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PubMed1995

The role of new quinolones in the treatment of respiratory tract infections.

Infections of the respiratory tract are the leading cause of antibacterial prescribing in both hospital and community practice. The microbial aetiology is diverse in both of these settings and differs in the distribution and virulence of the pathogens. Furthermore, in recent years the antibacterial susceptibility of many of the common pathogens has changed significantly. In particular, penicillin resistance has emerged among pneumococci, while beta-lactamase production among Haemophilus influenzae and many Gram-negative bacilli has led to alterations in first-line therapy options. The fluoroquinolone antibacterials have been used in selected respiratory tract infections, but concerns have remained with regard to their efficacy in infections caused by marginally susceptible organisms, and in particular pneumococcal infections. The availability of a number of quinolones with enhanced Gram-positive activity, which includes Streptococcus pneumoniae, is of considerable interest. In vitro data and preliminary clinical experience with sparfloxacin suggest that managing pneumococcal lung disease with this and future agents is a distinct possibility. One caveat must be considered, and that is the potential for more resistant strains of pneumococci emerging, against which even these new quinolones could prove less effective.

4-Quinolones↗
PubMed2000

Air leaks from the respiratory tract in mechanically ventilated children with severe respiratory disease.

Our objectives were to evaluate the frequency of air leaks (AL) from the respiratory tract (pneumothorax, pneumomediastinum, pneumoperitoneum, subcutaneous emphysema) in critically ill children on mechanical ventilation (MV) for severe respiratory diseases, and to examine whether AL could be correlated with specific clinical events or ventilator settings. The study constitutes a retrospective cohort of 80 consecutive critically ill children receiving MV for severe respiratory diseases between 1986 and 1993. Patients (mean age 2.9 +/- 0.6 years, 49 males and 31 females), were admitted to the Pediatric Intensive Care Unit (PICU) with acute respiratory syndrome (ARDS) (27%), asthma (15%), bronchiolitis (10%), pneumonia (21%), pulmonary congenital diseases (9%), or foreign body aspiration (18%). Patients were divided into two groups; those with AL (n=22) and those without air-leaks (non-AL) (n = 58). Air leaks developed in 22 of 80 patients or in 27.5%. Survival was significantly lower in the AL group, compared to the non-AL group (41% vs. 76%, P < 0.01). The odds ratio that a patient with multiple organ system failure (MOSF) or infection would develop AL was 2.96 and 2.19, respectively. Candida and Pseudomonas species were recovered with significantly higher frequency in the AL group compared with the non-AL group (P < 0.025). There was a strong positive correlation between the incidence of AL and high ventilatory pressures (PIP 36 vs. 29.7 cm H(2)O, P < 0.001), or large tidal volumes (V(T) 12 vs. 9 mL/kg, P < 0.05), suggesting that large volumes might elicit injury to the pulmonary epithelium. Multiple logistic regression analysis showed that only V(T) was independently associated with the development of AL in children with primary severe respiratory disease (r(2) = -0.38, P = 0.01). In conclusion, MV will produce AL, particularly when high peak airway pressures (barotrauma) or large tidal volumes (volotrauma) are delivered by the ventilator. Sepsis, MOSF, and lung superinfection with Pseudomonas or Candida species may be also important factors in the development of AL in critically ill children.

Acute Disease↗
PubMed2000

Effects of methacrolein on the respiratory tract in mice.

The acute respiratory effects of airborne exposure to methacrolein were studied in a recent refinement of the standard test method with mice (ASTM, 1984. American Society for Testing and Materials, Philadelphia). Irritation of the upper respiratory tract caused a concentration-dependent decrease in the respiratory rate of 2-26 ppm methacrolein. In this range, only a minor airflow limitation occurred in the lower respiratory tract, suggesting that the main effect of methacrolein is sensory irritation. During exposure, the sensory irritation response maintained the same level, i.e. no desensitisation occurred. The concentration 10.4 ppm methacrolein reduced the respiratory rate by 50% (RD50). The extrapolated threshold for the respiratory depressing effect, RD0, was 1.3 ppm. The sensory irritation effect of methacrolein was compared with results from closely related compounds in order to elucidate the mechanism of the interaction between methacrolein and the sensory irritant receptor.

