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Optimizing antibiotic prescribing for acute respiratory tract infections in an urban urgent care clinic.

OBJECTIVE: To decrease unnecessary antibiotic use for acute respiratory tract infections in adults in a point-of-service health care setting. DESIGN: Prospective, nonrandomized controlled trial. SETTING: An urban urgent care clinic associated with the major indigent care hospital in Denver, Colorado between October 2000 and April 2001. PATIENTS/PARTICIPANTS: Adults diagnosed with acute respiratory tract infections (bronchitis, sinusitis, pharyngitis, and nonspecific upper respiratory infection). A total of 554 adults were included in the baseline period (October to December 2000) and 964 adults were included in the study period (January to April 2001). INTERVENTIONS: A provider educational session on recommendations for appropriate antibiotic use recently published by the Centers for Disease Control and Prevention, and placement of examination room posters were performed during the last week of December 2000. Study period patients who completed a brief, interactive computerized education (ICE) module were classified as being exposed to the full intervention, whereas study period patients who did not complete the ICE module were classified as being exposed to the limited intervention. MEASUREMENTS AND MAIN RESULTS: The proportion of patients diagnosed with acute bronchitis who received antibiotics decreased from 58% during the baseline period to 30% and 24% among patients exposed to the limited and full intervention, respectively (P <.001 for intervention groups vs baseline). Antibiotic prescriptions for nonspecific upper respiratory tract infections decreased from 14% to 3% and 1% in the limited- and full-intervention groups, respectively (P <.001 for intervention groups vs baseline). CONCLUSION: Antibiotic use for adults diagnosed with acute respiratory tract infections can be reduced in a point-of-service health care setting using a combination of patient and provider educational interventions.

Acute Disease↗

Internalization of adenovirus by alveolar macrophages initiates early proinflammatory signaling during acute respiratory tract infection.

Adenovirus is a common respiratory pathogen which causes a broad range of distinct clinical syndromes and has recently received attention for its potential for in vivo gene delivery. Although adenovirus respiratory tract infection (ARTI) results in dose-dependent, local inflammation, the pathogenesis of this remains unclear. We hypothesized that alveolar macrophages (AMphi) rapidly internalize adenovirus following in vivo pulmonary administration and then initiate inflammatory signaling within the lung. To evaluate the role of AMphi in the induction of lung inflammation during ARTI in vivo, we directly assessed adenovirus uptake by murine AMphi and correlated uptake with the initiation of proinflammatory gene expression. Stimulation of cytokine (tumor necrosis factor alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and MIP-1alpha) expression in the lung was evaluated at the level of mRNA (by reverse transcription-PCR [RT-PCR]) and protein (by enzyme-linked immunosorbent assay) and by identification of cells expressing TNF-alpha and IL-6 mRNA in lung tissues (by in situ hybridization) and isolated lung lavage cells (by RT-PCR). Adenovirus, labeled with the fluorescent dye (Cy3), was rapidly and widely distributed on epithelial surfaces of airways and alveoli and was very rapidly ( approximately 1 min) localized within AMphi. At 30 min after infection AMphi but not airway epithelial or vascular endothelial cells expressed mRNA for TNF-alpha and IL-6, thus identifying AMphi as the cell source of initial cytokine signaling. IL-6, TNF-alpha, MIP-2, and MIP-1alpha levels progressively increased in bronchoalveolar lavage fluid after pulmonary adenovirus infection, and all were significantly elevated at 6 h (P < 0.05). To begin to define the molecular mechanism(s) by which adenovirus initiates the inflammatory signaling in macrophages, TNF-alpha expression from adenovirus-infected RAW264.7 macrophages was evaluated in vitro. TNF-alpha expression was readily detected in adenovirus-infected RAW cell supernatant with kinetics similar to AMphi during in vivo infection. Blockage of virus uptake at specific cellular sites, including internalization (by wortmannin), endosome acidification and/or lysis (by chloroquine) or by Ca(2+) chelation (by BAPTA) completely blocked TNF-alpha expression. In conclusion, results showed that during ARTI, (i) AMphi rapidly internalized adenovirus, (ii) expression of inflammatory mediators was initiated within AMphi and not airway epithelial or other cells, and (iii) the initiation of inflammatory signaling was linked to virion uptake by macrophages occurring at a point after vesicle acidification. These results have implications for our understanding of the role of the AMphi in the initiation of inflammation following adenovirus infection and adenovirus-mediated gene transfer to the lung.

