Inappropriate Empirical Treatment Research Articles

Inappropriate empirical antimicrobial treatment in bloodstream infections patients in the era of multidrug resistance

Background and objectives: Bloodstream infection (BSI) by multidrug-resistant Pseudomonas aeruginosa is a severe infection. This study aimed to evaluate and identify the predictors of mortality in patients who had bloodstream infection by carbapenem-resistant P. aeruginosa. Methods: This is a retrospective cohort study, approved by Committee of Ethics in Research with Human Participants, which included 87 consecutive patients hospitalized in a referral hospital in Brazil. Clinical and demographic information about each patient were obtained from hospital records. The Student’s T-test was used to compare continuous variables and x2 or Fisher’s exact tests to compare categorical variables. To determine independent risk factors for 30-day mortality, a multiple logistic regression model was used. A survival curve was constructed using the Kaplan–Meier method. Results: Among the patients, 87.3% use antibiotics previously, 60.9% received inadequate empirical treatment, and the 30-day mortality rate was 57.5%. Inappropriate antibiotic empirical therapy was independently associated with a 30-days death and mortality rate. Conclusion: These findings can show some insights about the relationship between higher mortality and inappropriate empirical therapy for patients with BSI by P. aeruginosa. There is a need for better diagnostic tests and infection control programs should focus on de-escalation the antibiotic inappropriate therapy, mainly in BSI caused by carbapenem-resistant P. aeruginosa.

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project.

ABSTRACTBiliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score ≤ 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected.IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.

Clinical Characteristics, Outcomes, and Risk Factors for Mortality in Patients with Stenotrophomonas maltophilia Bacteremia.

This study aimed to establish the clinical features, outcomes, and factors associated with mortality in patients with Stenotrophomonas maltophilia (S. maltophilia) septicemia. The characteristics and outcome data used in this retrospective study were collected from medical records at Songklanagarind Hospital. Risk factors for survival were analyzed using χ2-tests, Kaplan–Meier curves, and Cox regression. A total of 117 patients with S. maltophilia bacteremia were analyzed. The patients’ median age was 45 years, 77 (70%) were male, 105 (90%) had comorbidities, 112 (96%) had previously undergone carbapenem therapy, and over half of the patients were on invasive medical devices. Trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolone showed high susceptibility rates to S. maltophilia, with 93% and 88% susceptibility, respectively. Patients who received appropriate empirical antibiotic treatment had significantly reduced 14-day, 30-day, and in-hospital mortality rates than those who did not (p < 0.001). The days of hospital stay and costs for those who received appropriate and inappropriate empirical antimicrobial treatment were 21 and 34 days (p < 0.001) and 142,463 and 185,663 baht, respectively (p < 0.002). Our results suggest that an appropriate empirical antibiotic(s) is significantly associated with lower 30-day mortality in hospitalized patients with S. maltophilia septicemia.

Possible misdiagnosis, inappropriate empiric treatment, and opportunities for increased diagnostic testing for patients with vulvovaginal candidiasis-United States, 2018.

Vulvovaginal candidiasis (VVC) is a common cause of vaginitis, but the national burden is unknown, and clinical diagnosis without diagnostic testing is often inaccurate. We aimed to calculate rates and evaluate diagnosis and treatment practices of VVC and recurrent vulvovaginal candidiasis (RVVC) in the United States. We used the 2018 IBM® MarketScan® Research Databases, which include health insurance claims data on outpatient visits and prescriptions for >28 million people. We used diagnosis and procedure codes to examine underlying conditions, vaginitis-related symptoms and conditions, diagnostic testing, and antibacterial and antifungal treatment among female patients with VVC. Among 12.3 million female patients in MarketScan, 149,934 (1.2%) had a diagnosis code for VVC; of those, 3.4% had RVVC. The VVC rate was highest in the South census region (14.3 per 1,000 female patients) and lowest in the West (9.9 per 1000). Over 60% of patients with VVC did not have codes for any diagnostic testing, and microscopy was the most common test type performed in 29.5%. Higher rates of diagnostic testing occurred among patients who visited an OB/GYN (53.4%) compared with a family practice or internal medicine provider (24.2%) or other healthcare provider types (31.9%); diagnostic testing rates were lowest in the South (34.0%) and highest in the Midwest (41.0%). Treatments on or in the 7 days after diagnosis included systemic fluconazole (70.0%), topical antifungal medications (19.4%), and systemic antibacterial medications (17.2%). The low frequencies of diagnostic testing for VVC and high rates of antifungal and antibacterial use suggest substantial empiric treatment, including likely overprescribing of antifungal medications and potentially unnecessary antibacterial medications. These findings support a need for improved clinical care for VVC to improve both patient outcomes and antimicrobial stewardship, particularly in the South and among non-OB/GYN providers.