Acrolein↗
PubMed2003

Chlamydia pneumoniae carriage and infection in hospitalized children with respiratory tract diseases.

BACKGROUND: The importance of Chlamydia pneumoniae respiratory tract infection in childhood is under discussion. PATIENTS AND METHODS: 798 hospitalized children with respiratory tract diseases were prospectively studied during a 2-year period by polymerase chain reaction and enzyme immunoassay (PCR-EIA) detection from throat swabs. Paired serum samples were used to screen for Chlamydia antibodies. RESULTS: C. pneumoniae was detected by PCR-EIA in 74 children. Prevalence was 11% in lower and 4% in upper respiratory tract disease (p = 0.049) without age dependency. From November to February prevalence was elevated (42/277 vs. 32/521; p < 0.001). Using serology, prevalence of acute Chlamydia infection increased with age (p < 0.001) and the number of coinfections (p < 0.001), without seasonal variation. CONCLUSION: Characteristics of C. pneumoniae carriage in the respiratory tract in childhood differ from those in systemic infection.

Adolescent↗
PubMed1981

Mechanisms of infection in the respiratory tract.

Related to its potential vulnerability the respiratory tract has a very complex and effective defence apparatus. The interaction between these defence mechanisms and certain characteristics of aetiological agents results in a pattern in which initial infections by these agents tend to occur at specific sites in the tract. Infections in which the primary portal of entry is in the upper respiratory tract include Bordetella bronchiseptica and Haemophilus spp in pigs; Pasteurella spp in cattle, sheep, pigs; Mycoplasma spp in cattle, sheep, pigs and poultry; equine herpesvirus 1 in horses; infectious bovine rhinotracheitis in cattle; parainfluenza 3 in cattle and sheep; infectious laryngo-tracheitis and infectious bronchitis in poultry; feline viral rhinotracheitis and calicivirus in cats; Aujeszky's disease virus and swine influenza in pigs; and equine influenza in horses. Infections in which the primary portal of entry is in the lower respiratory tract include Aspergillus fumigatus in poultry and mammals, respiratory syncytial virus in cattle, distemper virus in dogs and adenovirus in cattle and dogs. A fuller understanding of the interactions between an agent and the host at the point of entry would make it much easier to develop effective vaccines and therapeutic agents.

Animals↗
PubMed1990

Quantification of nasopharyngeal bacteria for diagnosis of respiratory tract infection in children.

Agreement between clinical signs of bacterial respiratory tract infections and quantities of respiratory tract pathogens in nasopharynx was studied in 77 children, aged 6-13 years. Specimens were obtained from 27 clinically bacterial and 51 clinically non-bacterial respiratory tract infections, and in 124 instances from healthy children. Viable counts of Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, and beta-haemolytic streptococci were made from swab specimens suspended in saline before being plated on agar media. The frequency of these species in children with clinically bacterial, non-bacterial and no signs of respiratory tract infections were 85%, 47% and 26%, respectively. Bacterial counts greater than 10(4) colony-forming units (CFU)/ml of the pathogens occurred in 59% of clinically bacterial infections, as compared with 18% in clinically non-bacterial infections (p less than 0.001), the corresponding figures for counts greater than 10(3) CFU/ml being 85% and 41% (p less than 0.01), respectively. At neither level of bacterial count (i.e. greater than 10(4) or greater than 10(3], was there a significant difference between the healthy and those with a clinically non-bacterial infection. The quantification of bacteria in nasopharyngeal samples may thus be of clinical diagnostic value.

Bacteria↗
PubMed1998

Cefprozil and respiratory tract infections in children.

