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The emergence of resistant pneumococcus as a pathogen in childhood upper respiratory tract infections.

Streptococcus pneumoniae continues to be the most common organism causing acute otitis media and sinusitis in infants and children and remains an important bacterial cause of pneumonia, septic arthritis, and bacterial meningitis in the pediatric age group. The definition, incidence, and mechanisms for penicillin resistance in pneumococcus are reviewed here. Physicians caring for children should know and understand these important concepts. At present, for most respiratory infections in children penicillin-resistant pneumococcus does not represent a clinical dilemma as far as regarding alteration of empiric antibiotic therapy. However, as this problem continues to grow, especially for patients with recurrent otitis media or sinusitis, physicians will be facing upper respiratory infections that are more commonly caused by these isolates and the antibiotic management of infections in the respiratory tract caused by penicillin and other antibiotic-resistant pneumococcal isolates will require modification.

Child↗

Principles of appropriate antibiotic use for treatment of acute respiratory tract infections in adults: background, specific aims, and methods.

The need to decrease excess antibiotic use in ambulatory practice has been fueled by the epidemic increase in antibiotic-resistant Streptococcus pneumoniae. The majority of antibiotics prescribed to adults in ambulatory practice in the United States are for acute sinusitis, acute pharyngitis, acute bronchitis, and nonspecific upper respiratory tract infections (including the common cold). For each of these conditions-especially colds, nonspecific upper respiratory tract infections, and acute bronchitis (for which routine antibiotic treatment is not recommended)-a large proportion of the antibiotics prescribed are unlikely to provide clinical benefit to patients. Because decreasing community use of antibiotics is an important strategy for combating the increase in community-acquired antibiotic-resistant infections, the Centers for Disease Control and Prevention convened a panel of physicians representing the disciplines of internal medicine, family medicine, emergency medicine, and infectious diseases to develop a series of "Principles of Appropriate Antibiotic Use for Treatment of Acute Respiratory Tract Infections in Adults." These principles provide evidence-based recommendations for evaluation and treatment of adults with acute respiratory illnesses.This paper describes the background and specific aims of and methods used to develop these principles. The goal of the principles is to provide clinicians with practical strategies for limiting antibiotic use to the patients who are most likely to benefit from it. These principles should be used in conjunction with effective patient educational campaigns and enhancements to the health care delivery system that facilitate nonantibiotic treatment of the conditions in question.

Acute Disease↗

Initial antibiotic therapy for lower respiratory tract infection in the community: a European survey.

A survey of first-line antibiotic prescription in community-acquired lower respiratory tract infection (LRTI) by general practitioners (GP) was carried out simultaneously, using the same methodology in France, Germany, Italy, Spain and the UK. Data were obtained from 2,056 patients and 605 GPs. There was no antibiotic prescription in 17% of all LRTIs and 13% of community-acquired pneumonia (CAP) in the five countries taken together; and in 32% of all LRTIs and in 23% of CAP in Germany. Of patients with acute bronchitis, exacerbation of chronic bronchitis and viral lower respiratory tract infection, 87, 92 and 71% received antibiotics, respectively. The most frequent prescriptions were penicillins in France and the UK, third-generation cephalosporin in Italy, tetracycline in Germany and macrolide in Spain. The daily dosage of aminopenicillin prescribed was: 41% <1.5 g; 49% > or = 1.5 g and <3 g; and 10% > or = 3 g. In Italy, 53% of all antibiotics were injected in all LRTIs, and 71% in CAP; in contrast, antibiotic injection was lower than 2% both in the UK and Germany, with an average of 14% in the five countries combined. We conclude that there are variations in antibiotic prescription by GPs in Western Europe; differences are likely to be multifactorial, but could, in part, be explained by differences in health systems and sources of information available to GPs.

Adult↗

Guide to selection of fluoroquinolones in patients with lower respiratory tract infections.

