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Thomas M File

Publications and source records attributed to Thomas M File.

At least 37 records · Page 2Linked to original sources
PubMed2004

Antimicrobial therapy of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a common disorder that is potentially life-threatening, especially in older adults and patients with comorbid disease. Despite substantial progress in therapeutic options, CAP remains a primary cause of death from infectious disease in the United States. The mainstay of treatment for most patients is appropriate antimicrobial therapy This article reviews the principles for initial antimicrobial therapy, highlights some of the differences in approaches to antimicrobial drug selection in selected guidelines, and includes new recommendations for empiric and pathogen-directed therapy of CAP.

Ambulatory Care↗
PubMed2004

New insights in the treatment by levofloxacin.

Levofloxacin is widely regarded as one of the most important fluoroquinolones available today. It possesses excellent activity against a wide range of important pathogens, including those resistant to many other antimicrobials. While rates of resistance to other previously useful antimicrobial classes has grown, levofloxacin has maintained its efficacy, with generally very low rates of resistance around the world. It is indicated for a wide range of infections including community-acquired respiratory infections in adults, particularly community-acquired pneumonia (CAP), acute bacterial exacerbations of chronic bronchitis (AECB), and acute sinusitis. In addition, it is recommended for infections of skin and soft tissue, and the urinary tract. With postmarketing surveillance data available for the last decade, levofloxacin possesses an unparalleled database to demonstrate its clinical efficacy and safety. Remarkably, levofloxacin continues to expand its list of indications. The development of a new high-dose 750-mg schedule has the potential to decrease the duration of treatment as well as reduce the emergence of resistance.

Anti-Infective Agents↗
PubMed2004

Clinical implications of 750 mg, 5-day levofloxacin for the treatment of community-acquired pneumonia.

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.

Administration, Oral↗
PubMed2004

Managing patients with recurrent acute exacerbations of chronic bronchitis: a common clinical problem.

Chronic obstructive pulmonary disease (COPD) affects 15 million people and is the fourth leading cause of death in the United States. It places a considerable burden on the healthcare system, with exacerbations contributing to a significant proportion of this burden. Patients with recurrent exacerbation, who experience more than 2 exacerbations per year, are especially difficult to manage. Several potential host, pathogen, and treatment factors can be identified that contribute to recurrent exacerbation. Patients with recurrent exacerbations are often exposed to frequent courses of antimicrobials. Therefore, antimicrobial resistance among common bacterial pathogens is likely to be prevalent in this group of patients, and further complicates therapy in this already difficult-to-treat patient population. In the management of patients with recurrent exacerbation, one goal should be to decrease the frequency of exacerbations, for which several strategies are suggested. In this article, we will review available literature identified through an extensive search of Medline and PubMed on the characteristics and approach to management of these difficult-to-treat patients. There is a substantial need for more research to understand the etiology and identify efficacious interventions to reduce the frequency of exacerbations of COPD.

Acute Disease↗
PubMed2004

Guidelines for empiric antimicrobial prescribing in community-acquired pneumonia.

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.

Canada↗
PubMed2004

Gemifloxacin: a new, potent fluoroquinolone for the therapy of lower respiratory tract infections.

The fluoroquinolone gemifloxacin has recently been approved for the treatment of acute bacterial exacerbations of chronic bronchitis and mild community acquired pneumonia, including that caused by multidrug-resistant Streptococcus pneumoniae. Owing to the increasing prevalence of multidrug-resistant S. pneumoniae, as well as resistance to other common pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, it is important to have new, potent antimicrobial agents for the treatment of these infections. Gemifloxacin is the most potent antimicrobial agent in vitro for S. pneumoniae, and has excellent activity against the other key pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, including the atypical microorganisms. The clinical trial outcomes of several studies that have evaluated gemifloxacin show a range of superior clinical or bacteriologic outcomes against several current antimicrobials, including levofloxacin, clarithromycin, trovafloxacin and ceftriaxone. The safety profile of gemifloxacin is similar to that of approved agents to treat acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, with a low discontinuation rate of 2.2%. A nonphototoxic rash (usually a mild, maculopapular rash) was observed in 2.8% of patients in clinical studies.

Acute Disease↗
PubMed2003

Community-acquired pneumonia.

This seminar reviews important features and management issues of community-acquired pneumonia (CAP) that are especially relevant to immunocompetent adults in light of new information about cause, clinical course, diagnostic testing, treatment, and prevention. Streptococcus pneumoniae remains the most important pathogen; however, emerging resistance of this organism to antimicrobial agents has affected empirical treatment of CAP. Atypical pathogens have been quite commonly identified in several prospective studies. The clinical significance of these pathogens (with the exception of Legionella spp) is not clear, partly because of the lack of rapid, standardised tests. Diagnostic evaluation of CAP is important for appropriate assessment of severity of illness and for establishment of the causative agent in the disease. Until better rapid diagnostic methods are developed, most patients will be treated empirically. Antimicrobials continue to be the mainstay of treatment, and decisions about specific agents are guided by several considerations that include spectrum of activity, and pharmacokinetic and pharmacodynamic principles. Several factors have been shown to be associated with a beneficial clinical outcome in patients with CAP. These factors include administration of antimicrobials in a timely manner, choice of antibiotic therapy, and the use of a critical pneumonia pathway. The appropriate use of vaccines against pneumococcal disease and influenza should be encouraged. Several guidelines for management of CAP have recently been published, the recommendations of which are reviewed.

