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Treatment of respiratory tract infections with cephalosporin antibiotics.

Infections of the respiratory tract are among the most common causes for antibiotic prescribing. Their diagnosis within the community is generally limited to clinical criteria, and microbiological information is frequently lacking. Hospitalised patients with respiratory tract infections are more likely to undergo diagnostic sampling, but difficulties remain in reliably defining a microbial aetiology, thereby providing a confident basis for antibiotic selection. In considering the role of the cephalosporins in the treatment of respiratory tract infections, over 500 published articles have been reviewed. The pharmacokinetic considerations are discussed and the limitations of existing methodology are emphasised. Individual agents are reviewed by site of sepsis and conclusions are drawn from both comparative and non-comparative studies and in relation to currently recommended regimens. Although oral cephalosporins are widely used to treat upper respiratory tract infections, none is considered ideal, especially where Haemophilus influenzae is pathogenic. In the case of lower respiratory tract infections the beta-lactamase stable parenteral cephalosporins have become widely used to treat pneumonia in hospitalised patients, especially where Gram-negative enteric bacilli are of aetiological importance. However, the lack of activity of these drugs against Legionella spp., Mycoplasma pneumoniae and Coxiella burnetii must be emphasised. Another area of increasing use is in the treatment of infective exacerbations in patients suffering from cystic fibrosis of the lungs where Pseudomonas aeruginosa is pathogenic; ceftazidime in particular has proved a useful alternative to earlier antipseudomonal penicillin antibiotics.

Animals↗

Gamma interferon-dependent protection of the mouse upper respiratory tract following parenteral immunization with a respiratory syncytial virus G protein fragment.

The protective mechanisms induced in the mouse upper respiratory tract (URT) after intraperitoneal immunization with G2Na, a recombinant respiratory syncytial virus (RSV) G protein fragment (amino acid residues 130 to 230), were investigated. This protection was recently shown to be mediated by CD4(+) T cells and to be critically dependent on the cysteines and amino acids 193 and 194 (H. Plotnicky-Gilquin, A. Robert, L. Chevalet, J.-F. Haeuw, A. Beck, J.-Y. Bonnefoy, C. Brandt, C.-A. Siegrist, T. N. Nguyen, and U. F. Power, J. Virol. 74:3455-3463, 2000). On G2Na, we identified a domain (amino acid residues 182 to 198) responsible for the T-helper-cell activity. This region coincided with a peptide designed AICK (residues 184 to 198) which includes the previously identified murine and human T-helper-cell epitope on the native G protein (P. W. Tebbey, M. Hagen, and G. E. Hancock, J. Exp. Med. 188:1967-1972, 1998). Immunization with AICK, in alum or complete Freund's adjuvant, significantly reduced nasal RSV titers in normal BALB/c mice. However, although lung protection was induced, in contrast to the case with live RSV, neither AICK nor G2Na was able to prevent nasal infection in gamma interferon (IFN-gamma)-knockout mice. Anti-IFN-gamma neutralizing antibodies partially inhibited URT protection after administration to G2Na-immunized BALB/c mice. Furthermore, while purified CD4(+) T cells from BALB/c mice immunized with G2Na or AICK significantly reduced lung and nasal infection of naive recipient mice after adoptive transfer, the cells from IFN-gamma-knockout mice had no effect. Together, these results demonstrated for the first time that the T-helper-cell epitope of RSV G protein induces URT protection in mice after parenteral immunization through a Th1-type, IFN-gamma-dependent mechanism.

Adoptive Transfer↗

Cardiorespiratory patterns occurring in infants during and after recovery from respiratory tract infection.

During and after respiratory tract infections in 29 hospitalized infants, 12 cardiorespiratory measurements were performed on 24-hour recordings of ECG and respiratory activity. These measurements were compared with similar data obtained from 110 age-matched control infants without infection. Respiratory and heart rates during the state of regular breathing were increased during infection, as compared with recordings made after recovery. The numbers of short apneic pauses 3.6 to 6.0 seconds and greater than 6.0 to 12.0 seconds in duration, together with the duration of the overall longest apneic pause per recording, were reduced during infection compared with after recovery. The total durations of periodic breathing and of periodic apnea per recording were also reduced during infection compared with after recovery. These effects were consistent in 27 of the 29 cases, but in two, periodic breathing levels during infection exceeded the 90th percentile in age-matched controls and were reduced after recovery. Measurements made after recovery tended to conform more closely to values in the control infants. None of the 29 infants studied subsequently died or suffered chronic respiratory problems. This study suggests that prolonged apneic pauses or increased numbers of short pauses are not usually a consequence of respiratory tract infection in normal infants.

