One thousand one-hundred twenty unique patient admissions were included (410 vHAP, 710 VAP). Thirty-day ACM was greater for patients with vHAP compared with VAP (37.1% vs 28.5%; p = 0.003). Logistic regression analysis identified vHAP (adjusted odds ratio [AOR], 1.77; 95% CI, 1.51-2.07), vasopressor use (AOR, 2.34; 95% CI, 1.94-2.82), Charlson Comorbidity Index (1-point increments) (AOR, 1.21; 95% CI, 1.18-1.24), total antibiotic treatment days (1-d increments) (AOR, 1.13; 95% CI, 1.11-1.14), and Acute Physiology and Chronic Health Evaluation II score (1-point increments) (AOR, 1.04; 95% CI, 1.03-1.06) as independent predictors of 30-day ACM. The most common bacterial pathogens identified as causes of vHAP and VAP were Staphylococcus aureus, Enterobacterales species, and Pseudomonas aeruginosa. In this single-center cohort study with low rates of initial inappropriate antibiotic therapy, vHAP had greater 30-day ACM compared with VAP after adjusting for potential confounding variables including disease severity and comorbidities. This finding suggests that clinical trials enrolling patients with vHAP need to account for this outcome difference in their trial design and data interpretation.

The Clash of the Titans: COVID-19, Carbapenem-Resistant Enterobacterales, and First mcr-1-Mediated Colistin Resistance in Humans in Romania.

(1) Background: Antibiotic resistance and coronavirus disease-19 (COVID-19) represent a dual challenge in daily clinical practice, inducing a high burden on public health systems. Hence, we aimed to dynamically evaluate the impact of COVID-19 on patients with carbapenem-resistant Enterobacterales (CRE) urinary tract infections (UTIs), as well as the antibiotic resistance trends after the onset of the pandemic. (2) Methods: We conducted a prospective study including patients with CRE UTIs who were enrolled both pre- and during the pandemic from 2019 to 2022. We further performed a standardized and comparative clinical, paraclinical, and microbiological assessment between patients with and without COVID-19. (3) Results: A total of 87 patients with CRE UTIs were included in this study (46 pre-pandemic and 41 during the pandemic, of which 21 had associated Severe Acute Respiratory Syndrome Coronavirus-2 infection). Klebsiella pneumoniae was the main etiological agent of the UTIs, with the majority of strains (82.7%) being carbapenemase producers (mainly OXA-48 producers), while five of the 34 colistin-resistant isolates were harboring the mobile colistin resistance-1 (mcr-1) gene. COVID-19 patients presented a significantly worse outcome with higher rates of intensive care unit (ICU) admissions (66.7% for COVID patients vs. 18.2% for non-COVID patients, p < 0.001), while the fatality rates were also considerably higher among patients with concomitant viral infection (33.3% vs. 12.1%, p < 0.001). Besides COVID-19, additional risk factors associated with increased mortality were urinary catheterization, sepsis with K. pneumoniae, impaired liver and kidney function, and an inappropriate initial empiric antibiotic therapy. (4) Conclusions: COVID-19 showed a pronounced negative impact on patients with CRE UTIs, with significantly longer hospitalizations and higher ICU admissions and mortality rates.

Antibiotic susceptibility of bacterial strains and bacteriological profile from patients with lower respiratory tract infections in a teaching hospital

Lower respiratory tract infections (LRTI) are one of the commonest health problems demanding frequent consultation and hospitalization. Unnecessary and inappropriate initial antibiotic therapy is a potentially modifiable factor that is associated with increased mortality in patients with serious infections. To study bacterial profile and susceptibility pattern of lower respiratory tract infections in a teaching hospital.Prospective study done in the department of Microbiology at Prathima Institute of Medical Sciences, Nagunuru, Karimnagar, Telangana., Tover a period of 18 months ie from January 2019 to July 2020. A total of 120 samples from respiratory tract were studied for bacterial isolates and antibiotic susceptibility. A total of 120 cases were studied. The male to female ratio was 2:1. Among the bacterial isolates, 76.6% were Gram negative bacilli and 23.3% were gram positive cocci. Among Gram negative bacteria, the predominant bacterial isolate was Klebisella. pneumoniae (45.8%) followed by Pseudomonas. aeruginosa (28.3%.)Present study, was based on the pattern of resistance to commonly used antibiotics by organisms causing lower respiratory tract infections (LRTIs) in our institute. This may help us to study the more susceptible group of drugs in our institute which would help prepare an antibiogram and develop a policy for rational antibiotic prescription.

