In vitro activity of clindamycin, doxycycline, and trimethoprim/sulfamethoxazole against clinical isolates of ß-hemolytic Streptococcus spp. via BD Phoenix and broth microdilution.

We tested 85 isolates of ß-hemolytic Streptococcus spp. against trimethoprim/sulfamethoxazole (TMP/SMX), clindamycin, and doxycycline by broth microdilution (BMD) and BD Phoenix. Susceptibility rates via BMD for TMP/SMX, clindamycin, and doxycycline were 100%, 85.5%, and 56.6%, respectively. TMP/SMX is a potential monotherapy agent for ß-hemolytic Streptococcus skin and soft tissue infections.

Analysis of a beta-lactam allergy assessment protocol challenging diverse reported allergies managed by an antimicrobial stewardship program.

Objective: To assess the safety and efficacy of a novel beta-lactam allergy assessment algorithm managed by an antimicrobial stewardship program (ASP) team. Design: Retrospective analysis. Setting: One quaternary referral teaching hospital and one tertiary care teaching hospital in a large western Pennsylvania health network. Patients or participants: Patients who received a beta-lactam challenge dose under the beta-lactam allergy assessment algorithm. Interventions: A beta-lactam allergy assessment protocol was designed and implemented by an ASP team. The protocol risk stratified patients' reported allergies to identify patients appropriate for a challenge with a beta-lactam antibiotic. This retrospective analysis assessed the safety and efficacy of this protocol among patients receiving a challenge dose from November 2017 to July 2021. Results: Over a 45-month period, 119 total patients with either penicillin or cephalosporin allergies entered the protocol. Following a challenge dose, 106 (89.1%) patients were treated with a beta-lactam. Eleven patients had adverse reactions to a challenge dose, one of which required escalation of care to the intensive care unit. Of the patients with an unknown or low-risk reported allergy, 7/66 (10.6%) had an observed adverse reaction compared to 3/42 (7.1%) who had an observed reaction with a reported high-risk or anaphylactic allergy. Conclusions: Our implemented protocol was safe and effective, with over 90% of patients tolerating the challenge without incident and many going on to receive indicated beta-lactam therapy. This protocol may serve as a framework for other inpatient ASP teams to implement a low-barrier allergy assessment led by ASP teams.

Description of Hospitalizations due to the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Based on Vaccination Status.

Background: Limited descriptive data exist regarding the clinical characteristics of hospitalizations due to the severe acute respiratory syndrome coronavirus 2 Omicron variant based on vaccination status. Methods: This was a retrospective cohort study of all patients hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) between 15 January 2022 and 15 February 2022 across 9 hospitals in a large health network. Data were extracted by manual records review. Results: A total of 351 of 452 (77.7%) unvaccinated, 209 of 331 (63.1%) fully vaccinated, and 107 of 163 (65.6%) boosted patients hospitalized with a COVID-19 diagnosis were determined to be admitted specifically due to COVID-19 (P < .001). Most (85%) boosted patients admitted due to COVID-19 were at least 65 years old and/or had severe immunosuppression, compared to 72.2% of fully vaccinated and 60.7% of unvaccinated patients (P < .001). Significantly more unvaccinated patients (34.2%) required >6 L/minute of supplemental oxygen compared to fully vaccinated (24.4%) and boosted (25.2%) patients (P = .027). The age-adjusted vaccine effectiveness (VE) against hospitalization due to COVID-19 was estimated to be 81.1% and 94.1% for full vaccination and boosted status, respectively, whereas VE against mortality related to COVID-19 was estimated to be 84.7% and 94.8%, respectively. Conclusions: During the Omicron BA.1 sublineage wave, unvaccinated patients hospitalized with a COVID-19 diagnosis were more likely than vaccinated patients to be admitted specifically due to COVID-19. Despite being younger with fewer comorbidities, unvaccinated patients required higher levels of care. Vaccination with a booster provides the greatest protection against hospitalization and death from COVID-19.