Acute Disease↗

Increased psychosocial stress and decreased mucosal immunity in children with recurrent upper respiratory tract infections.

The association between psychosocial stress and susceptibility to upper respiratory tract infection was investigated in 45 children with a history of recurrent colds and flu, and in 45 healthy children of similar age and distribution. In addition, mucosal immune protection against upper respiratory tract infections was assessed by measuring the concentration of secretory immunoglobulin A (sIgA) and its ratio to albumin in saliva. Several dimensions of psychosocial stress, including exposure to stressful experiences, stress-prone personality traits, and signs of emotional disturbance were elevated in children with a history of recurrent colds and flu. Furthermore, lower sIgA/albumin ratios in these children indicated a deficiency in local mucosal immunity. Thus, the findings are consistent with the view that psychosocial stress depletes local immune protection against viral invasion or bacterial colonization of the upper respiratory tract; this depletion may increase susceptibility to colds and flu. Alternatively, psychological disturbances could develop in response to frequent illness.

Affective Symptoms↗

Treatment of lower respiratory tract infections with cefoperazone.

Fifteen patients with documented bacterial lower respiratory tract infections were treated with cefoperazone (2 gm every 12 hours, administered parenterally) as the single antibiotic therapy. Pulmonary infections included pneumonia (10), anaerobic lung abscess (2), bronchitis (2), and exacerbation of bronchiectasis (1); most of the patients had concomitant illnesses that compromised their host-immune status. Bacteria recovered from respiratory tract cultures included aerobic gram-negative bacilli (17), anaerobes (6), and aerobic gram-positive cocci (3). After therapy, lasting 5 to 28 days, nine patients had complete resolution of their infection, and the remaining six patients had significant clinical improvement. Diarrhea was the adverse reaction most commonly noted; others included an unusual reaction resembling serum sickness, and, in one patient treated for 24 days, hypotension and a subsequent decrease in renal function. Drug-related abnormalities in blood and serum values were few and mild. Cefoperazone was found to be effective in the treatment of lower respiratory tract infections.

Adult↗

Effects of the beige mutation on respiratory tract infection with Pseudomonas aeruginosa in mice.

The role of neutrophil proteinases in the pathogenesis of respiratory tract infections with Pseudomonas aeruginosa was evaluated by studying the course of murine respiratory tract infection with a clinical isolate of P. aeruginosa mucoid strain developed by the agarose beads method in C57BL/6J(bg/bg) mice (beige mice). Neutrophils of beige mice are known to have defects in elastase and cathepsin G, but to have normal ability to produce reactive oxygen species. Contrary to the reported high susceptibility of beige mice to bacterial infections, we found that intratracheal inoculation of approximately 10(5) colony-forming units (CFU) of P. aeruginosa enmeshed in agarose beads resulted in lower mortality (0/16 versus 16/16, p < .01), fewer CFU counts in the lungs on day 5 (p < .05), and fewer elastolytic lung tissue injuries in beige mice compared with C57BL/6(+/+) mice. In vitro bactericidal study, however, revealed that beige neutrophils killed fewer bacteria than those of C57BL/6(+/+) mice (p < .05). Neutrophil elastase activities in the supernatants of pulmonary lavaged fluids measured using methoxysuccinyl-alanyl-alanyl-prolyl-valine-4-methylcoumar-7-amide were lower (p < .05) in beige mice than those in the normal littermates, whereas neutrophil recruitment into the airways and production of superoxide anion measured as the superoxide dismutase inhibitable rate of cytochrome c reduction were not impaired. These results suggest that neutrophil proteinases play a key role in tissue injuries in the respiratory tract infection with P. aeruginosa.

Animals↗

[Patient compliance in the treatment of respiratory tract infections].

