Inappropriate Empirical Antibiotic Treatment Research Articles

A case-control study of the clinical and economic impact of infections caused by Carbapenemase-producing Enterobacterales (CPE).

The aim was to analyse the clinical and economic impact of carbapenemase-producing Enterobacterales (CPE) infections. Case-control study. Adult patients with CPE infections were considered cases, while those with non-CPE infections were controls. Matching criteria were age (± 5years), sex, source of infection and microorganism (ratio 1:2). Primary outcome was 30-day mortality. Secondary outcomes were 90-day mortality, clinical failure, hospitalisation costs and resource consumption. 246 patients (82 cases and 164 controls) were included. Klebsiella pneumoniae OXA-48 was the most common microorganism causing CPE infections. CPE cases had more prior comorbidities (p = 0.007), septic shock (p = 0.003), and were more likely to receive inappropriate empirical and definitive antibiotic treatment (both p < 0.001). Multivariate analysis identified septic shock and inappropriate empirical treatment as independent predictors for 7-day and end-of-treatment clinical failure, whereas Charlson Index and septic shock were associated with 30- and 90-day mortality. CPE infection was independently associated with early clinical failure (OR 2.18, 95% CI, 1.03-4.59), but not with end-of-treatment clinical failure or 30- or 90-day mortality. In terms of resource consumption, hospitalisation costs for CPE were double those of the non-CPE group. CPE cases had longer hospital stay (p < 0.001), required more long-term care facilities (p < 0.001) and outpatient parenteral antibiotic therapy (p = 0.007). The CPE group was associated with worse clinical outcomes, but this was mainly due to a higher comorbidity burden, more severe illness, and more frequent inappropriate antibiotic treatment rather than resistance patterns as such. However, the CPE group consumed more healthcare resources and incurred higher costs.

Epidemiology and risk factors for recurrence in biliary source bloodstream infection episodes in oncological patients.

We aimed to describe the characteristics and outcomes of biliary source bloodstream infections (BSIs) in oncological patients. Secondarily, we analyzed risk factors for recurrent BSI episodes. All episodes of biliary source BSIs in oncological patients were prospectively collected (2008-2019) and retrospectively analyzed. Logistic regression analyses were performed. A rule to stratify patients into risk groups for recurrent biliary source BSI was conducted. Four hundred biliary source BSIs were documented in 291 oncological patients. The most frequent causative agents were Escherichia coli (42%) and Klebsiella spp. (27%), and 86 (21.5%) episodes were caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The rates of MDR-GNB increased over time. Overall, 73 patients developed 118 recurrent BSI episodes. Independent risk factors for recurrent BSI episodes were prior antibiotic therapy (OR 3.781, 95% CI 1.906-7.503), biliary prosthesis (OR 2.232, 95% CI 1.157-4.305), prior admission due to suspected biliary source infection (OR 4.409, 95% CI 2.338-8.311), and BSI episode caused by an MDR-GNB (OR 2.857, 95% CI 1.389-5.874). With these variables, a score was generated that predicted recurrent biliary source BSI with an area under the receiver operating characteristic (ROC) curve of 0.819. Inappropriate empirical antibiotic treatment (IEAT) was administered in 23.8% of patients, and 30-d mortality was 19.5%. As a conclusion, biliary source BSI in oncological patients is mainly caused by GNB, with high and increasing MDR rates, frequent IEAT, and high mortality. Recurrent BSI episodes are frequent. A simple score to identify recurrent episodes was developed to potentially establish prophylactic strategies. IMPORTANCE This study shows that biliary source bloodstream infections (BSIs) in oncological patients are mainly caused by Gram-negative bacilli (GNB), with high and increasing rates of multidrug resistance. Importantly, recurrent biliary source BSI episodes were very frequent and associated with delays in chemotherapy, high rates of inappropriate empirical antibiotic therapy, and high 30-d mortality (19.5%). Using the variable independently associated with recurrent BSI episodes, a score was generated that predicted recurrent biliary source BSI with high accuracy. This score could be used to establish prophylactic strategies and lower the risk of relapsing episodes and the associated morbidity and mortality.

Microbiology and prognostic prediction model of bloodstream infection in patients with hematological malignancies.

