Preventing New Gram-negative Resistance Through Beta-lactam De-escalation in Hospitalized Patients With Sepsis: A Retrospective Cohort Study.

BACKGROUND: Whether antibiotic de-escalation reduces the risk of subsequent antibiotic resistance is uncertain. We sought to determine if beta-lactam (BL) antibiotic de-escalation is associated with decreased incidence of new Gram-negative resistance in hospitalized patients with sepsis. METHODS: In a retrospective cohort study, patients with sepsis who were treated with at least 3 consecutive days of BL antibiotics, the first 2 days of which were with a broad-spectrum BL agent defined as a spectrum score (SS) of ≥7 were enrolled. Patients were grouped into three categories: (1) de-escalation of beta-lactam spectrum score (BLSS), (2) no change in BLSS, or (3) escalation of BLSS. The primary outcome was the isolation of a new drug-resistant Gram-negative bacteria from a clinical culture within 60 days of cohort entry. Fine-Gray proportional hazards regression modeling while accounting for in-hospital death as a competing risk was performed. FINDINGS: Six hundred forty-four patients of 7742 (8.3%) patients developed new gram-negative resistance. The mean time to resistance was 23.7 days yielding an incidence rate of 1.85 (95% confidence interval [CI]: 1.71-2.00) per 1000 patient-days. The lowest incidence rate was observed in the de-escalated group 1.42 (95% CI: 1.16-1.68) per 1000 patient-days. Statistically significant reductions in the development of new gram-negative resistance were associated with BL de-escalation compared to no-change (hazards ratio (HR) 0.59 [95% CI: .48-.73]). CONCLUSIONS: De-escalation was associated with a decreased risk of new resistance development compared to no change. This represents the largest study to date showing the utility of de-escalation in the prevention of antimicrobial resistance.

Effect of Early Administration of Vasopressin on New-Onset Arrhythmia Development in Patients With Septic Shock: A Retrospective, Observational Cohort Study.

Background: Adjunctive vasopressin use in septic shock reduces catecholamine requirements and is associated with a lower incidence of new-onset arrhythmias (NOAs). The association of vasopressin timing on NOA development is ill-described. Objective: To determine whether early administration of vasopressin was associated with a lower incidence of NOA in septic shock patients. Methods: A retrospective analysis of intensive care unit (ICU) patients at a large, academic medical center. Septic shock patients who required vasopressin and norepinephrine were eligible for inclusion. Patients were excluded for receipt of other vasoactive agents, history of cardiac arrhythmias, or outside hospital admission. Early vasopressin was defined as receipt within 6 hours of septic shock onset. The primary outcome was incidence of NOA. Results: In total, 436 patients, 220 (50.4%) in the early and 216 (49.6%) in the late vasopressin group, were included. Early vasopressin was not associated with a lower incidence of NOA compared with late vasopressin (9% vs 7%, median absolute difference [95% confidence interval, CI]: -2.1 [-7.2, 3.0], P = 0.41). Early vasopressin patients were observed to have shorter shock duration (2 vs 4 days, median absolute difference [95% CI]: 2 [1, 2], P < 0.001), and ICU length of stay (6 vs 7 days, median absolute difference [95% CI]: 1 [0, 2], P = 0.02). Conclusions and Relevance: Early vasopressin use was not associated with a lower incidence of NOA. Additional studies are needed to elucidate the effect of vasopressin timing on NOA and other clinical outcomes.

Racial Disparities in Readmissions Following Initial Hospitalization for Sepsis.