Inappropriate Empiric Therapy Impacts Complications and Hospital Resource Utilization Differentially Among Different Types of Bacterial Nosocomial Pneumonia: A Cohort Study, United States, 2014-2019.

OBJECTIVES:Nosocomial pneumonia (NP) remains a costly complication of hospitalization fraught with subsequent complications and augmented resource utilization. Consisting of ventilated hospital-acquired bacterial pneumonia (vHABP), nonventilated hospital-acquired bacterial pneumonia (nvHABP), and ventilator-associated bacterial pneumonia (VABP), each may respond differently to inappropriate empiric treatment (IET). We explored whether IET affects the three pneumonia types differently.DESIGN:A multicenter, retrospective cohort study within the Premier Research database.SETTING:Acute care hospitals in the United States.PATIENTS:Patients with three types of NP were identified based on a previously published International Classification of Diseases, 9th Edition/International Classification of Diseases, 10th Edition Clinical Modification algorithm.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:We compared the impact of IET on hospital costs, length of stay (LOS), and development of Clostridium difficile infection (CDI), extubation failure (EF), and reintubation (RT). Marginal effects were derived from multivariable regression analyses. IET was present if no drug covering the organism recovered from the index culture was administered within 2 days of the culture date. Among 17,819 patients who met the enrollment criteria, 26.5% had nvHABP, 25.6% vHABP, and 47.9% VABP. Compared with non-IET, IET was associated with increased mean unadjusted hospital LOS across all NP types: nvHABP 12.5 versus 21.1, vHABP 16.7 versus 19.2, and VABP 18.6 versus 21.4 days. The adjusted marginal hospital LOS (4.9 d) and costs ($13,147) with IET were the highest in nvHABP. Incident CDI was rare and similar across NP types (2.4% nvHABP to 3.6% VABP). Both EF and RT were more common with IET in VABP (EF, 15.4% vs 19.2%; RT, 6.2% vs 10.4%), but not vHABP (EF, 15.1% vs 17.7%; RT, 8.1% vs 9.1%).CONCLUSIONS:Although IET is relatively uncommon, it affects resource utilization and the risk of complications differently across NP types. The impact of IET is greatest on both LOS and costs in nvHABP and is greater on VABP than vHABP in terms of EF and RT.

Risk Factors Associated with Poor Outcome in Patients with Infective Endocarditis: An Italian Single-Center Experience.

Background: Nowadays, infective endocarditis (IE) is still burdened by a high mortality. In the absence of an adequate prognostic stratification system, it is important to assess new predictors of poor outcomes. The aim of our study is to evaluate which factors were associated with higher mortality in IE patients. Methods: A retrospective cohort study enrolled patients with an IE diagnosis at the Infectious Diseases Clinic of the University ‘G. D’Annunzio’, Chieti, Italy from January 2013 to December 2019. For each patient, demographic, anamnestic and clinical information, embolic phenomena, laboratory and microbiologic data, treatment, and outcomes were collected and analyzed. A correlation analysis was performed. Results: Sixty-eight patients with EI were studied; among them, the mortality was 17.6%, 20.6%, and 23.5%, intra-hospital, at 1 month from discharge and at 6 months from discharge, respectively. Mortality was significantly correlated with age, estimated glomerular filtration rate, and procalcitonin values when considering either basal values (r = 0.266, p = 0.029), or values at 48–72 h from the start of an antibiotic therapy (r = 0.222; p < 0.05), cerebral embolization for 6-month mortality (r = 0.284; p = 0.019), and inadequate antibiotic therapy (r = 0.232, p < 0.05). Conclusions: Procalcitonin values, at EI diagnosis and at 48–72 h after starting antibiotics, are prognostic factors useful for stratifying patient risk, and for setting up a personalized treatment. Of note, cerebral embolization and an inappropriate empirical treatment were associated with a higher mortality in the short- and long-term.

Microbiology, empiric therapy and its impact on the outcomes of nonventilated hospital-acquired, ventilated hospital-acquired, and ventilator-associated bacterial pneumonia in the United States, 2014-2019.