Effectiveness of Dalbavancin Compared With Standard of Care for the Treatment of Osteomyelitis: A Real-world Analysis.

BACKGROUND: Preliminary data suggest that the effectiveness of dalbavancin may be similar to current standard-of-care (SoC) treatment options for osteomyelitis with an advantageous dosing schedule. METHODS: This was a retrospective, observational cohort study of adult patients diagnosed with osteomyelitis. Patients were matched 1:2 to dalbavancin (administered as 2 doses separated by 1 week) or SoC treatment for osteomyelitis according to the Charlson Comorbidity Index, site of infection, and causative pathogen. The primary objective was to determine the incidence of treatment failure after a 1-year follow-up period. Secondary objectives included hospital length of stay (LOS), infection-related 1-year readmission rates, and treatment-related adverse events. RESULTS: A total of 132 patients received dalbavancin (n = 42) or SoC (n = 90). Baseline characteristics, including rates of surgical intervention, were similar between the 2 treatment groups. Treatment failure was similar between those who received dalbavancin and SoC (21.4% vs 23.3%; P = .81). Patients who received dalbavancin had a shorter hospital LOS (5.2 days vs 7.2 days; P = .01). There was no difference in the rates of infection-related readmission between the dalbavancin and the SoC group (31% vs 31.1%; P = .99). There were numerically fewer adverse events in the dalbavancin group compared with the SoC group (21.4% vs 36.7%; P = .08). Peripherally inserted central catheter line-related complications were reported in 17.8% of patients in the SoC group. CONCLUSIONS: Dalbavancin administered as a 2-dose regimen is a safe and effective option for the treatment of osteomyelitis.

Outpatient vancomycin therapy: Acute kidney injury in individualized AUC-based goal trough ranges versus traditional trough dosing.

BACKGROUND: Recent changes to vancomycin guidelines recommend area under the curve concentration (AUC) monitoring in most patients, owing to similar effectiveness and reduced rates of acute kidney injury (AKI). OBJECTIVE: The purpose of this study was to assess the incidence of AKI in patients receiving vancomycin dosed by AUC-based goal troughs and vancomycin dosed by traditional trough goals (15-20 mcg/mL) in the outpatient setting. METHODS: Patients were included if they received vancomycin outpatient for at least 1 week. The primary objective was comparing the incidence of AKI in patients receiving vancomycin as an outpatient with trough goals derived from patient-specific AUC calculations determined as an inpatient with that of patients receiving vancomycin by traditional goal troughs. Secondary objectives included assessing the rate of treatment failure, AUC estimated trough range, and number of regimen changes required. RESULTS: There were 65 patients in the traditional trough dosing group and 53 patients in the AUC trough dosing group. The incidence of AKI was lower in the AUC trough group (5.7% vs. 23.1%; P = 0.01). There were no differences in the incidence of treatment failure. The median AUC estimated trough range was 11.4-17.1 mcg/mL. There were statistically significant less average regimen changes required in the AUC dosing group (1.13 vs. 1.64; P = 0.006). CONCLUSION: There was a statistically significant lower incidence of AKI in patients receiving vancomycin dosed by individualized AUC-based trough ranges compared with that of patients receiving traditional trough dosing. Developing a process for individualized AUC-based trough ranges can facilitate a convenient monitoring method to use the benefits of vancomycin AUC dosing as an outpatient.

Real-World Impact of the Accelerate PhenoTest BC Kit on Patients With Bloodstream Infections in the Improving Outcomes and Antimicrobial Stewardship Study: A Quasiexperimental Multicenter Study.

