BackgroundPublished guidelines for the treatment of healthcare-associated pneumonia (HCAP) recommend initial broad-spectrum antibiotics with appropriate de-escalation based on culture results. Guideline recommendations are based on data from intubated patients, in whom cultures are easily obtained. The approach to antibiotic de-escalation for culture-negative patients has not been addressed. Consequently, there are no published reports that describe the current standard of practice.Patients and methodsAll patients admitted to a university hospital with a diagnosis of HCAP, as defined by use of a pneumonia orderset, were identified retrospectively over a 2-year period. Antibiotics prescribed on admission, during hospital stay, and on discharge were recorded. De-escalation was defined as a change in the initial antibiotic therapy from broad- to narrow-spectrum coverage within 14 days of the initial prescription. The Pneumonia Severity Index was used for risk-adjustment.ResultsA total of 102 patients were included in the analysis; of these, 72% (n = 73) were culture-negative. There were more males in the culture-negative than culture-positive group; otherwise, baseline characteristics were similar. Antibiotic therapy was de-escalated in 75% of the culture-negative group and 77% of the culture-positive group (p = 1.00). Culture-negative patients were de-escalated approximately 1 day earlier than culture-positive patients (3.93 vs. 5.04 days, p = 0.03). Culture-negative patients who were de-escalated had a shorter length of hospitalization, lower hospital costs, and lower mortality rates. In 70% of the culture-negative patients, a respiratory fluoroquinolone was chosen for de-escalation.ConclusionIn this single-center study, most of the patients with culture-negative HCAP were safely de-escalated to a respiratory fluoroquinolone.

Current evidence indicates that heart failure (HF) confers a hyper-coagulable state that is associated with adverse events including stroke, systemic embolism, and mortality. This may be due to the elevated levels of pro-thrombotic and pro-inflammatory cytokines that are seen in patients with acute and chronic HF. Left ventricular wall motion abnormalities in patients with systolic dysfunction predispose to local thrombosis due to blood stasis as does atrial fibrillation (AF) which leads to blood stasis in regions of the atria. The high risk of thromboemboli in HF patients with AF has resulted in the use anticoagulation therapy to prevent the occurrence of catastrophic events. There is evidence, however, that the pro-inflammatory, pro-thrombotic state that exists in HF puts patients who are in sinus rhythm at risk. The novel oral anticoagulants (NOACs) have been shown in RCT to have at least equivalent efficacy in reducing stroke as warfarin while exposing patients to a lower risk of bleeding. The fact that the NOACs don't require routine monitoring to assure that patients remain within the therapeutic range and have relatively simple dosing requirements and a safer risk profile makes them attractive substitutes to warfarin in HF patients with atrial fibrillation and other conditions (e.g. deep venous thrombosis). Post hoc analyses from a subset of HF patients from the RCTs in AF patients have demonstrated similar findings as were reported in the entire populations that were included in the trials. As a result, NOACS are commonly used now in HF patients with AF. For HF patients with reduced ejection fraction in sinus rhythm, the use of warfarin in randomized clinical trials (RCT) to reduce stroke has been disappointing and associated with increase bleeding risk when compared to aspirin. The advantages of the NOACs over warfarin, however, raise the question of whether they might improve outcomes in HF patients who are in sinus rhythm. The currently ongoing COMMANDER-HF trial has been designed to address this issue. In this chapter we review evidence of existence of a prothombotic state in HF, the pharmacodynamics and clinical trials of the NOACs and the outcomes from NOAC substudies in the HF subgroup. We also discuss the rationale for using anticoagulation in HF independent of arrhythmia burden.