To explore whether microbiology profiles and the impact of inappropriate empiric treatment differ in the setting of hospital-acquired bacterial pneumonia that requires subsequent mechanical ventilation (vHABP) versus one that does not (nvHABP) versus ventilator-associated bacterial pneumonia (VABP). Multicenter retrospective cohort study within Premier Research database, 2014-2019. We identified cases based on a previously published International Classification of Disease, Ninth Revision/Tenth Revision Clinical Modification (ICD-9/ICD-10-CM) algorithm, and we compared the 3 groups with respect to the bacterial pathogens isolated from their blood, sputum, or lower airway samples, and their respective rates of exposure to inappropriate empiric treatment. Using regression modeling we computed the effect of inappropriate empiric treatment on outcomes. Among 17,819 patients who met enrollment criteria, 26.5% had nvHABP, 25.6% vHAPB, and 47.9% VABP. S. aureus (majority methicillin-susceptible) was the most frequently isolated organism, followed P. aeruginosa, K. pneumoniae, and E. coli with variations across the conditions. Rates of carbapenem resistance were highest in VABP (9.1%) and to third-generation cephalosporins in vHABP (14.9%). Patients with nvHABP were most likely to receive inappropriate empiric treatment (8.5%). Although inappropriate empiric treatment was associated with an increase in adjusted postinfection-onset hospital length of stay (2.3 days) and cost ($12,142), its greatest magnitude was in the nvHABP group (4.9 days, $13,147). Substantial microbiologic differences exist among populations who suffer nvHABP, vHABP, and VABP, and inappropriate empiric treatment significantly worsens utilization outcomes. Given the moderate rates of carbapenem resistance and third-generation cephalosporin resistance, all patients require empiric coverage for a range of bacteria, including those targeting extended-spectrum β-lactamase and carbapenem resistance where appropriate.

Impact of Inappropriate Empirical Antibiotic on Outcomes in Community-acquired Third Generation Cephalosporin Resistant Enterobacterales Bacteremia.

Currently, third generation cephalosporin resistant Enterobacterales (3GCRE) are becoming more common in community-acquired infection, leading to increasing consumption of carbapenems. Because community-acquired 3GCRE infections are generally less severe and of lower pathogenicity, the impact of inappropriate empirical antibiotics among patients with community-acquired 3GCRE bacteremia remains unknown. This prospective cohort study included adult patients with 3GCRE bacteremia from April 2018 to December 2021. Participants were followed for 30 days to measure the primary outcome of mortality. Propensity score analysis was performed to adjust for treatment selection bias. A total of 155 patients met the eligible criteria (42 participants in the appropriate antibiotics group, and 113 participants in the inappropriate antibiotics group). Eight participants in the inappropriate antibiotics group never received appropriate antibiotics, three of whom died before microbiological results were made available. The most common clinical syndromes were urinary tract infection (56.8%) and biliary tract infection (22.6%). The overall 30-day mortality rate was 12.9%, 14.3% in the appropriate empirical antibiotics group and 12.4% in the inappropriate empirical antibiotics group. After propensity score weighted adjustment, the 30-day mortality rate in the inappropriate group was non-inferior to the appropriate group (mean difference 1.9%; 95% confidence interval: -10.1 - 14.0). From the multivariate analysis, acute respiratory failure and primary bacteremia were associated with 30-day mortality. Among patients with community-acquired 3GCRE bacteremia, inappropriate empirical treatment given within 24 hours after the onset of bacteremia was non-inferior to appropriate antibiotics. In the setting of a high prevalence of 3GCRE carriage in community, adjustment to carbapenem might be tolerable among patients with community-acquired infections. ClinicalTrials.gov Identifier: NCT03765749.

Pediatric drug utilization evaluation of cefepime and piperacillin/tazobactam.

Drug utilization evaluation (DUE) is a systematic, criteria-based assessment of medicine that aims to optimize the appropriateness of antibiotic prescription. This study aimed to evaluate the performance of the DUE on prescriptions of two commonly used antibiotics in a pediatric population, cefepime and piperacillin/tazobactam, in a tertiary care hospital. This quasi-experimental study was conducted at the Department of Pediatrics, Ramathibodi Hospital, between March 2020 and August 2021. All hospitalized children aged 1 month to 20 years who received at least one dose of cefepime or piperacillin/tazobactam were enrolled. Before implementing the DUE, cefepime and piperacillin/tazobactam prescriptions were retrospectively evaluated using the DUE criteria. During the 6 month DUE implementation period, physicians voluntarily chose to use DUE to assess the prescriptions' appropriateness. Demographic data, antibiotic use, and clinical data were recorded. There were 304 prescriptions of cefepime and piperacillin/tazobactam, with 108 empirical prescriptions (72 patients) in the DUE group and 158 prescriptions (138 patients) in the non-DUE group. The appropriateness of empirical prescriptions of cefepime and piperacillin/tazobactam was significantly higher in the DUE group (93.5% vs. 83.5%; P = 0.003). Drug utilization evaluation was significantly associated with appropriate empirical prescriptions (adjusted OR 5.32: 95% CI 1.80-15.73; P = 0.003). Prescriptions in critical care wards and urinary tract infections (UTIs) were associated with not fulfilling the DUE criteria for appropriateness. Drug utilization evaluation could improve the appropriateness of empirical use of cefepime and piperacillin/tazobactam in pediatric patients. Patients in critical care units and with UTIs appeared to be associated with inappropriate empirical treatment.

