International guidelines for the treatment of community-acquired pneumonia in adults: the role of macrolides.
Antibiotics; Outpatients; Risk Assessment; Methicillin Resistance; Inpatients; Clinical Trials; Practice Guidelines; Drug Resistance; Microbial; Nonexperimental Studies; Pneumonia – Drug Therapy; Community-Acquired Infections – Drug Therapy; Pneumonia – Etiology; Macrolide – Therapeutic Use; Streptococcal Infections – Drug Therapy; Community-Acquired Infections – Etiology; Immune System – Drug Effects; Macrolide – Pharmacodynamics
The significance of community-acquired pneumonia (CAP) has led to the publication of guidelines from numerous international organisations. Because the macrolide class of antimicrobials is active against most of the key pathogens associated with CAP, agents from this class are commonly included in recommendations from these guidelines. However, there are differences among the various guidelines concerning the positioning of the macrolides for empirical therapy. An important factor concerning the use of macrolides for CAP is the emergence of resistance of Streptococcus pneumoniae over the past decade. The rate of S. pneumoniae resistance to macrolides ranges from 4 to 70% of strains in worldwide surveillance studies. The most common mechanisms of resistance include methylation of a ribosomal target encoded by the erm gene and efflux of the macrolides by a cell membrane protein transporter, encoded by the mef gene. S. pneumoniae strains with the mef gene are resistant at a lower level (with minimum inhibitory concentration [MIC] values generally 1-16 microg/ml) than erm resistant strains; and it is possible that such strains may be inhibited if sufficiently high levels of macrolide can be obtained at the infected site. Currently mef-associated resistance predominates in North America, whereas erm predominates in Europe. Until recently, reports of failure of treatment of CAP with macrolides has been rare, particularly for patients with low-risk for drug-resistant strains. However, since 2000, several patients treated with an oral macrolide who have subsequently required admission to the hospital for macrolide-resistant S. pneumoniae (MRSP) bacteraemia have been reported in the literature. Major issues, which are fundamental to the use of the macrolides as recommended in the various guidelines, include the importance of providing therapy for 'atypical' pathogens and the clinical significance of MRSP. Presently, the macrolides are more prominently recommended in the North American guidelines than in other parts of the world. The difference in the emphasis placed on the importance of the atypical pathogens as well as the expression of MRSP in North America compared with Europe partly explains this variance.
File T M Jr; Tan J S
Drugs
2003
2003-01-15
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.2165/00003495-200363020-00005" target="_blank" rel="noreferrer noopener">10.2165/00003495-200363020-00005</a>
Guidelines for empiric antimicrobial prescribing in community-acquired pneumonia.
Antibiotics; United States; Canada; Europe; Comparative Studies; Practice Guidelines; Drug Resistance; Pneumonia; Microbial; Antiinfective Agents; Community-Acquired Infections – Drug Therapy; Bacterial – Drug Therapy; Antibiotics – Administration and Dosage; Fluoroquinolone – Therapeutic Use; Macrolide – Therapeutic Use; Lactam – Therapeutic Use
Empiric antimicrobial prescribing for community-acquired pneumonia remains a challenge, despite the availability of treatment guidelines. A number of key differences exist between North American and European guidelines, mainly in the outpatient setting. The North American approach is to use initial antimicrobial therapy, which provides coverage for Streptococcus pneumoniae plus atypical pathogens. Europeans tend to focus on providing pneumococcal coverage with less emphasis on covering for an atypical pathogen. Ambulatory patients without comorbidity are more likely to receive macrolide therapy in North America, whereas in Europe these patients would probably receive a beta-lactam agent. Major issues that are fundamental to this difference include the importance of providing therapy for atypical pathogens and the clinical significance of macrolide-resistant S pneumoniae. Prospective data are required to evaluate which of these two approaches offers clinical superiority.
