Comparison of Empiric Antibiotic Treatment Regimens for Hospitalized, Non-severe Community-acquired Pneumonia: A Retrospective, Multicenter Cohort Study.

PURPOSE: Consensus guidelines for hospitalized, non-severe community-acquired pneumonia (CAP) recommend empiric macrolide + ß-lactam or respiratory fluoroquinolone monotherapy in patients with no risk factors for resistant organisms. In patients with allergies or contraindications, doxycycline + ß-lactam is a recommended alternative. The purpose of this study was to compare differences in outcomes among guideline-recommended regimens in this population. METHODS: This retrospective, multicenter cohort study included patients ≥18 years of age with CAP who received respiratory fluoroquinolone monotherapy, empiric macrolide + ß-lactam, or doxycycline + ß-lactam. Major exclusion criteria included patients with immunocompromising conditions, requiring vasopressors or invasive mechanical ventilation within 48 hours of admission, and receiving less than 2 days of total antibiotic therapy. The primary outcome was in-hospital mortality. Secondary outcomes included clinical failure, 14- and 30-day hospital readmission, and hospital length of stay. Safety outcomes included incidence of new Clostridioides difficile infection and aortic aneurysm ruptures. FINDINGS: Of 4685 included patients, 1722 patients received empiric respiratory fluoroquinolone monotherapy, 159 received empiric doxycycline + ß-lactam, and 2804 received empiric macrolide + ß-lactam. Incidence of in-hospital mortality was not observed to be significantly different among empiric regimens (doxycycline + ß-lactam group: 1.9% vs macrolide + ß-lactam: 1.9% vs respiratory fluoroquinolone monotherapy: 1.5%, P = 0.588). No secondary outcomes were observed to differ significantly among groups. IMPLICATIONS: We observed no differences in clinical or safety outcomes among three guideline-recommended empiric CAP regimens. Empiric doxycycline + ß-lactam may be a safe empiric regimen for hospitalized CAP patients with non-severe CAP, although additional research is needed to corroborate these observations with larger samples.

Clinical Response to Third-Line Angiotensin-II vs Epinephrine in Septic Shock: A Propensity-Matched Cohort Study.

BACKGROUND: The appropriate third-line vasopressor in septic shock patients receiving norepinephrine and vasopressin is unknown. Angiotensin-II (AT-II) offers a unique mechanism of action to traditionally used vasopressors in septic shock. OBJECTIVE: The objective of this study was to compare the clinical efficacy and safety of third-line AT-II to epinephrine in patients with septic shock. METHODS: A single-center, retrospective cohort study of critically ill patients was performed between April 1, 2019 and July 31, 2022. Propensity-matched (2:1) analysis compared adults with septic shock who received third-line AT-II to controls who received epinephrine following norepinephrine and vasopressin. The primary outcome was clinical response 24 hours after third-line vasopressor initiation. Additional efficacy and safety outcomes were investigated. RESULTS: Twenty-three AT-II patients were compared with 46 epinephrine patients. 47.8% of AT-II patients observed a clinical response at hour 24 compared with 28.3% of epinephrine patients (P = 0.12). In-hospital mortality (65.2% vs 73.9%, P = 0.45), cardiac arrhythmias (26.1% vs 26.1%, P = 0.21), and thromboembolism (4.3% vs 2.2%, P = 0.61) were not observed to be statistically different between groups. CONCLUSIONS AND RELEVANCE: Administration of AT-II as a third-line vasopressor agent in septic shock patients was not associated with significantly improved clinical response at hour 24 compared with epinephrine. Although underpowered to detect meaningful differences, the clinical observations of this study warrant consideration and further investigation of AT-II as a third-line vasopressor in septic shock.

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.

An International, Multicenter Evaluation of Comprehensive Medication Management by Pharmacists in ICU Recovery Centers.

