Mixed community-acquired lower respiratory tract infections

Although mixed infections are known to be clinically relevant in conditions such as nosocomial pneumonia and ventilator-related pneumonia, it is increasingly recognized that a substantial number of community-acquired lower respiratory tract infections may also be attributed to more than one pathogenic organism. A better definition of the true incidence of mixed infections in community-acquired lower respiratory tract infections is partly derived from recent advances in available diagnostic methods (eg, molecular biology). Two points still must be determined: whether the presence of a mixed infection is associated with altered outcomes and whether empirical antibiotic selection should be modified to account for potential polymicrobial infections.     

beta-lactam-antibiotics in the treatment of community-acquired respiratory tract infections with penicillin-resistant pneumococci

Streptococcus pneumoniae is still the most important pathogen of community-acquired respiratory tract infections. During the last decades in many countries an increase in the spread of antibiotic resistant strains (e. g. against beta-lactams, macrolides, tetracyclin) was observed. Resistance against penicillin is often associated with resistance against macrolides and other antibiotic classes. In Germany surveillance studies including isolates from patients with community-acquired respiratory tract infections have shown that about 14 % of strains show a reduced susceptibility against penicillin (MIC-values 0.12 - 1 mg/L) and up to 4 % are highly resistant against penicillin (MIC >/= 2 mg/L). Resistance against tetracycline or macrolides was detected in up to 12 and 15 % of strains, respectively. According to the treatment guidelines of the Paul-Ehrlich-Gesellschaft für Chemotherapie and the Deutschen Atemwegsliga penicillins and cephalosporins are recommended as first line antibiotics for the treatment of community-acquired respiratory tract infections. As pneumococcal strains with reduced susceptibility against penicillin show often also a reduced susceptibility against cephalosporins the questions arises which beta-lactam antibiotics should still be used in empirical treatment of such strains. beta-Lactam-antibiotics highly differ in their in-vitro-activity against S. pneumoniae and their pharmacokinetic properties. In different models is has been demonstrated for beta-lactams that an adequate clinical and bacteriological efficacy is achievable when the serum levels of the free, i. e. not protein bound fraction of drug exceeds the MIC of the pathogen for at least 40 to 50 % of the dosing interval (T > MIC). In a clinical situation where pneumococci with reduced susceptibility against penicillin cannot be ruled out, only beta-lactam antibiotics with favourable pharmacological properties (good in-vitro activity, high and long lasting serum levels) should be used for treatment.     

Update on pneumococcal infections of the respiratory tract

Respiratory illnesses are the leading reason for seeking medical care here in the United States. Streptococcus pneumoniae is the most common bacterial pathogen causing acute otitis media (AOM), sinusitis, and community-acquired pneumonia in both the pediatric and adult populations. The continued development of antibiotic resistance to an increasing number of different antibiotic classes by this organism has made the treatment of some of these infections more difficult. Recently, a heptavalent pneumococcal conjugate vaccine was approved for infants and toddlers, beginning at 2 months of age. Widespread implementation of this vaccine in the childhood population may have a significant impact on the amount of systemic disease seen with this organism.     

Telithromycin in the treatment of community-acquired pneumonia: a pooled analysis

The efficacy of telithromycin has been assessed in six Phase III studies involving adults with mild to moderate community-acquired pneumonia (CAP) with a degree of severity compatible with oral therapy. Patients received telithromycin 800 mg once daily for 7-10 days in three open-label studies (n=870) and three randomized, double-blind, comparator-controlled studies (n=503). Comparator antibacterials were amoxicillin 1000 mg three-times daily, clarithromycin 500 mg twice daily and trovafloxacin 200 mg once daily. Clinical and bacteriological outcomes were assessed 7-14 days post-therapy. Among telithromycin-treated patients, per-protocol clinical cure rates were 93.1 and 91.0% for the open-label and comparative studies, respectively. Telithromycin treatment was as effective as the comparator agents. High eradication and clinical cure rates were observed for infections caused by key pathogens: Streptococcus pneumoniae including isolates resistant to penicillin G and/or erythromycin A (95.4%), Haemophilus influenzae (89.5%) and Moraxella catarrhalis (90%). Telithromycin was also highly effective in patients with infections caused by atypical and/or intracellular pathogens and those at increased risk of morbidity. Telithromycin was generally well tolerated. Telithromycin 800 mg once daily for 7-10 days offers a convenient and well-tolerated first-line oral therapy for the empirical treatment of mild to moderate CAP.     

