Search PubMed⌕ Search

Biomedical subjects

M S Niederman

Publications and source records attributed to M S Niederman.

At least 91 records · Page 5Linked to original sources
PubMed1991

Delivery of topical antibiotics: pharmacokinetics and clinical problems.

Despite major advances in new therapeutic agents to treat pneumonia, pneumonia remains a major cause of morbidity and mortality in hospitalized patients. Topical antibiotics offer many potential advantages in the treatment and prevention of nosocomial pneumonia. These include a high delivery of the drug to the site of infection and the potential for little systemic absorption and, as a result, reduced side effects. The potential disadvantages include failure of topical therapy to reach all diseased areas of the lung and the emergence of resistant organisms. Failure of many of the previous clinical studies has been ascribed to these potential disadvantages. However, little attention has been paid in previous clinical studies to actual dosage and regional distribution of aerosolized antibiotics in the lung and the pharmacokinetics of the aerosol after deposition. One major exception to this has been the use of aerosolized pentamidine, in which careful attention has been paid to nebulizer design, dosage to the lung, regional distribution, and pharmacokinetics. It should serve as the model for the testing of topical antibiotics therapy in the future.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Atypical manifestations of pneumonia in the elderly.

This article focuses on the features of common lower respiratory-tract infections in the elderly, specifically those age-associated physiologic and immunologic changes that alter the classic clinical picture of infection. Attention is directed at the epidemiology and clinical features of pneumonia in community, institutionalized, and hospitalized individuals. Those treatment factors unique to an elderly patient are discussed.

Age Factors↗
PubMed1991

The impact of tracheal intubation on host defenses and risks for nosocomial pneumonia.

Nosocomial pneumonia remains a common complication in patients treated with endotracheal intubation and mechanical ventilation and continues to have a significant impact on the mortality rate of these patients. Epidemiologic studies have shown that the risk of pneumonia increases with the duration of intubation but that the period of highest risk is the first 2 weeks of therapy. Gram-negative bacteria account for most nosocomial pneumonias in intubated patients, but Staphylococcus aureus may also play a role in what may be a polymicrobial infection. In the most seriously ill individuals, and in those treated with long-term mechanical ventilation, Pseudomonas aeruginosa is a common pathogen. Endotracheal intubation and mechanical ventilation predispose to pneumonia for a variety of reasons (see Fig. 1). The endotracheal tube can have direct effects on the airway that result in a reduction in local host defenses. Thus, mucosal injury can reduce mucociliary function, while upper airway defenses are bypassed and the effectiveness of cough is reduced. Indirectly, intubation can result in an enhanced capacity of tracheobronchial cells to bind gram-negative bacteria, an effect that favors airway colonization and pneumonia. The injury to the airway can create binding sites for bacteria in the basement membrane of the bronchial tree and the stimulation of the secretion of mucus, which then stagnates and can create potential sites for bacterial adherence. The endotracheal tube also enhances bacterial entry to the lung by serving as a reservoir for bacteria to remain sequestered, safe from host defenses. Respiratory therapy devices can allow bacteria to proliferate and can then introduce them into the patient if not handled properly. Finally, patients who are ill enough to require intubation also have disease-associated impairments in systemic host defense, which add to the impairments caused by the use of an artificial airway. The host defense impairments that occur in mechanically ventilated patients can lead to respiratory tract infection in the form of either febrile tracheobronchitis or pneumonia. The diagnosis of pneumonia in intubated patients is difficult and controversial. It can be made by either clinical criteria or microbiologic criteria, the latter by using a bronchoscopically directed protected specimen brush. Therapy of pneumonia in mechanically ventilated patients is not always successful, and systemic antibiotics may need to be supplemented by topical antimicrobials. No clearly effective prophylactic strategy currently exists, but our understanding of pneumonia pathogenesis has led to some promising directions. As more data are collected, inhaled antibiotics, selective digestive decontamination, and enhancement of host defenses by cytokines and pre-formed antibodies may emerge as useful approaches.