Multidrug-Resistant Healthcare-Associated Infections in Neonates with Severe Respiratory Failure and the Impacts of Inappropriate Initial Antibiotic Therap.

Background: Multidrug-resistant (MDR) pathogens have emerged as an important issue in neonatal intensive care units (NICUs), especially in critically ill neonates with severe respiratory failure. We aimed to investigate neonatal healthcare-associated infections (HAIs) caused by MDR pathogens and the impacts of inappropriate initial antibiotic therapy on the outcomes. Methods: We retrospectively analyzed all cases of HAIs in neonates with severe respiratory failure in a tertiary-level NICU in Taiwan between January 2014 and May 2020. All clinical features, microbiology, therapeutic interventions, and outcomes were compared between the MDR-HAI and non-MDR HAI groups. Multivariate regression analyses were used to investigate independent risk factors for sepsis-attributable mortality. Results: A total of 275 critically ill neonates with severe respiratory failure who had HAIs were enrolled. Ninety-five cases (34.5%) were caused by MDR pathogens, and 141 (51.3%) cases had positive bacterial cultures from multiple sterile sites. In this cohort, the MDR-HAI group was more likely to receive inappropriate initial antibiotic therapy (51.0% versus 4.7%, respectively; p < 0.001) and exhibit delayed control of the infectious focus (52.6% versus 37.8%, respectively; p = 0.021) compared with the non-MDR HAI group. The sepsis-attributable and final in-hospital rates were 21.8% and 37.1%, respectively, and they were comparable between the MDR-HAI and non-MDR HAI groups. Empirically broad-spectrum antibiotics were prescribed in 76.7% of cases, and inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. Independent risk factors for sepsis-attributable mortality in neonates with severe respiratory failure included the presence of septic shock (OR: 3.61; 95% CI: 1.54–8.46; p = 0.003), higher illness severity (OR: 1.33; 95% CI: 1.04–1.72; p = 0.026), and neonates with bronchopulmonary dysplasia (OR: 2.99; 95% CI: 1.47–6.09; p = 0.003). Conclusions: MDR pathogens accounted for 34.5% of all neonatal HAIs in the NICU, but neither MDR pathogens nor inappropriate initial antibiotics were associated with final adverse outcomes. Because the overuse of broad-spectrum antibiotics has emerged as an important issue in critically ill neonates, the implementation of antimicrobial stewardship to promote the appropriate use of antimicrobials is urgently needed.

