IV-to-oral switch therapy for community-acquired pneumonia requiring hospitalization: focus on gatifloxacin

The majority of the 1.1 million patients hospitalized for community-acquired pneumonia (CAP) in the United States begin therapy with an intravenous antibiotic. A switch to oral therapy as soon as patients are clinically stable reduces the length of hospitalization and associated costs. Fluoroquinolones are appropriate candidates for switch therapy. Gatifloxacin is an excellent choice when a fluoroquinolone is being considered for sequential switch therapy in the treatment of CAP requiring hospitalization.     

Fluoroquinolones in the management of community‐acquired pneumonia

Aims: Review of the current guidelines for the use of respiratory fluoroquinolones in the management of community‐acquired pneumonia (CAP). Methods: Data were collected from recent clinical trials on fluoroquinolone therapy in patients with CAP and from updated recommendations of antimicrobial therapy in managing CAP, with a focus on current North American guidelines. Results: Randomised clinical trials of respiratory fluoroquinones (moxifloxacin, levofloxacin and gemifloxacin) in the treatment of CAP were identified and analysed. The bacteriology of CAP, and susceptibility rates, resistance rates and pharmacokinetic and pharmacodynamic properties of fluoroquinolones against causative pathogens in CAP, and adverse event profiles of these agents were described. Respiratory fluoroquinones have broad‐spectrum antibacterial activities against common causative pathogens in CAP and provide an important treatment option as monotherapy for outpatients with comorbidities and inpatients who are not admitted to the intensive care unit (ICU), including those with risk factors of drug‐resistant Streptococcus pneumoniae. For treatment of ICU patients with severe CAP, it is recommended that fluoroquinolones be used in combination with a β‐lactam. Recent studies also demonstrated a more rapid resolution of clinical symptoms with the use of highly potent respiratory fluoroquinolones. Discussion: Appropriate use of fluoroquinolone agents may shorten the duration of antimicrobial therapy and the length of hospital stay and contribute to the decreased development of resistance in patients with CAP. Adverse event profiles of these agents should be considered to facilitate the selection of an appropriate fluoroquinolone for appropriate CAP patients. Conclusion: The fluoroquinolone class, specifically those with adequate activity against respiratory pathogens, represents an important and convenient treatment option for patients with CAP.     

Safety and efficacy of sequential i.v. to p.o. moxifloxacin versus conventional combination therapies for the treatment of community-acquired pneumonia in patients requiring initial i.v. therapy

To compare the efficacy of sequential i.v. to p.o. moxifloxacin with ceftriaxone ± azithromycin ± metronidazole for the treatment of patients with community acquired pneumonia (CAP), a multi-centered, prospective, randomized, open label study was performed. CAP patients were randomized to moxifloxacin (400 mg/d—at least one i.v. dose) or ceftriaxone (at least one dose of 2 g i.v. q.d. followed by cefuroxime 500 mg p.o. b.i.d.) ± azithromycin, ± metronidazole (cephalosporin/macrolide control: CMC). The primary endpoint was clinical response at test-of-cure (TOC) visit. Bacteriological response at TOC was the secondary endpoint. Clinical cure was found in 83.3% (90/108) of moxifloxacin patients and 79.6% (90/113) of control patients. Microbiological responses were 81.8% (18/22) for moxifloxacin and 60.7% (17/28) for CMC patients. Drug-related adverse events occurred in 18.0% of moxifloxacin and 16% of CMC patients. It is concluded that i.v. to p.o. moxifloxacin is as effective as CMC for treatment of CAP and is a reliable alternative antimicrobial therapy.     

Performance of CURB‐65 and CURB‐age in community‐acquired pneumonia

Background: Community‐acquired pneumonia (CAP) is common and associated with significant mortality. In this study, we validated a newly proposed severity assessment rule for CAP, CURB‐age, and also compared with to the currently recommended criteria in UK, CURB‐65. Methods: We conducted a prospective study in three hospitals in Norfolk and Suffolk, UK. One hundred and ninety patients were included and followed up for 6 weeks. Results: Of 190 patients, 100 were men (53%). The age range was 18–101 years (median 76 years). Sixty‐five (34%) had severe pneumonia by CURB‐65 and 54 (28%) had severe pneumonia by CURB‐age. There were 54 deaths during follow‐up. There were 32 deaths (50%) in severe and 22 deaths (18%) in non‐severe group by CURB‐65. There were 27 deaths each in both the groups by CURB‐age (50% of severe cases and 20% of non‐severe cases). For CURB‐65, sensitivity, specificity, and positive and negative predictive values were 59.3% (45.0–72.4), 75.7% (67.6–82.7), 49.2% (36.6–61.9) and 82.4% (74.6–88.6), respectively. For CURB‐age, the respective values were 50.0% (31.1–63.9), 80.1% (72.4–86.5), 50.0% (36.1–63.9) and 80.1% (72.4–86.5). Exclusion of patients aged < 65 years did not alter the results. Conclusions: Despite better specificity in correctly identifying 6‐week mortality for CAP, CURB‐age appears to be less sensitive than CURB‐65. Our findings further assure the usefulness of CURB‐65 for predicting mortality in CAP.     