OBJECTIVES: To assess whether Black race is associated with a higher rate of all-cause readmission compared with White race following community-onset sepsis. DESIGN: Retrospective cohort study. SETTING: One-thousand three-hundred bed urban academic medical centers. PATIENTS: Three-thousand three-hundred ninety patients hospitalized with community-onset sepsis between January 1, 2010, and December 31, 2017. INTERVENTIONS: Community-onset sepsis was defined as patients admitted through the emergency department with an International Classification of Disease, ninth revision, Clinical Modification code for either severe sepsis (995.92) or septic shock (785.52). Beginning in 2015, we used International Classification of Disease, Tenth Revision, Clinical Modification codes R65.20 (severe sepsis) and R65.21 (septic shock). We excluded those individuals hospitalized at another acute care facility that were transferred to our facility. Race was abstracted electronically, and patients who expired or self-identified as a race other than Black or White race were excluded. Patients who experienced a subsequent hospitalization at our facility were considered to be readmitted. MEASUREMENTS AND MAIN RESULTS: Compared with White race, Black race demonstrated a significantly higher rate of all-cause readmission (60.8% vs 71.1%; p < 0.001), including a higher rate of readmission for sepsis (14.0% vs 19.8%; p < 0.001). Black patients also resided in zip codes with a lower median household income and were more likely to use public insurance compared with White race. Similar rates of comorbid diseases and disease burden were observed between the two groups, but vasopressors were less likely to be administered to Black patients. Multivariable analysis showed that Black race was associated with a 50% increased odds (odds ratio, 1.52, 99% CI, 1.25-1.84) in all-cause readmission risk compared with White race. CONCLUSIONS: Black race was associated with a higher rate of all-cause and sepsis readmission, possibly as a result of unaddressed health disparities, compared with White race. Programs addressing healthcare disparities should use readmission as another marker of equity.

Risk Factors and Outcomes for Ineffective Empiric Treatment of Sepsis Caused by Gram-Negative Pathogens: Stratification by Onset of Infection.

Sepsis and septic shock remain serious consequences of infections, with reported mortality rates in excess of 40 percent. Timely antibiotic therapy in cases of sepsis and septic shock is recognized as an important determinant of outcome. However, the administration of ineffective empirical treatment (IET) (an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results) is associated with excess mortality compared to effective empirical treatment (EET). We examined all hospitalized patients at Barnes-Jewish Hospital with a sterile site (blood or pleural, abdominal, cerebrospinal, synovial, and pericardial fluid) culture positive for Gram-negative (GN) bacteria combined with a primary or secondary ICD-9-CM code for severe sepsis (995.92) or septic shock (785.52) between January 2010 and October 2015. Variables significantly associated with early-onset (<48 h of hospitalization) IET of GN sterile site sepsis and septic shock included age, recent hospitalization, and prior intravenous antibiotics. Late-onset IET was associated with increasing numbers of hospitalization days before infection onset and prior intravenous antibiotic administration. For patients with early-onset infection, we found no difference in rates of survival between patients receiving IET and EET. However, patients in the late-onset infection group receiving IET had a statistically lower rate of survival than those receiving EET. These data suggest that risk factors and outcomes for IET can vary based on the time of onset of infection. Our results also highlight the importance of prior intravenous antibiotic exposure as a risk factor for IET in infections by GN bacteria regardless of the time of onset of infection.

Importance of Site of Infection and Antibiotic Selection in the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Sepsis.

In a retrospective analysis of 215 patients with carbapenem-resistant Pseudomonas aeruginosa sepsis, we observed a significantly higher risk of mortality associated with respiratory tract infection (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.04 to 1.39; P = 0.010) and lower risk with urinary tract infection (RR, 0.80; 95% CI, 0.71 to 0.90; P = 0.004). Aminoglycoside monotherapy was associated with increased mortality, even after adjusting for confounders (adjusted RR, 1.72; 95% CI, 1.03 to 2.85; P = 0.037), consistent across multiple sites of infection.

Sepsis-Associated Coagulopathy Severity Predicts Hospital Mortality.