A Large Multicenter Prospective Study of Community-Onset Healthcare Associated Bacteremic Urinary Tract Infections in the Era of Multidrug Resistance: Even Worse than Hospital Acquired Infections?

IntroductionHealthcare-associated (HCA) infections represent a growing public health problem. The aim of this study was to compare community-onset healthcare associated (CO-HCA) bacteremic urinary tract infections (BUTI) and hospital-acquired (HA)-BUTI with special focus on multidrug resistances (MDR) and outcomes.MethodsITUBRAS-project is a prospective multicenter cohort study of patients with HCA-BUTI. All consecutive hospitalized adult patients with CO-HCA-BUTI or HA-BUTI episode were included in the study. Exclusion criteria were: patients < 18 years old, non-hospitalized patients, bacteremia from another source or primary bacteremia, non-healthcare-related infections and infections caused by unusual pathogens of the urinary tract. The main outcome variable was 30-day all-cause mortality with day 1 as the first day of positive blood culture. Logistic regression was used to analyze factors associated with clinical cure at hospital discharge and with receiving inappropriate initial antibiotic treatment. Cox regression was used to evaluate 30-day all-cause mortality.ResultsFour hundred forty-three episodes were included, 223 CO-HCA-BUTI. Patients with CO-HCA-BUTI were older (p < 0.001) and had more underlying diseases (p = 0.029) than those with HA-BUTI. The severity of the acute illness (Pitt score) was also higher in CO-HCA-BUTI (p = 0.026). Overall, a very high rate of MDR profiles (271/443, 61.2%) was observed, with no statistical differences between groups. In multivariable analysis, inadequate empirical treatment was associated with MDR profile (aOR 3.35; 95% CI 1.77–6.35), Pseudomonas aeruginosa (aOR 2.86; 95% CI 1.27–6.44) and Charlson index (aOR 1.11; 95% CI 1.01–1.23). Mortality was not associated with the site of acquisition of the infection or the presence of MDR profile. However, in the logistic regression analyses patients with CO-HCA-BUTI (aOR 0.61; 95% CI 0.40–0.93) were less likely to present clinical cure.ConclusionThe rate of MDR infections was worryingly high in our study. No differences in MDR rates were found between CO-HCA-BUTI and HA-BUTI, in the probability of receiving inappropriate empirical treatment or in 30-day mortality. However, CO-HCA-BUTIs were associated with worse clinical cure.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00537-0.

Risk Factors for Relapse in Acute Bacterial Prostatitis: the Impact of Antibiotic Regimens.

ABSTRACTThe aim of the study was to analyze the risk factors for relapse in patients with acute bacterial prostatitis (ABP), focusing on the impact of different antibiotic regimens. We conducted an observational study of all patients diagnosed with ABP (irritative and/or obstructive urinary symptoms, temperature of >37.8°C, and the presence of bacteriuria in urine culture, in the absence of data suggesting pyelonephritis) from January 2017 to December 2018. The main outcome was relapse. We performed a multivariate analysis to identify the risk factors associated with relapse. A propensity score with inverse weighting was applied to attenuate antibiotic selection bias. We included 410 patients. The mean age was 68 years; 28.8% had diabetes mellitus, and 61.1% benign prostatic hyperplasia. The most common isolated bacteria were Escherichia coli (62.4%) and Klebsiella spp. (10%). The overall resistance rate was 39.5% to quinolones. The mortality rate was 1.2%, and the relapse rate was 6.3%. The only independent risk factor for relapse was inadequate antibiotic therapy (odds ratio [OR] 12.3; 95% confidence interval [95% CI], 3.5 to 43.1). When the antibiotic was modified according to the susceptibility pattern, the rates of relapse were 1.8% in those treated with ciprofloxacin, 3.6% with intravenous beta-lactam, 9.3% with co-trimoxazole, and 9.8% with oral (p.o.) beta-lactam (P = 0.03). Treatment with oral beta-lactam (OR, 5.3; 95% CI, 1.2 to 23.3) and co-trimoxazole (OR, 4.9; 95% CI, 1.1 to 23.2) were associated with a risk of relapse. In this large real-life observational study, a significantly higher relapse rate was observed when antibiotic treatment was inadequate. When the antibiotic was tailored, quinolones and intravenous beta-lactams had a lower relapse rate than co-trimoxazole and oral beta-lactams.IMPORTANCE In the manuscript, we report a large series of acute bacterial prostatitis cases and describe data about the etiology, antibiotic resistance rate, and outcome, specially focused on the risk factors for relapse. We found high rates of resistance to the most frequently used antibiotics and a high relapse rate in patients whose treatment was not adjusted according to their microbiological susceptibility. We did not observe differences, though, in mortality or relapse according to appropriate or inappropriate empirical treatment. What is new in this article is the different relapse rates observed depending upon the definitive adequate antibiotic used. Quinolones and intravenous (i.v.) beta-lactam have lower rates of relapse (1.8% and 3.6%, respectively) compared to co-trimoxazole and oral (p.o.) beta-lactam (3.3% and 9.8%, respectively). Clinicians should carefully choose an adequate antibiotic for definitive ABP treatment depending on the results of microbiological isolation, using quinolones as the first option. Whenever quinolones cannot be administered, i.v. beta-lactams seem to be the second-best option.