Apnea↗

A comparative study of the etiology of adult upper and lower respiratory tract infections in the community.

Lower respiratory tract infection and upper respiratory tract infection (URTI) are very common, but the etiology is not diagnosed in routine practice. The objective of this study was to determine and compare the frequency distribution of the various infectious etiologies for these diseases. One hundred seventy five adults in the community with febrile LRTI and 75 with febrile URTI were included in a purely serologically based prospective study. Paired sera were obtained for each of the patients and were tested by EIA or immunofluorescence methods to identify 14 different pathogens. Only a significant change in antibody titers between the paired sera was considered diagnostic. At least one infectious etiology was identified in 167 patients (67%). In the LRTI group, infection with at least one of 7 respiratory viruses was found in 88 patients (50%). One of the atypical pathogens was found in 40 patients (23%), of these Legionella spp. in 19 (11%) and Mycoplasma pneumoniae in 18 (10%). A bacterial etiology was found in 19 patients (11%), of these Streptococcus pneumoniae in 8 (5%) and beta-hemolytic streptococci group A in 5 (3%). The frequency distribution of etiologies in the URTI group was not significantly different from the LRTI group, except for M. pneumoniae that was identified in only one patient with URTI (p = 0.015). More than one etiologic agent was found in 42 (17%) of the patients. LRTI is caused by a broad spectrum of etiologies, with respiratory viruses predominating and a moderate, but significant, prevalence of atypical pathogens. The frequency distribution of etiologies for URTI is similar to LRTI. In a significant proportion of patients with URTI and LRTI there is serologic evidence of infection with more than one pathogen. The justification and benefit of distinguishing between URTI and LRTI in routine clinical work is doubtful. When a decision is reached to treat RTI patients with an antibiotic, it is logical to use a macrolide or tetracycline.

Adult↗

P53 in squamous metaplasia: a marker for risk of respiratory tract carcinoma.

Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of the grade of dysplasia, p53 immunoreactivity, proliferative activity, and Bcl-2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stained nuclei were counted. Normal bronchial epithelium obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43%). The positive predictive values of p53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 80%, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor the mitotic index distinguished patient groups with and without carcinoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.

Adenocarcinoma↗

Lower respiratory tract infections in children.

Lower respiratory tract infections-pneumonia, atypical pneumonia, bronchiolitis, and bronchitis-are responsible for much morbidity and mortality in the pediatric population. On a regular basis, pediatricians clinically diagnose these conditions and must make decisions regarding evaluation and treatment. The focus of this update is on new developments in the past year in the areas of epidemiology, etiology, diagnosis, treatment, and prevention of lower respiratory tract infections.

Child↗

Immunohistochemical p53 expression patterns in sarcomatoid carcinomas of the upper respiratory tract.

Sarcomatoid carcinoma of the upper respiratory tract is a phenotypically complex neoplasm that has triggered much thoughtful discussion regarding histogenic origin and morphologic classification. In particular, its putative epithelial lineage and distinction from a pseudosarcomatous reaction are sometimes questioned. Little is known about the genetic alterations underlying sarcomatoid carcinoma. Although about 45% of conventional squamous cell carcinomas of the upper respiratory tract harbor p53 mutations, the p53 status of sarcomatoid carcinomas is not well established. p53 immunohistochemical analysis using the monoclonal antibody D07 was performed on 23 sarcomatoid carcinomas of the upper respiratory tract. Twenty tumors were biphasic, having dual epithelial and spindled components. In four of these biphasic tumors, the epithelial and spindled components were separately analyzed for p53 gene mutations by sequence analysis. p53 immunohistochemistry was also performed on 19 cases of postradiation stromal atypia. Strong and diffuse p53 staining was detected in 18 (78%) of the 23 sarcomatoid carcinomas. When the spindled component was compared with its corresponding epithelial component, identical patterns of p53 protein expression were noted in 19 (95%) of the 20 biphasic tumors. Weak p53 staining was observed in one (5%) of the 19 cases of postradiation stromal atypia. In the four biphasic tumors evaluated by DNA sequence analysis, p53 status was always the same in the paired epithelial and spindle cell components. These findings help further dispel the notion that sarcomatoid carcinoma represents a reactive spindle cell proliferation (pseudosarcoma) or a collision between a carcinoma and a sarcoma (collision tumor). Instead, the epithelial and spindled components share a common pathway of tumorigenesis despite their conspicuous divergence at the phenotypic level.

