Risk of Infective Endocarditis in Streptococcus mitis Bloodstream Infections Among Patients with Neutropenia from Hematologic Malignancies.

Streptococcus mitis commonly causes bloodstream infections (BSIs) in neutropenic patients but infrequently results in infective endocarditis (IE) in this population. Among 210 patients with neutropenia and S. mitis BSI, 55% underwent cardiac imaging. None were diagnosed with S. mitis IE; 3 had recurrent S. mitis BSI within 12 weeks.

Evaluating Clinical Sequelae of the Carbapenem-Valproate Interaction: A Retrospective Analysis.

Background: Previous studies identified a rapid decrease in valproate serum concentrations when coadministered with a carbapenem; however, the specific consequences and subsequent therapy adjustments are not well described. We aimed to investigate the clinical and therapeutic implications of the carbapenem-valproate drug-drug interaction. Methods: This retrospective analysis included data from 2 large academic medical centers during January 2017 to June 2022. The primary outcome was incidence of seizures or behavioral events stratified by valproate indication. All adult patient encounters with concomitant administration of any carbapenem antimicrobial and valproate were included. Patients without prolonged exposure to valproate prior to hospitalization, without valproate levels pre- and post-carbapenem administration, with an admitting diagnosis of seizure, with exposure to other agents that decrease valproate concentrations, or who had a seizure during the hospitalization prior to carbapenem exposure were excluded. Results: Two hundred fifty-eight episodes of concomitant use among 78 unique adult patients were included. Valproate was used for seizure control in 41 patients (52.6%) and for mood-related disorders in 37 (47.4%). In those prescribed valproate for its antiepileptic properties, seizures occurred following carbapenem administration in 46.3% of encounters. In those taking valproate for mood-related disorders, 50.8% met the primary endpoint of behavioral disturbance. Conclusions: Our study demonstrates significant clinical implications of the carbapenem-valproate interaction. Clinicians should be aware of this interaction and consider alternative antimicrobial and/or antiepileptic agents whenever possible. Adding or increasing doses of antiepileptic agents and/or consultation with a neurologist prior to concomitant use should be considered when this combination cannot be avoided.

A Case Series of Rifabutin Use in Staphylococcal Prosthetic Infections.

This case series describes seven patients who received rifabutin in place of rifampin combined with conventional antimicrobial therapy for treatment of hardware-associated staphylococcal infections. Infection recurrence, defined as need for unplanned surgical intervention within the evaluable follow up period after starting rifabutin, occurred in two patients. Two patients experienced possible treatment-associated adverse effects. Findings support future work to examine rifabutin use, when rifampin is not suitable, for adjunctive treatment of staphylococcal hardware infections. IMPORTANCE This work evaluates real-world data and clinical outcomes when rifabutin is used in place of rifampin for adjunctive management of staphylococcal hardware-associated infections. This is the second case study looking at this specific use of rifabutin, signifying the current lack of clinical data in this area. Assessing use of rifabutin in this capacity is clinically important given its lower propensity for drug interactions compared to rifampin.

Baseline procalcitonin as a predictor of bacterial infection and clinical outcomes in COVID-19: A case-control study.

PURPOSE: Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients with COVID-19 can assist with patient management. The aim of this study is to evaluate whether procalcitonin (PCT) can predict clinical outcome and bacterial superinfection in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). METHODS: Adult patients diagnosed with SARS-CoV-2 by nasopharyngeal PCR who were admitted to a tertiary care center in Boston, MA with SARS-CoV-2 infection between March 17 and April 30, 2020 with a baseline PCT value were studied. Patients who were presumed positive for SARS-CoV-2, who lacked PCT levels, or who had a positive urinalysis with negative cultures were excluded. Demographics, clinical and laboratory data were extracted from the electronic medical records. RESULTS: 324 patient charts were reviewed and grouped by clinical and microbiologic outcomes by day 28. Baseline PCT levels were significantly higher for patients who were treated for true bacteremia (p = 0.0005) and bacterial pneumonia (p = 0.00077) compared with the non-bacterial infection group. Baseline PCT positively correlated with the NIAID ordinal scale and survival over time. When compared to other inflammatory biomarkers, PCT showed superiority in predicting bacteremia. CONCLUSIONS: Baseline PCT levels are associated with outcome and bacterial superinfection in patients hospitalized with SARS-CoV-2.

Multisociety statement on coronavirus disease 2019 (COVID-19) vaccination as a condition of employment for healthcare personnel.