Appropriateness of empirical antibiotic prescription for bloodstream infections in an emergency department from 2006 to 2018: impact of the spread of ESBL-producing Enterobacterales.

The spread of ESBL producers in the community may impact the management of patients with bloodstream infections (BSI) involving Enterobacterales in emergency departments. Thus, from 2006 to 2018, data for all BSI episodes involving Enterobacterales from the emergency department of a French teaching hospital were retrospectively included. Antimicrobial susceptibility test results and empirical antibiotic regimens were recorded. Treatment was considered as appropriate if all isolates were susceptible in vitro to at least one prescribed antibiotic. A total of 1369 BSI episodes in 1321 patients was included. Urinary tract infection was the main source of BSI (61%). The prevalence of ESBL producers increased from zero to 9.2/100 Enterobacterales BSI cases (p < 0.001), mainly Escherichia coli (6.9 cases/100 BSI in 2018); and no Klebsiella. Third-generation cephalosporins (3GC) were used most frequently (71.8%) and their use as monotherapy increased during the study period (p < 0.001). The rate of appropriate treatment decreased from 95.8 to 89.2% (p = 0.023). Appropriateness of treatment was greater using two drugs vs one (97.3% vs 89.3%, p < 0.001). Treatments with 3GC were appropriate in 92% and 98.3%, when used alone or with another antibiotic, respectively (p < 0.001). Among inappropriate treatments, 45% concerned 3GC, with 74.6% of them attributable to ESBL production. The spread of ESBL producers in the community had a direct impact on the rate of inappropriate empirical treatment. Local antimicrobial resistance monitoring is required to optimize the management of BSI in emergency departments.

Secondary Infections After Diagnosis of Severe Radiation Pneumonitis (SRP) Among Patients With Non-Small Cell Lung Cancer: Pathogen Distributions, Choice of Empirical Antibiotics, and the Value of Empirical Antifungal Treatment

This study aimed to assess pathogen distributions and antimicrobial sensitivity characteristics in patients with non-small cell lung cancer (NSCLC) with severe radiation pneumonitis (SRP) and secondary infections. Data from 1746 patients with NSCLC and SRP after thoracic radiation therapy from January 2009 to December 2020 were retrospectively analyzed. Pneumonia incidence, causative pathogens, and antibiotic resistance characteristics in patients with secondary lung infections were analyzed. Risk factors associated with mortality were identified through univariate and multivariate analyses. Antifungal drug efficacy and duration-related effects were assessed with Forest plots and receiver operating characteristic curves. Overall, 44.5% of patients with NSCLC and SRP (777 of 1746 patients) were diagnosed with secondary lung infections. In total, 899 bacterial strains were isolated from these patients, with Acinetobacter baumannii (n=206; 27%), Klebsiella pneumonia (n=200; 26.2%), and Pseudomonas aeruginosa (n=104; 13.6%) being the most common. Carbapenem and cefoperazone-sulbactam resistance rates of 52.7% and 32.2%, 28.8% and 26.4%, and 23.7% and 20.2% were observed for these isolates, respectively. Infection-related deaths occurred in 22.4% of patients with SRP. Independent risk factors for infection-related death included poor performance status scores, inappropriate empirical antimicrobial treatment, bacteria/fungal coinfection, and lack of empirical antifungal treatment. Receiver operating characteristic curves showed that the cutoff value of empirical antifungal treatment duration was 9 (area under the curve: 0.819). For patients with SRP and secondary lung infections, appropriate empirical antimicrobial treatment could decrease infection-related mortality, and cefoperazone-sulbactam may be an appropriate antibacterial drug. Empirical antifungal treatment for a minimum of 9 days might contribute to better outcomes. Although this represents a promising treatment approach for patients with SRP and secondary lung infections before antibacterial susceptibility testing, further prospective validation is essential.

