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Cefixime in the treatment of upper respiratory tract infections and otitis media.

An increasing number of clinical failures has been noted after treatment of upper respiratory tract infection and acute otitis media with conventional antibiotics. At present, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and group A beta-hemolytic streptococcus (GABHS) are the bacterial pathogens most frequently responsible for these infections. Although GABHS has so far not developed penicillin resistance, the frequency of bacteriological failures with either benzathine penicillin or penicillin V has increased. Firstly, a number of hypotheses have been put forward to explain this, including poor patient compliance and inactivation by beta-lactamase-producing oropharyngeal flora. Secondly, this has added to the demand for new agents to treat resistant streptococci. Cefixime, an orally active third-generation cephalosporin, has attracted considerable attention following the results of numerous clinical studies. Comparative studies between cefixime and conventional antibiotics for the treatment of upper respiratory tract infections and otitis media are summarized.

Cefixime↗

Characterization of the effects of an airborne mixture of chemicals on the respiratory tract and smoothing polynomial spline analysis of the data.

We expanded a previously published (Vijayaraghavan et al. 1994) computerized system to analyze the breathing pattern of unanesthetized mice in order better to recognize and quantify the effects of an airborne mixture of chemicals at three different levels of the respiratory tract. The airborne chemical mixture used was a machining fluid. Such fluids are widely used in industry and a large number of workers are exposed to these airborne mixtures. We found this mixture to be capable of inducing three types of effects on the respiratory tract: sensory irritation of the upper respiratory tract (S), airflow limitation along the conducting airways (A) and pulmonary irritation (P). Depending upon the exposure concentration, mainly S or P effects were obtained but an A effect was also identified. The three types of effects occurred at various times during the exposures and, furthermore, within a group of exposed animals some exhibited one type of effect while others exhibited another type. In order to analyze such complex data sets, two statistical methods for smoothing polynomial splines were utilized: the maximum likelihood (ML) method and generalized cross validation (GCV) method. The results indicated the previous methods used to characterize a single effect of airborne chemicals can now be extended to evaluate mixtures likely to induce multiple types of effects. However, statistical analysis methods, either the ML or GCV methods, or other appropriate methods are needed to evaluate the responses obtained due to the complex effects that a mixture can induce in comparison to single chemicals.

Aerosols↗

Total daily energy expenditure and incidence of upper respiratory tract infection symptoms in young females.

UNLABELLED: A group of 31 young females, tennis players and non-athletes, aged 16 +/- 2 years (range: 14 - 21 years), with a wide range of physical activity levels was used to investigate the relationship between total daily energy expenditure and the incidence of upper respiratory tract infection symptoms. METHODS: During a 12 week winter period, habitual daily activity (excluding training) was evaluated using a 3-day physical activity record. Tennis training was quantified using a validated method of estimating energy expenditure during play. Total daily energy expenditure was calculated from the sum of daily training plus mean habitual daily activity energy expenditures. The total group of subjects was divided in quartiles for total daily energy expenditure. A validated symptom checklist was used to assess the incidence and severity of upper respiratory tract infections, on a daily basis. RESULTS: The girls in the highest quartile of total daily energy expenditure (> or = 17,322 kJ/day) and in the lowest quartile (< or = 10,047 kJ/day) had the greatest incidence of URTI symptomatology, although the moderately active girls in quartile three (12,290 - 16,410 kJ/day) presented the lowest incidence. Significant differences in number of upper respiratory tract infection episodes, sickness days and symptomatology index were found between quartiles three and one (p < 0.05) and quartiles three and four (p < 0.01). Peak severity of symptoms was significantly lower in quartile three compared with all other quartiles (p < 0.05).

Adolescent↗

Ultrastructural studies on the respiratory tract of mice inoculated intranasally with L. fermentum.

The ultrastructural modifications of the respiratory tract of mice produced by the intranasally inoculated L. fermentum was evaluated. The genus Lactobacillus has been largely studied from the probiotic effect point of view in different ecological systems. Lactobacilli inoculated in 4 intranasal doses (1 x 10(9) CFU/dose) do not produce fundamental changes at the ultrastructural level in the organs of the respiratory tract studied. The most important finding was the presence of a cellular type with intracellular structures surrounded by membranes exhibiting electron dense paracristalline material parallel arranged.

Administration, Intranasal↗

Viral etiology of acute respiratory tract infections in children presenting to hospital: role of polymerase chain reaction and demonstration of multiple infections.

