Impact of rapid susceptibility testing on antimicrobial therapy and clinical outcomes in Gram-negative bloodstream infections.

BACKGROUND: Rapid antimicrobial susceptibility testing (rAST) has the potential to improve care of bloodstream infections. OBJECTIVES: The aim of this service evaluation was to assess the impact of rAST on antimicrobial therapy and clinical outcomes in patients with Gram-negative bloodstream infection. METHODS: A prospective service evaluation was conducted from March 2018 to December 2018. A rAST system (Alfred 60AST) was run Monday-Friday before midday and results were communicated to clinicians on the same day as positive blood culture, with subsequent conventional AST performed. Times to antibiotic therapy and clinical outcomes were compared between rAST and conventional AST. RESULTS: One hundred and ninety-one patients with Gram-negative bacteraemia were included (93 in the rapid group and 98 in the conventional group). Aminoglycoside combination therapy was stopped earlier in the rapid group [32 h (0-795) versus 54 h (4-216), P = 0.002]. The median time to optimal antibiotic based on AST results was significantly shorter than that in the conventional group [50 h (10-339) versus 69.5 h (20-872), P = 0.034]. In the subgroup of patients on ineffective empirical antibiotic, time to effective antibiotic was shorter in the rapid group [39.5 h (32-97) versus 57 h (49-83), P = 0.036]. No differences were found in 28 day mortality or length of stay. CONCLUSIONS: Rapid susceptibility testing resulted in faster discontinuation of aminoglycosides and a shorter time to starting effective and optimal antibiotic when compared with conventional AST results. rAST has potential clinical benefits and points to the need for larger future studies in areas of high antibiotic resistance.

Patient-Reported Outcomes from the Phase III Randomized IMmotion151 Trial: Atezolizumab + Bevacizumab versus Sunitinib in Treatment-Naïve Metastatic Renal Cell Carcinoma.

PURPOSE: Patient-reported outcomes (PRO) were evaluated in the phase III IMmotion151 trial (NCT02420821) to inform overall treatment/disease burden of atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Patients were randomized 1:1 to receive atezolizumab 1,200 mg intravenous (i.v.) infusions every 3 weeks (q3w) plus bevacizumab 15 mg/kg i.v. q3w or sunitinib 50 mg per day orally 4 weeks on/2 weeks off. Patients completed the MD Anderson Symptom Inventory (MDASI), National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19), and Brief Fatigue Inventory (BFI) at baseline, q3w during treatment, at end of treatment, and during survival follow-up. Longitudinal and time to deterioration (TTD) analyses for core and RCC symptoms and their interference with daily life, treatment side-effect bother, and health-related quality of life (HRQOL) were evaluated. RESULTS: The intent-to-treat population included 454 and 461 patients in the atezolizumab plus bevacizumab and sunitinib arms, respectively. Completion rates for each instrument were 83% to 86% at baseline and ≥ 70% through week 54. Milder symptoms, less symptom interference and treatment side-effect bother, and better HRQOL at most visits were reported with atezolizumab plus bevacizumab versus sunitinib. The TTD HR (95% CI) favored atezolizumab plus bevacizumab for core (HR, 0.50; 0.40-0.62) and RCC symptoms (HR, 0.45; 0.37-0.55), symptom interference (HR, 0.56; 0.46-0.68), and HRQOL (HR, 0.68; 0.58-0.81). CONCLUSIONS: PROs in IMmotion151 suggest lower overall treatment burden with atezolizumab plus bevacizumab compared with sunitinib in patients with treatment-naïve mRCC and provide further evidence for clinical benefit of this regimen.

[Beta-lactam antibiotics]. / Antibióticos betalactámicos.

Beta-lactam drugs, whose mechanism of action is inhibition of the last stage of bacterial cell wall synthesis, are the largest family of antimicrobial agents and the most widely used in current clinical practice. These drugs have a slow, time-dependent bactericidal action, generally good distribution in the body, and low toxicity. Modifications of the original molecule have led to new compounds with a greater antimicrobial spectrum and activity; nonetheless, the use and efficacy of beta-lactams is limited in some clinical settings, owing to the increasing emergence of antimicrobial resistance. Despite this problem, penicillin remains the treatment of choice in a large number of infections, cephalosporins have a wide range of indications, carbapenems are used in nosocomially-acquired infection and infection caused by multiresistant microorganisms, and beta-lactam inhibitors restore the spectrum of activity of their companion penicillins (aminopenicillins, ureidopenicillins) when resistance is caused by beta lactamase production.

Health care-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes.

BACKGROUND: Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. However, limited data exist to validate this entity. We aimed to ascertain the epidemiology, causative organisms, antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for HCAP requiring hospitalization. METHODS: Observational analysis of a prospective cohort of nonseverely immunosuppressed hospitalized adults with pneumonia. Patients who had recent contact with the health care system through nursing homes, home health care programs, hemodialysis clinics, or prior hospitalization were considered to have HCAP. RESULTS: Of 727 cases of pneumonia, 126 (17.3%) were HCAP and 601 (82.7%) were community acquired. Compared with patients with community-acquired pneumonia, patients with HCAP were older (mean age, 69.5 vs 63.7 years; P < .001), had greater comorbidity (95.2% vs 74.7%; P < .001), and were more commonly classified into high-risk pneumonia severity index classes (67.5% vs 48.8%; P < .001). The most common causative organism was Streptococcus pneumoniae in both groups (27.8% vs 33.9%). Drug-resistant pneumococci were more frequently encountered in cases of HCAP. Legionella pneumophila was less common in patients with HCAP (2.4% vs 8.8%; P = .01). Aspiration pneumonia (20.6% vs 3.0%; P < .001), Haemophilus influenzae (11.9% vs 6.0%; P = .02), Staphylococcus aureus (2.4% vs 0%; P = .005), and gram-negative bacilli (4.0% vs 1.0%; P = .03) were more frequent in HCAP. Patients with HCAP more frequently received an initial inappropriate empirical antibiotic therapy (5.6% vs 2.0%; P = .03). The overall case-fatality rate (< 30 days) was higher in patients with HCAP (10.3% vs 4.3%; P = .007). CONCLUSIONS: At present, a substantial number of patients initially seen with pneumonia in the emergency department have HCAP. These patients require a targeted approach when selecting empirical antibiotic therapy.