Beta‐lactam plus macrolides or beta‐lactam alone for community‐acquired pneumonia: A systematic review and meta‐analysis

It is unclear whether in the treatment of community‐acquired pneumonia (CAP) beta‐lactam plus macrolide antibiotics lead to better survival than beta‐lactam alone. We report a systematic review and meta‐analysis. Trials and observational studies published in English were included, if they provided sufficient data on odds ratio for all‐cause mortality for a beta‐lactam plus macrolide regimen compared with beta‐lactam alone. Two investigators independently searched for eligible articles. Of 514 articles screened, 14 were included: two open‐label randomized controlled trials (RCTs) comprising 1975 patients, one non‐RCT interventional study comprising 1011 patients and 11 observational studies comprising 33 332 patients. Random‐model meta‐analysis yielded an odds ratio for all‐cause death for beta‐lactam plus macrolide compared with beta‐lactam alone of 0.80 (95% CI 0.69–0.92, P = 0.002) with substantial heterogeneity (I² = 59%, P for heterogeneity = 0.002). Severity‐based subgroup analysis and meta‐regression revealed that adding macrolide had a favourable effect on mortality only for severe CAP. Of the two RCTs, one suggested that macrolide plus beta‐lactam lead to better outcome compared with beta‐lactam alone, while the other did not. Subgrouping based on study design, that is, RCT versus non‐RCT, which was almost identical to subgrouping based on severity, revealed substantial inter‐subgroup heterogeneity. Compared with beta‐lactam alone, beta‐lactam plus macrolide may decrease all‐cause death only for severe CAP. However, this conclusion is tentative because this was based mainly on observational studies.     

Prevalence and clinical features of Chlamydia pneumoniae pneumonia at Srinagarind Hospital, Khon Kaen, Thailand

Between October 2000 and December 2002, a prospective study was conducted among hospitalized community acquired pneumonia (CAP) patients admitted to Srinagarind Hospital, Khon Kaen, Thailand. The diagnosis of Chlamydia pneumoniae infection was based on serologic testing. The prevalence of C. pneumoniae among patients hospitalized with CAP was 8.7%; 24 cases of 276 hospitalized CAP patients. The mean age was 42.7 (range, 17-79) years and the male to female ratio was 1:2.4. More than half (54.2%) of them were without underlying disease. The mean duration of symptoms prior to admission was 5.5 (SD 3.7) days. Leukocytosis was found in 62.5% of patients. Localized patchy alveolar infiltration was the most common radiographic finding, followed by bilateral interstitial infiltration. Over half (52.4%) of the patients had a non-productive cough. Gram-positive diplococci or no organisms predominated in cases where adequate sputum was obtained. Dual infection was found in 45.8% of cases, mostly with Streptococcus spp or Klebsiella pneumoniae. Four patients (16.7%) had an initial clinical presentation of severe CAP; 3 of 4 had a dual infection. Ten patients (41.7%) received macrolides or a macrolide plus a third generation beta-lactam at the beginning of management. Two patients (8.3%) did not improve clinically and were transferred home. The average hospital stay was 11 .5 (range, 1-45) days. Parapneumonic effusions complicated 20.8% of the cases. Other complications included acute respiratory failure (16.7%), shock (8.3%), hospital-acquired pneumonia (8.3%), and acute renal failure (4.2%). We concluded that C. pneumoniae caused a wide variation of clinical presentations ranging from mild disease to severe CAP. Co-infection with other bacterial pathogens was a common finding. Use of macrolides or new fluoroquinolones as part of an initial therapeutic regimen should be considered to cover this organism.     

Impact of initial antibiotic choice on clinical outcomes in community-acquired pneumonia: analysis of a hospital claims-made database