BACKGROUND: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality. The Improving Outcomes and Antimicrobial Stewardship study seeks to evaluate the impact of the Accelerate PhenoTest BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs. METHODS: This multicenter, quasiexperimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX, to evaluate the impact this technology has on patients with BSIs. Laboratory and clinical data from hospitalized patients with BSIs (excluding contaminants) were compared between 2 arms, 1 that underwent testing on AXDX (post-AXDX) and 1 that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) and 30-day mortality. RESULTS: A total of 854 patients with BSIs (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared with the pre-AXDX arm (40.9 hours; P<.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 vs 13.9 hours; P<.0001) and first antimicrobial deescalation (36.0 vs 27.2 hours; P=.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX vs 6.0% post-AXDX), length of stay (7.0 pre-AXDX vs 6.5 days post-AXDX), and adverse drug events were not significantly different between arms. Length of stay was shorter in the post-AXDX arm (5.4 vs 6.4 days; P=.03) among patients with gram-negative bacteremia. CONCLUSIONS: For BSIs, use of AXDX was associated with significant decreases in TTOT, first antimicrobial modification, and time to antimicrobial deescalation.

Ceftolozane/tazobactam for refractory P. aeruginosa endocarditis: A case report and pharmacokinetic analysis.

We describe a case of a 48 years old male with left sided endocarditis and septic emboli secondary to a Pseudomonas aeruginosa strain that developed resistance to other ß-lactam antibiotics during therapy resulting in prolonged bacteremia. Blood cultures sterilized within 1 day of initiating ceftolozane/tazobactam 3 g every 8 hours in combination with ciprofloxacin. Steady state free ceftolozane plasma Cmax and Cmin concentrations were calculated to be 122.2µg/mL and 24.3µg/mL, respectively. The multidrug-resistant strain harbored chromosomal ß-lactamases OXA-486 and PDC-3, mutations in ampD and dacB predicted to lead to ampC over-expression, and mutations in OprD predicted to decrease outer membrane permeability. Following completion of a 42 day course and aortic valve replacement, the patient was deemed clinically cured without recurrence of infection at follow up 2 years later. To our knowledge, this is the first reported case to measure ceftolozane concentrations during the treatment of endocarditis which supports dose optimization approaches of severe endovascular disease due to multidrug resistant pathogens.

Impact of an Antimicrobial Stewardship Program-bundled initiative utilizing Accelerate Pheno™ system in the management of patients with aerobic Gram-negative bacilli bacteremia.

PURPOSE: Gram-negative bacteria (GNB) are a leading cause of bloodstream infections (BSI) and management is complicated by antibiotic resistance. The Accelerate Pheno™ system (ACC) can provide rapid organism identification and antimicrobial susceptibility testing (AST). METHODS: A retrospective, pre-intervention/post-intervention study was conducted to compare management of non-critically ill patients with GNB BSI before and after implementation of a bundled initiative. This bundled initiative included dissemination of a clinical decision algorithm, ACC testing on all GNB isolated from blood cultures, real-time communication of results to the Antimicrobial Stewardship Program (ASP), and prospective audit with feedback by the ASP. The pre-intervention period was January 2018 through December 2018, and the post-intervention period was May 2019 through February 2020. RESULTS: Seventy-seven and 129 patients were included in the pre-intervention and post-intervention cohorts, respectively. When compared with the pre-intervention group, the time from Gram stain to AST decreased from 46.1 to 6.9 h (p < 0.001), and the time to definitive therapy (TTDT) improved from 32.6 to 10.5 h (p < 0.001). Implementation led to shorter median total duration of antibiotic therapy (14.2 vs 9.5 days; p < 0.001) and mean hospital length of stay (7.9 vs 5.3 days; p = 0.047) without an increase in 30-day readmissions (22.1% vs 14%; p = 0.13). CONCLUSION: Implementation of an ASP-bundled approach incorporating the ACC aimed at optimizing antibiotic therapy in the management GNB BSI in non-critically ill patients led to reduced TTDT, shorter duration of antibiotic therapy, and shorter hospital length of stay without adversely affecting readmission rates.

Impact of a cefepime shortage on dosing regimens and outcomes in hospitalized adults with febrile neutropenia.

