Pseudomonal infections in patients with COPD: epidemiology and management

COPD is a common disease with increasing prevalence. The chronic course of the disease is characterized by acute exacerbations that cause significant worsening of symptoms. Bacterial infections play a dominant role in approximately half of the episodes of acute exacerbations of COPD. The importance of pseudomonal infection in patients with acute exacerbations of COPD stems from its relatively high prevalence in specific subgroups of these patients, and particularly its unique therapeutic ramifications. The colonization rate of Pseudomonas aeruginosa in patients with COPD in a stable condition is low.A review of a large number of clinical series of unselected outpatients with acute exacerbations of COPD revealed that P. aeruginosa was isolated from the patients' sputum at an average rate of 4%. This rate increased significantly in COPD patients with advanced airflow obstruction, in whom the rate of sputum isolates of P. aeruginosa reached 8-13% of all episodes of acute exacerbations of COPD. However, the great majority of bacteria isolated in these patients were not P. aeruginosa, but the three classic bacteria Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis. The subgroup of patients, with acute exacerbations of COPD, with the highest rate of P. aeruginosa infection, which approaches 18% of the episodes, is mechanically ventilated patients. However, even in this subgroup the great majority of bacteria isolated are the above-mentioned three classic pathogens. In light of these epidemiologic data and other important considerations, and in order to achieve optimal antibacterial coverage for the common infectious etiologies, empiric antibacterial therapy should be instituted as follows. Patients with acute exacerbations of COPD with advanced airflow obstruction (FEV(1) <50% of predicted under stable conditions) should receive once daily oral therapy with one of the newer fluoroquinolones, i.e. levofloxacin, moxifloxacin, gatifloxacin, or gemifloxacin for 5-10 days. Patients with severe acute exacerbations of COPD who are receiving mechanical ventilation should receive amikacin in addition to one of the intravenous preparations of the newer fluoroquinolones or monotherapy with cefepime, a carbapenem or piperacillin/tazobactam. In both subgroups it is recommended that sputum cultures be performed before initiation of therapy so that the results can guide further therapy.     

Iron status and neurobehavioral development of premature infants.

OBJECTIVE: This study was conducted to examine the relation between iron status and neurobehavioral development in premature infants. STUDY DESIGN: Infants born before 34 weeks postmenstrual age and who were medically stable were studied. Anemia was defined as hemoglobin < or =10 g/Dl and low iron stores as a serum ferritin concentration < or =75 microg/l. The infants were classified as anemic with low ferritin (Group 1; n=18), anemic with normal ferritin (Group 2; n=14), and nonanemic with normal ferritin (Group 3; n=21). A total of 18 reflexes were behaviorally evaluated at 37 weeks postmenstrual age and "reflex scores" were compared between the groups. Higher scores reflect a greater percentage of abnormal reflexes. RESULTS: Infants in group 1 (anemia/low ferritin) had a significantly higher reflex score (51.45+/-18.32%) than infants in Group 3 (38.32+/-17.75%). Group 2 had an intermediate score (45.40+/-21.70%), but not different from the other two groups. CONCLUSION: These data indicate that low iron status, both measured by anemia and ferritin levels, is related to poorer neurobehavioral status in premature infants.     

Further Characterization of a Transplantable Murine Osteogenic Sarcoma

A transplantable murine osteogenic sarcoma was characterized to determine its suitability as a model for human cancer and to evaluate specific end points to study therapeutic intervention. Palpable tumors developed at implantation sites following latent periods of 8 to 21 days and grew to 3 g masses within 60 days. The tumor model was predictable in its manner of tumor growth, tumor production of alkaline phosphatase, formation of pulmonary metastases, and the survival of the host. It was found to be sensitive to treatment with cyclophosphamide and vincristine and to a lesser extent to adriamycin and 4¹-epi-adriamycin. It did not show a response to treatment with cis-platinum, actinomycin D, or m-AMSA. Survival of the host is limited by the progression of metastatic disease and local control does not appreciably extend the median survival time. Thus, population survival should be used as a measure of the effectiveness of treatment of pulmonary metastases. Circulating alkaline phosphatase levels may best be used in assessing the response to treatment of the primary osteogenic sarcoma.     

CCR6, a CC Chemokine Receptor that Interacts with Macrophage Inflammatory Protein 3α and Is Highly Expressed in Human Dendritic Cells

Dendritic cells initiate immune responses by ferrying antigen from the tissues to the lymphoid organs for presentation to lymphocytes. Little is known about the molecular mechanisms underlying this migratory behavior. We have identified a chemokine receptor which appears to be selectively expressed in human dendritic cells derived from CD34⁺ cord blood precursors, but not in dendritic cells derived from peripheral blood monocytes. When stably expressed as a recombinant protein in a variety of host cell backgrounds, the receptor shows a strong interaction with only one chemokine among 25 tested: the recently reported CC chemokine macrophage inflammatory protein 3α. Thus, we have designated this receptor as the CC chemokine receptor 6. The cloning and characterization of a dendritic cell CC chemokine receptor suggests a role for chemokines in the control of the migration of dendritic cells and the regulation of dendritic cell function in immunity and infection.     

