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M S Niederman

Publications and source records attributed to M S Niederman.

At least 19 recordsLinked to original sources
PubMed2002

Acute exacerbation of chronic obstructive pulmonary disease and antibiotics: what studies are still needed?

The use of antibiotics in acute exacerbations of chronic bronchitis (AECBs) remains the subject of controversy despite considerable medical and socioeconomic implications. First, the contribution of bacterial infection to AECBs is difficult to assess in patients with chronic obstructive pulmonary disease (COPD) who are chronically colonized with respiratory pathogens. In addition, several studies suggest a major role of viral infections in AECBs. Secondly, it is unlikely that all COPD patients will benefit from antibiotics during AECBs. In particular, the benefit in mild COPD remains uncertain. Unfortunately, the number of studies complying with evidence-based medicine requirements is too small for definite recommendations in AECBs to be drawn up. Considering the impact of acute exacerbations of chronic bronchitis on chronic obstructive pulmonary disease patients, as well as the community, and the impact of antibiotic therapy on the development of bacterial resistance, there is an urgent need for the design of appropriate multicentric studies to define the usefulness of this type of treatment in acute exacerbations of chronic bronchitis.

Acute Disease↗
PubMed2001

Cost effectiveness in treating ventilator-associated pneumonia.

Ventilator-associated pneumonia is a common illness in intensive care unit patients. The costs of management are increased when infection involves resistant organisms, as well as unnecessary and prolonged therapy. Efforts at accurate diagnosis, therapy and prevention can reduce the cost impact of this illness.

Anti-Bacterial Agents↗
PubMed2001

Guidelines for the management of community-acquired pneumonia. Current recommendations and antibiotic selection issues.

Numerous guidelines for CAP have been developed, and although each is different, many principles are common to all recommendations. A guideline should focus on a wide range of issues surrounding the delivery of care, including advice about when to admit patients to the hospital or ICU; which antibiotic regimens to select for specific patient populations; which pathogens to target in empiric therapy; which diagnostic tests to order; how to assess the importance of specific causative pathogens, such as drug-resistant pneumococci, atypical pathogens, and gram-negative pathogens; how to evaluate the response to therapy and when to switch responding patients to oral therapy; and how to prevent CAP effectively through appropriate use of immunization against pneumococcus and influenza. Currently, many new antibiotic choices have emerged in the macrolide, quinolone, beta-lactam, ketolide, and oxazolidinone classes, and specific issues surrounding selection of these agents must be considered. All of the available data can be synthesized into a disease management guideline, and current therapy in the United States generally is consistent with existing recommendations. This consistency not only has led to more uniformity in patient care, but also has led to measurable benefits in patient outcomes, including reduced mortality for hospitalized patients with CAP. Guidelines not only are a useful tool for managing patients with CAP, but also they serve the purpose of defining current issues in patient care and stimulating the search for new tools and management approaches for this important clinical problem.

Algorithms↗
PubMed2001

Respiratory infection in the chronically critically ill patient. Ventilator-associated pneumonia and tracheobronchitis.

The long-term ventilated patient is at high risk for developing nosocomial pneumonia or tracheobronchitis. In general, the frequency of infection increases with the duration of mechanical ventilation, but the risk appears to be greatest in the first week of intubation. Although these types of infection are common and may have morbidity and mortality impact, the daily risk is less in the long-term ventilated patient than in the acutely ill intubated patient. This reduced daily risk may reflect a "survivor effect," with less healthy patients dying early in the hospital stay and not surviving long enough to undergo tracheostomy and long-term ventilation. A number of factors predispose these patients to infection, including host defense impairment and exposure to large numbers of bacteria. This exposure can occur through the airway, and proper care of respiratory therapy devices is essential to minimize the risk for infection. Most infections of the lower respiratory tract are preceded by airway colonization with EGN bacteria and, with improvement in host defenses and nutrition, infection in the face of colonization is less likely. In some patients, colonization can be eliminated. When the long-term ventilated patient does develop infection, it generally involves highly resistant gram-negative or gram-positive organisms and therapy should be prompt and appropriate. Not all such patients respond to systemic antibiotics, and the use of adjunctive aerosol therapy may have benefit for those with either tracheobronchitis or pneumonia, especially if highly resistant pathogens are present.

