Lionel A. Mandell

Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

Update of Practice Guidelines for the Management of Community-Acquired Pneumonia in Immunocompetent Adults

The Infectious Diseases Society of America (IDSA) produced guidelines for community-acquired pneumonia (CAP) in immunocompetent adults in 1998 and again in 2000 [1, 2]. Because of evolving resistance to antimicrobials and other advances, it was felt that an update should be provided every few years so that important developments could be highlighted and pressing questions answered. We addressed those issues that the committee believed were important to the practicing physician, including suggestions for initial empiric therapy for CAP. In some cases, only a few paragraphs were needed, whereas, in others, a somewhat more in-depth discussion was provided. Because many physicians focus on the tables rather than on the text of guidelines, it was decided that all of the information dealing with the initial empiric treatment regimens should be in tabular format with footnotes (tables 1–3). The topics selected for updating have been organized according to the headings used in the August 2000 CAP guidelines pub-

Community-Acquired Pneumonia in Adults: Guidelines for Management

This is part of the series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of community-acquired pneumonia. The targeted providers are internists and family practitioners. The targeted groups are immunocompetent adult patients. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy. Panel members and consultants are experts in adult infectious diseases. The guidelines are evidence based where possible. A standard ranking system is used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary and tables highlight the major recommendations. The guidelines will be listed on the IDSA home page at http://www.idsociety.org.

Canadian Guidelines for the Initial Management of Community-Acquired Pneumonia: An Evidence-Based Update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society

Lionel A Mandell MD FRCPC1, Thomas J Marrie MD FRCPC2, Ronald F Grossman MD FRCPC FACP3, Anthony W Chow MD FRCPC FACP4, Robert H Hyland MD FRCPC5, and the Canadian CAP Working Group* McMaster University, Hamilton, Ontario; Dalhousie University, Halifax, Nova Scotia; QEII Health Sciences Centre, Halifax, Nova Scotia; University of British Columbia, Vancouver, British Columbia; St Michael’s Hospital, Toronto, Ontario

A Comparison of Gemifloxacin and Clarithromycin in Acute Exacerbations of Chronic Bronchitis and Long-Term Clinical Outcomes

BACKGROUND Gemifloxacin is an enhanced-affinity quinolone with potent activity against lower respiratory tract pathogens. OBJECTIVE The efficacy and safety of a 5-day course of gemifloxacin were compared with those of a standard 7-day regimen of clarithromycin in patients with an acute exacerbation of chronic bronchitis (AECB). The impact of treatment on the long-term (26 weeks) clinical outcome was also assessed. METHODS The acute phase of this randomized, double-blind study was performed in 93 centers in 7 countries. Adult patients (age >40 years) with a history of chronic bronchitis and an Anthonisen type 1 acute exacerbation (increased dyspnea, cough, and sputum purulence) were eligible. Patients receiving systemic steroids at a dose of >10 mg prednisone or the equivalent were excluded. Patients were randomized to receive gemifloxacin 320 mg once daily for 5 days or clarithromycin 500 mg twice daily for 7 days. Clinical and bacteriologic response rates were assessed at the end-of-therapy visit (days 8-12), the week 2-3 follow-up visit (days 13-24), and the week 4-5 follow-up visit (days 25-38). The long-term phase (26 weeks), which included US and Canadian participants only, evaluated the proportion of patients who remained free of a recurrence of AECB requiring additional antimicrobial therapy after resolution of the initial episode. RESULTS Seven hundred twelve patients were randomized to treatment, 351 to gemifloxacin and 361 to clarithromycin. The long-term study included 438 patients, 214 receiving gemifloxacin and 224 receiving clarithromycin. Clinical success rates at the 2-3 week follow-up visit were 85.4% for gemifloxacin and 84.6% for clarithromycin. Bacteriologic success rates were 86.7% for gemifloxacin and 73.1% for clarithromycin. Significantly more patients receiving gemifloxacin than clarithromycin remained free of AECB recurrences (71.0% vs 58.5%, respectively; P = 0.016). Both treatments were well tolerated. CONCLUSIONS In the acute treatment of Anthonisen type 1 AECB, a 5-day course of gemifloxacin was at least as effective as a 7-day regimen of clarithromycin. In this population, significantly more patients receiving gemifloxacin remained free of AECB recurrence after 26 weeks compared with those receiving clarithromycin.

Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae: Contributions of Type II Topoisomerase Mutations and Efflux to Levels of Resistance

ABSTRACT We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates ofS. pneumoniae for which the ciprofloxacin MIC is ≥4 μg/ml and 28 isolates for which the ciprofloxacin MIC is ≤2 μg/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 μg/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 μg/ml) and high-level (MICs, 64 μg/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.

Canadian guidelines for the management of acute exacerbations of chronic bronchitis

Acute exacerbations of chronic bronchitis (AECB) account for over 1.5 million physician visits annually in Canada and are a cause of significant morbidity and mortality. This document represents a joint effort between respirologists, microbiologists, infectious disease specialists and family physicians to update the Canadian AECB guidelines published in 1994. Treatment recommendations are graded on the strength of evidence in the published literature where possible. The role for oral corticosteroid therapy in preventing treatment failures, speeding up recovery and delaying the time to next exacerbation is discussed. Risk factors for treatment failure were used to stratify patients into risk groups to help guide antibiotic treatment recommendations. The importance of emerging antimicrobial resistance to current antibiotics is reviewed and strategies to prevent future AECB episodes are suggested.

Summary of Canadian Guidelines for the Initial Management of Community-Acquired Pneumonia: An Evidence-Based Update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society

Community-acquired pneumonia (CAP) is a serious illness with a significant impact on individual patients and society as a whole. Over the past several years, there have been significant advances in the knowledge and understanding of the etiology of the disease, and an appreciation of problems such as mixed infections and increasing antimicrobial resistance. The development of additional fluoroquinolone agents with enhanced activity against Streptococcus pneumoniae has been important as well.It was decided that the time had come to update and modify the previous CAP guidelines, which were published in 1993. The current guidelines represent a joint effort by the Canadian Infectious Diseases Society and the Canadian Thoracic Society, and they address the etiology, diagnosis and initial management of CAP. The diagnostic section is based on the site of care, and the treatment section is organized according to whether one is dealing with outpatients, inpatients or nursing home patients.

Epidemiology and etiology of community-acquired pneumonia

The seriousness of community-acquired pneumonia (CAP), despite being a reasonably common and potentially lethal disease, often is under estimated by physicians and patients alike. CAP results in more than 10 million visits to physicians, 64 million days of restricted activity, and 600,000 hospitalizations. This article discusses the epidemiology and bacterial causes of CAP in immunocompetent adults and the severe acute respiratory syndrome coronavirus.

The battle against emerging antibiotic resistance: should fluoroquinolones be used to treat children?

Inappropriate use of antibiotic drugs in humans and animals has led to widespread resistance among microbial pathogens. Resistance is the phenotypic expression corresponding to genetic changes caused by either mutation or acquisition of new genetic information. In some cases, multidrug resistance occurs. Streptococcus pneumoniae is one of the most important respiratory pathogens, playing a major role in both upper and lower respiratory tract infections. Pneumococcal resistance to antimicrobials may be acquired by means of horizontal transfer followed by homologous recombination of genetic material from the normal flora of the human oral cavity or by means of mutation. Resistance to penicillins and macrolides has been increasing for some time, but, recently, fluoroquinolone resistance has become an issue as well. We are concerned that, if fluoroquinolones are approved for use in children, their widespread use will result in rapid emergence of pneumococcal resistance, because children are more often colonized in the nasopharynx with high-density populations of pneumococci than are adults.