Is a randomized trial of a short course of aminoglycoside added to β-lactam antibiotics for empirical treatment in critically ill patients with sepsis justified?

Ong, David S. Y.; Werkhoven, Cornelis H. van; Cremer, Olaf L.; Thwaites, Guy; Bonten, Marc J. M.

doi:10.1016/j.cmi.2017.09.020

Cited by 6 publications

(9 citation statements)

References 11 publications

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“…The absence of benefit, combined with widespread but heterogeneous use of short-term aminoglycosides calls for a randomized clinical trial, as we discussed before [22]. In such a study we would propose to use higher dosages of gentamycin and tobramycin.…”

Section: Discussionmentioning

confidence: 99%

Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection, a cohort study

Deelen

Rottier

Buiting

et al. 2021

Clinical Microbiology and Infection

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Objective: Short-course aminoglycosides as adjunctive empirical therapy to b-lactams in patients with a clinical suspicion of sepsis are used to broaden antibiotic susceptibility coverage and to enhance bacterial killing. We quantified the impact of this approach on 30-day mortality in a subset of sepsis patients with a Gram-negative bloodstream infection. Methods: From a prospective cohort study conducted in seven hospitals in the Netherlands between June 2013 and November 2015, we selected all patients with Gram-negative bloodstream infection (GN-BSI). Short-course aminoglycoside therapy was defined as tobramycin, gentamicin or amikacin initiated within a 48-hour time window around blood-culture obtainment, and prescribed for a maximum of 2 days. The outcome of interest was 30-day all-cause mortality. Confounders were selected a priori for adjustment using a propensity score analysis with inverse probability weighting.Results: A total of 626 individuals with GN-BSI who received b-lactams were included; 156 (24.9%) also received aminoglycosides for a median of 1 day. Patients receiving aminoglycosides more often had septic shock (31/156, 19.9% versus 34/470, 7.2%) and had an eight-fold lower risk of inappropriate treatment (3/156, 1.9% versus 69/470, 14.7%). Thirty-day mortality was 17.3% (27/156) and 13.6% (64/470) for patients receiving and not receiving aminoglycosides, respectively; yielding crude and adjusted odds ratios for 30-day mortality for patients treated with aminoglycosides of 1.33 (95% CI 0.80e2.15) and 1.57 (0.84e2.93), respectively.Conclusions: Short-course adjunctive aminoglycoside treatment as part of empirical therapy with blactam antibiotics in patients with GN-BSI did not result in improved outcomes, despite better antibiotic coverage of pathogens.

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Section: Discussionmentioning

confidence: 99%

Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection, a cohort study

Deelen

Rottier

Buiting

et al. 2021

Clinical Microbiology and Infection

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“…The reasons for this suggestion are the ability of AGs to reduce the risk of inappropriate empirical therapy, sterilize the bloodstream faster and act synergistically with b-lactam antibiotics 19,34. However, this approach has never been evaluated in randomized studies 35…”

Section: Discussionmentioning

confidence: 99%

Evaluation of aminoglycosides utilization in intensive care units of a teaching hospital in southern Iran

Vazin¹,

Mirjalili²,

Asadi³

2019

Pharm Pract (Granada)

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Background:Inappropriate use of antimicrobial agents is one of the most important factors in inducing resistance and prolonged hospitalization as well as increase in patient mortality rate.Objective:The aim of this study was to evaluate aminoglycosides (AGs) usage pattern at intensive care units (ICUs) of Nemazee hospital Shiraz, Iran.Methods:In this cross-sectional study, the usage pattern of AGs was evaluated during 32 months. Guidelines for AGs usage were approved by the drug and therapeutic committee of the hospital, and criteria were developed to assess 11 parameters involving AGs therapy, such as proper indication for the use of the drug, dosage and duration of therapy. Clinical parameters, such as microbial culture and sensitivity, serum creatinine (SCr) and creatinine clearance, and white blood cell count were evaluated.Results:Ninety-five patients were recruited, 50 male and 45 females. In most patients (64%) the origin of infection was hospital and only in 36% of them, community was the source. Ventilator associated pneumonia (27%), central nervous system (25%) and urinary tract infection (10%) were the most important indications for AGs prescription. Scores of AGs usage at Nemazee hospital was calculated as 5.9 out of 11, which meant that in only 54% of cases AGs prescription was based on guideline proposed by the Department of Clinical Pharmacy of Nemazee Hospital.Conclusions:Non-adherence to the guidelines occurred frequently in the ICUs of Nemazee hospital. Prescription of loading dose, and AGs level measurement were not done and evaluating microbiological data was often neglected. Incorporating pharmacists in the health care team and holding training programs for physicians and nurses with the goal of raising awareness about the proposed guideline.

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“…We read with interest the comments from Ong et al [1] regarding the need for a well-designed randomized controlled trial (RCT) to provide evidence to guide clinicians regarding the use of combined b-lactam antibiotic and aminoglycoside therapy for the management of critically ill patients with sepsis or septic shock. We would like to highlight the importance of appropriate dosing strategies and the inclusion of pharmacokinetic/pharmacodynamic (PK/PD) sub-studies to provide further evidence about the potential utility of combination therapy.…”

Section: Dear Sirmentioning

confidence: 99%

“…Ong et al [1] briefly highlight that previous meta-analyses primarily included studies investigating the combination of a b-lactam antibiotic and multiple daily dosing regimens of aminoglycosides. This is an important limitation given that current practice commonly involves single daily aminoglycoside dosing regimens, which increases the probability of achieving key PK/PD ratios associated with improved clinical cure rates when compared with traditional multiple daily dosing regimens [2].…”

Section: Dear Sirmentioning

confidence: 99%

“…First, given the influence of attaining optimal PK/ PD ratios for patient outcomes, any future RCT should consider concurrent PK/PD analyses involving the appropriate determination of both the antibiotic concentrations and the pathogen minimum inhibitory concentration (MIC) where possible. Moreover, characterizing PK/PD ratios in future RCTs, in combination with the randomization methods proposed by Ong et al [1], may allow further analyses that identify PK/PD targets for different patient populations. The implications of not performing a PK/PD analysis may lead to result misinterpretation because one of the treatment groups may have sub-maximal antimicrobial effects associated with sub-optimal dosing.…”

Section: Dear Sirmentioning

confidence: 99%

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Re: ‘Is a randomized trial of a short course of aminoglycoside added to β-lactam antibiotics for empirical treatment in critically ill patients with sepsis justified?’ Pharmacokinetic/pharmacodynamic considerations

Heffernan

Lipman

Roberts

2018

Clinical Microbiology and Infection

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Is a randomized trial of a short course of aminoglycoside added to β-lactam antibiotics for empirical treatment in critically ill patients with sepsis justified?

Cited by 6 publications

References 11 publications

Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection, a cohort study

Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection, a cohort study

Evaluation of aminoglycosides utilization in intensive care units of a teaching hospital in southern Iran

Re: ‘Is a randomized trial of a short course of aminoglycoside added to β-lactam antibiotics for empirical treatment in critically ill patients with sepsis justified?’ Pharmacokinetic/pharmacodynamic considerations

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