Anti-Bacterial Agents↗
PubMed2001

Can guidelines for the treatment of respiratory infections lead to reduced rates of antibiotic resistance?

Guidelines have been developed for the therapy of both community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), and, potentially, if applied appropriately, could lead to a containment or reduction in the frequency of antibiotic resistance. In the therapy of CAP, guidelines could minimize the use of excessive antibiotic therapy, and if they also improve the accuracy of therapy, they could minimize the emergence of resistant organisms in the community. However, the impact of such guidelines on resistance remains to be shown. In the near future, CAP guidelines could help contain the growing problem of quinolone-resistant pneumococci by advocating the use of the most effective of the new agents, administered at the optimal dosages. When managing HAP, the use of guidelines could improve outcome by leading to a greater percentage of patients receiving adequate empiric antibiotic therapy. It remains uncertain whether such an approach can minimize the emergence of antibiotic resistance, particularly in the intensive care unit (ICU), but it is clear that if guidelines are to be accurate, they must account for the resistance patterns that are unique to each individual hospital setting. To date, the use of computer-assisted guidelines for the therapy of nosocomial infections has been successful in minimizing the frequency of inadequate therapy, with no negative impact on antibiotic resistance. Antibiotic restriction policies have been proposed as a way to have an impact on resistance, with variable effects. In the future, antibiotic rotation is likely to be studied as a way to reduce resistance, particularly in the ICU, but a number of practical issues may limit the efficacy of such an approach.

Community-Acquired Infections↗
PubMed2001

Impact of antibiotic resistance on clinical outcomes and the cost of care.

Antibiotic-resistant organisms are common in intensive care unit infection and can be either Gram-positive or Gram-negative. A number of studies have evaluated whether these organisms can lead to excess morbidity, mortality, or cost. In general, the studies are confounded by a number of methodologic issues, including the selection of an appropriate control population. Cases and controls must be appropriately matched for the presence of infection, the presence of infection with similar organisms (but ones that are either antibiotic-sensitive or -resistant), and severity of illness. In addition, studies must account for the therapies given to patients who are infected with resistant organisms because resistance is an important risk factor for inadequate empirical therapy, and such therapy is itself a potent determinant of a number of adverse outcomes, including mortality. To date, the data with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus are inconsistent with regard to the effect on mortality rates, although infection with both organisms can lead to excess length of stay and increased cost of care. When studies have been adequately controlled and powered, infection with vancomycin-resistant enterococcus has had more of an effect on the mortality rate than infection with antibiotic-sensitive enterococci. Infection with resistant Gram-negatives also has adverse impact on outcome, with excess mortality being seen in patient groups infected with Acinetobacter and Pseudomonas aeruginosa. If we are to minimize the effect of resistance on medical outcomes and cost, it will be necessary to have a current knowledge of each intensive care unit's pathogens and susceptibility patterns, so that empirical therapy will have a good likelihood of being effective. In addition, new therapeutic agents may improve on the efficacy of older agents and could reduce cost if they allow for some patients to leave the hospital and to finish therapy with an oral formulation of a highly bioavailable agent.

Cross Infection↗
PubMed2001

Empiric antibiotic therapy and mortality among medicare pneumonia inpatients in 10 western states : 1993, 1995, and 1997.

