American Thoracic Society/Infectious Diseases Society Of America Research Articles

2584. Predictors of Clinically Significant Infection in Patients with Mycobacterium simiae Isolated from Respiratory Samples: a Retrospective Study from a Tertiary Care Center in Lebanon

Abstract Background Mycobacterium simiae is a rare slow-growing, non-tuberculous mycobacterium (NTM). It is predominant in Middle Eastern countries like Israel, Iran and Lebanon and is the most isolated NTM spp. at our institution (40%). Little is known about its reservoirs, pathogenesis, risk factors and indications for treatment. Methods We retrospectively studied patients with respiratory cultures showing M. simiae at the American University of Beirut Medical Center (AUBMC) over 19 years. We used the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) criteria to define NTM lung disease. Samples were cultured at AUBMC using Lowenstein-Jensen media and the BacT/ALERT system. NTM isolates were referred for speciation and susceptibility testing at Mayo Clinic, MN, USA. Results We identified 72 isolates from 66 patients. Most were obtained from sputum samples (57.6%), the rest from bronchoalveolar lavages (BAL). Acid-fast bacilli smear was positive in 27% of samples with no difference between sputum and BAL. The median age of patients was 64 years and 51.5% were females. Bronchiectasis (34.5%), chronic obstructive pulmonary disease (27.3%) and immunosuppression (33.3%) were common (Table 1). As per the ATS/IDSA criteria, 67.9% of patients had NTM lung disease. The most common symptoms were cough (83.3%) and sputum production (74.5%). All patients except 2 had abnormal findings on CT imaging like nodules (58.5%), tree in bud aspect (45.3%) and bronchiectasis (24.5%). Among those, 55.6% had abnormal CT findings preceding the M. simiae isolation. Bronchiectasis was more common in those who satisfied the ATS/IDSA criteria versus those who did not (38.9% vs 20.0%). Otherwise, we found no significant differences between both groups (Table 2). Treatment was given to 88.9% of patients who satisfied the NTM lung disease and 42.1% of those who did not (p< 0.001) with a median duration of 12 months. Of those with available follow-up, relapse was reported in 24% of cases. Characteristics of patients with M. simiae isolated from respiratory samples. BMI, body mass index, COPD, chronic obstructive pulmonary disease, AFB, acid-fast bacilli. *Median(Interquartile range) **Composite variable including hematologic malignancy, solid organ malignancy, hematopoietic transplantation, solid organ transplant, chronic steroids treatment, and active chemotherapy. Clinical and radiological differences between patients with M. simiae lung disease and those colonized according to the ATS/IDSA criteria. BMI, body mass index, COPD, chronic obstructive pulmonary disease. *Median (Interquartile range) Conclusion M. simiae is a significant cause of NTM lung disease at our institution with a high rate of relapse. Further research is required to understand its geographic restriction, predisposing factors, and identify patients at risk for clinically significant infection. Disclosures Souha S Kanj, MD, Gilead: Advisor/Consultant|Menarini: Advisor/Consultant|MSD: Advisor/Consultant|Pfizer: Advisor/Consultant

POLA PENGGUNAAN ANTIBIOTIK PADA PASIEN PNEUMONIA RAWAT INAP DI RSUD dr. GONDO SUWARNO TAHUN 2021

Pneumonia is an infection at the ends of the bronchioles and alveoli which causes acute inflammation of the lung parenchyma caused by various pathogens such as bacteria, fungi, viruses and parasites. Most are caused by bacteria. Inappropriate use of antibiotics can lead to increased resistance, wasted costs and does not achieve optimal clinical benefits in the prevention and treatment of infections and bacterial resistance to drugs. The purpose of this study was to determine the suitability of the use of antibiotics according to therapy with the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines. This research method is a type of descriptive non-experimental research with a retrospective approach using cross sectional. Data collection according to the prescription of inpatients at dr. Gondo Suwarno who received antibiotics. Then grouped by type of antibiotic, dose, class, and duration of antibiotic administration. The number of samples is 100. Then the data is adjusted between therapy and guidelines. Based on the results of the study, it was found that there were more male patients. The most widely used dosage form is injection. The most common class of antibiotics is the cephalosporin group. In CAP pneumonia, the number of patients was 46 with the accuracy of the type of drug levofloxacin as many as 12 (26.08%). In HAP pneumonia, the number of patients was 54, with the accuracy of the type of antibiotic levofloxacin in 16 (29.62%). The accuracy of the type of ceftriaxone drug was 22 (40.74%)

