Clinical Outcomes With Definitive Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia With Retained Daptomycin and Ceftaroline Combination Therapy vs De-escalation to Monotherapy With Vancomycin, Daptomycin, or Ceftaroline.

BACKGROUND: Lower mortality has been observed with combination therapy compared to monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia; however, there is a lack of evidence for continued combination therapy over de-escalation to monotherapy following bacteremia clearance. METHODS: This was a single-center, retrospective study evaluating patients with MRSA bacteremia hospitalized from November 1, 2011, through July 31, 2019. Patients who received three to ten days of combination therapy followed by de-escalation to monotherapy were directly compared to patients retained on combination therapy. The primary composite outcome included inpatient infection-related mortality, 60-day readmission, and 60-day bacteremia recurrence. RESULTS: A total of 286 patients with MRSA bacteremia were identified, with 146 patients omitted based on exclusion criteria. The study population included 66 in the combination therapy group and 74 in the monotherapy group. Study population was 51% female (n = 71) and 78% white (n = 109) with median age of 46 years (IQR 34.5-61). No significant difference was observed in the primary composite outcome (21% combination therapy group vs 24% monotherapy group; P =.66), with retained observations after controlling for confounders. Within this outcome, there was no significant difference in 60-day readmission (20% combination therapy group vs 18% monotherapy group; P =.75), bacteremia recurrence (3% combination therapy group vs 7% monotherapy group; P =.45), or inpatient infection-related mortality (2% combination therapy group vs 5% monotherapy group; P = 1.00). CONCLUSIONS: No difference was found in the composite outcome of 60-day bacteremia recurrence, readmission, or inpatient infection-related mortality for patients with MRSA bacteremia retained on combination therapy versus those de-escalated to monotherapy.

Effectiveness of short vs long-course perioperative antibiotics in lung transplant recipients with donor positive respiratory cultures.

Lung transplant recipients are at increased risk for infection in the early postoperative phase, thus perioperative antibiotics are employed. This retrospective study evaluated the efficacy of short- vs long-course perioperative antibiotics in lung transplant patients. Lung transplant patients with donor positive cultures between August 2013 and September 2019 were evaluated, excluding those with cystic fibrosis, death within 14 days and re-transplants. The primary outcome was 30-day freedom from donor-derived respiratory infection. A total of 147 patients were included (57 short vs 90 long-course). Median perioperative antibiotic duration was 6 days in the short-course vs 14 days in the long-course group (P < .0001). Thirty-day freedom from donor-derived respiratory infection was present in 56 (98%) patients in the short-course vs 85 (94%) patients in the long-course group (P = .41). There was no difference in development of Clostridioides difficile infections (P = .41), while cumulative ventilator time and time to post-op extubation were longer in the long-course group (P = .001 and .004, respectively). Among lung transplant recipients with positive donor respiratory cultures, short-course perioperative antibiotics were as effective as long-course antibiotics in preventing donor-derived bacterial respiratory infections.

Clinical outcomes following treatment of Enterobacter species pneumonia with piperacillin/tazobactam compared to cefepime or ertapenem.

BACKGROUND: Enterobacter spp. are a common cause of nosocomial pneumonia and treatment can be complicated by AmpC resistance. Carbapenems are the treatment of choice; however, alternatives are needed. Cefepime has been shown to be non-inferior to carbapenems. There are limited data to support the use of piperacillin/tazobactam. The objective of this study was to determine if piperacillin/tazobactam is non-inferior to cefepime or ertapenem for Enterobacter pneumonia treatment. OBJECTIVES: To compare the rate of clinical cure in patients with Enterobacter pneumonia receiving definitive treatment with piperacillin/tazobactam, cefepime, or ertapenem. Secondary outcomes included hospital mortality, infection-related length of stay, duration of mechanical ventilation, recurrent pneumonia, and resistance. METHODS: Retrospective, single-center study. RESULTS: Of 114 patients included, 59 received definitive treatment with piperacillin/tazobactam and 55 received cefepime or ertapenem. There was no difference in the proportion of patients who achieved clinical cure in the piperacillin/tazobactam group compared to the cefepime or ertapenem group (76.3% vs. 87.3%, P = 0.13). Treatment group was not associated with clinical cure when controlling for confounders in multivariable logistic regression (adjusted odds ratio [OR] 0.59, 95% confidence interval [CI] 0.15-2.37). The rate of recurrent pneumonia was 11.4% in the piperacillin/tazobactam group and 6.7% in the cefepime or ertapenem group (P = 0.48). Other secondary outcomes did not differ between the groups. CONCLUSIONS: In this retrospective study of patients with Enterobacter pneumonia, clinical cure with piperacillin/tazobactam was comparable to that with cefepime or ertapenem; however, a prospective trial with a larger population is needed to determine if definitive treatment with piperacillin/tazobactam is non-inferior to definitive treatment with cefepime or ertapenem.