Bacterial Adhesion↗
PubMed1990

Cardiovascular-pulmonary interaction in chronic obstructive pulmonary disease with special reference to the pathogenesis and management of cor pulmonale.

Chronic obstructive pulmonary disease (COPD), which here refers to a group of diseases that have in common the physiologic defect of airway obstruction, is often associated with severe hemodynamic consequences. This article provides an overview of cardiovascular function in COPD with emphasis on recent advances in detecting, quantifying, and treating pulmonary hypertension and its major cardiac complication, cor pulmonale.

Heart↗
PubMed1990

Utility of fiberoptic bronchoscopy in nonresolving pneumonia.

Although fiberoptic bronchoscopy (FOB) has been traditionally used to evaluate nonresolving pneumonia, its efficacy is unknown. We, therefore, reviewed FOB in 35 consecutive patients who had (1) a roentgenographic infiltrate, (2) cough, (3) either temperature greater than 38.1 degrees C, leukocytosis, sputum production, (4) symptoms present for at least ten days, and antibiotic therapy for at least one week. Known lung cancer and AIDS were excluded. Fiberoptic bronchoscopy was diagnostic in 86 percent (12/14) in whom a specific cause was found. No patient had endobronchial cancer. Two patients with nondiagnostic FOB and persistent systemic symptoms had open lung biopsy specimens showing Wegener's granulomatosis and bronchiolitis obliterans with organizing pneumonia (BOOP). Twenty-one patients with nondiagnostic FOB had no final diagnoses other than community-acquired pneumonia. We conclude that FOB is extremely useful in finding a specific diagnosis for a nonresolving pneumonia when a specific diagnosis can be made. Fiberoptic bronchoscopy was most likely to yield a specific diagnosis in nonsmoking patients with multilobar infiltrates of long duration and could have been avoided in older, smoking, or otherwise compromised patients with lobar or segmental infiltrates with no decrease in diagnostic yield in our series.

Adult↗
PubMed1990

Gram-negative colonization of the respiratory tract: pathogenesis and clinical consequences.

The normal upper and lower respiratory tract are not colonized by enteric gram-negative bacteria (EGNB), but when serious illness develops, both sites may harbor these organisms. Colonization at either site is more likely when the severity of illness increases, and in critically ill patients, Pseudomonas species are the most common colonizing organisms, especially in the tracheobronchial tree. Many of the risk factors for colonization by EGNB have also been recognized as predisposing conditions for nosocomial pneumonia, and colonization may precede and predict this infection. Colonization should be viewed as a marker of a sick patient who had multiple host impairments; it is these defects that often allow colonization to progress to invasive infection. One pathogenetic mechanism that mediates colonization is an increase in epithelial cell bacterial adherence for EGNB. Many of the clinical conditions that favor colonization lead to an alteration in epithelial cell surface susceptibility to bacterial binding. Factors that influence adherence include cellular variables, bacterial surface characteristics and exoproducts, and the microenvironmental conditions at the airway surface. In order for adherence to mediate colonization, mucociliary clearance and other lower respiratory tract defenses must be abnormal. Based on an understanding of colonization pathogenesis, rational strategies for nosocomial pneumonia prophylaxis may emerge.

Bacterial Adhesion↗
PubMed1990

Sepsis syndrome, the adult respiratory distress syndrome, and nosocomial pneumonia. A common clinical sequence.