BACKGROUND: Post-intensive care syndrome (PICS) is defined as a new or worsening impairment in physical, cognitive, or mental health following critical illness. Intensive care unit recovery centers (ICU-RC) are one means to treat patients who have PICS. The purpose of this study is to describe the role of pharmacists in ICU-RCs. RESEARCH QUESTION: What is the number and type of medication interventions made by a pharmacist at an ICU-RC at 12 different centers? STUDY DESIGN AND METHODS: This prospective, observational study was conducted in 12 intensive care units (ICUs)/ICU-RCs between September 2019 and July 2021. A full medication review was conducted by a pharmacist on patients seen at the ICU-RC. RESULTS: 507 patients were referred to the ICU-RC. Of these patients, 474 attended the ICU-RC and 472 had a full medication review performed by a pharmacist. Baseline demographic and hospital course data were obtained from the electronic health record and at the ICU-RC appointment. Pharmacy interventions were made in 397 (84%) patients. The median number of pharmacy interventions per patient was 2 (interquartile range [IQR] = 1,3). Medications were stopped and started in 124 (26%) and 91 (19%) patients, respectively. The number of patients that had a dose decreased and a dose increased was 51 (11%) and 43 (9%), respectively. There was no difference in the median total number of medications that the patient was prescribed at the start and end of the patient visit (10, IQR = 5, 15). Adverse drug event (ADE) preventive measures were implemented in 115 (24%) patients. ADE events were identified in 69 (15%) patients. Medication interactions were identified in 30 (6%) patients. INTERPRETATION: A pharmacist plays an integral role in an ICU-RC resulting in the identification, prevention, and treatment of medication-related problems. This paper should serve as a call to action on the importance of the inclusion of a pharmacist in ICU-RC clinics.

New antimicrobial treatment options for severe Gram-negative infections.

PURPOSE OF REVIEW: This review will provide rationale for the development of new antibiotics to treat severe or multidrug-resistant (MDR) Gram-negative infections. It will also provide an overview of recently approved and pipeline antibiotics for severe/MDR Gram-negative infections. RECENT FINDINGS: MDR Gram-negative infections are recognized as critical threats by global and national organizations and carry a significant morbidity and mortality risk. Increasing antibiotic resistance amongst Gram-negative bacteria, including carbapenem-resistant Acinetobacter baumannii , extended-spectrum ß-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa , with difficult-to-treat-resistance has made both empiric and definitive treatment of these infections increasingly problematic. In recent years, several antibiotics have been approved for treatment of MDR Gram-negative infections and ongoing clinical trials are poised to provide additional options to clinicians' armamentarium. These agents include various ß-lactam/ß-lactamase inhibitor combinations, eravacycline, plazomicin and cefiderocol. SUMMARY: Severe/MDR Gram-negative infections continue to be important infections due to their impact on patient outcomes, especially in critically ill and immunocompromised hosts. The availability of new antibiotics offers an opportunity to improve empiric and definitive treatment of these infections.

Impact of Stress Ulcer Prophylaxis Discontinuation Guidance in Mechanically Ventilated, Critically Ill Patients: A Pre-Post Cohort Study.

Purpose: Recent data highlight unclear efficacy and potential negative sequelae of stress ulcer prophylaxis (SUP) in the intensive care unit (ICU). Minimizing SUP exposure has pertinent clinical and other implications. This study assessed medication use and clinical outcomes before and after implementation of a practice guideline promoting early discontinuation of SUP in mechanically ventilated ICU patients. Methods: Retrospective, single-center, pre-post cohort study within a medical ICU at a large, academic medical center. Adult patients requiring mechanical ventilation and receiving SUP via a histamine-2 receptor antagonist (H2RA) or proton pump inhibitor (PPI) were eligible for inclusion. The clinical practice guideline was implemented on January 1, 2020. The impact of implementation was assessed via percent of patient-days with inappropriate SUP. Incidence of clinically important GI bleed was the primary safety outcome. Results: A total of 137 pre-guideline and 112 post-guideline patients were included. Comorbidity burden was similar between groups. A higher prevalence of baseline vasopressor receipt (39% vs 67%, P < .01) and acute kidney injury (56% vs 69%, P = .04) was observed in post-guideline patients. Post-guideline patients experienced a significantly lower percentage of patient-days of inappropriate SUP (25% vs 50%, P < .01) as well as higher rates of SUP discontinuation before extubation (71% vs 12%, P < .01) and during ICU stay (93% vs 50%, P < .01). Post-guideline patients observed a significantly lower incidence of SUP at hospital discharge (4% vs 35%, P < .01). No differences in bleeding outcomes were observed, though post-guideline patients experienced longer durations of mechanical ventilation, ICU stay, and hospital stay. Conclusions: Implementation of an early SUP discontinuation guideline was associated with significant improvements in SUP prescribing practices. Baseline differences between groups likely explain observed differences in clinical outcomes.