BACKGROUND: Much controversy exists regarding the initial choice of antibiotics and selected outcomes for patients with community-acquired pneumonia (CAP). METHODS: The investigators analyzed a hospital claims-made database to assess the impact of initial antibiotic choice on 30-day mortality, total hospital costs, and hospital length of stay (LOS). Fine risk groups allowed for stratification for variations in the severity of illness. Patients were divided into five monotherapy groups (ie, ceftriaxone, "other" cephalosporins, fluoroquinolones, macrolides, or penicillins) and four groups that received dual therapy (ie, the agents listed above, except macrolides) plus macrolides. Patients also were stratified by age (ie, > 65 years of age and < 65 years of age). Severely ill patients were excluded. RESULTS: Overall, 44,814 persons met the criteria for inclusion. Among monotherapy patients, those who received macrolides had the least mortality but were the least ill. Patients who received dual therapy generally had shorter LOSs, lower total hospital charges, and decreased mortality compared with those who received monotherapy. Differences among dual-therapy regimens regarding outcomes studies were noted. Patients who were < 65 years of age had lower mortality rates, shorter LOSs, and lower hospital charges than did the more elderly patients. Within this group, those who received dual therapy had better outcomes than those who received monotherapy. CONCLUSIONS: We confirmed the value of dual therapy employing macrolides as a second agent in decreasing mortality from CAP, and we provided similar data regarding shorter LOSs and lower hospital charges. This appears to hold for a younger population. Differences among dual-therapy regimens (all employing macrolides) appear to exist and may be clinically relevant.     

Epidemiological survey on incidence and treatment of community acquired pneumonia in Italy

STUDY OBJECTIVES: To estimate annual incidence of community acquired pneumonia (CAP) in an Italian general population sample. DESIGN AND PARTICIPANTS: Two hundred and eighty-seven family practitioners (64.6% of those selected) recorded suspected or ascertained CAP cases for 1 year. Information on smoking habit, respiratory symptoms and signs, co-morbidity, antibiotic and corticosteroid therapy, hospitalization, mortality and recovery were obtained. RESULTS: Six hundred and ninety-nine case forms were collected (53.1% females, mean age 59.6+/-19.5, 20.6% smokers). CAP incidence rates per 1000 population were: 1.69 in men vs. 1.71 in women; 2.33 in the North vs. 1.29 in the Centre-South of Italy; between 0.73 in 14-, and 3.34 in 64+year-old subjects. Main symptoms and signs were cough (73.3%), crackles (72.8%), dullness (57.3%), asthenia (53.4%). 59.5% of subjects had concurrent diseases, mostly cardiac and respiratory. 77.2% of cases had chest X-ray (with parenchymal density in 90.6%). Phlegm microbiological examination was performed in 12.8% of cases. First choice antibiotics were cephalosporins (45.8%), macrolides (20.2%), other beta-lactams (18.6%), and fluoroquinolones (12.2%). Rates of hospitalization and of mortality were 31.8% and 6.0%, respectively. CONCLUSION: This study confirmed that the annual CAP incidence rate in the general population of South Europe is about 2 per 1000 population and showed a wide choice of antibiotic treatment.     

Influence of age on the clinical differentiation of atypical pneumonia in adults

Background and objective: The Japanese Respiratory Society (JRS) scoring system is a useful tool for the early and simple presumptive diagnosis of atypical pneumonia (Mycoplasma pneumoniae and Chlamydia pneumoniae pneumonia). However, it has been suggested that it is difficult to diagnose atypical pneumonia in the elderly using this system. In the present study, we evaluated the accuracy and usefulness of the JRS scoring system for diagnosing atypical pneumonia in different age groups. Methods: Cases of M. pneumoniae (n = 262), C. pneumoniae (n = 98) and common bacterial pneumonia (n = 364) were analysed. Results: For both atypical pneumonias, the frequency of comorbid illnesses and being in a higher risk category were significantly greater in elderly (age ≥60 years) than in non‐elderly patients (age <60 years). One or more additional aetiological factors were more frequently present in elderly than in non‐elderly patients. The diagnostic sensitivity and specificity for atypical pneumonia were 39% and 88%, respectively, in the elderly group, and 86% and 88%, respectively, in the non‐elderly group. When the patients were stratified into 10‐year age groups, the diagnostic sensitivity was highest in the 18‐ to 29‐year age group and decreased from the youngest to the oldest age group. Conclusions: These results indicate that it is difficult to distinguish between atypical pneumonia and bacterial pneumonia in the elderly using the JRS scoring system. When treating patients aged ≥60 years, physicians should use fluoroquinolones or β‐lactam antibiotics + macrolides as empirical first‐choice drugs so as to always provide antibiotic protection against potential atypical pathogens.     