BACKGROUND: Drug shortages may negatively impact outcomes in hospitalized patients. A cefepime dosing regimen of 1 gram every 6 hours (1 g q6h) has shown to provide similar exposures above target minimum inhibitory concentrations compared to the regimen of 2 g q8h approved by the United States Food and Drug Administration (FDA) for febrile neutropenia. Our objective was to determine if the dosing regimen of 1 g q6h amidst a cefepime shortage is an appropriate alternative for the treatment of febrile neutropenia. METHODS: A retrospective chart review of hospitalized patients who received cefepime for febrile neutropenia over a two-year period was performed. Patients were grouped based on cefepime dosing strategy: 2 g q8h vs. 1 g q6h. The primary objective was to compare time to defervescence after cefepime initiation. Secondary objectives included all-cause 30-day mortality, duration of antibiotic therapy, and inpatient length of stay. RESULTS: Seventy-five patients in each arm were included. There were no differences in baseline age or severity of illness between groups. There was no difference in the primary objective as median time to defervescence was similar between the 2 g q8h and 1 g q6h groups (69.0 vs. 65.3 h: p= 0.67). Additionally, no differences were found in the secondary objectives of all-cause 30-day mortality (10.7% vs. 9.3%: p = 0.79), duration of therapy (80.8 vs. 88.0 h: p = 0.34), or length of stay (9 vs. 7 days: p = 0.50). CONCLUSIONS: Our study identified no differences in clinical outcomes with cefepime 1 g q6h compared to the traditional FDA-approved 2 g q8h regimen for the treatment of febrile neutropenia.

Therapeutic Options for the Treatment of Coronavirus Disease (COVID-19).

Coronavirus disease 2019 (COVID-19) has resulted in an unprecedented pandemic, challenging practitioners to identify safe and effective therapeutic options in a limited amount of time. The rapid genomic sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provided a significant number of therapeutic targets. Repurposed and investigational agents are being studied for use in COVID-19. Although knowledge is rapidly expanding in regard to COVID-19 and there is promise with a few agents, there are no definitely proven effective therapies at this time. Supportive care remains the mainstay of therapy while ongoing clinical trials are being conducted.

Impact of a Multiplex Polymerase Chain Reaction Assay on the Clinical Management of Adults Undergoing a Lumbar Puncture for Suspected Community-Onset Central Nervous System Infections.

Patients admitted from the community with a suspected central nervous system (CNS) infection require prompt diagnostic evaluation and correct antimicrobial treatment. A retrospective, multicenter, pre/post intervention study was performed to evaluate the impact that the BioFire® FilmArray® meningitis/encephalitis (ME) panel run in-house had on the clinical management of adult patients admitted from the community with a lumbar puncture (LP) performed for a suspected CNS infection. The primary outcome was the effect that this intervention had on herpes simplex virus (HSV) polymerase chain reaction (PCR) turnaround time (TAT). Secondary outcomes included the effect that this intervention had on antiviral days of therapy (DOT), total antimicrobial DOT, and hospital length of stay (LOS). A total of 81 and 79 patients were included in the pre-intervention and post-intervention cohorts, respectively. The median HSV PCR TAT was significantly longer in the pre-intervention group (85 vs. 4.1 h, p < 0.001). Total antiviral DOT was significantly greater in the pre-intervention group (3 vs. 1, p < 0.001), as was total antimicrobial DOT (7 vs. 5, p < 0.001). Pre-intervention hospital LOS was also significantly longer (6.6 vs. 4.4 days, p = 0.02). Implementing the ME panel in-house for adults undergoing an LP for a suspected community-onset CNS infection significantly reduced the HSV PCR TAT, antiviral DOT, total antimicrobial DOT, and hospital LOS.

Risk Factors for Unnecessary Antibiotic Prescribing for Acute Respiratory Tract Infections in Primary Care.