This consensus statement by the Society for Healthcare Epidemiology of America (SHEA) and the Society for Post-Acute and Long-Term Care Medicine (AMDA), the Association for Professionals in Epidemiology and Infection Control (APIC), the HIV Medicine Association (HIVMA), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) recommends that coronavirus disease 2019 (COVID-19) vaccination should be a condition of employment for all healthcare personnel in facilities in the United States. Exemptions from this policy apply to those with medical contraindications to all COVID-19 vaccines available in the United States and other exemptions as specified by federal or state law. The consensus statement also supports COVID-19 vaccination of nonemployees functioning at a healthcare facility (eg, students, contract workers, volunteers, etc).

Remdesivir use and outcomes during the FDA COVID-19 emergency use authorization period.

BACKGROUND: Remdesivir (RDV) was approved for treatment of coronavirus disease 2019 (COVID-19), in May 2020 under US Food and Drug Administration emergency use authorization (EUA). Clinical outcomes related to RDV use in hospitalized patients during the EUA period are not well described. METHODS: We conducted a retrospective study of patients who received RDV under EUA. The primary outcome was clinical recovery by day 14 as determined by an eight-category ordinal scale. Secondary outcomes included recovery and survival to day 28, and adverse events. Recovery and survival were calculated using a stratified log-rank Kaplan-Meier estimator and a Cox proportional hazards model. RESULTS: Overall, 164 patients received RDV between May and October 2020, and 153 (93.3%) had evaluable data. Most (77.1%) were hospitalized within 10 days of symptom onset, and 79.7% started RDV within 48 hours. By days 14 and 28, 96 (62.7%) and 117 patients (76.5%) met the definition of clinical recovery, respectively. Median time to recovery was 6 days [interquartile range (IQR) 4-12]. Mortality rates were 6.5% and 11.8% by days 14 and 28, respectively. Age and time to start of RDV after hospital admission were predictive of recovery and 28-day mortality. CONCLUSIONS: In this real-world experience, outcomes after 5 days of RDV therapy were comparable to those of clinical trials. Disease severity, age, and dexamethasone use influenced clinical outcomes. Time to RDV initiation appeared to affect recovery and 28-day mortality, a finding that should be explored further. Mortality rate decreased over the analysis period, which could be related to dexamethasone use and improved management of COVID-19.

Therapeutic drug monitoring of flucytosine in a cardiac transplant patient receiving continuous veno-venous hemofiltration and intermittent hemodialysis: A case report.

Invasive candidiasis is one of the common infections in solid organ transplant recipients. Guidelines recommend echinocandins or liposomal amphotericin with consideration of flucytosine (5-fluorocytosine; 5-FC) as synergistic therapy for treatment of select deep-seated Candida infections, including complex endovascular infections. Flucytosine undergoes extensive renal elimination; however, optimal dosing in patients with renal impairment, or those requiring renal replacement therapy (RRT), is not well-established. We describe a case of a 60-year old female who underwent orthotopic heart transplant complicated by Candida parapsilosis complex fungemia with mediastinitis and development of end-stage renal disease requiring RRT. Flucytosine therapeutic drug monitoring was performed on continuous veno-venous hemofiltration (CVVH) and intermittent hemodialysis (iHD) to guide appropriate dosing. Our results support 5-FC doses of 25 mg/kg daily while undergoing CVVH with a low fluid replacement rate and 21 mg/kg post-iHD or 17 mg/kg daily while receiving thrice weekly iHD.

Assessment and Optimization of the Empiric Treatment of Urinary Tract Infections in an Academic Emergency Department Observation Unit.