Impact of appropriate empirical antibiotics on clinical outcomes in Klebsiella pneumoniae bacteraemia.

Klebsiella pneumoniae infections can cause septic shock, multiorgan failure, and death. This retrospective cohort study included adults with K pneumoniae bacteraemia treated from 1 January 2009 to 30 June 2017. Demographics, microbiology, and outcomes were analysed. The primary outcome was 90-day all-cause mortality; secondary outcomes were intensive care unit (ICU) and hospital mortalities, ICU and hospital lengths of stay, and ICU ventilator duration. In total, 984 patients had K pneumoniae bacteraemia; of them, 686 received appropriate empirical antibiotics. Overall, 205 patients required intensive care. Older age (odds ratio [OR]=1.60; 95% confidence interval [CI]=1.120-2.295; P=0.010), chronic kidney disease (OR=1.81; 95% CI=1.181- 2.785; P=0.007), mechanical ventilation (OR=1.79; 95% CI=1.188-2.681; P=0.005), pneumonia (OR=1.50; 95% CI=1.030-2.187; P=0.034), and carbapenem-resistant or extended-spectrum betalactamase (ESBL)-producing isolates (OR=12.51; 95% CI=7.886-19.487; P<0.001) were associated with greater risk of inappropriate empirical treatment. Ninety-day mortality was significantly higher among patients with inappropriate empirical treatment; independent predictors included pneumonia (hazard ratio [HR]=2.94; 95% CI=2.271-3.808; P<0.001), gastrointestinal infection (HR=2.77; 95% CI=2.055-3.744; P<0.001), failed empirical antibiotics (HR=2.45; 95% CI=1.928-3.124; P<0.001), older age (HR=1.79; 95% CI=1.356-2.371; P<0.001), solid tumour (HR=1.77; 95% CI=1.401-2.231; P<0.001), carbapenem-resistant or ESBL-producing isolates (HR=1.64; 95% CI=1.170-2.297; P=0.004), patients admitted through the Department of Medicine (HR=1.39; 95% CI=1.076-1.800; P=0.012), and higher total Sequential Organ Failure Assessment score (HR=1.09; 95% CI=1.058-1.112; P=0.023). Among ICU patients, inappropriate empirical antibiotic treatment was significantly associated with increased ventilator duration and 90-day mortality. Klebsiella pneumoniae bacteraemia was associated with high 90-day and ICU mortalities; 90-day mortality increased with inappropriate empirical antibiotic treatment.

Predictors of mortality in patients with carbapenem-resistant Klebsiella pneumoniae infection: a meta-analysis and a systematic review.

Cases of carbapenem-resistant Klebsiella pneumoniae infection have been increasing. Patients with carbapenem-resistant Klebsiella pneumoniae infection have a poor prognosis and a high mortality rate. Identification of potential risk factors associated with carbapenem-resistant Klebsiella pneumoniae infection-related mortality may help improve patient outcomes. Embase, PubMed, and the Cochrane Library databases were searched to identify articles describing predictors of mortality in patients with carbapenem-resistant Klebsiella pneumoniae infection. The quality of articles was assessed with the Newcastle-Ottawa Scale score (NOS). Review Manager was used for statistical analyses. Twenty-seven observational studies were included in the analysis. Factors associated with higher mortality were septic shock [odds ratio (OR): 4.41, 95% CI: 3.17-6.15], congestive heart failure (OR: 2.65, 95% CI: 1.71-4.13), chronic obstructive pulmonary disease (COPD; OR: 2.43, 95% CI: 1.87-3.15), chronic kidney disease (CKD; OR: 1.78, 95% CI: 1.43-2.22), diabetes mellitus (OR: 1.41, 95% CI: 1.16-1.72), mechanical ventilation (OR: 1.65, 95% CI: 1.25-2.18), and inappropriate empirical antimicrobial treatment (OR: 1.25, 95% CI: 1.03-1.52). The average Acute Physiology and Chronic Health Evaluation (APACHE) II score at the time of diagnosis of carbapenem-resistant Klebsiella pneumoniae infection was considerably higher in patients who did not survive than in those who survived (weighted mean difference: 5.86, 95% CI: 2.46-9.26). Patient condition, timing appropriate antimicrobial treatment, and disease severity according to the APACHE II score are the most important risk factors for death in patients with carbapenem-resistant Klebsiella pneumoniae infection. Our finding may help predict patients' outcomes and improve management for them. 20210417EuEGX/INPLASY2020100037.