Machine learning to predict vasopressin responsiveness in patients with septic shock.

STUDY OBJECTIVES: The objective of this study was to develop and externally validate a model to predict adjunctive vasopressin response in patients with septic shock being treated with norepinephrine for bedside use in the intensive care unit. DESIGN: This was a retrospective analysis of two adult tertiary intensive care unit septic shock populations. SETTING: Barnes-Jewish Hospital (BJH) from 2010 to 2017 and Beth Israel Deaconess Medical Center (BIDMC) from 2001 to 2012. PATIENTS: Two septic shock populations (548 BJH patients and 464 BIDMC patients) that received vasopressin as second-line vasopressor. INTERVENTION: Patients who were vasopressin responsive were compared with those who were nonresponsive. Vasopressin response was defined as survival with at least a 20% decrease in maximum daily norepinephrine requirements by one calendar day after vasopressin initiation, without a third-line vasopressor. MEASUREMENTS: Two supervised machine learning models (gradient-boosting machine [XGBoost] and elastic net penalized logistic regression [EN]) were trained in 1000 bootstrap replications of the BJH data and externally validated in the BIDMC data to predict vasopressin responsiveness. MAIN RESULTS: Vasopressin responsiveness was similar among each cohort (BJH 45% and BIDMC 39%). Mortality was lower for vasopressin responders compared with nonresponders in the BJH (51% vs. 73%) and BIDMC (45% vs. 83%) cohorts, respectively. Both models demonstrated modest discrimination in the training (XGBoost area under receiver operator curve [AUROC] 0.61 [95% confidence interval (CI) 0.61-0.61], EN 0.59 [95% CI 0.58-0.59]) and external validation (XGBoost 0.68 [95% CI 0.63-0.73], EN 0.64 [95% CI 0.59-0.69]) datasets. CONCLUSION: Vasopressin nonresponsiveness is common and associated with increased mortality. The models' modest performances highlight the complexity of septic shock and indicate that more research will be required before clinical decision support tools can aid in anticipating patient-specific responsiveness to vasopressin.

Sepsis Prediction for the General Ward Setting.

Objective: To develop and evaluate a sepsis prediction model for the general ward setting and extend the evaluation through a novel pseudo-prospective trial design. Design: Retrospective analysis of data extracted from electronic health records (EHR). Setting: Single, tertiary-care academic medical center in St. Louis, MO, USA. Patients: Adult, non-surgical inpatients admitted between January 1, 2012 and June 1, 2019. Interventions: None. Measurements and Main Results: Of the 70,034 included patient encounters, 3.1% were septic based on the Sepsis-3 criteria. Features were generated from the EHR data and were used to develop a machine learning model to predict sepsis 6-h ahead of onset. The best performing model had an Area Under the Receiver Operating Characteristic curve (AUROC or c-statistic) of 0.862 ± 0.011 and Area Under the Precision-Recall Curve (AUPRC) of 0.294 ± 0.021 compared to that of Logistic Regression (0.857 ± 0.008 and 0.256 ± 0.024) and NEWS 2 (0.699 ± 0.012 and 0.092 ± 0.009). In the pseudo-prospective trial, 388 (69.7%) septic patients were alerted on with a specificity of 81.4%. Within 24 h of crossing the alert threshold, 20.9% had a sepsis-related event occur. Conclusions: A machine learning model capable of predicting sepsis in the general ward setting was developed using the EHR data. The pseudo-prospective trial provided a more realistic estimation of implemented performance and demonstrated a 29.1% Positive Predictive Value (PPV) for sepsis-related intervention or outcome within 48 h.

Prospective Nasal Screening for Methicillin-Resistant Staphylococcus aureus in Critically Ill Patients With Suspected Pneumonia.