Successful ceftazidime‐avibactam treatment of post‐surgery Burkholderia multivorans genomovar II bacteremia and brain abscesses in a young lung transplanted woman with cystic fibrosis

Burkholderia cepacia complex (Bcc) includes several phenotypically similar but genotypically distinct gram‐negative bacteria (GNB) that can colonize the respiratory tract of Cystic Fibrosis (CF) patients. Pathogens are difficult to treat due to intrinsic resistance to multiple antibiotics and are associated to a more rapid decline in lung function and to increased mortality, particularly after lung transplantation. For all these reasons, chronic infection by Burkholderia (B) cenocepacia is presently considered a relative or absolute contraindication in almost all lung transplant centres. We report the case of a young adult CF patient chronically colonized by B multivorans genomovar II, with diabetes and end‐stage renal disease treated with renal replacement therapy: a few months after lung transplantation, she developed post‐surgery B multivorans bacteremia and multiple brain abscesses. This severe infection did not improve despite multiple standard antibiotic regimen. The introduction of ceftazidime‐avibactam, a new β‐lactam/ β‐lactamase inhibitor combination resulted in clinical recovery and in radiological and biochemical improvement.     

冬季社区获得性肺炎的病原菌及耐药性分析

目的：了解2013年冬季该院社区获得性肺炎（ community acquired pneumonia ,CAP）住院患者中致病菌的构成比、常见致病菌的耐药情况,为CAP的诊断及经验治疗提供依据。方法回顾性分析2013－10-2014－03该院收治所有确诊为CAP患者108例的临床资料及病原学检查资料。结果108例患者送检痰标本128例,检出致病菌64株,检出率为50．0％,肺炎克雷伯杆菌、白色念珠菌为前两位菌种。肺炎克雷伯杆菌对碳青霉烯类、第三代头孢菌素、喹诺酮类药物敏感性较高,对第一代、二代头孢菌素及大环内酯类药物耐药性较高。结论冬季获得性肺炎致病菌以革兰阴性菌为主,最常见为肺炎克雷伯杆菌。对于老年患者,合并慢性阻塞性肺疾病、支气管扩张等基础病的患者应重视抗革兰阴性菌治疗。     

Empiric treatment in hospitalized community-acquired pneumonia. Impact on mortality, length of stay and re-admission

OBJECTIVE: To evaluate adherence to guidelines when choosing an empirical treatment and its impact upon the prognosis of community-acquired pneumonia (CAP). METHODS: A prospective multicentre study was conducted in 425 CAP patients hospitalized on ward. Initial empirical treatment was classified as adhering or not to Spanish guidelines. Adherent treatment was defined as an initial antimicrobial regimen consisting of beta-lactams plus macrolides, beta-lactam monotherapy and quinolones. Non-adherent treatments included macrolide monotherapy and other regimens. Initial severity was graded according to pneumonia severity index (PSI). The end point variables were mortality, length of stay (LOS) and re-admission at 30 days. RESULTS: Overall 30-day mortality was 8.2%, the mean LOS was 8+/-5 days, and the global re-admission rate was 7.6%. Adherence to guidelines was 76.5%, and in most cases the empirical treatment consisted of beta-lactam and macrolide in combination (57.4%). Logistic regression analysis showed that other regimens were associated with higher mortality OR=3 (1.2-7.3), after adjusting for PSI and admitting hospital. Beta-lactam monotherapy was an independent risk factor for re-admission. LOS was independently associated with admitting hospital and not with antibiotics. CONCLUSIONS: A high adherence to CAP treatment guidelines was found, though with considerable variability in the empirical antibiotic treatment among hospitals. Non-adherent other regimens were associated with greater mortality. Beta-lactam monotherapy was associated with an increased re-admission rate.     

