Editing Sepsis (section)

=== Antibiotics ===

Two sets of blood cultures (aerobic and anaerobic) are recommended without delaying the initiation of antibiotics. Cultures from other sites such as respiratory secretions, urine, wounds, cerebrospinal fluid, and catheter insertion sites (in situ for more than 48 hours) are recommended if infections from these sites are suspected.<ref name= "SSC–G2016"/> In severe sepsis and septic shock, [[broad-spectrum antibiotic]]s (usually two, a [[β-lactam antibiotic]] with broad coverage, or broad-spectrum [[carbapenem]] combined with [[Quinolone antibiotic|fluoroquinolones]], [[macrolide]]s, or [[aminoglycoside]]s) are recommended. The choice of antibiotics is important in determining the survival of the person.<ref name="Marik2014Chest"/><ref name="SSC–G2016"/> Some recommend they be given within one hour of making the diagnosis, stating that for every hour of delay in the administration of antibiotics, there is an associated 6% rise in mortality.<ref name=Soong2012 /><ref name="Marik2014Chest"/> Others did not find a benefit with early administration.<ref name=Sterling2015/>

Several factors determine the most appropriate choice for the initial antibiotic regimen. These factors include local patterns of bacterial sensitivity to antibiotics, whether the infection is thought to be a [[Hospital-acquired infection|hospital]] or community-acquired infection, and which organ systems are thought to be infected.<ref name="Marik2014Chest"/><ref name="Gauer et al" /> Antibiotic regimens should be reassessed daily and narrowed if appropriate. Treatment duration is typically 7–10&nbsp;days with the type of antibiotic used directed by the results of cultures. If the culture result is negative, antibiotics should be de-escalated according to the person's clinical response or stopped altogether if an infection is not present to decrease the chances that the person is infected with [[multiple drug resistance]] organisms. In case of people having a high risk of being infected with [[multiple drug resistance|multiple drug resistant]] organisms such as ''[[Pseudomonas aeruginosa]]'', ''[[Acinetobacter baumannii]]'', the addition of an antibiotic specific to the gram-negative organism is recommended. For [[Methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] (MRSA), [[vancomycin]] or [[teicoplanin]] is recommended. For ''[[Legionella]]'' infection, addition of [[macrolide]] or [[fluoroquinolone]] is chosen. If fungal infection is suspected, an [[echinocandin]], such as [[caspofungin]] or [[micafungin]], is chosen for people with severe sepsis, followed by [[triazole]] ([[fluconazole]] and [[itraconazole]]) for less ill people.<ref name= "SSC–G2016"/> Prolonged antibiotic prophylaxis is not recommended in people who has SIRS without any infectious origin such as [[acute pancreatitis]] and [[burn]]s unless sepsis is suspected.<ref name= "SSC–G2016"/>

Once-daily dosing of [[aminoglycoside]] is sufficient to achieve peak plasma concentration for a clinical response without kidney toxicity. Meanwhile, for antibiotics with low volume distribution (vancomycin, teicoplanin, colistin), a loading dose is required to achieve an adequate therapeutic level to fight infections. Frequent infusions of beta-lactam antibiotics without exceeding the total daily dose would help to keep the antibiotics level above [[minimum inhibitory concentration]] (MIC), thus providing a better clinical response.<ref name= "SSC–G2016"/> Giving beta-lactam antibiotics continuously may be better than giving them intermittently.<ref name=Roberts2016/> Access to [[therapeutic drug monitoring]] is important to ensure adequate drug therapeutic level while at the same time preventing the drug from reaching a toxic level.<ref name= "SSC–G2016"/>