File T M Jr; Garau J; Blasi F; Chidiac C; Klugman K; Lode H; Lonks JR; Mandell L; Ramirez J; Yu V
Chest
2004
2004-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1378/chest.125.5.1888" target="_blank" rel="noreferrer noopener">10.1378/chest.125.5.1888</a>
Evolution of amoxicillin/clavulanate in the treatment of adults with acute bacterial rhinosinusitis and community-acquired pneumonia in response to antimicrobial-resistance patterns.
Antibiotics; Drug Resistance; Microbial; Microbial Culture and Sensitivity Tests; Pneumonia – Drug Therapy; Community-Acquired Infections – Drug Therapy; Pneumonia – Microbiology; Community-Acquired Infections – Microbiology; Bacteria – Drug Effects; Combined – Therapeutic Use; Rhinosinusitis – Drug Therapy; Rhinosinusitis – Microbiology
Current treatment guidelines for community-acquired respiratory tract infections no longer depend solely on the characteristics of the patient and the clinical syndrome, but on those of the offending pathogen, including presence and level of antimicrobial resistance. The most common respiratory tract pathogens known to cause acute bacterial rhinosinusitis (ABRS) and community-acquired pneumonia (CAP) include Streptococcus pneumoniae and Haemophilus influenzae. The prevalence of antimicrobial resistance, especially b-lactum and macrolide resistance, among S pneumoniae and H influenzae has increased dramatically during the past 2 decades, diminishing the activity of many older antimicrobials against resistant organisms. A pharmacokinetically enhanced formulation of amoxicillin/clavulanate has been developed to fulfill the need for an oral b-lactam antimicrobial that achieves a greater time that the serum drug concentration exceeds the minimum inhibitory concentration (T \textgreater MIC) of antimicrobials against pathogens than conventional formulations to improve activity against S pneumoniae with reduced susceptibility to penicillin. The b-lactamase inhibitor clavulanate allows for coverage of b-lactamase-producing pathogens, such as H influenzae and M catarrhalis. This article reviews the rationale for, and evolution of, oral amoxicillin clavulanate for ABRS and CAP. Copyright © 2004 by Elsevier Science (USA).
File T M Jr; Benninger MS; Jacobs MR
Clinics in Laboratory Medicine
2004
2004-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.cll.2004.03.003" target="_blank" rel="noreferrer noopener">10.1016/j.cll.2004.03.003</a>
Community-acquired pneumonia.
Disease Progression; Community-Acquired Infections; Immunocompetence; Drug Resistance; Pneumonia; Bacterial; Microbial; Severity of Illness; Antibiotics – Therapeutic Use; Community-Acquired Infections – Diagnosis; Community-Acquired Infections – Drug Therapy; Community-Acquired Infections – Microbiology; Bacterial – Drug Therapy; Bacterial – Microbiology; Bacterial – Prevention and Control; Community-Acquired Infections – Prevention and Control; Bacterial – Diagnosis; Streptococcus – Drug Effects; Vaccines – Therapeutic Use
File T M Jr
Lancet
2003
2003-12-13
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0140-6736(03)15021-0" target="_blank" rel="noreferrer noopener">10.1016/s0140-6736(03)15021-0</a>
Community-acquired pneumonia: recent guidelines for therapy.
Pneumonia – Drug Therapy; Community-Acquired Infections – Drug Therapy; Pneumonia – Microbiology; Community-Acquired Infections – Microbiology
The Infectious Diseases Society of America advocates using pathogen-directed therapy whenever possible to help reduce the emergence of drug resistance. Options for empiric therapy for outpatients include a macrolide, a new fluoroquinolone with enhanced activity against Streptococcus pneumoniae, and doxycycline. A newer fluoroquinolone is an appropriate option when drug-resistant S pneumoniae is a concern. For patients requiring hospitalization in a general ward, the preferred options are a beta-lactam plus a macrolide or a new fluoroquinolone with activity against S pneumoniae.
File T M Jr
Journal of Respiratory Diseases
1999
1999-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Clinical implications of 750 mg, 5-day levofloxacin for the treatment of community-acquired pneumonia.