We carried out a prospective de-escalation study based on methicillin-resistant Staphylococcus aureus (MRSA) nasal cultures in intensive care unit patients with suspected pneumonia. Days of anti-MRSA therapy was significantly reduced in the intervention group (2 [0-3] days vs 1 [0-2] day; P < .01). Time to MRSA de-escalation was also shortened in the intervention group.

Short- Versus Standard-Course Nonmacrolide Antibiotic Treatment in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Retrospective, Observational Cohort Study.

PURPOSE: In critically ill patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and without positive microbiological data, the efficacy and tolerability of short-course nonmacrolide antibiotics are ill-described and have pertinent implications in antimicrobial stewardship. This study compared the efficacy and tolerability of nonmacrolide antibiotic strategies in critically ill patients with AECOPD and without pertinent positive microbiological testing. METHODS: This single-center, retrospective cohort study was conducted in culture-negative critically ill adults admitted to an intensive care unit (ICU) between July 1, 2014, and July 1, 2019, for the treatment of AECOPD. Included patients received treatment with an empiric corticosteroid, azithromycin, and/or a nonmacrolide antibiotic. Patients treated with a nonmacrolide antibiotic for ≤3 and >3 days made up the short- and standard-course groups, respectively. The prevalence of in-hospital mortality, progression to the need for ventilation, and/or readmission for AECOPD within 30 days (primary composite end point) was compared between the two groups. Additional end points included hospital and ICU lengths of stay (LOS), all-cause 30-day readmission, and prevalence of antibiotic-related adverse events. FINDINGS: A total of 135 patients were included (short course, 66; standard course, 69). The differences in the primary composite end point (short vs standard, 24.2% vs 39.1%; P = 0.06) and its individual components were not significant. The median ICU LOS (2 vs 3 days) and hospital LOS (4 vs 6 days) were shorter in the short-course group (both, P < 0.01). Multivariate logistic regression confirmed no association between group assignment and the primary end point. IMPLICATIONS: Short-course nonmacrolide therapy in patients with AECOPD and no positive microbiological testing was not associated with differences in mortality, progression to ventilation, readmission rate, or prevalence of adverse drug events. Larger-scale prospective studies are needed to validate these findings.

Evaluation of Amiodarone Use for New-Onset Atrial Fibrillation in Critically Ill Patients With Septic Shock.

Objective: To describe the use of amiodarone in critically ill, septic shock patients experiencing new-onset atrial fibrillation (NOAF) during the acute resuscitative phase of septic shock. Methods: Single-center, retrospective review of adult medical or surgical intensive care unit (ICU) patients with septic shock and NOAF. All patients received amiodarone for NOAF during the acute resuscitative phase of septic shock. The cohort was analyzed via descriptive statistics. Associations between amiodarone exposure and clinical outcomes were analyzed via a Cox proportional-hazards model. An a priori defined sensitivity analysis of hospital survivors was also employed. Main Results: A total of 239 patients were included in the analysis. Patients had a median baseline Charlson Comorbidity Index of 4 (interquartile range [IQR]: 2-6) and were acutely ill with a median Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 18 (IQR: 13-22) and an incidence of mechanical ventilation of 85%. In-hospital mortality was 56% with median ICU and hospital length of stay (LOS) of 9 and 15 days, respectively. Included patients received a median of 2760 (IQR: 1110-6415) mg of intravenous (IV) amiodarone during their ICU stay. Receipt of more than or equal to 2700 mg of amiodarone was identified as an independent factor associated with longer ICU LOS (hazard ratio [HR]: 1.30; 95% confidence interval [CI], 1.10-2.28). In a sensitivity analysis of hospital survivors (n = 105), receipt of more than or equal to 2700 mg of amiodarone remained independently associated with longer ICU LOS (HR: 1.64; 95% CI, 1.05-2.58). Conclusions: Exposure to more than or equal to 2700 mg of amiodarone in the setting of NOAF and septic shock is positively correlated with longer ICU LOS. Identifying opportunities to limit amiodarone exposure and address/resolve potential precipitating causes of NOAF in this clinical scenario may reduce the morbidity associated with septic shock.