2184. Predictors of Pneumococcal Urinary Antigen Test Positivity in Patients with Community-acquired Pneumonia: A Meta-analysis and Systematic Review

Abstract Background The 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines argue against routine pneumococcal urinary antigen testing (pUAT), except in patients with severe community-acquired pneumonia (CAP). Recent studies, however, have suggested that these recommendations identify a low-risk population, resulting in missed opportunities for antimicrobial stewardship. The optimal patient population for pUAT thus remains unknown. Our objective was to summarize predictors of pUAT positivity among patients hospitalized with CAP as determined by previous observational studies. Methods We systematically searched MEDLINE, Embase, Web of Science, and Scopus for articles related to urinary antigen tests and community-acquired pneumonia. Studies published until August 26, 2021, were included if risk factors for pUAT positivity in adult patients with CAP were evaluated with multivariable analyses. No language filters or limits were applied in order to capture all potentially relevant material. Two investigators independently screened studies, extracted, and compiled data. Results Of the 1,144 studies that were screened, 9 met the inclusion criteria, representing 8,536 patients who underwent pUAT. The most frequent independent risk factors associated with a positive pUAT were intensive care unit (ICU) admission (OR 1.77, 95% CI 1.27 – 2.48, I2 = 21%) (Figure 1) and female sex (OR 1.53, 95% CI 1.19 – 1.97, I2 = 36%) (Figure 2). Laboratory parameters such as C-reactive protein (OR 0.26, 95% CI 0.02 – 4.49, I2 = 93%) and BUN (OR 1.36, 95% CI 0.84 – 2.19, I2 = 93%) were not significantly associated with pUAT positivity. Many variables were inconsistently reported and thus could not be combined for analysis, including age > 65, current smoking, history of emphysema, hyponatremia, certain markers of severity, and antibiotic history. Figure 1:Forest plot of the association between ICU admission and positive pneumococcal UAT. The vertical line corresponds to the no difference point between the two groups. Squares, the size of which indicates the proportion of information given by each study, correspond to ORs. Horizontal lines represent the 95% CIs. The diamond indicates the pooled odds ratios. df = degrees of freedom; IV = inverse variance Figure 2:Forest plot of the association between female sex and positive pneumococcal UAT. The vertical line corresponds to the no difference point between the two groups. Squares, the size of which indicates the proportion of information given by each study, correspond to ORs. Horizontal lines represent the 95% CIs. The diamond indicates the pooled odds ratios. df = degrees of freedom; IV = inverse variance Conclusion Consistent with current guidelines, ICU admission, an indication of severe CAP, appears to be an important predictor of pUAT positivity. Additionally, however, female sex was significantly associated with pUAT positivity. Recognition of these risk factors can assist in identifying patient populations most likely to benefit from pUAT and may be considered in future CAP guidelines. Disclosures Abhishek Deshpande, MD, PhD, Clorox: Grant/Research Support|Merck: Advisor/Consultant|Seres Therapeutics: Grant/Research Support.

Effectiveness of Beta-Lactam plus Doxycycline for Patients Hospitalized with Community-Acquired Pneumonia.

Despite clinical practice guideline recommendations to use doxycycline as part of combination therapy for some patients hospitalized with pneumonia, there is minimal evidence supporting this recommendation. Our aim was to examine the association between beta-lactam plus doxycycline and mortality for patients hospitalized with community-acquired pneumonia. We identified patients >65 years of age admitted to any US Department of Veterans Affairs hospital in fiscal years 2002-2012 with a discharge diagnosis of pneumonia. We excluded those patients who did not receive antibiotic therapy concordant with the 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) clinical practice guidelines. Using propensity score matching, we examined the association of doxycycline with 30- and 90-day mortality. Our overall cohort was comprised of 70533 patients and 5282 (7.49%) received doxycycline. Unadjusted 30-day mortality was 6.4% for those who received a beta-lactam plus doxycycline versus 9.1% in those who did not (P < .0001), and 90-day mortality was 13.8% for those who received a beta-lactam + doxycycline versus 16.8% for those who did not (P < .0001). In the propensity score matched models, both 30- (odds ratio 0.72, 95% confidence interval [CI], .63-.84) and 90-day (0.83, 95% CI, .74-.92) mortality were significantly lower for those who received doxycycline. In this retrospective observational cohort study, we found that doxycycline use, as part of guideline-concordant antibiotic therapy, was associated with lower 30- and 90-day mortality than regimens without doxycycline. While this supports the safety and effectiveness of antibiotic regimes that include doxycycline, additional studies, especially randomized clinical trials, are needed to confirm this.

