さまよう薬剤師のブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections.

Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections

www.ncbi.nlm.nih.gov

 

2013年に報告された、重症な急性感染症に対する抗菌薬のcontinuous infusions vs intermittent infusionsに関するCochraneレビュー

 

 

 

 

SUMMARY

 

f:id:akinohanayuki:20170611134933p:plain

 

Abstract

 

BACKGROUND: 

 

Intravenous broad-spectrum antibiotics are indicated for the treatment of severe infections. However, the emergence of infections caused by multi-drug resistant organisms in conjunction with a lack of novel antibiotics has prompted the investigation of alternative dosing strategies to improve clinical efficacy and tolerability. To optimise pharmacokinetic and pharmacodynamic antibiotic parameters, continuous antibiotic infusions have been compared to traditional intermittent antibiotic infusions.

 

OBJECTIVES: 

 

To compare the clinical efficacy and safety of continuous intravenous administration of concentration-dependent and time-dependent antibiotics to traditional intermittent intravenous administration in adults with severe acute bacterial infections.

 

SEARCH METHODS: 

 

The following electronic databases were searched in September 2012: The Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S). The reference lists of all relevant material, the Internet and the trials registry www.clinicaltrials.gov for completed and ongoing trials were also searched.

 

SELECTION CRITERIA: 

 

Randomized controlled trials in adults with a bacterial infection requiring intravenous antibiotic therapycomparing continuous versus intermittent infusions of antibiotics were included. Both time-dependent and concentration-dependent antibiotics were considered.

 

DATA COLLECTION AND ANALYSIS: 

 

Three independent authors performed data extraction for the included studies. All data was cross-checked and disagreements resolved by consensus. An intention to treat analysis was conducted using a random-effects model.

 

MAIN RESULTS: 

 

Twenty-nine studies met inclusion criteria with a combined total of over 1,600 patients. The majority of included studies were judged to be at unclear or high risk of bias with regard to randomisation sequence generation, allocation concealment, blinding, management of incomplete outcome data, selective outcome reporting, and other potential threats to validity. No studies were judged to be at low risk of bias for all methodological quality items assessed. There were no differences in all-cause mortality (n=1241, RR 0.89, 95% CI 0.67 - 1.20, p=0.45), infection recurrence (n=398, RR 1.22, 95% CI 0.35 - 4.19, p=0.76), clinical cure (n=975, RR 1.00, 95% CI 0.93 - 1.08, p=0.98), and superinfection post-therapy (n=813, RR 1.08, 95% CI 0.60 - 1.94, p=0.79). There were no differences in safety outcomes including adverse events (n=575, RR 1.02, 95% CI 0.94 - 1.12, p=0.63), serious adverse events (n=871, RR 1.36, 95% CI 0.80 - 2.30, p=0.26), and withdrawal due to adverse events (n=871, RR 2.03, 95% CI 0.52 - 7.95, p=0.31). A difference was observed in the subgroup analyses of clinical cure in septic versus non-septic patients, where intermittent antibiotic infusions were favoured for clinical cure in septic patients. However, this effect was not consistent between random-effects and fixed-effects analyses. No differences were found in sensitivity analyses conducted.

 

AUTHORS' CONCLUSIONS: 

 

There were no differences in mortality, infection recurrence, clinical cure, superinfection post-therapy, and safety outcomes when comparing continuous infusions of intravenous antibiotics to traditional intermittent infusions of antibiotics. However, the wide confidence intervals suggest that beneficial or harmful effects cannot be ruled out for all outcomes. Therefore, the current evidence is insufficient to recommend the widespread adoption of continuous infusion antibiotics in the place of intermittentinfusions of antibiotics. Further large prospective randomised trials, with consistent and complete reporting of clinical outcome measures, conducted with concurrent pharmacokinetic and pharmacodynamic studies in special populations are required to determine whether adoption of continuous antibiotic infusions is warranted in specific circumstances.

 

Implications for practice

 

No differences in mortality, infection recurrence, clinical cure, and super infection post-therapy were found when continuous infusions of intravenous antibiotics were compared with traditional intermittent antibiotic infusions. However, the wide confidence intervals suggest that beneficial or harmful effects cannot be ruled out for all outcomes. Although no evidence of statistical heterogeneity was found, some clinically meaningful heterogeneity between studies is likely and should be considered. Also, no differences in safety outcomes between the two interventions were apparent. Because several trials did not report data for clinically important outcomes, and because confidence intervals for effect estimates were wide, it is possible that the analyses in this review are underpowered because of lack of data. Therefore, the current available evidence is insufficient to recommend the widespread adoption of continuous infusion antibiotics in the place of standard intermittent antibiotic infusions.

 

f:id:akinohanayuki:20170611135515p:plain

f:id:akinohanayuki:20170612054716p:plain

 

f:id:akinohanayuki:20170612054739p:plain

f:id:akinohanayuki:20170612054752p:plain

感想

 

微妙な結果。さらなる検討が求められる。

頻回投与の手技が大変なPCG以外は、持続投与を臨床選択できない。

 

個人的には、持続投与に興味あるのですが。

 

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