Coagulation and inflammation biomarkers may help predict the severity of community‐acquired pneumonia

Background and objective: There are limited data on the relationship between the severity of community‐acquired pneumonia (CAP) and biomarkers of inflammation and coagulation. The aim of this study was to evaluate the association between the severity of CAP and serum levels of antithrombin III (AT‐III), protein C (P‐C), D‐dimers (D‐D) and CRP, at hospital admission. Methods: This was a prospective observational study in 77 adults (62.3% men), who were hospitalized for CAP. The severity of CAP was assessed using the confusion, uraemia, respiratory rate ≥30 breaths/min, low blood pressure, age ≥65 years (CURB‐65) score. Results: Forty patients (52%) had severe CAP (CURB‐65 score 3–5). Serum levels of AT‐III were lower and levels of D‐D and CRP were higher in patients with severe CAP than in patients with mild CAP (CURB‐65 score 0–2) (P < 0.001 for all comparisons). Levels of P‐C were lower in patients with severe CAP compared with those with mild CAP, but the difference was not significant (P = 0.459). At a cut‐off point of 85%, AT‐III showed a sensitivity of 80% and a specificity of 75%, as a determinant of the need for hospitalization. At a cut‐off point of 600 ng/mL, D‐D showed a sensitivity of 90% and a specificity of 75% and at a cut‐off point of 110 mg/L, CRP showed a sensitivity of 83% and a specificity of 79%, as determinants of the need for hospitalization. Conclusions: Serum levels of AT‐III, D‐D and CRP at admission appear to be useful biomarkers for assessing the severity of CAP.     

Foot infections in diabetes (DFIs) in the out‐patient setting: an Italian multicentre observational survey

Aims To conduct a multicentre observational study to describe management of foot infections in diabetes in the out‐patient setting in Italy. Patients and methods Ten centres equally distributed nationwide were asked to collect, by means of a spreadsheet (Access/Excel Microsoft program), data concerning 30 consecutive diabetic patients with foot infections deemed suitable for antibiotic treatment in the out‐patient setting. Centres with ≥ 5 years’ experience of out‐patient management were selected. Data from 271 consecutive patients treated as out‐patients were collected and analysed by the central coordinator. Statistical analysis was performed using the SPSS statistical software package. Results Lesions were mainly located at the toes and midfoot (33.6 and 30.2%, respectively); 63 (23.2%) patients had multiple ulcers. Seventy (25.8%) patients also had concomitant osteomyelitis. Three hundred and four pathogens, including Gram‐positive and Gram‐negative aerobes and anaerobes, were isolated in 219/271 patients (80.8%) by culturing debrided tissue (71.2%) or purulent material (28.8%). Infections were polymicrobial in 33.8% of patients. The most common pathogens were Staphylococcus aureus (27.3%) and Pseudomonas spp. (20.4%); enterobacteriaceae, enterococci, streptococci and anaerobes accounted for 11.5, 7.6, 6.9 and 1.9%, respectively. Antibiotics were frequently administered by parenteral route and frequently in combination. Piperacillin/tazobactam was the parenteral antibiotic most frequently utilized (21.1%). Cure/improvement was observed in 93.4% of patients. Conclusions Foot ulcers in diabetes are common and serious; the aetiology is often polymicrobial, often including S. aureus and Pseudomonas spp. Treatment in the out‐patient setting is safe and effective, and penicillins together with β‐lactamase inhibitors and fluoroquinolones are the most frequent choice.     

社区获得性肺炎255例治疗与国内外指南推荐方案对比研究

目的了解北京地区三甲医院对社区获得性肺炎(CAP)治疗的现状,并与国内外CAP指南治疗标准进行比较,为我国CAP指南的推广和应用提供循证医学依据。方法以2002-07~2004-06北京大学人民医院呼吸科收治的255例CAP患者为研究对象,通过回顾性研究,比较中国CAP诊疗指南中病情评估与Fine危险分层的相关性;比较中国CAP病情评估标准所分1组和2组患者联合使用抗菌药物的差异及抗菌药物选择的差异。结果中国CAP指南病情评估标准与Fine危险分层有良好的相关性(P=0·0000);按中国CAP指南病情评估标准,不符合住院标准组与符合住院标准组患者在选择单一抗菌药物方面差异有显著性意义(P=0·0290),在选择青霉素和第三代头孢菌素方面差异也具有显著性意义(P=0·0001;P=0·005)。不符合住院标准组与符合住院标准组患者新氟喹诺酮类抗菌药物使用比例均偏高,两组无统计学差异(P=0·182)。结论中国CAP指南病情评估标准与Fine危险分层有很好的相关性,能准确区分不同风险患者。加强对中国CAP诊治指南的贯彻执行,进一步规范CAP治疗标准任重而道远。     