OBJECTIVES: To assess whether sepsis-associated coagulopathy predicts hospital mortality. DESIGN: Retrospective cohort study. SETTING: One-thousand three-hundred beds urban academic medical center. PATIENTS: Six-thousand one-hundred forty-eight consecutive patients hospitalized between January 1, 2010, and December 31, 2015. INTERVENTIONS: Mild sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.2 and less than 1.4 plus platelet count less than or equal to 150,000/µL but greater than 100,000/µL; moderate sepsis-associated coagulopathy was defined with either an international normalized ratio greater than or equal to 1.4 but less than 1.6 or platelets less than or equal to 100,000/µL but greater than 80,000/µL; severe sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.6 and platelets less than or equal to 80,000/µL. MEASUREMENTS AND MAIN RESULTS: Hospital mortality increased progressively from 25.4% in patients without sepsis-associated coagulopathy to 56.1% in patients with severe sepsis-associated coagulopathy. Similarly, duration of hospitalization and ICU care increased progressively as sepsis-associated coagulopathy severity increased. Multivariable analyses showed that the presence of sepsis-associated coagulopathy, as well as sepsis-associated coagulopathy severity, was independently associated with hospital mortality regardless of adjustments made for baseline patient characteristics, hospitalization variables, and the sepsis-associated coagulopathy-cancer interaction. Odds ratios ranged from 1.33 to 2.14 for the presence of sepsis-associated coagulopathy and from 1.18 to 1.51 for sepsis-associated coagulopathy severity for predicting hospital mortality (p < 0.001 for all comparisons). CONCLUSIONS: The presence of sepsis-associated coagulopathy identifies a group of patients with sepsis at higher risk for mortality. Furthermore, there is an incremental risk of mortality as the severity of sepsis-associated coagulopathy increases.

Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship.

INTRODUCTION: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. RESULTS: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.

Clinical implications for patients treated inappropriately for community-acquired pneumonia in the emergency department.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the most common infections presenting to the emergency department (ED). Increasingly, antibiotic resistant bacteria have been identified as causative pathogens in patients treated for CAP, especially in patients with healthcare exposure risk factors. METHODS: We retrospectively identified adult subjects treated for CAP in the ED requiring hospital admission (January 2003-December 2011). Inappropriate antibiotic treatment, defined as an antibiotic regimen that lacked in vitro activity against the isolated pathogen, served as the primary end point. Information regarding demographics, severity of illness, comorbidities, and antibiotic treatment was recorded. Logistic regression was used to determine factors independently associated with inappropriate treatment. RESULTS: The initial cohort included 259 patients, 72 (27.8%) receiving inappropriate antibiotic treatment. There was no difference in hospital mortality between patients receiving inappropriate and appropriate treatment (8.3% vs. 7.0%; p = 0.702). Hospital length of stay (10.3 ± 12.0 days vs. 7.0 ± 8.9 days; p = 0.017) and 30-day readmission (23.6% vs. 12.3%; p = 0.024) were greater among patients receiving inappropriate treatment. Three variables were independently associated with inappropriate treatment: admission from long-term care (AOR, 9.05; 95% CI, 3.93-20.84), antibiotic exposure in the previous 30 days (AOR, 1.85; 95% CI, 1.35-2.52), and chronic obstructive pulmonary disease (AOR, 2.05; 95% CI, 1.52-2.78). CONCLUSION: Inappropriate antibiotic treatment of presumed CAP in the ED negatively impacts patient outcome and readmission rate. Knowledge of risk factors associated with inappropriate antibiotic treatment of presumed CAP could advance the management of patients with pneumonia presenting to the ED and potentially improve patient outcomes.

Clostridium difficile infection: a multicenter study of epidemiology and outcomes in mechanically ventilated patients.

OBJECTIVES: Clostridium difficile is a leading cause of hospital-associated infection in the United States. The purpose of this study is to assess the prevalence of C. difficile infection among mechanically ventilated patients within the ICUs of three academic hospitals and secondarily describe the influence of C. difficile infection on the outcomes of these patients. DESIGN: A retrospective cohort study. SETTING: ICUs at three teaching hospitals: Barnes-Jewish Hospital, Mayo Clinic, and Creighton University Medical Center over a 2-year period. PATIENTS: All hospitalized patients requiring mechanical ventilation for greater than 48 hours within an ICU were eligible for inclusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 5,852 consecutive patients admitted to the ICU were included. Three hundred eighty-six (6.6%) patients with development of C. difficile infection while in the hospital (5.39 cases/1,000 patient days). Septic shock complicating C. difficile infection occurred in 34.7% of patients. Compared with patients without C. difficile infection (n = 5,466), patients with C. difficile infection had a similar hospital mortality rate (25.1% vs 26.3%, p = 0.638). Patients with C. difficile infection were significantly more likely to be discharged to a skilled nursing or rehabilitation facility (42.4% vs 31.9%, p < 0.001), and the median hospital (23 d vs 15 d, p < 0.001) and ICU length of stay (12 d vs 8 d, p < 0.001) were found to be significantly longer in patients with C. difficile infection. CONCLUSIONS: Clostridium difficile infection is a relatively common nosocomial infection in mechanically ventilated patients and is associated with prolonged length of hospital and ICU stay, and increased need for skilled nursing care or rehabilitation following hospital discharge.

