Archive for January, 2017

Executive Summary: Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society

Clinical Infectious Diseases September 15, 2016 V.63 N.5 P. 575-582           


Andre C. Kalil, Mark L. Metersky, Michael Klompas, John Muscedere, Daniel A. Sweeney, Lucy B. Palmer, Lena M. Napolitano, Naomi P. O’Grady, John G. Bartlett, Jordi Carratalà, Ali A. El Solh, Santiago Ewig, Paul D. Fey, Thomas M. File, Jr, Marcos I. Restrepo, Jason A. Roberts, Grant W. Waterer, Peggy Cruse, Shandra L. Knight, and Jan L. Brozek

1Department of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha

2Division of Pulmonary and Critical Care Medicine, University of Connecticut School of Medicine, Farmington

3Brigham and Women’s Hospital and Harvard Medical School

4Harvard Pilgrim Health Care Institute, Boston, Massachusetts

5Department of Medicine, Critical Care Program, Queens University, Kingston, Ontario, Canada

6Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego

7Department of Medicine, Division of Pulmonary Critical Care and Sleep Medicine, State University of New York at Stony Brook

8Department of Surgery, Division of Trauma, Critical Care and Emergency Surgery, University of Michigan, Ann Arbor

9Department of Critical Care Medicine, National Institutes of Health, Bethesda

10Johns Hopkins University School of Medicine, Baltimore, Maryland

11Department of Infectious Diseases, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute, Spanish Network for Research in Infectious Diseases, University of Barcelona, Spain

12Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, Veterans Affairs Western New York Healthcare System, New York

13Thoraxzentrum Ruhrgebiet, Department of Respiratory and Infectious Diseases, EVK Herne and Augusta-Kranken-Anstalt Bochum, Germany

14Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha

15Summa Health System, Akron, Ohio

16Department of Medicine, Division of Pulmonary and Critical Care Medicine, South Texas Veterans Health Care System and University of Texas Health Science Center at San Antonio

17Burns, Trauma and Critical Care Research Centre, The University of Queensland

18Royal Brisbane and Women’s Hospital, Queensland

19School of Medicine and Pharmacology, University of Western Australia, Perth, Australia

20Library and Knowledge Services, National Jewish Health, Denver, Colorado

21Department of Clinical Epidemiology and Biostatistics and Department of Medicine, McMaster University, Hamilton, Ontario, Canada

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances.

These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel’s recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.



January 27, 2017 at 8:14 am

IDSA GUIDELINE – Executive Summary: 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis

Clinical Infectious Diseases September 15, 2016 V.63 N.6 P.717-722

John N. Galgiani, Neil M. Ampel, Janis E. Blair, Antonino Catanzaro, Francesca Geertsma, Susan E. Hoover, Royce H. Johnson, Shimon Kusne, Jeffrey Lisse, Joel D. MacDonald, Shari L. Meyerson, Patricia B. Raksin, John Siever, David A. Stevens, Rebecca Sunenshine, and Nicholas Theodore

1Valley Fever Center for Excellence

2Division of Infectious Diseases, University of Arizona, Tucson

3Division of Infectious Diseases, Mayo Clinic, Scottsdale, Arizona

4Division of Pulmonary and Critical Care, University of California, San Diego

5Department of Pediatrics, Infectious Diseases, Stanford University School of Medicine, California

6Division of Sanford Health, Sioux Falls, South Dakota

7David Geffen School of Medicine at UCLA, Department of Medicine, Kern Medical Center, Bakersfield, California

8Department of Rheumatology, University of Arizona, Tucson

9Department of Neurosurgery School of Medicine, University of Utah, Salt Lake City

10Division of Thoracic Surgery, Northwestern University, Feinberg School of Medicine

11Division of Neurosurgery, John H. Stroger Jr Hospital of Cook County, Chicago, Illinois

12Arizona Pulmonary Specialists, Ltd, Phoenix

13Division of Infectious Diseases, Stanford University School of Medicine, California

14Career Epidemiology Field Officer Program, Division of State and Local Readiness, Office of Public Health Preparedness and Response, Centers for Disease Control and Prevention

15Maricopa County Department of Public Health

16Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona

It is important to realize that guidelines cannot always account for individual variation among patients.

They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances.

Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere.

Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes.

These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications.

Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.


