A theory-informed assessment of the barriers and facilitators to nurse-driven antimicrobial stewardship.

BACKGROUND: Nurses represent an underused workforce for performing antimicrobial stewardship (AMS) activities. Before engaging nurses in these activities, barriers and facilitators to the targeted behavior change should be identified using a validated model. METHODS: This was a prospective, qualitative, descriptive study to determine the barriers and facilitators to the promotion of intravenous (IV) to oral (PO) antimicrobials by nurses. Semi-structured 1-on-1 interviews of nurses were conducted from January-February 2017. Interviews were analyzed for themes within the domains of the theoretical domains framework (TDF) by directed-content analysis. RESULTS: Evaluation of the 14 TDF domains revealed 9 modifiable barriers to nurse promotion of IV to PO step-down, including insufficient knowledge, lack of prescriber cooperation, lack of self-confidence, and low priority activity. Nine facilitators that could enhance nurse promotion of step-down were identified, including capability to assess patients for step-down, ability to communicate assessment results to the team, and preexistence of a variety of resources available for nurse education and training. Nurses perceived that increased step-down rates would increase nursing efficiency. CONCLUSIONS: Nurses have the potential to improve AMS through promotion of IV to PO step-down of antimicrobials. Themes pertaining to barriers and facilitators of nurses' participation in IV to PO step-down of antimicrobials were identified.

Factors influencing quality of life in patients with active tuberculosis.

BACKGROUND: With effective treatment strategies, the focus of tuberculosis (TB) management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL) experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews. METHODS: English, Cantonese, and Punjabi-speaking subjects with active TB who were receiving treatment were eligible for recruitment into the study. Gender-based focus group sessions were conducted for the inner city participants but individual interviews were conducted for those who came to the main TB clinic or were hospitalized. Facilitators used open-ended questions and participants were asked to discuss their experiences of being diagnosed with tuberculosis, what impact it had on their lives, issues around adherence to anti-TB medications and information pertaining to their experience with side effects to these medications. All data were audio-recorded, transcribed verbatim, and analyzed using constant comparative analysis. RESULTS: 39 patients with active TB participated. The mean age was 46.2 years (SD 18.4) and 62% were male. Most were Canadian-born being either Caucasian or Aboriginal. Four themes emerged from the focus groups and interviews. The first describes issues related to the diagnosis of tuberculosis and sub-themes were identified as 'symptoms', 'health care provision', and 'emotional impact'. The second theme discusses TB medication factors and the sub-themes identified were 'adverse effects', 'ease of administration', and 'adherence'. The third theme describes social support and functioning issues for the individuals with TB. The fourth theme describes health behavior issues for the individuals with TB and the identified sub-themes were "behavior modification" and "TB knowledge." CONCLUSION: Despite the ability to cure TB, there remains a significant impact on QOL. Since much attention is spent on preventative or curative mechanisms, the impact of this condition on QoL is often not considered. Attention to the issues experienced by patients being treated for TB may optimize adherence and treatment success.

Once-daily cefazolin and probenecid for skin and soft tissue infections.

OBJECTIVE: To review the pharmacokinetic and clinical evidence for the use of once-daily cefazolin and probenecid in the treatment of skin and soft tissue infections (SSTI). DATA SOURCES: MEDLINE (1966-July 2003), EMBASE (1980-July 2003), and PubMed (1966-July 2003) databases for English language, human reports were searched. Search terms included cefazolin, probenecid, cellulitis, and soft tissue infections. STUDY SELECTION AND DATA EXTRACTION: Studies that described pharmacokinetic and clinical outcomes that evaluated the use of cefazolin in conjunction with probenecid for SSTI were included. All studies were evaluated independently by both authors. For pharmacokinetic studies, the effect of probenecid on the pharmacokinetics of cefazolin was evaluated. For clinical trials, efficacy and safety endpoints were evaluated. For efficacy endpoints, definition of cure was used as defined by each trial. DATA SYNTHESIS: In all 3 pharmacokinetic studies identified, the addition of probenecid to cefazolin therapy prolonged the half-life and increased serum concentrations of cefazolin. This process allowed serum concentrations to be above the minimal inhibitory concentrations (MIC) for the most likely skin pathogens (Staphylococcus aureus, beta-hemolytic streptococci) at the end of the dosing interval. In the first of 2 clinical trials, 7 (7%) of 96 patients receiving intravenous ceftriaxone 2 g and oral probenecid 1 g daily were reported to fail therapy compared with 8 (8%) of 98 patients receiving intravenous cefazolin 2 g and oral probenecid 1 g daily. In the second clinical trial, clinical success was reported in 51 (86%) of 59 patients receiving the same doses of cefazolin and probenecid as above compared with 55 (96%) of 57 patients receiving intravenous ceftriaxone 1 g and oral placebo daily. CONCLUSIONS: Limited pharmacokinetic and clinical data suggest that intravenous cefazolin 2 g and oral probenecid 1 g daily is an effective regimen in the treatment of SSTI.