Comparative Efficacies and Tolerabilities of Intravenous Azithromycin Plus Ceftriaxone and Intravenous Levofloxacin with Step-Down Oral Therapy for Hospitalized Patients with Moderate to Severe Community-Acquired Pneumonia

Objective: To compare the efficacy and tolerability of ceftriaxone plus azithromycin with those of levofloxacin in the treatment of hospitalized patients with moderate to severe community-acquired pneumonia (CAP). Design: Randomized, open-label multicenter trial with 1 : 1 treatment allocation in an inpatient setting. Patients: 212 male or female inpatients with a clinical diagnosis of CAP were included in the study. In each treatment group >50% of patients had a pneumonia severity index of IV or V. Interventions: Open-label treatment with either intravenous (IV) ceftriaxone 1g and IV azithromycin 500mg daily or IV levofloxacin 500mg daily. Patients who improved clinically were switched to oral follow-on therapy with either azithromycin 500 mg/day or levofloxacin 500 mg/day. At the clinician’s discretion, oral cefuroxime axetil was added to the treatment regimen of patients who received oral azithromycin if a macrolide resistant pneumococcal isolate was documented. Results: Overall, both study treatments were well tolerated. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 91.5% of patients treated with ceftriaxone plus azithromycin and 89.3% (95% CI ?7.1%, 11.4%) of patients treated with levofloxacin at the end of therapy visit and in 89.2% and 85.1% (95% CI ?6.7%, 14.8%) patients, respectively, at the end of study visit. Bacteriological eradication rates for both treatments were equivalent with the exception of Streptococcus pneumoniae; 44% of isolates were eradicated with levofloxacin compared with 100% of isolates with ceftriaxone plus azithromycin. Conclusions: As acknowledged by international CAP treatment guidelines, the combination of a third-generation cephalosporin and a macrolide is at least as efficacious as monotherapy with a fluoroquinolone with enhanced anti-pneumococcal activity, for hospitalized patients with moderate to severe CAP. Combined medication with a macrolide and third-generation cephalosporin may be preferred over fluoroquinolones as first-line therapy of hospitalized patients with CAP to minimize the development of multiresistant nosocomial Gram-negative bacilli.     

Chlamydia pneumoniae and Mycoplasma pneumoniae

Mycoplasma pneumoniae infection occurs worldwide and is the most common cause of community-acquired pneumonia (CAP) in 5- to 20-year-olds. The most reliable diagnostic test is the enzyme immunoassay, which allows immunoglobulin (Ig)G and IgM titration and presents 92% sensitivity and 95% specificity on paired samples. Potentially active drugs are tetracyclines, macrolides, ketolides, lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. Chlamydia pneumoniae accounts for 6 to 20% of CAP cases, depending on several factors such as setting of the studied population, age group examined, and diagnostic methods used. The current gold standard for serological diagnosis of acute infection is microimmunofluorescence testing. Tetracyclines and erythromycin show good in vitro activity and so far have been the most commonly employed drugs in the treatment of C. pneumoniae infection. New macrolides, ketolides, and new fluoroquinolones are other potentially effective drugs.     

Effect of macrolides as part of initial empiric therapy on length of stay in patients hospitalized with community-acquired pneumonia

BACKGROUND: The choice of antibiotics to treat community-acquired pneumonia (CAP) is primarily empiric, and the effect of this choice on length of stay (LOS) and mortality is largely unknown. OBJECTIVE: To examine the impact of antibiotic choice on these outcomes in general medical patients hospitalized with CAP. METHODS: One hundred patients hospitalized with CAP were prospectively identified. Seventy-six met inclusion criteria and were entered into the study. After hospital discharge, each medical chart was examined by 2 independent physicians who verified the admitting diagnosis and entered the data for antimicrobial regimens, a CAP mortality prediction tool, a social and disposition index, and other health outcomes. Patients were stratified according to the antibiotic received. Simple regression techniques were used to examine the correlation between initial therapy, specifically, ceftriaxone sodium or a macrolide, and LOS and mortality. RESULTS: Patients who received macrolides within the first 24 hours of admission had a markedly shorter LOS (2.8 days) than those not so treated (5.3 days; P = .01). This effect diminished as the interval before administering macrolides increased. Including ceftriaxone as part of the initial therapy did not appear to affect LOS. Patients given a macrolide for initial treatment did not differ significantly from those not treated in terms of mean age, mortality prediction tool score, or Social and Disposition Index score. Eleven of the 12 patients who received macrolides also received a beta-lactam antibiotic. CONCLUSION: Use of macrolides as part of an initial therapeutic regimen appears to be associated with shorter LOS.     