In recent years, with the continuous development of treatments for hematological malignancies (HMs), the remission and survival rates of patients with HMs have been significantly improved. However, because of severe immunosuppression and long-term recurrent neutropenia during treatment, the incidence and mortality of bloodstream infection (BSI) were all high in patients with HMs. Therefore, we analyzed pathogens' distribution and drug-resistance patterns and developed a nomogram for predicting 30-day mortality in patients with BSIs among HMs. In this retrospective study, 362 patients with positive blood cultures in HMs were included from June 2015 to June 2020 at West China Hospital of Sichuan University. They were randomly divided into the training cohort (n = 253) and the validation cohort (n = 109) by 7:3. A nomogram for predicting 30-day mortality after BSIs in patients with HMs was established based on the results of univariate and multivariate logistic regression. C-index, calibration plots, and decision curve analysis were used to evaluate the nomogram. Among 362 patients with BSIs in HMs, the most common HM was acute myeloid leukemia (48.1%), and the most common pathogen of BSI was gram-negative bacteria (70.4%). The final nomogram included the septic shock, relapsed/refractory HM, albumin <30g/l, platelets <30×109/l before BSI, and inappropriate empiric antibiotic treatment. In the training and validation cohorts, the C-indexes (0.870 and 0.825) and the calibration plots indicated that the nomogram had a good performance. The decision curves in both cohorts showed that the nomogram model for predicting 30-day mortality after BSI was more beneficial than all patients with BSIs or none with BSIs. In our study, gram-negative bacterial BSIs were predominant in patients with HMs. We developed and validated a nomogram with good predictive ability to help clinicians evaluate the prognosis of patients.

Influence of Appropriate Empirical Antibiotic Treatment on the Prognosis of ICU Patients with HAP Caused by Carbapenem-Resistant Gram-Negative Bacteria.

In patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infection, the impact of appropriate empirical antibiotic treatment (AEAT) initialized before culture results were available remains controversial. We aimed to investigate the effect of AEAT on the prognosis of critically ill patients with hospital-acquired pneumonia (HAP) caused by CRGNB. Patients with CRGNB-infected HAP and received empirical antibiotic treatment (EAT) for at least 3 days in the intensive care unit (ICU) of a tertiary teaching hospital in China from February 2017 to September 2021 were included in the retrospective cohort study. Patients were categorized into AEAT and inappropriate empirical antibiotic treatment (IEAT) groups based on whether they received EAT covering CRGNB. The associations of AEAT with ICU and 28-day mortality were assessed using multivariable logistic regression model. A total of 94 patients were enrolled, including 29 patients in AEAT group and 65 patients in IEAT group. Patients in AEAT group had a higher Sequential Organ Failure Assessment (SOFA) score (P = 0.003), levels of procalcitonin (PCT) (P = 0.001), and lactic acid (LAC) (P = 0.026); while patients in the IEAT group had a higher platelet count (PLT) (P = 0.001). There was no significant difference in the length of ICU stay between the two groups (P = 0.051). Compared with IEAT, AEAT was associated with an increased risk of 28-day mortality in the univariable logistic regression model (OR: 2.618, 95% CI: 1.063-6.448). However, after adjusted for SOFA score, PLT, PCT, and LAC level, the association between AEAT and 28-day mortality diminished (OR: 1.028, 95% CI: 0.353-2.996). AEAT showed no significant association with ICU mortality in neither univariable (OR: 1.167, 95% CI: 0.433-3.142) nor multivariable (OR: 0.357, 95% CI: 0.097-1.320) models. AEAT showed no significant influence on ICU or 28-day mortality in critically ill patients with HAP caused by CRGNB infection.

Pseudomonas Bacteremia in Children: Clinical and Microbiologic Features and Risk Factors of Mortality: A Retrospective Cohort Study.