Newer fluoroquinolones such as levofloxacin, moxifloxacin, gatifloxacin and gemifloxacin have several attributes that make them excellent choices for the therapy of lower respiratory tract infections. In particular, they have excellent intrinsic activity against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and the atypical respiratory pathogens. Fluoroquinolones may be used as monotherapy to treat high-risk patients with acute exacerbation of chronic bronchitis, and for patients with community-acquired pneumonia requiring hospitalisation, but not admission to intensive care. Overall, the newer fluoroquinolones often achieve clinical cure rates in > or =90% of these patients. However, rates may be lower in hospital-acquired pneumonia, and this infection should be treated on the basis of anticipated organisms and evaluation of risk factors for specific pathogens such as Pseudomonas aeruginosa. In this setting, an antipseudomonal fluoroquinolone may be used in combination with an antipseudomonalbeta-lactam. Concerns are now being raised about the widespread use, and possibly misuse, of fluoroquinolones and the emergence of resistance among S. pneumoniae, Enterobacteriaceae and P. aeruginosa. A number of pharmacokinetic parameters such as the peak concentration of the antibacterial after a dose (C(max)), and the 24-hour area under the concentration-time curve (AUC24) and their relationship to pharmacodynamic parameters such as the minimum inhibitory and the mutant prevention concentrations (MIC and MPC, respectively) have been proposed to predict the effect of fluoroquinolones on bacterial killing and the emergence of resistance. Higher C(max)/MIC or AUC24/MIC and C(max)/MPC or AUC24/MPC ratios, either as a result of dose administration or the susceptibility of the organism, may lead to a better clinical outcome and decrease the emergence of resistance, respectively. Pharmacokinetic profiles that are optimised to target low-level resistant minor subpopulations of bacteria that often exist in infections may help preserve fluoroquinolones as a class. To this end, optimising the AUC24/MPC or C(max)/MPC ratios is important, particularly against S. pneumoniae, in the setting of lower respiratory tract infections. Agents such as moxifloxacin and gemifloxacin with high ratios against this organism are preferred, and agents such as ciprofloxacin with low ratios should be avoided. For agents such as levofloxacin and gatifloxacin, with intermediate ratios against S. pneumoniae, it may be worthwhile considering alternative dose administration strategies, such as using higher dosages, to eradicate low-level resistant variants. This must, of course, be balanced against the potential of toxicity. Innovative approaches to the use of fluoroquinolones are worth testing in further in vitro experiments as well as in clinical trials.

Anti-Infective Agents↗

[Report of experiences with the oral cephalosporin-derivative cephaclor in respiratory tract infections].

The oral cephalosporin derivative Cefaclor was administered to 22 patients with respiratory tract infections at a daily dosage of 3 x 500 mg. The average duration of the Cefaclor therapy was 10 days. In all patients improvement of the clinical picture and of objective criteria, such as fever, cough and sputum was observed. It was not possible to objectivate side effects by laboratory parameters. Gastrointestinal disturbances and allergic symptoms were only present in individual cases but did not significantly influence the clinical efficacy of Cefaclor.

Administration, Oral↗

[The pharmacokinetics of 1,000 mg erythromycin lactobionate i. v. in patients with respiratory tract infections (author's transl)].

Pharmacokinetic data were determined in 16 patients with respiratory tract infections who had received 1,000 mg erythromycin lactobionate i. v. The infusion lasted 60 or 30 minutes. The peak concentrations were 33.3 mg/l (60 min group) and 34.4 mg/l (30 min group). The elimination half-lives were 2.0 h and 1.9 h. The concentrations are considerably higher than those found following the peroral administration of erythromycin. We did not find a cumulative effect after four administrations at 12-hour intervals. The clinical efficacy was good.

Administration, Oral↗

Antibiotics for upper respiratory tract infections. Follow-up utilization and antibiotic use.

OBJECTIVES: To examine the effects of antibiotic prescribing during an initial visit for viral respiratory tract infections on future care seeking and the cost of care. MATERIALS AND METHODS: Retrospective analysis of recorded visits for viral respiratory tract infections (N = 49,862) between January 1, 1995, and December 31, 1997, to practices in a large network of affiliated practices that use the same electronic medical record. RESULTS: Patients receiving antibiotics at the initial visit were less likely to return for a second visit, but this difference was small (15.4% vs 17.4%, P < .001). When returning for the second visit, those who received an antibiotic on the initial visit were prescribed more expensive antibiotics than those who had not received an antibiotic on the initial consultation. Overall, cost from initial antibiotic use outweighed any benefit from reduced utilization in adults and children. CONCLUSIONS: Antibiotic prescribing at an initial contact for a viral respiratory tract illness may reduce the likelihood that an individual will return for a subsequent visit, but adds substantial costs to care for the initial antibiotic and for more expensive antibiotics used on subsequent visits.

Adolescent↗

Cefpodoxime - utility in respiratory tract infections and typhoid fever.