The survey on outpatients compliance in the treatment of respiratory tract infections was performed in Croatia during April 1996. A total of 213 physicians, 201 adult patients, and 178 parents of sick children were polled by the appropriate questionnaires. The results have shown that in the treatment of respiratory tract infections physicians commonly prescribe thrice-daily antibiotic regimens for 8-10 days. Concerning patients' knowledge, 85% of patients deem that regularity, and 64% that duration of antibiotic administration influences treatment outcome. Over 80% of patients are compliant with once-or twice-daily regimens, but only 50% take regularly and timely drugs that are dosed every 6 or 8 hours. Common reasons for irregular taking of antibiotics are forgetfulness and dosing during sleeping. In terms of appropriate duration of antibiotic therapy, about 20% of patients usually take antibiotic for 8-10 days, 60% for 5-7 days, and 20% for < or = 4 days. It may be concluded that the patients are poorly compliant with oral antibiotics treatment.

Adult↗

Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection.

The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection (ARTI). Study material comprised routine nasopharyngeal aspirates obtained during 2 winter seasons (November-May) 1999-2000 and 2001-2002 from children hospitalized at the Departments of Paediatrics, Hvidovre Hospital and Amager Hospital, Denmark. hMPV was detected in 11 (2.9%) and RSV in 190 (49.6%) ARTI episodes by real-time reverse transcription-polymerase chain reaction using primers targeting the hMPV N gene and the RSV L gene. Two children were co-infected with hMPV and RSV. They were excluded from statistical analysis. Hospitalization for ARTI caused by hMPV was restricted to very young children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p < 0.001). Overall symptoms and clinical findings were similar among hMPV and RSV positive episodes, but more RSV-infected children required respiratory support. hMPV is present in young Danish children hospitalized with ARTI although less frequent than RSV and with a tendency to a milder clinical course.

Acute Disease↗

Dysfunction of peripheral blood granulocyte oxidative metabolism in children with recurrent upper respiratory tract infections.

Granulocytes play a key role in the defence against bacterial infections. Their dysfunction may both predispose to and result from infections. The oxidative metabolism of peripheral blood granulocytes was studied in 50 children aged from 1 to 10 years, with recurrent upper respiratory tract infections and/or tonsillar hypertrophy. Four groups of patients were recruited: 15 healthy controls, seven patients with idiopathic tonsillar hypertrophy, 12 patients with upper respiratory tract infections and 16 patients with upper respiratory tract infections with concurrent tonsillar hypertrophy. The ability of granulocytes to produce reactive oxygen species was assessed by nFMLP-induced chemiluminescence. Both increased and depressed granulocyte activity was observed in all studied groups, with the exception of controls. Altered granulocyte function was observed in 30% of patients in the idiopathic tonsillar hypertrophy group. In children with recurrent infections abnormal chemiluminescence results were found in from 75% to nearly 90% of patients. This preliminary study demonstrates the possible relationship between recurrent upper respiratory tract infections, tonsillar hypertrophy and impaired peripheral blood granulocyte chemiluminescence.

Child↗

Effect of upper respiratory tract infection in patients with neuromuscular disease.

Respiratory muscle strength during acute upper respiratory tract infection (URI) was assessed in patients with various forms of neuromuscular disease. Vital capacity (VC), oxygen saturation, end-tidal PCO2, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were determined in 25 stable patients with various forms of neuromuscular disease. Thirteen episodes of URI developed in 10 patients. Respiratory parameters were reassessed within 24-36 h following the onset of symptoms in each patient. In patients with URI, mean baseline VC, MIP, and MEP were 1.16 L +/- 0.14, 49.2 cm H2O +/- 6.8, and 35.5 cm H2O +/- 3.8 and fell to 1.01 L +/- 0.15, 37.1 cm H2O +/- 6.2, and 25.5 cm H2O +/- 3.0 during URI (p < 0.05 for each), respectively. Mean baseline PCO2 and oxygen saturation were 39.1 mm Hg +/- 1.1 and 95.1% +/- 1.0, and during URI, 43.9 mm Hg +/- 2.1 (p < 0.05) and 95.0% +/- 1.0 (NS), respectively. Five episodes of significant hypercapnia were observed in 4 patients. All parameters returned to near baseline values following recovery. We conclude that patients with various forms of neuromuscular disease develop reductions in respiratory muscle strength in association with URI. Unlike normal subjects, however, these decrements in respiratory muscle function may result in symptoms of shortness of breath, reductions in vital capacity, and acute hypercapnia in this patient population.

Acute Disease↗

Antimicrobial susceptibility of Bordetella bronchiseptica isolates from porcine respiratory tract infections.