Pseudomonas bacteremia is most commonly acquired in hospital. The aim of this study was to investigate the clinical features and antibiotic susceptibility, mortality rate and risk factors of mortality in children with Pseudomonas bacteremia. A retrospective cohort study that included children 18 years of age or younger admitted to a tertiary hospital with Pseudomonas bacteremia between 2005 and 2020. A total of 196 patients with Pseudomonas bacteremia were identified. The proportional rate of Pseudomonas bacteremia was 33.9/100,000 hospital days. Underlying disease was documented in 81.1% of patients, 61% had hemato-oncological disease. Pseudomonas bacteremia was healthcare related in 180 (91.8%) episodes. Multidrug-resistant (MDR) Pseudomonas accounted for 16 (8.2%) and difficult-to-treat organism to 3 (1.5%) of all isolates. Thirty-day mortality was reported in 27 (13.8%) patients, all had Pseudomonas aeruginosa . In multivariate regression analysis, the first model showed that younger age [ P = 0.038, odds ratio (OR) = 1.095, 95% confidence interval (CI): 1.005-1.192] and inappropriate empiric antibiotic treatment ( P = 0.004, OR = 3.584, 95% CI: 1.490-8.621) were significantly associated with higher mortality. The second model also showed higher morality in younger age ( P = 0.021, OR = 1.114, 95% CI: 1.016-1.221) and MDR isolates ( P = 0.001, OR = 9.725, 95% CI: 2.486-38.039). Significant morbidity and mortality due to Pseudomonas bacteremia, but relatively lower mortality than previously published. Although young age, MDR isolates and inappropriate antibiotic treatment have been associated with increased mortality, these factors, especially with low prevalence of MDR isolates, may reflect the baseline mortality rate in vulnerable hosts with continuous contact with healthcare facilities facing such severe infection, and more efforts should be made to emphasize infection control practices to prevent such severe infection.

Establishment of Mortality Risk Prediction Model for Bloodstream Infections in Patients with Hematological Diseases

Backgrounds: In recent years, with the continuous development of treatment for hematological diseases, the remission rate and survival rate of patients have been significantly improved. However, due to the progression of the hematological disease and immunosuppression, the incidence of bloodstream infection was greatly increased in patients with hematological disease. The occurrence of bloodstream infection had many negative effects on patients with hematological diseases, including the increase in mortality, the adding of medical bills, the prolongation of hospitalization period, and so on. West China Hospital is a national center for diagnosing and treating difficult and critical diseases in Western China. In our center, we found that the incidence of bloodstream infection in hematological patients was not low, and it was often one of the common causes of death. So, our purpose was to explore the risk factors for the 30-day death and establish a mortality risk prediction model in patients with bloodstream infections in hematological diseases, to provide evidence for the prevention and treatment of bloodstream infection in hematological diseases. Methods: The clinical data of 412 strains of pathogens of bloodstream infection from patients with hematological diseases were retrospectively collected from June 2015 to June 2020 in the Department of Hematology, West China Hospital, Sichuan University. Statistical analysis was conducted with IBM SPSS Statistics (version 26.0). 70% of the patients were randomly selected as the development group and 30% as the validation group. Results: A total of 338 patients with hematological diseases with positive blood culture were collected and 412 strains of pathogens of bloodstream infection were isolated. The most common primary hematological disease was acute myeloid leukemia, accounting for 44.2%. Among the included cases, the 7-day and 30-day mortality rates of all patients were 5.6% and 32.0%, respectively. All cases were randomly divided into the development group (n = 289) and validation group (n = 123) by 7:3. Univariate and multivariate logistic regression analysis revealed that septic shock [P = 0.001, OR = 4.126], albumin < 30g/L [P < 0.001, OR = 3.622], platelets < 30×109/L before infection [P = 0.002, OR = 4.202], bleeding [P = 0.029, OR = 2.308], placement of urinary ducts [P = 0.008, OR = 3.769], and inappropriate empiric antibiotic treatment [P = 0.007, OR = 2.523] were independent risk factors for 30-day death after bloodstream infection in patients with hematological diseases. In the light of the results of multivariate analysis, the equation of risk prediction model of 30-day death for bloodstream infections in patients with hematological diseases was established as follows: P = ea/ (1 + ea), a=-4.172 + (1.417 × septic shock) + (1.287 × albumin < 30g/L) + (1.436 × platelets < 30×109/L before infection) + (0.836 × bleeding) + (1.327 × placement of urinary ducts) + (0.925 × inappropriate empiric antibiotic treatment). The Hosmer-Lemeshow Chi-square test showed P = 0.582, and the area under ROC curve was 0.863±0.022 [95%CI (0.820-0.906)], indicating that the model had a good prediction coincidence and discriminant validity. The model was verified using the data of the validation group, and the results exhibited that the sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate were 97.3%, 86.0%, 75.0%, 98.7%, and 89.4%, respectively. Discussion and Conclusions: This study showed that about 32.0% of patients with bloodstream infections died within 30 days, which was consistent with other data reported at home and abroad. In the mortality risk prediction model established in this study, the four risk factors for death included septic shock, albumin < 30g/L, placement of urinary ducts, and inappropriate empirical antibiotic treatment, which have also been reported in other studies. A notable finding in this study was the identification of previously unnoted risk factors for death, including platelets < 30×109/L before infection and bleeding. The prediction model in our study was verified that the model had a good prediction coincidence, discriminant validity, and clinical predictive value, which can provide evidence for clinicians to evaluate the death risk and make individualized treatment plans for patients.

