A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Epidemiology and treatment of invasive Bartonella spp. infections in the United States.

OBJECTIVES: Bartonella spp., renowned for cat-scratch disease, has limited reports of dissemination. Tissue and blood cultures have limitations in detecting this fastidious pathogen. Molecular testing (polymerase chain reaction, PCR) and cell-free DNA have provided an avenue for diagnoses. This retrospective observational multicenter study describes the incidence of disseminated Bartonella spp. and treatment-related outcomes. METHODS: Inclusion criteria were diagnosis of bartonellosis via diagnosis code, serology testing of blood, polymerase chain reaction (PCR) of blood, 16/18S tests of blood or tissue, cultures of blood or tissue, or cell-free DNA of blood or tissue from January 1, 2014, through September 1, 2021. Exclusions were patients who did not receive treatment, insufficient data on treatment course, absence of dissemination, or retinitis as dissemination. RESULTS: Patients were primarily male (n = 25, 61.0%), white (n = 28, 68.3%), with mean age of 50 years (SD 14.4), and mean Charlson comorbidity index of 3.5 (SD 2.1). Diagnosis was primarily by serology (n = 34, 82.9%), with Bartonella henselae (n = 40, 97.6%) as the causative pathogen. Treatment was principally doxycycline with rifampin (n = 17, 41.5%). Treatment failure occurred in 16 (39.0%) patients, due to escalation of therapy during treatment (n = 5, 31.3%) or discontinuation of therapy due to an adverse event or tolerability (n = 5, 31.3%). CONCLUSIONS: In conclusion, this is the largest United States-based cohort of disseminated Bartonella spp. infections to date with a reported 39% treatment failure. This adds to literature supporting obtaining multiple diagnostic tests when Bartonella is suspected and describes treatment options.

Trimethoprim/Sulfamethoxazole vs Minocycline for the Treatment of Nonurinary Monomicrobial Stenotrophomonas maltophilia Infections in Hospitalized Patients.

BACKGROUND: Stenotrophomonas maltophilia is an opportunistic, gram-negative bacillus with few therapeutic options due to a high level of intrinsic resistance. Trimethoprim/sulfamethoxazole (SXT) is recommended as the first-line treatment; however, minocycline (MIN) has been shown to have similar clinical outcomes in treating S. maltophilia and addresses concern for increasing resistance to SXT. OBJECTIVE: The objective of this study is to evaluate the efficacy and safety outcomes of nonurinary, monomicrobial infections due to S. maltophilia in hospitalized patients treated with MIN or SXT. METHODS: This was a retrospective study of hospitalized adult patients receiving MIN or SXT for nonurinary monomicrobial S. maltophilia infection from April 1, 2018 to March 31, 2020. The primary outcome was clinical disposition classified as rates of clinical failure, clinical improvement, or clinical success. RESULTS: Eighty-two patients (88.2%) received MIN and 11 patients (11.8%) received SXT initially. Clinical failure occurred in 16 (19.5%) patients in the MIN group and in 4 (36.4%) patients in the SXT group (P = 0.242). Clinical improvement occurred in 11 (13.4%) patients in the MIN group and in 1 (9.1%) patient in the SXT group (P = 1.0). Clinical success occurred in 55 (67.1%) patients in the MIN group and in 6 (54.5%) patients in the SXT group (P = 0.503). Total duration of antimicrobial therapy (P = 0.3198), in-hospital mortality (P = 1.0), hospital length of stay (P = 0.9668), intensive care unit (ICU) length of stay (P = 0.1384), and 30-day readmission (P = 0.686) were similar between groups. CONCLUSIONS AND RELEVANCE: Rates of clinical failure, clinical improvement, or clinical success were similar between MIN and SXT for nonurinary monomicrobial S. maltophilia infections.

Pharmacist-Driven Methicillin-Resistant S. aureus Polymerase Chain Reaction Testing for Pneumonia.

