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Dosing of amoxicillin/clavulanate given every 12 hours is as effective as dosing every 8 hours for treatment of lower respiratory tract infection. Lower Respiratory Tract Infection Collaborative Study Group.

In this double-blind study, 557 patients with lower respiratory tract infection were randomly assigned to receive amoxicillin/clavulanate orally either every 12 hours (875/125 mg) or every 8 hours (500/125 mg) for 7-15 days. For the 455 patients evaluable for clinical efficacy at the end of therapy, clinical success was similar in the two groups: 93% and 94% in the 12-hour and 8-hour groups, respectively (P = .42). Bacteriologic success at the end of therapy was also comparable: 97% and 91% in the 12-hour and 8-hour groups, respectively (P = .86). The occurrence of adverse events related to treatment was similar for the two groups, but fewer patients in the 12-hour group reported moderate or severe diarrhea. Amoxicillin/clavulanate (875/125 mg) given every 12 hours is as effective and safe as every-8-hours administration of the combination (500/125 mg) for the treatment of lower respiratory tract infection.

Adolescent↗

The epidemiology of respiratory tract infections.

Respiratory tract infections (RTIs) are the most common, and potentially most severe, of infections treated by health care practitioners. Lower RTIs along with influenza, are the most common cause of death by infection in the United States. Risk factors for pneumonia and other respiratory tract infections include: extremes of age (very young and elderly), smoking, alcoholism, immunosuppression, and comorbid conditions. The microbial cause of RTIs vary depending on the infection (i.e., pneumonia compared with acute bacterial sinusitis), setting (i.e., community-acquired compared with nosocomial), and other factors. The causative pathogens associated with CAP have changed in prevalence over time. Although Streptococcus pneumoniae remains the most common causative pathogen, a number of newer pathogens, such as Chlamydia pneumoniae and sin nombre virus, have been recognized in recent years. The emerging antimicrobial resistance of respiratory pathogens (most notably S. pneumoniae) has also increased the challenge for appropriate management of RTI. An awareness of the epidemiology and cause of specific respiratory infections should optimize care.

Adolescent↗

Efficacy of a polyvalent bacterial lysate in children with recurrent respiratory tract infections.

Respiratory tract infections (RTIs) are the most frequent infections in humans, particularly in children. In addition to intervention, increasing interest is focusing on immunomodulatory therapy for recurrent RTIs, which indicate a reduced defense capacity of the respiratory mucosa. LW 50020, an oral immunomodulator that contains the antigens of seven bacteria common in RTIs, has reduced the number, duration, and severity of RTIs in children and adults. This 56-week placebo-controlled, double-blind study in 188 children investigated whether the efficacy of the standard schedule (immunization cycle + one booster cycle) would be enhanced by additional booster cycles. Efficacy and safety over the long term were also assessed. The rate of infection was reduced by 50% with the standard schedule and could not be further decreased by two consecutive booster cycles. With both schedules, this reduction was sustained during a 28-week treatment-free observation period that followed the 28-week treatment period. The number of adverse drug reactions was low, and all were transient, expected, and nonserious. These results confirm that LW 50020 is an effective and safe strategy for RTIs.

Adjuvants, Immunologic↗

Multicenter evaluation of the efficacy and safety of gatifloxacin in Mexican adult outpatients with respiratory tract infections.

Respiratory tract infections (RTIs), the most common indication for outpatient antimicrobial therapy, impose a heavy medical and societal burden and present a difficult therapeutic challenge in the face of increasing pathogen resistance worldwide. Gatifloxacin is a new broad-spectrum fluoroquinolone with excellent activity against prevalent respiratory bacteria, including penicillin-resistant Streptococcus pneumoniae and atypical pathogens. A multicenter, open-label, noncomparative surveillance study carried out in Mexico evaluated the safety and efficacy of oral gatifloxacin 400 mg once daily in 17,923 adult outpatients with community-acquired pneumonia (CAP) (n = 3322), acute exacerbations of chronic bronchitis (AECB) (n = 5885), and acute bacterial sinusitis (n = 8716). Voluntary, unpaid physician participation contributed to an unbiased study design. Physician-assessed global rate of cure or improvement was 96.3%; efficacy was 95.8% in CAP, 96.1% in AECB, and 96.4% in sinusitis. The incidences of relapse (1.5%) and therapeutic failure (0.7%) were low. The most commonly reported adverse events, nausea (2.76%), headache (2.20%), and dizziness (1.33%), were generally mild and self-limited. Oral gatifloxacin 400 mg once daily is effective and safe for patients with CAP, AECB, and acute sinusitis.

Acute Disease↗

Can antimicrobial activity be sustained? An appraisal of orally administered drugs used for respiratory tract infections.