Mycoplasma pneumoniae among Hospitalized Patients with Acute Respiratory Tract Infections in an Indian Tertiary Care Hospital: an Underreported Health Problem.

ABSTRACTThe epidemiology of Mycoplasma pneumoniae (Mp) is poorly understood in India. The present study was conducted to identify the prevalence of Mp in a large set of patients with acute respiratory tract infections (ARI) in an Indian tertiary hospital. During 2015–2020, we tested throat swab specimens from patients with the clinical diagnosis of ARI (n = 1,098) by a real-time PCR and compared the demographic, clinical, laboratory, and outcome data of Mp-positive and Mp-negative patients. During the study period, 5% (55/1,098) of the tested samples were positive for Mp by PCR. School-aged children and young adults represented 36% (20/55) of the cases and 47.3% (26/55) of the cases were registered during the summer and monsoon. Among the Mp-positive patients, 61.8% (34/55) had underlying conditions; the most common were malignancy (n = 12; 21.8%) and hypertension (n = 6; 10.9%). Fever (98.2% versus 84.9%; P = 0.006), and pharyngitis (27.3% versus 16.3%; P = 0.034) were significantly common in the Mp-positive group than Mp-negative group. Among the Mp-positive group, 20% (11/55) of patients were admitted to an intensive care unit and a total of 7/55 (12.7%) patients received ventilatory support. The mortality in the Mp-positive cohort was 13.3%. The study provides baseline data regarding Mp prevalence and clinical characteristics. The application of molecular assays for diagnosing this pathogen among hospitalized patients with ARI could reduce inappropriate empirical antibiotic treatment and improve patient outcomes. Further large-scale studies are required to avoid the underdiagnosis of Mp infections in India and such studies should address some research gaps, such as macrolide resistance and molecular typing.IMPORTANCE M. pneumoniae (Mp) is a significant pathogen causing atypical pneumonia but by far these infections are underreported clinical entities in India. In the present study, we report the prevalence of Mp and describe the demographic and baseline clinical data of Mp-positive cases in an Indian tertiary care hospital. Our study may improve the clinician’s awareness of this important agent of respiratory infection therefore timely and accurate diagnostic tools can be applied for patient management decisions and outcomes.

Short- and long-term mortality in patients with urosepsis caused by Escherichia coli susceptible and resistant to 3rd generation cephalosporins

BackgroundThe aim of this study was to compare short- and long-term mortality among patients with urosepsis caused by Escherichia coli susceptibile (EC-SC) and resistant (EC-RC) to 3rd generation cephalosporins.MethodsA retrospective cohort study that included all patients with E. coli urosepsis admitted to a 700-bed hospital from January 2014 until December 2019. Mortality up to 30 days, 6 months and 1 year was assessed using logistic multivariate regression analysis and Cox regression analysis.ResultsA total of 313 adult were included, 195 with EC-SC and 118 patients with EC-RC. 205 were females (74%), mean age was 79 (SD 12) years. Mean Charlson score was 4.93 (SD 2.18) in the EC-SC group and 5.74 (SD 1.92) in the EC-RC group. Appropriate empiric antibiotic therapy was initiated in 245 (78.3%) patients, 100% in the EC-SC group but only 42.5% in the EC-RC group. 30-day mortality occurred in 12 (6.3%) of EC-SC group and 15 (12.7%) in the EC-RC group. Factors independently associated with 30-day mortality were Charlson score, Pitt bacteremia score, fever upon admission and infection with a EC-RC. Appropriate antibiotic therapy was not independently associated with 30-day mortality. Differences in mortality between groups remained significant one year after the infection and were significantly associated with the Charlson co-morbidity score.ConclusionsMortality in patients with urosepsis due to E. coli is highly affected by age and comorbidities. Although mortality was higher in the EC-RC group, we could not demonstrate an association with inappropriate empirical antibiotic treatment. Mortality remained higher at 6 months and 1 year long after the infection resolved but was associated mainly with co-morbidity.

