BackgroundSporadic studies in antimicrobial therapy have evaluated the effects of infusion rates on therapeutic and economic outcomes, and new findings may challenge the regular infusion regimen.MethodsFocusing on studies comparing the outcomes of different infusion regimens, the relevant literature was identified by searching PubMed, Web of Science, and Scopus from January 1, 2013 to March 1, 2018. Papers were finally chosen using a PRISMA flowchart.ResultsAntimicrobials with the superiority of prolonged infusion to standard infusion in terms of efficacy and safety include meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin. The strategy of concomitantly reducing total daily dose and prolonging infusion time may cause treatment failure (eg, imipenem). Extended infusion of piperacillin/tazobactam has pharmacoeconomic advantage over standard infusion. Prolonged infusion of voriconazole is inferior to standard infusion because of lower efficacy caused by pharmacokinetic changes. Comparable outcomes following standard infusion and continuous infusion were observed with norvancomycin and nafcillin. Factors determining whether prolonged infusion has a benefit over standard infusion include MIC of bacterial pathogens, bacterial density, diagnosis, disease severity, total daily dose, and renal function.ConclusionTo maximally preserve the effectiveness of current antimicrobials, effective interventions should be implemented to enhance the application of optimal infusion strategies. For reducing nephrotoxicity, prolonged infusion of meropenem is better than conventional infusion in neonates with Gram-negative late-onset sepsis, and continuous infusion of vancomycin is superior to intermittent infusion. For increasing efficacy, prolonged or continuous infusion of time-dependent antimicrobials (eg, meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin) is an optimal choice. Nevertheless, such advantages may only be demonstrated in special clinical circumstances and special populations (eg, patients with a sequential organ failure assessment (SOFA) score≥9, respiratory tract infections, urinary or intra-abdominal infections, or infections caused by less susceptible pathogens would benefit from prolonged infusion of piperacillin/tazobactam).

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Objective This study aimed to evaluate the effect of a comprehensive antimicrobial stewardship program (ASP) and provide clinical evidence for the scientific stewardship of antimicrobials in intensive care units (ICUs) of a teaching hospital.Methods Between January 2013 and December 2018, we conducted a prospective study, based on an antimicrobial computerized clinical decision support system (aCDSS) deployed in 2015 in ICUs of a tertiary and teaching hospital. The primary outcomes included initial and overall use prevalence of antimicrobials. The second outcomes were the detection rate of common clinical isolates before and after therapeutic antimicrobial use, and the change in patterns of resistance of 5 common clinical isolates in the ICU.Results Various types of broad-spectrum antimicrobial use prevalence continued to increase from 2013 to 2015, since 2016, where initial use of carbapenems and glycopeptides were counterbalanced by an increase in use of the first/second-generation cephalosporins, β-lactam and β-lactamase inhibitor combinations and linezolid. From 2015 to 2018, the proportion of extended-broad spectrum antimicrobials alone, wide-coverage therapy and combination therapy decreased significantly (P<0.05). Similarly, where use of carbapenems, glycopeptides, third/fourth-generation cephalosporins and anti-fungi agents were counterbalanced by an increase in overall use of the first/second-generation cephalosporins and β-lactam and β-lactamase inhibitor combinations. A total of 21891 strains of bacteria and fungi were detected in ICUs from 2015 to 2018, of them, 6.5% (1426/21891) strains were detected before antimicrobial treatment. The detection proportion of Staphylococcus aureus , Escherichia coli , Klebsiella pneumoniae and fastidious bacteria were significantly higher before antimicrobial treatment (P<0.05), while Acinetobacter baumannii , Burkholderia cepacia , and Candida spp were significantly lower in all non-repetitive clinical isolates (P<0.05).Conclusions The implementation of a comprehensive ASP combining CDSS in ICUs seems to be effective to improve outcomes on antimicrobial utilization and clinical isolates distribution in critically ill patients.