Major bacteria of community-acquired respiratory tract infections in Turkey

To determine the bacterial etiology of lower respiratory tract infections (LRTIs) in Turkey, quantitative cultures of sputum were carried out. The major pathogens for LTRIs were found to be Haemophilus influenzae, followed by Streptococcus pneumoniae and Moraxella catarrhalis. Only 6.1% of the H. inlfuenzae and all strains of M. catarrhalis were beta-lactamase producers. An E-test showed that 31.2% of the S. pneumoniae strains had an intermediate resistance to penicillin, and the remaining strains were susceptible; no fully resistant strains were detected.     

左氧氟沙星静脉／口服序贯治疗老年社区获得性下呼吸道感染

目的 观察左氧氟沙星静脉／口服序贯治疗老年下呼吸道感染的疗效和安全性。方法 100例老年下呼吸道感染患者分成两组，分别予左氧氟沙星500mg／d静脉／口服序贯治疗或全程静脉治疗。结果 序贯治疗有效率84％，菌清除率69．2％。全程静脉治疗有效率86％，菌清除率72．7％。两组不良反应均轻微。结论 左氧氟沙星静脉／口服序贯治疗老年社区获得性下呼吸道感染有效，安全。     

Treatment of community-acquired lower respiratory tract infections during pregnancy

The incidence of lower respiratory tract infection (LRTI) in women of child-bearing age is approximately 64 per 1000 population. The spectrum of illness ranges from acute bronchitis, which is very common, through influenza virus infection and exacerbations of underlying lung disease, to pneumonia, which, fortunately is uncommon (<1.5% LRTI), but can be severe. Acute bronchitis is generally mild, self-limiting and usually does not require antibacterial therapy. Influenza virus infection in pregnant women has been recently related to increased hospitalization for acute cardiorespiratory conditions. At present, the safety of the newer neuraminidase inhibitors for the treatment of influenza virus infection has not been established in pregnancy and they are not routinely recommended. In influenza virus infection complicated by pneumonia, antibacterial agents active against Staphylococcus aureus and Streptococcus pneumoniae superinfection should be used. There are few data on infective complications of asthma or COPD in pregnancy. The latter is rare, as patients with COPD are usually male and aged over 45 years. Management is the same as for nonpregnant patients. The incidence and mortality of pneumonia in pregnancy is similar to that in nonpregnant patients. Infants born to pregnant patients with pneumonia have been found to be born earlier and weigh less than controls. Risk factors for the development of pneumonia include anemia, asthma and use of antepartum corticosteroids and tocolytic agents. Based on the few available studies, the main pathogens causing pneumonia are S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and viruses. Beta-Lactam and macrolide antibiotics therefore remain the antibiotics of choice in terms of both pathogen coverage and safety in pregnancy. In HIV-infected pregnant patients, recurrent bacterial pneumonia, but not Pneumocystis carinii pneumonia (PCP), is more common than in nonpregnant patients. Trimethoprim/sulfamethoxazole (cotrimoxazole) has not definitely been associated with adverse clinical outcomes despite theoretical risks. Currently it is still the treatment of choice in PCP, where mortality remains high. In conclusion, there are few data specifically related to pregnant women with different types of LRTI. Where data are available, no significant differences compared with nonpregnant patients have been identified. In considering the use of any therapeutic agent or investigation in pregnant patients with LRTI, safety aspects must be carefully weighed against potential benefit. Otherwise, management strategies should not differ from those for nonpregnant patients. Further research in this area is warranted.     