Factors Associated with Gram-Negative Bacteremia and Mortality in Neutropenic Patients with Hematologic Malignancies in a High-Resistance Setting.

Patients with hematological malignancies (HMs) have a substantial incidence of febrile neutropenic episodes. Gram-negative bacteremia (GNB) is still the major cause of these episodes. We evaluated the factors associated with GNB and mortality of bacteremic patients with HMs in a high-resistance setting. We conducted a prospective cohort study from March 2018 to June 2019 with 66 bacteremic and 132 non-bacteremic patients. Regression analyses were used to identify factors associated with GNB and 30-day mortality. The mean age was 53.83±15.21 years, and 129 (65.2%) of the patients were male. In multivariable analysis, factors independently associated with GNB were male gender, duration of hospitalization and neutropenia before the febrile neutropenic episode, leukemias and allogeneic transplant recipients, radiotherapy, receiving glucocorticosteroids, colonization with resistant microorganisms. All-cause mortality and 30-day mortality were 47.0% and 30.3% in cases of GNB, compared to non-bacteremic controls 25.0% and 10.6%, respectively. Sepsis, duration of hospitalization before the febrile neutropenic episode, carbapenem-resistant GNB, and inappropriate empirical antibiotic treatment was found as factors associated with 30-day mortality. Prior antibiotic exposure particularly beta-lactamase inhibitor combinations and carbapenems during the past 30 days was more frequent in the bacteremic group. An increasing trend was observed in multidrug-resistant (MDR) bacteria (p=0.03) and carbapenem-resistant Enterobacterales (p=0.02) over the years. By considering the risk factors associated with GNB and 30-day mortality that we detected in our study among neutropenic patients, a personalized approach for the management of febrile neutropenic patients can be designed by means of an effective antimicrobial stewardship program including the appropriate use of broad-spectrum antibiotics.

Risk factors of methicillin-resistant Staphylococcus aureus bacteremic pneumonia in the emergency department

The infection rate of methicillin-resistant Staphylococcus aureus (MRSA) has increased worldwide and MRSA bacteremic pneumonia is associated with a high mortality rate. This is a retrospective study conducted at a university hospital in Korea involving adult patients diagnosed as bacteremic pneumonia caused by S. aureus in the ED between January 2009 and December 2019. We compared MRSA bacteremic pneumonia patients (n = 56) to methicillin-susceptible S. aureus bacteremic pneumonia patients (n = 49). Our study showed that that underlying hypertension (OR = 5.68; 95% CI = 2.00–16.11; p = 0.001) and cerebrovascular disease (OR = 3.54; 95% CI = 1.06–11.75; p = 0.038), recent intravenous therapy within 1 month (OR = 8.38; 95% CI = 2.88–24.38; p = 0.0001), and pleural effusion on chest radiography (OR = 5.77; 95% CI = 1.79–18.57; p = 0.003) were independent risk factors for MRSA bacteremic pneumonia presenting to the ED. Although MRSA infection has been more frequently derived from the community than before, inappropriate empiric antibiotic treatment was overwhelmingly observed in the majority of patients in our study. Considering the resistance of MRSA to the typical empiric regimen prescribed for community-acquired pneumonia, emergency physicians should pay attention to the predictors for MRSA bacteremic pneumonia including pleural effusion on chest radiography when deciding on the appropriate empiric antimicrobial therapy for pneumonia patients in the ED.

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 Readmission Following Discharge of Patients With Gram-Negative Bacteremia: A Retrospective Cohort Study.

