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.

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.

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.

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.

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.

Accurate Identification of Infection Source in Burn Trauma Patients With Central Line Infection to Determine Appropriate Treatment Option As Well As Proper Public Reporting.

With the advent of the Patient Safety Movement in the late 1990s and the CMS (Centers for Medicare & Medicaid Services) nonreimbursement program for never events, there has been much focus on the prevention and accurate identification of health care-associated infections such as central line-associated bloodstream infections (CLABSIs). There has certainly been a national effort to decrease the occurrence of these infections. With the implementation of patient safety initiatives such as the central line prevention bundle, there has been a considerable reduction in the number of CLABSIs except for patients with burn trauma. Because of the compromised nature of these patients, the number of CLABSIs has not decreased similarly to other types of patients. In addition, these patients may have a secondary infection that was not accurately or timely identified. With CLABSIs, proper identification of primary and secondary infections is very important, particularly when identifying treatment options and ensuring accurate public reporting of health care-associated infection information.

Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections.

We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P = 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.

Appropriateness of antibiotic management of uncomplicated skin and soft tissue infections in hospitalized adult patients.

BACKGROUND: Skin and soft tissue infections (SSTIs) are a leading cause for hospitalizations in the United States. Few studies have addressed the appropriateness of antibiotic therapy in the management of SSTIs without complicating factors. We aimed to determine the appropriateness of antibiotic treatment duration for hospitalized adult patients with uncomplicated SSTIs. METHODS: This was a retrospective analysis performed at two academic medical centers in Pittsburgh, Pennsylvania on patients aged 18 years and older with primary ICD-9 code for SSTIs admitted August 1st, 2014-March 31st, 2015. The primary outcome was the appropriateness of antibiotic treatment duration for uncomplicated SSTIs. Secondary objectives included the appropriateness of antibiotic agent spectrum, duration of inpatient length of stay (LOS), utilization of blood cultures and advanced imaging modalities, and re-hospitalization for SSTI within 30 days of discharge from the index admission. RESULTS: A total of 163 episodes were included in the cohort. The mean duration of total antibiotic therapy was 12.6 days. Appropriate duration was defined as receipt of total antibiotic duration of less than 10 days and occurred in 20.2% of patients. Twenty eight percent of patients received antibiotics for greater than 14 days. Seventy three (44.8%) patients received greater than 24 h of inappropriate extended spectrum gram-negative coverage; 65 (39.9%) received anaerobic coverage. CONCLUSIONS: In the majority of patients, treatment duration was excessive. Inappropriate broad spectrum antibiotic selection was utilized with regularity for SSTIs without complicating factors. The management of uncomplicated SSTIs represents a significant opportunity for antimicrobial stewardship.

Spontaneous fungal peritonitis: a devastating complication of cirrhosis.

Spontaneous bacterial peritonitis is a well-known complication of cirrhosis; however, spontaneous fungal peritonitis (SFP) is less well-recognised and described. Our objective was to determine the clinical characteristics, treatment outcomes and factors associated with death among patients with SFP. We performed a retrospective cohort study using the primary outcome of all-cause mortality at 28 days. Twenty-five patients were included; Candida species were the causative pathogen in all cases. At the onset of SFP, patients were critically ill, median APACHE II and MELD scores were 22 and 30.3, respectively. The 28-day mortality rate was 56%; six patients died prior to culture positivity. Among the remaining patients, there were no differences in rates of death by treatment regimen (P = 0.55). APACHE II score at the onset of SFP was an independent predictor of death (OR = 1.46, 95% CI = 1.02-2.08, P = 0.04). In conclusion, SFP develops among critically ill patients with cirrhosis and is associated with high rates of death. Directed antifungal therapy did not improve patient outcomes. Future studies assessing the benefit of early or pre-emptive antifungal therapy are warranted.

KPC-producing Klebsiella pneumoniae strains that harbor AAC(6')-Ib exhibit intermediate resistance to amikacin.

The aminoglycoside-modifying enzyme AAC(6')-Ib is common among carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains. We investigated amikacin (AMK) activity against 20 AAC(6')-Ib-producing CR-Kp strains. MICs clustered at 16 to 32 µg/ml. By the time-kill study, AMK (1× and 4× the MIC) was bactericidal against 30% and 85% of the strains, respectively. At achievable human serum concentrations, however, the majority of strains showed regrowth, suggesting that AAC(6')-Ib confers intermediate AMK resistance. AMK and trimethoprim-sulfamethoxazole (TMP-SMX) were synergistic against 90% of the strains, indicating that the combination may overcome resistance.

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.

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.

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.

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.