Cefpodoxime is a oral third generation cephalosporin active against most of gram positive and gram negative bacteria except Pseudomonas, B. fragilis and Entrococcous. Clinical studies have confirmed efficacy of cefpodoxime in acute otitis media, sinusitis and tosillopharyngitis. Twice daily administration and safety profile increases compliance and decreases failure rate. It has a role as switch over therapy from intravenous ceftriaxone in serious respiratory tract infections (RTIs). In areas where common respiratory pathogens show decreased sensitivity to penicillins and macrolides cefpodoxime can be used as empirical first line therapy in respiratory tract infections. It seems to be a promising molecule in pediatric typhoid fever because of its excellent activity against Salmonella species but clinical trials are limited.

Administration, Oral↗

Levels of gamma interferon and interleukin-4 are inversely related to the levels of their corresponding autoantibodies in patients with lower respiratory tract infection.

To study the involvement of cytokines and their corresponding autoantibodies (Aabs) in inflammatory mechanisms in patients with lower respiratory tract infections, blood samples were taken from patients at the time of admission to the hospital and before treatment. Cell-released capturing enzyme-linked immunosorbent assay was used to measure the levels of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) produced spontaneously by peripheral mononuclear cells (PMNC). ELISA was used to measure Aabs to these cytokines in sera. The levels of both cytokines were inversely related to the levels of their corresponding Aabs. While a high level of IFN-gamma was observed together with a low level of anti-IFN-gamma Aab, decreased IL-4 levels were observed with increased levels of Aabs to IL-4. Immunoglobulins were purified, digested to obtain Fab fragments, and tested for specificity and cross-reactivity. The Aabs and their Fab fragments were tested in cytokine biological assays and showed neutralizing effects. Our data demonstrated increased levels of the proinflammatory cytokine IFN-gamma and decreased release of the anti-inflammatory cytokine IL-4 during early presentation of lower respiratory tract infection. The levels of these cytokines were inversely related to the levels of their corresponding Aabs that exhibited regulatory effects on the cytokine biological function in vitro.

Adult↗

Rapid identification of nine microorganisms causing acute respiratory tract infections by single-tube multiplex reverse transcription-PCR: feasibility study.

Acute respiratory tract infections (ARIs) are leading causes of morbidity and, in developing countries, mortality in children. A multiplex reverse transcription-PCR (RT-PCR) assay was developed to allow in one test the detection of nine different microorganisms (enterovirus, influenza A and B viruses, respiratory syncytial virus [RSV], parainfluenzaviruses type 1 and type 3, adenovirus, Mycoplasma pneumoniae, and Chlamydia pneumoniae) that do not usually colonize the respiratory tracts of humans but, if present, must be assumed to be the cause of respiratory disease. Clinical samples from 1,118 children admitted to the Department of Pediatrics because of an ARI between November 1995 and April 1998 were used for a first clinical evaluation. Detection of one of the microorganisms included in the assay was achieved for 395 of 1,118 (35%) clinical samples, of which 37.5% were RSV, 20% were influenza A virus, 12.9% were adenovirus, 10.6% were enterovirus, 8.1% were M. pneumoniae, 4.3% were parainfluenzavirus type 3, 3.5% were parainfluenzavirus type 1, 2.8% were influenza B virus, and 0.2% were C. pneumoniae. Seasonal variations in the rates of detection of the different organisms were observed, as was expected from the literature. The levels of concordance with the data obtained by commercially available enzyme immunoassays were 95% for RSV and 98% for influenza A. The results show that the multiplex RT-PCR-enzyme-linked immunosorbent assay is a useful and rapid diagnostic tool for the management of children with ARI. Studies of the overall benefit of this method with regard to the use of antibiotics, the use of diagnostic procedures including additional microbiological tests, and hospitalization rate and duration are warranted.

Acute Disease↗

Prevention of recurrent respiratory tract infections in children using a ribosomal immunotherapeutic agent: a clinical review.