Efficacy of combination therapy versus monotherapy in the treatment of Stenotrophomonas maltophilia pneumonia.

BACKGROUND: Stenotrophomonas maltophilia is intrinsically resistant to several antibiotics, making it potentially challenging to treat. Studies have demonstrated treatment failures and resistance development with monotherapy (MT); however, clinical data are limited with combination therapy (CT). OBJECTIVES: To compare clinical outcomes with CT versus MT for S. maltophilia pneumonia. METHODS: This was a retrospective cohort study of patients admitted between November 2011 and October 2017 with S. maltophilia pneumonia who received at least 48 h of effective therapy. The primary outcome was clinical response after 7 days of effective therapy with CT versus MT. Secondary outcomes included development of a non-susceptible isolate, 30 day microbiological cure, infection recurrence, infection-related mortality and all-cause mortality. The Wilcoxon rank sum test, the Pearson χ2 test and Fisher's exact test were utilized for univariate analyses. A multivariable logistic regression model was used to assess clinical response while adjusting for confounding variables. RESULTS: Of 252 patients with S. maltophilia pneumonia included, 38 received CT and 214 received MT. There was no difference in 7 day clinical response with CT versus MT (47.4% versus 39.7%, P = 0.38), even after controlling for immune status, APACHE II score and polymicrobial pneumonia (adjusted OR 1.51, 95% CI 0.63-3.65). Thirty day microbiological cure (P = 0.44), recurrence (P = 0.53), infection-related mortality (P = 0.19) and isolation of a non-susceptible isolate during or after therapy (P = 1.00 each) were also similar between both groups; however, 30 day all-cause mortality was greater with CT (P = 0.03). CONCLUSIONS: CT had similar rates of clinical efficacy and resistance development compared with MT for S. maltophilia pneumonia.

Clinical Outcomes with Penicillin Versus Alternative ß-Lactams in the Treatment of Penicillin-Susceptible Staphylococcus aureus Bacteremia.

OBJECTIVES: To identify the impact of penicillin versus alternative ß-lactams on clinical outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Adult patients with PSSA bacteremia treated with a ß-lactam as definitive therapy. MEASUREMENTS: The primary outcome was a composite end point of 30-day clinical failure (change in PSSA therapy due to persistent or worsening signs and symptoms, PSSA bacteremia recurrence or persistence, and/or infection-related mortality) in patients treated with penicillin versus alternative ß-lactams. Secondary outcomes included infection-related and hospital length of stay (LOS), 90-day recurrence, 90-day infection-related readmission, 30-day all-cause mortality, adverse drug events (ADEs), and 30-day change in PSSA therapy due to ADEs. A subgroup analysis comparing penicillin, nafcillin, and cefazolin was also conducted. MAIN RESULTS: For the 122 patients who were included, the most common definitive therapies were nafcillin (37%), cefazolin (29%), and penicillin (21%). No difference was found in 30-day clinical failure (4% vs 11%, p=0.46), infection-related LOS (12 days vs 11 days, p=0.39), hospital LOS (12.5 days vs 12 days, p=0.69), 90-day recurrence (p=1.00), 90-day infection-related readmission (p=1.00), or 30-day all-cause mortality (p=0.45) between penicillin and other ß-lactams. The prevalence of ADEs was different among penicillin, nafcillin, and cefazolin (p=0.049), with nafcillin requiring more changes in therapy (p=0.005). CONCLUSIONS: Definitive therapy with penicillin had similar efficacy compared with alternative ß-lactams for the treatment of PSSA bacteremia. However, nafcillin was associated with more ADEs requiring a change in therapy.