Adult↗

Recurrent respiratory tract infections in paediatric patients.

Paediatric respiratory tract infections are one of the most common reasons for physician visits and hospitalisation, and are associated with significant morbidity and mortality. The role of physicians and other healthcare professionals has expanded from merely treating disease to implementing measures aimed at health maintenance and disease prevention. Therefore, children with recurrent respiratory tract infections represent a great challenge for the paediatrician, from both therapeutic and preventive standpoints. The paediatrician must first determine whether these recurrent infections are because of host-derived factors or are the result of increased environmental exposure. Host-derived factors may be nonimmunological or related to host immunodeficiency. The leading cause of recurrent respiratory tract infections throughout the world is increased environmental exposure in children attending nursery school or daycare centres. Acute otitis media in children is of particular concern because of its high incidence, frequent recurrence, and serious long term sequelae, e.g. hearing loss. The socioeconomic impact of these recurrent infections is staggering, and there remains much scope for devising methods for their treatment and prevention. Recent approaches have included the encouragement of breastfeeding, the use of intravenous immunoglobulin and respiratory syncytical virus immune globulin, as well as methods of stimulating immunity, such as ribosomal immunotherapy.

Child Day Care Centers↗

Risk factors for severe respiratory syncytial virus-associated lower respiratory tract infection in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract infection that can be a life-threatening disease in infants and children. This study was conducted to look for independent risk factors for severe respiratory syncytial virus-associated lower respiratory tract infection (RSV-LRI) that required oxygen supplementation or mechanical ventilation. METHODS: Medical records of patients younger than 4 years hospitalized with RSV-LRI at Shizuoka Red Cross Hospital from July 1, 1995 to June 30, 1999 were reviewed. The patients were compared using univariate and multivariate logistic regression analysis. RESULTS: A total of 157 patients were hospitalized with RSV-LRI at Shizuoka Red Cross Hospital from the study time period. Of these, 20 patients (12.7%) were diagnosed with severe RSV-LRI. Subjects younger than 3 months of age had an odds ratio (OR) of 59.9 (95% confidence interval (CI) 14.7_244.0) for the dependent variable of severe RSV-LRI (P<0.0001). Subjects with a history of congenital heart disease also had an OR of 99.2 (95% C1 8.5-1160.1) (P<0.0005). CONCLUSIONS: Infants younger than 3 months without any underlying diseases may be at high risk for severe RSV-LRI. Respiratory syncytial virus prophylaxis is needed not only for high-risk patients, but for healthy early infants.

Age Factors↗

Antibiotic treatment of common bacterial respiratory tract infection in general practice.

Respiratory tract infections, particularly in children, are some of the most common conditions seen in general practice. It would seem reasonable, therefore, that these conditions would be treated well. However, analysis of the figures taken from the Australian Morbidity Survey conducted by The Royal Australian College of General Practitioners shows that whilst most general practitioners use antibiotics satisfactorily, there are a few occasions in which it is fairly obvious that there is a lack of knowledge of the action of a particular antibiotic against a specific organism. This article is not intended to be a treatise on the microbiology of different respiratory tract infections and antibiotic use, but it is intended to be a guide to the treatment of common respiratory infections as seen in general practice.

Anti-Bacterial Agents↗

[Respiratory tract hemorrhage].

Bleeding from the respiratory tract can be met in everyday clinical practice. The number of patients with bleeding is not small, which implies that every physician should have adequate knowledge in order to react promptly, when needed. We have underlined the causes and the accessory factors which promote bleeding, localization--upper and lower respiratory tract, diagnostic methods which are available, prevention and treatment of bleeding.

Hemorrhage↗

The effect of inhaled steroids on the upper respiratory tract.

The incidence of upper respiratory tract Candidiasis secondary to steroid aerosol treatment is disputed, and varies from series to series. We found a very low incidence of thrush, but a significant number of abnormalities of the upper respiratory tract in a random selection of asthmatics on steroid inhaler. A minority had positive Candida cultures, but 37 per cent had symptoms which were minor and self-limiting, but a complaint of hoarseness in asthmatics on steroid inhalers should be referred to a laryngologist, even if there is no evidence of fungal infection in order to ascertain the nature of the laryngeal abnormality, such as adductor cord paralysis, or even carcinoma. This study also implies that the history from a patient with laryngeal or pharyngeal symptoms is incomplete unless the patient's aerosol medication is also taken into account, as signs and symptoms in this group of patients are usually reversible when alternative treatment for asthma is instituted.

