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During a prospective study of 8 months duration conducted in the Department of Internal Medicine and the Department of Pulmonary Diseases of the Academic Medical Centre, Amsterdam, Gram stainings of sputa and urine were performed for all patients whose clinical symptoms indicated an acute urinary tract infection or pulmonary infection. On the test request, the physician reported which antibiotic treatment he would prescribe if a microscopic examination was not available. The results of the Gram stain were discussed by the microbiologist with the physician, and the antibiotic therapy recommended by the microbiologist was recorded. This recommendation was compared with the antibiotic prescription noted in the patient record 1 day later. Two days after the results of final cultures and susceptibility tests became available, the patient record was again investigated for changes in the antibiotic regimen. Of 57 urine samples and 103 sputa, 27 and 85, respectively, were derived from patients with an infection of the urinary tract or respiratory tract. The results of the Gram stain confirmed the physician's suspicion 91% of the time for urinary tract infections and 81% of the time for pulmonary infections. In 67% of the patients with suspected lower respiratory tract infections and in 58% of patients with suspected urinary tract infections, the antibiotic treatment recommended on the basis of the results of the Gram stain differed significantly from the antibiotic treatment that the physician would have prescribed had a microscopic examination not been performed. The microbiologist's advice on antibiotic treatment was followed in 79% of the cases of respiratory tract infection and in 65% of the cases of urinary tract infection. The antibiotic treatment was adjusted to the final results of culture and antimicrobial susceptibility testing in 54% of the urinary tract infections and in 31% of the respiratory tract infections. The results indicate that the examination of sputa and urine in patients suspected to have an infection of the respiratory tract or urinary tract influences the antibiotic choice considerably.
Eighty-four patients with lower respiratory tract infections participated in a randomised double-blind parallel multicenter trial in order to compare the efficacy of cefaclor and amoxycillin as treatment for lower respiratory tract infections and their ability to influence colonization resistance. Cefaclor was given to 40 patients and amoxycillin to 44 patients perorally in doses of 250 mg t.i.d. for seven days in a double-blind fashion. Sputum, oropharyngeal and intestinal specimens were taken for microbial analysis to isolate the causative pathogen of the lower respiratory tract infection and to follow the microflora changes before, during and after antibiotic treatment. The clinical outcome showed 92.5% cured or improved patients on cefaclor versus 88.4% on amoxycillin. The difference in clinical outcome between the two treatment groups was not statistically significant. Among the pathogenic bacteria isolated, Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae dominated. There was no difference between the two treatments with regard to microbiological efficacy. Treatment with cefaclor did not cause any significant impact on the oropharyngeal microflora. Administration of amoxycillin caused a significant reduction of the number of Streptococcus salivarius and Veillonella cocci, while an increase in number of enterobacteria was seen in the oropharyngeal microflora. In the intestinal flora, cefaclor significantly reduced the number of streptococci, staphylococci and anaerobic cocci, while the number of enterococci, enterobacteria, bacteroides and Candida albicans significantly increased. The intestinal microflora was partly influenced by amoxycillin treatment. Thus there was a significant increase in the number of enterobacteria, anaerobic gram-positive rods and bacteroides. In conclusion, none of these agents caused any major disturbances in the colonization resistance in patients with lower respiratory tract infections.
Respiratory viruses cause significant morbidity and mortality. The management of these infections can be improved by a rapid diagnosis and administration of available virus-specific therapy. The goal of this study was to compare R-Mix, an engineered tissue monolayer for rapid shell vial (SV) diagnosis of viral respiratory infections, with conventional tissue culture (TC) and conventional respiratory SV (primary rhesus monkey kidney (RhMK) and Hep2 monolayers). The primary outcome measure was sensitivity for detection of influenza A and B, respiratory syncytial virus, parainfluenza 1-3, and adenovirus. The study was performed in two phases: (1) the three methods were compared using 250 nasal washes from children with lower respiratory tract infections; (2) a modified R-Mix SV harvesting schedule (SV were harvested at 24 and 120 h) was compared with TC and conventional RhMK/Hep2 SV using 311 respiratory specimens. A total of 110 viruses were identified in the first and 55 in the second phase. Diagnostic accuracies of R-Mix harvested at 24, 48, and 120 h were 98%, whereas for TC varied between 99 and 100%, and for RhMK/Hep2 SV between 98 and 99%. Sensitivities of R-Mix harvested at 24, 48, and 120 h were 26, 75, and 47%, respectively, whereas for TC varied between 60 and 94%, and for RhMK/Hep2 SV between 62 and 85%. R-Mix harvested at 48 h represent a valuable substitute for RhMK/Hep2 SV because they have comparable sensitivities and diagnostic accuracies, but R-Mix offers several technical advantages. In contrast, R-Mix harvested at 24h did not seem a very useful diagnostic tool. The utility of R-Mix harvested at 120 h, which accelerated the diagnosis of 16% of positive specimens in study phase 2, needs further investigation.