January 27, 2017 at 8:10 am

IDSA GUIDELINE – Executive Summary: Official American Thoracic Society-Centers for Disease Control and Prevention-Infectious Diseases Society of America Clinical Practice Guidelines -Treatment of Drug-Susceptible Tuberculosis

Clinical Infectious Diseases October 1, 2016 V.63 N.7 P.853-867

Payam Nahid1, Susan E. Dorman2, Narges Alipanah1, Pennan M. Barry3, Jan L. Brozek4, Adithya Cattamanchi1, Lelia H. Chaisson1, Richard E. Chaisson2, Charles L. Daley5, Malgosia Grzemska6, Julie M. Higashi7, Christine S. Ho8, Philip C. Hopewell1, Salmaan A. Keshavjee9, Christian Lienhardt6, Richard Menzies10, Cynthia Merrifield1, Masahiro Narita12, Rick O’Brien13, Charles A. Peloquin14, Ann Raftery1, Jussi Saukkonen15, H. Simon Schaaf16, Giovanni Sotgiu17, Jeffrey R. Starke18, Giovanni Battista Migliori11, and Andrew Vernon8

1University of California, San Francisco

2Johns Hopkins University, Baltimore, Maryland

3California Department of Public Health, Richmond

4McMaster University, Hamilton, Ontario, Canada

5National Jewish Health, Denver, Colorado

6World Health Organization, Geneva, Switzerland

7Tuberculosis Control Section, San Francisco Department of Public Health, California

8Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

9Harvard Medical School, Boston, Massachusetts

10McGill University, Montreal, Quebec, Canada

11WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri Care and Research Institute, Tradate, Italy

12Tuberculosis Control Program, Seattle and King County Public Health, and University of Washington, Seattle

13Ethics Advisory Group, International Union Against TB and Lung Disease, Paris, France

14University of Florida, Gainesville

15Boston University, Massachusetts

16Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa

17University of Sassari, Italy

18Baylor College of Medicine, Houston, Texas

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association.

Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline.

This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis.

For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology.

Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions.

Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided.

The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research.

See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.


January 27, 2017 at 8:07 am

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial.

BMJ Open. 2015 Mar 11;5(3):e006723.

Shaw E1, Miró JM2, Puig-Asensio M3, Pigrau C3, Barcenilla F4, Murillas J5, Garcia-Pardo G6, Espejo E7, Padilla B8, Garcia-Reyne A9, Pasquau J10, Rodriguez-Baño J11, López-Contreras J12, Montero M13, de la Calle C2, Pintado V14, Calbo E15, Gasch O16, Montejo M17, Salavert M18, Garcia-Pais MJ19, Carratalà J1, Pujol M1; Spanish Network for Research in Infectious Diseases (REIPI RD12/0015); Instituto de Salud Carlos III, Madrid, Spain; GEIH (Hospital Infection Study Group).

Collaborators (47)

Author information

1Hospital Universitari de Bellvitge-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.

2Hospital Universitari Clínic-IDIBAPS, Barcelona, Spain.

3Hospital Universitari Vall d’Hebron, Barcelona, Spain.

4Hospital Universitari Arnau de Vilanova, Lleida, Spain.

5Hospital Universitari Son Espases, Mallorca, Spain.

6Hospital Universitari Joan XXIII, Tarragona, Spain.

7Hospital Universitari de Terrassa, Terrassa, Barcelona, Spain.

8Hospital Universitario Gregorio Marañon, Madrid, Spain.

9Hospital Universitario 12 de Octubre, Madrid, Spain.

10Hospital Universitario Virgen de las Nieves, Granada, Spain.

11Hospital Universitario Virgen Macarena, Sevilla, Spain.

12Hospital Universitari Santa Creu i Sant Pau, Barcelona, Spain.

13Hospital Universitari Parc de Salut Mar, Barcelona, Spain.

14Hospital Universitario Ramón y Cajal, Madrid, Spain.

15Hospital Universitari Mutúa de Terrassa, Barcelona, Spain.

16Corporació Sanitaria Parc Taulí, Sabadell, Barcelona, Spain.

17Hospital Universitario de Cruces, Barakaldo, Spain.

18Hospital Universitari i Politècnic la Fe, Valencia, Spain.

19Hospital Universitario Lucus Augusti, Lugo, Spain.



Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone.


A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis.


The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study.



January 26, 2017 at 3:39 pm

Treatment Options for Carbapenem-Resistant Enterobacteriaceae Infections.

Open Forum Infect Dis. 2015 May 5;2(2):ofv050.

Morrill HJ1, Pogue JM2, Kaye KS3, LaPlante KL4.

Author information

1Veterans Affairs Medical Center , Infectious Diseases Research Program , Providence, Rhode Island ; College of Pharmacy, Department of Pharmacy Practice , University of Rhode Island , Kingston.