BACKGROUND: Viral lower respiratory tract infections are a leading cause of hospitalization for young children. METHODS: We used polymerase chain reaction (PCR) and conventional methods of cell culture and antigen detection to establish the viral etiology of acute respiratory tract infections in 75 hospitalized children. RESULTS: One or more viral pathogens were detected in 65 (87%) children, with respiratory syncytial virus being the most commonly identified virus (36 children). Other viruses identified included influenza virus types A and B, parainfluenzavirus type 3, adenovirus, enterovirus, rhinovirus, coronavirus and human metapneumovirus. PCR increased the diagnostic yield significantly compared with antigen detection and culture, with 39 (21%) diagnoses identified by this method. Multiple infections were identified in 20 (27%) children. CONCLUSIONS: PCR-based methodologies offer increased sensitivity for the detection of most respiratory viruses in young children. The inclusion of PCR into diagnostic testing strategies is needed to broaden our understanding of the natural ecology of respiratory viruses and the significance of multiple infections.

Acute Disease↗

Human metapneumovirus in infants and young children in Thailand with lower respiratory tract infections; molecular characteristics and clinical presentations.

UNLABELLED: Human metapneumovirus (hMPV) is a recently identified Paramyxovirus. The clinical features and molecular characteristics of hMPV in Asian populations have so far remained obscure. OBJECTIVE: The present study was designed to investigate the prevalence of hMPV in infants and young children presented with acute lower respiratory tract infection (ALRI) and to identify the molecular characteristics and clinical presentations. METHODS: There were 236 nasopharyngeal secretions (NPs) collected from infants and children presented with ALRI at King Chulalongkorn Memorial hospital between March 2001 and September 2003. Reverse transcriptase-polymerase chain reaction (RT-PCR) applying specific primers was done to identify hMPV and hRSV. Phylogenetic analysis of hMPV N, F and L genes was also performed. RESULTS: Of the 220 (236) infants and young children tested, positive results were found in 12 specimens (5.4%). The mean age of children with hMPV infections was 22+/-11 months. They mostly presented with fever with cough (100%) and upper respiratory tract symptoms (10/12, 83%). Eleven of twelve infants (92%) were hospitalized. Additionally, phylogenetic analysis identified two distinct lineages of hMPV. CONCLUSION: Our results demonstrated the prevalence, molecular characterization and clinical spectrum of hMPV infection in infants and young children presented with lower respiratory tract infections in Thailand.

Base Sequence↗

[The nutritional status change the effectiveness of a dietary supplement of lactic bacteria on the emerging of respiratory tract diseases in children].

One hundred children 6 to 24 month old, normal or undernourished according to weight for height index, received during three months--autumn to winter--a dietary supplement of live Lactobacillus acidophilus and Lactobacillus Casei, 10(7)-10(8)/ml in fermented milk (LB) or an equivalent amount of fluid milk (L) as control. Children's follow-up was performed as outpatients in the Hospital Posadas (Great Buenos Aires). Episodes of respiratory tract infections were recorded and classified according to severity as: Pneumonia (N); Bronchitis (B), Recurrent Obstructive Bronchitis (BOR) and upper respiratory tract infections (CVAS). 58% of children fitted the study protocol, 22 in the LB and 36 in the L group; 21 were undernourished and 37 presented normal weight/height. No deaths were recorded. Total episodes were 103: 34 in LB and 69 in L, that means a frequency of 1.55 and 1.92 episodes/children respectively. In LB a maximum of 3 episodes/children was recorded, meanwhile the number reached 7 in L (p = 0.0373). Severity was higher in L than LB: 0.06 vs. 0 for N; 0.69 vs. 0.45 for B + BOR and 1.17 vs. 1.09 for CVAS. In the control group frequency of severe pathologies was about twice in undernourished than in normal: 0.08 vs. 0.04 for N; 1.08 vs. 0.50 for B + BOR; no difference was found for CVAS. Live lactobacillus supplement suppressed pneumonia and decreased bronchitis in undernourished as well as in normal. In this study undernutrition not only increased the chance of suffering severe acute respiratory tract infections but also impaired the effectiveness of the supplement to decrease severity. The effect is explained on the basis of the immunocompetence depression linked to an inadequate nutritional status.

Animals↗

[Clinical studies and sputum levels of ceftriaxone once daily administration in respiratory tract infection].