Risk factors for nontuberculous mycobacterial pulmonary disease (NTM-PD) in Croatia

The incidence, geographical distribution and clinical relevance of different nontuberculous mycobacteria (NTM) in Croatia are well described. There are few data on the risk factors for developing NTM pulmonary disease (NTM-PD) in this setting. We conducted aretrospective cohort study on all Croatian residents with NTM isolated from respiratory samples in the period from 2006 to 2015 with follow-up to 2018. The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines were used to establish NTM-PD diagnosis. Clinical, radiological and treatment data were collected from hospital records. Risk analysis calculations were made on the 439 isolation episodes that were classified as definitive NTM-PD (n = 137) or no disease (n = 302). Female gender, presence of bronchiectasis, low BMI and long-term systemic corticosteroid treatment were independent risk factors associated with NTM-PD. Hemoptysis and malaise were presenting symptoms independently associated with NTM-PD. Chronic obstructive pulmonary disease (COPD) and low/moderate dose inhaled corticosteroid (ICS) treatment were not associated with NTM-PD. High dose ICS treatment was asignificant risk factor for developing NTM-PD (aOR = 4.73, CI 1.69-13.23 p = 0.003). The NTM-PD patients in Croatia are similar to those in other published cohorts in terms of their characteristics and risk factors. The significant dose-dependent association between ICS use and NTM-PD adds to the body of evidence suggesting that high dose ICS use is associated with NTM-PD.

Diagnostic Validity of Gastric Aspirate Culture in Nontuberculous Mycobacterial Pulmonary Disease.

Rationale: Although gastric aspirate culture is used for diagnosing pulmonary tuberculosis, its usefulness in diagnosing pulmonary infections of nontuberculous mycobacteria (NTM) is unknown.Objectives: To investigate the diagnostic validity of gastric aspirate culture for acid-fast bacilli in NTM pulmonary disease (NTM-PD).Methods: Gastric aspirates were collected from patients with suspected NTM-PD at the Osaka Toneyama Medical Center between December 2006 and February 2018. Patients with a final diagnosis of pulmonary tuberculosis, an observation period of less than 6 months, or fewer than three conducted sputum cultures were excluded from the study. NTM-PD was diagnosed as per American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) criteria. We retrospectively examined the diagnostic validity of gastric aspirate culture in Mycobacterium avium complex (MAC)-PD and M. kansasii-PD by comparing culture results with final diagnoses. This was done first for all patients, and subsequently for patients with negative results for early sputum cultures. In addition, we compared the time required for an NTM-PD diagnosis based on gastric aspiration with that based on ATS/IDSA criteria.Results: Among 475 total patients, 119 (25.1%) had positive NTM gastric aspirate cultures and 154 (32.4%) fulfilled the ATS/IDSA criteria for NTM-PD. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPVs) of gastric aspiration were 63.9%, 95.8%, 83.5%, and 88.8% in MAC-PD and 82.4%, 99.6%, 87.5%, and 99.3% in M. kansasii-PD, respectively. Sensitivity, specificity, PPV, and NPV of gastric aspirate cultures of the 378 patients who were undiagnosed based on sputum culture within 120 days were 34.0%, 95.5%, 51.6%, and 91.1% for MAC-PD and 75.0%, 99.5%, 60.0%, and 99.7% for M. kansasii-PD, respectively. Furthermore, gastric aspirate cultures tested in addition to bronchoscopy yielded incremental sensitivity of 8.7% (95.7% vs. 87.0%) and an NPV of 1.3% (99.3% vs. 98.0%) in MAC-PD. In patients with NTM-PD with NTM-positive gastric aspirate cultures, the period between gastric aspirate collection and the positive culture result was shorter than the time between gastric aspirate collection and NTM-PD diagnosis (6 [9-36] d vs. 25 [12-69] d, median [interquartile range], P < 0.0001].Conclusions: In settings where acid-fast bacilli pulmonary diseases are suspected, gastric aspirate culture may be helpful for diagnosing MAC-PD and M. kansasii-PD.

Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study.

An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p < 0.01). S. pneumoniae remains the most common pathogen in patients hospitalized with CAP. Multinational CPG recommendations for patients with CAP seem to appropriately cover the most common pathogens and should be strongly encouraged for the management of CAP patients.Electronic supplementary materialThe online version of this article (10.1007/s10096-020-03870-3) contains supplementary material, which is available to authorized users.

Variability in the Management of Adults With Pulmonary Nontuberculous Mycobacterial Disease.