Adult; Female; Male; Human; Chi Square Test; Funding Source; Retrospective Design; T-Tests; Kaplan-Meier Estimator; Random Assignment; McNemar's Test; Double-Blind Studies; Log-Rank Test; Pneumonia – Drug Therapy; Community-Acquired Infections – Drug Therapy; Ofloxacin – Administration and Dosage
OBJECTIVE: To evaluate the time to symptom resolution and i.v.-to-p.o. transition in community-acquired pneumonia (CAP) patients treated with 750 mg or 500 mg levofloxacin. RESEARCH DESIGN: A retrospective, subset analysis of a multicenter, randomized, double-blind, controlled trial comparing 750 mg levofloxacin for 5 days to 500 mg levofloxacin for 10 days for the treatment of CAP. PATIENTS AND METHODS: A total of 528 CAP patients were included. Baseline symptoms were re-evaluated on Day 3 of therapy, and time to i.v.-to-p.o. transition was recorded for inpatients. RESULTS: For the overall population, 67.4% of patients receiving 750 mg levofloxacin had resolution of fever by Day 3 of therapy, compared to 54.6% of 500 mg treated patients (P = 0.006). Patients who started on 750 mg levofloxacin i.v. (N = 108) transitioned to p.o. in an average of 2.68 days while those starting on 500 mg i.v. (N = 124) transitioned in 2.95 days (P = 0.144). The median time for i.v.-to-p.o. switch was 2.35 days and 2.75 days for patients receiving 750 mg and 500 mg levofloxacin, respectively (P = 0.098, log rank test). By Day 3 of therapy, 68% of patients receiving the 750 mg dose had transitioned from i.v. to p.o. levofloxacin, compared with 61% of the 500 mg group (P = 0.280). The safety profiles were comparable for the two regimens. CONCLUSIONS: The 750 mg levofloxacin dose resulted in a greater proportion of patients with resolution of CAP symptoms by Day 3 when compared with 500 mg therapy. Consequently, the 750 mg regimen trended toward more rapid transition to p.o., potentially resulting in lower overall drug costs. Time to switch from i.v. to p.o. was determined by the investigators' discretion rather than a set protocol. Additionally, length of stay data was not collected in this study, which can significantly impact overall healthcare costs. Further research is required to fully understand the economic impact of the 750 mg, 5-day levofloxacin regimen.
File T M Jr; Milkovich G; Tennenberg AM; Xiang JX; Khashab MM; Zadeikis N
Current Medical Research & Opinion
2004
2004-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1185/030079904x2556" target="_blank" rel="noreferrer noopener">10.1185/030079904x2556</a>
The Science of Selecting Antimicrobials for Community-Acquired Pneumonia (CAP)
Antibiotics; Human; Practice Guidelines; Drug Resistance; Pneumonia; Drug Therapy; Microbial; Combination; Microbial Culture and Sensitivity Tests; Antiinfective Agents; Streptococcus; Gram-Negative Bacteria; Antibiotics – Therapeutic Use; Community-Acquired Infections – Drug Therapy; Bacterial – Drug Therapy; Macrolide – Therapeutic Use; Quinolone – Therapeutic Use; Lactam – Therapeutic Use; Legionnaires' Disease – Drug Therapy
File T M
Journal of Managed Care Pharmacy
2009
2009-03-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.18553/jmcp.2009.15.s2.5" target="_blank" rel="noreferrer noopener">10.18553/jmcp.2009.15.s2.5</a>
Uncomplicated Pure Cellulitis: No Need to Cover for MRSA?
Treatment Outcomes; Cellulitis; Methicillin-Resistant Staphylococcus Aureus; Antibiotics – Therapeutic Use; Community-Acquired Infections – Drug Therapy; Staphylococcal Infections – Drug Therapy; Cellulitis – Drug Therapy; Cellulitis – Diagnosis; Cellulitis – Microbiology; Streptococcal Infections – Drug Therapy
Watkins Richard R
Infectious Disease Alert
2013
2013-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Statin Use Is Associated With a Lower Risk of Community-acquired Staphylococcus aureus Bacteremia.
