Larissa Pisney

Bio: Larissa Pisney is an academic researcher from University of Colorado Denver. The author has contributed to research in topics: Health informatics & Health informatics tools. The author has an hindex of 4, co-authored 10 publications receiving 57 citations. Previous affiliations of Larissa Pisney include University of Colorado Hospital & Anschutz Medical Campus.

Advantages of Outpatient Treatment with Long-Acting Lipoglycopeptides for Serious Gram-Positive Infections: A Review

Abstract: Treatment of serious gram-positive infections presents multiple challenges. Treatment often results in prolonged hospitalization for administration of intravenous antimicrobials and presents an inefficient use of hospital resources. Prolonged hospitalization is typically also unfavorable to patient preferences and potentially subjects patients to additional health care-associated complications. Current strategies of transition to outpatient settings-outpatient parenteral antimicrobial therapy and use of oral antibiotics-often do not adequately serve vulnerable populations for whom there is often no alternative to inpatient therapy. Specifically, people who use drugs, those who cannot reliably adhere to unsupervised treatment (poor mental or physical health), people with complicating life circumstances (e.g., homelessness, incarceration, rural location), and those with inadequate health insurance remain hospitalized for weeks longer than persons without such conditions. We suspected that long-acting lipoglycopeptides (laLGP), such as dalbavancin and oritavancin, may be useful in patient transitions to outpatient settings. Thus, we conducted a search of the peer-reviewed literature using the PubMed, Google Scholar, and MEDLINE databases. Based on accumulating literature, it appears that laLGPs offer a reliable alternative therapeutic strategy that addresses many of the personal and systemic barriers to the traditional transitioning approaches. Current evidence also suggests that these agents may be cost-effective from patient, payer, and hospital perspectives. Barriers to broader use of laLGPs include, among others, a relative lack of prospective data regarding efficacy in serious infections, a narrow United States Food and Drug Administration-approved indication restricted to only acute bacterial skin and skin structure infections, and lack of reimbursement infrastructure for inpatient settings.

Carbapenem-resistant Enterobacteriaceae rectal screening during an outbreak of New Delhi metallo-β-lactamase-producing Klebsiella pneumoniae at an acute care hospital.

Abstract: We describe the results of carbapenem-resistant Enterobacteriaceae (CRE) screening as part of an outbreak investigation of New Delhi metallo-β-lactamase–producing CRE at a tertiary care university teaching hospital. The manual method for CRE screening was useful for detecting patients with asymptomatic CRE carriage but was time-consuming and costly.

Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae Producing New Delhi Metallo-Beta-Lactamase — Denver, Colorado, 2012

Abstract: On August 16, 2012, the Colorado Department of Public Health and Environment was notified of two patients at an acute-care hospital in Denver with carbapenem-resistant Enterobacteriaceae (CRE), specifically Klebsiella pneumoniae (CRKP), isolated from respiratory specimens during July-August. Both isolates produced New Delhi metallo-beta-lactamase (NDM). A review of microbiology records identified a third patient with NDM-producing CRKP isolated from a respiratory specimen, admitted in May. Active surveillance cultures in September identified an additional five patients colonized with NDM-producing CRKP. An investigation was launched by the hospital and the Colorado Department of Public Health and Environment to guide infection control measures and limit transmission.

Impact of pre-transplant carbapenem-resistant Enterobacterales colonization and/or infection on solid organ transplant outcomes.

Abstract: The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.

Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of infection and 90-day mortality in critically ill patients, an observational study.

Abstract: Background Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as an urgent public health threat. Intestinal colonization with CRE has been identified as a risk factor for the development of systemic CRE infection, but has not been compared to colonization with third and/or fourth generation cephalosporin-resistant (Ceph-R) Enterobacteriaceae. Moreover, the risk conferred by colonization on adverse outcomes is less clear, particularly in critically ill patients admitted to the intensive care unit (ICU). Methods We carried out a cohort study of consecutive adult patients screened for rectal colonization with CRE or Ceph-R upon ICU entry between April and July 2013. We identified clinical variables and assessed the relationship between CRE or Ceph-R colonization and subsequent systemic CRE infection within 30 days (primary outcome) and all-cause mortality within 90 days (secondary outcome). Results Among 338 ICU patients, 94 (28%) were colonized with either Ceph-R or CRE. 26 patients developed CRE infection within 30 days of swab collection; 47% (N = 17/36) of CRE-colonized and 3% (N = 2/58) of Ceph-R colonized patients. 36% (N = 13/36) of CRE-colonized patients died within 90 days compared to 31% (N = 18/58) of Ceph-R-colonized and 15% (N = 37/244) of non-colonized patients. In a multivariable analysis, CRE colonization independently predicted development of a systemic CRE infection at 30 days (aOR 10.8, 95% CI2.8–41.9, p = 0.0006); Ceph-R colonization did not (aOR 0.5, 95% CI0.1–3.3, p = 0.5). CRE colonization was associated with increased 90-day mortality in a univariable analysis (p-value 0.001), in a multivariable model, previous hospitalization and medical ICU admission were independent predictors of 90-day mortality whereas CRE colonization approached significance (aOR 2.3, 95% CI1.0–5.3, p = 0.056). Conclusions Our study highlights the increased risk of CRE infection and mortality in patients with CRE colonization at the time of ICU admission. Future studies are needed to assess how CRE colonization can guide empiric antibiotic choices and to develop novel decolonization strategies.