The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%. Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

Editorial introductions

Current Opinion in Infectious Diseases was launched in 1988. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of infectious diseases is divided into 11 sections that are reviewed once a year. Each section is assigned to a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Matteo BassettiMatteo BassettiMatteo Bassetti is Head of the Infectious Diseases Division of the Santa Maria Misericordia University Hospital in Udine and Associate Professor of Infectious Diseases at the University of Udine, Italy. Dr Bassetti studied at the University of Genoa School of Medicine, Italy and continued his medical education at the Yale University School of Medicine, New Haven, USA with an Infectious Diseases fellowship. Dr Bassetti is chair of the Critically Ill Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the secretary of the Infectious Diseases Group of the European Organisation for Research and Treatment of Cancer (EORTC). Dr Bassetti is also co-chair of the Intra-abdominal Infections Study Group and secretary of the Bone, Skin and Soft Tissue Infections of the International Society of Chemotherapy (ISC). He is the vice-president of Italian Society of Anti-infective Therapy (SITA). He is member-elected (2018–2022) of International Council of the Immunocompromised Host Society (ICHS). He serves on the editorial board of several journals including Intensive Care Medicine (Associate-Section Editor), Nature Scientific Reports, Italian Journal of Medicine (Section Editor), Drugs in Context (Associate editor), Journal of Infection and Public Health, Journal of Global Antimicrobial Resistance, Reviews in Medical Microbiology, GMS Infectious Diseases, Journal of Chemotherapy, Infectious Disease, Clinical Microbiology and Antimicrobial Chemotherapy and is a reviewer for several international journals. Author or co-author of more than 350 papers (H index 51; 10500 citations) published in international peer-review journals on antibiotic therapy, fungal infections, antimicrobial resistances, infections in immunocompromised patients and critically ill patients. Michael S. NiedermanMichael S. NiedermanProfessor Michael S. Niederman is Clinical Director and Associate Chief in the division of Pulmonary and Critical Care Medicine at Weill Cornell Medical Center, New York, and Professor of Clinical Medicine at Weill Cornell Medical College, New York. Prior to this, he was Professor in the Department of Medicine at State University of New York at Stony Brook, and Chairman of the Department of Medicine at Winthrop University Hospital in Mineola, New York for sixteen years. He obtained his medical degree from the Boston University School of Medicine, Massachusetts, and then completed his training in internal medicine at the Northwestern University School of Medicine, Illinois, before undertaking a Pulmonary and Critical Care fellowship at Yale University School of Medicine, Connecticut. His interests lie in respiratory tract infections, and include mechanisms of airway colonization, the management of community - and hospital-acquired pneumonia, the role of guidelines for pneumonia, and the impact of antibiotic resistance on the management and outcomes of respiratory tract infections. He has published over 400 peer-reviewed or review articles, and has lectured widely both nationally and internationally. Prof. Niederman served as co-chairman of the committees that created the American Thoracic Society 1993 and 2001 guidelines for the treatment of community-acquired pneumonia, as well as the 1996 and 2005 committees that wrote guidelines for the treatment of nosocomial pneumonia. In addition, he was a member of the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) committee that published guidelines for community-acquired pneumonia in 2007 and co-lead author of the 2017 European Respiratory Society/European Society of Intensive Care Medicine (ERS/ESICM) guidelines for nosocomial pneumonia. He served for 6 years as a member of the Board of Regents of the American College of Chest Physicians and in 2013 was elected as a Master of the American College of Physicians. He is also Editor-in-Chief of Clinical Pulmonary Medicine, and serves on the editorial boards of Critical Care Medicine, Intensive Care Medicine, Critical Care, and Chest. He has previously served on the editorial board of The American Journal of Respiratory and Critical Care Medicine.

Pulmonary isolation and clinical relevance of nontuberculous mycobacteria during nationwide survey in Serbia, 2010-2015.