1630. What is Treatment Time Zero Among Hospitalized Patients with Bacteremia?

BackgroundCommon operational definitions of antibiotic exposures in infectious diseases research do not accurately reflect actual treatment, as daily changes in clinical presentation (i.e. improvement, worsening) and clinical information (i.e. causative organism, susceptibilities) lead to frequent changes in treatment, both within empiric and definitive treatment periods. Common definitions create periods of ‘ignored’ exposures, and we’ve previously shown that antibiotic treatments during ‘ignored’ periods vary widely. Therefore, we assessed the distribution of important time points for antibiotic treatments for Staphylococcus aureus bacteremia.MethodsOur retrospective cohort study included hospital admissions in the national Veterans Affairs (VA) Healthcare System with S. aureus positive blood cultures from 2010 to 2018. Admissions with inappropriate initial antibiotic therapy for S. aureus were excluded. We implemented daily exposure mapping to identify antibiotic exposures and changes in treatment on each day of the admission until discharge, or 30 days post-admission for longer stays, and in relation to the culture final report date.ResultsWe identified 21,947 admissions meeting our inclusion criteria. Antibiotic initiation most often occurred on the culture collection date (68.7%) or the day after (22.6%). Median time to the culture final report date from the culture collection date was 4 days (interquartile range [IQR] 3 to 5). Among those with changes in therapy (n=19,392, 88.4%), median time to first change in therapy was 2 days prior to the culture final report date (IQR -3 to -1). The first change in therapy occurred before the culture final report date for 76.3% of admissions and on the culture final report date for 11.9% of admissions. Further changes were common on the culture final report date (49.5%) and the day after the final report date (45.3%).ConclusionChanges in antibiotic therapy are common prior to finalization of culture reports. While initial culture results and provider knowledge of these initial results are not date/time-stamped, initial change within a reasonable period from culture collection appears to be more accurate in defining empiric and definitive treatment periods than commonly used operational definitions.Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support)

Gram-negative bacilli bacteremia: a 7 year retrospective study in a referral Brazilian tertiary-care teaching hospital.

Introduction. Bloodstream infection is one of the most frequent and challenging hospital-acquired infections and it is associated with high morbidity, mortality and additional use of healthcare resources.Hypothesis/Gap Statement: Bloodstream infections have consequences for the patient, such as the evolution to mortality and inappropriate empirical antibiotic prescription, especially when caused by multidrug-resistant Gram-negative bacilli.Objective. To assess the impact of bloodstream infection and the status of multidrug resistance (MDR) in the evolution of patients who received inappropriate initial antibiotic therapy.Methods. A retrospective surveillance was conducted on nosocomial bloodstream infections caused by Gram-negative bacilli (GNB) from January 2012 to December 2018 in an adult intensive care unit of a Brazilian tertiary teaching hospital.Results. We identified 270 patients with GNB nosocomial bacteremia. Non-survivors were older (with an average age of 58.8 years vs 46.9 years, P=<0.0001), presented more severe illnesses, were immunosuppressed (73.7 vs 37.6%, P=<0.0001), were more likely to have septic shock (55.8 vs 22.4%, P=<0.0001) and had an increased usage of mechanical ventilators (98.6 vs 89.6%, P=0.0013) than survivors. In a logistic regression model, inappropriate empirical antibiotic therapy was not an independent predictor of mortality, different from mechanical ventilator (P=<0.0001; OR=28.0; 95% CI=6.3-123.6), septic shock (P=0.0051; OR=2.5; 95% CI=1.3-4.9) and immunosuppression (P=0.0066; OR=2.6; 95% CI=1.3-5.2). In contrast, in a separate model, MDR was strongly associated with the prescription of inappropriate initial antibiotic therapy (P=0.0030; OR=5.3; 95% CI=1.7-16.1). The main isolated pathogens were Acinetobacter baumannii (23.6 %) and Klebsiella pneumoniae (18.7 %). The frequency of MDR organisms was high (63.7 %), especially among non-fermenting bacilli (60.9 %), highlighting A. baumannii (81.6 %) and Pseudomonas aeruginosa (41.8 %).Conclusion. Illness severity (septic shock and immunosuppression) and mechanical ventilation were identified as predictors of mortality. Additionally, MDR was a major determinant of inappropriate antibiotic empirical therapy, but not associated with mortality, and both characteristics were not statistically associated with death.

Impacts of Multidrug-Resistant Pathogens and Inappropriate Initial Antibiotic Therapy on the Outcomes of Neonates with Ventilator-Associated Pneumonia.