New Perspectives on Antimicrobial Agents: Ceftolozane-Tazobactam.

Ceftolozane-tazobactam (C/T) is a new fifth-generation cephalosporin/beta-lactamase inhibitor combination approved by the Food and Drug Administration and the European Medicines Agency for treatment of complicated intraabdominal infections, complicated urinary tract infections, and hospital-acquired pneumonia in adult patients. This review will briefly describe the pharmacology of C/T and focus on the emerging clinical trial and real-world data supporting its current utilization. Additionally, our synthesis of these data over time has set our current usage of C/T at Barnes-Jewish Hospital (BJH). C/T is primarily employed as directed monotherapy at BJH when Pseudomonas aeruginosa isolates are identified with resistance to other beta-lactams. C/T can also be used empirically in specific clinical situations at BJH prior to microbiological detection of an antibiotic-resistant P. aeruginosa isolate. These situations include critically ill patients in the intensive care unit (ICU) setting, where there is a high likelihood of infection with multidrug-resistant (MDR) P. aeruginosa; patients failing therapy with a carbapenem; specific patient populations known to be at high risk for infection with MDR P. aeruginosa (e.g., lung transplant and cystic fibrosis patients); and patients know to have previous infection or colonization with MDR P. aeruginosa.

Effect of Vasopressin Dose on Hemodynamic Response in Obese Patients With Septic Shock: A Retrospective Observational Study.

BACKGROUND: No clear association between standard vasopressin doses and body mass index exists, despite potential pharmacokinetic and pharmacodynamic variability among patients with septic shock. It is unknown if higher doses may alter hemodynamic response. OBJECTIVE: The purpose of this study was to evaluate the effect of vasopressin dose on hemodynamic response in obese patients with septic shock. METHODS: A single-center, retrospective cohort study was conducted in adult, obese patients with septic shock receiving catecholamine vasopressors and vasopressin. Patients were analyzed according to vasopressin dose received: standard dose (≤0.04 U/min) and high dose (>0.04 U/min). The primary outcome was percentage change in norepinephrine equivalent (NEQ) dose. RESULTS: A total of 182 patients were included in the analysis, with 136 in the standard-dose vasopressin group and 46 in the high-dose vasopressin group. There was no difference in percentage change in NEQ dose at 6 hours after standard- or high-dose vasopressin attainment (-28.6% vs -19.1%; P = 0.166). A greater increase in mean arterial pressure (MAP) at 6 hours was observed with receipt of high-dose vasopressin (23.3% vs 15.3%; P = 0.023). Duration of shock and length of stay were significantly longer in patients who received high-dose vasopressin, with no difference in in-hospital mortality. CONCLUSION AND RELEVANCE: This represents the first analysis comparing standard and higher doses of vasopressin in obese patients with septic shock. Receipt of high-dose vasopressin was not associated with a difference in catecholamine requirement or improved outcomes. Further studies are warranted to provide guidance on the use of high-dose vasopressin in septic shock.

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.

Comparison of Sepsis Definitions as Automated Criteria.

OBJECTIVES: Assess the impact of heterogeneity among established sepsis criteria (Sepsis-1, Sepsis-3, Centers for Disease Control and Prevention Adult Sepsis Event, and Centers for Medicare and Medicaid severe sepsis core measure 1) through the comparison of corresponding sepsis cohorts. DESIGN: Retrospective analysis of data extracted from electronic health record. SETTING: Single, tertiary-care center in St. Louis, MO. PATIENTS: Adult, nonsurgical inpatients admitted between January 1, 2012, and January 6, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the electronic health record data, 286,759 encounters met inclusion criteria across the study period. Application of established sepsis criteria yielded cohorts varying in prevalence: Centers for Disease Control and Prevention Adult Sepsis Event (4.4%), Centers for Medicare and Medicaid severe sepsis core measure 1 (4.8%), International Classification of Disease code (7.2%), Sepsis-3 (7.5%), and Sepsis-1 (11.3%). Between the two modern established criteria, Sepsis-3 (n = 21,550) and Centers for Disease Control and Prevention Adult Sepsis Event (n = 12,494), the size of the overlap was 7,763. The sepsis cohorts also varied in time from admission to sepsis onset (hr): Sepsis-1 (2.9), Sepsis-3 (4.1), Centers for Disease Control and Prevention Adult Sepsis Event (4.6), and Centers for Medicare and Medicaid severe sepsis core measure 1 (7.6); sepsis discharge International Classification of Disease code rate: Sepsis-1 (37.4%), Sepsis-3 (40.1%), Centers for Medicare and Medicaid severe sepsis core measure 1 (48.5%), and Centers for Disease Control and Prevention Adult Sepsis Event (54.5%); and inhospital mortality rate: Sepsis-1 (13.6%), Sepsis-3 (18.8%), International Classification of Disease code (20.4%), Centers for Medicare and Medicaid severe sepsis core measure 1 (22.5%), and Centers for Disease Control and Prevention Adult Sepsis Event (24.1%). CONCLUSIONS: The application of commonly used sepsis definitions on a single population produced sepsis cohorts with low agreement, significantly different baseline demographics, and clinical outcomes.

