Search

Pneumonia causes a significant burden of disease worldwide. Although all populations are at risk of pneumonia, those at extremes of age and those with immunosuppressive disorders, underlying respiratory disease, and critical illness are particularly vulnerable. Although clinical practice guidelines addressing the management and treatment of pneumonia exist, few of the supporting studies focus on the crucial contributions of the host in pneumonia pathogenesis and recovery. Such essential considerations include the host risk factors that lead to susceptibility to lung infections; biomarkers reflecting the host response and the means to pursue host-directed pneumonia therapy; systemic effects of pneumonia on the host; and long-term health outcomes after pneumonia. To address these gaps, the Pneumonia Working Group of the Assembly on Pulmonary Infection and Tuberculosis led a workshop held at the American Thoracic Society meeting in May 2018 with overarching objectives to foster attention, stimulate research, and promote funding for short-term and long-term investigations into the host contributions to pneumonia. The workshop involved participants from various disciplines with expertise in lung infection, pneumonia, sepsis, immunocompromised patients, translational biology, data science, genomics, systems biology, and clinical trials. This workshop report summarizes the presentations and discussions and important recommendations for future clinical pneumonia studies. These recommendations include establishing consensus disease and outcome definitions, improved phenotyping, development of clinical study networks, standardized data and biospecimen collection and protocols, and development of innovative trial designs. [ABSTRACT FROM AUTHOR]

Background Pharyngeal and rectal Neisseria gonorrhoeae and Chlamydia trachomatis play important roles in infection and antibacterial resistance transmission, but no US Food and Drug Administration (FDA)–cleared assays for detection at these sites existed prior to this study. The objective was to estimate performance of assays to detect those infections in pharyngeal and rectal specimens to support regulatory submission. Methods We performed a cross-sectional, single-visit study of adults seeking sexually transmitted infection testing at 9 clinics in 7 states. We collected pharyngeal and rectal swabs from participants. The primary outcome was positive and negative percent agreement for detection of N. gonorrhoeae and C. trachomatis for 3 investigational assays compared to a composite reference. Secondary outcomes included positivity as well as positive and negative predictive values and likelihood ratios. Subgroup analyses included outcomes by symptom status and sex. Results A total of 2598 participants (79% male) underwent testing. We observed N. gonorrhoeae positivity of 8.1% in the pharynx and 7.9% in the rectum and C. trachomatis positivity of 2.0% in the pharynx and 8.7% in the rectum. Positive percent agreement ranged from 84.8% to 96.5% for different anatomic site infection combinations, whereas negative percent agreement was 98.8% to 99.6%. Conclusions This study utilized a Master Protocol to generate diagnostic performance data for multiple assays from different manufacturers in a single study population, which ultimately supported first-in-class FDA clearance for extragenital assays. We observed very good positive percent agreement when compared to a composite reference method for the detection of both pharyngeal and rectal N. gonorrhoeae and C. trachomatis. Clinical Trials Registration NCT02870101. [ABSTRACT FROM AUTHOR]

Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics. [ABSTRACT FROM AUTHOR]

Antibacterial resistance is increasing globally and has been recognized as a major public health threat. Antibacterial stewardship is the coordinated effort to improve the appropriate use of antibiotics with the aim to decrease selective pressure for multidrug-resistant organisms in order to preserve the utility of antibacterial agents. This article describes the activities of the Antibacterial Resistance Leadership Group (ARLG) in the area of antibacterial stewardship. To date, the ARLG has focused intensely on development of rapid diagnostic tests, which (when coupled with educational and institutional initiatives) will enable the robust stewardship that is needed to address the current crisis of antibacterial resistance. In addition to exploring the effectiveness of stewardship techniques in community hospitals, the ARLG has also developed strategy trials to assess the feasibility of reducing antibacterial usage while preserving patient outcome. [ABSTRACT FROM AUTHOR]