Naso- and oropharyngeal potential respiratory pathogens in adults with nonpneumonic lower respiratory tract infection

The objective of this prospective study was to determine positive isolation rates for potential respiratory pathogens (PRPs) in the naso- and oropharynx of adults hospitalized for nonpneumonic lower respiratory tract infection (NPLRTI), compared with patients with community-acquired pneumonia (CAP) and healthy controls. The study population was 315 non-chronic obstructive pulmonary disease adults hospitalized with febrile lower respiratory tract infection (158 NPLRTI and 157 CAP) and 450 control subjects. Each participant was sampled by oropharyngeal swab, nasopharyngeal swab, and nasopharyngeal washings that were tested by conventional bacteriologic methods to identify PRP. At least 1 of the samples was positive for at least 1 of the 3 PRP bacteria in 55 NPLRTI patients (35%) compared with 51 CAP patients (33%) (NS) and 100 controls (22%) (P = 0.003 compared with NPLRTI and P = 0.02 compared with CAP). Samples were positive for Streptococcus pneumoniae in 14 NPLRTI patients (9%) compared with 29 CAP patients (19%) (P = 0.02) and 16 controls (4%) (NPLRTI P = 0.015, CAP P < 0.0001). The corresponding rates for Haemophilus influenzae were 23 (15%), 16 (10%), and 60 (13%) (NS for all 3 comparisons), and for Moraxella catarrhalis, 28 (18%), 25 (16%), and 48 (11%), respectively (NPLRTI versus controls, P = 0.03, NS other comparisons). We conclude that the rate of positive naso/oropharyngeal isolates for at least 1 of the 3 PRP bacteria in NPLRTI patients is similar to the corresponding rates for CAP patients and is higher in both groups than in controls.     

Somatostatin analogue treatment attenuates histological findings of inflammation and increases mRNA expression of interleukin-1 beta in the articular tissues of rats with ongoing adjuvant-induced arthritis

Objective Somatostatin is a neuropeptide with modulatory effects on the immune system and the function of synovial cells; it has antiangiogenic and antiproliferative properties. This study aimed to evaluate the clinical, histological, and articular tissue cytokine mRNA response to somostatin treatment in rat adjuvant-induced arthritis (AIA).Methods Adjuvant-induced arthritis was induced in a total of 68 Lewis rats by immunization with complete Freunds adjuvant. Twenty-four rats were treated with a long-acting somostatin analogue 14 days after disease induction. Twenty-four untreated rats served as controls. The severity of arthritis was scored weekly for 42 days. In a second experiment, 20 rats (ten treated, ten controls) were killed 21 days after treatment for assessment of joint histopathology and articular tissue cytokine mRNA expression.Results Somatostatin analogue treatment significantly reduced histological scores of early inflammatory changes and increased articular tissue mRNA expression of interleukin-1 beta (IL-1). A trend toward improvement in physical scores of joint inflammation was seen in the treated group. Late destructive changes were not significantly different.Conclusion Treatment with a somostatin analogue attenuated early inflammatory changes in AIA joints and increased mRNA expression of IL-1 in the articular tissues of rats with ongoing arthritis. Improvement in the physical findings of joint inflammation was mild.     

Pseudomonal Infections in Patients with COPD

COPD is a common disease with increasing prevalence. The chronic course of the disease is characterized by acute exacerbations that cause significant worsening of symptoms. Bacterial infections play a dominant role in approximately half of the episodes of acute exacerbations of COPD. The importance of pseudomonal infection in patients with acute exacerbations of COPD stems from its relatively high prevalence in specific subgroups of these patients, and particularly its unique therapeutic ramifications. The colonization rate of Pseudomonas aeruginosa in patients with COPD in a stable condition is low.A review of a large number of clinical series of unselected outpatients with acute exacerbations of COPD revealed that P. aeruginosa was isolated from the patients’ sputum at an average rate of 4%. This rate increased significantly in COPD patients with advanced airflow obstruction, in whom the rate of sputum isolates of P. aeruginosa reached 8–13% of all episodes of acute exacerbations of COPD. However, the great majority of bacteria isolated in these patients were not P. aeruginosa, but the three classic bacteria Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis. The subgroup of patients, with acute exacerbations of COPD, with the highest rate of P. aeruginosa infection, which approaches 18% of the episodes, is mechanically ventilated patients. However, even in this subgroup the great majority of bacteria isolated are the above-mentioned three classic pathogens.In light of these epidemiologic data and other important considerations, and in order to achieve optimal antibacterial coverage for the common infectious etiologies, empiric antibacterial therapy should be instituted as follows. Patients with acute exacerbations of COPD with advanced airflow obstruction (FEV₁ <50% of predicted under stable conditions) should receive once daily oral therapy with one of the newer fluoroquinolones, i.e. levofloxacin, moxifloxacin, gatifloxacin, or gemifloxacin for 5–10 days. Patients with severe acute exacerbations of COPD who are receiving mechanical ventilation should receive amikacin in addition to one of the intravenous preparations of the newer fluoroquinolones or monotherapy with cefepime, a carbapenem or piperacillin/tazobactam. In both subgroups it is recommended that sputum cultures be performed before initiation of therapy so that the results can guide further therapy.