Prolonged infusion antibiotics for suspected gram-negative infections in the ICU: a before-after study.

BACKGROUND: ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results. OBJECTIVE: To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection. METHODS: We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011). RESULTS: A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329). CONCLUSIONS: Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Fluid balance and cardiac function in septic shock as predictors of hospital mortality.

INTRODUCTION: Septic shock is a major cause of morbidity and mortality throughout the world. Unfortunately, the optimal fluid management of septic shock is unknown and currently is empirical. METHODS: A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, Missouri). Consecutive patients (n = 325) hospitalized with septic shock who had echocardiographic examinations performed within 24 hours of shock onset were enrolled. RESULTS: A total of 163 (50.2%) patients with septic shock died during hospitalization. Non-survivors had a significantly larger positive net fluid balance within the 24 hour window of septic shock onset (median (IQR): 4,374 ml (1,637 ml, 7,260 ml) vs. 2,959 ml (1,639.5 ml, 4,769.5 ml), P = 0.004). The greatest quartile of positive net fluid balance at 24 hours and eight days post-shock onset respectively were found to predict hospital mortality, and the greatest quartile of positive net fluid balance at eight days post-shock onset was an independent predictor of hospital mortality (adjusted odds ratio (AOR), 1.66; 95% CI, 1.39 to 1.98; P = 0.004). Survivors were significantly more likely to have mild left ventricular dysfunction as evaluated by bedside echocardiography and non-survivors had slightly elevated left ventricular ejection fraction, which was also found to be an independent predictor of outcome. CONCLUSIONS: Our data confirms the importance of fluid balance and cardiac function as outcome predictors in patients with septic shock. A clinical trial to determine the optimal administration of intravenous fluids to patients with septic shock is needed.

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

Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection, accounting for 22% of all nosocomial infections. The available studies to date have not attempted to assess whether confounding factors may account for the observed difference in mortality for the two forms of nosocomial pneumonia associated with mechanical ventilation, namely ventilated HAP (vHAP) and ventilator-associated pneumonia (VAP). OBJECTIVES: To determine if vHAP is an independent predictor of mortality among patients with nosocomial pneumonia. DESIGN SETTING AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day all-cause mortality (ACM). RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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.

Septic shock attributed to Candida infection: importance of empiric therapy and source control.

BACKGROUND: Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. METHODS: A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). RESULTS: Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. CONCLUSIONS: The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical outcomes.

The determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment*.

OBJECTIVE: To identify the determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment. DESIGN: A retrospective cohort study of hospitalized patients with blood culture positive septic shock (January 2002-December 2007). SETTING: Barnes-Jewish Hospital, a 1,250-bed urban teaching hospital. PATIENTS: Four hundred thirty-six consecutive patients with septic shock and a positive blood culture. INTERVENTIONS: Data abstraction from computerized medical records. MEASUREMENTS AND MAIN RESULTS: Septic shock was associated with bloodstream infection due to Gram-negative bacteria (59.2%) and Gram-positive bacteria (40.8%). Two hundred twenty-four patients (51.4%) died during their hospitalization. The presence of infection attributed to antibiotic-resistant bacteria was similar for patients who survived and expired (22.6% vs. 20.1%; p = .516). Multivariate logistic regression analysis demonstrated that infection acquired in the intensive care unit (adjusted odds ratio 1.99; 95% confidence interval 1.52-2.60; p = .011) and increasing Acute Physiology and Chronic Health Evaluation II scores (one-point increments) (adjusted odds ratio 1.11; 95% confidence interval 1.09-1.14; p < .001) were independently associated with a greater risk of hospital mortality, whereas infection with methicillin-susceptible Staphylococcus aureus (adjusted odds ratio 0.32; 95% confidence interval 0.20-0.52; p = .017) was independently associated with a lower risk of hospital mortality. Patients infected with methicillin-susceptible Staphylococcus aureus infections were statistically younger and had lower Charlson comorbidity and Acute Physiology and Chronic Health Evaluation II scores compared to patients with non-methicillin-susceptible Staphylococcus aureus infections. CONCLUSIONS: Among patients with septic shock who receive appropriate initial antibiotic treatment, acquisition of infection in the intensive care unit and severity of illness appear to be the most important determinants of clinical outcome.