Outcomes of Macrolide Deescalation in Severe Community-acquired Pneumonia.

PURPOSE: Current data suggest potential benefits with ß-lactam plus macrolide combination therapy for empiric treatment of intensive care unit (ICU) patients with severe community-acquired pneumonia (CAP). However, it is unclear whether deescalation to ß-lactam monotherapy in the absence of positive results on diagnostic tests, such as the BioFire FilmArray Respiratory Panel 2 (BioFire polymerase chain reaction [PCR]), affects clinical outcomes. The purpose of this study was to compare outcomes between patients with negative BioFire PCR results deescalated to ß-lactam monotherapy with those not deescalated. METHODS: This single-center, retrospective cohort study assessed the in-hospital mortality rates of critically ill adults with CAP treated for ≥48 h with combination ß-lactam and azithromycin therapy. Additional end points included hospital length of stay (LOS), ICU LOS, duration of mechanical ventilatory support, 30-day readmission, and incidence of azithromycin-related adverse effects. FINDINGS: A total of 94 patients were included: 53 in the deescalation group and 41 in the nondeescalation group. No difference was observed with respect to in-hospital mortality (2.4% vs 11.3%, P = 0.312), although patients in the deescalated group experienced shorter ICU (1.9 vs 3.4 days, P = 0.029) and hospital LOS (6 vs 7 days, P = 0.025). No differences were found between groups with respect to additional secondary end points. Simple logistic regression confirmed that deescalation was not associated with hospital mortality (odds ratio = 0.17, 95% CI, 0.02-1.70). IMPLICATIONS: In this study of ICU patients with severe CAP and a negative BioFire PCR result, deescalation from combination ß-lactam and macrolide therapy to ß-lactam monotherapy was not associated with increased in-hospital mortality but was associated with decreased hospital and ICU LOS. Larger prospective studies are warranted to verify these findings.

New antibiotics for community-acquired pneumonia.

PURPOSE OF REVIEW: This review provides the rationale for the development of new antibiotics to treat community-acquired pneumonia (CAP). It also provides an overview of the new antibiotics targeting CAP that have recently received approval by the regulatory agencies, and those antibiotics that are in the development pipeline. RECENT FINDINGS: CAP is one of the most common reasons for hospitalization and carries a significant morbidity and risk of mortality. Increasing antibiotic resistance amongst the common bacterial pathogens associated with CAP, especially staphylococci and Streptococcus pneumoniae, has made the empiric treatment of this infection increasingly problematic. Moreover, failure of initial empiric therapy to cover the causative agents associated with CAP can be associated with worse clinical outcomes. There have been several antibiotics newly approved or in development for the treatment of CAP. These agents include delafloxacin, omadacycline, lefamulin, solithromycin, nemonoxacin, and ceftaroline. Their major advantages include activity against methicillin-resistant Staphylococcus aureus and macrolide-resistant Strep. pneumoniae. SUMMARY: CAP continues to be an important infection because of its impact on patient outcomes especially in the elderly and immunocompromised hosts. The availability of new antibiotics offers an opportunity for enhanced empiric treatment of the antibiotic-resistant bacterial pathogens associated with CAP.