: BackgroundIt is unknown whether neonatal ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) pathogens and inappropriate initial antibiotic treatment is associated with poor outcomes after adjusting for confounders. Methods: We prospectively observed all neonates with a definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and March 2020. All clinical features, therapeutic interventions, and outcomes were compared between the MDR–VAP and non-MDR–VAP groups. Multivariate regression analyses were used to investigate independent risk factors for treatment failure. Results: Of 720 neonates who were intubated for more than 2 days, 184 had a total of 245 VAP episodes. The incidence rate of neonatal VAP was 10.1 episodes/per 1000 ventilator days. Ninety-six cases (39.2%) were caused by MDR pathogens. Neonates with MDR–VAP were more likely to receive inadequate initial antibiotic therapy (51.0% versus 4.7%; p < 0.001) and had delayed resolution of clinical symptoms (38.5% versus 25.5%; p = 0.034), although final treatment outcomes were comparable with the non-MDR–VAP group. Inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. The VAP-attributable mortality rate and overall mortality rate of this cohort were 3.7% and 12.0%, respectively. Independent risk factors for treatment failure included presence of concurrent bacteremia (OR 4.83; 95% CI 2.03–11.51; p < 0.001), septic shock (OR 3.06; 95% CI 1.07–8.72; p = 0.037), neonates on high-frequency oscillatory ventilator (OR 4.10; 95% CI 1.70–9.88; p = 0.002), and underlying neurological sequelae (OR 3.35; 95% CI 1.47–7.67; p = 0.004). Conclusions: MDR–VAP accounted for 39.2% of all neonatal VAP in the neonatal intensive care unit (NICU), but neither inappropriate initial antibiotics nor MDR pathogens were associated with treatment failure. Neonatal VAP with concurrent bacteremia, septic shock, and underlying neurological sequelae were independently associated with final worse outcomes.

Risk Factors of Initial Inappropriate Antibiotic Therapy and the Impacts on Outcomes of Neonates with Gram-Negative Bacteremia.

Background: Timely appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. However, the relevant data and significant impacts have not been well studied in the neonatal intensive care unit (NICU). Methods: An 8-year (1 January 2007–31 December 2014) cohort study of all NICU patients with gram-negative bacteremia (GNB) in a tertiary-care medical center was performed. Inadequate empirical antibiotic therapy was defined when a patient did not receive any antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture sampling. Neonates with GNB treated with inadequate antibiotics were compared with those who received initial adequate antibiotics. Results: Among 376 episodes of Gram-negative bacteremia, 75 (19.9%) received inadequate empirical antibiotic therapy. The cause of inadequate treatment was mostly due to the pathogen resistance to prescribed antibiotics (88.0%). Bacteremia caused by Pseudomonas aeruginosa (Odds ratio [OR]: 20.8, P < 0.001) and extended spectrum β-lactamase (ESBL)-producing bacteria (OR: 18.4, P < 0.001) had the highest risk of inadequate treatment. Previous exposure with third generation cephalosporin was identified as the only independent risk factor (OR: 2.52, 95% CI: 1.18–5.37, P = 0.018). Empirically inadequately treated bacteremias were significantly more likely to have worse outcomes than those with adequate therapy, including a higher risk of major organ damage (20.0% versus 6.6%, P < 0.001) and infectious complications (25.3% versus 9.3%, P < 0.001), and overall mortality (22.7% versus 11.0%, P = 0.013). Conclusions: Inadequate empirical antibiotic therapy occurs in one-fifth of Gram-negative bacteremias in the NICU, and is associated with worse outcomes. Additional prospective studies are needed to elucidate the optimal timing and aggressive antibiotic regimen for neonates who are at risk of antibiotic-resistant Gram-negative bacteremia.