STUDY OBJECTIVES: To examine the association of empiric inpatient antibiotic treatment of community-acquired pneumonia (CAP) with mortality, and whether this association varies from year to year. DESIGN: Population-based, retrospective study adjusting for demographics, comorbidities, and clinical characteristics. SETTING: Acute-care hospitals in 10 western states. PATIENTS: A group of 10,069 Medicare beneficiaries aged > or = 65 years who were hospitalized with CAP during fiscal years 1993, 1995, and 1997. MEASUREMENTS AND RESULTS: We examined the risk for mortality during the 30 days after admission to the hospital. The impact of specific antibiotic regimens varied greatly from year to year. In 1993, therapy with a macrolide plus a beta-lactam was associated with significantly lower mortality than therapy with either a beta-lactam alone (adjusted odds ratio [AOR], 0.42; 95% confidence interval [CI], 0.25 to 0.69) or other regimens that did not include a macrolide, beta-lactam, or fluoroquinolone (AOR, 0.35; 95% CI, 0.20 to 0.62). Those associations were not observed in 1995 or 1997. Lower mortality was associated with fluoroquinolone monotherapy compared with beta-lactam monotherapy in 1997 (AOR, 0.27; 95% CI, 0.07 to 0.96) and with macrolide monotherapy compared with other regimens in 1995 (AOR, 0.24; 95% CI, 0.06 to 0.93), but the number of patients who received these regimens was small. CONCLUSIONS: The inclusion of a macrolide or a fluoroquinolone in initial empiric CAP treatment was associated with improved survival, but this association varied from year to year, perhaps as a result of a temporal variation in the incidence of atypical pathogen pneumonia. Improved testing and surveillance for atypical pathogen pneumonia are needed to guide empiric therapy.

Aged↗
PubMed2001

Cost-effectiveness of gatifloxacin vs ceftriaxone with a macrolide for the treatment of community-acquired pneumonia.

STUDY OBJECTIVE: To determine the cost-effectiveness of sequential IV to oral gatifloxacin therapy vs IV ceftriaxone with or without IV erythromycin to oral clarithromycin therapy to treat community-acquired pneumonia (CAP) patients requiring hospitalization. PATIENTS: Two hundred eighty-three patients enrolled in a randomized, double-blind, clinical trial were eligible for inclusion in the cost-effectiveness analysis. METHODS: Data collected included patient demographics, clinical and microbiological outcomes, length of stay (LOS), and antibiotic-related LOS (LOSAR). Costs evaluated include drug acquisition (level 1); plus costs of preparation, dispensing, and administration, treating adverse events, and clinical failures (level 2); plus hospital per diem costs (level 3). Robustness of economic findings was tested using sensitivity analyses. RESULTS: Two hundred three patients were clinically and economically evaluable (98 receiving gatifloxacin and 105 receiving ceftriaxone). IV erythromycin was administered to 35 patients in the ceftriaxone-treated group. Oral conversion was achieved in 98% of patients in each group. Clinical cure and microbiological eradication rates did not differ statistically (98% and 97% with gatifloxacin vs 92% and 92% with ceftriaxone, respectively). Overall, neither geometric mean LOS nor LOSAR differed significantly (4.2 days and 4.1 days with gatifloxacin vs 4.9 days and 4.9 days with ceftriaxone, respectively). Treatment failures in the ceftriaxone group contributed to a mean incremental increase in LOSAR of 1.09 days and increased mean cost per patient. The geometric mean costs per patient (level 3) were $5,109 for gatifloxacin and $6,164 for ceftriaxone (p = 0.011). The cost-effectiveness ratios (mean cost per expected success) were $5,236:1 and $7,047:1 for gatifloxacin and ceftriaxone, respectively. CONCLUSIONS: Gatifloxacin monotherapy for CAP patients requiring hospitalization is clinically effective and provides an economic advantage compared to the regimen of ceftriaxone with or without erythromycin IV with a switch to oral clarithromycin.

Adolescent↗
PubMed2000

Antibiotic therapy of exacerbations of chronic bronchitis.

