In the Literature

Two-Fifths of Sepsis-2 Patients Fail to Meet Sepsis-3 Definition: Is This Good or Bad?

Sterling SA, Puskarich MA, Glass AF, Guirgis F, Jones AE. The impact of the Sepsis-3 septic shock definition on previously defined septic shock patients. Crit Care Med 2017. doi:10.1097/CCM.0000000000002512.

The latest iteration of the consensus definitions of “sepsis and septic shock,” published in early 2016 [1], represented a significant departure from those of the past. Sepsis is now defined as simply “life threatening organ dysfunction caused by a dysregulated host response to infection.” Septic shock was redefined as sepsis with “circulatory and metabolic abnormalities profound enough to substantially increase mortality”—and more practically as a requirement for vasopressor administration to maintain a mean arterial pressure >65 mm Hg and a serum lactate level >2 mmol in the absence of hypovolemia. The overly sensitive systemic inflammatory response syndrome (SIRS) criteria were discarded. The Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) scores were recommended to be used for prognostic, but not diagnostic, purposes. Having a positive qSOFA score requires the presence of at least 2 of the following: respiratory rate ≥22 breaths/minute, altered mental status as evidenced by a Glasgow Coma Scale score <15, and systolic blood pressure ≤100 mm Hg.

In an examination of 2593 first infection events recorded in a large US database, 1526 met SIRS criteria, whereas criteria for SOFA and qSOFA were met by 1080 and 378, respectively, with corresponding mortality rates of 9%, 13%, and 23%, respectively [2].

Sterling and colleagues set out to evaluate the impact of the new criteria for septic shock by applying them to patients in 2 clinical trials that used the older criteria. Of the 470 patients meeting the previous criteria, 200 (42.6%) failed to meet Sepsis-3 criteria. The median SOFA score of these 200 patients was only 5 compared to 9 in the 270 (57.4%) who met Sepsis-3 criteria. Among the former, blood cultures were positive in 33%, compared to 51% among those meeting Sepsis-3, and the associated mortality rates were 14.4% and 28.5%, respectively. Of note is that the presence of a normal serum lactate concentration accounted for 41% of the 200 cases that failed to meet Sepsis-3 criteria.

Thus, while Sepsis-3 criteria for septic shock identify a cohort with greater risk of mortality than do the older criteria, the 14.4% mortality associated with the latter is not inconsequential. One potential unintended consequence of the new criteria is that some patients who could benefit from early recognition of and intervention for serious infection may suffer for lack of meeting the Sepsis-3 criteria. This concern is consistent with those raised by Machado and colleagues who, while agreeing that the older SIRS criteria have poor discriminant value, assert that they still have “an important role in identifying patients with infection who may benefit from antimicrobial therapy, fluids and additional screening for organ dysfunction” [3]. Large prospective studies will be necessary to resolve this issue.

References

Early Intravenous-to-Oral Switch in Pediatric Bacteremic Osteoarticular Infection due to Staphylococcus aureus

McNeil JC, Kaplan SL, Vallejo JG. The influence of the route of antibiotic administration, methicillin susceptibility, vancomycin duration, and serum trough concentration on outcomes of pediatric Staphylococcus aureus bacteremic osteoarticular infection. Pediatr Infect Dis J 2017; 36:572–7.

Our pediatric colleagues seem to have taken the lead in the use of largely orally administered therapy for hematogenous osteoarticular infection. For example, a retrospective analysis of a total of 2060 children and adolescents with osteomyelitis of various etiologies found no difference in outcomes in a comparison of those discharged to receive outpatient parenteral antibiotic therapy (OPAT) via a peripherally inserted central catheter (PICC) with those who were instead discharged on oral antibiotics [1]. The etiology was Staphylococcus aureus in 1240 (60.2%), and 336 of the 2060 (16.3%) were methicillin resistant (MRSA). Of note is that 158 (15.0%) of the OPAT group had a PICC-related complication that led to an emergency department visit, hospitalization, or both.

An important issue that was not addressed in that study, however, was the use of oral antibiotics in patients whose blood cultures had been positive. Addressing this lack, McNeil and colleagues reviewed their single-center experience in the treatment of 192 children with hematogenous osteoarticular infection due to S. aureus, 35 of which were MRSA. Osteomyelitis was present in 176 (91.7%) and septic arthritis in 96 (50%). Blood cultures were positive in 102 (53.1%) and positivity was associated with more complicated disease, but not with an increased frequency of long-term complications. Blood cultures yielded MRSA in 35 (34.3%) of the bacteremic patients. MRSA bacteremia was associated with a longer duration of fever, bacteremia, hospitalization, and a greater frequency of surgical intervention.

Twenty-six of the 102 (25.4%) patients with bacteremic osteoarticular infection (BOAI) were discharged to home on oral antibiotics, whereas 68 (66.6%) received OPAT, and 8 (7.8%) received intravenous antibiotic throughout their course of therapy. Those completing therapy on oral antibiotics had a median duration of hospitalization of 8.5 days, having received a median of 7 days of intravenous antibiotic administration. There was no difference in the incidence of development of long-term orthopedic complications between those who were discharged on oral antibiotics and those who received all their treatment intravenously.

Among the 35 patients with BOAI due to MRSA, all but 1 (who received clindamycin for the entire course) were initially treated with vancomycin, which was given for a median duration of 7 days (interquartile range, 4–23 days). The median duration of negative blood cultures before a change in antibiotic administration was 2 days. There was no difference in the occurrence of long-term orthopedic complications in comparing those who received <7 days and those with >7 days of vancomycin. Outcomes were not improved by achievement of vancomycin trough concentrations >15 μg/mL, but this concentration was associated with an increased risk of acute kidney injury. All with <7 days of vancomycin therapy subsequently received clindamycin to complete there treatment.

The results of this study support early transition to oral therapy in children with BOAI due to S. aureus, including those due to MRSA. While the pathophysiology of hematogenous bone infection may be quite different in children relative to adults, it is likely that this therapeutic approach applies to adults as well. It would nonetheless be of importance to definitively to determine whether bacteremia with S. aureus, including MRSA, can be successfully treated in adults with largely orally administered antibiotics.

Reference