The Antibacterial Resistance Leadership Group (ARLG) Laboratory Center (LC) leads the evaluation, development, and implementation of laboratory-based research by providing scientific leadership and supporting standard/specialized laboratory services. The LC has developed a physical biorepository and a virtual biorepository. The physical biorepository contains bacterial isolates from ARLG-funded studies located in a centralized laboratory and they are available to ARLG investigators. The Web-based virtual biorepository strain catalogue includes well-characterized gram-positive and gram-negative bacterial strains published by ARLG investigators. The LC, in collaboration with the ARLG Leadership and Operations Center, developed procedures for review and approval of strain requests, guidance during the selection process, and for shipping strains from the distributing laboratories to the requesting investigators. ARLG strains and scientific and/or technical guidance have been provided to basic research laboratories and diagnostic companies for research and development, facilitating collaboration between diagnostic companies and the ARLG Master Protocol for Evaluating Multiple Infection Diagnostics (MASTERMIND) initiative for evaluation of multiple diagnostic devices from a single patient sampling event. In addition, the LC has completed several laboratory-based studies designed to help evaluate new rapid molecular diagnostics by developing, testing, and applying a MASTERMIND approach using purified bacterial strains. In collaboration with the ARLG's Statistical and Data Management Center (SDMC), the LC has developed novel analytical strategies that integrate microbiologic and genetic data for improved and accurate identification of antimicrobial resistance. These novel approaches will aid in the design of future ARLG studies and help correlate pathogenic markers with clinical outcomes. The LC's accomplishments are the result of a successful collaboration with the ARLG's Leadership and Operations Center, Diagnostics and Devices Committee, and SDMC. This interactive approach has been pivotal for the success of LC projects. [ABSTRACT FROM AUTHOR]

The Statistical and Data Management Center (SDMC) provides the Antibacterial Resistance Leadership Group (ARLG) with statistical and data management expertise to advance the ARLG research agenda. The SDMC is active at all stages of a study, including design; data collection and monitoring; data analyses and archival; and publication of study results. The SDMC enhances the scientific integrity of ARLG studies through the development and implementation of innovative and practical statistical methodologies and by educating research colleagues regarding the application of clinical trial fundamentals. This article summarizes the challenges and roles, as well as the innovative contributions in the design, monitoring, and analyses of clinical trials and diagnostic studies, of the ARLG SDMC. [ABSTRACT FROM AUTHOR]

The Antibacterial Resistance Leadership Group (ARLG), with funding from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, was created in June 2013. Its mission is to develop, prioritize, and implement a clinical research agenda that addresses the public health threat of antibacterial resistance. This article reports on the progress that the ARLG has made to date in fulfilling its mission. Since inception, the ARLG has received and reviewed >70 study proposals, initiated >30 studies, executed >300 agreements, included data from >7000 subjects, published >45 manuscripts, and provided opportunities for 26 mentees. Despite this substantial progress, there remains significant work to be accomplished. This article also describes the considerable challenges that lie ahead. [ABSTRACT FROM AUTHOR]

Focuses on the changes in expectations of parents of college students from higher education institutions in the U.S. Data from Cooperative Institutional Research Program Freshman Surveys on educational attainment of parents, divorce rates among parents, compositions and constellations of the families; Strategies to be adopted by the institutions to deal with the involvement of parents in education.