Antimicrobial Activity of Ceftazidime-Avibactam against Gram-Negative Organisms Collected from U.S. Medical Centers in 2012

Abstract: The activities of the novel β-lactam–β-lactamase inhibitor combination ceftazidime-avibactam and comparator agents were evaluated against a contemporary collection of clinically significant Gram-negative bacilli. Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits Ambler class A, C, and some D enzymes. A total of 10,928 Gram-negative bacilli—8,640 Enterobacteriaceae, 1,967 Pseudomonas aeruginosa, and 321 Acinetobacter sp. isolates—were collected from 73 U.S. hospitals and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Ceftazidime was combined with avibactam at a fixed concentration of 4 μg/ml. Overall, 99.8% of Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Ceftazidime-avibactam was active against extended-spectrum β-lactamase (ESBL)-phenotype Escherichia coli and Klebsiella pneumoniae, meropenem-nonsusceptible (MIC ≥ 2 μg/ml) K. pneumoniae, and ceftazidime-nonsusceptible Enterobacter cloacae. Among ESBL-phenotype K. pneumoniae strains, 61.1% were meropenem susceptible and 99.3% were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Among P. aeruginosa strains, 96.9% were inhibited at a ceftazidime-avibactam MIC of ≤8 μg/ml, and susceptibility rates for meropenem, ceftazidime, and piperacillin-tazobactam were 82.0, 83.2, and 78.3%, respectively. Ceftazidime-avibactam was the most active compound tested against meropenem-nonsusceptible P. aeruginosa (MIC50/MIC90, 4/16 μg/ml; 87.3% inhibited at ≤8 μg/ml). Acinetobacter spp. (ceftazidime-avibactam MIC50/MIC90, 16/>32 μg/ml) showed high rates of resistance to most tested agents. In summary, ceftazidime-avibactam demonstrated potent activity against a large collection of contemporary Gram-negative bacilli isolated from patients in U.S. hospitals in 2012, including organisms that are resistant to most currently available agents, such as K. pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and meropenem-nonsusceptible P. aeruginosa.

Population genomic analysis of 1,777 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates, Houston, Texas: Unexpected abundance of clonal group 307

Abstract: Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K. pneumoniae , it is imperative to understand the population genomic structure of strains causing human infections. To address this knowledge gap, we sequenced the genomes of 1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured from patients in the 2,000-bed Houston Methodist Hospital system between September 2011 and May 2015, representing a comprehensive, population-based strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused more infections than those of well-studied epidemic CG258. Strains varied markedly in gene content and had an extensive array of small and very large plasmids, often containing antimicrobial resistance genes. Some patients with multiple strains cultured over time were infected with genetically distinct clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase 1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse strains showed that the global transcriptome of each strain was unique and highly variable. Experimental mouse infection provided new information about immunological parameters of host-pathogen interaction. We exploited the large data set to develop whole-genome sequence-based classifiers that accurately predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We conclude that analysis of large, comprehensive, population-based strain samples can assist understanding of the molecular diversity of these organisms and contribute to enhanced translational research. IMPORTANCE Klebsiella pneumoniae causes human infections that are increasingly difficult to treat because many strains are resistant to multiple antibiotics. Clonal group 258 (CG258) organisms have caused outbreaks in health care settings worldwide. Using a comprehensive population-based sample of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae strains, we show that a relatively uncommon clonal type, CG307, caused the plurality of ESBL-producing K. pneumoniae infections in our patients. We discovered that CG307 strains have been abundant in Houston for many years. As assessed by experimental mouse infection, CG307 strains were as virulent as pandemic CG258 strains. Our results may portend the emergence of an especially successful clonal group of antibiotic-resistant K. pneumoniae .