Use of fluoroquinolones in lower respiratory tract infections (LRTI)

In view of their antimicrobial activity and pharmacological properties, fluoroquinolens should be suitable for the treatment of lower respiratory tract infections - specially of Gram-negative bacterial etiology. These drugs have been studied extensively in animal models of respiratory tract infections and found to be as efficacious as the comparative drugs - mostly modern betalactam antibiotics. In patients, a number of well-controlled randomized studies in lower respiratory tract infections (LRT) have been published comparing standard treatments (aminopenicillins, tetracyclines, etc.) with new fluoroquinolones. In general, the rates of cure and improvement ranged between 82% and 89% for enoxacin, ciprofloxacin, ofloxacin and pefloxacin. Fleroxacin has been studied in three clinical studied in the treatment of LRTI. It showed the same efficacy as the comparators (amoxicillin, ceftazidine) in the treatment of Gram-negative LRTI; tolerance data in these studies showed higher incidence of adverse events in the fleroxacin group versus the amoxicillin group and similar incidence of adverse events in the fleroxacin group versus the ceftazidine group. The numbers of premature treatment-withdrawal were low and not significantly different.     

老年人下呼吸道细菌感染对抗生素敏感性的监控

目的：探讨老年人下呼吸道感染致病菌株对抗生素的敏感性及产β－内酰胺酶的情况。方法：采用微量肉汤稀释法及纸片法测定了54株致病菌对20种抗生素的敏感性，并进行了β－内酰胺酶的研究。结果：G^ 菌14株（26％），以凝固酶阴性葡萄球菌为主，以万古霉素、利福平为最敏感。G^-菌40株（74％），克雷白菌属多见，亚胺硫霉素、阿米卡星、头孢他啶的抗菌活性最强，覆盖率广。结论：产酶20株（39％），主要分布在葡萄球菌、阴沟杆菌、枸橼酸杆菌。应开展细菌药物敏感性监测，以强调临床合理使用抗生素。     

Cefotaxime therapy of lower respiratory tract infections in intensive-care patients

Cefotaxime is one of two third-generation cephalosporins (the other being ceftriaxone) that undergo significant metabolism and is the only third-generation cephalosporin for which an active metabolite has been identified. Cefotaxime was administered intravenously in doses of 6 g per day to 20 patients with serious infections of the lower respiratory tract due to organisms susceptible to cefotaxime (isolates of Enterobacteriaceae and of Pseudomonas aeruginosa). It was administered with gentamicin in some high-risk patients. Cefotaxime resulted in mean peak concentrations of 32 mu/ml (cv% = 53) and of 29.5 micrograms/ml (cv% = 65) respectively after the first and after the last dose of a regimen of 2 g every 8 hours. The half-life value averaged 1.8 h and 6.4 h for cefotaxime and its desacetyl metabolite respectively. The average value of the metabolite at the end of short infusion was 11.5 micrograms/ml (cv% = 31) after the initial dose and 15.5 micrograms/ml (cv% = 37) after the last administered dose. Overall results were 75% patients cured or improved; 83% of the patients with nosocomial pulmonary infections due to Enterobacteriaceae were cured; 50% of the patients with Pseudomonas aeruginosa infections were cured and 25% improved despite the pathogen not being eradicated. No serious toxicity was observed.     

Pharmacotherapy for lower respiratory tract infections

Introduction: Bacterial infections play an important role as etiological agents in acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and exacerbations of non-cystic fibrosis (CF) bronchiectasis. In acute bronchitis and asthma exacerbations their role is less well defined than with patients with COPD. The clinical features, causative pathogens and therapies of common acute respiratory tract infections are detailed in this review.

Areas covered: This article covers medical literature published in any language from 2000 to 2014, on ‘lower respiratory tract infections’, identified using PubMed, MEDLINE and ClinicalTrial.gov. The search terms used were ‘COPD exacerbations’, ‘bronchiectasis’, ‘macrolides’ and ‘inhaled antibiotics’.

Expert opinion: Given that almost half of AECOPD are caused by bacteria, administration of antibacterial agents is recommended for patients with severe exacerbations or severe underlying COPD. Chronic prophylactic use of macrolides seems to be of benefit, particularly in patients with bronchiectasis and chronic mucous hypersecretion. In an effort to manage chronic airway infection non-CF bronchiectasis due to drug-resistant pathogens, aerosolized antibiotics may be of value, and the data from recent studies are examined to demonstrate the potential value of this therapy, which is often used as an adjunctive measure to systemic antimicrobial therapy.     