2Department of Pharmacy Services.

3Division of Infectious Diseases , Detroit Medical Center, Wayne State University , Michigan.

4Veterans Affairs Medical Center , Infectious Diseases Research Program , Providence, Rhode Island ; College of Pharmacy, Department of Pharmacy Practice , University of Rhode Island , Kingston ; Division of Infectious Diseases , Warren Alpert Medical School of Brown University , Providence, Rhode Island.


This article provides a comprehensive review of currently available treatment options for infections due to carbapenem-resistant Enterobacteriaceae (CRE).

Antimicrobial resistance in Gram-negative bacteria is an emerging and serious global public health threat. Carbapenems have been used as the “last-line” treatment for infections caused by resistant Enterobacteriaceae, including those producing extended spectrum ß-lactamases.

However, Enterobacteriaceae that produce carbapenemases, which are enzymes that deactivate carbapenems and most other ß-lactam antibiotics, have emerged and are increasingly being reported worldwide.

Despite this increasing burden, the most optimal treatment for CRE infections is largely unknown. For the few remaining available treatment options, there are limited efficacy data to support their role in therapy.

Nevertheless, current treatment options include the use of older agents, such as polymyxins, fosfomycin, and aminoglycosides, which have been rarely used due to efficacy and/or toxicity concerns. Optimization of dosing regimens and combination therapy are additional treatment strategies being explored.

Carbapenem-resistant Enterobacteriaceae infections are associated with poor outcomes and high mortality. Continued research is critically needed to determine the most appropriate treatment.


January 26, 2017 at 3:36 pm

Therapeutic options for carbapenemase-producing Enterobacteriaceae.

Rev Esp Quimioter. 2015 Sep;28 Suppl 1:12-5.

[Article in Spanish]

Salgado P, Gilsanz F, Maseda E1.

Author information

1Emilio Maseda, Servicio de Anestesia y Reanimación, Hospital Universitario La Paz; Paseo de la Castellana 261, 2846, Madrid, Spain.


Carbapenemase-producing Enterobacteriaceae (CPE) has spread worldwide becoming a threat to public health. However, no randomized clinical trials about the efficacy of optimizing antibiotic treatment have been published. Experimental studies have been designed to find combinations of antibiotics with synergistic activity.

Their main aim has been increasing the speed of bacterial destruction and decreasing resistance. The latest guidelines recommend combination therapy. The carbapenems has been chosen as the basis of such therapy.

We face limited therapeutic options. Polymyxins, fosfomycin and gentamicin have reemerged in this context, becoming the basis of multiple combination regimens, with beneficial effects both in vitro and in murine models of infection.


January 26, 2017 at 3:32 pm

The Antimicrobial Therapy Puzzle: Could Pharmacokinetic-Pharmacodynamic Relationships Be Helpful in Addressing the Issue of Appropriate Pneumonia Treatment in Critically Ill Patients?

Clin Infect Dis. June 15, 2006 V.42 N.12 P.1764-1771

Reviews of Anti-Infective Agents

Louis D. Saravolatz, Federico Pea, and Pierluigi Viale

1Institute of Clinical Pharmacology and Toxicology, Department of Experimental and Clinical Pathology and Medicine, Udine, Italy

2Clinic of Infectious Diseases, Department of Medical and Morphological Research, Medical School, University of Udine, Udine, Italy

Until recently, the in vitro susceptibility of microorganisms was considered the only fundamental aspect for antibiotic efficacy in treating pneumonia. However, the relevance of pharmacokinetic-pharmacodynamic relationships in optimizing drug exposure has been progressively highlighted.

Antimicrobial agents were divided into concentration-dependent or time-dependent groups, with the most consistently relevant pharmacodynamic parameters for efficacy being either the ration of the plasma peak concentration to the minimum inhibitory concentration or the time the plasma concentration persists above the minimum inhibitory concentration of the etiological agent, respectively.

For the adequate treatment of pneumonia, optimal pharmacodynamic exposure should be ensured also at the infection site. To investigate this, a methodologically correct approach may be to detect drug concentration levels in the epithelial lining fluid and in the alveolar macrophages for extracellular and intracellular pathogens, respectively.

From this perspective, the pharmacokinetic factors—only in some instances—support the achievement of optimal exposure during the treatment of pneumonia with fixed standard dosing regimens of antimicrobials; conversely, in other instances, the pharmacokinetic factors suggest the need for an implemented dosage regimen or even the choice of a different drug.