OBJECTIVE: To determine independent risk factors for inappropriate antibiotic prescribing for acute respiratory tract infections (ARIs) in internal medicine (IM) residency-based primary care offices. PATIENTS AND METHODS: A retrospective study was conducted to measure antibiotic prescribing rates, and multivariable analysis was utilized to identify predictors of inappropriate prescribing among patients presenting to IM residency-based primary care office practices. Patients with an office visit at either of 2 IM residency-based primary care office practices from January 1, 2016, through December 31, 2016, with a primary encounter diagnosis of ARI were included. RESULTS: During the study period, 911 unique patient encounters were included with 518 for conditions for which antibiotics were considered always inappropriate. Antibiotics were not indicated in 85.8% (782 of 911) of encounters. However, antibiotics were prescribed in 28.4% (222 of 782) of these encounters. Inappropriate antibiotic prescribing occurred in 111 of 518 (21.4%) encounters for conditions for which antibiotics are always inappropriate. Using multivariable logistic regression analysis to assess for independent risk factors when adjusted for other potential risk factors for office visits at which antibiotics were not indicated, IM resident-associated visits (odds ratio, 0.25; 95% CI, 0.18-0.36) was the only variable independently associated with lower risk of inappropriate antibiotic prescribing. CONCLUSION: For ARI visits at which antibiotics were not indicated, IM resident comanagement was associated with lower rates of inappropriate prescribing.

Acute Exacerbations of Chronic Obstructive Pulmonary Disease With a Low Procalcitonin Concentration: Impact of Antibiotic Therapy.

BACKGROUND: Patients admitted with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often are prescribed antibiotics. Studies have shown that the use of procalcitonin (PCT) to guide the decision to initiate antibiotic therapy in AECOPD has resulted in less antibiotic use and similar outcomes compared with standard of care. We evaluated patients with AECOPD and low PCT concentrations to determine whether antibiotic therapy was associated with improved outcomes. METHODS: We retrospectively evaluated adult patients admitted with AECOPD who had a peak PCT concentration <0.25 µg/mL. Patients were evaluated based on their antibiotic exposure: ≤24 hours vs >24 hours. We also evaluated outcomes based upon the duration of azithromycin therapy: ≤24 hours vs >24 hours. The primary outcome was all-cause 30-day readmissions. Secondary outcomes included length of stay (LOS) and COPD-related 30-day readmissions. RESULTS: One hundred sixty-one and 195 patients received ≤24 hours vs >24 hours of antibiotic therapy, respectively. The cohort with ≤24 hours of antibiotics had a shorter LOS (2.8 vs 3.7 days; P = .01). There were no differences in all-cause 30-day readmissions (15.5% vs 17.4%; P = .63) or COPD-related 30-day readmissions (11.2% vs 12.3%; P = .74). Additionally, patients receiving ≤24 hours of azithromycin had a shorter LOS (3.0 vs 3.8 days; P = .002) and there were no differences in all-cause 30-day readmissions (16.2% vs 17.1%; P = .82) or COPD-related 30-day readmissions (11.9% vs 11.6%; P = .94). CONCLUSIONS: For adult patients hospitalized with nonsevere AECOPD and low PCT concentrations, antibiotic therapy beyond 24 hours did not improve outcomes.

Role of Technology in Antimicrobial Stewardship.

Because of the increasing plague of antimicrobial resistance and antibiotic misuse, antimicrobial stewardship programs (ASPs) are now a mandatory entity in all US hospitals. ASPs can use technological advances, such as the electronic medical record and clinical decision support systems, to impact a larger patient population with more efficiency. Additionally, through the use of mobile applications and social media, ASPs can highlight and propagate educational information regarding antimicrobial utilization to patients and providers in a widespread and timely manner. In this article, the authors describe how technology can play an important role in antimicrobial stewardship.

Impact of an antimicrobial stewardship program on healthcare-associated Clostridium difficile rates at a community-based teaching hospital.

We conducted a pre-intervention/post-intervention study to assess the rate of healthcare-associated Clostridium difficile infections (HA-CDI) before and after the implementation of an antimicrobial stewardship program (ASP). Upon implementation of our ASP, the usage of targeted antimicrobials, including ceftriaxone, clindamycin, fluoroquinolones and carbapenem antibiotics, were significantly reduced. There was also a significant reduction in HA-CDI/1000 patient-days following ASP implementation (0.84 vs. 0.28; P = 0.035).

