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Biomedical subjects

M S Niederman

Publications and source records attributed to M S Niederman.

At least 73 records · Page 4Linked to original sources

An approach to empiric therapy of nosocomial pneumonia.

Because many studies show that antibiotic therapy is effective for nosocomial pneumonia, it is necessary to have an approach to antibiotic selection to reduce mortality. Empiric therapy can be chosen, based on an assessment of patient risk factors for specific organisms and on an evaluation of the severity of illness present. Empiric regimens must be selected from a knowledge of antibiotic pharmacodynamics, as well as from an appreciation of the antimicrobial spectrum of the various antibacterials. When using such an approach, it is necessary to realize the limitations of effective therapy and to evaluate a number of relevant issues if the patient is not improving during treatment.

Anti-Infective Agents↗

Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group.

Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79% of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobacteriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE II score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and effective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from patients.

Adult↗

Empirical therapy of community-acquired pneumonia.

An empiric approach to the therapy of community-acquired pneumonia (CAP) is needed because of the limitations of traditional approaches to antibiotic selection. The use of sputum Gram's stain and culture tests to guide initial therapy is potentially inaccurate and of limited use. Clinical syndromes cannot be reliably used to predict microbial pathogens, primarily because host, as well as bacterial factors, contribute to the presence of specific clinical signs and symptoms. The routine use of extensive diagnostic testing on all patients with CAP is expensive and of limited clinical usefulness. An empirical approach is presented that is based on an assessment of three factors that can help to predict the likely etiologic pathogens and thus guide initial therapy. These factors are the place of therapy, the presence of advanced age and/or comorbidity, and the severity of illness on initial clinical presentation. When these factors are used to guide empirical therapy, it is important to recognize and appropriately evaluate the nonresponding patient, and it is in this setting that an extensive diagnostic evaluation may be most useful.

Age Factors↗

Severe pneumonia in the elderly.

The elderly are more susceptible to pneumonia and more likely to die from this infection than younger populations. Older patients with pneumonia requiring hospitalization are more likely to develop complications necessitating longer hospital stays. This article focuses on features of common lower respiratory tract infections and physiologic and immunologic characteristics of elderly patients that might obscure classic clinical presentation of pneumonia. Treatment factors unique to elderly patients with severe pneumonia are also discussed.

Age Factors↗

Nosocomial pneumonia in the elderly patient. Chronic care facility and hospital considerations.

By nature, nosocomial infections in general, and pneumonia specifically, are opportunistic, preying on patients who are already seriously ill. These infections are a major source of morbidity and mortality for these individuals. Among the elderly, pneumonia is more common and more likely to lead to death. The author reviews the epidemiology and risk factors for nosocomial pneumonia among the elderly.

Aged↗

Nonresolving and slowly resolving pneumonia. Diagnosis and management in the elderly patient.

Pneumonia is both more prevalent in the elderly and more severe. This article reviews the approach to nonresolving or slowly resolving pneumonia in the elderly. Specific attention will be given to the natural history of commonly occurring pneumonias in this age group, related host defense impairments, unusual infectious causes of slowly resolving pneumonia, and noninfectious mimics of pneumonia.

Aged↗

Nonresolving pneumonia in steroid-treated patients with obstructive lung disease.

PURPOSE: To review autopsy-proven cases of opportunistic pneumonia and determine how many of these patients had received corticosteroid therapy for obstructive lung disease in order to define whether this therapy was the major risk factor predisposing to infection. PATIENTS AND METHODS: All autopsies performed at Winthrop-University Hospital over a 5-year period were reviewed, and 30 cases of opportunistic pneumonia were identified. In eight of 30 cases, corticosteroid therapy for chronic obstructive pulmonary disease (COPD) was the only identifiable risk factor for opportunistic infection. The other 22 patients had other well-defined risk factors for infection. Chart review of the eight patients with COPD was undertaken to define the clinical features of their infections. RESULTS: All eight patients had a progressive multilobar pneumonia that failed to resolve, either clinically or radiographically, despite the use of multiple broad-spectrum antibiotics. In four cases, the infection was community-acquired, while in the other four cases, it was nosocomial in origin. Despite the presence of a nonresolving pneumonia, opportunistic infection was generally not considered as a diagnostic possibility, with only one case being correctly diagnosed antemortem. Autopsy examination documented Aspergillus species as being responsible for six episodes of pneumonia, Candida albicans accounting for one episode, and cytomegalovirus accounting for one episode. CONCLUSION: Based on this experience, it is clear that corticosteroid therapy of COPD can lead to opportunistic pulmonary infection, in or out of the hospital. This diagnosis should be considered when patients receiving this therapy develop a pneumonia that fails to respond to broad-spectrum antibiotics.

Aged↗

Pneumonia complicating pregnancy.

Although pregnancy is infrequently complicated by pneumonia, lung infection by bacteria, viruses, and fungi can pose serious maternal and fetal hazards. Pneumonia may lead to preterm labor and certain infecting agents, most notably the HIV virus, can cross the placenta and lead to neonatal infection. There is some evidence that the incidence of pneumonia in pregnancy may be increasing among certain populations. In addition, infections caused by viruses (varicella and influenza) and fungal agents, ordinarily controlled by cell-mediated immunity, may be more virulent to pregnant women, thereby adding to maternal mortality. Beyond the influence of these pregnancy-induced changes in immunity, there are certain physiologic changes in pregnancy that make it more difficult for the pregnant woman to sustain any type of respiratory infectious insult. Certain types of pneumonias, particularly influenza and aspiration, may be avoided if patients at risk are identified and existing strategies for prevention are applied. When the pregnant women is treated for lung infection, the safety of antimicrobial agents must be considered, and therapy may differ from that used in the nonpregnant patient.