Respiratory tract infections (RTIs) represent a major cause of illness worldwide. Therefore, it is of great concern that common RTI pathogens have become increasingly resistant to many of the antimicrobial agents used for therapy. For example, Haemophilus influenzae and Moraxella catarrhalis have become resistant to beta-lactam drugs by producing efficient beta-lactamases (> 35 and 90% of strains, respectively). More recently, pneumococci have become more resistant through the mechanism of altered penicillin-binding proteins (PBPs). The rate of penicillin nonsusceptible isolates has risen to > 25% in the United States (1994-1995). It is important to monitor the resistance characteristics of such pathogens and, if possible, to use regionally acquired data to guide empiric selection of therapeutic agents for RTIs. Currently, some antimicrobials remain effective against the majority of these three bacterial species, as exemplified by amoxicillin/clavulanic acid. Furthermore, amoxicillin alone seems to possess greater inhibition than other orally administered beta-lactams at clinically achievable concentrations against pneumococci with altered PBPs. It is critical that steps are taken to limit resistance problems, particularly through; 1) education of prescribers and the public; 2) initiation of the development of novel drugs with alternative modes of action or stability to existing resistance mechanisms; and 3) by continuing to generate quality susceptibility testing data to guide empiric chemotherapy against bacterial pathogens causing RTI.

Administration, Oral↗

Clinical requirements in the treatment of today's respiratory tract infections.

Respiratory tract infections (RTIs) are among the most frequent infections in man and lower tract infections account substantially for the overall mortality in hospitals. Regarding the etiology of pneumonias, one has to consider different pathogenic mechanisms, age of the patients, underlying diseases, concomitant medications, symptomatologies, seasonal influences, and clinical conditions, e.g. intensive care environment and mechanical ventilation. To optimize the rational management of respiratory infections, identification of the etiologic agent would be desirable. The decision of how to treat is often based on epidemiologic, clinical, and radiological assessments. Epidemiologic studies have shown a pronounced difference in the etiologic spectrum between community- and hospital-acquired RTIs. In community-acquired pneumonias, pneumococci, Haemophilus influenzae, Legionella, Mycoplasma and viruses predominate, whereas in nosocomially acquired pneumonias, Enterobacteriaceae, e.g. Klebsiella, Proteus, Enterobacter as well as Pseudomonas and staphylococci comprise the most frequent isolates. Empirical therapy has to cover all possible etiologic pathogens which most likely cause the infection. In addition, an adequate kinetic profile, e.g. once or twice daily dosing, sufficient pulmonary tissue or fluid penetration, and acceptable tolerance and costs are prerequisites for optimal therapy. Drugs of choice for the treatment of community-acquired pneumonia are aminobenzylpenicillins or macrolides. Oral cephalosporins exhibit excellent activity against many bacterial pathogens of typical community-acquired pneumonia, and are active against beta-lactamase-producing H. influenzae.

Drug Resistance, Microbial↗

[Current approaches to the clinical virologic diagnosis of viral respiratory tract infections].

Respiratory viruses (respiratory syncytial virus, influenza virus type A and B, parainfluenza virus and adenovirus) can cause a wide variety of human disease. Viral respiratory diseases in adults and children cause significant morbidity and mortality. Proper and rapid diagnosis of these etiological agents is necessary for the appropriate use of effective antiviral drugs and to decrease unnecessary antibiotic therapy. Many virology laboratories detect respiratory viruses by inoculating conventional cell culture tubes with respiratory samples and then examining for cytopathic effect or hemadsorption. However, this procedure can require many days or even weeks for viral detection and identification, providing culture results to clinicians in a period of time that may not be clinically useful. Laboratory diagnosis of respiratory virus infections has become easier and more rapid with the use of immunofluorescent antibody tests, shell vial culture methods, and molecular biological assays. In this review article, the specificities and sensitivities of these assays were compared on the basis of recent studies, and the favorable ones for the routine diagnosis were updated.

Adenovirus Infections, Human↗

Intranasal monoclonal IgA antibody to respiratory syncytial virus protects rhesus monkeys against upper and lower respiratory tract infection.

Respiratory syncytial virus (RSV), the major cause of lower respiratory tract disease in infants, is thought to infect the upper airways before spreading to the lower respiratory tract. A rhesus monkey model of RSV infection after upper airway inoculation was used to test the protective effect of intranasal treatment with HNK20, a mouse monoclonal IgA antibody against RSV F glycoprotein. HNK20 was administered once daily for 2 days before RSV challenge and 4 days after challenge. Treatment with 0.5 mg/kg HNK20 reduced viral shedding in the nose, throat, and lungs by 3-4 log10/mL (P < or = .002). All monkeys developed RSV neutralizing antibody in serum, even in the absence of detectable viral replication. Neutralizing concentrations of monoclonal antibody remained in nasal secretions for > 1 day after treatment. These results suggest that nose-drop application of monoclonal antibody could provide convenient and effective protection against RSV infection in human infants at risk of severe lower respiratory tract disease.