Systemic sepsis and pneumonia are common predisposing factors for ARDS, which can serve as the initial manifestation of the multisystem organ failure syndrome. Primary pneumonia that necessitates ICU admission leads to ARDS in approximately 10% of patients. Systemic infection can also lead to ARDS, but when bacteremia alone is present, the risk is low (probably less than 5%). If the septic syndrome with a hemodynamic and end-organ response develops, the ARDS may follow in as many as 40% of patients. When multiple risk factors for acute lung injury are present, the risk of developing ARDS rises dramatically. The septic syndrome, acute lung injury, and multiorgan failure are closely tied to one another because bacterial cell walls can activate inflammatory mediators, such as interleukin-1 and tumor necrosis factor, which can in turn lead to the septic syndrome and inflammatory injury to the lung. Clinical features, more than serum markers, have been the best predictors of whether lung injury will follow sepsis, indicating that the mere presence of mediators alone cannot cause ARDS and that there are individual susceptibility factors in the effects of these mediators. With the advent of monoclonal antibodies and new anti-inflammatory drugs, prevention of progression from sepsis to multiorgan failure may become possible. Pneumonia is the most common infection that complicates ARDS once it is established, and the mortality rate may approach 90%. The existence of acute lung injury, its predisposing conditions, coexisting illnesses, and the therapeutic interventions used for patients with lung injury all can interfere with lung host defenses and set the stage for bacterial infection of the already-injured lung. This infection appears to add to the propagation of the multiple system organ failure that has already begun. In the future, it may become possible to prevent this infection, which would be a welcome development, because currently, we are stymied in our efforts to diagnose and treat pneumonia in the setting of acute lung injury. Preventive efforts will follow from an understanding of the pathogenesis of pneumonia and in the future may include topical antibiotics, selective digestive decontamination, and prophylactic passive immunotherapy.

Acute Disease↗
PubMed1989

Patterns and routes of tracheobronchial colonization in mechanically ventilated patients. The role of nutritional status in colonization of the lower airway by Pseudomonas species.

Tracheobronchial colonization by Gram-negative bacteria is common in mechanically ventilated patients. Pseudomonas sp are commonly isolated from the lower airways. We hypothesized that Pseudomonas sp would preferentially colonize the lower airway and would be more common in patients with poor nutritional status. We serially collected 75 pairs of upper and lower respiratory tract cultures from 14 patients treated with mechanical ventilation for at least one week, examined patterns of airway colonization and routes of bacterial entry for Pseudomonas sp and other enteric Gram-negative bacteria (EGNB), and related these findings to host-associated factors, including nutritional status. Pseudomonas sp were the most common species isolates taken from the lower airway, found in nine of 14 patients and in 41.3 percent of all cultures. In contrast to other EGNB, Pseudomonas sp were found significantly (p less than or equal to 0.05) more often in the tracheobronchial tree (31 of 75 cultures) than in the oropharynx (18 of 75 cultures). Primary colonization of the lower airway by Pseudomonas sp was found in four patients, while other EGNB never followed this pattern when subjects were studied with cultures taken every third day. A host-related factor related to lower airway colonization by Pseudomonas species was poor nutritional status, assessed by a multifactorial index (p less than or equal to 0.01). We conclude that in mechanically ventilated patients, Pseudomonas sp colonize the lower airway in a different pattern and by a different route from those of other EGNB. The findings that Pseudomonas sp preferentially colonize the tracheobronchial tree may be important for the design of strategies to prevent airway colonization. The recognition that poor nutritional status, a potentially modifiable host-related factor, favors lower airway growth of Pseudomonas sp suggests one direction for future infection-control efforts.

Adult↗
PubMed1989

Respiratory infections and acute lung injury in systemic illness.