The rates of pulmonary colonization and disease due to nontuberculous mycobacteria (NTM) appear to be increasing globally, but diversity of species recovered as well as clinical relevance of NTM isolates differ considerably by geographic region. The first nationwide study of isolation frequency and clinical significance of NTM in Serbia included all patients with respiratory specimens yielding a positive NTM culture over the six-year period, 2010–2015. We analyzed trends in annual NTM isolation and NTM pulmonary disease (PD) incidence rates, with NTM PD cases defined in accordance with microbiological criteria established by the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA). 777 pulmonary NTM isolates were collected from 565 patients, of whom 126 (22.3%) met the ATS/IDSA criteria. The annual NTM isolation and NTM PD incidence rates per 100,000 changed over 2010–2015 from 0.9 to 1.6 (p = 0.1746) and from 0.18 to 0.48 (p = f0.0040), respectively. Both isolation and disease rates increased considerably with age, while higher NTM PD rates were also associated with residence in urbanized areas. Diversity of NTM species isolated was shown to be region-specific, with M. xenopi as the most prevalent species (17.3%), and increasing isolation rates of rapid growing mycobacteria (RGM) (p = 0.0072). M. xenopi was also the most common cause of NTM PD (28.6%), followed by RGM (27.8%). With 73% clinically relevant isolates, M. abscessus was identified as the most clinically relevant NTM species. While NTM PD obviously remains a rare disease in Serbia, the overall results justify recognition of NTM as pathogens of rising importance, and require further characterization of their epidemiology in the country.

Editorial introductions

Current Opinion in Infectious Diseases was launched in 1988. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of infectious diseases is divided into 11 sections that are reviewed once a year. Each section is assigned to a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Matteo BassettiMatteo BassettiProfessor Matteo Bassetti is Head of the Infectious Diseases Division of the Santa Maria Misericordia University Hospital, Udine, Italy and Associate-Professor of Infectious Diseases at the University of Udine. He studied at the University of Genoa School of Medicine, Italy and continued his medical education at the Yale University School of Medicine, Connecticut, USA with an infectious diseases fellowship. He also completed a PhD in solid organ transplantation and infectious diseases at the University of Genoa School of Medicine. Professor Bassetti is the chair of the Critically Ill Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and a member of the executive committee of the Infectious Diseases Group of the European Organisation for Research and Treatment of Cancer (EORTC). Professor Bassetti is also co-chair of the Intra-Abdominal Infections Study Group and secretary of the Bone, Skin and Soft Tissue Infections of the International Society of Chemotherapy (ISC). Professor Bassetti is the vice-president of Italian Society of Anti-Infective Therapy (SITA). He serves on the editorial board of several journals including Intensive Care Medicine (Associate-Section Editor), Journal of Global Antimicrobial Resistance, Journal of Infection and Public Health, Italian Journal of Medicine (Section Editor), Reviews in Medical Microbiology, Journal of Chemotherapy, and Scientific Reports and is reviewer for various international journals. Prof. Bassetti has authored or co-authored over 250 papers published in international peer-reviewed journals with more than 7000 citations (H-index 42). His main interests are bacterial resistance, fungal infections and infections in critically ill patients. Michael S. NiedermanMichael S. NiedermanProfessor Michael S. Niederman is Clinical Director and Associate Chief in the division of Pulmonary and Critical Care Medicine at Weill Cornell Medical Center, New York, and Professor of Clinical Medicine at Weill Cornell Medical College, New York. Prior to this, he was Professor in the Department of Medicine at State University of New York at Stony Brook, and Chairman of the Department of Medicine at Winthrop University Hospital in Mineola, New York for sixteen years. He obtained his medical degree from the Boston University School of Medicine, Massachusetts, and then completed his training in internal medicine at the Northwestern University School of Medicine, Illinois, before undertaking a pulmonary and critical care fellowship at Yale University School of Medicine, Connecticut. His interests lie in respiratory tract infections, and include mechanisms of airway colonization, the management of community- and hospital-acquired pneumonia, the role of guidelines for pneumonia, and the impact of antibiotic resistance on the management and outcomes of respiratory tract infections. He has published over 400 peer-reviewed or review articles, and has lectured widely both nationally and internationally. Prof. Niederman served as co-chairman of the committees that created the American Thoracic Society 1993 and 2001 guidelines for the treatment of community-acquired pneumonia, as well as the 1996 and 2005 committees that wrote guidelines for the treatment of nosocomial pneumonia. In addition, he was a member of the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) committee that published guidelines for community-acquired pneumonia in 2007 and co-lead author of the 2017 European Respiratory Society/European Society of Intensive Care Medicine (ERS/ESICM) guidelines for nosocomial pneumonia. He served for 6 years as a member of the Board of Regents of the American College of Chest Physicians and in 2013 was elected as a Master of the American College of Physicians. He is also Editor-in-Chief of Clinical Pulmonary Medicine, and serves on the editorial boards of Critical Care Medicine, Intensive Care Medicine, Critical Care, and Chest. He has previously served on the editorial board of The American Journal of Respiratory and Critical Care Medicine.