BackgroundShort-term readmission is an important outcome reflecting the poor trajectory of sepsis survivors. The aim of this study was to identify the major risk factors for 30-day readmission among patients with gram-negative bacteremia.MethodsThis was a retrospective cohort study including all consecutive adults hospitalized in the medical departments in a referral hospital in Israel with gram-negative bacteremia between 2011 and 2020, who were discharged alive. Predictors for 30-day readmission were investigated, considering death after discharge as a competing event. Cephalosporin resistance was our predictor of interest. Subdistribution hazard ratios (HRs) of the cumulative incidence function were investigated using the Fine and Gray multivariable competing-risk regression model. The prediction models were cross-validated using the k-fold method.ResultsAmong 2196 patients surviving hospitalization with gram-negative bacteremia, the mean age was 70 ± 16 years and 432 (19.6%) were readmitted within 30 days. Variables associated with readmission hazards were Arab ethnicity, active malignancy, conditions requiring immunosuppression, anxiolytics or hypnotics, anticoagulant or antiplatelet therapy, discharge with a nasogastric tube, higher predischarge heart rate, duration of antibiotic therapy during hospitalization, and bacteremia caused by cephalosporin-resistant bacteria (HR, 1.23 [95% confidence interval {CI}, .99–1.52]). The area under the receiver operating characteristic curve for this model was 75.5% (95% CI, 71.3%–79.1%). In secondary models, cephalosporin resistance, inappropriate empirical antibiotic treatment, and lower predischarge albumin were significantly associated with readmission.ConclusionsThirty-day readmissions among patients with gram-negative bacteremia surviving the index admission were high. Readmission was related to comorbidities and infections caused by multidrug-resistant infections.Main point: Among 2196 adults surviving hospitalization with gram-negative bacteremia, 432 (19.6%) were rehospitalized within 30 days. Comorbidities, inappropriate empirical antibiotic treatment, bacteremia caused by cephalosporin-resistant bacteria, predischarge heart rate, and albumin were associated with readmissions.

Impact of inappropriate empirical antibiotic treatment on clinical outcomes of urinary tract infections caused by Escherichia coli: a retrospective cohort study

We aimed to determine the clinical impact of inappropriate empirical antibiotic treatment (IEAT) compared with appropriate empirical antibiotic treatment (AEAT) in hospitalised patients with urinary tract infections (UTIs) caused by Escherichia coli (E. coli). This retrospective cohort study included adult patients with a primary diagnosis of UTI who were treated with empirical antibiotics at a tertiary hospital in southern China over a 2-year period. Clinical data of patients who received IEAT were compared with those of patients receiving AEAT. We used multivariable logistic regression to identify the predictors for receiving IEAT and the risk factors affecting clinical outcomes. A total of 213 patients were enrolled (median age, 61 years), of whom 103 (48.4%) received IEAT. IEAT was associated with empirical use of fluoroquinolones, male sex and age-adjusted Charlson comorbidity index (aCCI) score >6. Hospital length of stay (LOS) was longer for patients who received IEAT than for those who received AEAT (13.6 ± 8.6 days vs. 10.8 ± 7.9 days; P=0.008). IEAT was an independent risk factor for longer LOS along with aCCI score ≥2, lung disease and cardiac disease. Empirical use of fluoroquinolones for UTIs should be avoided, especially in male patients with aCCI score >6. Improved empirical antimicrobial therapy may have a beneficial impact in reducing bacterial resistance and healthcare costs by decreasing the LOS. Therefore, interventions to promote in-depth antibiotic stewardship programmes in China are needed.

Multidrug-resistant, gram-negative infections in high-risk haematologic patients: an update on epidemiology, diagnosis and treatment.

Multidrug-resistant Gram-negative bacilli (MDR-GNB) infections are a significant cause of morbidity and mortality in high-risk hematologic patients. Early diagnosis and management of antibiotic treatment in these patients is a challenge for physicians. This review focuses on the latest literature reports that concern the epidemiology, diagnosis and treatment of MDR-GNB infections in this population. High-risk haematological patients have several risk factors that make them particularly susceptible to MDR-GNB infections. Few studies have examined the implementation of rapid diagnostic methods for multidrug resistance, and their impact on management in this population. Inappropriate empiric antibiotic treatment in these patients has been described frequently and is associated with poor outcomes. Knowledge of the local epidemiology of MDR-GNB is a basic requirement to guide empiric antibiotic treatments in each centre. New diagnosic tests might help in faster identification of MDR-GNB infections. Appropriate empiric antibiotic treatment is crucial for improving patients' prognosis. Important strategies to reduce inadequate antibiotic treatment include better risk stratification for MDR-GNB infection and the introduction of new, more broad-spectrum antibiotic therapies.