Respiratory tract infections (RTIs) are the most frequent infections in humans, particularly in children. In addition to intervention, increasing interest is focusing on immunomodulatory therapy for recurrent RTIs, which indicate a reduced defense capacity of the respiratory mucosa. LW 50020, an oral immunomodulator that contains the antigens of seven bacteria common in RTIs, has reduced the number, duration, and severity of RTIs in children and adults. This 56-week placebo-controlled, double-blind study in 188 children investigated whether the efficacy of the standard schedule (immunization cycle + one booster cycle) would be enhanced by additional booster cycles. Efficacy and safety over the long term were also assessed. The rate of infection was reduced by 50% with the standard schedule and could not be further decreased by two consecutive booster cycles. With both schedules, this reduction was sustained during a 28-week treatment-free observation period that followed the 28-week treatment period. The number of adverse drug reactions was low, and all were transient, expected, and nonserious. These results confirm that LW 50020 is an effective and safe strategy for RTIs.
Respiratory organs of newborn rats inoculated intranasally with broth culture of Myc. hominis were studied by the histological, histochemical and immunofluorescence methods. Tracheitis and development of purulent and interstitial pneumonia with a hemorrhagic component were revealed 24 hours after the infection. These changes were observed up to the 7th day of the experiment. At the same period a specific fluorescence of the Myc. hominis antigen was found by the antibody fluorescent test. The present study pointed to the pathogenicity of the Myc. hominis for the respiratory tract of the newborn rats.
We measured NCF activity and examined the characteristics of NCF in bronchoalveolar lavage (BAL) fluid, sputum and culture media of alveolar macrophages. Several kinds of NCF were detected in BAL fluid obtained from normal volunteers, and at least a part of these NCF was thought to be derived from alveolar macrophages. NCF activity, especially complement-derived NCF, was increased in BAL fluid and in sputum obtained from patients with chronic respiratory tract infection. In patients with idiopathic interstitial pneumonia, alveolar macrophage-derived NCF as well as complement derived NCF were increased in BAL fluid. These results indicate that different types of NCF may increase in response to the disease state or pathogenesis, and play important roles in neutrophil accumulation in the respiratory tract.
Respiratory tract infections (RTIs), the most common indication for outpatient antimicrobial therapy, impose a heavy medical and societal burden and present a difficult therapeutic challenge in the face of increasing pathogen resistance worldwide. Gatifloxacin is a new broad-spectrum fluoroquinolone with excellent activity against prevalent respiratory bacteria, including penicillin-resistant Streptococcus pneumoniae and atypical pathogens. A multicenter, open-label, noncomparative surveillance study carried out in Mexico evaluated the safety and efficacy of oral gatifloxacin 400 mg once daily in 17,923 adult outpatients with community-acquired pneumonia (CAP) (n = 3322), acute exacerbations of chronic bronchitis (AECB) (n = 5885), and acute bacterial sinusitis (n = 8716). Voluntary, unpaid physician participation contributed to an unbiased study design. Physician-assessed global rate of cure or improvement was 96.3%; efficacy was 95.8% in CAP, 96.1% in AECB, and 96.4% in sinusitis. The incidences of relapse (1.5%) and therapeutic failure (0.7%) were low. The most commonly reported adverse events, nausea (2.76%), headache (2.20%), and dizziness (1.33%), were generally mild and self-limited. Oral gatifloxacin 400 mg once daily is effective and safe for patients with CAP, AECB, and acute sinusitis.
Respiratory tract infections (RTIs) are expensive for MCOs and cause significant morbidity among their members. Although awareness of resistance to antibiotics is increasing, antibiotic selection for community-acquired RTIs remains largely empiric. When making formulary decisions, Pharmacy and Therapeutics Committees may want to consider the spectrum of coverage that an antibiotic provides and its vulnerability to resistance development. Through appropriate formulary management and provider education, MCOs can promote successful clinical and economic outcomes. This article examines the current status of antibiotic therapy for community-acquired RTIs and encourages the incorporation of new parameters into MCO formulary decision processes.
Respiratory tract infections are a major public health issue. Prevention in high risk populations relies mainly on vaccination against Influenza and S. pneumoniae. Vaccination of health-care workers is highly recommended, to decrease absenteism, but above all to protect high risk patients. New conjugate vaccines have shown their effectiveness in the paediatric population. In patients with chronic bronchitis or COPD, immunomodulatory agents (OM-85 BV) and anti-oxidants (NAC) are probably contributive in decreasing exacerbation rates. Inhaled corticosteroids decrease exacerbations in a well defined group of severe COPD. In patients with diffuse bronchiectasis, the immunomodulatory effect of macrolides, and the use of inhaled corticosteroids should be confirmed by larger clinical investigations.