Impact of Procalcitonin Guidance on Management of Adults Hospitalized with Chronic Obstructive Pulmonary Disease Exacerbations.

BACKGROUND: Antibiotics are often prescribed for hospitalized patients with chronic obstructive pulmonary disease (COPD) exacerbations. The use of procalcitonin (PCT) in the management of pneumonia has safely reduced antibiotic durations, but limited data on the impact of PCT guidance on the management of COPD exacerbations remain. OBJECTIVE: To determine the impact of PCT guidance on antibiotic utilization for hospitalized adults with exacerbations of COPD. DESIGN: A retrospective, pre-/post-intervention cohort study was conducted to compare the management of patients admitted with COPD exacerbations before and after implementation of PCT guidance. The pre-intervention period was March 1, 2014, through October 31, 2014, and the post-intervention period was March 1, 2015, through October 31, 2015. PARTICIPANTS: All patients with hospital admissions during the pre- and post-intervention period with COPD exacerbations were included. Patients with concomitant pneumonia were excluded. INTERVENTION: Availability of PCT laboratory values in tandem with a PCT guidance algorithm and education. MAIN MEASURES: The primary outcome was duration of antibiotic therapy for COPD. Secondary objectives included duration of inpatient length of stay (LOS) and 30-day readmission rates. KEY RESULTS: There were a total of 166 and 139 patients in the pre- and post-intervention cohorts, respectively. There were no differences in mean age (66.2 vs. 65.9; P = 0.82) or use of home oxygenation (34% vs. 39%; P = 0.42) in the pre- and post-intervention groups, respectively. PCT guidance was associated with a reduced number of antibiotic days (5.3 vs. 3.0; p = 0.01) and inpatient LOS (4.1 days vs. 2.9 days; P = 0.01). Respiratory-related 30-day readmission rates were unaffected (10.8% vs. 9.4%; P = 0.25). CONCLUSIONS: Utilizing PCT guidance in the management of COPD exacerbations was associated with a decreased total duration of antibiotic therapy and hospital LOS without negatively impacting hospital readmissions.

Impact of Procalcitonin Guidance with an Educational Program on Management of Adults Hospitalized with Pneumonia.

BACKGROUND: Community-acquired pneumonia and healthcare-associated pneumonia are often treated with prolonged antibiotic therapy. Procalcitonin (PCT) has effectively and safely reduced antibiotic use for pneumonia in controlled studies. However, limited data exist regarding PCT guidance in real-world settings for management of pneumonia. METHODS: A retrospective, preintervention/postintervention study was conducted to compare management for patients admitted with pneumonia before and after implementation of PCT guidance at 2 teaching hospitals in Pittsburgh, Pennsylvania. The preintervention period was March 1, 2014 through October 31, 2014, and the postintervention period was March, 1 2015 through October 31, 2015. RESULTS: A total of 152 and 232 patients were included in the preintervention and postintervention cohorts, respectively. When compared with the preintervention group, mean duration of therapy decreased (9.9 vs 6.0 days; P < .001). More patients received an appropriate duration of 7 days or less (26.9% vs 66.4%; P < .001). Additionally, mean hospital length of stay decreased in the postintervention group (4.9 vs 3.5 days; P = .006). Pneumonia-related 30-day readmission rates (7.2% vs 4.3%; P = .26) were unaffected. In the postintervention group, patients with PCT levels <0.25 µg/L received shorter mean duration of therapy compared with patients with levels >0.25 µg/L (4.6 vs 8.0 days; P < .001), as well as reduced hospital length of stay (3.2 vs 3.9 days; P = .02). CONCLUSIONS: In this real-world study, PCT guidance led to shorter durations of total antibiotic therapy and abridged inpatient length of stay without affecting hospital readmissions.