Bacterial Infections↗

Characterization of Pseudomonas aeruginosa adherence to cultured hamster tracheal epithelial cells.

This study reports an in vitro system that allows the convenient study of both microenvironmental and bacterial factors affecting adherence of Pseudomonas aeruginosa to tracheal epithelium. Primary cultures of mixed ciliated and nonciliated epithelial cells isolated from hamster tracheas were grown on collagen-coated multiwell plates containing 10(5) epithelial cells/well at confluence. When 10(7) 14C-labeled P. aeruginosa (nonmucoid, strain Y-4) suspensions were added to each well, 8.13 +/- 2.6% (mean +/- SD) of the initial inoculum bound to the cultured cells, an amount comparable to that measured using suspensions of human tracheal epithelial cells and the same bacteria. The bacteria adhered preferentially to the cultured cells rather than to an acellular collagen matrix. Five additional nonmucoid strains of P. aeruginosa also bound well to the cultured cells, while two mucoid strains were less adherent. Strains of two other gram-negative bacteria, Pseudomonas maltophilia and Klebsiella pneumoniae, did not bind significantly, emphasizing the bacterial species specificity of the adherence interaction being measured. The binding interaction with P. aeruginosa was both pH-sensitive and altered by the presence of the divalent cation calcium. Thus, the in vitro assay system described provides a consistent surface of tracheal epithelial cells that binds P. aeruginosa in a specific manner and can be used to examine the effects of bacterial variables and microenvironmental conditions that may be present in the human airway.

Animals↗

Benefits of a multidisciplinary pulmonary rehabilitation program. Improvements are independent of lung function.

We evaluated the conditions of 33 patients who completed an outpatient pulmonary rehabilitation program to determine what types of improvements occurred, and whether these changes were related to the baseline degree of ventilatory impairment, to determine whether rehabilitation was beneficial to patients, regardless of the degree of underlying lung dysfunction. Endurance measurements, including sustained submaximal performance on a cycle ergometer and the 12-minute walk distance (1,349 +/- 625 feet to 1,700 +/- 670 feet) increased significantly (p less than 0.01), as did multiple educational and subjective parameters. Maximal exercise performance on a graded cycle test improved very little, with a decline in the ventilatory equivalent for oxygen consumption (VE/VO2) being the only significant change (48.2 +/- 28.3 L/ml to 36.6 +/- 8.7 L/ml). Of the observed changes, only one endurance measurement, the sustained submaximal exercise performance, correlated with FEV1 (r = 0.5, p less than 0.01), but only if it was expressed as an absolute number (liters) and not as percent predicted. Lung function did not correlate with changes in the 12-minute walk distance, in maximal exercise performance on the cycle ergometer or with changes in educational and subjective parameters. We conclude that because the magnitude of change in both physiologic and psychologic parameters was not directly related to lung function, the benefits of rehabilitation can extend to all patients with chronic lung disease, regardless of the severity of preexisting pulmonary dysfunction.

Aged↗

Neutrophil-endothelial cell interaction in critical illness.

Sepsis syndrome frequently results in endothelial injury in many organ systems. To evaluate neutrophil-pulmonary endothelial cell interaction in the sepsis syndrome, we studied 39 critically ill patients prospectively and 20 normal volunteers. Thirteen patients with sepsis (mean age, 71.4 years), 14 patients in an intensive care unit control group (mean age 65.4 years), and 12 patients admitted with acute myocardial infarction (mean age, 66.8 years) were evaluated. Blood samples were drawn from septic patients within 24 hours and from ICU and MI patients within 72 hours of admission. All sepsis patients were culture positive, 6 of 13 from the blood. Both renal failure and ARDS developed in 54 percent of septic patients. 51Cr-labelled neutrophils were prepared and added to bovine pulmonary endothelial cell monolayers with and without added phorbol myristate acetate. Endothelial cells with adherent PMA and nonadherent PMN's, were harvested and radioactivity in each fraction measured with a gamma scintillation counter. Baseline and maximally stimulated (PMA, 3.0 ng/ml) neutrophil adherence to endothelial cells were similar in all patients groups. However, in septic patients, PMA-stimulated PMN adherence was reduced at lower doses, most significantly in those who developed ARDS within 24 to 48 hours of admission (p less than 0.05). Seventy-one percent of patients who developed ARDS had reduced stimulated adherence (PMA 1.0 ng/ml) compared to 22 percent of critically ill patients who did not. We conclude that diminished adherence of neutrophils to endothelium in response to low-level PMA stimulation is significantly more common in patients with sepsis who develop ARDS. Our findings suggest that PMN-endothelial cell interaction is altered by the time sepsis is clinically recognized but before the development of ARDS. We speculate that the observed reduction in adherence of the PMN to endothelial cells may be a consequence of down-regulation by mediators generated in the inflammatory response to sepsis and/or the need for active participation of septic endothelium in this interaction.

Aged↗