Quantitative culture of bronchoalveolar lavage fluid in community-acquired lower respiratory tract infections.

To evaluate the diagnostic value of quantitative bacterial culture of bronchoalveolar lavage (BAL) fluid obtained by fibreoptic bronchoscopy, 67 consecutive immunocompetent adult patients admitted to hospital with community-acquired lower respiratory tract infections from September 1997 to May 1998 were investigated. Results were compared to the findings in eight healthy control persons investigated in February 1998. There was no difference between study patients and control persons when quantitative culture of total cumulative bacterial findings or bacteria categorized as members of the oropharyngeal normal flora were compared. The culture of normal flora in bronchial washings probably reflects contamination of the lower airways with secretions from upper arways by the fibreoptic procedure itself, as fractionated sampling showed a 10-fold reduct on in quantitative culture results when a primary bronchial washing was compared to a secondary sampling from the same bronchus in the control group. Twenty-four (36%) of 67 patients were cultured as positive in the study group while all control persons were cultured as negative for bacteria categorized as potential pathogens. With a threshold value for positive culture of 10(4) cfu ml(-1) the specificity of lavage culture of potential pathogenic bacteria in relation to actual lower airway infection was 100%. Therefore, quantitative bacterial culture of potential pathogenic bacteria in BAL fluid is very specific but only positive in about one-third of unselected immunocompetent adult patients with a lower respiratory tract infection.     

降钙素原指导抗生素治疗策略在社区获得性下呼吸道感染中应用的荟萃分析

目的 评价降钙素原指导抗生素治疗策略在下呼吸道感染治疗中的有效性及安全性.方法 以procalcitonin、lower respiratory tract infections、community acquired pneumonia、exacerbations of COPD、exacerbations of chronic obstructive pulmonary diseases、acute bronchitis及asthma为检索词,检索PubMed、Embase数据库(检索时间为1990年1月至2010年12月)及Cochrane图书馆临床对照试验数据库(2010年第8期).以降钙素原、下呼吸道感染、社区获得性肺炎、慢性阻塞性肺病急性加重期、慢性阻塞性肺病急性加重、急性支气管炎、支气管哮喘为检索词,检索万方数据库、中国期刊全文数据库及中国生物医学文献数据库,检索时间为1990年1月至2010年12月,同时检索纳入文献的参考文献,对纳入文献逐个进行质量评价和资料提取.进行统计学分析时,计数资料采用优势比,计量资料采用加权均数差.采用RevMan 4.2.2软件对数据合并进行统计分析.结果 纳入5篇文献,共2322例患者.降钙素原指导治疗组较常规治疗组抗生素使用天数下降[加权均数差( WMD)为2.58 d,95％ CI为-3.13～ -2.04,Z=9.36,P＜0.001],抗生素处方率下降(OR =0.23,95％ CI为0.12～0.44,Z=4.52,P＜0.001),治疗过程中抗生素的费用下降(WMD为- 91.72美元,95％ CI为- 109.44～ - 74.00,Z=10.15,P＜0.001),月内随访感染再发率下降(OR=0.70,95％ CI为0.5～0.97,Z=2.13,P＜0.05),差异均具有统计学意义;而治疗过程中ICU入住率下降(OR =0.8,95％ CI为0.59～ 1.09,Z=1.41,P＞0.05),院内病死率上升(OR=1.01,95％ CI为0.69～1.48,Z=0.07,P＞0.05),住院总天数减少(WMD为-0.27 d,95％ CI为-0.9～0.35,Z=0.86,P＞0.05),治疗成功率上升(OR =1.04,95％ CI为0.65 ～ 1.65,Z=0.16,P＞0.05).结论 对于急诊以及住院治疗的下呼吸道感染患者,使用降钙素原指导抗生素治疗策略可明显减少抗生素的使用,且对疗效和住院时间的影响不明显.     

Community-acquired lower respiratory tract infections: etiology and treatment.