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA., Methods: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality., Findings: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses., Interpretation: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms., Funding: National Institutes of Health., Competing Interests: Declaration of interests All authors report funding support from the Antibacterial Resistance Leadership Group of the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID; UM1AI104681) during the conduct of this study. Additionally, during the conduct of this study, and outside of the submitted work, the authors report the following disclosures. KSK reports consulting fees paid directly to him by Merck, Shionogi, Qpex, and Micrux. JG-D reports grants and contracts paid to her institution from NIH, BARDA, Janssen Research & Development LLC, Pfizer, BioNTech SE, GCAR, Hoffman La-Roche, I-Mab Bioppharma, Rebiotix, Target Health, LLC OBO Lilly USA, GlaxoSmithKline, Summit Limited, Cidara Therapeutics, Merck Sharp & Dohme, Seres Therapeutics; and Infectious Diseases Society of America Research Committee participation paid to her directly. SSK reports speaker and advisory board payments from Pfizer, Astellas, Novartis, Merck, and Gilead. JMO reports speaker payments from Pfizer, MSD, and Biotoscana; and board participation on the Chair Ethics Committee. SLV-B reports personal fees from Pfizer, Biotoscana, and MSD; meeting support from MSD and Pfizer; and data safety monitoring board participation with MSD and GlaxoSmithKline. PT reports honoraria payments to his institution from Aj Biologics and bioMérieux. GW reports payment to his institution from Allergan for contracted activities. LMA reports grants and contracts paid to her institution from Rainmakers/CDC multisystem inflammatory syndrome in adults with SARS-CoV-2, and Regeneron study co-investigator; consulting and honoraria paid directly to them from Medscape for CME lectures, and Ferring Pharmaceuticals for advisory board participation; and volunteer work as the director of the IDSA Board of Directors. KO reports payments for educational events and presentations from Pfizer, MSD, AstraZeneca, and Farma de Colombia; meeting support from Pfizer, MSD, and Gilead; and expert testimony support from Pfizer, bioMérieux, and MSD. MES reports speaker fees from Pfizer (Argentina); advisory board participation for Wockhardt; consultancy for Basilea; and data safety monitoring board participation with Fulcrum Therapeutics. JMM reports grants from Pfizer, MSD, and bioMérieux, the National Fund for Scientific and Technological Development; and the Agencia Nacional de Investigation y Desarrollo Millennium Science Initiative/Millennium Initiative for Collaborative Research on Bacterial Resistance, Government of Chile. DLP reports grants and contracts paid to his institution from Merck, Pfizer, and Shionogi; consulting and honoraria payments to him by Merck, Shionogi, QPex, Spero Therapeutics, Sumitomo, Pfizer, and bioMérieux; meeting support from Shionogi; and board and committee participation with Symvivo, and AMR action fund. SE reports grants from the NIAID and the NIH and Degruter (Editor in Chief for Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Dickinson, Atricure, Roviant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, SVB Leerink; payments from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks; meeting support from the US Food and Drug Administration, the Deming Conference on Applied Statistics, the Clinical Trial Transformation Initiative, the Council for International Organizations of Medical Sciences, the International Chinese Statistical Association Applied Statistics Symposium, and the Antimicrobial Resistance and Stewardship Conference; and board member participation for the NIH, the Breast International Group, the University of Pennsylvania, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, the American Statistical Association, the Society for Clinical Trials, and the Frontier Science Foundation. RAB reports grants and contracts, paid to his institution, by VenatoRx, Wockhardt, and Merck; payments made to him by Pfizer to moderate meeting sessions; patents with Case Western Reserve University on the development of boronic acid transition state inhibitors for β-lactamases (WO2022187362A1, US9949995B2, and US20170252326A1); and payment for participation on a data safety monitoring board, safety oversight committee support, and Logistics Associate for DMID-CROMS (contractor) with Technical Resources International. MVV reports contracts, consulting fees, and honoraria payments from Pfizer and MSD; consulting fees from West Quimica Colombia; and honoraria from bioMérieux. RP reports grants from BioFire Diagnostics, ContraFect, and TenNor Therapeutics; is a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Day Zero Diagnostics, Torus Biosystems, Mammoth Biosciences, and Qvella, for which monies are paid to Mayo Clinic; is a consultant to Netflix and CARB-X; has a patent on Bordetella pertussis and parapertussis PCR issued (US8507201B2), a patent on a device and method for sonication (with royalties paid by Samsung to Mayo Clinic; US7076117B2), and a patent on an anti-biofilm substance issued (US8802414B2); receives an editor's stipend from the Infectious Diseases Society of America; and receives honoraria from the National Board of Medical Examiners, UpToDate, and the Infectious Diseases Board Review Course. CAA reports the grants and contracts paid to his institution from NIH and NIAID, MeMed Diagnostics, Entasis Therapeutics, Merck Pharmaceuticals, and Harris County Public Health; payments to him for UpToDate royalties, reimbursement of meeting attendance, and speaking from Infectious Diseases Society of America, American Society for Microbiology, Society of Hospital Epidemiology of America, European Society for Clinical Microbiology and Infectious Diseases, bioMérieux Foundation, Sociedad Argentina de Infectologia, Sociedad Chilena de Infectologia, Sociedad Colombiana de Infectologia, Panamerican Society for Infectious Diseases, Brazilian Society for Infectious Diseases, reviewer participation as part of the NIH grant Review Study Sections, travel expenses from the Infectious Disease Society of America (IDSA) Board of Directors, and for Editor in Chief for Antimicrobial Agents and Chemotherapy; non-paid participation with WHO Antibacterial Pipeline Advisory Group; and participation on the IDSA Board of Directors. HFC reports participation on a Merck data safety monitoring board for molnupiravir paid directly to him, stock ownership in Moderna and Merck, and a position as expert witness for Lilly and Nexus Pharmaceuticals. VGF reports grants to his institution from the NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, ContraFect, Karius, Genentech, Regeneron, Basilea, and Janssen; royalties from UpToDate; personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines, MedImmune, Bayer, Basilea, Affinergy, Janssen, ContraFect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche; editorial stipend from Infectious Diseases of America; pending patent for a host gene expression signature diagnostic for sepsis (US9850539B2); and stock options with Valanbio and ArcBio. YD reports grants from Entasis, Asahi Kasei Pharma, Shionogi, and Kanto Chemical paid to his institution; consulting fees paid directly to him from Meiji Seika Pharma, Shionogi, Gilead, MSD, Chugai, and bioMérieux; and speaker payments from MSD, Shionogi, AstraZeneca, Teijin Healthcare, Gilead, FujiFilm Toyama Chemical, bioMerieux, HU Frontier, and Eiken Chemical paid to him. DvD reports grants and contracts from the NIH and Merck paid to his institution outside of the published work; and consultancy for Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, and Karius. MJS reports contract payments to his institution from Merck, Allergan, BioFire Diagnostics, Affinity Biosensors, and SNIPRBiome; personal consulting fees from Shionogi; and data and safety monitoring board participation for Spero Therapeutics., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Pneumonia causes a significant burden of disease worldwide. Although all populations are at risk of pneumonia, those at extremes of age and those with immunosuppressive disorders, underlying respiratory disease, and critical illness are particularly vulnerable. Although clinical practice guidelines addressing the management and treatment of pneumonia exist, few of the supporting studies focus on the crucial contributions of the host in pneumonia pathogenesis and recovery. Such essential considerations include the host risk factors that lead to susceptibility to lung infections; biomarkers reflecting the host response and the means to pursue host-directed pneumonia therapy; systemic effects of pneumonia on the host; and long-term health outcomes after pneumonia. To address these gaps, the Pneumonia Working Group of the Assembly on Pulmonary Infection and Tuberculosis led a workshop held at the American Thoracic Society meeting in May 2018 with overarching objectives to foster attention, stimulate research, and promote funding for short-term and long-term investigations into the host contributions to pneumonia. The workshop involved participants from various disciplines with expertise in lung infection, pneumonia, sepsis, immunocompromised patients, translational biology, data science, genomics, systems biology, and clinical trials. This workshop report summarizes the presentations and discussions and important recommendations for future clinical pneumonia studies. These recommendations include establishing consensus disease and outcome definitions, improved phenotyping, development of clinical study networks, standardized data and biospecimen collection and protocols, and development of innovative trial designs.