Azithromycin and lower respiratory tract infections

Azithromycin is a macrolide antibiotic that has been structurally modified from erythromycin with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to erythromycin. This allows once-daily administration for 3-5 days of treatment compared with traditional multi dosing 7-10-day treatment regimens. It has been successfully employed in lower respiratory tract infections. Recent data indicate that azithromycin may exert anti-inflammatory/immunomodulatory effects that may be of use in the treatment of both acute and chronic airway diseases. This review examines the role of azithromycin in lower respiratory tract infections analysing published data on exacerbations of chronic bronchitis, community-acquired pneumonia and cystic fibrosis both in adults and children. In addition, pharmacokinetic and pharmacodynamic properties of the drug are also considered.     

头孢布烯治疗下呼吸道感染

目的：观察头孢布烯对下呼吸道感染的疗效。方法：下呼吸道感染６４例（男性３９例，女性２５例，年龄４８±ｓ１４ａ），采用头孢布烯２００ｍｇ，ｐｏ，ｂｉｄ，疗程１０．３±２．４ｄ。结果：临床有效率８８％（５６／６４），细菌清除率８９％（４７／５３）。临床分离病原菌５３株。体外药敏试验显示头孢布烯敏感率９１％，耐药率（９％）与头孢他啶（１１％）、头孢噻肟（１３％）、头孢哌酮（１５％）无显著性差异（Ｐ＞０．０５）。治疗过程中副作用发生率３％，且轻微。结论：头孢布烯是一种治疗下呼吸道感染的高效而安全的抗生素。     

Azithromycin and lower respiratory tract infections

Azithromycin is a macrolide antibiotic that has been structurally modified from erythromycin with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to erythromycin. This allows once-daily administration for 3 – 5 days of treatment compared with traditional multi dosing 7 – 10-day treatment regimens. It has been successfully employed in lower respiratory tract infections. Recent data indicate that azithromycin may exert anti-inflammatory/immunomodulatory effects that may be of use in the treatment of both acute and chronic airway diseases. This review examines the role of azithromycin in lower respiratory tract infections analysing published data on exacerbations of chronic bronchitis, community-acquired pneumonia and cystic fibrosis both in adults and children. In addition, pharmacokinetic and pharmacodynamic properties of the drug are also considered.     

Steady-state pharmacokinetics of rufloxacin in elderly patients with lower respiratory tract infections.

The pharmacokinetics of rufloxacin, after repeated doses, was evaluated in 12 elderly patients with lower respiratory tract infections. Patients were given a single loading dose of 400 mg on the first day of treatment and single daily maintenance doses of 200 mg for the next 6-9 days. Serum concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at regular intervals during treatment and fitted to a one-compartment open model for repeated doses. The maximum serum concentration after the first dose was 6.46 +/- 1.06 (mean +/- SEM) micrograms/ml and was reached in 4.3 +/- 0.8 h after the first administration. The elimination half-life was 28.7 +/- 4.1 h. The area under the serum levels-time curve from 0 to 24 h was 103 +/- 14 micrograms/h/ml after the first dose. On the last day of observation it increased to 155 +/- 28 micrograms/h/ml, with a mean extent of accumulation of 2.3 +/- 0.3 times. The elimination half-life was comparable to those in other studies in healthy young subjects, while plasma levels were about 80% higher. These results suggest that in elderly patients elevated drug concentrations may be reached in the serum. Although no untoward reactions related either to the drug concentration in serum or the dose have been noted with rufloxacin, this patient population should nevertheless be monitored carefully for adverse effects.     

异帕米星治疗下呼吸道感染

目的：观察异帕米星对下呼吸道感染的疗效。方法：下呼吸道感染４２例（男性３２例，女性１０例；年龄５６±ｓ１３ａ），以异帕米星注射液４００ｍｇ／ｄ，静脉滴注，疗程８．７±２．３ｄ．结果：临床有效率８１％（３４／４２），细菌清除率６９％（２４／３５）。临床分离的６１株革兰阴性（Ｇ－）杆菌作体外药敏测定显示对异帕米星的耐药率为３０％，明显低于庆大霉素的耐药率（４８％）。结论；异帕米星治疗下呼吸道感染疗效满意。     