Recurrent respiratory tract infections (RRTIs) in children constitute a serious problem worldwide. Some children experience considerable morbidity as a result of RRTIs and receive repeated courses of antibacterials that are not effective against viral infectious agents and can increase bacterial resistance. Furthermore, the direct and indirect costs of RRTIs to the community are substantial. In this article, we review the available clinical evidence relating to use of the bacterial immunostimulant Ribomunyl for the prevention of RRTIs in children. The product is composed of ribosomal fractions from four bacteria involved in RRTIs as well as a membrane fraction from one of these bacteria (Klebsiella pneumoniae). Ribomunyl stimulates production of specific humoral and secretory antibodies against the four bacterial strains included in the compound. The product also stimulates non-specific immunity. Thus, Ribomunyl stimulates both the innate and acquired immune systems and offers preventive efficacy against both bacterial and viral infections. To perform this review, we searched the MEDLINE database for articles on Ribomunyl and then included only those publications that described placebo-controlled studies, complied with Good Clinical Practice standards, used the product in official registered indications, and administered it at the recommended dosages. In this way, we were able to generate a comprehensive profile of use of the product and draw valid conclusions about its clinical role. In clinical trials of children, Ribomunyl reduced the number of upper or lower RRTIs, the primary outcome measures. Other favorable results relating to efficacy parameters that served as secondary outcome measures in these studies included a reduction in antibacterial treatments, shorter duration of recurrent episodes, reduced need for other medications such as expectorants, smaller number of lost school days or parent absenteeism from work, less fever, and reduced hearing loss. Studies focusing on particular conditions, such as otitis media, or those that included specific patient groups, such as very young children, reported similar findings. Adverse events occurred very rarely and were mild. Their frequency was similar to that reported in placebo groups, and consisted mostly of fever, otorhinolaryngologic symptoms, and cutaneous events. In conclusion, this review clearly demonstrated that Ribomunyl is effective in preventing upper and lower RRTIs in children. Ribomunyl provided a reduction in the number, duration, and severity of infectious episodes and, thereby, reduced antibacterial use and the likelihood of consequent development of bacterial resistance. Ribomunyl also decreased absence from work or school, which has important economic consequences.

Adjuvants, Immunologic↗

Meta-analysis on the association between environmental tobacco smoke (ETS) exposure and the prevalence of lower respiratory tract infection in early childhood.

The aim of this study was to obtain quantitative information from published data on the association between environmental tobacco smoke (ETS) exposure and the prevalence of serious lower respiratory tract infections (LRTI) in infancy and early childhood. We identified 21 relevant publications on the relation between ETS and the prevalence of serious LRTI by reviewing reference lists in relevant reports and by conducting manual and computer searches (Medline database; Dissertation abstracts index of Xerox University Microfilms) of published reports between 1966 and 1995. Thirteen studies were included in a quantitative overview using random effects modeling to derive pooled odds ratios. Sensitivity analyses were conducted to test the decision rules used in extracting odds ratio data. The results of community and hospital studies are broadly consistent and show that the child of a parent who smokes is at approximately twice the risk of having a serious respiratory tract infection in early life that requires hospitalization. This association was pronounced in children younger than age two and diminished after the age of two. The combined odds ratio for hospitalization for lower respiratory tract infections in infancy or early childhood is 1.93 (95% CI 1.66-2.25); the combined odds ratio of prevalence of serious LRTI at age less than 2 years, between 0 and 6 years, and between 3 and 6 years were 1.71 (95% CI 1.33-2.20); 1.57 (1.28-1.91), and 1.25 (0.88-1.78), respectively. There was no evidence of heterogeneity across the studies in these combined odds ratios. We conclude that this meta-analysis provides strong evidence that exposure to ETS causes adverse respiratory health outcomes such as either a serious LRTI or hospitalization for LRTI. New public health campaigns are urgently needed to discourage smoking in the presence of young children.

Age Distribution↗

[A clinical study on lomefloxacin to find appropriate dose levels in the treatment of respiratory tract infections].

A comparative clinical study of lomefloxacin hydrochloride (LFLX) was performed to confirm the optimal dose of LFLX for treatment of respiratory tract infections. Daily dosages of LFLX, 400 mg (200 mg b.i.d.) and 600 mg (200 mg t.i.d.) were allocated by the randomization method. Treatment period was 7-14 days. Of a total of 136 cases, 14 cases were excluded from evaluation of clinical efficacy and 4 cases from evaluation of safety. There were no differences in the background factors of the patients between the 2 dosage groups. The clinical efficacy rates, judged by a committee, were 76.4% (42/55) for the 400 mg group and 74.6% (50/67) for the 600 mg group. No significant difference was observed between the 2 groups (P = 1.000). Incidences of adverse effects were 1.6% (1/64) for the 400 mg group and 2.9% (2/68) for the 600 mg group. Incidences of abnormal laboratory test values were 3.4% (2/58) for the 400 mg group and 1.6% (1/63) for the 600 mg group. No significant differences were found between the 2 groups. These adverse effects and abnormal laboratory test values improved with the cessation of the administration of the drug. From these results, a dose of 400 mg (200 mg b.i.d.) LFLX seems to be better than that of 600 mg (200 mg t.i.d.) LFLX in the treatment of respiratory tract infections.

Adolescent↗

[Clinical research on repeated infantile respiratory tract infection treated by fang-gan mixture].

