Treatment Considerations for CNS Infections Caused by Vancomycin-Resistant Enterococcus faecium: A Focused Review of Linezolid and Daptomycin.

OBJECTIVE: To review the current literature describing pharmacology, pharmacokinetics/pharmacodynamics (PK/PD), efficacy, and safety of linezolid and daptomycin for the treatment of central nervous system (CNS) infections caused by vancomycin-resistant Enterococcus (VRE) faecium. DATA SOURCES: A literature search of PubMed/MEDLINE databases was conducted (from 1950 to April 2020) utilizing the following key terms: vancomycin-resistant Enterococcus, VRE, meningitis, ventriculitis, CNS infection, daptomycin, and linezolid. STUDY SELECTION AND DATA EXTRACTION: All relevant studies and case reports describing the treatment of VRE faecium from the CNS with linezolid or daptomycin were included. DATA SYNTHESIS: A total of 17 reports describing 22 cases were identified. There were 15 of 19 cases involving linezolid that reported clinical cure, of which 53.3% were monotherapy. Only 5 of 9 cases involving intravenous (IV) daptomycin resulted in cure; all 4 cases reporting daptomycin administration via the intrathecal or intraventricular route achieved clearance from the cerebrospinal fluid (CSF). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The preferred treatment option for VRE faecium infections involving the CNS remains unclear. Supporting evidence through observational case reports have described varying outcomes with linezolid and daptomycin. This review compares reported outcomes between the 2 agents and provides a thorough discussion on drug- and patient-specific variables to consider. CONCLUSIONS: Linezolid monotherapy appears to be safe and effective for the treatment of susceptible-VRE faecium CNS infections, with consideration of therapeutic drug monitoring in special populations and with prolonged treatment duration. Daptomycin is an effective treatment option via intrathecal or intraventricular administration when neurosurgical access is available. The role of IV daptomycin remains inconclusive.

Prevalence of a Cefazolin Inoculum Effect Associated with blaZ Gene Types among Methicillin-Susceptible Staphylococcus aureus Isolates from Four Major Medical Centers in Chicago.

The efficacy of cefazolin with high-inoculum methicillin-susceptible Staphylococcus aureus (MSSA) infections remains in question due to therapeutic failure inferred as being due to an inoculum effect (InE). This study investigated the local prevalence of a cefazolin InE (CInE) and its association with staphylococcal blaZ gene types among MSSA isolates in the Chicago area. Four medical centers in Chicago, IL, contributed MSSA isolates. Cefazolin MICs (C-MIC) were determined at 24 h by the broth microdilution method using a standard inoculum (SI; 5 × 105 CFU/ml) and a high inoculum (HI; 5 × 107 CFU/ml). The CInE was defined as (i) a ≥4-fold increase in C-MIC between SI and HI and/or (ii) a pronounced CInE, i.e., a nonsusceptible C-MIC of ≥16 µg/ml at HI. PCR was used to amplify the blaZ gene, followed by agarose gel electrophoresis and sequencing to determine the gene type. Approximately 269 MSSA isolates were included. All but one isolate were susceptible to cefazolin at SI, and 97% remained susceptible at HI. A total of 196 isolates (73%) were blaZ positive, with the blaZ types led by gene type C (40%). CInE was seen in 45 blaZ-positive isolates (23%), with 44 (22%) presenting a ≥4-fold increase in C-MIC (SI to HI) and 5 (3%) a pronounced CInE. Four of the five met both definitions of CInE, two of which expressed the type A gene. The prevalence of a pronounced CInE associated with the type A blaZ gene from MSSA isolates in Chicago is low. Our predilection for cefazolin use, even early in the management of hospitalized MSSA infections, is tenable.

Treatment outcomes with cefazolin versus oxacillin for deep-seated methicillin-susceptible Staphylococcus aureus bloodstream infections.