The role of antibiotics in acute exacerbations of chronic bronchitis (AECB) remains controversial because patients commonly harbor the same bacteria in their sputum at times of stability and at times of acute illness. However, prospective randomized controlled trials do show a benefit for the use of antibiotics, compared with placebo, in AECB, particularly if patients have at least 2 of the following 3 symptoms: increased dyspnea, increased sputum volume, increased sputum purulence. In this setting, antibiotics have value, leading to a more rapid resolution of symptoms and a more rapid return of peak flow rate, compared with placebo. In addition, antibiotics may prevent some patients from developing secondary pneumonia and may prolong the time between exacerbations. When antibiotics are used, a variety of factors must be considered in choosing an agent. These include the likelihood of antibiotic-resistant bacteria, a factor that relates to defining subsets of patients. Patients can fall into 1 of 3 categories, each with a different suggested therapy. These categories include simple AECB, complicated AECB, and AECB at risk for infection with P. aeruginosa. In addition, an antibiotic should be chosen with pharmacokinetics and pharmacodynamic behavior in mind. In the future, research will need to confirm that careful selection of specific agents for specific patients can lead to improved patient outcomes, but already some preliminary data are supporting this concept.

Anti-Bacterial Agents↗
PubMed2000

Differential patterns of apoptosis in resolving and nonresolving bacterial pneumonia.

Infection with either Streptococcus sanguis or Streptococcus pneumoniae type 25 causes acute pneumonitis in rats. Pneumonia caused by S. sanguis resolves over the course of 8 d, whereas pneumonia caused by S. pneumoniae type 25 progresses to fibrosis. To examine the role of apoptosis in these models, we performed assays with the terminal deoxynucleotidyltransferase-uridine nucleotide end-labeling technique on tissue sections from rat lungs at various times, and quantified the results with image analysis. Apoptosis was a feature of both the acute and resolving stages of pneumonia. The pattern and extent of apoptosis were similar in both models during the acute stage, and the number of apoptotic nuclei increased in both models through 4 d after infection. Although there were differences in the cellular pattern of apoptosis after 2 d and 4 d of infection, the extent of apoptosis was the same in both models. After 8 d, major differences were observed. In the resolving model, apoptosis was limited primarily to an abscess in the base of the lung. In the nonresolving model, apoptosis was persistent. We also found that cyclin-dependent kinase-5 expression is upregulated during apoptosis induced by bacterial infection. These data indicate that the location and timing of apoptosis may determine whether pneumonia resolves or progresses to fibrosis.

Animals↗
PubMed2000

Acute exacerbation of COPD: factors associated with poor treatment outcome.

OBJECTIVES: To determine the effect of age, severity of lung disease, severity and frequency of exacerbation, steroid use, choice of an antibiotic, and the presence of comorbidity on the outcome of treatment for an acute exacerbation of COPD. DESIGN: A retrospective chart analysis over 24 months. SETTING: A university Veterans Affairs medical center. PATIENTS: Outpatients with COPD who were treated with an antibiotic over a period of 24 months for an acute exacerbation of COPD. METHODS: Severity of an acute exacerbation of COPD was defined using the criteria of Anthonisen et al: increased dyspnea, increased sputum volume, and increased sputum purulence. Severity of lung disease was stratified based on FEV(1) percent predicted using American Thoracic Society guidelines (stage I, FEV(1) > or = 50%; stage II, FEV(1) 35 to 49%; stage III, FEV(1) < 35%). Treatment outcome was judged successful when the patient had no return visit in 4 weeks for a respiratory problem. Failure was defined as a return visit for persistent respiratory symptoms that required a change of an antibiotic in < 4 weeks. RESULTS: One-hundred seven patients with COPD (mean age +/- SD, 66.9 +/- 9.5 years) experienced 232 exacerbations over 24 months. First-line antibiotics (trimethoprim-sulfamethoxazole, ampicillin/amoxicillin, and erythromycin) were used to treat 78% of all exacerbations. Treatment failure was noted in 12.1% of first exacerbations and 14. 7% of all exacerbations, with more than half the failures requiring hospitalization. Host factors that were independently associated with treatment failure included the following: FEV(1) < 35% (46.4% vs 22.4%; p = 0.047), use of home oxygen (60.7% vs 15.6%; p < 0. 0001), frequency of exacerbation (3.8 +/- 2.0 vs 1.6 +/- 0.91; p < 0. 001), history of previous pneumonia (64.3% vs 35.1 p < 0.007), history of sinusitis (28.6% vs 8.8%; p < 0.009) and use of maintenance steroids (32.1% vs 15.2% p = 0.052). Using stepwise logistic regression analysis to identify the top independent variables, the use of home oxygen (p = 0.0002) and frequency of exacerbation (p < 0.0001) correctly classified failures in 83.3% of the patients. Surprisingly, age, the choice of an antibiotic, and the presence of any one or more comorbidity did not affect the treatment outcome. CONCLUSION: The results of our study suggest that patient host factors and not antibiotic choice may determine treatment outcome. Prospective studies in appropriately stratified patients are needed to validate these findings.