Pseudomonas infections among hospitalized adults in Latin America: a systematic review and meta-analysis

BackgroundTreatment of resistant Pseudomonas aeruginosa infection continues to be a challenge in Latin American countries (LATAM). We synthesize the literature on the use of appropriate initial antibiotic therapy (AIAT) and inappropriate initial antibiotic therapy (IIAT) in P. aeruginosa infections, and the literature on risk factors for acquisition of resistant P. aeruginosa among hospitalized adult patients in LATAM.MethodsMEDLINE, EMBASE, Cochrane, and LILAC were searched between 2000 and August 2019. s and full-text articles were screened in duplicate. Random effects meta-analysis was conducted when studies were sufficiently similar.ResultsThe screening of 165 citations identified through literature search yielded 98 full-text articles that were retrieved and assessed for eligibility, and 19 articles conducted in Brazil (14 articles), Colombia (4 articles), and Cuba (1 article) met the inclusion criteria. Of 19 eligible articles, six articles (840 subjects) examined AIAT compared to IIAT in P. aeruginosa infections; 17 articles (3203 total subjects) examined risk factors for acquisition of resistant P. aeruginosa; and four articles evaluated both. Four of 19 articles were rated low risk of bias and the remaining were deemed unclear or high risk of bias. In meta-analysis, AIAT was associated with lower mortality for P. aeruginosa infections (unadjusted summary OR 0.48, 95% CI 0.28–0.81; I2 = 59%), compared to IIAT and the association with mortality persisted in subgroup meta-analysis by low risk of bias (3 articles; unadjusted summary OR 0.46, 95% CI 0.28–0.81; I2 = 0%). No meta-analysis was performed for studies evaluating risk factors for acquisition of resistant P. aeruginosa as they were not sufficiently similar. Significant risk factors for acquisition of resistant P. aeruginosa included: prior use of antibiotics (11 articles), stay in the intensive care unit (ICU) (3 articles), and comorbidity score (3 articles). Outcomes were graded to be of low strength of evidence owing to unclear or high risk of bias and imprecise estimates.ConclusionOur study highlights the association of AIAT with lower mortality and prior use of antibiotics significantly predicts acquiring resistant P. aeruginosa infections. This review reinforces the need for rigorous and structured antimicrobial stewardship programs in the LATAM region.

Does inappropriate initial antibiotic therapy affect in-hospital mortality of patients in the emergency department with Escherichia coli and Klebsiella pneumoniae bloodstream infections?

Extended-spectrum β-lactamase (ESBL)-positive bloodstream infection (BSI) is on the rise worldwide. The purpose of this study is to evaluate the impact of inappropriate initial antibiotic therapy (IIAT) on in-hospital mortality of patients in the emergency department (ED) with Escherichia coli and Klebsiella pneumoniae BSIs. This retrospective single-center cohort study included all adult patients with E. coli and K. pneumoniae BSIs between January 2007 and December 2013, who had undergone a blood culture test and initiation of antibiotics within 6 h of ED registration time. Multiple logistic regression was used to adjust for bacterial species, IIAT, time to antibiotics, age, sex, quick Sepsis Related Organ Failure Assessment (qSOFA) score ⩾ 2, and comorbidities. A total of 3533 patients were enrolled (2967 alive and 566 deceased, in-hospital mortality rate 16%). The patients with K. pneumoniae ESBL-positive BSI had the highest mortality rate. Non-survivors had qSOFA scores ⩾ 2 (33.6% vs 9.5%, P < 0.001), more IIAT (15.0% vs 10.7%, P = 0.004), but shorter mean time to antibiotics (1.70 vs 1.84 h, P < 0.001). A qSOFA score ⩾ 2 is the most significant predictor for in-hospital mortality; however, IIAT and time to antibiotics were not significant predictors in multiple logistic regression analysis. In subgroup analysis divided by qSOFA scores, IIAT was still not a significant predictor. Severity of the disease (qSOFA score ⩾ 2) is the key factor influencing in-hospital mortality of patients with E. coli and K. pneumoniae BSIs. The time to antibiotics and IIAT were not significant predictors because they in turn were affected by disease severity.

Ignorance of pre-ED healthcare setting is a factor leading to inappropriate initial antibiotic treatment of sepsis in ED and poor outcomes in ICU.

