Transition from intravenous to oral antimicrobial therapy in patients with uncomplicated and complicated bloodstream infections.

BACKGROUND: The role of oral antimicrobial agents in the management of bloodstream infections (BSI) is currently evolving. OBJECTIVES: This narrative review summarizes and appraises clinical studies that examined transition from intravenous to oral antimicrobials or compared effectiveness of various oral agents for definitive therapy of uncomplicated and complicated BSI in adults. SOURCES: Relevant English-language studies from MEDLINE (since inception) and presented abstracts at international scientific meetings (since 2017). CONTENT: Emerging data suggest potential utility of oral switch strategy, particularly to oxazolidinones, as an alternative to standard intravenous therapy in low-risk patients with uncomplicated Staphylococcus aureus BSI. Moreover, results of recent randomized clinical trials are promising that combination oral regimens may play a role in antimicrobial management of complicated Gram-positive BSI, including infective endocarditis, septic arthritis and osteomyelitis. Whereas oral fluoroquinolones have been used successfully for decades in both uncomplicated and complicated Gram-negative BSI, recent studies suggest that trimethoprim-sulfamethoxazole and aminopenicillins represent alternative oral options in uncomplicated Enterobacteriaceae BSI. Oral azoles have been used for definitive therapy of Candida species BSI and are currently recommended by the international management guidelines. IMPLICATIONS: Recent studies demonstrate that early transition from intravenous to oral therapy is a feasible and effective strategy in most patients with BSI due to Gram-negative bacteria, obligate anaerobic bacteria and Candida species. Oral antimicrobial combinations may be considered in select patients with complicated Gram-positive BSI after 10-14 days of intravenous therapy. Future studies will determine the role of oral agents for switch therapy in uncomplicated Gram-positive BSI.

Evaluation of early clinical failure criteria for gram-negative bloodstream infections.

OBJECTIVES: The aim was the development of early clinical failure criteria (ECFC) to predict unfavourable outcomes in patients with Gram-negative bloodstream infections (GN-BSI). METHODS: Adults with community-onset GN-BSI who survived hospitalization for ≥72 hr at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 1, 2010 to June 30, 2015 were identified. Multivariable logistic regression was used to examine the association between clinical variables between 72 and 96 hr after GN-BSI and unfavourable outcomes (28-day mortality or hospital length of stay >14 days from GN-BSI onset). RESULTS: Among 766 patients, 225 (29%) had unfavourable outcomes. After adjustments for Charlson Comorbidity Index and appropriateness of empirical antimicrobial therapy in multivariable model, predictors of unfavourable outcomes included systolic blood pressure <100 mmHg or vasopressor use (adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.2-2.9), heart rate >100 beats/minute (aOR 1.7, 95% CI 1.1-2.5), respiratory rate ≥22 breaths/minute or mechanical ventilation (aOR 2.1, 95% CI 1.4-3.3), altered mental status (aOR 4.5, 95% CI 2.8-7.1), and white blood cell count >12 000/mm3 (aOR 2.7, 95% CI 1.8-4.1) between 72 and 96 hr after index GN-BSI. Area under receiver operating characteristic curve of ECFC model in predicting unfavourable outcomes was 0.77 (0.84 and 0.71 in predicting 28-day mortality and prolonged hospitalization, respectively). CONCLUSIONS: Risk of 28-day mortality or prolonged hospitalization can be estimated between 72 and 96 hr after GN-BSI using ECFC. These criteria may have clinical utility in management of GN-BSI and may improve methodology of future investigations assessing response to antimicrobial therapy based on a standard evidence-based definition of early clinical failure.