Acute Disease↗
PubMed2000

The role of bacteria in exacerbations of COPD. A constructive view.

The role of infection in exacerbations of COPD remains controversial and incompletely understood. Although some investigators believe that bacteria are not important for patients with exacerbation, we disagree and believe that patients with at least two of the three cardinal symptoms of exacerbation should receive antibiotic therapy. With an open-minded view of the area, we review the data, showing that bacteriologic studies, pathologic investigations, and clinical trials all support roles for bacteria and antibiotic therapy in this disease. Still, many questions remain, and future studies will be needed to better define the mechanisms of bacterial invasion in the bronchitic patient and to develop effective vaccines to prevent exacerbations. In the meantime, we must rely on antibiotic therapy, and we will need prospective studies to corroborate preliminary findings showing that different patients may require different therapies; thus, patient subsetting may be vital in the selection of antibiotic therapy for exacerbations of COPD.

Anti-Bacterial Agents↗
PubMed1999

Treatment cost of acute exacerbations of chronic bronchitis.

In 1994, the National Center for Health Statistics estimated that more than 14 million people (54 per thousand) had chronic bronchitis and sought treatment for 90.9% of their acute episodes. However, few studies have been done on the treatment cost of chronic bronchitis using national data. We conducted a retrospective analysis of claims for patients treated for acute exacerbations of chronic bronchitis (AECB) to assess the frequency of services rendered and the costs to the health care system. Records were selected for the study based on a primary diagnosis of AECB according to the International Classification of Diseases, Ninth Revision, code. Medicare was the primary source of data on patients aged > or =65 years; data from the National Healthcare and Cost Utilization Project, the National Ambulatory Medical Care Survey, and the National Hospital Ambulatory Medical Care Survey were used for patients aged <65 years. We calculated a total treatment cost of $1.2 billion for patients aged > or =65 years and $419 million for patients aged <65 years. These calculations were based on the following: 280,839 hospital discharges resulting in hospital costs of $1.1 billion for the 207,540 patients aged > or =65 years, and $408 million for the 73,299 patients aged <65 years. The mean hospital length of stay was 6.3 days with a mean cost of $5497 for patients aged > or =65 years and 5.8 days with a mean cost of $5561 for younger patients. Room and board represented the largest percentage of the mean hospital costs of AECB. Inpatient physician services cost $32 million and $11 million for the 2 age groups, respectively. Diagnosis-specific data for outpatient services were found to be less reliable than inpatient data, possibly due to diagnostic coding omissions; 331,000 outpatient office visits for AECB were found for those aged > or =65 years and 237,000 visits for those aged <65 years, resulting in respective total outpatient costs of $24.9 million and $15.1 million. If the number of outpatient visits remain consistent with 1994 levels, there would be 5.8 million visits annually for those aged > or =65 years and 4.2 million visits for those aged <65 years; total outpatient costs would be $452 million and $317 million, respectively. Because the treatment costs of AECB are largely the costs of hospitalization, any new therapy that allows more patients to be treated in the outpatient setting is likely to generate significant savings.

Aged↗