Impact of Gram stain results on initial treatment selection in patients with ventilator-associated pneumonia: a retrospective analysis of two treatment algorithms

BackgroundVentilator-associated pneumonia (VAP) is a common and serious problem in intensive care units (ICUs). Several studies have suggested that the Gram stain of endotracheal aspirates is a useful method for accurately diagnosing VAP. However, the usefulness of the Gram stain in predicting which microorganisms cause VAP has not been established. The purpose of this study was to evaluate whether a Gram stain of endotracheal aspirates could be used to determine appropriate initial antimicrobial therapy for VAP.MethodsData on consecutive episodes of microbiologically confirmed VAP were collected from February 2013 to February 2016 in the ICU of a tertiary care hospital in Japan. We constructed two hypothetical empirical antimicrobial treatment algorithms for VAP: a guidelines-based algorithm (GLBA) based on the recommendations of the American Thoracic Society-Infectious Diseases Society of America (ATS-IDSA) guidelines and a Gram stain-based algorithm (GSBA) which limited the choice of initial antimicrobials according to the results of bedside Gram stains. The GLBA and the GSBA were retrospectively reviewed for each VAP episode. The initial coverage rates and the selection of broad-spectrum antimicrobial agents were compared between the two algorithms.ResultsDuring the study period, 219 suspected VAP episodes were observed and 131 episodes were assessed for analysis. Appropriate antimicrobial coverage rates were not significantly different between the two algorithms (GLBA 95.4% versus GSBA 92.4%; p = 0.134). The number of episodes for which antimethicillin-resistant Staphylococcus aureus agents were selected as an initial treatment was larger in the GLBA than in the GSBA (71.0% versus 31.3%; p < 0.001), as were the number of episodes for which antipseudomonal agents were recommended as an initial treatment (70.2% versus 51.9%; p < 0.001).ConclusionsAntimicrobial treatment based on Gram stain results may restrict the administration of broad-spectrum antimicrobial agents without increasing the risk of treatment failure.Trial registrationUMIN-CTR, UMIN000026457. Registered 8 March 2017 (retrospectively registered).

Time to Guideline-Based Empiric Antibiotic Therapy in the Treatment of Pneumonia in a Community Hospital

Purpose: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines for hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health care-associated pneumonia (HCAP) stress the importance of initiating prompt appropriate empiric antibiotic therapy. This study’s purpose was to determine the percentage of patients with HAP, VAP, and HCAP who received guideline-based empiric antibiotic therapy and to determine the average time to receipt of an appropriate empiric regimen. Methods: A retrospective chart review of adults with HAP, VAP, or HCAP was conducted at a community hospital in suburban Birmingham, Alabama. The hospital’s electronic medical record system utilized International Classification of Diseases, Ninth Revision (ICD-9) codes to identify patients diagnosed with pneumonia. The percentage of patients who received guideline-based empiric antibiotic therapy was calculated. The mean time from suspected diagnosis of pneumonia to initial administration of the final antibiotic within the empiric regimen was calculated for patients who received guideline-based therapy. Results: Ninety-three patients met the inclusion criteria. The overall guideline adherence rate for empiric antibiotic therapy was 31.2%. The mean time to guideline-based therapy in hours:minutes was 7:47 for HAP and 28:16 for HCAP. For HAP and HCAP combined, the mean time to appropriate therapy was 21:55. Conclusion: Guideline adherence rates were lower and time to appropriate empiric therapy was greater for patients with HCAP compared to patients with HAP.

First you have to row a little boat

See article, page 348

Telavancin for Hospital-Acquired Pneumonia: Clinical Response and 28-Day Survival

U.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality. The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in a post hoc analysis. ATS/IDSA criteria were applied in a blind fashion to the original all-treated (AT) group. Clinical cure rates at final follow-up were determined in the refined AT and clinically evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively). The exploratory endpoint of 28-day survival was evaluated for the ATS/IDSA-AT group. Noninferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%) and ATS/IDSA-CE (83% versus 80%) groups. Cure rates favored telavancin in ATS/IDSA-CE patients where Staphylococcus aureus was the sole pathogen (86% versus 75%). Overall, 28-day survival rates were similar in the telavancin (76%) and vancomycin (77%) groups but lower in telavancin-treated patients with preexisting moderate-to-severe renal impairment (creatinine clearance [CLCR] of <50 ml/min). Telavancin should be administered to patients with moderate-to-severe renal impairment only if treatment benefit outweighs the risk or if no suitable alternatives are available.

Is a Strategy Based on Routine Endotracheal Cultures the Best Way to Prescribe Antibiotics in Ventilator-Associated Pneumonia?