131 cases of repeated infantile respiratory tract infection were selected and divided into 3 groups: fang-gan mixture (FGM) group, levamisole group, and the control group. The results showed that the total effective rate of FGM was 97.7%, which was more effective than the levamisole group. Its effective rate still reached 90.9% after 1 month of stopping treatment, and compared with the treatment period, there were no significant differences (P greater than 0.05). There were three parts of changes on clinical manifestation after patients using FGM: (1) The occurrence times reduced obviously; (2) the course of disease shortened obviously; (3) syndrome of patients relieved obviously. FGM was also more effective than the levamisole group in relieving symptoms and signs (P less than 0.05). Both the FGM and the levamisole groups could increase the body immunity function. After treatment both of salivary sIgA and PHA skin test were higher than before treatment (P less than 0.05).

Adolescent↗

[Antibiotics in lower respiratory tract infection].

THE AIM OF THE STUDY: Comparison of clinical outcome of lower respiratory tract infections in small children treated or not treated with antibiotics. MATERIAL AND METHODS: Eighty seven children aged from 2 months to 5 years admitted to hospital with mild to moderate bronchitis and/or pneumonia were randomly allocated to one of two groups: group A children were treated with antibiotics and group B patients were not. The children remained under close clinical observation. The clinical outcome was considered good if symptoms of the disease decreased after 72 hours. In case of no clinical improvement or worsening, the children from group B received antibiotics and in children from group A antibiotic therapy was changed. RESULTS AND CONCLUSIONS: There were no significant differences between the two groups in the course of the disease, the frequency of pulmonary complications and recurrence during one month of follow-up.

Administration, Oral↗

Why do family doctors prescribe antibiotics for upper respiratory tract infection?

The prescribing behaviour of family doctors in Hong Kong towards upper respiratory tract infections (URTIs), and the major clinical factors that might affect such behaviour, were studied. Members of the Hong Kong College of Family Physicians were surveyed; 801 completed the questionnaire with an overall response rate of 65%. Purulent nasal discharge, purulent sputum, persistent fever over three days, patients looking unwell, exudates on throat, inflamed eardrums and cervical lymphadenopathy made more than half the respondents 'likely' or 'very likely' to prescribe antibiotics. Those in private practice and those who graduated in Hong Kong were more likely to prescribe antibiotics, while fellows of the College were less likely to do so. Vocational training and higher qualifications in family medicine/general practice, however, revealed minimal effect. Our results showed that many doctors are still prescribing antibiotics when they encounter URTI patients presenting with clinical factors that have been proven to have no or little benefit from antibiotics.

Adult↗

[Therapeutic efficacy of imipenem/cilastatin sodium on respiratory tract infections in lung cancer patients].

Imipenem/cilastatin sodium (IPM/CS) was used to treat respiratory tract infections (RTI) in 54 patients with lung cancer. Out of the 54 patients studied, 53 were evaluable for the utility of IPM/CS; 42 had pneumonia, 9 had obstructive pneumonia, 1 had a lung abscess and 1 had acute bronchitis. The efficacy rate was 71.7%. Seventeen causative organisms were isolated from 14 patients. They included Staphylococcus aureus 5 strains, Staphylococcus epidermidis 4 strains, Staphylococcus sp. 2 strains, Enterococcus faecalis 1 strain, Pseudomonas aeruginosa 2 strains, Pseudomonas fluorescens 2 strains, Acinetobacter sp. 1 strain, and the eradication rate was 81.8%. Clinical adverse effects (nausea and vomiting) were observed in 1 patient. Abnormalities in laboratory test results were observed in 3 patients. They disappeared or returned to normal values after completion of therapy or discontinuation of IPM/CS administration. IPM/CS appears to be a useful antibiotic for RTI in patients with lung cancer.

Adenocarcinoma↗

Acute respiratory tract infections in children. A three-year follow-up from birth.

Respiratory tract infections (RTIs) in small children account for a considerable proportion of health care expenditure. In 113 children, followed for the first three years of life, we studied the frequency of acute RTI and its relationship to the factors: type of day-care, age, sex, family size, living conditions, allergic predisposition, family smoking habits, and season. To elucidate the influence of age, the frequency of acute RTI and its relationship to type of day-care was longitudinally studied on a quarterly basis. The frequency of acute RTI diagnosis increased gradually from birth culminating in a peak at the beginning of the second year. Besides age and season, type of day-care was the only factor studied to show any relationship with the frequency of acute RTI diagnosis. Up to the age of almost 2 1/2 years, children attending day-care centres accounted for more RTI diagnoses than did those in home care or family day-care, categories with comparable frequencies.

Acute Disease↗