The current therapy for community-acquired lower respiratory tract infections is often empiric, usually involving administration of a beta-lactam or macrolide. However, the increasing prevalence of antibiotic resistance in frequently isolated respiratory tract pathogens has complicated the antimicrobial selection process. This review will discuss the incidence of various respiratory pathogens, as well as update the clinician on the various antimicrobial alternatives available, with particular emphasis on the role of the newer fluoroquinolones in the treatment of acute exacerbations of chronic bronchitis and community-acquired pneumonia.     

Activity of telithromycin against key pathogens associated with community-acquired respiratory tract infections

OBJECTIVES: To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with telithromycin in respiratory tract infections. METHODS: The activity of telithromycin was determined by in vitro susceptibility testing of key respiratory tract pathogens isolated from patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating the clinical efficacy of telithromycin. RESULTS: In this pooled analysis, telithromycin mode minimum inhibitory concentration (MIC) and MIC90, respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626); 0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789), respectively. CONCLUSIONS: High levels of in vitro susceptibility to telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.     

Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired lower respiratory tract infections.

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.     

2012年中国成人社区获得性呼吸道感染主要致病菌耐药性的多中心研究

目的 调查2012年我国11家医院成人社区获得性呼吸道感染病原菌的耐药性.方法 收集2012年1-12月全国11家中心分离的599株成人社区获得性呼吸道感染病原菌,其中肺炎链球菌381株,流感嗜血杆菌137株,卡他莫拉菌81株.采用琼脂稀释法测定抗菌药物的MIC值.结果 50％(300/599)的菌株分离自60岁以上的患者,16.2％(97/599)的菌株分离自40岁以下的患者.按照肺炎链球菌口服青霉素的折点判定标准,56.7％(216/381)的肺炎链球菌为青霉素不敏感菌株(PNSSP),肺炎链球菌对大环内酯类的耐药率超过90％(345/381),对口服头孢菌素的耐药率为39.9％ ～50.7％(152 ～ 193株).肺炎链球菌对左氧氟沙星和莫西沙星的敏感度分别为97.8％(372/381)和99％(377/381).PNSSP对头孢曲松、阿莫西林/克拉维酸、头孢克洛、头孢呋辛的耐药率显著高于青霉素敏感菌株(PSSP).流感嗜血杆菌对除氨苄西林(71.5％,272/381)和头孢克洛(75.2％,286/381)外的抗菌药物的敏感度均超过90％.流感嗜血杆菌中β-内酰胺酶阳性率为21.9％(30/137),且β-内酰胺酶阳性菌株对氨苄西林、头孢克洛、氯霉素和四环素的耐药性显著高于β-内酰胺酶阴性菌株.氟喹诺酮类药物对流感嗜血杆菌的作用效果明显.除克林霉素、阿奇霉素和克拉霉素对卡他莫拉菌作用较差外,其他药物对卡他莫拉菌均具有较高的抗菌活性.结论 大环内酯类和口服头孢菌素类药物对肺炎链球菌、流感嗜血杆菌和卡他莫拉菌的抗菌活性有限,左氧氟沙星和莫西沙星对肺炎链球菌、流感嗜血杆菌和卡他莫拉菌仍具有较高的抗菌活性.     

Antibody treatment of lower respiratory tract infections

Antibody treatment of lower respiratory infection has a long history of success and is receiving renewed interest. A variety of polyclonal and monoclonal preparations are clinically available. Although used primarily for infection prophylaxis, these agents have limited applications in the treatment of established infections. Immune serum was the first effective treatment for pneumococcal pneumonia. Although long-supplanted by the advent of antibiotics, passive immunotherapy for pneumococcal and other infections is being revisited in an era of increasing antibiotic resistance and growing numbers of immunocompromised individuals. Limited clinical evidence supports the use of immune globulins in the treatment of pertussis and severe streptococcal infection. Bone marrow transplant recipients with lower respiratory infections caused by cytomegalovirus or respiratory syncytial virus also may benefit by adjunctive treatment with immune globulins. Additional indications for antibody treatment of respiratory infection may develop with further investigation.