加替沙星治疗下呼吸道感染

目的 :评价加替沙星治疗下呼吸道感染的临床疗效及安全性。方法 :66例病人分成 2组。加替沙星组 34例 [男性 19例 ,女性 15例 ,年龄 (35±s11)a];左氧氟沙星组 32例 [男性 18例 ,女性 14例 ,年龄 (38± 12 )a]。分别给予加替沙星 0 .4g静脉滴注qd ;左氧氟沙星 0 .2 g静脉滴注bid治疗。疗程均为 7～ 14d。结果 :加替沙星组和左氧氟沙星组的总有效率分别为 91%和 91% ,细菌清除率为90 %和 90 %。不良反应发生率分别为 6%和6%。 2组差别无显著意义 (P >0 .0 5 )。结论 :加替沙星亦是治疗下呼吸道感染安全有效的药物     

ICU患者下呼吸道感染的细菌分布和耐药性分析

目的探讨ICU患者下呼吸道感染细菌分布特征及耐药性分析。方法收集我院2008年10月至2010年10月间ICU病房患者240例痰液标本进行菌株鉴定和药敏实验。结果 240例患者痰液标本分离出病原菌210例,阳性率占75%。其中革兰阴性杆菌占70%,革兰阴性球菌占21%,真菌占9%,以铜绿假单胞菌居首位,其次为金黄色葡萄球菌,肺炎克雷伯氏菌,不动杆菌属和真菌。结论革兰阴性杆菌为ICU病房患者医院感染主要病原菌,对常用抗菌药呈高度耐药特征,并有上升趋势。根据细菌培养及药物敏感实验合理选用抗菌药物,是防止抗菌素滥用,控制院内感染病原传播的关键。     

Inhaled colistin for lower respiratory tract infections

Introduction: Lower respiratory tract infections, due to Pseudomonas aeruginosa or Acinetobacter baumannii, are frequently encountered in patients with cystic fibrosis (CF) or in patients developing nosocomial pneumonias. Both of these conditions bear a high mortality risk and aggressive antibiotic therapy is necessary. Inhaled antibiotics might represent an effective therapeutic approach for these diseases as it has demonstrated good bactericidal efficacy and safety in both preclinical and clinical studies. This colistin formulation might be useful particularly in patients with respiratory tract infections due to multidrug-resistant Gram-negative bacteria. Its main advantages are a better safety profile with a minimal or absent risk of nephrotoxicity.

Areas covered: This paper discusses the available systemic formulations of colistin, with pharmacokinetic and safety profiles, followed by an overview of inhaled antibiotics in lower respiratory tract infections.

Expert opinion: Inhaled colistin should be used selectively as monotherapy in chronic infections with P. aeruginosa in CF patients, whereas in patients with hospital/ventilator-acquired pneumonia (HAP/VAP), it should be used in a combined regimen with systemic antibiotics.     

Antimicrobial therapy for lower respiratory tract infections

The principles of antimicrobial therapy of lower respiratory tract infections are discussed. Making a differential diagnosis of possible causative agents of an infection is the corner-stone of rational antimicrobial therapy. Antimicrobial therapy should only be instituted when the patient will benefit from the treatment, which can not be taken for granted in the case of bronchitis.     

Inhaled colistin for lower respiratory tract infections

INTRODUCTION: Lower respiratory tract infections, due to Pseudomonas aeruginosa or Acinetobacter baumannii, are frequently encountered in patients with cystic fibrosis (CF) or in patients developing nosocomial pneumonias. Both of these conditions bear a high mortality risk and aggressive antibiotic therapy is necessary. Inhaled antibiotics might represent an effective therapeutic approach for these diseases as it has demonstrated good bactericidal efficacy and safety in both preclinical and clinical studies. This colistin formulation might be useful particularly in patients with respiratory tract infections due to multidrug-resistant Gram-negative bacteria. Its main advantages are a better safety profile with a minimal or absent risk of nephrotoxicity. AREAS COVERED: This paper discusses the available systemic formulations of colistin, with pharmacokinetic and safety profiles, followed by an overview of inhaled antibiotics in lower respiratory tract infections. EXPERT OPINION: Inhaled colistin should be used selectively as monotherapy in chronic infections with P. aeruginosa in CF patients, whereas in patients with hospital/ventilator-acquired pneumonia (HAP/VAP), it should be used in a combined regimen with systemic antibiotics.     