Adult↗
PubMed2003

Emergence of levofloxacin-resistant pneumococci in immunocompromised adults after therapy for community-acquired pneumonia.

We describe 4 patients infected with levofloxacin-resistant pneumococci after therapy for community-acquired pneumonia (CAP). The 4 patients had 15 episodes of CAP; Streptococcus pneumoniae was isolated from blood or sputum samples obtained during 14 of the episodes. The underlying medical condition was Bruton agammaglobulinemia in 3 patients and chronic lymphoid leukemia in the other. The initial episode of CAP in each patient was due to a levofloxacin-susceptible strain. One of 4 reinfections and 5 of 6 relapses were due to levofloxacin-resistant strains. All of these strains had amino acid substitutions in the quinolone-resistance-determining region of the genes parC and gyrA. The time between episodes of pneumonia varied from 1 to 4 months. In immunocompromised patients with suspected or proven pneumococcal infection, it may be prudent not to use fluoroquinolone monotherapy empirically when the patient has a history of fluoroquinolone therapy in at least the past 4 months.

Adult↗
PubMed2003

Management of community-acquired pneumonia: a focus on conversion from hospital to the ambulatory setting.

Patients with community-acquired pneumonia (CAP) are treated in hospital or in the ambulatory care setting depending on the severity of illness. Despite numerous guidelines proposed, there is no agreement on specific criteria for hospitalization other than the clinicians' experience. The purpose of this review is to discuss the importance of the appropriate choice and timely administration of antibacterial agents, either in the hospital or in the outpatient setting. Since a high proportion of CAP patients will not have an etiologic agent identified at the time of initiation of treatment, the choice of antibacterial therapy is usually empiric. Antibacterial agents with activity against pneumococci and atypical pathogens causing pneumonia are the preferred choices. Macrolides, doxycycline, or respiratory fluoroquinolones have been recommended by various guidelines committees in North America for the treatment of pneumonia in patients with or without underlying comorbidities. Because of the increasing resistance to beta-lactams as well other antibacterial agents such as macrolides, doxycycline, and sulfamethoxazole/trimethoprim (cotrimoxazole), it is important that clinicians are aware of local statistics on resistance to Streptococcus pneumoniae, as infection with this bacterium is associated with high rates of morbidity and mortality. More recently, fluoroquinolone resistance has been reported, but the percentage of pneumococcal strains resistant to this agent is relatively low compared with the other antibacterial agents. Switch (intravenous to oral) therapy is recommended for hospitalized patients with CAP to facilitate early discharge, which has been shown to improve patient satisfaction and reduce hospital costs. Early conversion to oral therapy has not been shown to be associated with increased complications or higher mortality. Following prompt intravenous therapy and stabilization, patients with CAP should be treated with oral therapy in the ambulatory setting.

Ambulatory Care↗
PubMed2003

A new dosing paradigm: high-dose, short-course fluoroquinolone therapy for community-acquired pneumonia.

The goals of optimal antimicrobial therapy are to treat infection effectively, to improve the clinical condition of the patient, and to prevent the emergence of resistant bacterial strains. For ideal drug usage the World Health Organization recommends administering the correct drug by the best route, in the right amount, at optimum intervals for the appropriate period, and after an accurate diagnosis. This article discusses the use of high-dose, short-course fluoroquinolone therapy as an effective option for patients with community-acquired pneumonia.

Community-Acquired Infections↗
PubMed2003

International guidelines for the treatment of community-acquired pneumonia in adults: the role of macrolides.

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.

Adjuvants, Immunologic↗
PubMed2002

Legionnaires disease with bacteremic coinfection.

We describe 6 patients who had bacteremic community-acquired pneumonia and unsuspected Legionella pneumophila coinfection. We reviewed case records of patients who were diagnosed as having a recent Legionella infection on the basis of either the presence of L. pneumophila serogroup 1 antigen in urine or a 4-fold increase in L. pneumophila antibody level and with a blood culture that yielded a bacterium other than L. pneumophila. Three patients were diagnosed with legionellosis on the basis of the presence of antigen in urine, and 3 were diagnosed on the basis of a 4-fold increase in antibody titer. Of these 6 patients, 4 were infected with Streptococcus pneumoniae, 1 with Streptococcus pyogenes, and 1 with Enterobacter cloacae. L. pneumophila infection in these patients may have predisposed them to concomitant bacteremia. Initial empiric antimicrobial therapy for patients who live in areas of endemicity and who are smokers should be treated with antimicrobial agents that have activity against pneumococcus and Legionella species.

Aged↗