Ceftriaxone resistance and adequacy of initial antibiotic therapy in community onset bacterial pneumonia.

ABSTRACT: Much remains unknown about the impact of initial antibiotic adequacy on mortality in community onset bacterial pneumonia (COBP). Therefore, we performed a study to determine how the adequacy of initial antibiotic therapy affects in-hospital mortality for patients with COBP.We carried out a retrospective cohort study among the 11 BJC Healthcare community and academic hospitals in Missouri and Illinois. The electronic medical records for BJC Healthcare were queried to obtain a set of patient admissions with culture positive (respiratory or blood) COBP admitted from January 1, 2016 through December 31, 2019. Patients with COBP required an International Classification of Diseases (ICD)-10 diagnostic code for pneumonia, admission to the hospital through an emergency department, a chest radiograph with an infiltrate, an abnormal white blood cell count or temperature, an order for 1 or more new antibiotics, and a positive respiratory or blood culture. Antibiotic selection was deemed adequate if the patient had organisms susceptible to at least one of the antibiotics received according to in vitro testing using standard laboratory breakpoints.Among 36,645 screened pneumonia admissions, 1843 met criteria for culture positive COBP. Eight hundred nineteen (44.4%) had ceftriaxone-resistant (CTX-R) organisms and 1024 had ceftriaxone-sensitive (CTX-S) organisms. The most common CTX-R pathogens were methicillin resistant Staphylococcus aureus (46.9%), Pseudomonas species (38.4%), and Escherichia coli (4.5%). On the day of admission 71% of all patients were given adequate antibiotic treatment (62.2% of CTX-R and 77.9% of CTX-S). Unnecessarily broad initial treatment was administered to 57.1% of CTX-S patients. In a logistic regression model accounting for comorbidities and severity of illness, inadequate therapy on the day of admission was associated with higher in-hospital mortality (P = .005). Among CTX-S patients who were adequately treated, initial use of unnecessarily broad antibiotics was associated with increased in-hospital mortality (P = .003).Ceftriaxone resistance was common in this cohort of culture positive COBP patients. Inappropriate coverage on day of admission was associated with greater likelihood of in-hospital mortality.

Assessment of Antibiotic De-escalation by Spectrum Score in Patients With Nosocomial Pneumonia: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant mortality. Guidelines recommend empiric broad-spectrum antibiotics followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure. METHODS: This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016 to 2019. Patients were enrolled if they met predefined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). The primary outcome was composite treatment failure, defined as all-cause mortality or readmission for pneumonia within 30 days of diagnosis. RESULTS: Of 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs 1026 NDE). Groups were well matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs 50.6%, P = .011). There was no difference in composite treatment failure (35.0% DE vs 33.8% NDE, P = .604). De-escalation was not associated with treatment failure on multivariable Cox regression analysis (hazard ratio, 1.13; 95% confidence interval, 0.96-1.33). Patients receiving DE had fewer antibiotic days (median 9 vs 11, P < .0001), episodes of Clostridioides difficile infection (2.2% vs 3.8%, P = .046), and hospital days (median 20 vs 22 days, P = .006). CONCLUSIONS: De-escalation and NDE resulted in similar rates of 30-day treatment failure; however, DE was associated with fewer antibiotic days, episodes of C difficile infection, and days of hospitalization.

Characteristics and outcomes among a hospitalized patient cohort with Streptococcus pneumoniae infection.