Appropriate initial antibiotic therapy is critical for successfully treating sepsis. In the emergency department (ED), clinicians often rely on septic symptoms to guide empirical therapy. The aim of this study was to investigate whether history of contacting pre-ED healthcare setting is easy to be neglected and whether the patients received more inappropriate initial antibiotic therapy and developed poorer outcomes. Septic patients (n=453) admitted from ED to the intensive care unit (ICU) between 2014 and 2017 were retrospectively selected. Appropriate antibiotic treatment or not was determined by checking whether the selected antibiotics can effectively eradicate the bacteria identified. Various indexes were compared between patients with appropriate and inappropriate initial antibiotic treatments, including septic symptoms (qSOFA scores) in ED, septic-severity change in ICU (SOFA-score ratios), and septic outcomes (APACHE II scores, stay length, 30-day survival probability). These indexes were also compared between pre-ED healthcare and pre-ED community patients. In comparison with pre-ED community patients, pre-ED healthcare patients received more inappropriate initial antibiotic treatment in ED, showing poorer outcomes in ICU, including septic severity, stay-lengths in ICU and 30-day survival probabilities. Pre-ED settings is more significant than qSOFA scores to predict the inappropriate initial antibiotic treatment. Pre-ED healthcare settings, which are indexes for infection with antibiotic resistant pathogens, are easy to be neglected in the first hour in ED. We suggested that standard operating procedure for getting enough information of pre-ED settings should be incorporated to the 1h bundle of sepsis guideline.

Usefulness of Early C-Reactive Protein Kinetics in Response and Prognostic Assessment in Infected Critically Ill Patients: An Observational Retrospective Study.

The ideal biomarker to assess response and prognostic assessment in the infected critically ill patient is still not available.The aims of our study were to analyze the association between early C-reactive protein kinetics and duration and appropriatenessof antibiotic therapy and its usefulness in predicting mortality in infected critically ill patients. We have carried out an observational retrospective study in a cohort of 60 patients with community-acquiredpneumonia, aspiration pneumonia and bacteremia at an intensive care unit. We have collected C-reactive protein consecutive serumlevels for eight days as well as duration and appropriateness of initial antibiotic therapy. C-reactive protein kinetic groups were definedbased on the levels at days 0, 4 and 7. With a follow-up of one year, we have evaluated mortality at different time-points. We have obtained three different C-reactive protein kinetic groups from the sample: fast response, delayed but fast responseand delayed and slow response. We did not find statistically significant associations between C-reactive protein kinetics and early (intensivecare unit, hospital and 28-days) or late (six months and one year) mortality and antibiotic therapy duration (p > 0.05). Althoughthere were no statistically significant differences between the appropriateness of antibiotic therapy and the defined groups (p = 0.265),no patient with inappropriate antibiotic therapy presented a fast response pattern. Several studies suggest the importance of this protein in infection. Early C-reactive protein kinetics is not associated with response and prognostic assessment in infected critically ill patients.Nevertheless, a fast response pattern tends to exclude initial inappropriate antibiotic therapy.

Poor clinical outcomes associated with community-onset urinary tract infections due to extended-spectrum cephalosporin-resistant Enterobacteriaceae.

Resistance to extended-spectrum cephalosporins (ESC) among Enterobacteriaceae (EB) is increasingly prevalent. We sought to determine the clinical outcomes associated with community-onset ESC-resistant (ESC-R) EB urinary tract infections (UTIs) in a US health system. Retrospective cohort study.PatientsAll patients presenting to the emergency departments (EDs) or outpatient practices with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed subjects 1:1 on study year. Multivariable logistic regression analyses were performed to evaluate the association between ESC-R EB UTI and the outcomes of clinical failure and inappropriate initial antibiotic therapy (IIAT). A total of 302 patients with community-onset EB UTI were included, with 151 exposed and unexposed. On multivariable analyses, UTI due to an ESC-R EB was significantly associated with clinical failure (odds ratio [OR], 7.07; 95% confidence interval [CI], 3.16-15.82; P<.01). Other independent risk factors for clinical failure included infection with Citrobacter spp and need for hemodialysis. UTI due to an ESC-R EB was also significantly associated with IIAT (OR, 4.40; 95% CI, 2.64-7.33; P<.01). Community-onset UTI due to an ESC-R EB organism is significantly associated with clinical failure, which may be due in part to IIAT. Further studies are needed to determine which patients in the community are at high risk for drug-resistant infection to help inform prompt diagnosis and appropriate antibiotic prescribing for ESC-R EB.