Patterns of Initial Antibiotic Therapy for Community-Acquired Pneumonia in U.S. Hospitals, 2000 to 2009

BackgroundAlthough clinical guidelines for management of community-acquired pneumonia (CAP) in non–intensive care unit (“non-ICU”) hospitalized patients have changed substantially over the last decade, it is unknown how treatment of this disease has evolved over this period.MethodsUsing data from > 100 U.S. hospitals, we identified all adults (aged ≥ 18 years) hospitalized for CAP between January 1, 2000, and June 30, 2009 (“study period”). We excluded patients admitted to ICU < 24 hours of admission, those not starting antibiotics < 24 hours of admission, those not receiving antibiotics for ≥ 48 hours (if alive), and those with probable healthcare-associated pneumonia. We defined “initial therapy” as all parenteral antibiotics received ≤ 24 hours of admission, and we examined changes in such therapy over the study period. The statistical significance of changes in initial therapy was ascertained using 2-tailed χ² tests.ResultsWe identified 40,392 patients who met all selection criteria. In 2000, the most frequently used initial regimens were levofloxacin (24.0% of all such admissions), ceftriaxone (9.0%), cefotaxime (7.3%), ceftriaxone plus levofloxacin (3.2%) and azithromycin plus cefotaxime (3.0%); in 2009, they were ceftriaxone plus azithromycin (18.5%), levofloxacin (12.7%), ceftriaxone (6.6%), moxifloxacin (4.7%) and ceftriaxone + levofloxacin (3.2%). Use of single-agent regimens declined between 2000 and 2009 (from 48.2%–30.0%); use of vancomycin almost doubled (13.1%–23.3%). All findings were statistically significant (P < 0.01).ConclusionsInitial antibiotic therapy for non-ICU CAP has changed substantially in the United States over the past decade, in line with evidence of widespread antibiotic resistance, evolving treatment guidelines and, most recently, quality improvement initiatives that tie hospital payments to guideline-based care.     

Etiology of community-acquired pneumonia in hospitalized patients in chile: the increasing prevalence of respiratory viruses among classic pathogens

BACKGROUND AND STUDY OBJECTIVES: The range and relative impact of microbial pathogens, particularly viral pathogens, as a cause of community-acquired pneumonia (CAP) in hospitalized adults has not received much attention. The aim of this study was to determine the microbial etiology of CAP in adults and to identify the risk factors for various specific pathogens. METHODS: We prospectively studied 176 patients (mean [+/- SD] age, 65.8 +/- 18.5 years) who had hospitalized for CAP to identify the microbial etiology. For each patient, sputum and blood cultures were obtained as well as serology testing for Mycoplasma pneumoniae and Chlamydophila pneumoniae, urinary antigen testing for Legionella pneumophila and Streptococcus pneumoniae, and a nasopharyngeal swab for seven respiratory viruses. RESULTS: Microbial etiology was determined in 98 patients (55%). S pneumoniae (49 of 98 patients; 50%) and respiratory viruses (32%) were the most frequently isolated pathogen groups. Pneumococcal pneumonia was associated with tobacco smoking of > 10 pack-years (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2 to 5.4; p = 0.01). Respiratory viruses were isolated more often in fall or winter (28%; p = 0.011), and as an exclusive etiology tended to be isolated in patients >/= 65 years of age (20%; p = 0.07). Viral CAP was associated with antimicrobial therapy prior to hospital admission (OR, 4.5; 95% CI, 1.4 to 14.6). CONCLUSIONS: S pneumoniae remains the most frequent pathogen in adults with CAP and should be covered with empirical antimicrobial treatment. Viruses were the second most common etiologic agent and should be tested for, especially in fall or winter, both in young and elderly patients who are hospitalized with CAP.     