We have discussed the relationship between systemic illness, infection, and lung disease. As we have seen, patients with a wide variety of disease states, including advanced age, diabetes mellitus, alcoholism, collagen vascular disease, cancer, heart failure, and organ transplantation are potentially at increased risk for pneumonia because of disease-related impairments in host defenses. In addition, two virtually ubiquitous conditions in hospitalized patients, malnutrition and therapeutic interventions (especially with common medications), frequently add to the risk of airway invasion by bacterial pathogens. Systemic illness not only makes lung infection more common, but may adversely affect outcome and resolution, as well as determine the clinical presentation of pneumonia. In one particular population, the intubated and mechanically ventilated patient, the risk of infection is particularly high, and nosocomial pneumonia is a major cause of mortality. To the extent that the host response itself leads to the symptoms and signs of infection, systemically ill individuals may have subtle clinical features when serious bacterial invasion is present. Many components of the host defense system can become abnormal with serious illness, but a common mechanism that ties many systemic diseases to pneumonia is an alteration in airway epithelial cell receptivity for bacteria, namely, bacterial adherence, a process that mediates airway colonization, the first pathogenetic step on the road to pneumonia. The impetus for understanding how serious illness promotes lung infection is that once these mechanisms are identified, potential preventative strategies to minimize infection risk in the individual with systemic disease may be developed. The relationship among systemic illness, the lung, and infection also exists in a different direction: infection of a systemic nature (the septic syndrome) can lead to disease in the lung (ARDS). We have described the features of the septic syndrome and identified how it may lead to lung injury, usually by indirect means, through activation of inflammatory mediators that are carried to the lung via the vasculature. Although it is frequently impossible to predict which specific patient with systemic sepsis will develop acute lung injury, the current state of knowledge does permit us to identify high-risk individuals. Surprisingly, clinical assessment rather than biochemical testing is the best predictor of the development of acute lung injury. Patients with severe injury, profound shock and multiple systemic insults are most prone to acute lung injury in the presence of systemic sepsis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1988

Non-cardiogenic pulmonary edema after pericardial drainage for cardiac tamponade.

We report a patient who developed adult respiratory distress syndrome following relief of pericardial tamponade. Because of increasing recognition of pulmonary edema in this situation, we recommend gradual removal of pericardial fluid with hemodynamic monitoring to limit the massive fluid shifts which appear to herald this dire complication.

Adult↗
PubMed1987

"When the pneumonia doesn't get better".

Nonresolving pneumonia is a common and frequently misunderstood problem faced by the practicing pulmonologist. While radiographic resolution of most infections is relatively long and lags behind clinical signs of recovery, data suggest that a variety of host defense problems are a consequence of systemic illness and are often involved. When such factors are not implicated, other specific etiologies should be sought, including unusual organisms like mycobacteria, higher order bacteria, and fungi. Noninfectious causes for delayed resolution include neoplastic disease, immunologic disease, thromboemboli, and inhalation injuries. This article discusses the natural history of common pneumonias to establish the usual clinical limits of resolution and outlines a diagnostic strategy to use when these limits are exceeded.

Airway Obstruction↗
PubMed1987

Strategies for the prevention of pneumonia.

Pneumonia remains a major source of morbidity and economic cost to our society, despite the availability of new antibiotics for therapy. To truly reduce the impact of this illness, serious efforts at preventing infection must be undertaken. In the area of community-acquired infections, safe and effective vaccines are available against S. pneumoniae, the most common pneumonic pathogen, and influenza. High-risk individuals (Table 2), who should be considered for vaccination, include: the elderly; residents of chronic-care facilities; and patients with chronic cardiac, respiratory, renal, and hematologic illnesses. Influenza vaccine is effective in preventing infections in such high-risk populations, including the elderly. There is some controversy about the efficacy of pneumococcal vaccine in an at-risk population with severe co-morbid illness, but there is little doubt that the vaccine is effective in a more healthy elderly population. Both patients and physicians fail to appreciate the safety and utility of these vaccines as evidenced by their low rates of use. Remarkably, only about 10 per cent of appropriate persons have ever received the pneumococcal vaccine, even though it needs to be given only once in a lifetime. In the area of nosocomial pneumonia, several strategies for prevention have proven to be useful. Most promising is the use of topical antibiotics in the upper and lower airway. Although the efficacy of this approach is well established, its safety has been questioned in prior studies. For many reasons, this position should be reevaluated, and this therapy should be considered for use in carefully selected patients at risk, using modern techniques of aerosol therapy. Active investigation into vaccines against gram-negative bacterial look to yield promising results in the future. In addition, passive "serum" therapy with preformed antibodies is a strategy for preventing gram-negative lung infection that has shown use in animal studies and may circumvent certain logistical problems of vaccine therapy. Infection control methods and sensible handling of respiratory therapy equipment are simple, yet effective, means for preventing contamination of the airway in mechanically ventilated patients. Finally, for patients both in and out of the hospital, an understanding of the nature of host defense impairments leading to pneumonia will allow for strategies to boost host defenses.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗
PubMed1987

Reversal of sleep apnea in uremia by dialysis.