The objectives of this study were to evaluate if a strategy based on routine endotracheal aspirate (ETA) cultures is better than using the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines to prescribe antimicrobials in ventilator-associated pneumonia (VAP). This was a prospective, observational, cohort study conducted in a 15-bed ICU and comprising 283 patients who were mechanically ventilated for ≥48 h. Interventions included twice-weekly ETA; BAL culture was done if VAP was suspected. BAL (collected at the time of VAP) plus ETA cultures (collected≤7 days before VAP) (n=146 different pairs) were defined. We compared two models of 10 days of empirical antimicrobials (ETA-based vs ATS/IDSA guidelines-based strategies), analyzing their impact on appropriateness of therapy and total antimicrobial-days, using the BAL result as the standard for comparison. Complete ETA and BAL culture concordance (identical pathogens or negative result) occurred in 52 pairs; discordance (false positive or false negative) in 67, and partial concordance in two. ETA predicted the etiology in 62.4% of all pairs, in 74.0% of pairs if ETA was performed≤2 days before BAL, and in 46.2% of pairs if ETA was performed 3 to 7 days before BAL (P=.016). Strategies based on the ATS/IDSA guidelines and on ETA results led to appropriate therapy in 97.9% and 77.4% of pairs, respectively (P<.001). The numbers of antimicrobial-days were 1,942 and 1,557 for therapies based on ATS/IDSA guidelines and ETA results, respectively (P<.001). The ATS/IDSA guidelines-based approach was more accurate than the ETA-based strategy for prescribing appropriate, initial, empirical antibiotics in VAP, unless a sample was available≤2 days of the onset of VAP. The ETA-based strategy led to fewer days on prescribed antimicrobials.

Effects of adherence to ventilator-associated pneumonia treatment guidelines on clinical outcomes

Two guidelines are currently available to guide Japanese clinicians caring for patients with ventilator-associated pneumonia (VAP): the 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines or the 2008 Japanese Respiratory Society (JRS) guidelines. We aimed to measure compliance with guideline recommendations for VAP in Japanese intensive care units (ICUs) and to assess the effects of guideline-compliant treatment on outcomes. We retrospectively reviewed the records of all patients with microbiologically confirmed VAP in five Japanese ICUs between January 1, 2006, and December 31, 2009. We evaluated whether empiric antibiotic prescriptions were guideline compliant and correlated compliance with clinical outcomes. Among the 95 patients with VAP who were included, 85 patients received empiric antibiotics. Of these, therapy of 62 patients (73%) was appropriate based on in vitro sensitivity testing. Using ATS/IDSA criteria, 16 patients (19%) received guideline-compliant therapy and 69 patients (81%) received noncompliant treatment. Using JRS criteria, 24 patients (28%) received guideline-compliant therapy and 61 patients (72%) received noncompliant treatment. All-cause 28-day mortality was 24%. When compared to patients who received noncompliant therapy, there were no differences in 28-day mortality rates for patients who received ATS/IDSA guideline-compliant regimens (25 vs. 25%, p=1.00) or JRS guideline-compliant regimens (21 vs. 26%, p=0.78). Our study demonstrates poor compliance with guideline-recommended antibiotic therapy for VAP in Japanese ICUs. Compliance with current VAP guidelines was not associated with increased rates of appropriate antibiotic treatment or improved 28-day mortality.

Clinical features of healthcare‐associated pneumonia (HCAP) in a Japanese community hospital: Comparisons among nursing home‐acquired pneumonia (NHAP), HCAP other than NHAP, and community‐acquired pneumonia

More than 100000 Japanese die of pneumonia every year. The number of people residing in nursing homes is increasing with the ageing of the population. In 2005, the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) published important guidelines for the management of healthcare-associated pneumonia (HCAP). In Japan, however, the optimum strategy for management of HCAP is still unclear. The purpose of this study was to clarify the clinical features of patients with HCAP. Patients (n = 202) who were consecutively admitted with a diagnosis of acute pneumonia between October 2007 and September 2009 were retrospectively evaluated. Using the ATS/IDSA guidelines, patients were divided into three groups: a community-acquired pneumonia (CAP) group (n = 123), a nursing home-acquired pneumonia (NHAP) group (n = 46) and a HCAP other than NHAP (O-HCAP) group (n = 33). These groups were then compared with respect to laboratory data, microbiological findings and mortality. Thirty-day mortality in the NHAP group (10.9%) tended to be higher than that in the CAP group (3.3%) or the O-HCAP group (0%). The pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae in the CAP group, methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae in the NHAP group, and S. pneumoniae and K. pneumoniae in the O-HCAP group. The NHAP group was clinically different from the O-HCAP group, based on bacteriological examination and mortality rates. In order to accurately diagnose, and formulate optimum treatment strategies for Japanese patients, the categories of HCAP, as specified in the ATS/IDSA guidelines, should not be applied directly either to patients with NHAP or those with O-HCAP.