1605. Differences in Clinical Characteristics of Third Generation Cephalosporin Resistance and Treatment Outcomes in Escherichia coli and Klebsiella pneumoniae Bacteremia in Patients with Liver Cirrhosis

BackgroundThis study aimed to identify characteristics of third-generation cephalosporin (3GC) resistance in Escherichia coli bateremia (ECB) and Klebsiella pneumoniae bacteremia (KPB) in patients with liver cirrhosis (LC), and to investigate the effects of appropriateness of empirical antibiotic treatment on outcomes.MethodsWe retrospectively collected demographic, clinical and microbiological information on all ECB and KPB episodes in LC patients ≥ 18 years of age hospitalized to a tertiary-care teaching hospital in South Korea from 2007 to 2018. Clinical characteristics associated with 3GC resistance and treatment failure were analyzed using a multivariate logistic regression model. Treatment failure was defined as persistent bacteremia for ≥ 7 days, or relapsed bacteremia ≤ 30 days, or all-cause mortality ≤ 30 days.Results3GC resistance rates of E. coli were 30.3% overall and increased significantly during the study period (P=0.001), while the rates of K. pneumoniae were not changed (24.3% overall) (P=0.994). Of total 356 ECB and KPB episodes, 112 were caused by 3GC resistant strains. The factor associated with 3GC resistance was isolation of 3GC resistant strain ≤ 1 year in both ECB (OR, 7.754; 95% CI, 2.094~28.716) and KPB (OR, 2.774; 1.318~5.838). In ECB, beta-lactam or fluoroquinolone treatment ≤ 30 days was another factor associated with 3GC resistance (OR, 2.774; 95% CI, 1.318~5.838), but not in KPB. The factor associated with treatment failure was high MELD score in both ECB (OR, 1.193 at 1 increase; 95% CI, 1.118~1.272) and KPB (OR, 1.163; 95% CI 1.083~1.250). Additionally, in ECB, non-alcoholic LC (OR 3.262; 95% CI 1.058~10.063), high Charlson Comorbidity Index (OR, 1.285; 95% CI 1.066~1.548), and inappropriate empirical antibiotic treatment (OR, 3.194; 95% CI 1.207~8.447) were associated with treatment failure.ConclusionDuring the study period, 3GC resistance increased in ECB, but not in KPB. In ECB, the severity of the underlying disease and the appropriateness of empirical antibiotics were associated with treatment failure, but there was no correlation in KPB. In ECB of LC patients, the appropriateness of empirical antibiotics was a factor associated with treatment outcome, and is the only correctable factor in the clinical setting.Disclosures All Authors: No reported disclosures

Routine Intraoperative Bacterial Culture May Be Needed in Complicated Appendicitis.

PurposeChoosing the appropriate antibiotic is important for treatment of complicated appendicitis. However, increasing multidrug resistant bacteria have been a serious problem for successful treatment. This study was designed to identify bacteria isolated from patients with complicated appendicitis and reveal their susceptibilities for antibiotics and their relationship with patient clinical course.MethodsThis study included patients diagnosed with complicated appendicitis and examined the bacterial cultures and antimicrobial susceptibilities of the isolates. Data were retrospectively collected from medical records of Kangbuk Samsung Hospital from January 2008 to February 2018.ResultsThe common bacterial species cultured in complicated appendicitis were as follows: Escherichia coli (n=113, 48.9%), Streptococcus spp. (n=29, 12.6%), Pseudomonas spp. (n=23, 10.0%), Bacteriodes spp. (n=22, 9.5%), Klebsiella (n=11, 4.8%), and Enterococcus spp. (n=8, 3.5%). In antibiotics susceptibility testing, the positive rate of extended-spectrum beta lactamase (ESBL) was 9.1% (21 of 231). The resistance rate to carbapenem was 1.7% (4 of 231), while that to vancomycin was 0.4% (1 of 231). E. coli was 16.8% ESBL positive (19 of 113) and had 22.1% and 19.5% resistance rates to cefotaxime and ceftazidime, respectively. Inappropriate empirical antibiotic treatment (IEAT) occurred in 55 cases (31.8%) and was significantly related with organ/space surgical site infection (SSI) (7 of 55, P=0.005).ConclusionThe rate of antibiotic resistance organisms was high in community-acquired complicated appendicitis in Koreans. Additionally, IEAT in complicated appendicitis may lead to increased rates of SSI. Routine intraoperative culture in patients with complicated appendicitis may be an effective strategy for appropriate antibiotic regimen.