MICs for 349 Bordetella bronchiseptica isolates from respiratory tract infections of swine were determined by broth microdilution. The lowest MIC at which 90% of isolates tested are inhibited (MIC90) was that of tetracycline and enrofloxacin (0.5 microg/ml), whereas the highest MIC90s were those of tilmicosin and cephalothin (32 microg/ml) as well as streptomycin (256 microg/ml).

Animals↗

In vitro activity of trimethoprim alone compared with trimethoprim-sulfamethoxazole and other antimicrobials against bacterial species associated with upper respiratory tract infections.

Trimethoprim-sulfamethoxazole has been used to treat various respiratory tract infections. Nevertheless, for many patients, intolerance of the sulfonamide component precludes use of this combination. This study examined the activity of trimethoprim alone in comparison to that of trimethoprim-sulfamethoxazole and other antimicrobials against bacterial species implicated in respiratory tract infections. For Haemophilus influenzae, minimal inhibitory concentrations of trimethoprim were equal to or one dilution greater than those of trimethoprim-sulfamethoxazole, with 56 of 58 strains inhibited by the former at < or = 0.25 microgram/ml. All oxacillin-susceptible Staphylococcus aureus and 96.7% of Streptococcus pyogenes were inhibited by trimethoprim < or = 2 micrograms/ml. In contrast, only 50% of Streptococcus pneumoniae were inhibited by this concentration of trimethoprim, whereas 93.3% were susceptible to the combination at < or = 2/38 micrograms/ml. All oxacillin-resistant S. aureus and all Moraxella catarrhalis were resistant to trimethoprim, although many of the former and all of the latter were susceptible to trimethoprim-sulfamethoxazole.

Anti-Bacterial Agents↗

Diagnosis methods for pneumococcal etiology determination in lower respiratory tract infections.

A comparative study of etiological diagnosis in lower respiratory tract infections (LRTI), by conventional bacteriological methods and by pneumococcal antigen direct detection in sputum was performed. This work followed the establishing of rapid methods place, respectively of coagglutination (CoA), counterimmunoelectrophoresis (CIE), within the methodology of bacteriological diagnosis in lower respiratory tract infections presenting pneumococcal etiology. The results of investigations performed on 84 sputa from LRTI patients proved the utility of CoA method in determining a rapid etiological diagnosis, important for applying an emergence targetted antibiotherapy. CoA method, with the reagents in use, covering only 10 out of 83 serological types of S. pneumoniae in not capable of replacing conventional methods of bacteriological diagnosis; they complete each other, increasing the efficiency of etiological diagnosis in LRTI. CIE method is less sensitive and more difficult to perform, being less useful in rapid etiological diagnosis of LRTI.

Adult↗

[Successful total laryngectomy in three cases with severe motor and intellectual disabilities syndrome for the management of repetitive lower respiratory tract infections].

Total laryngectomy was successfully performed for the management of repetitive lower respiratory tract infections in three cases with severe motor and intellectual disabilities syndrome. The patients were thirteen, ten and nine years of age and had cerebral palsy, mental retardation and epilepsy which resulted from neonatal asphyxia and seizures. To treat repetitive lower respiratory tract infections, the patients underwent the operation at the age of nine years and a month, seven years and six months, and six years and eleven months, respectively. Postoperatively, the respiratory tract infections were remarkably reduced for two to four years. Total laryngectomy is one of the best methods for the prevention of aspiration pneumonia, because it separates trachea and esophagus completely. The operation is indicated for children with influx of saliva into trachea and gastroesophageal reflux. The family should recognize that this operation causes permanent loss of voice and speech. The bronchoscopy, upper gastrointestinal tract barium studies and esophageal pH monitoring should be performed before the operation. Our cases fulfilled all of these indications. Laryngectomy should be considered as an effective method of respiratory management for cases of severe motor and intellectual disabilities syndrome, although its application should be carefully examined from the point of improvement of quality of life for patients.

Adolescent↗

Predictors of an antibiotic prescription by GPs for respiratory tract infections: a pilot.