Adolescent↗

Azithromycin for acute lower respiratory tract infections.

BACKGROUND: The spectrum of acute lower respiratory tract infection ranges from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Annually approximately five million people die of acute respiratory tract infections. Among these, pneumonia represents the most frequent cause of mortality, hospitalization and medical consultation. Azithromycin is a new macrolide antibiotic, structurally modified from erythromycin and is noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae). OBJECTIVES: To compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to January Week 3, 2004), and EMBASE (January 1988 to 2003). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials, which compared azithromycin to amoxycillin or amoxycillin/clavulanic acid in patients with clinical evidence of acute LRTI: acute bronchitis, pneumonia, and acute exacerbation of chronic bronchitis were studied. DATA COLLECTION AND ANALYSIS: The criteria for assessing study quality were generation of allocation sequence, concealment of treatment allocation, blinding, and completeness of the trial. All types of acute lower respiratory tract infections were initially pooled in the meta-analyses. Funnel plot was used to examine publication bias. The heterogeneity of results was investigated by the forest plot and Chi-square test. Index of I(2) was also used to measure inconsistency results among trials. Subgroup analysis was conducted for age, types of respiratory tract infection and types of antibiotic in control groups. Sensitivity analysis was conducted under the condition of trial size and concealment of treatment allocation. MAIN RESULTS: Fourteen trials with 2,521 enrolled patients used 2,416 patients in the analysis. A total of 1,350 patients received azithromycin and 1,066 received amoxicillin or amoxicillin-clavulanic acid. The pooled analysis of all trials showed that there was no significant difference in the incidence of clinical failure on about day 10 to 14 after therapy started between the two groups (relative risk (RR) (random effects) 0.96; 95% CI 0.58 to 1.57). Sensitivity analysis showed that a reduction of clinical failure in azithromycin-treated patients (RR 0.52; 95% CI 0.24 to 1.12) in three adequately concealed studies, compared to RR 1.14 (95% CI 0.62 to 2.08) in eleven studies with inadequate concealment. Eleven trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.98; 95% CI 0.91 to 1.07). The reduction of adverse events in azithromycin group was RR 0.75 (95% CI 0.56 to 1.00). REVIEWERS' CONCLUSIONS: There is unclear evidence that azithromycin is superior to amoxicillin or amoxicillin-clavulanic acid in treating acute LRTI. Future trials with high methodological quality are needed.

Acute Disease↗

The upper and lower respiratory tracts differ in their requirement of IFN-gamma and IL-4 in controlling respiratory mycoplasma infection and disease.

The purpose of this study is to evaluate the significance of IFN-gamma and IL-4 production in controlling mycoplasma infection and the pathogenesis of disease in the upper and lower respiratory tract. By using IFN-gamma knockout and IL-4 knockout BALB/c mice, we were able to study the contribution of these cytokines in the development of pathogenesis and/or protection in response to mycoplasma respiratory infection, in both the upper and lower respiratory tracts. The loss of either IFN-gamma or IL-4 does not affect disease pathogenesis or mycoplasma organism numbers in the upper respiratory tract. However, in the absence of IL-4, the nasal passages developed a compensatory immune response, characterized by higher numbers of macrophages and CD8(+) T cells, which may be masking detrimental effects due to IL-4 deficiency. This is in contrast to the lower respiratory tract, where the loss of IFN-gamma, but not IL-4, leads to higher mycoplasma numbers and increased disease severity. The loss of IFN-gamma impacted the innate immune system's ability to effectively clear mycoplasma, as the number of organisms was higher by day 3 postinfection. This higher organism burden most likely impacted disease pathogenesis; however, the development of Th2 cell-mediated adaptive immune response most likely contributed to lesion severity at later time points during infection. Our studies demonstrate that the upper and lower respiratory tracts are separate and distinct in their cytokine requirements for generating immunity against mycoplasma infection.

Animals↗

Microbiology of common infections in the upper respiratory tract.