Clinical preference for a semisynthetic penicillin (oxacillin or nafcillin) over cefazolin for deep-seated methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI) perseveres despite limited data to support this approach. A retrospective cohort study of patients treated for MSSA BSI with either oxacillin or cefazolin was performed across two medical centers in Chicago, IL. The outcome measures included documented in-hospital treatment failure, all-cause in-hospital mortality, duration of MSSA BSI, and incidence of documented adverse events. Of 161 patients with MSSA BSI, 103 (64%) received cefazolin, and 58 (36%) received oxacillin. The identified sources of BSI were central line (37.9%), osteoarticular (18%), and skin and soft tissue (17.4%). Patients with endocarditis (29/52 [44.2%]) and other deep-seated infections (23/52 [55.8%]) were classified under the subset of deep-seated infections (52/161 [32.3%]). Multivariate models found deep-seated infection (adjusted odds ratio [aOR], 4.52; 95% confidence interval [CI], 1.23 to 16.6; P = 0.023), metastatic disease (aOR, 4.21; 95% CI, 1.13 to 15.7; P = 0.033), and intensive care unit (ICU) onset of infection (aOR, 4.80; 95% CI, 1.26 to 18.4; P = 0.022) to be independent risk factors for in-hospital treatment failure. Treatment group was not an independent predictor of failure (aOR, 3.76; 95% CI, 0.98 to 14.4; P = 0.053). The rates of treatment failure were similar among cefazolin-treated (5/32 [15.6%]) and oxacillin-treated (4/20 [20.0%]) patients (P = 0.72) in the subset of deep-seated infections. Mortality was observed in 1 (1%) and 3 (5.2%) cases of cefazolin- and oxacillin-treated patients, respectively (P = 0.13). Cefazolin was not associated with higher rates of treatment failure and appears to be an effective alternative to oxacillin for treatment of deep-seated MSSA BSI.

A Multicenter Retrospective Study Evaluating Intravenous to Oral Antibiotic Stepdown for Uncomplicated Streptococcal Bacteremia.

Background: The purpose of this study was to compare the efficacy and safety of intravenous (IV) versus oral (PO) stepdown therapy for uncomplicated streptococcal bacteremia. Methods: This multicenter, retrospective study included adult patients with uncomplicated streptococcal bacteremia between 1 July 2019 and 1 July 2022. Patients who received IV therapy for the full treatment course were compared to patients who transitioned to PO therapy after initial IV therapy. The primary outcome was clinical success, defined as absence of infection recurrence, infection-related readmission, and infection-related mortality at 90 days. Secondary outcomes included microbiological success, length of stay (LOS), and IV line-associated complications. Results: Of 238 patients included, 47.1% received PO stepdown therapy. Clinical success occurred in 94.4% and 94.6% in the IV only and PO stepdown groups, respectively (P = .946). Patients who transitioned to PO therapy received a median duration of IV therapy of 3.9 days (interquartile range, 2.9-7.3 days). Line complications were more frequent in the IV only group, primarily driven by catheter-related infections (7.2% vs 0%, P = .002). LOS was significantly shorter in the PO stepdown group (5.5 vs 9.2 days, P < .001). Conclusions: Patients transitioned to PO antibiotics for uncomplicated streptococcal bacteremia had similar rates of clinical success compared to patients who received only IV therapy. With consideration of infectious source, severity of illness, and comorbidities, PO stepdown following initial IV antibiotics for uncomplicated streptococcal bacteremia in select patients is a reasonable approach that may result in decreased LOS and line-related complications.

Impact of COVID-19 pandemic on training of pharmacy residents and fellows: Results from a national survey of postgraduate pharmacy trainees.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has impacted the activities of healthcare workers, including postgraduate pharmacy trainees. Quality training experiences must be maintained to produce competent pharmacy practitioners and maintain program standards. METHODS: A cross-sectional survey of postgraduate pharmacy trainees in the United States was conducted to evaluate training experience changes and assess perceived impacts on residents and fellows following the COVID-19 pandemic's onset. RESULTS: From June 4 through June 22, 2020, 511 pharmacy trainees in 46 states completed the survey. Participants' median age was 26 (interquartile range [IQR], 25-28) years, with included responses from postgraduate year 1 residents (54% of sample), postgraduate year 2 residents (40%), and postgraduate fellows (6%). Compared to experiences prior to the onset of the COVID-19 pandemic, fewer trainees conducted direct patient care (38.5% vs 91.4%, P < 0.001), more worked from home (31.7% vs 1.6%, P < 0.001), and less time was spent with preceptors per day (2 [IQR, 2-6] hours vs 4 [IQR, 1-4] hours, P < 0.001). Sixty-five percent of respondents reported experiencing changes in their training program, 39% reported being asked to work in areas outside of their routine training experience, and 89% stated their training shifted to focus on COVID-19 to some degree. Most respondents perceived either major (9.6%) or minor (52.0%) worsening in quality of experience, with major and minor improvement in quality of experience reported by 5.5% and 8.4% of respondents, respectively. CONCLUSION: Pharmacy resident/fellow experiences were perceived to have been extensively impacted by the COVID-19 pandemic in varying ways. Our findings describe shifts in postgraduate training and may aid in the development of best practices for optimizing trainee experiences in future crises.