Sequential IV/PO moxifloxacin treatment of patients with severe community-acquired pneumonia

BACKGROUND: IV/PO moxifloxacin was evaluated in the treatment of hospitalized patients with severe community-acquired pneumonia (CAP). METHODS: Data were pooled from two prospective, randomized studies. In the multinational study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD or IV/ PO amoxicillin clavulanate 1200/625 mg TID +/- IV/PO clarithromycin 500 mg BID. In the North American study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD, IV/ PO alatrofloxacin/trovafloxacin 200 mg QD, or IV/PO levofloxacin 500 mg QD. The primary endpoint was clinical success at the test-to-cure visit. Severe CAP was defined according to the 1993 ATS criteria. RESULTS: In the clinically valid population, clinical success rates were 88% (167/190) for moxifloxacin- and 83% (155/186) for comparator-treated patients (95% CI = -1.9%, 12.2%). Corresponding clinical success rates for the microbiologically valid population were 87% (59/68) and 84% (54/64), respectively (95% CI = 8.6%, 15.0%). A switch from IV to PO therapy was made by day 5 of therapy for 73% of moxifloxacin- vs. 60% of comparator-treated patients (P < 0.01). Clinical success rates were similar in a retrospective analysis using the revised 2001 ATS definition of severe CAP. Mortality rates were 6% (15/241) and 10% (24/238) in the moxifloxacin and comparator treatment groups, respectively. The incidence of drug-related adverse events was similar in both treatment groups. CONCLUSION: Sequential IV/PO moxifloxacin 400 mg QD is as safe and effective as other fluoroquinolones and a beta-lactam/macrolide combination for treating hospitalized patients with severe CAP.     

大肠埃希菌和肺炎克雷伯菌中质粒AmpCβ内酰胺酶基因型的检测

目的了解产质粒介导的AmpC酶大肠埃希菌和肺炎克雷伯菌的耐药性和基因型。方法收集2002年1月至2004年5月间呼吸科临床标本中分离的大肠埃希菌和肺炎克雷伯菌共110株，用酶提取物三维试验检测AmpC酶；用等电聚焦电泳、耐药质粒电转化试验、聚合酶链反应（PCR）及测序确定AmpC酶基因型。结果大肠埃希菌和肺炎克雷伯菌中AmpC酶检出率分别为9．30％（4／43），4．48％（3／67）。药敏试验结果显示产酶株对头孢西丁全部耐药，对第三代头孢菌素、酶抑制剂、氨曲南、阿米卡星及环丙沙星均有不同程度耐药，对头孢吡肟及亚胺培南较敏感。7株产AmpC酶菌株中有5株通过电转化试验可将头孢西丁耐药性传递给受体菌，经PCR扩增和测序证实为质粒介导DHA-1型AmpC酶。结论临床分离的大肠埃希菌和肺炎克雷伯菌中已经出现产质粒介导AmpC酶菌株，其耐药性能够水平传播，给临床抗感染治疗带来重大威胁。     

老年住院患者抗生素相关性腹泻调查

目的 探讨老年住院患者抗生素相关天性腹泻(AAD)的发病持点、危险因素及其防治策略。方法 对2003年2月1日住在本院的33l例老年患者进行回顾性调查，分析其在此后1个月内发生AAD的情况。结果 使用抗生素的248例老年住院患者中有6l例(100例次)发生AAD，发生率23.70％。AAD与使用抗生素种类、联合用药数量及疗程、住院天数、疾病严重程度、采用医疗干预措施等危险因素有关。较易引起AAD的抗生素为广谱青霉素或加酶抑制剂(21.62％)、第四代头孢菌素类(20.59％)、第三代头孢菌素类(20.45％)、碳青霉烯类(20.0％)等。所有AAD患者，在积级治疗基础疾锅的同时，经停用、减量、换用抗生素，服用微生态制剂，加强支持治疗后，痊愈及好转者48例(78例次)，有效百分率78％；复发者13例(2l例次)，复发百分率3l％，治疗无效者12例(2l例次)，无效百分率2l％；死亡l例,病死百分率l％。结论 只有提高临床医生对AAD的认识，加强预防措施，合理使用抗生素，才能有效地减少住院老年患者AAD的发生率.