BACKGROUND: Antibiotics are over-prescribed for respiratory tract infections in Australia. OBJECTIVES: The aim of this study was to describe the clinical predictors of GPs' prescribing of antibiotics. METHODS: We used Clinical Judgment Analysis to study the responses of GPs to hypothetical paper-based vignettes of a 20-year-old with a respiratory tract infection. The nature of four symptoms and signs (colour of nasal mucous discharge; soreness of the throat; presence of fever; and whether any cough was productive of sputum) was varied and their effect on prescribing measured using logistic regression. RESULTS: Twenty GPs participated. The nature of each symptom and sign significantly predicted prescribing of an antibiotic. Cough productive of yellow sputum; presence of sore throat; fever; and coloured nasal mucus increased the probability of an antibiotic being prescribed. CONCLUSIONS: GPs are influenced by clinical signs and symptoms to use antibiotics for respiratory infections for which there is poor evidence of efficacy from the literature.

Adult↗

Empiric use of cefepime in the treatment of lower respiratory tract infections in children.

BACKGROUND: These studies were designed to assess the efficacy and safety of cefepime, a fourth generation cephalosporin, for the treatment of serious infections, including lower respiratory tract infections (LRTI) in children. METHODS: Four clinical trials of cefepime for the treatment of serious bacterial infections enrolled 259 children with LRTI. In 3 trials cefepime was compared with ceftazidime (n = 166), cefotaxime (n = 16) or cefuroxime (n = 12). One trial was noncomparative (n = 65). RESULTS: Treatment with cefepime 50 mg/kg/ dose administered every 8 to 12 h produced a satisfactory clinical response (clinical signs of infection resolved or improved with no evidence of recurrent infection at posttreatment follow-up) in 88 to 100% of patients, comparable with comparator therapy. In children from whom a causative pathogen was identified, bacteriologic eradication was comparable between cefepime and comparator therapy. Cefepime was as safe and well-tolerated as comparator therapy. Few treatment-related clinical or laboratory adverse events were noted and were equivalent to comparator in all studies. CONCLUSION: Cefepime is as effective, safe and well-tolerated for the empiric treatment of children with LRTI as comparator agents but offers the advantage of an enhanced spectrum of activity for Gram-positive and Gram-negative pathogens compared with second or third generation cephalosporins.

Adolescent↗

Sociocultural differences in patients' expectations at consultations for upper respiratory tract infection.

Among 214 patients consulting their general practitioner with upper respiratory tract infection, differences in expectation were apparent between Whites, Afro-Caribbeans and Asians. Significantly more Asians (84%) wanted prescriptions for antibiotics and/or other medication than did Afro-Caribbeans (72%) or Whites (47%) (P<O.001). There were no significant differences in terms of what was received but Asians tended to be dissatisfied with the outcome of the consultation. Self-medication before consultation was attempted by 82% of patients; 48% took two or more preparations. Afro-Caribbeans had taken significantly more preparations per person than other groups (P<0.05). Sociocultural factors may influence patients' expectations at consultations for upper respiratory tract infection.

Consumer Behavior↗

Young Malaysian children with lower respiratory tract infections show low incidence of chlamydial infection.

OBJECTIVE: The incidence of Chlamydia pneumoniae and Chlamydia trachomatis infection was studied among infants and young children admitted to hospital for the management of lower respiratory tract infections, over a 12 month period. METHODOLOGY: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods. RESULTS: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively. CONCLUSION: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia.

Child, Preschool↗

Prospective hospital study of community acquired lower respiratory tract infection in the elderly.

A prospective study of community acquired lower respiratory tract infection in the elderly was carried out over a 15-month period. During this time 127 consecutive admissions to two acute geriatric medical wards were studied. An aetiology was established in 77 (61%) of cases. Streptococcus pneumoniae was identified in 37% of patients. Haemophilus influenzae in 18% and Branhamella catarrhalis in 10%. Infection with Mycoplasma pneumoniae was found in only one episode and no cases of Legionella pneumophilia were diagnosed. A significant number of patients had multiple bacterial pathogens isolated: 18% of all bacterial pathogens isolated were ampicillin resistant. Fourteen patients died (11%). Lower respiratory tract infection is a frequent cause of hospital admission for those aged over 65 and is often regarded as a preterminal event. Adequately treated however, mortality is no higher than in the general population. Knowledge of the likely pathogens allows early and appropriate antibiotic therapy for these patients whether at home or on admission to hospital.

Aged↗