Lower neutrophil-to-lymphocyte ratio predicts high risk of multidrug-resistant Pseudomonas aeruginosa infection in patients with hospital-acquired pneumonia.

Background and purposeHospital-acquired pneumonia (HAP) remains an important cause of morbidity and mortality despite advances in antimicrobial therapy. The emergence of multidrug resistant (MDR) Pseudomonas aeruginosa (PA) is of major concern. Our aim was to evaluate the risk factors and prognosis of HAP due to MDR-PA infection.Patients and methodsIn a retrospective observational study, we collected data on all episodes of HAP caused by PA (PA-HAP) occurring from January 2013 to December 2016. Characteristics of patients with drug-sensitive PA were compared with those with MDR-PA. Data of demographic, underlying conditions, peripheral neutrophil-to-lymphocyte ratio (NLR), and clinical outcomes were collected and analyzed.ResultsOne hundred fifty-seven patients with PA-HAP were included, of which 69 (43.9%) patients were diagnosed with MDR-PA infection. There were significant differences between MDR-PA group and non-MDR-PA group on the following variables: initial inappropriate antibiotic therapy (P<0.001, OR 0.103, 95% CI 0.044–0.244), admission in more than two departments in previous 30 days (P<0.001, OR 0.186, 95% CI 0.072–0.476), and NLR level (P=0.020, OR 0.911, 95% CI 0.843–0.985). The effect of antibiotic treatment was significantly different (P<0.001, OR 4.263, 95% CI 2.142–8.483). The 30-day mortality was higher in MDR-PA group than that in non-MDR-PA group (P<0.001).ConclusionWe have shown that lower NLR level was identified as a clinical predictor of MDR-PA infection in HAP patients. Even with goal-directed therapy, MDR-PA infection implicates poor outcomes in patients with HPA.

Primary pyomyositis in North India: a clinical, microbiological, and outcome study.

Background/AimsPyomyositis is an infective condition with primary involvement of the skeletal muscles. There is sparse recent literature on patients with pyomyositis.MethodsThis study was carried out at emergency services of a tertiary care center located in subtropical area of Indian subcontinent.ResultsSixty-two patients of primary pyomyositis formed the study cohort. Mean age of occurrence was 29.9 ± 14.8 years. There were 54 men. Twelve patients had underlying medical diseases. Muscle pain was seen in all 62 patients. Forty-eight patients (77.4%) had the fever. Most common site of involvement was thigh muscles (n = 29, 46.8%). Forty-nine patients (79%) presented in the suppurative stage of illness. Patients with comorbidities were older (age: median 36 years [interquartile range (IQR), 25 to 47] vs. 24 years [IQR, 16 to 35], p = 0.024), had higher culture positivity with gram-negative organisms (8/9 [88.89%] vs. 6/29 [20.69%], p = 0.001). Importantly, higher number of these patients received inappropriate antibiotics initially. Patients with positive pus culture result had higher complication rate (32/38 [84.21%] vs. 10/18 [55.56%], p = 0.044). Six patients (9.7%) had in-hospital mortality. Lower first-day serum albumin, initial inappropriate antibiotic therapy, and advanced form of the disease at presentation were associated with increased in-hospital mortality.ConclusionsPrimary pyomyositis is not an uncommon disease entity. Patients with comorbidities were more likely to receive initial inappropriate antibiotic therapy. Patients with positive pus culture report had the higher rate of complications. Lower first-day serum albumin, initial inappropriate antibiotic therapy and advanced form of the disease at presentation were associated with increased in-hospital mortality.