EDITORIAL COMMENT

Standard urine cultures typically result in 48 hours or longer, and in practice this often leads to empiric antibiotic treatment of presumed infections, including the suboptimal use of antibiotics. In one study, 23% of emergency room patients with positive urine cultures received inappropriate empiric antibiotic treatment requiring later intervention following discharge. 1 Lingenfelter E Drapkin Z Fritz K et al. ED pharmacist monitoring of provider antibiotic selection aids appropriate treatment for outpatient UTI. Am J Emerg Med. 2016; 34: 1600 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar In the current era of rampant antibiotic resistance, rapid diagnosis of infections and associated antibiotic resistance are desperately needed to expedite targeted treatment, and minimize overuse and inappropriate use of antibiotics. Culture-independent assays, such as the one described in the accompanying paper, may result in as few as 6 hours. The current study is a timely investigation comparing standard urinary cultures and a multiplex PCR-based assay in detecting bacteria in patients with UTI symptoms. The authors conclude that the multiplex PCR assay was noninferior to standard cultures in detection of bacteria in symptomatic patients. This study is a step forward in the implementation of culture-independent assays in the diagnosis and treatment of UTI.

Comparison of Risk Factors and Outcomes in Carbapenem-Resistant and Carbapenem-Susceptible Gram-Negative Bacteremia.

Background:Carbapenem-resistant Gram-negative bacteremia (CR-GNB) is seen with increasing frequency and result in high mortality. The aim of this study was to compare the risk factors and results of carbapenem-resistant and carbapenem-susceptible Gram-negative bacteremia and to determine the factors related to mortality.Methods:The study was conducted as a retrospective observational comparative case series between June 2016 and November 2017 in Şişli Hamidiye Etfal Training and Research Hospital. The patients were divided into two groups as carbapenem-susceptible and carbapenem-resistant according to antibiotic susceptibility data of blood cultures. The risk factors for the development of carbapenem resistance, length of hospital stay, mortality rates, and mortality related factors were investigated between these two groups.Results:Two hundred and eleven cases were included in the study. Of these cases, 54 were resistant to carbapenem and 157 were susceptible to carbapenem. Mortality occurred in 60 (28.4%) patients. The 14 and 28 day mortality rates of patients with carbapenem resistance were significantly higher than those without carbapenem resistance. There was no statistically significant difference between two groups in length of stay in the hospital after bacteremia. Pittsburgh bacteremia score, cardiovascular disease, urinary catheterization, and inappropriate empirical antibiotic therapy were the most significant risk factors for mortality.Conclusions:Carbapenem resistance is associated with increased mortality and inappropriate empirical antibiotic treatment increases mortality. Therefore, patients should be evaluated for risk factors in predicting CR-GNB and treatment for resistant pathogens should be applied in appropriate patients.

Changing epidemiology of bloodstream infection in a 25-years hematopoietic stem cell transplant program: current challenges and pitfalls on empiric antibiotic treatment impacting outcomes.

We aimed to describe epidemiology changes in bloodstream infections (BSI) episodes in hematopoietic stem cell transplant (HSCT) recipients throughout a 25-year period (1993-2017), comparing five-year time spans, and we evaluate their impact on inappropriate empirical antibiotic treatment (IEAT) and mortality. During the study period, 1164 BSI episodes were documented in patients undergoing HSCT (71.6% allogenic and 29% autologous). A significant decrease in gram-positive cocci (GPC) and increase in gram-negative bacilli (GNB) were observed (p < 0.001). Among GP, coagulase-negative staphylococci (CoNS) significantly decreased whereas rising E. faecium BSI was documented. Among GNB, E. coli, Pseudomonas aeruginosa and K. pneumoniae rates increased. Multidrug-resistant (MDR) GNB, especially ESBL-E. coli and MDR-P. aeruginosa, emerged in 2008 and has gradually increased. IEAT against MDR-P. aeruginosa, but not in other MDR-GNB, augmented throughout the study period. Overall, 30-day and related mortality rates were 12.7% and 7.7% respectively, both increasing over time (p < 0.001 and p = 0.025). In GNB, 30-day and related mortality were 18.5% and 12.8%, respectively, increasing over time (p < 0.001 and p = 0.004). To conclude, important BSI epidemiological changes were described in a 25-year period. Concerning increase in IEAT for P. aeruginosa infections and rising 30-day mortality rate were documented.

Inappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug Resistance.

We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality. This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006-2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes. Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19-4.91]), shock at onset (4.62 [2.49-8.56]), and pneumonia (3.01 [1.55-5.83]). IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa-related BSI mortality and in turn is the only modifiable factor to improve outcomes.