BACKGROUND: Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) can be detected using nasal swab polymerase chain reaction (PCR) assay and is associated with clinical MRSA infection. The MRSA nasal PCR has a rapid turnaround time and a negative predictive value for MRSA pneumonia of >98%; however, data are limited in critically ill patients. OBJECTIVE: The purpose of this study is to determine the impact of a pharmacist-driven algorithm, utilizing MRSA PCR nasal screening on duration of anti-MRSA therapy in patients admitted to the intensive care unit (ICU) with suspected pneumonia. METHODS: A single-center pre/post study was conducted in 4 ICUs at a large tertiary care community hospital. Adult patients admitted to the ICU initiated on vancomycin or linezolid for pneumonia managed using a pharmacist-driven MRSA PCR algorithm were included in the algorithm cohort. A historical cohort with standard management was matched 1:1 by age, type of pneumonia, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The primary outcome was duration of anti-MRSA therapy. Secondary outcomes included MRSA rates, number of vancomycin levels, new onset of acute kidney injury (AKI), ICU length of stay (LOS), hospital LOS, and mortality. RESULTS: Of the 245 patients screened, 50 patients met inclusion criteria for the algorithm cohort and were matched to 50 patients in the historical cohort. The duration of anti-MRSA therapy was significantly lower compared with the historical cohort (47 vs 95 hours; P < 0.001). Secondary outcomes were similar between groups for MRSA rates, new onset of AKI, LOS, and mortality. There were less vancomycin levels ordered in the algorithm cohort (2 vs 3, P = 0.026). CONCLUSIONS: A pharmacist-driven MRSA PCR algorithm significantly reduced anti-MRSA duration of therapy in critically ill patients with pneumonia. Future studies should validate these results in critically ill populations and in settings where MRSA pneumonia is more prevalent.

Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury.

It has been established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocyte pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists in the current pandemic. ACE2 serves as a regulatory enzyme in maintaining homeostasis between proinflammatory angiotensin II and anti-inflammatory angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome. Augmentation of the ACE2/Ang 1,7 axis represents a critical target in the supportive management of coronavirus disease 2019-associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists, requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.

Cefiderocol for the Treatment of Adult and Pediatric Patients With Cystic Fibrosis and Achromobacter xylosoxidans Infections.

Treatment options for Achromobacter xylosoxidans are limited. Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses. Pretreatment in vitro resistance was seen in 3 of 8 cases. Clinical response occurred after 11 of 12 treatment courses. However, microbiologic relapse was observed after 11 of 12 treatment courses, notably without emergence of resistance.

Clinical Utility of Methicillin-Resistant Staphylococcus aureus Nasal Screening for Antimicrobial Stewardship: A Review of Current Literature.

Significant clinical and financial consequences are associated with both inadequate and unnecessary exposure to broad-spectrum antibiotics. As such, antimicrobial stewardship programs seek objective, reliable, and cost-effective tests to identify patients at highest or lowest risk for drug-resistant organisms to guide empirical antimicrobial selection. Use of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA in lower respiratory tract infections has led to significant reductions in duration of vancomycin therapy. The clinical utility of MRSA nasal screening in other types of infection remains less clear. This review describes the performance of MRSA nasal screening in predicting MRSA infection, highlights practical considerations for use of MRSA nasal screening, and provides guidance for incorporating MRSA nasal screening into clinical practice. With a high negative predictive value when the prevalence of MRSA is low, MRSA nasal screening is a valuable antimicrobial stewardship tool with potential applications beyond lower respiratory tract infections. In appropriately selected patients, negative MRSA nasal screening can prevent initiation or guide discontinuation of anti-MRSA therapy. Antimicrobial stewardship programs should develop institutional guidelines to promote proper use of MRSA nasal screening. Pharmacists are well positioned to assist with education, interpretation, and application of MRSA nasal screening results.

Localization of ISG15 and conjugated proteins in bovine endometrium using immunohistochemistry and electron microscopy.

The interferon-stimulated gene ISG15, a ubiquitin homolog, becomes conjugated to and regulates uterine proteins in response to conceptus-derived interferon-tau on d 18 of pregnancy. It was hypothesized here that cellular localization of ISG15 within endometrial cells might provide insight regarding function. Uteri were collected from cows (approximately 21-d estrous cycle) on d 17-21/0 of the estrous cycle and pregnancy and d 23, 45, and 50 of pregnancy. Intracellular ISG15 and its conjugates were present on d 17 of pregnancy, peaked to highest levels from d 18 to 23 and then declined to low but detectable levels by d 45 (P < 0.05) based on Western blotting. ISG15 and its conjugates were not detected on d 50 of pregnancy or during the estrous cycle. Immunohistochemistry revealed that ISG15 was localized throughout the endometrium on d 18-23, with heaviest staining in the sublumenal stratum compactum and the glandular epithelium throughout the stratum spongiosum. By d 45 and 50, ISG15 was lightly stained only in the stratum compactum immediately beneath the lumenal epithelium. Using transmission electron microscopy and immunogold labeling, ISG15 was specifically localized to organelles and compartments of endometrial epithelial cells and stromal cells: nucleus, perinuclear space, cytosol, mitochondria, rough endoplasmic reticulum, and cell membrane. This specific localization in epithelial and stromal cells led to the conclusion that ISG15 has diverse intracellular functions. The sustained presence of conjugated ISG15 through d 50 of pregnancy might reflect stabilization of conjugated proteins in response to implantation and the development of the placenta.