BACKGROUND: Poor adherence to evidence-based guidelines and overuse of broad-spectrum antibiotics has been noted in the emergency department (ED). There is limited evidence on guideline-congruent empiric therapy for urinary tract infections (UTIs) and uropathogen susceptibilities in the ED observation unit (EDOU). OBJECTIVE: The primary objective was to evaluate the prescribing patterns for the empiric treatment of UTI in the EDOU. Secondary objectives were to analyze uropathogen susceptibilities in the EDOU and implement an algorithm for the empiric treatment of UTI. METHODS: This study retrospectively reviewed adult patients who received empiric UTI treatment in the EDOU from January 1, 2018 to April 1, 2018. Eligible patients were categorized as having either uncomplicated or complicated cystitis, or pyelonephritis based on their clinical diagnosis. Antimicrobial therapy was evaluated in accordance with national practice guidelines, institutional guidelines, and local antimicrobial susceptibility patterns. RESULTS: Patients with uncomplicated or complicated cystitis (n = 115) were provided guideline-congruent empiric treatment in 87% of cases. Patients with pyelonephritis (n = 35) were provided guideline-congruent empiric treatment in 57% of cases. Susceptibility patterns of uropathogens isolated from this patient sample differed slightly from the institutional antibiogram, notably depicting a lower Escherichia coli susceptibility rate. Fluoroquinolones were prescribed for a longer than recommended duration in 18 patients (60%). CONCLUSIONS: The majority of patients in this study were provided guideline-congruent empiric therapy. Nevertheless, there are opportunities to optimize empiric UTI treatment and improve antibiotic stewardship in the EDOU.

Beta-lactam antibiotic test doses in the emergency department.

BACKGROUND: Facilitating beta-lactam antibiotic use in patients reporting beta-lactam allergies in acute care settings is important to individual patient outcomes and public health; however, few initiatives have targeted the Emergency Department (ED) setting. METHODS: We implemented pathways for patients reporting prior penicillin and/or cephalosporin hypersensitivity as part of a hospital guideline in the ED of a large academic medical center in the United States. We described beta-lactam test doses, pathway compliance, hypersensitivity reactions (HSRs), and allergy record updating associated with ED-administered beta-lactam test doses from October 2016 to June 2018. RESULTS: 310 beta-lactam antibiotic test doses were administered to patients with penicillin and/or cephalosporin allergy histories in the study period (average volume 15/month [standard deviation 4]). Test doses were to cephalosporins (85%), penicillins (12%), and carbapenems (4%). 219 (71%) of test doses were compliant with the pathways. Ten patients (3.2%; 95% CI 1.6%-5.9%) had HSRs; five HSR patients (50%) had beta-lactams administered that were not pathway compliant. The allergy record was updated in 146 (47%) of patients, with improvement over the study period (p < 0.001). CONCLUSIONS: Inpatient approaches to prescribing beta-lactams in patients reporting beta-lactam allergies can be operationalized in the ED. Additional efforts are required to ensure guideline compliance and appropriate allergy documentation.

Outcomes from an inpatient beta-lactam allergy guideline across a large US health system.

OBJECTIVE: To assess the safety of, and subsequent allergy documentation associated with, an antimicrobial stewardship intervention consisting of test-dose challenge procedures prompted by an electronic guideline for hospitalized patients with reported ß-lactam allergies. DESIGN: Retrospective cohort study. SETTING: Large healthcare system consisting of 2 academic and 3 community acute-care hospitals between April 2016 and December 2017. METHODS: We evaluated ß-lactam antibiotic test-dose outcomes, including adverse drug reactions (ADRs), hypersensitivity reactions (HSRs), and electronic health record (EHR) allergy record updates. HSR predictors were examined using a multivariable logistic regression model. Modification of the EHR allergy record after test doses considered relevant allergy entries added, deleted, and/or specified. RESULTS: We identified 1,046 test-doses: 809 (77%) to cephalosporins, 148 (14%) to penicillins, and 89 (9%) to carbapenems. Overall, 78 patients (7.5%; 95% confidence interval [CI], 5.9%-9.2%) had signs or symptoms of an ADR, and 40 (3.8%; 95% CI, 2.8%-5.2%) had confirmed HSRs. Most HSRs occurred at the second (ie, full-dose) step (68%) and required no treatment beyond drug discontinuation (58%); 3 HSR patients were treated with intramuscular epinephrine. Reported cephalosporin allergy history was associated with an increased odds of HSR (odds ratio [OR], 2.96; 95% CI, 1.34-6.58). Allergies were updated for 474 patients (45%), with records specified (82%), deleted (16%), and added (8%). CONCLUSION: This antimicrobial stewardship intervention using ß-lactam test-dose procedures was safe. Overall, 3.8% of patients with ß-lactam allergy histories had an HSR; cephalosporin allergy histories conferred a 3-fold increased risk. Encouraging EHR documentation might improve this safe, effective, and practical acute-care antibiotic stewardship tool.

Recurrent Relatively Resistant Salmonella infantis Infection in 2 Immunocompromised Hosts Cleared With Prolonged Antibiotics and Fecal Microbiota Transplantation.

