To our knowledge, this is the largest real-world, multicenter study of dalbavancin use for Gram-positive BSI. Dalbavancin has recently become more accepted as an option for step-down therapy for BSI. Patients were more frequently PWID (40%) who received dalbavancin for BSI in this study compared to other recent single-center US studies examining dalbavancin for osteomyelitis, deep-seated infections, or Staphylococcus BSI [15, 17, 18]. The high proportion of PWID is demographically consistent with the average patient age in our series, along with the bimodal distribution of age centered on patients 30 and 60 years old (Fig. 1). Dalbavancin is used in the PWID population due to difficulties in discharge, placement, and the tendency to avoid central lines. Indeed, 34% of patients received dalbavancin because the patient could not be discharged with a PICC in our analysis. The pathogens targeted by dalbavancin were similar to European real-world studies, with Staphylococcus aureus being the most prevalent, and coagulase-negative Staphylococcus, Streptococcus spp., Enterococcus spp., and other pathogens less common [12, 13]. However, the higher proportion of MRSA in our real-world cohort compared to these previous studies reflects the high prevalence of PWID in urban US hospitals.

Our cohort also found a high proportion of complicated BSI treated with dalbavancin compared to other observational studies. The recommended length of therapy for uncomplicated BSI is 2 weeks, and 4 weeks for complicated BSI. Importantly, the median length of stay with dalbavancin use in our study was much shorter than the recommended durations of treatment for Gram-positive BSI. If patients had not received dalbavancin, then they may not have been able to be discharged due to complex discharge situations. Therefore, dalbavancin administration may have saved upwards of a median 5 inpatient days for uncomplicated BSI and a median 15 inpatient days for complicated BSI. Administration was timed primarily on the day of discharge (45%), next most prior to discharge which was likely inpatient (27%), and lastly received post-discharge or assumed outpatient (25%) or only treated outpatient/in clinics (2.6%). Reimbursement for drug administration in addition to saving inpatient hospital days may play a large role in the timing of administration. As expected, complicated BSI had numerically worse outcomes compared to uncomplicated BSI, although the difference was not statistically significant. This was likely the result of longer bacteremia durations, reflecting higher disease burden, difficult source control, and higher-risk patients. It should be noted that in both complicated and uncomplicated BSI, the majority of patients completed the planned duration of dalbavancin therapy.

Literature supports dalbavancin attaining adequate staphylococcal coverage for 5–8 weeks when using two 1500-mg doses 1 week apart, which adds heterogeneity to defining the “duration of dalbavancin coverage” that classically is thought to last 7–14 days [22,23,24,25]. While dalbavancin 1500 mg was most common for BSI (68%), the timing of subsequent doses was variable. Differences in institutional clinical preferences and experience may explain the variable dalbavancin regimens and their timings relative to discharge (Table 3), highlighting a possible need for further standardization. Another important consideration is whether the BSI is uncomplicated or complicated, as dalbavancin doses averaged more than two in complicated BSI (Table 5). Despite rather heterogeneous dosing regimens, outcomes were favorable with low rates of 90-day mortality, 90-day recurrence, 90-day infection-related readmission, and low adverse-event rates. In fact, most patients (70%) completed dalbavancin treatment without a negative outcome. Although, the all-cause 90-day readmission rate in this population may seem high at 27%, it is in line with other dalbavancin studies such as Molina et al., with 26.2% and Veve et al. with 26–32% 90-day all-cause readmission rates compared with standard of care [15, 18]. These readmission rates are likely due to the vulnerability of the study patient population that are diagnosed with these infections.

The results from our study can provide real-world context to compare against the upcoming results from the DOTS randomized controlled trial [29]. The DOTS study has begun recruitment to answer the clinical question of dalbavancin (1500 mg on day 1 and 1500 mg on day 8) against standard of care in complicated S. aureus BSI, after blood culture clearance. Results are anticipated for this study some time in 2023–2024 [29, 30]. The positive outcomes on 90-day mortality, 90-day recurrence, 90-day infection-related readmission, and low adverse events in our study all compare favorably to the standard of care intravenous arms in single-center retrospective studies and in smaller randomized controlled trials [11, 14, 15, 17, 18]. These data suggest that dalbavancin can theoretically save inpatient days of therapy and possibly have non-inferior outcomes compared with standard of care, but more rigorous prospective randomized trials are needed. Even though our study did not have a comparator arm, smaller observational studies and randomized controlled trials have shown similar success rates to our own, as well as similar success rates to standard of care intravenous antibacterials [11, 14, 15, 17, 18].

This study has several limitations. First, it was a retrospective study that captured data mostly from large academic centers, which may not be applicable to smaller community hospitals, especially given the high cost of dalbavancin. Second, there was no comparator group. Third, some patients were lost to follow-up leading to missing values. This is particularly important given the concern for development of drug-resistant isolates over time, due to the long half-life of dalbavancin resulting in potentially sub-inhibitory concentrations for long periods of time. Investigators have documented at least four cases of resistance to dalbavancin, and this remains a concern for real-world practice [31,32,33,34]. However, no rise in dalbavancin or vancomycin MIC was noted in our study, although only seven isolates were available in 1 year of isolate follow-up. Lastly, certain data were not consistently available, such as any information on reimbursement or specific locations for dalbavancin administration, whether in an infusion center or inpatient.