Background: Carbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA., Methods: CRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Clinical data and bacteria were collected, and whole genome sequencing was done. This trial is registered with ClinicalTrials.gov, number NCT03646227., Findings: 1040 patients with unique isolates were included, 449 (43%) with infection and 591 (57%) with colonisation. The CDC-defined CRE admission rate was 57 per 100 000 admissions (95% CI 45-71). Three subsets of CDC-defined CRE were identified: carbapenemase-producing Enterobacterales (618 [59%] of 1040), non-carbapenemase-producing Enterobacterales (194 [19%]), and unconfirmed CRE (228 [22%]; initially reported as CRE, but susceptible to carbapenems in two central laboratories). Klebsiella pneumoniae carbapenemase-producing clonal group 258 K pneumoniae was the most common carbapenemase-producing Enterobacterales. In 449 patients with CDC-defined CRE infections, DOOR outcomes were not significantly different in patients with carbapenemase-producing Enterobacterales, non-carbapenemase-producing Enterobacterales, and unconfirmed CRE. At 30 days 107 (24%, 95% CI 20-28) of these patients had died., Interpretation: Among patients with CDC-defined CRE, similar outcomes were observed among three subgroups, including the novel unconfirmed CRE group. CDC-defined CRE represent diverse bacteria, whose spread might not respond to interventions directed to carbapenemase-producing Enterobacterales., Funding: National Institutes of Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Intensive care units (ICUs) are an appropriate focus of antibiotic stewardship program efforts because a large proportion of any hospital's use of parenteral antibiotics, especially broad-spectrum, occurs in the ICU. Given the importance of antibiotic stewardship for critically ill patients and the importance of critical care practitioners as the front line for antibiotic stewardship, a workshop was convened to specifically address barriers to antibiotic stewardship in the ICU and discuss tactics to overcome these. The working definition of antibiotic stewardship is "the right drug at the right time and the right dose for the right bug for the right duration." A major emphasis was that antibiotic stewardship should be a core competency of critical care clinicians. Fear of pathogens that are not covered by empirical antibiotics is a major driver of excessively broad-spectrum therapy in critically ill patients. Better diagnostics and outcome data can address this fear and expand efforts to narrow or shorten therapy. Greater awareness of the substantial adverse effects of antibiotics should be emphasized and is an important counterargument to broad-spectrum therapy in individual low-risk patients. Optimal antibiotic stewardship should not focus solely on reducing antibiotic use or ensuring compliance with guidelines. Instead, it should enhance care both for individual patients (by improving and individualizing their choice of antibiotic) and for the ICU population as a whole. Opportunities for antibiotic stewardship in common ICU infections, including community- and hospital-acquired pneumonia and sepsis, are discussed. Intensivists can partner with antibiotic stewardship programs to address barriers and improve patient care.