Ceftriaxone (CTRX), a new cephalosporin, was investigated by once daily administration for its clinical efficacy and safety on respiratory tract infections. The results obtained are summarized as follows: 1. Clinical responses to CTRX of a total of 39 cases with respiratory tract infections were excellent in 12 cases, good in 23, fair in 3, poor in 1 with an efficacy rate of 89.7%. Against acute bronchitis, lung abscess, bronchiectasis, chronic bronchitis and obstructive pneumonia, efficacy rates were 100%. 2. Serum levels and urinary excretion rates of CTRX were investigated in 2 cases after intravenous drip infusion of the drug at doses of 1 g and 2 g, respectively. Although urinary excretion rate tended to decrease with the deterioration of renal functions, prolongation of serum half-life was slight in those patients with normal liver function. In 1 case, it remained at 1.9 micrograms/ml at 12 hours and in another at 0.9 microgram/ml at 22 hours in sputum. According to the results, it appears that once daily administration of CTRX is effective and well tolerated in patients with acute respiratory infections.

Adult↗

Role of anaerobic beta-lactamase-producing bacteria in upper respiratory tract infections.

Bacteroides sp. (Bacteroides melaninogenicus, Bacteroides oralis and Bacteroides fragilis), peptostreptococci and Fusobacterium sp. are important pathogens in upper respiratory tract infections. A recent increase in numbers of beta-lactamase-producing strains of anaerobic Gram-negative bacteria in upper respiratory tract infections has been associated with increased failure rates of penicillins in eradication of these infections. These infections include chronic otitis media, chronic sinusitis and mastoiditis, chronic recurrent tonsillitis and lung abscesses. The indirect pathogenicity of these organisms is apparent through their ability not only to survive penicillin therapy but also to protect penicillin-susceptible pathogens from the drug. These direct and indirect virulence characteristics of anaerobic bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections.

Bacteroides↗

[Bacteria isolated from chronic upper and lower respiratory tract infections and the associated therapeutic strategies--in paranasal sinusitis].

Nasal sinusitis, tonsillitis, and pharyngolaryngitis typify upper respiratory tract infections, while bronchitis and pneumonia typify lower respiratory tract infections. Cases of paranasal sinusitis with severe suppuration are reportedly becoming less frequent, while those of chronic catarrhal paranasal sinusitis and edematous allergic paranasal sinusitis are becoming more so, The primary factor in paranasal sinusitis, a typical infectious disease encountered in otolaryngology, is bacterial infection. The main causative bacteria are Streptococcus pneumoniae, reported in 13.4% of cases, Haemophilus influenzae in 12.8% Moraxella catarrhalis in 5.5%, Staphylococcus aureus in 26.5%, Pseudomonas aeruginosa in 5.2%, and anaerobes. The incidence of strains resistant to antimicrobial agents has grown for S. pneumoniae, H. influenzae, and M. catarrhalis and decreased for S. aureus and P. aeruginosa. Acute exacerbation or severe suppuration in chronic paranasal sinusitis requires the administration of antimicrobial agents, with the same agent administered 2 weeks for maximal effect. First-line agents are AMPC/CVA, SBTPC, CDTR-PI, CFPN-PI, and GFLX for adults, with ASPC, SBPC, ACPC, CTRX, CMZ, FMOX, PAPM/BP, and MEPM injected in severe cases. Attention must be paid to strains that resist cephems and macrolides, such as PISP, PRSP, and BLNAR. In refractory chronic paranasal sinusitis, attention must also be paid to biofilms produced by S. aureus and P. aeruginosa. Suitable antimicrobial agents should be determined for treating of chronic paranasal sinusitis, in addition to the best procedure to ensure early recovery from inflammation, such as puncturing or irrigating the maxillary sinus, injecting a suitable agent, nebulization, and/or surgically widening the middle meatus.

Anti-Infective Agents↗

Inhalation of beta 2 agonists impairs the clearance of nontypable Haemophilus influenzae from the murine respiratory tract.