Two immunocompromised patients with relapsing gastrointestinal infection with relatively resistant Salmonella infantis were cured with prolonged ertapenem followed by encapsulated fecal transplant.

Therapeutic drug concentrations of isavuconazole following the administration of isavuconazonium sulfate capsules via gastro-jejunum tube: A case report.

Invasive fungal infections are a common complication in immunocompromised patients, such as organ transplant recipients. Isavuconazole is a broad-spectrum azole antifungal for the treatment of aspergillosis and mucormycosis. The package insert for isavuconazole recommends against opening the capsule for administration through enteral feeding tubes. We describe the case of a 68-year-old man with a complex post-lung transplant course receiving isavuconazole for presumed invasive aspergillosis (bronchial alveolar lavage galactomannan index of >3.75) therapy administered through a gastrostomy-jejunostomy tube (G-J tube). Therapeutic drug monitoring was performed to ensure appropriate absorption. Peak and trough concentrations were measured in the early and late phases of the treatment course and resulted in trough levels of 2.7 mcg/mL and 4.0 mcg/mL, which is consistent with previously published trough concentrations of isavuconazole when the capsule was administered intact. This case report suggests that opening isavuconazole capsules and administration through a G-J tube results in appropriate absorption and serum drug levels comparable to intact capsules.

HCV Therapy Follow-up Fractionation (CTF2) by Intra-PBMC Nested RNA PCR Recognizes Early Virologic Response and Relapse.

Background and Aims: Sustained virologic response is evaluated by single-step reverse transcription (SRT) PCR assay, which assesses hepatitis C virus (HCV) clearance from plasma but not from tissues such as peripheral blood mononuclear cells (PBMCs). Persistence of HCV RNA in PBMCs beyond end of treatment (EOT) is associated with nonresponse. Our goal was to measure intra-PBMC HCV RNA levels during oral antiviral therapy according to the HCV therapy follow-up fractionation (CTF2) protocol. Methods: Compensated chronic HCV patients (n = 2 78 SRT-PCR positive) were scheduled to receive oral antiviral therapy. Subjects were followed-up by SRT and intra-PBMCs HCV RNA PCR at the end of the 2nd, 6th, 10th, 14th, 18th and 24th weeks to evaluate virus clearance from plasma and PBMCs, respectively. The CTF2 protocol evaluated SRT and PBMC PCR status at each follow-up point for determining therapy continuation or interruption to address cost effectiveness. Results: All patients tested negative by SRT PCR after therapy for 2 weeks. Application of the CTF2 protocol revealed: a) increasing HCV clearance rate from 75.9% at the end of 10th week to 90.3% at the end of 24th week (p < 0.00001); b) faster clearance of HCV from plasma compared to PBMCs at each point of follow-up until the 18th week (p < 0.05); c) higher viral elimination rates diagnosed by PBMC HCV RNA PCR(-) compared to PBMC HCV RNA PCR(+) from the 6th to 24th week of treatment (p < 0.0001); d) higher over-time increase curve of combined plasma and PBMC HCV RNA determined negativity compared to the decline in positivity curves by PBMC PCR at the 6th-18th week compared to the 24th week (p < 0.01)-these results validated treatment continuation; and e) solitary evaluation of EOT sustained HCV infection and relapses by PBMC HCV RNA (p < 0.001). Conclusions: Early elimination of serum and tissue (PBMC) HCV infection by oral antiviral therapy can be achieved and evaluated during a cost-effective CTF2 protocol application.

Prospective evaluation of a continuous infusion vancomycin dosing nomogram in critically ill patients undergoing continuous venovenous haemofiltration.

OBJECTIVES: The most optimal method of attaining therapeutic vancomycin concentrations during continuous venovenous haemofiltration (CVVH) remains unclear. Studies have shown continuous infusion vancomycin (CIV) achieves target concentrations more rapidly and consistently when compared with intermittent infusion. Positive correlations between CVVH intensity and vancomycin clearance (CLvanc) have been noted. This study is the first to evaluate a CIV regimen in patients undergoing CVVH that incorporates weight-based CVVH intensity (mL/kg/h) into the dosing nomogram. METHODS: This was a prospective, observational study of patients undergoing CVVH and receiving CIV based on the nomogram. The primary outcome was achievement of a therapeutic vancomycin concentration (15-25 mg/L) at 24 h. Secondary outcomes included the achievement of therapeutic concentrations at 48 and 72 h. RESULTS: The nomogram was analysed in 52 critically ill adults. Vancomycin concentrations were therapeutic in 43/52 patients (82.7%) at 24 h. Of the nine patients who were not therapeutic at 24 h, seven were supratherapeutic and two were subtherapeutic. The mean (SD) concentration was 20.1 (4.2) mg/L at 24 h, 20.7 (3.7) mg/L at 48 h and 21.9 (3.5) mg/L at 72 h. Patients with CVVH intensity >20 mL/kg/h experienced higher CLvanc at 24 h compared with patients with CVVH intensity <20 mL/kg/h (3.1 versus 2.6 L/h; P = 0.013). CONCLUSIONS: By incorporating CVVH intensity into the CIV dosing nomogram, the majority of patients achieved therapeutic concentrations at 24 h and maintained them within range at 48 and 72 h. Additional studies are required to validate this nomogram before widespread implementation may be considered.