头孢哌酮-舒巴坦治疗下呼吸道感染73例

目的：观察头孢哌酮-舒巴坦治疗下呼吸道感染的临床疗效及细菌对该药的耐药性。方法：下呼吸道感染住院病人７３例［男性５３例,女性２０例,年龄（５７ ± ｓ １４） ａ］,应用头孢派酮一舒巴坦 ２． ０ ｇ,加入 ０． ９％氯化钠注射液 １００ ｍｌ。中静脉滴注, ｂｉｄ,疗程（１０ ± ３） ｄ;并对我院临床分离的 ７３８株致病菌进行药敏试验。结果：应用头孢哌酮－舒巴坦治疗的有效率为 ９２％,细菌清除率为 ８４％。头孢哌酮－舒巴坦对临床分离的革兰阴性杆菌的敏感性为 ９４％,对革兰阳性球菌的敏感性为 ８６％。结论：头孢哌酮－舒巴坦治疗下呼吸道感染的临床疗效好,细菌耐药性低,是一种抗菌谱广、杀菌作用强的耐酶抗生素。     

The role of fluoroquinolones in respiratory tract infections: community acquired pneumonia

Newer fluoroquinolones may play an important role in the management of community acquired pneumonia. They retain activity similar to older fluoroquinolones against Gram-negative bacteria and are significantly more active against Gram-positive bacteria, especially pneumococci. They are also active against bacteria causing atypical pneumonia, penicillin-sensitive and -resistant and macrolide-sensitive and -resistant pneumococci and against beta-lactamase producing and non-producing Haemophilus influenzae. They have similar or slightly lower activity than ciprofloxacin against other Gram-negative organisms. They have rapid bactericidal activity and attain good lung tissue levels. Clinical studies show results similar or better than older treatments. Their impact on ecology and resistance remains to be elucidated but data on side effects and toxicity must be carefully evaluated.     

Susceptibility of bacteria isolated from patients with lower respiratory tract infections to antibiotics (1986)

Enlisting the help of various research institutions across the nation, Ikemoto et al. have been pooling cultures of clinical isolates of respiratory tract infections and mapping out the correlations between patient backgrounds and the causative bacteria and the changes in the sensitivity spectra of the bacteria to various antibacterial and antibiotic agents annually since 1981. The following is a report of the 1986 findings. During the period from September, 1986 to March, 1987, 558 cases of respiratory infections were reported at 17 institutions across the nation and a total of 657 apparent causative strains were isolated from sputum samples. Of these strains, 75 strains of Staphylococcus aureus, 108 of Streptococcus pneumoniae, 150 of Haemophilus influenzae, 107 of Pseudomonas aeruiginosa (non-mucoid production type), 21 of P. aeruginosa (mucoid production type), 32 of Klebsiella pneumoniae, 8 of Escherichia coli, and 55 of Branhamella catarrhalis were subjected to MIC determination of various antibacterial and antibiotic agents to map drug sensitivities. In addition, diagnoses, age distributions by diagnoses, frequencies of infectious diseases, types of isolated bacteria, and usage statuses of the antibacterial and antibiotic agents the times of at isolation were also investigated. MIC determinations were carried out to investigate susceptibilities of causative organisms of respiratory tract infections to various antibacterial and antibiotic agents. From the 558 cases of respiratory tract infections, 657 strains were detected at concentrations not less than 10(4-6)/ml and identified to be the causative organisms. Of these strains, 603 could be used for MIC determination. An overwhelming majority of major causative bacteria, inclusive of H. influenzae and S. pneumoniae, showed sensitivity patterns similar to the sensitivity patterns found a year earlier, P. aeruginosa alone, however, showed some increase in its susceptibility to penicillin and cephem antibiotics. Regarding patient backgrounds, the age distribution was heavily biased towards the higher end of the scale, which patients with ages of 50 or higher accounting for 77.9%, compared to 73.5% in 1985. When the patients were classified by diagnoses, chronic bronchitis, bacterial pneumonia and bronchiectasis accounted for the majority of the infections: 28.7%, 23.3%, and 19.0%, respectively. The percentages of chronic bronchitis and bacterial pneumonia 28.7% and 23.3%, respectively, were somewhat higher in 1986 than in 1985. The disease which was comparatively frequent in all age groups was bronchiectasis, which accounted for 44.0% in patients with ages 29 years or lower, 18.4% in patients between 30 years and 69 years, and 16.7% in patients with ages 70 years or higher. The next most frequent infection was bacterial pneumonia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Susceptibility of bacteria isolated from patients with lower respiratory tract infections to antibiotics (1985)

