The main results of this retrospective study assessing the impact of the implementation of a multidisciplinary NSTI care bundle are as follows: (1) the NSTI care bundle was associated with a marked increase in yearly admissions; (2) it was associated with an increase in day 60-censored hospital survival in univariable analysis, which was not maintained after adjustment for admission characteristics; and (3) it did not allow for significantly altering key pre-defined patient management endpoints.
The increase in yearly patient recruitment (Fig. 1) per se could be an interesting benefit of our bundle. Indeed, in a recent study by Audureau et al. [8], patients managed in centers admitting a high volume of NSTI cases (defined by 3 or more yearly cases) had a lower 28-day mortality, even after adjusting for potential confounding factors. Bernal et al. found that mortality was lower for patients whose initial surgical debridement was performed by a surgeon experienced in NSTIs [16], further highlighting the potential benefits of being managed in centers with high case volumes. Although yearly patient recruitment increased between the pre- and post-implementation periods, there was no increase in the rate of patients who were transferred to our center from another facility. As the incidence of NSTI is not thought to be rising [17, 18], this could nevertheless be due to our communication policy, by an increase of direct referral by pre-hospital medical teams or general practitioners as well as by an increase of spontaneous patient consultation to our center’s “dermatological emergency ward”. As the inclusion criteria for our study was surgically confirmed NSTI, an increase in incidence due to erroneous diagnosis is unlikely, but could be due to the increased awareness, experience and training of physicians regarding NSTI in our center.
The survival benefit associated with the post-implementation period was not maintained after adjustment for admission characteristics (Fig. 2, Table 2). The main hypothesis is that bundle impact could have been undermined because our center was already experienced in the management of NSTIs. Indeed, there was no significant difference regarding the main management endpoints between the pre- and post-implementation periods (Fig. 3). The rate of patients rapidly undergoing surgery and receiving adequate antibiotics, even before implementation of the bundle, is difficult to compare to the literature. It was markedly high compared to some studies [19], and lower compared to others [20, 21]. Nevertheless, the rate of patients transferred from other centers in our series, of more than 50% both in the pre- and post-implementation periods, is much higher than in previous studies evaluating NSTIs at a national level (Audureau et al. 13% [8], Holena et al. 10% [22], Ingraham et al. 30% [23]) but similar to that of series from experienced centers such as the one by Bernal et al. (59%) [16]. Besides this homogenous management, other explaining factors could be a lack of power due to the rarity of NSTIs or a change in patient characteristics associated with the increase in the number of admissions, as highlighted by the lesser proportion of patients with nosocomial infections, known to be more severe [24, 25]. Figure 1 illustrates that the mortality difference between groups seems to develop after day 30. We speculate this could reflect the impact of age and pre-existing comorbidities on mortality, rather than that of the first 48 h of management on which our bundle mainly focused. Finally, the fact that antibiotics administered before admission were a protective factor for hospital survival in the multivariable model is remarkable and may have limited our ability to demonstrate a benefit of antibiotics administered within 24 h of hospital admission.
This work has several limitations, the first of which being its monocentric retrospective design, limiting the generalization of its results. Second, time to surgery was measured in days, not in hours, which could have undermined our ability to demonstrate its impact on outcome. As patients were identified with two different methods according to the period of inclusion (electronic records or prospective database) and because 14 patients with important missing data were excluded without imputation, we cannot exclude a selection bias. Antibiotic treatment was not evaluated for adequacy to documentation, duration, de-escalation and side effects. We could not obtain time to administration in hours, due to the retrospective design of the study. Finally, elements not included in our bundle and that were not evaluated could have impacted outcome, such as use of anti-toxinic antibiotics or negative-pressure wound therapy [26].
Our study also has several strengths, the first of which is a well-defined diagnosis as a main inclusion criterion. Indeed, an important part of the literature on NSTIs has included patients based on an electronic record diagnosis of NSTIs, a major selection bias for a disease with a challenging diagnosis [23]. We only included surgically proven NSTIs, and in spite of this restrictive definition, the second strength of this cohort is its large size. Finally, we applied a rigorous methodology to this before–after study, defining key management endpoints a priori, and choosing a strong outcome measure (i.e., hospital mortality).
Interestingly, during the conduction of this project, the only other report, to our knowledge, of a multidisciplinary bundle of care for NSTIs was published. Although focusing on ICU patients, this much smaller series found a very similar benefit on mortality to their bundle (40% vs 15% after implementation, compared to 30% vs 15% in our work), highlighting this approach’s potential interest [27]. By contrast to the hospital that conducted this research, our center has been a referral center for NSTIs for several decades. Standard of care before bundle implementation likely rendered patient management homogeneous, making it difficult to show a statistically significant difference on a solid outcome like mortality. Nevertheless, our work confirms the feasibility of standardizing multidisciplinary care for NSTIs on a larger scale.