A Retrospective Analysis of Treatment and Clinical Outcomes among Patients with Methicillin-Susceptible Staphylococcus aureus Bloodstream Isolates Possessing Detectable mecA by a Commercial PCR Assay Compared to Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates.

mecA-positive Staphylococcus aureus isolates phenotypically susceptible to cefoxitin (mecA-methicillin-sensitive S. aureus [MSSA]) have been identified. We describe the treatment and outcomes among patients with mecA-MSSA bloodstream infections (BSI) and MRSA BSI matched 1:1 for age, BSI origin, and BSI type (n = 17 per group). Compared to MRSA BSI patients, mecA-MSSA BSI patients more often experienced clinical failure (58.8% and 11.8%, P = 0.010), driven largely by persistent bacteremia (35.3% and 11.8%). mecA-MSSA BSI patients may be at higher risk for poor clinical outcomes.

Addressing Inpatient Beta-Lactam Allergies: A Multihospital Implementation.

Addressing inaccurate penicillin allergies is encouraged as part of antibiotic stewardship in the inpatient setting. However, implementing interventions targeted at the 10% to 15% of inpatients reporting a previous penicillin allergy can pose substantial logistic challenges. We implemented a computerized guideline for patients with reported beta-lactam allergy at 5 hospitals within a single health care system in the Boston area. In this article, we describe our implementation roadmap, including both successes achieved and challenges faced. We explain key implementation steps, including assembling a team, stakeholder engagement, developing or selecting an approach, spreading the change, establishing measures, and measuring impact. The objective was to detail the lessons learned while empowering others to be part of this important, multidisciplinary work to improve the care of patients with reported beta-lactam allergies.

Results of a local combination therapy antibiogram for Pseudomonas aeruginosa isolates: is double worth the trouble?

PURPOSE: To determine the frequency at which fluoroquinolones and aminoglycosides demonstrate in vitro activity against non-urinary, non-skin/skin structure Pseudomonas aeruginosa isolates exhibiting decreased susceptibilities to one or more ß-lactam agents. METHODS: ß-lactam-non-susceptible P. aeruginosa isolates recovered from blood, bone, lower respiratory tract, pleural fluid, cerebrospinal fluid, or peritoneal fluid cultures between October 2010 and October 2014 were reviewed from four community hospitals within a single health-system. Only the first isolate per patient was included for analysis. The likelihood that each isolate was susceptible to a non-ß-lactam antimicrobial was then determined and summarized within a combination antibiogram. RESULTS: In total, 179 P. aeruginosa isolates with decreased susceptibilities to one or more ß-lactam agents were assessed. Because no appreciable differences in antimicrobial susceptibility profile were observed between hospitals, the isolates were evaluated in aggregate. Susceptibility rates for ß-lactam monotherapy ranged from 34% to 75%. Aminoglycosides possessed increased antibacterial activity compared to fluoroquinolones. Tobramycin was the non-ß-lactam most likely to expand antimicrobial coverage against ß-lactam-non-susceptible P. aeruginosa with activity against 64%, 66%, and 65% of cefepime-, piperacillin-tazobactam-, and meropenem-non-susceptible isolates, respectively (p < 0.001 for all). CONCLUSIONS: The results of this study support the use of aminoglycosides over fluoroquinolones for achieving optimal, empiric antimicrobial combination therapy for P. aeruginosa when dual antimicrobial therapy is clinically necessary. Future efforts aimed at optimizing combination therapy for P. aeruginosa should focus on systemic interventions that limit the selection of fluoroquinolones in combination with ß-lactams to expand coverage based on local susceptibility rates.