Administration, Intranasal↗

[Respiratory tract infection and respiratory syncytial virus in young infants].

We investigated the role of respiratory syncytial virus (RSV) in respiratory tract infections of up-to-3-months old infants. This prospective study was carried out from April 1993 to March 1994. Detection of RSV antigen in nasopharyngeal specimens was done by enzyme immunoassay using TESTPACK RSV at our out patient clinic. During this study period, 65 young infants with respiratory tract infection visited our clinic. Seventeen patients (26%) were diagnosed as having RSV infection. Fifteen out of the 17 infants with RSV infection were observed in spring and winter. Fourteen out of the 17 infants with RSV infection had acute bronchiolitis or pneumonia. In contrast to RSV infection, only three patients out of the 48 infants with non-RSV infection had lower respiratory tract infection. In conclusion, the majority of young infants infected with RSV suffered from bronchiolitis or pneumonia.

Antigens, Viral↗

An update on the pathophysiology of rhinovirus upper respiratory tract infections.

Upper respiratory tract infections are one of the most common infectious diseases in man and are characterized by relatively mild symptoms. However, complications of bacterial super-infection or asthma exacerbations are not seldomly seen. Most upper respiratory tract infections are caused by rhinoviruses. The rhinovirus is a non-enveloped 30 nm RNA-virus with over 100 serotypes that belongs to the Picornaviridae family and only replicates in primates. It is characterized by a single positive stranded genome acting not only as a template for RNA synthesis, but also encoding for a single polypeptide necessary for viral replication. The viral capsid has an icosahedral symmetry and demonstrates deep canyons, with a receptor-binding domain. Rhinoviruses are transmitted mainly via direct- or indirect contact with infected secretions and invade their host by binding to the ICAM-1 receptor on the nasal epithelium. Typical for rhinovirus upper respiratory tract infections are isolated scattered foci of infected epithelium, not showing any striking damage or cytopathic alterations, between large areas of normal epithelium. Today there is still little detailed knowledge on the pathophysiology of common cold, especially on the aspect of cellular migration and defense. A better understanding in mechanisms underlying this cellular response would not only have therapeutical consequences, but may also explain the relationship between viral infectious rhinitis and asthma or atopy. During a rhinovirus infection, a selective neutrophil and monocyte recruitment is observed. In vitro and in vivo data have demonstrated a time-limited, rhinovirus-induced increase in bradykinin, cytokine, chemokine and sICAM-1 concentrations. Epithelial derived proinflammatory cytokines initiate an adhesion cascade and activate T lymphocytes that create a TH1-type cytokine environment within the infected tissue, necessary to eradicate the virus infection. The selective recruitment of neutrophils seems linked to increased concentrations of the chemokine IL-8 and common cold symptoms. It is doubtful that the cytokine-regulated-production of specific neutralising immunoglobulins is necessary for recovery from viral illnesses and presumably only contributes to a late and temporary protection against rhinovirus reinfection. These observations confirm the crucial role that cytokines and mediators play in the pathogenesis of a rhinovirus infection by mediating chemotaxis, transmigration and activation of inflammatory- and immunocompetent cells.

Animals↗

Comparison of bronchoalveolar lavage and catheter lavage to confirm ventilator-associated lower respiratory tract infection.

Lower respiratory tract infection (LRTI) is a well recognised complication of artificial ventilation in intensive care units (ICU). Ideally, specimens for microbiological analysis should be obtained during bronchoscopy, but this is not always possible. Therefore, the microbiological diagnosis of lower respiratory tract infection by broncho-alveolar lavage (BAL) obtained during bronchoscopy was compared with catheter lavage (CL) with a balloon-tipped catheter. Adult patients with clinical evidence of lower respiratory tract infection in an adult ICU were randomly assigned to undergo BAL followed by CL or vice versa. Forty ml of normal saline 0.9% were instilled and then aspirated with a flexible bronchoscope to obtain BAL. A similar volume was instilled and aspirated with a 12-gauge Foley balloon-tipped catheter to obtain a CL sample. The number of inflammatory cells, epithelial cells and organisms seen by microscopy were quantified. Culture results were semi-quantified and classified as negative, positive, equivocal or contaminated. Seventy-nine paired specimens were obtained from 66 patients, including specimens from 10 patients taken on two or more occasions. Only 20% of BAL and 16% of CL had one or more epithelial cells and bacteria were seen in 26 BAL and 21 CL specimens, respectively; 35% of BAL and CL specimens were positive and there was a discrepancy in the culture result in only two cases. Staphylococcus aureus was the pathogen isolated most frequently and polymicrobial lower respiratory infection was diagnosed on 10 occasions (15%). CL fluid is as reliable as BAL in diagnosing lower respiratory tract infection in ICU. This approach does not require bronchoscopic expertise and utilises convenient laboratory techniques.