BACKGROUND: Nontypable Haemophilus influenzae (NTHi) is a common bacterial pathogen causing human respiratory tract infections under permissive conditions such as chronic obstructive pulmonary disease. Inhalation of beta2-receptor agonists is a widely used treatment in patients with chronic obstructive pulmonary disease. The aim of this study was to determine the effect of inhalation of beta2 agonists on the host immune response to respiratory tract infection with NTHi. METHODS: Mouse alveolar macrophages were stimulated in vitro with NTHi in the presence or absence of the beta2 receptor agonists salmeterol or salbutamol. In addition, mice received salmeterol or salbutamol by inhalation and were intranasally infected with NTHi. End points were pulmonary inflammation and bacterial loads. RESULTS: Both salmeterol and salbutamol inhibited NTHi induced tumor necrosis factor-alpha (TNFalpha) release by mouse alveolar macrophages in vitro by a beta receptor dependent mechanism. In line, inhalation of either salmeterol or salbutamol was associated with a reduced early TNFalpha production in lungs of mice infected intranasally with NTHi, an effect that was reversed by concurrent treatment with the beta blocker propranolol. The clearance of NTHi from the lungs was impaired in mice treated with salmeterol or salbutamol, an adverse effect that was prevented by propranolol and independent of the reduction in TNFalpha. CONCLUSION: These data suggest that inhalation of salmeterol or salbutamol may negatively influence an effective clearance of NTHi from the airways.

Administration, Inhalation↗

Once-daily dosing regimen for aminoglycoside plus betalactam combination therapy of serious lower respiratory tract infections.

Aminoglycosides are important antibacterial agents for treatment of serious gram-negative bacillary infections including lower respiratory tract infection. Once-daily aminoglycosides result in higher peak and lower trough plasma concentrations than conventional multiple daily dosing regimens; once-daily aminoglycoside therapy is equally effective, generally less toxic and much less expensive and therefore this regimen is more and more frequently used for treatment of suspected or confirmed gram-negative bacillary infections and of febrile episodes in neutropenic patients, in particular in combination with an appropriate betalactam antibiotic. Despite the lack of studies on this topic, once-daily aminoglycosides in combination with a betalactam agent can be used in subjects with lower respiratory tract infection, including patients with cystic fibrosis, in which tobramycin appears to be the aminoglycoside antibiotic of choice.

Administration, Oral↗

Comparative anatomy of mammalian respiratory tracts: the nasopharyngeal region and the tracheobronchial region.

Silicone rubber casts of the respiratory tract were used in morphological studies of the human, baboon, rhesus monkey, dog, rabbit, guinea pig, rat, hamster, and mouse. In these studies, the trachea of the specimen was opened by tracheotomy, and silicone rubber (734 RTV) was introduced through the trachea to form nasopharyngeal and tracheobronchial casts. Measurements were made on the nasal structures, and the lungs were observed for species variation in branching pattern and number of lobes per lung. While species differences in respiratory tract anatomy are known to exist, the present study provides a focus for toxicologists when extrapolating toxicological results from one species to another.

Adult↗

Association between cigarette smoking and acute respiratory tract illness in young adults.

The association of cigarette smoking with the occurrence and severity of an acute respiratory tract illness (ARTI) was studied. Clinical data were obtained prospectively on 867 men and women with an ARTI and on a control group of 289 women. Three hundred seven (57%) of the 534 women in the ARTI group were smokers, compared with 97 (34%) of the 289 women in the control group, a highly significant difference. Of the 867 men and women with ARTIs, 506 were smokers. Smokers had a statistically significant greater likelihood of having a lower respiratory tract illness (57% v 45%), a longer duration of cough (8.9 v 6.8 days), and a greater frequency of abnormal auscultatory findings (31% v 20%) than did the 361 nonsmokers. Cigarette smoking may thus contribute to the substantial morbidity and lost productivity resulting from ARTI.

Acute Disease↗

Antimicrobial agents in lower respiratory tract infections in Dutch general practice.

This study describes the prescription of antimicrobial agents in cases of lower respiratory tract infections in Dutch general practice. A secondary analysis of data from the National Study of Illness and Procedures of The Netherlands Institute of Primary Health Care (a nationwide group of 161 general practitioners with data from 334,449 patients) had been carried out. Antimicrobial agents were prescribed in 30% of all contacts: in about half of the first contacts and contacts for recurrences, and in one out of six repeat contacts. The prescription rates were associated with diagnosis and reason for encounter but rarely with older age or comorbidity. Amoxycillin and doxycycline were most frequently prescribed. While most lower respiratory tract infections are virus-induced and antibiotics are not effective in most cases, antimicrobial agents might still be overprescribed.

Anti-Bacterial Agents↗

A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico.