Respiratory tract infections are the leading cause of children's visits to physicians. Antibiotic resistance is increasing among the three most common bacterial respiratory pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, which cause acute otitis media and sinusitis. Therefore clinicians may need to reexamine their treatment strategies because these infections may cause complications. Antibiotic selection in such infections should take into account local bacterial resistance patterns, anticipated clinical efficacy against S. pneumoniae, H. influenzae and M. catarrhalis, including penicillin-resistant and beta-lactamase-producing strains, as well as the safety profile and compliance-enhancing features of the drug.

Cephalosporins↗
PubMed2002

Clinical efficacy of cefpodoxime in respiratory tract infection.

Acute otitis media (AOM), sinusitis and tonsillopharyngitis are respiratory tract infections frequently encountered by primary-care physicians. Increasing bacterial resistance, particularly in Streptococcus pneumoniae, which is one of the most important respiratory tract bacteria implicated in community-acquired respiratory tract infections, has led to concern about the current options for empirical antibiotic treatment and has prompted a search for effective alternative treatments. Data from in vitro studies show that cefpodoxime has good activity against the main respiratory tract pathogens, S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. Clinical studies confirm the efficacy of cefpodoxime in AOM, sinusitis and tonsillopharyngitis. As with all broad-spectrum antibiotics, there is the risk of promotion of bacterial resistance associated with overuse. However, if used with care, cefpodoxime can be considered as an alternative for empirical treatment of bacterial respiratory tract infections encountered in general practice, particularly where penicillins and macrolides have reduced efficacy against the main bacterial pathogens.

Adult↗
PubMed1977

Effect of respiratory infection on the elution of benzo[a]pyrene from carbon particles in the respiratory tract of mice.

The effect of respiratory infection by PR8 influenza virus on the elution of bnezo[a]pyrene (BaP) from carbon particles in the respiratory tract of mice was studied. In mice, this virus produces, among other pheneomena, a proteinaceous effusion and mixed cellular exudate in the alveolar parenchyma during the acute phase of infection. If BaP-coated carbon particles are introduced into the respiratory tract during the acute stage of infection, the rate of BaP elution from the carbon particles is increased. When BaP-coated carbon particles were instilled in the respiratory tract either 1 wk before or 2 wk after the acute stage of infection, the BaP elution rate from carbon particles were similar to that in uninfected animals.

Animals↗
PubMed2002

The effect of respiratory tract infections on reported asthma symptoms.

BACKGROUND: Wheezing and chest tightness is associated with respiratory tract infections. Thus the occurrence of respiratory tract infections may influence the prevalence of asthma. AIMS: To assess the strength of relation between two main symptoms of asthma and the prevalence of respiratory tract infections in children with and without asthma. METHODS: The study population was 3,796 children, four years of age, whose parents had answered a questionnaire on respiratory symptoms and asthma. The prevalence of wheezing and chest tightness in the last 12 months and four weeks was estimated according to the occurrence of respiratory tract infections during the corresponding time periods; 95% confidence intervals of the prevalence and the statistical significance of the differences in the prevalence by using chi-square test were calculated. RESULTS: The prevalence of wheezing and chest tightness was higher in children who had experienced respiratory tract infections than in those who had not. The prevalence of wheezing was 17.5% among children who had experienced bronchitis and 3.0% among children whom had not (p<0.001). The prevalence of chest tightness in the last 12 months was 3.7% (95% CI 3.1-4.1) among children without asthma and 59.3% (95% CI 53.4-65.2) among children with asthma (p<0.001). The prevalence of wheezing and chest tightness increased with increasing number of different types of respiratory tract infections among children without asthma (p<0.001) and tended to be so among children with asthma. CONCLUSIONS: These findings have implications for the interpretation of results from epidemiological studies using respiratory symptoms as a health-related outcome of asthma.

Asthma↗
PubMed2003

RSV-induced bronchiolitis but not upper respiratory tract infection is accompanied by an increased nasal IL-18 response.

The aim of this study was to investigate potential differences in the local nasal immune response between bronchiolitis and upper respiratory tract infection induced by respiratory syncytial virus (RSV). Nasal brush samples were obtained from 14 infants with RSV bronchiolitis and from 8 infants with RSV upper respiratory tract infection. The samples were taken during infection (acute phase) and 2-4 weeks later (convalescent phase). Cytospin preparations were stained immunohistochemically for T cells, macrophages, and eosinophils. Staining also took place for intercellular adhesion molecule-1 (ICAM-1), T-helper 1 (Th1)-like (interleukin-12 [IL-12], interferon-gamma [IFN-gamma]), Th2-like (IL-4, IL-10), and proinflammatory cytokines (IL-6, IL-8, IL-18). During both RSV-induced bronchiolitis and upper respiratory tract infection, cellular inflammation was observed. This was characterised by an increase in the numbers of nasal macrophages, which tended to be higher in bronchiolitis than in upper respiratory tract infection. Numbers of T lymphocytes and ICAM-1 positive cells increased during both bronchiolitis and upper respiratory tract infection. There were no differences between numbers in the groups. Interestingly, a distinct nasal proinflammatory cytokine response was observed in RSV-induced bronchiolitis. This is characterised by an increase in the number of IL-18 positive cells. This increase is specific for bronchiolitis, as a similar increase could not be detected in RSV-induced upper respiratory tract infection. Numbers of IL-6 and IL-12 positive cells were higher in both bronchiolitis and upper respiratory tract infection, and there were no differences between the groups. By contrast, the number of IL-8, IFN-gamma, IL-4, and IL-10-positive cells remained constant. In conclusion, clear differences were found in nasal immune responses of children with RSV-induced upper respiratory tract infection or bronchiolitis. The induction of a strong IL-18 response was typical for bronchiolitis, as this could not be observed in RSV-induced upper respiratory tract infection, and could explain the eosinophilia that is observed frequently during bronchiolitis.

Bronchiolitis↗
PubMed1999

Respiratory tract infections due to direct and reflux aspiration in children with severe neurodisability.

Lower respiratory tract infections in children with severe neurodisability are usually caused by aspiration of stomach contents from gastroesophageal reflux (GOR) or direct aspiration (DA) of food due to oral and pharyngeal motor problems. To determine the contributions and interactions of GOR and DA, oesophageal 24-hour pH monitoring and feeding videofluoroscopy were performed in 34 children (age range 7 months to 16 years, mean 7 years) who had severe physical and learning disabilities and who were slow feeders. Subjects were divided into three groups according to the frequency of their respiratory tract infections. Subjects in group 1 had no respiratory tract infections (N=10); five had GOR and none had DA. Subjects in group 2 had minor respiratory tract infections but had not received more than one course of antibiotics for this in the previous year (N=8); two had GOR alone, four had DA alone, and two had neither. All subjects in group 3 had recurrent respiratory tract infections (N=16); one had GOR alone, seven had DA alone, and eight had both GOR and DA. This study suggests that oral and pharyngeal motor problems are the major cause of respiratory tract infection in children with severe neurodisability. These problems lead to DA and, if GOR is present, to the aspiration of stomach contents. Those children with both DA and GOR are more likely to have severe respiratory tract infections which may lead to gastrostomy feeding (together with fundoplication). GOR without sufficient oral and pharyngeal motor problems to cause DA is less likely to cause respiratory tract infection in children with severe neurodisability.

Adolescent↗
PubMed1990

Persistence of intrinsic neurones and possible phenotypic changes after extrinsic denervation of human respiratory tract by heart-lung transplantation.

Respiratory tract nerves have cell bodies outside (sensory, sympathetic) and inside (parasympathetic) the organ and contain bioactive peptides. These include calcitonin gene-related peptide and tachykinins (sensory nerves), vasoactive intestinal polypeptide (parasympathetic nerves), and neuropeptide with tyrosine (sympathetic nerves). Because transplantation interrupts the extrinsic nerve supply to the tissues, we have examined transplanted human respiratory tracts (n = 11) removed at retransplantation 2 to 42 months after the primary transplant in order to determine whether any nerves and peptide synthesis persist. As controls to establish nerve distribution in human respiratory tract, tissues were obtained from 10 lung resections and five autopsies. Cryostat sections were immunostained to demonstrate the general neural marker PGP 9.5, neuropeptides, and the catecholamine-synthesizing enzyme tyrosine hydroxylase. Nerves immunoreactive for PGP 9.5 were detected in all transplanted tissues. They were fewer in number overall than in control tissue, significantly so in epithelium of trachea and bronchus where they were present sparsely in only three cases. Nerves immunoreactive for tyrosine hydroxylase were significantly fewer in the transplants. Peptide-immunoreactive nerves were also reduced in number in the transplants, except for vasoactive intestinal polypeptide, which was only significantly changed in blood vessels in the lung. Ganglion cells immunoreactive for tyrosine hydroxylase and neuropeptide with tyrosine were seen in the transplanted tissues in five cases, but never in the control tissues. We conclude that whereas some nerves and neuropeptide synthesis persist after extrinsic pulmonary denervation, potentially significant changes also occur, including the appearance in intrinsic parasympathetic neurones of immunoreactivity for a catecholamine-synthesizing enzyme and a peptide normally found in sympathetic nerves.

Adult↗
PubMed1999

The impact of climate on the prevalence of respiratory tract infections in early childhood in Lahore, Pakistan.

BACKGROUND: Respiratory tract infections are a major health problem in developing countries. The aim of this study was to analyse the impact of the climate on the prevalence of upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI) in four socioeconomically different groups in a developing country. METHODS: A prospective cohort study was conducted among children in four socioeconomically different groups in Lahore, Pakistan. Monthly observations were made on 1476 infants born during 1984-1987 and followed for 24 months. Prevalence of URTI and LRTI was analysed according to age, area of living, family size, time of birth, the season of the year and climate variables such as rain, temperature and humidity. RESULTS: Low monthly average minimum day temperature was associated with high prevalence of URTI and LRTI. For LRTI the impact of temperature was larger for boys, children living in larger families and children living in the poorer areas. This pattern was not seen for URTI. A peak in prevalence for LRTI was shown at 5-6 months of age for LRTI and at 10-12 months of age for URTI. CONCLUSIONS: Temperature is related to prevalence of URTI and LRTI in a developing society. The effect of temperature on health varies between different subgroups. These effects should be considered in planning health actions to prevent respiratory tract infections.

Age Distribution↗
PubMed1997

Systemic and local immune responses of four cases with lower respiratory tract illness due to reinfection with respiratory syncytial virus.

Four infants and children who had tracheobronchitis or bronchiolitis by respiratory syncytial virus (RSV) reinfection were presented. Their clinical features, systemic and local immune reactions to RSV were compared with those of eleven age-matched patients who had lower respiratory tract illness with primary RSV infection. Moderate antibody activities in their nasopharyngeal secretions and sera which were comparable to those of convalescent phase of primary infection were observed within several days after onset of illness; however, their clinical symptoms, such as fever or wheezing, lasted almost as long as in primary RSV infection. These observations suggest that the higher serum and secretory antibody activity to RSV during acute phase does not always bring about clinical amelioration in RSV reinfection. The contribution of immunopathological reaction between RSV and RSV-specific antibodies might also be considered as a cause of inflammation during the acute phase of RSV reinfection.

Antibody Formation↗
PubMed2004

Experimental human metapneumovirus infection of cynomolgus macaques (Macaca fascicularis) results in virus replication in ciliated epithelial cells and pneumocytes with associated lesions throughout the respiratory tract.

A substantial proportion of hitherto unexplained respiratory tract illnesses is associated with human metapneumovirus (hMPV) infection. This virus also was found in patients with severe acute respiratory syndrome (SARS). To determine the dynamics and associated lesions of hMPV infection, six cynomolgus macaques (Macaca fascicularis) were inoculated with hMPV and examined by pathological and virological assays. They were euthanized at 5 (n = 2) or 9 (n = 2) days post-infection (dpi), or monitored until 14 dpi (n = 2). Viral excretion peaked at 4 dpi and decreased to zero by 10 dpi. Viral replication was restricted to the respiratory tract and associated with minimal to mild, multi-focal erosive and inflammatory changes in conducting airways, and increased numbers of macrophages in alveoli. Viral expression was seen mainly at the apical surface of ciliated epithelial cells throughout the respiratory tract, and less frequently in type 1 pneumocytes and alveolar macrophages. Both cell tropism and respiratory lesions were distinct from those of SARS-associated coronavirus infection, excluding hMPV as the primary cause of SARS. This study demonstrates that hMPV is a respiratory pathogen and indicates that viral replication is short-lived, polarized to the apical surface, and occurs primarily in ciliated respiratory epithelial cells.

Animals↗
PubMed1993

[Parenteral cephalosporins for the treatment of lower respiratory tract infections].

In most cases of respiratory tract infection, antibiotic therapy has to be initiated before the results of microbiological examination are available. The four most common pathogens of acute exacerbations of chronic bronchitis are pneumococci, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus. Pneumococci are the predominant pathogens of community-acquired pneumonia, followed by H. influenzae and staphylococci. Legionella, mycoplasma and chlamydia vary in frequency according to the population studied. Staphylococci, Pseudomonas, Enterobacter and Klebsiella spp. as well as H. influenzae are the major pathogens of secondary pneumonia. For reasons of cost and environmental problems, oral antibiotics ought to be used whenever possible considering the severity of the infection and patient circumstance. Parenteral antibiotics are indicated in severe infections in order to provide high therapeutic drug levels. Second generation cephalosporins are appropriate for initial therapy of lower respiratory tract infections. In case of severe infection, cephalosporins should be combined with an aminoglycoside, ureidopenicillin or quinolone. Cefuroxime has shown good clinical efficacy and tolerance in lower respiratory tract infections.

Bronchitis↗
PubMed2001

Burkholderia cepacia lower respiratory tract infection associated with exposure to a respiratory therapist.

OBJECTIVE: To investigate and control a nosocomial outbreak of Burkholderia cepacia lower respiratory tract infection. DESIGN: Outbreak investigation and case-control study. SETTING: A 260-bed community hospital. PATIENTS: Participants were mechanically ventilated intensive care patients without cystic fibrosis. A case was defined as a hospitalized patient with a sputum culture positive for B. cepacia between January 1 and November 6, 1998. METHODS: Respiratory therapy infection control policies and practices were reviewed; laboratory and environmental studies and a retrospective case-control study were conducted. Case-patients were matched with control-patients on age, gender, diagnosis, and type of intensive care unit. RESULTS: Nine case-patients were identified; B. cepacia likely caused pneumonia in seven and colonization in two. Two respiratory therapy practices probably contributed to the transmission of B. cepacia: multidose albuterol vials were used among several patients, and nebulizer assemblies often were not dried between uses. B. cepacia was grown from cultures of three previously opened multidose vials; pulsed-field gel electrophoresis patterns of B. cepacia from seven case-patients and two multidose vials were indistinguishable. Case-patients had longer durations of heated humidified mechanical ventilation (mean, 9.8 days vs 4.4 days; P=.03) and were more likely to have exposure to one particular respiratory therapist than controls (odds ratio, undefined; 95% confidence interval, 4.7-infinity; P=.001). The association with the respiratory therapist, a temporary employee, persisted after controlling for duration of heated humidified ventilation. No new B. cepacia infections were identified after control measures were implemented. CONCLUSIONS: B. cepacia probably was transmitted among patients through use of extrinsically contaminated multidose albuterol vials. Respiratory therapy departments must pay close attention to infection control practices, particularly among new or temporary staff.

Aged↗