Cefazolin vs. anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections in acutely ill adult patients: Results of a systematic review and meta-analysis.

A systematic literature review and meta-analysis was conducted to evaluate the comparative efficacy and tolerability of cefazolin vs. anti-staphylococcal penicillins (ASPs) for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). Utilizing published regression models, included studies were stratified into subgroups of high and low pre-probability of mortality. Cefazolin was associated with significantly lower rates of treatment failure (odds ratio [OR]: 0.70; 95% confidence interval [CI]: 0.61-0.82; P<0.001; I2 = 14%) and crude, all-cause mortality (OR: 0.69; 95% CI: 0.59-0.81; P<0.001; I2 = 18%) compared with ASP therapy. Overall risk of treatment-related adverse drug reactions was numerically lower with cefazolin (OR: 0.39; 95% CI: 0.15-1.00; P = 0.05). Subgroup sensitivity analyses of studies conducted in less severely ill patients were similar to the combined analysis. The role of cefazolin in the most severely ill patients with MSSA BSI should be prospectively evaluated.

Successful Treatment of Cerebral Toxoplasmosis Using Pyrimethamine Oral Solution Compounded From Inexpensive Bulk Powder.

A price increase of pyrimethamine tablets in the United States has made the life-saving drug difficult to acquire for hospitalized patients who need it most. We report the successful use of a pyrimethamine oral suspension compounded from an economical bulk powder in a patient with acute toxoplasmic encephalitis.

Implementation of a cefazolin-based stewardship pathway for methicillin-susceptible Staphylococcus aureus bloodstream infections paired with infectious diseases consultation.

Methicillin-susceptible Staphylococcus aureus (MSSA) infections have been successfully treated both with cefazolin and antistaphylococcal penicillins; cefazolin appears effective in MSSA bloodstream infections (BSIs). Thus, our antimicrobial stewardship programme (ASP) implemented a clinical pathway supporting cefazolin use in MSSA-BSIs and restricting oxacillin use to infectious diseases (ID) consultation due to cefazolin's lower cost and more convenient dosing. This before and after quasi-experimental study was conducted to describe the impact on outcomes and process of care measures associated with implementing this pathway among patients with MSSA-BSI. Definitive treatment with cefazolin increased over the study period from 17.3% to 69.8% post-implementation. Clinical failure (5.8% vs. 2.3%; P = 0.62) and in-hospital mortality (3.8% vs. 0%; P = 0.50) were rare pre- and post-implementation. Median hospital length of stay among survivors was similar between pre- and post-implementation periods (P = 0.31). Duration of bacteraemia [median (IQR) 3 (2-4) days vs. 2 (2-3) days; P = 0.002] and rates of re-infection after culture clearance (9.6% vs. 0%; P = 0.06) were reduced post-implementation. Frequency of source control (P = 0.71) and time to source control (P = 0.52) were similar between study periods. Significant increases in ID consultations (33.3% [3/9] vs. 73.3% [22/30]; P = 0.047) and median (IQR) 24-h daily doses [2 (1-3) g vs. 6 (3-6) g; P < 0.01] were seen for patients treated with cefazolin post-implementation. ASPs may find implementation of a similar pathway to be an effective means of improving the care of patients infected with MSSA.

Improving time to optimal Staphylococcus aureus treatment using a penicillin-binding protein 2a assay.

The penicillin-binding protein 2a (PBP2a) assay is a quick, accurate and inexpensive test for determining methicillin susceptibility in Staphylococcus aureus. A pre-post-study design was conducted using a PBP2a assay with and without the impact of an antimicrobial stewardship intervention to improve time to optimal therapy for methicillin-susceptible and methicillin-resistant S. aureus isolates. Our results demonstrate significantly improved time to optimal therapy and support the use of a PBP2a assay as part of an programme for all healthcare facilities, especially those with limited resources.

A Student-Led Health Education Initiative Addressing Health Disparities in a Chinatown Community.

Together with community advocates, professional student organizations can help improve access to health care and sustain services to address the health disparities of a community in need. This paper examines the health concerns of an underserved Chinese community and introduces a student-led health education initiative that fosters service learning and student leadership. The initiative was recognized by the American Association of Colleges of Pharmacy (AACP) and received the 2012-2013 Student Community Engaged Service Award.