January 26, 2017 at 3:26 pm

Carbapenemase-Producing Enterobacteriaceae in Swine Production in the United States: Impact and Opportunities

Antimicrobial Agents & Chemotherapy February 2017 V.61 N.2 e02348-16

Timothy J. Johnson

The discovery of carbapenemase-producing Enterobacteriaceae in U.S. swine production is troubling and underscores a tumultuous period where the outlook on the battle against superbugs is bleak. However, all is not lost. This commentary highlights both the good and the bad that can come from such findings, including those of a recent study published by Mollenkopf et al.


January 25, 2017 at 2:35 pm

In Vitro Tolerance of Drug-Naive Staphylococcus aureus Strain FDA209P to Vancomycin

Antimicrobial Agents & Chemotherapy February 2017 V.61 N.2 e01154-16

Madhuri Singh, Miki Matsuo, Takashi Sasaki, Yuh Morimoto, Tomomi Hishinuma, and Keiichi Hiramatsu

Department of Microbiology, Faculty of Medicine, Juntendo University, Tokyo, Japan

The mechanisms underlying bacterial tolerance to antibiotics are unclear. A possible adaptation strategy was explored by exposure of drug-naive methicillin-susceptible Staphylococcus aureus strain FDA209P to vancomycin in vitro.

Strains surviving vancomycin treatment (vancomycin survivor strains), which appeared after 96 h of exposure, were slow-growing derivatives of the parent strain.

Although the vancomycin MICs for the survivor strains were within the susceptible range, the cytokilling effects of vancomycin at 20-fold the MIC were significantly lower for the survivor strains than for the parent strain.

Whole-genome sequencing demonstrated that ileS, encoding isoleucyl-tRNA synthetase (IleRS), was mutated in two of the three vancomycin survivor strains.

The IleRS Y723H mutation is located close to the isoleucyl-tRNA contact site and potentially affects the affinity of IleRS binding to isoleucyl-tRNA, thereby inhibiting protein synthesis and leading to vancomycin tolerance. Introduction of the mutation encoding IleRS Y723H into FDA209P by allelic replacement successfully transferred the vancomycin tolerance phenotype.

We have identified mutation of ileS to be one of the bona fide genetic events leading to the acquisition of vancomycin tolerance in S. aureus, potentially acting via inhibition of the function of IleRS.


January 25, 2017 at 2:34 pm

Carbapenemase-Producing Enterobacteriaceae Recovered from the Environment of a Swine Farrow-to-Finish Operation in the United States

Dixie F. Mollenkopf, Jason W. Stull, Dimitria A. Mathys, Andrew S. Bowman, Sydnee M. Feicht, Susan V. Grooters, Joshua B. Daniels, and Thomas E. Wittum

aDepartment of Veterinary Preventive Medicine, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA

bDepartment of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA

Carbapenem-resistant Enterobacteriaceae (CRE) present an urgent threat to public health. While use of carbapenem antimicrobials is restricted for food-producing animals, other β-lactams, such as ceftiofur, are used in livestock.

This use may provide selection pressure favoring the amplification of carbapenem resistance, but this relationship has not been established. Previously unreported among U.S. livestock, plasmid-mediated CRE have been reported from livestock in Europe and Asia.

In this study, environmental and fecal samples were collected from a 1,500-sow, U.S. farrow-to-finish operation during 4 visits over a 5-month period in 2015.

Samples were screened using selective media for the presence of CRE, and the resulting carbapenemase-producing isolates were further characterized. Of 30 environmental samples collected from a nursery room on our initial visit, 2 (7%) samples yielded 3 isolates, 2 sequence type 218 (ST 218) Escherichia coli and 1 Proteus mirabilis, carrying the metallo-β-lactamase gene blaIMP-27 on IncQ1 plasmids.

We recovered on our third visit 15 IMP-27-bearing isolates of multiple Enterobacteriaceae species from 11 of 24 (46%) environmental samples from 2 farrowing rooms. These isolates each also carried blaIMP-27 on IncQ1 plasmids.

No CRE isolates were recovered from fecal swabs or samples in this study. As is common in U.S. swine production, piglets on this farm receive ceftiofur at birth, with males receiving a second dose at castration (≈day 6). This selection pressure may favor the dissemination of blaIMP-27-bearing Enterobacteriaceae in this farrowing barn.

The absence of this selection pressure in the nursery and finisher barns likely resulted in the loss of the ecological niche needed for maintenance of this carbapenem resistance gene.


January 25, 2017 at 2:32 pm

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