Adolescent↗

The continuing challenge of lower respiratory tract infections.

Lower respiratory tract infections have been a major cause of morbidity and mortality among humans since the dawn of history. The initial hope that the era of antibiotics would remove this scourge has been replaced by the more realistic view that although antimicrobial agents represent a major therapeutic advance, they have not yet solved all of the problems of lower respiratory tract infections. The pneumococcus, for example, causes mortality in a certain number of patients despite antimicrobial therapy. An even greater challenge is being imposed by the emergence of antimicrobial resistance among important bacterial pathogens, especially Streptococcus pneumoniae.

Centers for Disease Control and Prevention, U.S.↗

Role of inflammation in respiratory tract infections.

In respiratory tract infections, leukocytes are recruited to the lungs, where they help remove invading organisms through phagocytic clearance. In some instances, however, the normal inflammatory response may be as destructive as it is defensive. The neutrophils secrete a proteolytic enzyme, neutrophil elastase, which has emerged as a major culprit in the pathogenesis of inflammatory airway disease. This enzyme has been found to strip the bronchial epithelium, reduce ciliary beating, and stimulate excess mucus secretion, leading to mucus retention, bacterial proliferation, and recurrent infections. Neutrophil elastase also stimulates epithelial cell interleukin-8 secretion and produces other chemoattractant cleavage products that lead to further neutrophil recruitment. It also impairs host defenses by damaging the major opsonophagocytic receptor on the neutrophil and by weakening the efficacy of immunoglobulins. For this reason, an important goal in the treatment of respiratory tract infections should be to prevent or shorten the duration of neutrophil elastase release. A number of different approaches have been proposed or attempted in an effort to modulate the proteinase burden. These include direct inhibition of elastase and interference with the recruitment, adherence, and degranulation of neutrophils. An even more fundamental approach would start in the bone marrow, where attempts might be made to modulate or modify neutrophil precursors so as to limit the destructive potential of the mature neutrophils.

Bone Marrow Cells↗

[Serological screening examinations of atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae) in respiratory tract infection].

Lower respiratory tract infections are a heterogeneous group of disorders induced by plenty of pathogens. Atypical bacteria play an important role in the respiratory tract pathology. In our study 90 patients with acute infection of the respiratory tract were examined in serological screening test for Mycoplasma pneumonia and Chlamydia pneumoniae. It was confirmed that in 21 patients with community acquired pneumonia Mycoplasma pneumonia antibodies were detected in 38% and Chlamydia pneumoniae in 10%. In our opinion this screening serological tests are useful for early diagnosis of atypical bacterial infections of the respiratory tract.

Acute Disease↗

[Reduced natural killer function in children with recurrent respiratory tract infections].

Respiratory infections are the major cause of disease in childhood in the industrialized areas of the world. This essentially depends on two factors: immunological immaturity and immunological naivety. In most cases a virus has been considered the causative agent in respiratory infection. A defect in immune responses has been described in children with recurrent respiratory infections and in particular a decrease in CD4/CD8 T lymphocyte ratio or in IL-2 and IFN-gamma production. Our results show that Natural Killer (NK) cell activity is defective in children with recurrent respiratory infections. That is particularly noteworthy since NK cells play an important role in host defense against viral infections. At present it is difficult to understand whether the NK defect is a primary defect or it is secondary to viral infections. Further studies will help to clarify whether NK decreased activity depends on a cell damage directly caused by virus or it depends on the decreased levels of cytokines.

Adolescent↗

The scope of lower respiratory tract infection.

Lower respiratory tract infections (LRTI) are commonly classified as either bronchitis or pneumonia, and these infections are associated with an extremely high morbidity in the community, as well as a high mortality in those patients that require hospitalisation. Therefore, such infections place a huge burden, both economically and as a user of health services, on the entire health care system. The antibiotic treatment of community-acquired pneumonia caused by gram-negative organisms or staphylococci is controversial, and these organisms may cause one-third of the cases of community-acquired pneumonia. Nosocomial pneumonia is caused even more often by gram-negative bacteria, and as such the development of rational and effective antibiotic therapy to cover these organisms is very important.

Anti-Bacterial Agents↗

Upper respiratory tract infections.

Upper respiratory tract infections are among the most common acute infections in humans. This review discusses the clinically important aspects of the epidemiology, etiology, clinical presentation, diagnosis, management, complications, and prevention of the common cold, pharyngitis, otitis media, and sinusitis. Most episodes of the common cold and pharyngitis are of viral origin, and curative therapy is not available. Streptococcal pharyngitis, acute otitis media, and sinusitis are secondary to bacterial infections, and antibiotic therapy is important.

Anti-Bacterial Agents↗