Risk Assessment; Drug Resistance; Microbial; Neutrophils; Community-Acquired Infections – Drug Therapy; Cell Physiology – Drug Effects; Staphylococcus Aureus – Drug Effects; Bacteremia – Risk Factors; Biofilms – Drug Effects; Simvastatin – Administration and Dosage; Statins – Economics; Statins – Therapeutic Use
A population-based case-control study from Denmark found the use of statins was associated with a decreased risk for community-associated Staphylococcus aureus bacteremia, with the greatest benefit from higher doses.
Watkins Richard R
Infectious Disease Alert
2017
2017-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia.
80 and over; 80 and Over; Aged; Bacteria; Bacteria/isolation & purification; Bacterial – Drug Therapy; Bacterial/*drug therapy; Ceftriaxone – Administration and Dosage; Ceftriaxone – Adverse Effects; Ceftriaxone/administration & dosage/adverse effects; Cephalosporins – Administration and Dosage; Cephalosporins – Adverse Effects; Cephalosporins/*administration & dosage/*adverse effects; Community-Acquired Infections – Drug Therapy; Community-Acquired Infections/*drug therapy; Double-Blind Method; Double-Blind Studies; Female; Human; Humans; Infusions; Intravenous; Male; Middle Age; Middle Aged; Pneumonia; Randomized Controlled Trials; Treatment Outcome; Treatment Outcomes
OBJECTIVES: Ceftaroline, the active form of the prodrug ceftaroline fosamil, is a novel cephalosporin with bactericidal activity against important pathogens associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and common Gram-negative pathogens. FOCUS 1 is a randomized, double-blinded, Phase III study that was conducted to evaluate the efficacy and safety of ceftaroline fosamil in treating patients with CAP. The primary objective was to determine non-inferiority [lower limit of 95% confidence interval (CI) \textgreater/= -10%] in clinical cure rates achieved with ceftaroline fosamil compared with those achieved with ceftriaxone in the clinically evaluable (CE) and modified intent-to-treat efficacy (MITTE) populations. METHODS: Patients hospitalized in a non-intensive care unit setting with CAP of Pneumonia Outcomes Research Team (PORT) risk class III or IV requiring intravenous (iv) therapy were randomized (1:1) to receive 600 mg of ceftaroline fosamil iv every 12 h or 1 g of ceftriaxone iv every 24 h. Patients also received two 500 mg doses of oral clarithromycin every 12 h administered on day 1. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 1 registration number NCT00621504 (http://clinicaltrials.gov/ct2/show/NCT00621504). RESULTS: Of 613 enrolled patients, 298 received ceftaroline fosamil and 308 received ceftriaxone. Baseline characteristics between treatment groups were comparable. Clinical cure rates were as follows: CE population, 86.6% (194/224) for ceftaroline fosamil and 78.2% (183/234) for ceftriaxone [difference (95% CI), 8.4% (1.4, 15.4)]; and MITTE population, 83.8% (244/291) for ceftaroline fosamil and 77.7% (233/300) for ceftriaxone [difference (95% CI), 6.2% (-0.2, 12.6)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE population were 88.9% (24/27) and 66.7% (20/30) for ceftaroline fosamil and ceftriaxone, respectively. Both agents were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations because of an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, insomnia and nausea, and the most common AEs for ceftriaxone-treated patients were hypokalaemia, hypertension, nausea and diarrhoea. CONCLUSIONS: Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.
File Thomas M Jr; Low Donald E; Eckburg Paul B; Talbot George H; Friedland H David; Lee Jon; Llorens Lily; Critchley Ian A; Thye Dirk A
The Journal of antimicrobial chemotherapy
2011
2011-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/jac/dkr096" target="_blank" rel="noreferrer noopener">10.1093/jac/dkr096</a>
Does empiric therapy for atypical pathogens improve outcomes for patients with CAP?