Collaborated studies on species of respiratory tract infection (RTI)-related organisms for their identification and drug susceptibilities have been carried out since 1981 at about 20 centers in Japan. On this occasion, the data obtained between 1982 and 1985 were reanalyzed to determine whether or not drug susceptibilities differed depending upon diseases, from which the organisms were isolated. The results summarized below were obtained in this study. 1. Among Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and Pseudomonas aeruginosa examined, differences in drug susceptibilities according to different diseases were found among S. aureus and also mucoid strains of P. aeruginosa. 2. Susceptibility to beta-lactam antibiotics was definitely lower in S. aureus strains isolated from pneumonia than in those isolated from chronic bronchitis and bronchiectasia. 3. The isolation frequency of methicillin-and cefazolin-resistant strains of S. aureus was 30.3% and 25.9%, respectively, and was especially high among strains isolated from pneumonia. The antibiotic potency of minocycline against S. aureus, including methicillin resistant S. aureus, was the strongest among 9 drugs examined; S. aureus maintained relatively sufficient sensitivity to dicloxacillin among beta-lactam antibiotics. 4. Mucoid producing strains of P. aeruginosa isolated from chronic bronchitis had slightly lower drug susceptibility than those isolated from bronchiectasia. 5. When drug susceptibilities of H. influenzae were compared among groups separated according to diseases using MIC50, MIC80 and MIC90 as indicators, there were no clear differences. The isolation frequency of ampicillin (ABPC)-resistant strains, however, was clearly different among diseases; namely, resistant strains were the most and the least frequently isolated from chronic bronchitis and from pneumonia, respectively. In addition, the drug susceptibility of H. influenzae isolated in 1985 was analyzed in relation to the production of beta-lactamase. As a result, it was suspected that some factors, other than beta-lactamase, participated in the mechanism of ABPC-resistance. 6. These results suggest that drugs to be used for the chemotherapy of RTI should be selected considering the fact that drug susceptibilities of the pathogens differ, even among the same species, according to diseases.     

Susceptibility of bacteria isolated from patients with lower respiratory tract infections to antibiotics (1987)

Since 1981, in cooperation with research institutions across the nation, Ikemoto, et al. have been collecting clinical isolates from patients with respiratory tract infections and conducting an annual retrospective survey of patients' background factors and of isolated strains and their sensitivities to various antibacterial agents and antibiotics. In the period from October, 1987 to September, 1988, 17 institutions participated in the survey and a total of 706 strains which were demonstrated to be causative organisms were isolated from 562 patients with respiratory tract infections. Strains were mostly isolated from the sputum. The taxonomic breakdown of these strains was: Staphylococcus aureus (69 strains), Streptococcus pneumoniae (120), Haemophilus influenzae (170), Mucoid-producing Pseudomonas aeruginosa (42), Non-mucoid-producing P. aeruginosa (87), Escherichia coli (11), Klebsiella pneumoniae (35), Brahamella catarrharis (72), etc. Of these strains, 629 were used to determine MICs of various antibacterial agents and antibiotics for susceptibility analyses. Relationships between patient backgrounds and diagnoses and between infections diseases and causative organisms were also investigated. Most of the major causative organisms, such as H. influenzae and P. aeruginosa, showed no substantial changes from previous years, with regard to their sensitivities to antibiotic agent, but S. aureus, particularly methicillin/cephem-resistant strains of S. aureus (MCRSA) showed somewhat lower sensitivity to beta-lactams, and as in recent years, to ofloxacin, a new quinolone drug, as well. Regarding background factors of patients, the age distribution was heavily concentrated in age brackets of 50 years and older, thus patients in these age group accounted for 75.2% of all the patients, which was comparable to 73.5% in 1985 and 77.9% in 1986. Among infections encountered, bacterial pneumonia was most frequent at 28.3%, followed by chronic bronchitis (27.2%) and bronchiectasis (16.0%). Bacterial pneumonia was actually the most frequent, throughout the entire age groups accounting for 34.3% of patients up to 29 years, 26.6% in the group of 30-69 years and 30.7% in patients aged 70 years and older. Chronic bronchitis was next most frequent and accounted for 20.0%, 26.4% and 30.7% among the three age groups, respectively. Breaking down clinical isolates by diagnosis, H. influenzae, S. pneumoniae and P. aeruginosa were isolated frequently from most of the infectious diseases.(ABSTRACT TRUNCATED AT 400 WORDS)