Timing in antibiotic therapy: when and how to start, de-escalate and stop antibiotic therapy. Proposals from a stablished antimicrobial stewardship program

The current morbimortality of serious infections is unacceptable and there is a need to promote the increase in the efficacy of empirical and targeted antibiotherapy. This could be achieved by initiatives coming from ASP teams aimed at promoting increased efficacy of antibiotic therapy .In the optimization of the antibiotic therapy there are several critical points in which an adequate timing could achieve benefits in the survival of patients with severe infections: prompt initiation of empirical treatment; de-escalation performance, appropriate targeted treatment; and finally, curtail antibiotic duration. (AU)

Retrospective evaluation of the utility of blood cultures in dogs (2009-2018): 45 cases.

BACKGROUND: There is no consensus on obtaining blood cultures routinely in companion animals with suspected sepsis, and there is a paucity of evidence concerning their utility. The objectives of this retrospective study were to determine the yield of positive blood cultures from hospitalized dogs, the prevalence of resistant bacteria, and the frequency and nature of changes to antimicrobial therapy once the culture result became available. KEY FINDINGS: Forty-five dogs had a blood culture submitted over a 10-year period, of which 9(20%) yielded positive growth and 36 (80%) yielded no bacterial growth. The most frequent reasons for submission of blood culture were pyrexia of unknown origin (n = 14), suspected soft tissue infection (7), and suspected discospondylitis (7). The most frequent final diagnoses were soft tissue infection (n = 11), discospondylitis (7), and unknown (6). No significant difference was found between the culture-positive versus culture-negative groups with regard to the most frequent reasons for blood culture (P = 0.55), final diagnoses (P = 0.80), survival until the blood culture result (P = 0.37), or whether the infection was hospital- or community-acquired (P = 0.99). There were significantly more immunosuppressed dogs in the culture-positive group (P = 0.02). Resistance to one or more antimicrobials was documented in all dogs with susceptibility reported. In the culture-positive dogs, 63% had antimicrobial de-escalation and none had escalation, whereas 19% of the culture-negative dogs had de-escalation and 7% had escalation. CONCLUSION: Blood cultures were submitted infrequently, but the proportion of resistance was higher than expected and supports the use of blood cultures in cases of suspected infection resulting in bacteremia.

Transoral robotic surgery and neck dissection for HPV-positive oropharyngeal carcinoma: Importance of nodal count in survival.

BACKGROUND: In this study we determine the survival in patients with HPV-positive oropharyngeal carcinoma treated with transoral robotic surgery (TORS), neck dissection and risk-adapted adjuvant therapy. METHODS: We retrospectively identified 122 patients with HPV-positive oropharyngeal carcinoma treated with TORS and neck dissection between 2011 and 2018. Survival probability was calculated. We determined the effect of the type of neck dissection performed (modified radical neck dissection-MRND vs. selective neck dissection - SND), extranodal extension (ENE), margin status, and presence of ≥ 5 metastatic nodes on survival. RESULTS: Our patient population had a five-year overall survival of 91.0% (95% C.I. 85-97%). The five-year probability of recurrence or cancer-associated death was 0.0977 (95% C.I. 0.0927-0.1027). The five-year probability of cancer-associated death was 0.0528 (95% C.I. 0.048-0.0570). All patients who died of their disease had distant metastasis. Our PEG dependence rate was 0%. Patients with ENE and positive margins who underwent adjuvant chemoradiation did not have worse survival. Presence of ≥ 5 metastatic nodes portended worse survival after controlling for age, positive ENE and margins. Low yield (<18 nodes) on neck dissection worsened DFS on multivariable analysis. Furthermore, patients who underwent SND did not have worse OS than those who underwent MRND. CONCLUSION: Our study demonstrates that surgery could be simplified by performing TORS with SND rather than MRND. The one true poor prognostic factor in HPV-positive oropharyngeal carcinoma patients who undergo surgery is high nodal burden. Patients with high nodal burden are much more likely to die from their disease.

Comparing cisplatin-Chemoradiotherapy to Cetuximab-radiotherapy in HPV+ "low-risk" locally advanced oropharyngeal squamous cell carcinoma: lessons from De-escalate study.