Obstructive sleep apnea (OSA) is a common syndrome occurring in 1% to 4% of the population. While obesity is the most common predisposition to OSA, metabolic disorders have been associated with this syndrome. We describe a patient who presented with severe OSA while in an advanced untreated uremic state, which resolved following intensive dialysis. We speculate that the sleep disturbances, which are common in uremia, may be accounted for in some patients by OSA and may resolve with specific therapy for advanced renal failure.

Aged↗
PubMed1986

Influence of sputum IgA and elastase on tracheal cell bacterial adherence.

Bacterial adherence is an important pathogenetic mechanism for airway colonization, but the influence of airway proteins on this phenomenon is largely unknown. We measured tracheal cell bacterial binding in 13 subjects with chronic tracheostomy and related these results to measurements of sputum IgA, elastase activity, and total protein from the same subjects. Tracheal cell adherence was related directly to sputum elastase activity (r = 0.61, p = 0.02); and elastase activity, primarily a serine protease, was higher in subjects colonized by Pseudomonas aeruginosa than in those without this finding (p = 0.02). Sputum levels of IgA/mg protein were related inversely to tracheal cell adherence (r = 0.64, p = 0.02). Sputum IgA concentrations, in turn, were affected by host nutritional status and airway elastase activity. Evidence that elastase can degrade sputum IgA was provided by an inverse relationship observed between these 2 proteins (r = 0.56, p = 0.04) and by in vitro mixing experiments showing fragmentation of IgA by purified neutrophil elastase. In addition, sucrose density gradient separation indicated IgA fragmentation to have occurred in vivo. These data suggest that, once adherence leads to airway colonization, the resulting inflammatory response may foster microbial growth by an elastase-dependent IgA cleavage and hence enhanced tracheal cell adherence.

Adult↗
PubMed1986

The interaction of infection and the adult respiratory distress syndrome.

Infection, particularly that involving the respiratory tract, is commonly seen in the patient with ARDS. It can be either an etiologic factor leading to the syndrome or a complicating factor leading to a high likelihood of mortality. Pneumonia develops in up to 70% of individuals with ARDS, and when present, converts the syndrome to its most severe and mortal form. In addition, when systemic injury coexists with any type of infection, ARDS will develop with an increased frequency. Nosocomial pneumonia results when upper and lower respiratory tract defenses fail and these sites are overwhelmed by bacteria. Colonization of the oropharynx and tracheobronchial tree, both of which are common in critically ill patients, precedes the development of pneumonia. In the patient with ARDS, all levels of host antibacterial defenses may be impaired, thus accounting for the high incidence of both colonization and pneumonia. These impairments result from the acute lung injury itself, coexisting systemic illnesses, therapeutic interventions, and acquired malnutrition. Once pneumonia develops in the course of acute lung injury, diagnosis is exceedingly difficult and potentially inaccurate. With proper application of the protected specimen brush, inserted bronchoscopically, diagnostic accuracy may improve. Therapy must be undertaken early and with agents directed at likely pathogens, particularly P. aeruginosa and other gram-negative bacilli. In the future, preventive efforts against pneumonia may be effective for the ARDS patient. Strategies that may be effective include hyperalimentation, judicious use of all pharmacotherapy, active and passive antibacterial vaccines, airway microenvironment manipulation, and the use of aerosolized antibiotics.

Cross Infection↗