BACKGROUND: The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured. OBJECTIVE: We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections and rates stratified by household and personal characteristics. DESIGN: A double-blind, randomized, placebo-controlled trial was carried out in which 736 children aged 6-15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo, zinc daily, vitamin A and zinc together, or placebo. Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections. RESULTS: Vitamin A supplementation was associated with a 27% increase in diarrheal disease [risk ratio (RR): 1.27; 95% CI: 1.10, 1.45; P < 0.001] and a 23% increase in cough with fever (RR: 1.23; 95% CI: 1.02, 1.47; P = 0.02), whereas zinc had no effect on these outcomes. Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors, piped water, and indoor bathrooms. Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated. Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers. CONCLUSIONS: Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City. Vitamin A and zinc have more heterogeneous effects in different subgroups of children.

Confidence Intervals↗

Inhibitory and bactericidal effects of hydrogen peroxide production by Streptococcus pneumoniae on other inhabitants of the upper respiratory tract.

An inverse correlation between colonization of the human nasopharynx by Streptococcus pneumoniae and Haemophilus influenzae, both common upper respiratory pathogens, has been reported. Studies were undertaken to determine if either of these organisms produces substances which inhibit growth of the other. Culture supernatants from S. pneumoniae inhibited growth of H. influenzae, whereas culture supernatants from H. influenzae had no effect on the growth of S. pneumoniae. Moreover, coculture of S. pneumoniae and H. influenzae led to a rapid decrease in viable counts of H. influenzae. The addition of purified catalase prevented killing of H. influenzae in coculture experiments, suggesting that hydrogen peroxide may be responsible for this bactericidal activity. H. influenzae was killed by concentrations of hydrogen peroxide similar to that produced by S. pneumoniae. Hydrogen peroxide is produced by the pneumococcus through the action of pyruvate oxidase (SpxB) under conditions of aerobic growth. Both an spxB mutant and a naturally occurring variant of S. pneumoniae, which is downregulated in SpxB expression, were unable to kill H. influenzae. A catalase-reversible inhibitory effect of S. pneumoniae on the growth of the respiratory tract pathogens Moraxella catarrhalis and Neisseria meningitidis was also observed. Elevated hydrogen peroxide production, therefore, may be a means by which S. pneumoniae is able to inhibit a variety of competing organisms in the aerobic environment of the upper respiratory tract.

Coculture Techniques↗

[Clinical and bacteriological effects of cefetamet pivoxil against community-acquired respiratory tract infections. Part II].

We investigated clinical and bacteriological effects of cefetamet pivoxil (CEMT-PI) in community-acquired respiratory tract infections and obtained the following findings. That method was approximately equal to that of investigation in 1994. 1. Of the 431 respiratory tract infection cases that were treated with CEMT-PI according to a same protocol at a total of 41 institutions in Tokyo, Kanagawa-ken, Saitama-ken and Chiba-ken from January to the beginning of March 1996. Outpatients accounted for 98.1% of the subjects. Regarding genders to patients, slightly more females (52.6%) than males were included. Diagnoses given to these patients included pharyngo-laryngitis (53.5%), tonsillitis (20.4%) and acute bronchitis (19.1%). 2. We investigated clinical efficacy rates (the ratio of those excellent + good) classified by diseases. The improvement rates of pharyngo-laryngitis, tonsillitis and acute bronchitis were more than 85.0%. Other cases were small in number. That of chronic bronchitis-acute increasing change for the worse was 66.7%, pneumonia was 50.0% and bronchiectasis infection was 16.7%. It was not studied that clinical efficacy rates among those who were treated with 1 CEMT-PI tablet twice and among those who were given 2 tablets twice were significant level. 3. For the bacteriological study, a written material describing the method of collecting specimens, storage and transport in detail was distributed to the above mentioned institutions. The isolation and identification of suspected causative bacteria, determination of minimum inhibitory concentrations (MICs) and investigation of beta-lactamase production were conducted all together at section of studies, Tokyo Clinical Research Center. Suspected causative bacteria were detected from 274 (63.6%) cases. They included 88 strains of Haemophilus influenzae, 47 strains of Streptococcus pneumoniae, 42 strains of Streptococcus pyogenes, 20 strains of Moraxella subgenus Branhamella catarrhalis and 17 strains of Klebsiella pneumoniae subsp. pneumoniae. Suspected causative bacteria classified by diseases were S. pyogenes (tonsillitis), S. pneumoniae (acute bronchitis and secondary infection of chronic respiratory infection) and H. influenzae (pharyngo-laryngitis), and the detection frequency of those was high. The clinical efficacies (the ratio of improvement) classified by suspected causative bacteria were 84.4% against organism that was indicating CEMT and were 69.2% against organism that was not indicating CEMT.

Adult↗