BACKGROUND: Human papillomavirus-associated oropharyngeal cancer (HPV-OSCC) is rapidly increasing in incidence and has unique epidemiologic, molecular, and biologic characteristics. Standard combined modality therapies for head and neck cancer confer a significant risk of morbidity. However, patients with HPV-OSCC are diagnosed at a younger age and have a superior prognosis; this spurs the development of treatment deintensification trials that attempt to decrease treatment-related morbidity without compromising efficacy. MAIN BODY: The De-Escalate-HPV is a randomized phase 3 study that compares the standard treatment, radiation and cisplatin, with radiation and epidermal growth factor receptor (EGFR) inhibitor cetuximab in patients with low-risk HPV-OSCC. CONCLUSION: In this commentary, we aim to discuss the results of the De-Escalate-HPV study.

Switching to Clopidogrel in Patients With Acute Coronary Syndrome Managed With Percutaneous Coronary Intervention Initially Treated With Prasugrel or Ticagrelor: Systematic Review and Meta-analysis.

Objective: To evaluate the effects of switching from ticagrelor or prasugrel to clopidogrel in acute coronary syndrome (ACS) patients managed with percutaneous coronary intervention on major adverse cardiovascular events (MACEs) and bleeding. Data Sources: We searched MEDLINE, EMBASE, CENTRAL, bibliographies of relevant articles, and clinicaltrials.gov for eligible articles published from inception to January 27, 2019. Study Selection and Data Extraction: We included randomized controlled trials (RCTs) and cohort and case-control studies that reported on ≥1 outcome of interest. Primary outcomes were MACE and major bleeding, and the secondary outcome was any bleeding. Data Synthesis: From 483 articles, we included 7 relevant studies (2 RCTs, 5 cohort studies) at high/unclear risk of bias. Random-effects meta-analysis revealed inconclusive effects on MACE (hazard ratio [HR] = 1.00, 95% CI = 0.59-1.68; I2 = 82%), major bleeding (HR = 0.51; 0.19-1.35; I2 = 91%), and any bleeding (HR = 0.64; 0.38-1.07; I2 = 85%). Similar nonsignificant results were obtained in secondary analyses evaluating risk ratios. Relevance to Patient Care and Clinical Practice: Ticagrelor and prasugrel, are now considered preferred therapy over clopidogrel in patients with ACS. Switching from these potent P2Y12 inhibitors to clopidogrel is commonly performed to reduce bleeding risk, other adverse effects, or costs. Current best-available evidence is inconclusive regarding the effects of switching to clopidogrel on the risk of MACE and bleeding. Overall, studies were underpowered to detect clinically important differences. Conclusions: Until adequately powered trials demonstrate an advantage to switching to clopidogrel from prasugrel or ticagrelor, clinicians may consider this approach as clinically indicated on an individual, case-by-case basis.

Comparative safety and costs of stepping down asthma medications in patients with controlled asthma.

BACKGROUND: Limited data exist regarding outcomes after stepping down asthma medication. OBJECTIVE: We sought to compare the safety and costs of stepping down asthma controller medications with maintaining current treatment levels in patients with controlled asthma. METHODS: Patients with persistent asthma were identified from the US Medical Expenditure Panel Survey years 2000-2010. Each patient had Medical Expenditure Panel Survey data for 2 years, and measurement was divided into 5 periods of 4 to 5 months each. Eligibility for stepping down asthma controller medications included no hospitalizations or emergency department visits for asthma in periods 1 to 3 and no systemic corticosteroid and 3 or less rescue inhalers dispensed in periods 2 and 3. Steps were defined by type and dose of chronic asthma medication based on current guidelines when comparing period 4 with period 3. The primary outcome of complete asthma control in period 5 was defined as no asthma hospitalizations, emergency department visits, and dispensed systemic corticosteroids and 2 or fewer dispensed rescue inhalers. Multivariable analyses were conducted to assess safety and costs after step down compared with those who maintained the treatment level. RESULTS: Overall, 29.9% of patients meeting the inclusion criteria (n = 4235) were eligible for step down; 89.4% (95% CI, 86.4% to 92.4%) of those who stepped down had preserved asthma control compared with 83.5% (95% CI, 79.9% to 87.0%) of those who were similarly eligible for step down but maintained their treatment level. The average monthly asthma-related cost savings was $34.02/mo (95% CI, $5.42/mo to $61.24/mo) with step down compared with maintenance of the treatment level. CONCLUSION: Stepping down asthma medications in those whose symptoms were controlled led to similar clinical outcomes at reduced cost compared with those who maintained their current treatment level.