Infection due to Streptococcus pneumoniae (SP) requiring hospitalization is common. However, recent clinical studies describing patient characteristics and outcomes for SP infection in adults requiring hospitalization are lacking. Our goal was to evaluate patient characteristics, contemporary antibiotic resistance, and clinical outcomes among hospitalized adults with SP infections.A retrospective cohort study was conducted at Barnes-Jewish Hospital (1350 beds) in St. Louis, Missouri, USA for years 2012 through 2016. During the study period, 358 hospitalized adults, excluding those with meningitis, were identified with SP infection. Forty-four patients (12.3%) died within 30 days of the identification of their infection. Among these infections, 99 (27.7%) were assessed to be hospital-acquired and 259 (72.3%) were community-onset infections. The majority of infections involved the respiratory tract (88.5%). Azithromycin resistance was the most common antibiotic resistance at 51.4%, followed by enteral penicillin resistance (45.3%), trimethoprim-sulfamethoxazole (34.1%), second-generation cephalosporin (cefuroxime) (30.7%), and meropenem (22.6%). There were 70 isolates (19.6%) classified as multidrug resistant. Independent predictors of hospital mortality included increasing weight in 1-kilogram increments (adjusted odds ratio [AOR], 1.02; 95% CI, 1.01 - 1.02; P = .048), increasing Charlson Comorbidity Index scores (AOR, 1.31; 95% CI, 1.21 - 1.42; P = .001), and the presence of septic shock (AOR, 3.89; 95% CI, 2.31 - 6.57; P = .009). The median [interquartile range] hospital length of stay was 8.1 days [4.5 days, 16.8 days].Hospitalized patients with infection attributed to SP have significant 30-day mortality and use of hospital resources. Antibiotic resistance is common among isolates associated with infection. Determinants of mortality are primarily severity of illness, underlying comorbidities and increasing patient weight. Efforts to improve the treatment and prevention of SP infections are needed.

Duration of Exposure to Antipseudomonal ß-Lactam Antibiotics in the Critically Ill and Development of New Resistance.

STUDY OBJECTIVE: Minimizing the duration of broad-spectrum antimicrobial exposure in the critically ill is a commonly used strategy aimed at preventing resistance. Our objective was to correlate the duration of exposure to antipseudomonal ß-lactam antibiotics with the development of new resistance in critically ill patients. DESIGN: Single-center, retrospective cohort study. SETTING: A large, academic, tertiary care hospital. PATIENTS: A total of 7118 adults with a discharge diagnosis of severe sepsis or septic shock who received at least one dose of cefepime, meropenem, or piperacillin-tazobactam during their hospitalization between 2010 and 2015. MEASUREMENTS AND MAIN RESULTS: Cohort entry was defined as the first day of any antipseudomonal ß-lactam initiation, and exposure was defined as the cumulative days of any antipseudomonal ß-lactam exposure during the 60-day follow-up period. The primary outcome was development of new resistance to any antipseudomonal ß-lactam > 3 days after cohort entry. New resistance was defined as detection of resistance to any antipseudomonal ß-lactam not identified within 180 days before cohort entry. Patients without an outcome (i.e., did not develop new resistance) or who died by day 60 were censored. Cox proportional hazards models were performed to assess the risk of development of new resistance to any antipseudomonal ß-lactam with each additional day of exposure. Analyses of each individual antipseudomonal ß-lactam were evaluated as secondary outcomes. Each additional day of exposure to any antipseudomonal ß-lactam resulted in an adjusted hazard ratio (aHR) of 1.04 (95% confidence interval [CI] 1.04-1.05) for new resistance development. The risk of developing new resistance to cefepime, meropenem, and piperacillin-tazobactam for each additional day of exposure resulted in an aHR of 1.08 (95% CI 1.07-1.09), 1.02 (95% CI 1.01-1.03), and 1.08 (95% CI 1.06-1.09), respectively. CONCLUSION: Among critically ill patients who receive antipseudomonal ß-lactam antibiotics, each additional day of exposure to cefepime, meropenem, and piperacillin-tazobactam is associated with an increased risk of new resistance development.