Multiple antimicrobial resistance and outcomes among hospitalized patients with complicated urinary tract infections in the US, 2013\u20132018: a retrospective cohort study

BackgroundComplicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes.MethodsWe conducted a retrospective cohort study of patients hospitalized with a culture-positive non-CR cUTI. Triple resistance (TR) was defined as resistance to > 3 of the following: 3rd generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin. Multivariable models quantified the impact of TR and inappropriate empiric therapy (IET) on mortality, hospital LOS, and costs.ResultsAmong 23,331 patients with cUTI, 3040 (13.0%) had a TR pathogen. Compared to patients with non-TR, those with TR were more likely male (57.6% vs. 47.7%, p < 0.001), black (17.9% vs. 13.6%, p < 0.001), and in the South (46.3% vs. 41.5%, p < 0.001). Patients with TR had higher chronic (median [IQR] Charlson score 3 [2, 4] vs. 2 [1, 4], p < 0.001) and acute (mechanical ventilation 7.0% vs. 5.0%, p < 0.001; ICU admission 22.3% vs. 18.6%, p < 0.001) disease burden. Despite greater prevalence of empiric carbapenem exposure (43.3% vs. 16.2%, p < 0.001), patient with TR were also more likely to receive IET (19.6% vs. 5.4%, p < 0.001) than those with non-TR. Although mortality was similar between groups, TR added 0.38 (95% CI 0.18, 0.49) days to LOS, and $754 (95% CI $406, $1103) to hospital costs. Both TR and IET impacted the outcomes among cUTI patients whose UTI was not catheter-associated (CAUTI), but had no effect on outcomes in CAUTI.ConclusionsTR occurs in 1 in 8 patients hospitalized with cUTI. It is associated with an increase in the risk of IET exposure, as well as a modest attributable prolongation of LOS and increase in total costs, particularly in the setting of non-CAUTI.

Risk Factors and Outcomes of Antibiotic-resistant Pseudomonas aeruginosa Bloodstream Infection in Adult Patients With Acute Leukemia.

Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common complication in patients with acute leukemia (AL), and the prevalence of antibiotic-resistant strains poses a serious problem. However, there is limited information regarding antibiotic resistance, clinical characteristics, and outcomes of PA BSI in AL patients. This study explored characteristics associated with the clinical outcomes of AL patients with PA BSI and analyzed factors associated with BSI caused by multidrug-resistant (MDR) or carbapenem-resistant strains. This single-center retrospective study enrolled hospitalized AL patients who developed PA BSI during January 2014-December 2019. The Kaplan-Meier method was used to plot survival curves. Multivariate logistic regression analyses were also performed. Of 293 eligible patients with PA BSI, 55 (18.8%) received inappropriate empirical antibiotic therapy within 48 hours of BSI onset, whereas up to 65.8% MDR-PA BSI patients received inappropriate empirical treatment. The 30-day mortality rate was 8.5% for all patients. However, the 30-day mortality rates were 28.9% and 5.5% in MDR-PA BSI and non-MDR-PA BSI patients, respectively (P < .001). On multivariate analysis, previous use of quinolones (odds ratio [OR], 5.851 [95% confidence interval {CI}, 2.638-12.975]) and piperacillin/tazobactam (OR, 2.837 [95% CI, 1.151-6.994]) were independently associated with MDR-PA BSI; and MDR-PA BSI (OR, 7.196 [95% CI, 2.773-18.668]), perianal infection (OR, 4.079 [95% CI, 1.401-11.879]), pulmonary infection (OR, 3.028 [95% CI, 1.231-7.446]), and age ≥55 years (OR, 2.871 [95% CI, 1.057-7.799]) were independent risk factors for 30-day mortality. MDR increases mortality risk in PA BSI patients, and previous antibiotic exposure is important in MDR-PA BSI development. Rational antibiotic use based on local antimicrobial susceptibility and clinical characteristics can help reduce antibiotic resistance and mortality.

A prospective study of epidemiology characteristics and outcomes of bloodstream infections in older patients.

