The early antibiotic therapy in septic patients - milestone or sticking point?

Worldwide, the annual prevalence of sepsis is estimated at 19 million cases [1]. The mortality rates in severe sepsis were reduced to 20% to 30% because of advances in training, recognition, surveillance, monitoring, and rapid initial antibiotic therapy and organ support [1],[2]. The most recent update of the Surviving Sepsis Campaign guidelines was published in 2013 [3]. A consensus committee provided valuable and clear recommendations on treatment of sepsis and septic shock (Table 1). One of the main focuses is the administration of a broad-spectrum antibiotic (Table 2) [3]. It is recommended that antimicrobials be administrated within the first hour of recognition of septic shock and severe sepsis without septic shock [4]–[7]. Moreover, it is recommended that initial anti-infective therapy include one or more drugs that have activity against all likely pathogens and penetrate in adequate concentrations into the target tissue [3]. The selected antibiotic strategy should anticipate the site of infection, medical and culture history, and local microbial susceptibility results, all in an emergency situation [1],[8].

With respect to the previously reported investigations, Hranjec and colleagues [13] presented data from a 2-year, quasi-experimental before-and-after observational study of hemodynamically stable patients admitted to a surgical ICU. In the first year, patients suspected of having an infection (n =101, aggressive approach, de-escalating strategy) had blood cultures and antimicrobial therapy was started. In the second year, patients suspected of having an infection (n =100, conservative approach, escalating strategy) had an antimicrobial therapy only after objective findings confirmed an infection. The conservative approach was associated with lower all-cause mortality: (13/100) 13% versus (27/101) 27%, P =0.015. The odds ratio for the risk of mortality in the aggressive approach group was 2.5 (95% CI 1.5 to 4.0) in comparison with the conservative group. In this investigation, waiting for objective data to diagnose infection before treatment with antimicrobial agents for suspected infection does not worsen the mortality.

Early broad-spectrum antimicrobial therapy is necessary within the ‘golden hour’ in septic shock and, as a milestone, reduces mortality. However, the use of broad-spectrum antimicrobial agents may be associated with induction of resistance among common pathogens and therefore may be a sticking point. In septic patients without sepsis-associated hypotension, diagnostic measure may be beneficial before an antibiotic therapy starts. New research is urgently needed concerning different strategies that would balance early administration of antibiotics against the potential harmful effects to patients and resistance. New research strategies have to test a de-escalating strategy with restriction of specific broad-spectrum antibiotics in the initial therapy to the most critically ill patients and patients with suspicion of multidrug-resistant pathogens, against an escalating strategy in less critically ill patients. Moreover, further studies are needed to distinguish between more and less critically ill patients, to differentiate patients’ backgrounds, and to determine indicators for patients who profit from an escalating or de-escalating strategy.