Impact of guideline-consistent therapy on outcome of patients with healthcare-associated and community-acquired pneumonia

A new category of healthcare-associated pneumonia (HCAP) has been added in the most recent American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines, since multidrug-resistant (MDR) pathogens are more common in patients with HCAP than in those with community-acquired pneumonia (CAP). The optimal empirical management of patients with HCAP remains controversial and adherence to guidelines is inconsistent. A retrospective cohort study of 3295 adults admitted for pneumonia in an academic centre of Canada, between 1997 and 2008. MDR pathogens were more common among patients with HCAP than in those with CAP, but less so than in other studies. Compared with patients with CAP, those with HCAP had a higher all-cause 30 day mortality [68/563 (12%) versus 201/2732 (7%); P < 0.001] and more frequent need for mechanical ventilation [78/563 (14%) versus 276/2732 (10%); P = 0.01]. In patients with CAP, mortality was lower when treatment was concordant with guidelines [86/1557 (6%) versus 109/1097 (10%) if discordant; adjusted odds ratio 0.6 (0.4-0.8); P < 0.001]. In HCAP, mortality was similar whether or not empirical treatment was concordant with guidelines [6/35 (17%) versus 18/148 (12%) if discordant; P = 0.4]. However, 30 day mortality tended to be higher when the empirical treatment was microbiologically ineffective [4/22 (18%) versus 17/187 (9%) when effective; P = 0.3]. HCAP is associated with worse outcomes than CAP. MDR pathogens were implicated in only a small fraction of HCAP cases. In our study, unlike CAP, non-respect of current HCAP guidelines had no adverse effect on the ultimate outcome. Strategies for the empirical management of HCAP should be tailored to the local epidemiological context.

Medical resource utilization among community-acquired pneumonia patients initially treated with levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily: A US-based study

ABSTRACTObjective: The 2007 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines recommend that community-acquired pneumonia (CAP) patients admitted to hospital wards initially receive respiratory fluoroquinolone monotherapy or β-lactam plus macrolide combination therapy. There is little evidence as to which regimen is preferred, or if differences in medical resource utilization exist between therapies. Thus, the authors compared length of hospital stay (LOS) and length of intravenous antibiotic therapy (LOIV) for patients who received initial levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily (‘combination therapy’).Research design and methods: Adult hospital CAP cases from January 2005 to December 2007 were identified by principal discharge diagnosis code. Patients with a chest infiltrate and medical notes indicative of CAP were included. Direct intensive care unit admits and healthcare-associated cases were excluded. A propensity score technique was used to balance characteristics associated with initial antimicrobial therapy using multivariable regression to derive the scores. Propensity score categories, defined as propensity score quintiles, rather than propensity scores themselves, were used in the least squares regression model to assess the impact of LOS and LOIV.Results: A total of 495 patients from six hospitals met study criteria. Of these, 313 (63%) received levofloxacin and 182 (37%) received combination therapy. Groups were similar with respect to age, sex, most comorbidities, presenting signs and symptoms, and Pneumonia Severity Index (PSI) risk class. Patients on combination therapy were more likely to have heart failure and receive pre-admission antibiotics. Adjusted least squares mean (±SE) LOS and LOIV were shorter with levofloxacin versus combination therapy: LOS, 4.6 ± 0.17 vs. 5.4 ± 0.22 days, p < 0.01; and LOIV, 3.6 ± 0.17 vs. 4.8 ± 0.21 days, p < 0.01. Results for PSI risk class III or IV patients were: LOS, 5.0 ± 0.30 vs. 5.9 ± 0.37 days, p = 0.07; and LOIV, 3.7 ± 0.33 vs. 5.2 ± 0.39 days, p < 0.01. Due to the retrospective study design, limited sample size, and scope (single health-network), the authors encourage replication of this study in other data sources.Conclusions: Given the LOS and LOIV reductions of 0.8 and 1.2 days, respectively, utilization of levofloxacin 750 mg daily for CAP patients admitted to the medical floor has the potential to result in substantial cost savings for US hospitals.