This study aimed to investigate the characteristics of bloodstream infections (BSIs) in older patients and describe the differences between community-acquired, hospital-acquired and health care-associated BSIs. A prospective observational study was conducted at the University Hospital of Heraklion, Crete, Greece. Epidemiology, clinical characteristics and outcomes of BSIs were recorded. During a four-year period, 113 BSIs were recorded. Of them, 42% occurred in male patients; patients' mean age was 80years. BSIs were community-acquired in 76% of patients, hospital-acquired in 12% and health care-associated in 12%. The most commonly isolated bacteria were E coli and K pneumoniae. Thirty-day mortality from detection of BSIs was 27%. Patients with fever, without septic shock and with appropriate empirical treatment were less likely to die. Community-acquired, health care-associated and hospital-acquired BSIs had different presentation, microbiology and outcomes. Older patients had a high mortality. The absence of fever, inappropriate empirical treatment and septic shock were independent mortality predictors.

Fatality of Staphylococcus aureus infections in a Greek university hospital: role of inappropriate empiric treatment, methicillin resistance, and toxin genes' presence.

The aim of the present study was to identify predictors of fatality among patients with S. aureus infections requiring hospitalization. Cases hospitalized with S. aureus infections at the University General Hospital of Patras, Greece, during a 4-year period (2013-2016) were studied. mecA, lukS/lukF-PV (Panton-Valentine leukocidin, PVL), tst (toxic shock syndrome toxin), fnbA (fibronectin-binding protein A), eta, and etb (epidermolytic toxins) genes' carriage was detected by PCR in 149 selected patients. Among 464 patients, 346 were included (118 with missing data). Primary bacteremia predominated (44.2%), followed by lower respiratory tract infections (13.6%), deep seated infections (9.8%), osteoarticular (9.5%), and catheter-related bloodstream infections (6.1%). Methicillin-resistant S. aureus (MRSA) represented 33.8% of infections and were less likely to receive appropriate empiric treatment (79.5% versus 97.4%; P < 0.001). Thirty-day fatality was 14.5%. Multivariate analysis revealed that development of septic shock, Charlson Comorbidity Index, lower respiratory tract infection, bacteremia (primary or secondary), MRSA, and CRP was significantly associated with fatality. Appropriate empiric treatment was a predictor of good prognosis. Thirty-two out of 149 S. aureus (21.5%) carried lukS/lukF-PV genes, whereas, 14 (9.4%), 133 (78.7%), four (2.7%), and one (0.7%) carried tst, fnbA, eta, and etb genes, respectively. No difference was found among toxin genes' presence and mortality. PVL was significantly more frequently found among MRSA as compared to MSSA (45.1% versus 9.2%; P < 0.001). MRSA represented one third of the infections requiring hospitalization and were independently associated with fatality, probably since were more likely to receive inappropriate antibiotic treatment as compared to MSSA.

1455. Epidemiology, Empiric Treatment, and Outcomes Among Hospitalized Patients With Complicated Urinary Tract Infections in the United States, 2013–2018

BackgroundComplicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite the frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes.MethodsWe performed a multicenter retrospective cohort study in ~180 hospitals in the Premier database, 2013–2018. Using an ICD-9/10-based algorithm we identified all adult patients hospitalized with cUTI and a positive blood or urine culture (CR excluded). We examined with the impact of triple resistance (TR; resistance to >3 of the following drugs/classes: third-generation cephalosporin [C3R], fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin), on the risk of receiving IET. We derived multivariate models to compute the impact of IET on hospital outcomes.ResultsAmong 23,331 patients with cUTI (96.2% community-onset), 3,040 (13.0%) had a TR pathogen. Compared with those with non-TR, patients with TR were more likely male (57.6% vs. 47.7%), black (17.9% vs. 13.6%), and in the South (46.3% vs. 41.5%), P < 0.001 each; had a higher median Charlson score (3 vs. 2), and were more likely to need early ICU (22.3% vs. 18.6%) and mechanical ventilation (7.0% vs. 5.0%), P < 0.001 each. Patients with TR were hospitalized at centers with higher median prevalence of both C3R (16.3% vs. 14.4%) and TR (15.1% vs. 12.2%), P < 0.001 each. IET was more frequent in TR than non-TR group (19.6% vs. 5.4%) despite greater empiric carbapenem use in TP (43.3% vs. 16.2%), P < 0.001 each. Though IET did not have an impact on adjusted hospital mortality or 30-day readmission rate, it was associated with excess adjusted resource utilization ($1,364 in costs and 0.66 day in length of stay).ConclusionAmong hospitalized patients with cUTI, TR is common, and is associated with a nearly 4-fold increase in exposure to IET, which in turn contributes to excess resource utilization. Given the high prevalence of TR, clinicians should consider a lower threshold for broader empiric treatment in appropriate patients.Disclosures All authors: No reported disclosures.