Early Administration of Adjuvant β‐Lactam Therapy in Combination with Vancomycin among Patients with Methicillin‐Resistant Staphylococcus aureus Bloodstream Infection: A Retrospective, Multicenter Analysis

Abstract

Receipt of COMBO therapy did not decrease the rate of clinical failure but was associated with expedited bacteremia clearance. Early adjuvant β-lactam therapy deserves continued evaluation and clinical consideration.

Treatment strategies for persistent methicillin‐resistantStaphylococcus aureusbacteraemia

“…Although there was no difference in mortality and metastatic infection, the mean duration of bacteraemia in the combination therapy group was 1.94 days compared to 3 days in the standard group (ratio of means 0.65, 95% CI 0.41‐1.02) . Another retrospective study which evaluated 97 patients demonstrated similar outcomes in which β‐lactam plus vancomycin combination compared to vancomycin monotherapy resulted in improvements to bacteraemia clearance (median time to clearance of 3 days vs 4 days, respectively, P = 0.047) with no improvements in treatment failures (24.6% vs 30%, respectively, P = 0.55) . Trinh et al found that vancomycin plus cefazolin compared to vancomycin monotherapy resulted in fewer treatment failures (24% vs 52%, respectively, P = 0.006) and fewer cases of persistent MRSA bacteraemia (15% vs 35%, respectively, P = 0.023).…”

Adjuvant β-Lactam Therapy Combined with Vancomycin or Daptomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: a Systematic Review and Meta-analysis

“…1 ). After applying the inclusion/exclusion criteria, a total of 15 studies ( 6 , 18 – 31 ) comprising a total of 2,594 patients were included (1,189 patients in the standard therapy [STAN] group and 1,405 patients in the STAN therapy combined with β-lactams [COMBO] group), including 7 studies ( 21 – 27 ) based on the combination of VAN, 5 studies ( 6 , 28 – 31 ) based on the combination of DAP, and 3 studies ( 18 – 20 ) based on the combination of daptomycin or vancomycin. Among the included studies, the β-lactam of choice was ceftaroline in four studies ( 20 , 29 – 31 ), cefazolin in three studies ( 19 , 23 , 25 ), flucloxacillin in two studies ( 19 , 22 ), cloxacillin in one study ( 19 ), and cefepime in one study ( 27 ).…”

“…Among the included studies, the β-lactam of choice was ceftaroline in four studies ( 20 , 29 – 31 ), cefazolin in three studies ( 19 , 23 , 25 ), flucloxacillin in two studies ( 19 , 22 ), cloxacillin in one study ( 19 ), and cefepime in one study ( 27 ). In six cohort studies, β-lactams generally comprised more than 3 antibacterial agents ( 18 , 21 , 26 , 28 ) or unknown varieties ( 6 , 24 ). Among the included studies, 3 were randomized controlled trials (RCTs) ( 19 , 22 , 30 ), 12 were retrospective cohort studies, 10 were multicenter studies, 4 were conducted at a single center, and 1 was unknown.…”

“…The quality of the 12 included cohort studies was evaluated using the Newcastle-Ottawa scale (NOS). There were a total of seven studies with NOS scores of ≥6 points, of which three scored 7 points ( 18 , 26 , 28 ) and four scored 6 points ( 20 , 21 , 27 , 31 ). Studies published in the abstract form all scored <6 points, of which three ( 23 – 25 ) scored 3 points and one ( 29 ) scored 4 points.…”

A Phase 1, Randomized, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S, an Anti- Staphylococcus aureus Thiomab Antibody-Antibiotic Conjugate, in Healthy Volunteers

“…More recent antistaphylococcal antibiotics such as ceftaroline (approved for acute bacterial skin and skin structure infection [ABSSSI] and communityacquired bacterial pneumonia [CABP] [25]) and telavancin (approved for ABSSSI and hospital-acquired bacterial pneumonia [HABP] [26]) are used as salvage therapy or in combination therapy to treat complicated S. aureus infections. Combination therapy with beta-lactams for MRSA infections results in more rapid clearance of S. aureus from the blood (27,28), but this has not translated into improved clinical outcomes (29). The recent ARREST trial in patients with S. aureus bacteremia, which assessed the superiority of adjunctive rifampin in combination with SOC antibiotics to SOC antibiotics alone, showed a positive trend toward reducing infection recurrence in patients treated with adjunctive rifampin (23).…”