Mycophenolate mofetil for solid organ transplantation: does the evidence support the need for clinical pharmacokinetic monitoring?

The need for clinical pharmacokinetic monitoring (CPM) of the immunosuppressant mycophenolate mofetil (MMF) has been debated. Using a previously developed algorithm, the authors reviewed the evidence to support or refute the utility of CPM of MMF. First, MMF has proven efficacy for prevention of organ rejection in renal and cardiac transplant populations. In addition, the pharmacologically active form of MMF, mycophenolic acid (MPA), can be measured readily in plasma, and relationships between the incidence of rejection and MPA predose concentrations and MPA area under the curve (AUC) have been reported. A lower limit of the therapeutic range (MPA predose concentrations >1.55 microg/mL, as measured by enzyme multiplied immunoassay technique [EMIT], or MPA AUC >30 or 40 microg. h/mL, as measured by high-performance liquid chromatography [HPLC]) has been suggested to prevent rejection in renal allograft patients. Similarly, in cardiac transplant patients, decreased incidences of organ rejection have been reported in patients with MPA concentrations >2 or 3 microg/mL (using EMIT) and total AUC values >42.8 microg. h/mL (using HPLC). However, the relationship between pharmacokinetic parameters and adverse events in renal and cardiac transplant patients remains unclear. Due to the nature of antirejection therapy, the pharmacologic response of MMF is not readily assessable, and therapy is life-long. MPA pharmacokinetics exhibit large inter- and intrapatient variability and may be altered in specific patient populations due to changes in protein binding, concomitant disease states, or interactions with concurrent immunosuppressants. Therefore, on the basis of current evidence, CPM can provide more information regarding efficacy of MMF than clinical judgment alone in select patient populations. However, further randomized, prospective trials are required to clarify unresolved issues. Specifically, an upper limit of the therapeutic range, above which the risk of side effects is increased, needs to be elucidated for MMF therapy. Other future directions for research include determining a practical limited sampling strategy for MPA AUC; clarifying the relationship between free MPA concentrations, efficacy, and toxicity; and defining the pharmacodynamic relationship between activity of inosine monophosphate dehydrogenase (the enzyme inhibited by MPA) and risk of rejection or adverse effects.

Valacyclovir versus acyclovir for HSV prophylaxisin neutropenic patients.

BACKGROUND: It is common practice to administer acyclovir as prophylaxis to patients with hematologic malignancies during neutropenia; however, effective therapy requires frequent dosing, which is difficult in this setting. Valacyclovir has greater oral bioavailability and requires less frequent dosing. OBJECTIVE: To evaluate the efficacy and safety of valacyclovir compared with acyclovir. METHODS: Patients who had been treated with chemotherapy or stem-cell transplantation were randomized to receive acyclovir 400 mg orally 3 times daily (n = 51), valacyclovir 500 mg orally twice daily (n = 48), or valacyclovir 250 mg orally twice daily (n = 52) during neutropenia. RESULTS: Clinical success, defined as the absence of an active herpes simplex virus (HSV) lesion or asymptomatic viral shedding, was similar between the 3 groups (acyclovir 96%, valacyclovir 500 mg 95%, valacyclovir 250 mg 100%). The overall rates of adverse events were similar in the 3 groups. CONCLUSIONS: Prophylactic treatment with valacyclovir is an effective and safe alternative to acyclovir for the prevention of HSV reactivation in patients with hematologic malignancies.