Systematic review of the impact of appropriate versus inappropriate initial antibiotic therapy on outcomes of patients with severe bacterial infections

Bassetti, Matteo; Rello, Jordi; Blasi, Francesco; Goossens, Herman; Sotgiu, Giovanni; Tavoschi, Lara; Zasowski, Evan J; Arber, Mick; McCool, Rachael; Patterson, Jacoby V.; Longshaw, Christopher; Lopes, Sara; Manissero, Davide; Nguyen, Sean; Tone, K; Aliberti, Stefano

doi:10.1016/j.ijantimicag.2020.106184

Cited by 55 publications

(44 citation statements)

References 51 publications

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“…However, 30% of patients with a positive gram-positive or gram-negative bacterial culture did not receive antibacterial therapy within the first 48 hours of culture collection and were therefore categorized as receiving IET. Other studies have reported that delays in antibiotic treatment can negatively impact patient outcomes and costs [ 11 , 24–27 ]. This study shows that delays are further exacerbated in the era of COVID-19 and could be an important contributor to IET, which is associated with increased mortality and hospital LOS.…”

Section: Discussionmentioning

confidence: 99%

Effect of Inadequate Empiric Antibacterial Therapy on Hospital Outcomes in SARS-CoV-2-Positive and -Negative US Patients With a Positive Bacterial Culture: A Multicenter Evaluation From March to November 2020

Puzniak

Bauer

Moise

et al. 2021

Open Forum Infectious Diseases

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Background Increased utilization of antimicrobial therapy has been observed during the coronavirus disease 2019 pandemic. We evaluated hospital outcomes based on the adequacy of antibacterial therapy for bacterial pathogens in US patients. Methods This multicenter retrospective study included patients with ≥24 hours of inpatient admission, ≥24 hours of antibiotic therapy, and discharge/death from March-November 2020 at 201 US hospitals in the BD Insights Research Database. Included patients had a test for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and a positive bacterial culture (gram-positive or gram-negative). We used generalized linear mixed models to evaluate the impact of inadequate empiric therapy (IET), defined as therapy not active against the identified bacteria or no antimicrobial therapy in the 48 hours following culture, on in-hospital mortality and hospital and intensive care unit (ICU) length of stay (LOS). Results Of 438,888 SARS-CoV-2 tested patients, 39,203 (8.9%) had positive bacterial cultures. Among patients with positive cultures, 9.4% were SARS-CoV-2 positive, 74.4% had a gram-negative pathogen, 25.6% had a gram-positive pathogen, and 44.1% received IET for the bacterial infection. The odds of mortality were 21% higher for IET (odds ratio 1.21 [95% confidence interval (CI), 1.10–1.33]; P<.001) compared with adequate empiric therapy. IET was also associated with increased hospital LOS(16.1 [95% CI, 15.5–16.7] vs 14.5 [95% CI 13.9–15.1] days; (P<.001). Both mortality and hospital LOS findings remained consistent for SARS-CoV-2-positive and -negative patients. Conclusions Bacterial pathogens continue to play an important role in hospital outcomes during the pandemic. Adequate and timely therapeutic management may help ensure better outcomes.

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Section: Discussionmentioning

confidence: 99%

Effect of Inadequate Empiric Antibacterial Therapy on Hospital Outcomes in SARS-CoV-2-Positive and -Negative US Patients With a Positive Bacterial Culture: A Multicenter Evaluation From March to November 2020

Puzniak

Bauer

Moise

et al. 2021

Open Forum Infectious Diseases

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“…Bassetti and colleagues identified 114 studies of appropriate therapy, 63 of which specifically dealt with sepsis and septic shock. The strongest positive impact of appropriate antibiotic treatment was observed among those with septic shock [14]. Appropriate therapy in sepsis not only significantly reduced in-hospital mortality (OR 0.44, 95% Confidence Interval 0.37-0.52) but also reduced length of stay by approximately 5 days [14].…”

Section: Timing Of Appropriate Therapy-septic Shockmentioning

confidence: 98%

Timing of antibiotic therapy in the ICU

et al. 2021

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Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics.

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“…Similarly, while the ELSO Infectious Disease Task Force does not recommend antibiotic prophylaxis on ECMO, 74% of centers reported performing it [ 29 , 30 ]. The risk of BSIs and the well-established consequence of delayed or inappropriate antimicrobial therapy must be balanced with the negative impact of antibiotics on microbiota and subsequent infections [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic yield of routine daily blood culture in patients on veno-arterial extracorporeal membrane oxygenation

et al. 2021

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Background Bloodstream infections (BSIs) are frequent on veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Performing routine blood cultures (BCs) may identify early paucisymptomatic BSIs. We investigated the contribution of systematic daily BCs to detect BSIs on V-A ECMO. Methods This was a retrospective study including all adult patients requiring V-A ECMO and surviving more than 24 h. Our protocol included routine daily BCs, from V-A ECMO insertion up to 5 days after withdrawal; other BCs were performed on-demand. Results On the 150 V-A ECMO included, 2146 BCs were performed (1162 routine and 984 on-demand BCs); 190 (9%) were positive, including 68 contaminants. Fifty-one (4%) routine BCs revealed BSIs; meanwhile, 71 (7%) on-demand BCs revealed BSIs (p = 0.005). Performing routine BCs was negatively associated with BSIs diagnosis (OR 0.55, 95% CI [0.38; 0.81], p = 0.002). However, 16 (31%) BSIs diagnosed by routine BCs would have been missed by on-demand BCs. Independent variables for BSIs diagnosis after routine BCs were: V-A ECMO for cardiac graft failure (OR 2.43, 95% CI [1.20; 4.92], p = 0.013) and sampling with on-going antimicrobial therapy (OR 2.15, 95% CI [1.08; 4.27], p = 0.029) or renal replacement therapy (OR 2.05, 95% CI [1.10; 3.81], p = 0.008). Without these three conditions, only two BSIs diagnosed with routine BCs would have been missed by on-demand BCs sampling. Conclusions Although routine daily BCs are less effective than on-demand BCs and expose to contamination and inappropriate antimicrobial therapy, a policy restricted to on-demand BCs would omit a significant proportion of BSIs. This argues for a tailored approach to routine daily BCs on V-A ECMO, based on risk factors for positivity.

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Systematic review of the impact of appropriate versus inappropriate initial antibiotic therapy on outcomes of patients with severe bacterial infections

Cited by 55 publications

References 51 publications

Effect of Inadequate Empiric Antibacterial Therapy on Hospital Outcomes in SARS-CoV-2-Positive and -Negative US Patients With a Positive Bacterial Culture: A Multicenter Evaluation From March to November 2020

Effect of Inadequate Empiric Antibacterial Therapy on Hospital Outcomes in SARS-CoV-2-Positive and -Negative US Patients With a Positive Bacterial Culture: A Multicenter Evaluation From March to November 2020

Timing of antibiotic therapy in the ICU

Diagnostic yield of routine daily blood culture in patients on veno-arterial extracorporeal membrane oxygenation

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