Anti-Bacterial Agents/*therapeutic use; Antibiotic Prophylaxis; Antibiotics – Therapeutic Use; Clinical Trials; Clinical Trials as Topic; Community-Acquired Infections – Drug Therapy; Community-Acquired Infections – Microbiology; Community-Acquired Infections/drug therapy/microbiology; Humans; Pneumonia – Drug Therapy; Pneumonia – Microbiology; Pneumonia/*drug therapy/microbiology
The present controversy regarding the need to cover atypical pathogens in the empiric therapy of community-acquired pneumonia is related to several issues, including the relevance of terminology, imprecise diagnostic methods, and perceived contradictory results of published evidence. Studies evaluating the time to clinical recovery and the use of earlier endpoints for evaluation suggest that appropriate therapy provides a benefit if an atypical pathogen is a pathogen. Because recent surveillance studies suggest these pathogens are common and until there is the availability of accurate, cost-effective, and easily interpreted laboratory tests to provide the etiologic diagnosis at the time of point of care, empiric therapy of atypical pathogens is supported.
File Thomas M Jr; Marrie Thomas J
Infectious disease clinics of North America
2013
2013-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.idc.2012.11.005" target="_blank" rel="noreferrer noopener">10.1016/j.idc.2012.11.005</a>
Case studies of lower respiratory tract infections: community-acquired pneumonia.
Acute – Microbiology; Adult; Adult/microbiology; Aged; Anti-Bacterial Agents/*therapeutic use; Antibiotics – Therapeutic Use; Antitubercular Agents – Therapeutic Use; Antitubercular Agents/therapeutic use; Community-Acquired Infections – Diagnosis; Community-Acquired Infections – Drug Therapy; Community-Acquired Infections/diagnosis/drug therapy; Cough; Cough – Microbiology; Cough/microbiology/virology; Diagnosis; Differential; Dyspnea; Fatal Outcome; Female; Fever – Microbiology; Fever/microbiology; Hemoptysis – Microbiology; Hemoptysis/microbiology; Human; Human – Complications; Human – Diagnosis; Human/complications/*diagnosis; Humans; Hypotension – Microbiology; Hypotension/microbiology; Influenza; Leukopenia – Microbiology; Leukopenia/microbiology; Male; Methicillin-Resistant Staphylococcus Aureus; Methicillin-Resistant Staphylococcus aureus/*isolation & purification; Miliary/diagnosis/drug therapy; Multiple Organ Dysfunction Syndrome – Microbiology; Multiple Organ Failure/microbiology; Mycobacterium Tuberculosis; Mycobacterium tuberculosis/isolation & purification; Pneumonia – Diagnosis; Pneumonia – Drug Therapy; Pneumonia – Microbiology; Pneumonia – Therapy; Pneumonia/*diagnosis/*drug therapy/microbiology/therapy; Practice Guidelines; Practice Guidelines as Topic; Respiratory Distress Syndrome; Risk Factors; Severity of Illness Index; Severity of Illness Indices; Smoking; Smoking/adverse effects; Staphylococcal Infections – Diagnosis; Staphylococcal Infections – Drug Therapy; Staphylococcal Infections – Microbiology; Staphylococcal Infections – Therapy; Staphylococcal Infections/*diagnosis/*drug therapy/microbiology/therapy; Tuberculosis; Tuberculosis – Diagnosis; Tuberculosis – Drug Therapy
Community-acquired pneumonia (CAP) is a common and potentially serious illness with significant human and economic costs to society. The recent collaborative statement from the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) represents the most up-to-date evidence-based guidelines from North America, incorporating important advances in the management of patients with CAP. The cases presented in this review highlight many of the recent recommendations from the IDSA/ATS guidelines.
File Thomas M Jr
The American journal of medicine
2010
2010-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.amjmed.2010.02.002" target="_blank" rel="noreferrer noopener">10.1016/j.amjmed.2010.02.002</a>