A Real-world Multicenter Outpatient Experience of Ceftolozane/Tazobactam.

Background: Ceftolozane/tazobactam (C/T) is indicated for the treatment of complicated intra-abdominal infection (IAI), complicated urinary tract infection (UTI), and hospital-acquired/ventilator-associated bacterial pneumonia caused by susceptible bacteria. As real-world data are limited, we report utilization and associated outcomes of C/T use in the outpatient setting. Methods: This is a multicenter, retrospective study of patients who received C/T between May 2015 and December 2020. Demographics, infection types, C/T utilization characteristics, microbiology, and health care resource utilization were collected. Clinical success was defined as complete or partial symptom resolution at completion of C/T. Persistent infection and discontinuation of C/T were deemed nonsuccess. Logistic regression analysis was used to identify predictors associated with clinical outcomes. Results: A total of 126 patients (median age, 59 years; 59% male; median Charlson index, 5) from 33 office infusion centers were identified. Infection types included 27% bone and joint infection (BJI), 23% UTI, 18% respiratory tract infection (RTI), 16% IAI, 13% complicated skin and soft tissue infection (cSSTI), and 3% bacteremia. The median daily dose of C/T was 4.5 g, primarily administered via elastomeric pumps as intermittent infusion. The most common gram-negative pathogen was P. aeruginosa (63%), 66% of which was multidrug-resistant and 45% carbapenem-resistant. Enterobacterales was identified in 26% of isolates, of which 44% were extended-spectrum beta-lactamase producers. The overall clinical success rate of C/T was 84.7%. Nonsuccessful outcomes were due to persistent infections (9.7%) and drug discontinuations (5.6%). Conclusions: C/T was successfully used in the outpatient setting to treat a variety of serious infections with a high prevalence of resistant pathogens.

Appropriate cleaning reduces potential risk of spore transmission from patients with Clostridioides difficile infection treated in outpatient infusion centers.

OBJECTIVES: Patients with Clostridioides difficile infection (CDI) who receive treatment at outpatient infusion centers (OICs) pose a risk for spore transmission. We investigated C. difficile contamination in the environment of CDI and non-CDI patients and evaluated the effectiveness of standard cleaning. METHODS: This is a multicenter, non-conventional study including 8 OICs between October 2019 and December 2020. Samples were collected at baseline, after infusion, and after cleaning CDI and non-CDI areas. Cleaning was performed using hypochlorite and non-hypochlorite products for CDI and non-CDI, respectively. Samples were cultured for toxigenic C. difficile and strain-typed via fluorescent PCR ribotyping and whole-genome sequencing. RESULTS: The overall C. difficile contamination rate was 7.9% (156/1969) with 8.1% in patient and 5.6% in non-patient care areas, respectively. For CDI areas, contamination rates were 5.9% at baseline, 15.0% after infusion, and significantly reduced to 6.2% after cleaning (P = 0.004). For non-CDI areas, contamination was similar at baseline (9.5%), after infusion (7.6%), and after cleaning (4.3%). The difference in C. difficile-positive samples after infusion was significant for CDI vs. non-CDI (15.0% vs. 7.6%, P = 0.004). Overall contamination was 11.5% for floors, 7.9% for infusion chairs, and 3.8% for equipment (P = 0.001). The most frequent ribotypes were F014-020 (42.6%), F106 (15.6%), F255 (6.1%), F001 (5.2%) and F027 (3.5%). Cleaning resulted in elimination of F106, F255, F001, F027 and partial reduction of F014-020. CONCLUSIONS: Environmental C. difficile contamination was increased after CDI infusions and significantly reduced after cleaning with a hypochlorite solution, reducing the potential risk of spore transmission to others.

Recurrent Clostridioides difficile infection worsens anxiety-related patient-reported quality of life.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with high recurrence rates impacting health-related quality of life (HrQOL). However, patient-reported data are lacking particularly in the outpatient setting. We assessed changes in HrQOL over time in patients treated with bezlotoxumab at US infusion centers and determined clinical factors associated with HrQOL changes. METHODS: The HrQOL survey was conducted in adult patients with CDI, who received bezlotoxumab in 25 US outpatient infusion centers. The survey was adapted from the Cdiff32 instrument to assess anxiety-related changes to HrQOL and completed on the day of infusion (baseline) and at 90 days post bezlotoxumab (follow-up). Demographics, disease history, CDI risk factors, and recurrence of CDI (rCDI) at 90-day follow-up were collected. Changes in HrQOL scores were calculated and outcomes assessed using a multivariable linear regression model with P < 0.05 defined as statistically significant. RESULTS: A total of 144 patients (mean age: 68 ± 15 years, 63% female, median Charlson index: 4, 15.9% rCDI) were included. The overall mean baseline and follow-up HrQOL scores were 26.4 ± 11.5 and 56.4 ± 25.0, respectively. At follow-up, this score was significantly higher for patients who had primary CDI (34.5 ± 21.7) compared to those with multiple rCDI (24.7 ± 21.0; P = 0.039). The mean HrQOL change at follow-up was significantly higher for patients without rCDI (34.1 ± 28.8 increase) compared to patients with rCDI (6.7 ± 19.5 increase; P < 0.001), indicating improvement in anxiety. CONCLUSIONS: Using the Cdiff32 instrument, we demonstrated that HrQOL worsened significantly in patients with further rCDI. These findings support the use of Cdiff32 in assessing CDI-related humanistic outcomes.

Real-world Experience of Bezlotoxumab for Prevention of Clostridioides difficile Infection: A Retrospective Multicenter Cohort Study.