Background: Fungal infections are of increasing incidence and importance in immunocompromised and immunocompetent patients. Timely diagnosis relies on appropriate use of laboratory testing in susceptible patients. Methods: The relevant literature related to diagnosis of invasive pulmonary aspergillosis, invasive candidiasis, and the common endemic mycoses was systematically reviewed. Meta-analysis was performed when appropriate. Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: This guideline includes specific recommendations on the use of galactomannan testing in serum and BAL and for the diagnosis of invasive pulmonary aspergillosis, the role of PCR in the diagnosis of invasive pulmonary aspergillosis, the role of β-d-glucan assays in the diagnosis of invasive candidiasis, and the application of serology and antigen testing in the diagnosis of the endemic mycoses. Conclusions: Rapid, accurate diagnosis of fungal infections relies on appropriate application of laboratory testing, including antigen testing, serological testing, and PCR-based assays.

Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group's specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia.

Background: Various transmission routes contribute to spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospitalized patients. Patients with readmissions during which CRKP is again isolated ("CRKP readmission") potentially contribute to transmission of CRKP., Objective: To evaluate CRKP readmissions in the Consortium on Resistance against Carbapenems in K. pneumoniae (CRaCKLe)., Design: Cohort study from December 24, 2011, through July 1, 2013., Setting: Multicenter consortium of acute care hospitals in the Great Lakes region., Patients: All patients who were discharged alive during the study period were included. Each patient was included only once at the time of the first CRKP-positive culture., Methods: All readmissions within 90 days of discharge from the index hospitalization during which CRKP was again found were analyzed. Risk factors for CRKP readmission were evaluated in multivariable models., Results: Fifty-six (20%) of 287 patients who were discharged alive had a CRKP readmission. History of malignancy was associated with CRKP readmission (adjusted odds ratio [adjusted OR], 3.00 [95% CI, 1.32-6.65], P<.01). During the index hospitalization, 160 patients (56%) received antibiotic treatment against CRKP; the choice of regimen was associated with CRKP readmission (P=.02). Receipt of tigecycline-based therapy (adjusted OR, 5.13 [95% CI, 1.72-17.44], using aminoglycoside-based therapy as a reference in those treated with anti-CRKP antibiotics) was associated with CRKP readmission., Conclusion: Hospitalized patients with CRKP-specifically those with a history of malignancy-are at high risk of readmission with recurrent CRKP infection or colonization. Treatment during the index hospitalization with a tigecycline-based regimen increases this risk.

Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance.