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Current issues in the management of bacterial respiratory tract disease: the challenge of antibacterial resistance.

The worldwide burden of respiratory tract disease is enormous. Resistance to penicillins, macrolides, and cephalosporins is now detected among the leading bacterial pathogens that cause respiratory tract infections (RTIs)-Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The increasing role of atypical/intracellular pathogens (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila) in RTIs, as well as their increase in antibiotic resistance prevalence, continues to be of great concern. More recently introduced treatment options for RTIs include the newer respiratory fluoroquinolones, along with the macrolides and azalides. Although these agents demonstrate good activity against common respiratory pathogens, reduced susceptibility to these agents has been reported. The ketolides are recently developed antibacterial agents with targeted-spectrum activity against common respiratory tract pathogens, including atypical/intracellular pathogens, and a low potential for inducing resistance. These promising new drugs have shown in vitro and in vivo efficacy in the treatment of community-acquired RTIs, such as community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial maxillary sinusitis.

Animals↗

Neutralizing antibody to bovine adenovirus serotype 3 in healthy cattle and cattle with respiratory tract disease.

A serosurvey of healthy cattle for the presence of serum-neutralizing antibody to bovine adenovirus serotype 3 (BAV-3) established the widespread prevalence of this agent in Iowa cattle. Of the animals studied, 19.1% (involving 157 calves that represented 40 outbreaks (herds) of respiratory tract disease) seroconverted to BAV-3. This pathogen was implicated serologically as being involved in the cause of respiratory tract disease in six herds. Bovine adenovirus serotype 3 was isolated from cattle in two of these herds. Based on seroconversion and lack of isolation of other viral agents, it appeared that BAV-3 could have been the sole virus involved in the respiratory tract disease in one of these two herds. In another herd, seroconversion was observed only to BAV-3, but other viral agents as well as BAV-3 were isolated. The remaining four herds presented a problem because the cattle seroconverted to more than one agent and additional viral agents were isolated from some animals. Whether the disease manifestations observed in these six herds were due solely or in part to BAV-3 can only be speculated. Cattle are capable of undergoing a natural infection, as indicated by seroconversion, in the absence of overt clinical signs of illness. It appears that maternal (passive) antibody decreases to a point at which infection by this virus becomes possible and an active immune response occurs.

Adenoviridae↗

Cytomegalovirus infection in low-birth-weight infants with acute respiratory tract disease.

To determine a participation of cytomegalovirus (CMV) infection in acute respiratory tract disease (ARTD) of low-birth-weight (LBW) infants, specific antibodies against CMV antigens, IgG antibodies against early antigens of CMV (IgG EA) and IgM antibodies against membrane antigens of CMV (IgG MA) were analyzed. The frequency of IgG EA in patients with ARTD was higher than that in controls (46% vs. 32%), and the geometrical mean titer (GMT) of IgG EA in the patients was also higher than that in controls (50.2 vs. 20.1). Five of 15 ARTD patients had IgM MA, and the frequency was significantly higher than that of controls (33% vs. 1.3%, p less than 0.01). Eleven of 15 LBW patients with ARTD had a history of blood transfusions during the neonatal period, and 5 of them had significant IgM MA indicating active CMV infection. All 4 LBW patients without blood transfusion were negative for IgM MA. These results suggest a close relationship of CMV infection to ARTD of LBW infants, but it remains for further studies whether blood transfusion is a primary source of CMV infection in LBW infants.

Acute Disease↗

Passive smoke exposure in infants and children with respiratory tract diseases.

1. The adverse effect of passive smoke exposure on the respiratory tract, particularly in infants and children, is not an issue of dispute. It was the objective of this study to analyse the extent and the intensity of passive smoke exposure in infants and children with respiratory tract diseases, and compare the information obtained with parents' subjective assessment. At the time of admission to the hospital, the parents of 295 infants and children (aged 1 month to 11 years) were questioned by the physician as to the smoking habits in the families' homes. An HPLC method was employed to determine simultaneously nicotine, cotinine and trans-3'-hydroxycotinine in the children's urine. 2. The sum of the nicotine metabolites turned out to be a sensitive marker in determining passive smoke exposure. Measurements revealed passive smoke exposure in 66% of the children, the frequency in younger children being significantly (P < 0.001) higher than in children over 5 years (84% vs 52%). The average concentration of nicotine metabolites in younger passive smokers was significantly (P < 0.001) higher when compared to the older ones (193 nmol/l vs 86 nmol/l). Forty-nine per cent of the parents assessed that their children had experienced passive smoke exposure, and another 10% emphasised that they only smoked in the absence of their child. In children with cystic fibrosis and bronchial asthma, the number of passive smokers as assessed by their parents were lower by 65% and 29% respectively when compared to the findings obtained from measurements. In children without respiratory diseases, the difference was as little as 18%. 3. Parents when questioned in conjunction with an illness of their children, tended to understate, or even withhold the truth about, passive smoke exposure. Therefore, reliable information on passive smoke exposure of patients can only be obtained through objective measurements.

Adult↗

Comparison of results of thoracic radiography, cytologic evaluation of bronchoalveolar lavage fluid, and histologic evaluation of lung specimens in dogs with respiratory tract disease: 16 cases (1996-2000).

OBJECTIVE: To compare results of thoracic radiography, cytologic evaluation of bronchoalveolar lavage (BAL) fluid, and histologic evaluation of biopsy and necropsy specimens in dogs with respiratory tract disease and to determine whether histologic evaluation provides important diagnostic information not attainable by the other methods. DESIGN: Retrospective study. ANIMALS: 16 dogs. PROCEDURE: BAL fluid was classified as normal, neutrophilic, eosinophilic, mononuclear, mixed, neoplastic, or nondiagnostic. Radiographic abnormalities were classified as interstitial, bronchial, bronchointerstitial, or alveolar. Histologic lesions were classified as inflammatory, fibrotic, or neoplastic, and the predominant site of histologic lesions was classified as the alveoli, interstitium, or airway. RESULTS: The predominant radiographic location of lesions correlated with the histologic location in 8 dogs. Of 11 dogs with histologic evidence of inflammatory disease, 8 had inflammatory BAL fluid. Of the 2 dogs with histologic evidence of neoplasia, 1 had BAL fluid suggestive of neoplasia, and the other had BAL fluid consistent with septic purulent inflammation. Two dogs without any histologic abnormalities had mononuclear or nondiagnostic BAL fluid. Two dogs with histologic evidence of fibrosis had mononuclear or mixed inflammatory BAL fluid. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that although thoracic radiography, cytologic evaluation of BAL fluid, and histologic evaluation of lung specimens are complementary, each method has limitations in regard to how well results reflect the underlying disease process in dogs with respiratory tract disease. Lung biopsy should be considered in cases where results of radiography and cytology are nondiagnostic.

Animals↗

Epizootics of respiratory tract disease in swine in Belgium due to H3N2 influenza virus and experimental reproduction of disease.

In Belgium, influenza virus was isolated from swine in 22 epizootics of respiratory tract disease in swine during 1984. In 8 of the epizootics, H3N2 influenza virus, related to the A/Port Chalmers/1/73 strain, was isolated. Intratracheal inoculation of the isolates induced clinical signs. It was concluded that the A/Port Chalmers/1/73 strain was established in the Belgian swine population and was responsible for the epizootics of respiratory tract disease in swine.

Animals↗

Effects of tilmicosin treatment on Pasteurella haemolytica organisms in nasal secretion specimens of calves with respiratory tract disease.

OBJECTIVE: To determine the effect of tilmicosin treatment on number of Pasteurella haemolytica (PH) organisms in nasal secretion specimens of calves with respiratory tract disease. ANIMALS: 206 British mixed-breed beef calves, 2 to 5 months old. PROCEDURE: In 2 separate studies of outbreaks, calves (study 1, n = 101; study 2, n = 105) that developed respiratory tract disease after transport to a feedlot were treated with tilmicosin. Nasal secretion specimens were examined for PH organisms to determine the status of colonization. RESULTS: In both studies, PH serotypes A1 and A6 were isolated. In study 1, tilmicosin treatment eliminated or markedly reduced the number of PH organisms in calves on days 1, 4, and 5 after treatment. In study 2, tilmicosin treatment eliminated PH organisms in calves on days 1, 2, 5, and 6 after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, tilmicosin treatment increased the number of culture-positive calves that became culture-negative and decreased the number of culture-negative calves that became culture-positive for up to 6 days after treatment. Tilmicosin treatment decreased the number of PH organisms in nasal secretion specimens, which indicated that fewer PH organisms were available to infect the lungs or to infect other calves. By reducing colonization, prophylactic use of tilmicosin before transport or at the time of arrival at a feedlot is likely to reduce the incidence of acute respiratory tract disease in calves for the initial several days after arrival, which is the period when they are most susceptible to infectious organisms.

Animals↗

[Therapy of chronic respiratory tract diseases (author's transpl)].

Except in the case of exogenous allergic asthma, the therapy of chronic respiratory tract diseases must be predominantly symptomatic due to the polyaetiology and inhomogeneity of these diseases. Effective treatment of the main pathophysiological symptoms is important for the course and prognosis of the disease. These symptoms usually consist of hypersecretion, infection and bronchial obstruction. With the exception of "infective asthma", bronchial infections are not present at the onset of the illness. Such infections usually result as complications of a disease from which the patient is already suffering, and are essentially the consequence of disruption of the automatic clearance mechanism of the bronchial system and impairment of immunological defence against infection. The best form of therapy is that which is specifically directed at the individual bronchial infection for a period of two weeks. Permanent antibiotic prophylaxis is to a large extent obsolete today. In addition to treatment of bronchial infection, the removal of bronchial obstruction is also very important. Modern bronchospasmolytics are now among the most effective agents, provided the obstruction is actually "reversible". A low dose of oral corticosteroids - administered with caution - is justified should it not be possible to reduce pulmonary resistance to below the "dyspnoea threshold" of the patient.

Anti-Bacterial Agents↗

Cytomegalovirus infection in acute respiratory tract disease accompanying hepatitis in infancy.

To elucidate relationship between acute respiratory tract diseases (ARTD) accompanying hepatitis and cytomegalovirus (CMV) infection in infancy, 74 full-term inpatients with ARTD and 34 control patients without ARTD or hepatitis were subjected to this study. By determining specific antibodies to CMV, IgG early antigen (IgG EA) and IgM membrane antibody (IgM MA) which are markers of active CMV replication, the following results were obtained. Thirty-one (41%) of the 74 patients with ARTD and 12 of the 34 control group (35%) had significant IgG EA (greater than or equal to 1:8). The geometric mean reciprocal titer in the group with ARTD (1:33.0) was higher than that in the control group (1:15.3). On the other hand, while 6 of the 74 patients with ARTD (8%) had significant IgM MA (greater than or equal to 1:8), none of the control group had positive IgM MA. Out of the 74 patients with ARTD, 8 (10%) patients, all except one being younger than 2-month-old, also had hepatitis. Of the 8 patients with hepatitis, 6 (75%) had significant IgG EA. The geometric mean reciprocal titer of the patients with hepatitis was higher than that of the patients without hepatitis, the titer being 1:42.6 and 1:30.7, respectively. On the other hand, 3 of the 8 patients with hepatitis (37%) had significant IgM MA while only 3 of the 66 patients without hepatitis (4.5%) had IgM MA. The frequencies of IgM MA between two groups were significantly different (p less than 0.05). CMV infection may be involved in some infants with ARTD, particularly in younger infants with both of ARTD and hepatitis.

Acute Disease↗

Aerosolized ribavirin in mechanically ventilated children with respiratory syncytial virus lower respiratory tract disease: a prospective, double-blind, randomized trial.

OBJECTIVE: To study the effect of ribavirin aerosol therapy on the immediate clinical course of mechanically ventilated children with respiratory syncytial virus lower respiratory tract disease. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Pediatric intensive care unit (ICU) of a university teaching hospital. PATIENTS: Forty-one children requiring mechanical ventilation for respiratory syncytial virus lower respiratory tract disease. INTERVENTIONS: Patients were stratified by the presence or absence of and underlying disease and then randomized to receive aerosolized ribavirin (20 mg/mL) or saline for 18 hrs/day for 5 days or until endotracheal extubation, whichever came first. MEASUREMENTS AND MAIN RESULTS: Dependent variables included the time course of the illness and the change in FIO2, ventilatory rate, PaO2/FIO2 ratio, and ventilatory-efficiency index of patients while they received aerosol therapy. Ribavirin- and placebo-treated patient groups were not significantly different in the number of ventilator days (6.4 +/- 6.9 vs. 8.2 +/- 10.1; p = .5), oxygen days (10.8 +/- 7.7 vs. 12.2 +/- 11.8; p = .9), ICU days (7.9 +/- 7.0 vs. 10.3 +/- 11.0; p = .7), or hospital days (12.9 +/- 9.7 vs. 16.2 +/- 14.0; p = .6) after the initiation of aerosol therapy. The change in FIO2, ventilatory rate, PaO2/FIO2 ratio, or ventilatory-efficiency index did not differ between the two groups. No ventilator malfunction was observed. There were six deaths caused by intractable hypoxemia in patients with underlying cardiopulmonary disease. Four of these deaths were in the placebo group and two in the ribavirin group (p = .5). CONCLUSIONS: Ribavirin aerosol therapy can be safely administered to mechanically ventilated children with severe respiratory syncytial virus lower respiratory tract disease. However, this therapy does not appear to affect immediate clinical outcome in such patients.

Aerosols↗