BACKGROUND: Bezlotoxumab is approved for prevention of recurrence of Clostridioides difficile infection (CDI) in adults receiving standard of care (SoC) therapy based on findings from MODIFY clinical trials. However, utilization practices and validation of trial results in the real world are limited. METHODS: Records of patients receiving bezlotoxumab between April 2017 and December 2018 across 34 infusion centers in the United States were retrospectively reviewed. Recurrent CDI (rCDI), defined as diarrhea lasting ≥2 days resulting in treatment, was assessed 90 days postbezlotoxumab. RESULTS: The study cohort included 200 patients (median age, 70 years; 66% female; median Charlson comorbidity index, 5), of whom 86% (n = 173) had prior CDI episodes and 79% (n = 158) had ≥2 risk factors for rCDI. SoC antibiotics included vancomycin (n = 137, 68%), fidaxomicin (n = 60, 30%), and metronidazole (n = 3, 2%). Median time from C. difficile stool test to bezlotoxumab and initiation of SoC to bezlotoxumab were 15 days and 11 days, respectively. Within 90 days, 31 of 195 patients (15.9%) experienced rCDI, which corresponds to a success rate of 84.1%. Patients with ≥2 CDI recurrences prebezlotoxumab had a higher risk of subsequent rCDI compared with those with 1 recurrence or primary CDI (hazard ratio, 2.77; 95% confidence interval, 1.14-6.76; P = .025). CONCLUSIONS: This real-world multicenter study demonstrated successful prevention of rCDI with bezlotoxumab comparable to clinical trial results regardless of type of SoC and timing of infusion. Multiple prior CDI recurrences were associated with a higher risk of subsequent rCDI, supporting the use of bezlotoxumab earlier in the disease course.

Outpatient treatment of osteomyelitis with telavancin.

Telavancin is a lipoglycopeptide antibiotic with bactericidal activity against Gram-positive pathogens including Staphylococcus aureus, the most frequent cause of osteomyelitis. Treatment is often challenging due to needs for surgical intervention along with prolonged administration of intravenous antimicrobials, frequently in an outpatient setting. This was a retrospective analysis of the efficacy and safety of telavancin for treatment of osteomyelitis provided as outpatient parenteral antimicrobial therapy (OPAT) in physician office infusion centres. Medical records of 60 patients receiving telavancin for osteomyelitis in 22 physician office infusion centres from 2010 to 2011 and 2013 to 2015 were reviewed. Of these, 60% were treated without hospitalisation, 37% had orthopaedic hardware and 56% had concurrent infections. Staphylococcus aureus was the most common pathogen (78%), primarily methicillin-resistant. The median duration of telavancin treatment in the outpatient setting was 21 days (range 3-105 days). Telavancin was used as first-line therapy in 32% of cases, following prior antibiotic failure in 47% and due to intolerance to previous agents in 22%, predominantly daptomycin or vancomycin. The telavancin dose was 10 mg/kg/day, adjusted for renal function in 25% of patients. The majority of patients self-administered telavancin at home via an elastomeric infusion pump. Overall clinical success was 73%. No significant differences in outcomes were observed with the presence of hardware, concurrent infection, concomitant therapies or type of osteomyelitis. Telavancin-associated adverse events occurred in 57%, with discontinuation in three patients (5%). These data demonstrate the effective and safe OPAT use of telavancin, providing an alternative for successful treatment of patients with osteomyelitis.

Successful treatment of polymicrobial calcaneal osteomyelitis with telavancin, rifampin, and meropenem.

OBJECTIVE: To report a case of multidrug-resistant osteomyelitis successfully treated with telavancin, rifampin, and meropenem. CASE SUMMARY: An 18-year-old male with spina bifida was treated primarily in the outpatient setting over the course of 133 days with multiple antimicrobials for a recurrent right calcaneal wound and osteomyelitis infection. Initial cultures were positive for methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus, which were treated with intravenous vancomycin 1 g every 12 hours, increased after 13 days to 1.5 g every 12 hours with addition of rifampin 300 mg twice daily, both of which were discontinued on day 22 due to leukopenia (white blood cell count 3.0 × 10(3)/µL) and neutropenia (absolute neutrophil count 0.2 × 10(3)/µL). Daptomycin 8 mg/kg/day was then initiated with rifampin 300 mg twice daily; treatment was discontinued after 49 days due to an elevated creatine kinase level of 1831 U/L (baseline 86). Intravenous meropenem 1 g every 8 hours was again initiated on day 83 following additional identification of quinolone-resistant Pseudomonas aeruginosa from the soft tissue of the right foot. Intravenous vancomycin 1 g every 12 hours was also restarted at this time for persistent coagulase-negative Staphylococcus and oral rifampin 300 mg twice daily was again added. Adverse events again required the discontinuation of vancomycin on day 91. The eventual drug therapy regimen consisted of telavancin 750 mg/day for 42 days, meropenem for 50 days, and oral rifampin for 50 days. At the end of treatment, the patient's right heel wound had almost completely closed. He was without recurrence or treatment-related adverse events at follow-up 1 year later. DISCUSSION: Antimicrobial selection for osteomyelitis infections presents a challenge to the clinician due to patient intolerance, increasing antimicrobial resistance, and variable antimicrobial penetration at the site of infection. To our knowledge, this is the first case report of the successful use of a regimen including telavancin for the treatment of a recurrent, coagulase-negative Staphylococcus osteomyelitis infection. CONCLUSIONS: In this complex case involving a polymicrobial infection of the right calcaneal bone and surrounding soft tissue, eventual drug therapy including telavancin, meropenem, and rifampin resulted in a successful clinical response.