The management of upper respiratory tract infections has become more difficult because of the recent increase in the number of penicillin-resistant organisms. The bacteria that predominate in otitis media and sinusitis can resist penicillin through the production of the enzyme beta-lactamase (Haemophilus influenzae and Moraxella catarrhalis in acute infections and Staphylococcus aureus and Prevotella and Fusobacteria spp in chronic infections) or through changes in penicillin-binding sites (Streptococcus pneumoniae). beta-lactamase-producing bacteria can express their pathogenicity directly through their ability to cause infections and indirectly by production of the enzyme, thus protecting penicillin-susceptible pathogens from penicillins. This phenomenon may explain penicillin's failure in the treatment of Group A beta-hemolytic streptococcal (GABHS) tonsillitis. An additional cause for penicillin failure is the absence among the normal tonsillar bacterial flora of streptococcal species that are capable of interfering with the growth of GABHS. Proper use of antimicrobial therapy, including those therapies that are effective against penicillin-resistant bacteria, is the cornerstone of management of upper respiratory tract infections.

Adult↗

[Treatment of upper respiratory tract infections].

Today most upper respiratory tract infections are mild and of short duration with minor risk of complications. Hence, the effects of antibiotic treatment are marginal. The only and most important reason for treatment is to stop dissemination. Penicillin V should be the first drug of choice. A review of the literature about antibiotic treatment of upper respiratory tract infections shows that most published studies exclude two categories of patients: children below the age of 6 months and patients who are severely ill. Therefore, there is an additional need for further studies focused on select groups of patients to investigate the benefit, if any, of antibiotic treatment as well as to study the effect of introducing near-patient-tests and the use of extended microbiological service in daily clinical practice.

Anti-Bacterial Agents↗

Incidence of respiratory syncytial virus infection in infants and young children referred to the emergency departments for lower respiratory tract diseases in Italy.

BACKGROUND: Respiratory Syncytial Virus (RSV) is the leading cause of emergency visits and hospitalization for acute lower respiratory tract infections (LRTI) in infants and young children worldwide. To collect specific epidemiological data on the incidence of RSV infection among infants referred to Emergency Departments (ED) for LRTI in a Mediterranean country, an Italian multicenter epidemiological surveillance program was established. METHODS: Eight pediatric centers throughout Italy participated in this study. The study population included 272 children < or =4 years of age, admitted to the ED between October 2000 and April 2001 for respiratory problems that might be possibly related to LRTI. 152 children were <1 year of age, 50 between 1 and 2 years, and 70 >2 years of age. Data regarding medical history and physical examination were recorded for each child, whereas an immunoenzymatic RSV test (TestPack RSV, Abbott) was performed on nasal and pharyngeal secretions. RESULTS: Out of 272 tested children, 85 were positive for RSV. The peak of the RSV epidemic occurred in February, with an earlier start and end of the RSV season in the northern and central regions, compared to the southern regions. Major risk factors for RSV infection were younger age (p<0.05) and low weight at birth (p<0.05). Among children positive for RSV infection, 55.2% were <1 year of age, 18.3% were between 1 and 2 years, and 25.7% were > 2 years of age. RSV positivity was associated with a higher rate of hospitalization in the whole study population (p<0.01) and especially in the children < or =12 months of age (p<0.01). Clinical evidence of lower respiratory tract involvement, was also more frequently observed in RSV positive than in RSV negative children, both in the whole study population (p<0.01) and in the < or =12 months of age subgroup (p<0.01). CONCLUSION: These data confirm that the patterns of RSV infection in Italy are similar to those reported for other countries in the northern hemisphere: RSV is associated with a higher risk of hospitalization and clinically evident LRTI involvement than respiratory infections of other etiologies, especially in infants.

Child, Preschool↗

Detection of Simkania negevensis by culture, PCR, and serology in respiratory tract infection in Cornwall, UK.

Respiratory tract infections are often treated empirically without investigation to detect the aetiological agent, which may be a virus or a bacterium, including atypical pathogens such as Chlamydophila pneumoniae or Mycoplasma pneumoniae. Recently, several types Chlamydia-like intracellular bacteria have been detected in environmental samples and clinical specimens. Little is known of their geographical distribution and potential pathogenicity. We describe the detection, by PCR and isolation in cell culture, of Simkania negevensis in nasopharyngeal aspirates of paediatric patients with bronchiolitis in Cornwall, UK. We also present serological evidence of exposure to the organism in 62% of adult patients and 46% of a sample of pregnant women. Empirical treatment of serious respiratory tract infection should consider the possible contribution of these organisms.

Adolescent↗