Clinical characteristics and prognostic risk factors of healthcare-associated pneumonia in a Korean tertiary teaching hospital.

The 2016 American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) guidelines removed the concept of healthcare-associated pneumonia (HCAP). We examined whether the 2016 ATS/IDSA guidelines are applicable in Korea.We conducted a retrospective, observational study of pneumonia patients who were hospitalized at a tertiary teaching hospital from March 2012 to February 2014. Identified pathogens that were not susceptible to β-lactams, macrolides, and fluoroquinolones were defined as community-acquired pneumonia drug-resistant pathogens (CAP-DRPs). We analyzed the risk factors for 28-day mortality and the occurrence rate of CAP-DRPs.Of the 1046 patients, 399 were classified with HCAP and 647 with CAP. HCAP patients were older and had more comorbidities than CAP patients. Initial pneumonia severity index (PSI) was higher in patients with HCAP than with CAP. HCAP was associated with not only an increased rate of CAP-DRPs (HCAP, 19.8%; CAP, 4.0%; P < .001) but also an increased rate of inappropriate initial antibiotic therapy (IIAT) (HCAP, 16.8%; CAP, 4.6%; P < .001). HCAP was also associated with an increased 28-day mortality rate compared with CAP (HCAP, 14.5%; CAP, 6.3%; P < .001). In a multivariable analysis, PSI was an independent risk factor for 28-day mortality in HCAP patients (odds ratio 1.02, 95% confidence interval 1.01–1.04). CAP-DRPs and IIAT were not associated with mortality.Patients with HCAP revealed higher rates of CAP-DRPs, IIAT, and mortality than patients with CAP. However, CAP-DRPs and IIAT were not associated with mortality. PSI was the main predictive factor for 28-day mortality in patients with HCAP.

Poor Clinical Outcomes Associated with Community-Onset Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae Urinary Tract Infections

BackgroundUrinary tract infections (UTIs) are the most common bacterial infection among adults in the community. Recent data suggest an increase in bacterial resistance to first line antibiotics used for UTI, though the impact on clinical outcomes is unclear. The objective of our study was to determine clinical outcomes associated with community-onset extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae (EB) UTI.MethodsA retrospective cohort study was conducted in a large health system from 2010 to 2013. All patients presenting to an emergency department or outpatient clinic with UTI due to EB were included. Exposed subjects were those with an EB demonstrating resistance to an ESC (ceftriaxone or ceftazidime). Unexposed subjects were those with ESC-susceptible EB UTIs and were matched to cases 1:1 based on study year. Multivariable logistic regression analyses were performed to evaluate the association between ESC-R EB UTI and 1) clinical failure (defined as ongoing symptoms, repeat positive culture, or need for additional antibiotics within 7 days); 2) inappropriate initial antibiotic therapy (IIAT) (defined as failure to receive an antibiotic to which the organism was susceptible within 48 hours of presentation).ResultsA total of 302 patients with community-onset EB UTI were included. On multivariable analyses, a UTI with an ESC-R EB was significantly associated with clinical failure (odds ratio [OR] 5.12, 95% confidence interval [CI] 2.79–9.39, P < 0.01). Other variables independently associated with clinical failure included presence of pyelonephritis at the time of UTI diagnosis (OR 2.15, 95% CI 1.14–4.03, p 0.02) and infection with Citrobacter species (OR 29.56, 95% CI 4.46–195.91, P < 0.01). ESC-R EB UTI was also associated with IIAT on multivariable analysis (OR 3.73, 95% CI 2.25–6.21, P < 0.01).ConclusionCommunity-onset UTI due to an ESC-R EB organism is associated with a significantly increased risk of clinical failure, which may be due in part to the use of inappropriate initial antibiotic therapy. Further studies are needed to determine which patients in the community are at high risk for drug-resistant infection to help inform prompt urine culture ordering and appropriate antibiotic prescribing for ESC-R EB.Disclosures All authors: No reported disclosures.