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Respiratory tract infections (RTIs) represent a major cause of illness worldwide. Therefore, it is of great concern that common RTI pathogens have become increasingly resistant to many of the antimicrobial agents used for therapy. For example, Haemophilus influenzae and Moraxella catarrhalis have become resistant to beta-lactam drugs by producing efficient beta-lactamases (> 35 and 90% of strains, respectively). More recently, pneumococci have become more resistant through the mechanism of altered penicillin-binding proteins (PBPs). The rate of penicillin nonsusceptible isolates has risen to > 25% in the United States (1994-1995). It is important to monitor the resistance characteristics of such pathogens and, if possible, to use regionally acquired data to guide empiric selection of therapeutic agents for RTIs. Currently, some antimicrobials remain effective against the majority of these three bacterial species, as exemplified by amoxicillin/clavulanic acid. Furthermore, amoxicillin alone seems to possess greater inhibition than other orally administered beta-lactams at clinically achievable concentrations against pneumococci with altered PBPs. It is critical that steps are taken to limit resistance problems, particularly through; 1) education of prescribers and the public; 2) initiation of the development of novel drugs with alternative modes of action or stability to existing resistance mechanisms; and 3) by continuing to generate quality susceptibility testing data to guide empiric chemotherapy against bacterial pathogens causing RTI.
The respiratory tract epithelium in many vertebrate species has a neuroepithelial endocrine (NEE) system. This system is composed of solitary NEE cells or organoid cell groups called neuroepithelial bodies (NEBs). In response to chemical and physical stimuli, NEE cells may release bioactive substances. Serotonin, one of the biogenic amines, well-known as a constricter of smooth muscle, can be found in NEE cells, serotonin-immunoreactive cells can be used as a marker for these cells. Comparative histological studies of lower vertebrates can improve our understanding of mammalian respiratory systems. The Tokyo salamander (Hynobius neblosus tokyoensis Tago), classified as Ulodera, is particularly useful for comparative studies of respiration. In this study, the serial sections of respiratory tract of the Tokyo salamander were stained by a commonly used staining method and by an immunocytochemical method for serotonin, and the distribution of serotonin-immunoreactive cells in the respiratory tract was examined. The respiratory tract was found to be connected to the alimentary tract via an aditus laryngis, which opens on the medio-ventral side of the esophagus. The laryngotrachea was slit-like or elliptically shaped with a total length of about 3.5 mm, joining the aditus laryngis. The laryngotrachea was supported by a pair of lateral cartilages, and a fibromuscular layer was seen between the cartilages and the epithelium. In the cranial region, a laryngeal sphincter was seen around the laryngotrachea. The laryngotrachea branches into a pair of tube-like lungs, that are about 17-20 mm in length. Two apposed primary trabeclae run along the entire length of the lung wall, perpendicular to the axis, and containing the pulmonary arteries and veins. The lungs were divided into two portions: 1) an airway portion (trabeclae, septa) in which smooth muscles surrounding the large vessels were well developed, and 2) a respiratory portion which was give that name because it has well developed capillary networks that were assumed to be involved in gas exchange. The lumen of the laryngotrachea and the pulmonary airway portion contained pseudostratified cilio-mucous epithelium. In the caudaldorsal region of the laryngotrachea adjacent to the lungs, the non-ciliated respiratory epithelium was seen lining the capillaries. In cilio-mucous epithelium of the laryngotrachea, all serotonin-immunoreactive cells were solitary. They apposed to be columnar, cuboidal, triangular, oval, and flask- or spindle-shaped. Solitary serotonin-immunoreactive cells were classified "open type cell" with appical process reaching to the luminal surface and "closed type cell" insulated from the lumen by an epithelial lining. In the pulmonary airway portion, serotonin-immunoreactive cells were solitary cells and in clusters. Serotonin-immunoreactive cells were widely distributed throughout the respiratory tract, but they tended to be found mainly in the cranial portion. The density was highest in the area with the laryngeal sphincter, and decreased caudally in the laryngotrachea and lung. No serotonin-immunoreactive cells were found in the respiratory portion of the dorsal-caudal area of the laryngotrachea or in the part of the lung with non-ciliated cells. So the structure and distribution of serotonin-immunoreactive cells in the respiratory tract of the Tokyo salamander are similar to those of NEE cells and NEBs in mammalian respiratory systems. The density of serotonin-immunoreactive cells appears to be related to the distribution of smooth muscles in the fibromuscular layer and airway portion. The cells may be involved in regulation of the respiratory system. Serotonin is released in response to stimulation, which could result in constriction of the fibromuscular layer and shrinkage of the laryngotracheal cavity, and may regulate pulmonary volume by constricting smooth muscles