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Table 1 Summary and key recommendations

From: Timing of antibiotic therapy in the ICU

1. Timing of antibiotic therapy is an important determinant of outcome especially in patients with septic shock and other life threatening infections. Numerous clinical studies have demonstrated that delaying the administration of antibiotic therapy, even by an hour or two in septic shock, can be associated with greater risk of death
2. Ideally antimicrobial therapy should be initiated within three to five hours after infection onset in hospitalized patients, but immediately if possible when septic shock is present. All efforts should be taken to avoid administrative barriers to achieving this goal at the local hospital level
3. The recommendations on timing of antimicrobial therapy appear similar regardless of the offending pathogen. However, the relationship between timing of antimicrobial administration and outcome has been best established in the medical literature for patients with bacterial and fungal infections, especially bloodstream infections and septic shock
4. In addition to the timely administration of antibiotic therapy, careful consideration must be given to achieving timely source control of the infection including the removal of infected hardware (e.g., central venous catheters, intravascular ports) and drainage of infected fluid collections. Timely source control will allow for optimal antibiotic efficacy by lessening the influence of pathogen density in order to better achieve both clinical and microbiologic resolution of the infection
5. Timely administration of antibiotics for life threatening infections must also include consideration for the selection of appropriate antimicrobial therapy (i.e., an antimicrobial regimen that is demonstrated to have in vitro activity against the offending pathogens causing the infection). Many observational clinical studies, both retrospective and prospective as well as one randomized trial in patients with Gram negative bacterial bloodstream infections, have demonstrated that the delayed administration of an appropriate antimicrobial regimen is associated with increased mortality. The association between delayed administration of an appropriate antimicrobial regimen and increased mortality has been shown for both community and hospital acquired infections, sepsis, septic shock, bloodstream infections, and nosocomial pneumonia
6. Prolonged infusion times of β-lactam antibiotics over three to four hours, as opposed to infusion times of less than one hour, should be considered as an adjunctive approach towards improving antibiotic efficacy and reducing the propensity for the emergence of antibiotic resistance. Although, the available literature is mixed on the overall benefit of prolonged β-lactam infusions, there appears to be little likelihood for any increased adverse effects from prolonged infusion times
7. Timely de-escalation of empiric broad-spectrum antimicrobial regimens given to achieve appropriate treatment of life threatening infections should occur based on available microbiology results and the clinical response of the patient. Avoidance of unnecessarily prolonged administration of broad-spectrum agents, based on available pathogen identification and susceptibility testing, should be routinely performed as the risk of resistance emergence increases incrementally with each day of antibiotic administration without a demonstrable ceiling effect
8. With advances in molecular diagnostics for infectious diseases and machine learning/artificial intelligence algorithms for the prediction of infection occurrence, as well as the etiology of infection, achieving both more timely administration of appropriate antimicrobial therapy and lower propensity for resistance emergence should become more feasible. Future research should be directed at advancing these approaches for the care of infected critically ill patients