Doxycycline vs. levofloxacin in the treatment of community‐acquired pneumonia

Background: Community‐acquired pneumonia (CAP) affects 5–10 million adults annually in the United States with approximately 1·1 million hospitalizations. Current guidelines recommend fluoroquinolones as monotherapy for treatment of CAP in general medical wards and doxycycline monotherapy for outpatient therapy only. Fluoroquinolones are expensive and development of bacterial resistance to them has become a concern. Therefore, we studied whether doxycycline is as efficacious as levofloxacin in treatment of CAP in general medical wards. Methods: In this prospective double‐blinded trial, non‐pregnant adults with clinical and radiological evidence of pneumonia requiring hospitalization were enrolled. Patients who were septic, hypoxic requiring intubations, nursing home residents, diagnosed with severe hepatic or renal dysfunction, recently hospitalized or immunocompromised were excluded from the study. Subjects were randomly assigned to either i.v. levofloxacin 500 mg daily or doxycycline 100 mg twice daily. After discharge, patients were followed for 2 months. Results: There were 30 patients in the levofloxacin group and 35 patients in the doxycycline group. Groups were comparable in both clinical and laboratory profiles. Additionally, efficacy of treatment was not significantly different between the two groups (P = 0·844). Length of stay was 5·7 ± 2·05 days in the levofloxacin group and 4·0 ± 1·82 days in the doxycycline group (P < 0·0012). Failure rate was similar in both groups (P = 0·893). Total antibiotic cost was $122·07 ± 15·84 for levofloxacin and $64·98 ± 24·4 for doxycycline (P < 0·0001). Conclusions: Our study supports doxycycline as an effective and economical alternative therapy for levofloxacin in the empirical treatment of CAP in general medical wards.     

Cytokine responses,microbial aetiology and short‐term outcome in community‐acquired pneumonia

Background

The inflammatory response to community‐acquired pneumonia (CAP) is orchestrated through activation of cytokine networks and the complement system. We examined the association of multiple cytokines and the terminal complement complex (TCC) with microbial aetiology, disease severity and short‐term outcome.

Materials and methods

Plasma levels of 27 cytokines and TCC were analysed in blood samples obtained at hospital admission, clinical stabilization and 6‐week follow‐up from 247 hospitalized adults with CAP. Fourteen mediators were included in final analyses. Adverse short‐term outcome was defined as intensive care unit (ICU) admission and 30‐day mortality.

Results

Cytokine and TCC levels were dynamic in the clinical course of CAP, with highest levels seen at admission for most mediators. Admission levels of cytokines and TCC did not differ between groups of microbial aetiology. High admission levels of IL‐6 (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.18‐1.84, P = .001), IL‐8 (OR 1.79, 95% CI 1.26‐2.55, P = .001) and MIP‐1β (OR 2.28, 95% CI 1.36‐3.81, P = .002) were associated with a CURB‐65 severity score of ≥3, while IL‐6 (OR 1.37, 95% CI 1.07‐1.74, P = .011) and MIP‐1β (OR 1.86, 95% CI 1.03‐3.36, P = .040) were associated with a high risk of an adverse short‐term outcome.

Conclusions

In this CAP cohort, admission levels of IL‐6, IL‐8 and MIP‐1β were associated with disease severity and/or adverse short‐term outcome. Still, for most mediators, only nonsignificant variations in inflammatory responses were observed for groups of microbial aetiology, disease severity and short‐term outcome.     

左氧氟沙星与克拉霉素为基础的三联疗法治疗十二指肠球部溃疡的对比研究

目的比较以左氧氟沙星与克拉霉素为基础的三联疗法对十二指肠球部溃疡（DU）合并幽门螺杆菌（Hp）感染的愈合率及Hp根除率。方法137例Hp阳性的DU（A1期）患者随机分为两组：左氧氟沙星组（A组）69例;克拉霉素组（B组）68例。A组：埃索关拉唑20mg＋阿莫西林1．0g,每天2次1：7服;左氧氟沙星0．5g,每天1次口服。B组：埃索美拉唑20mg＋阿莫西林1．0g＋克拉霉素0．5g,每天2次口服。连续7天,然后两组均继续给予埃索美拉唑20mg,每天1次口服,共21天。用药结束后1～2周再次对患者进行内镜及Hp检查,观察溃疡愈合及HP转阴情况。结果左氧氟沙星组溃疡愈合率为91．3％,克拉霉素组为89．7％,两组之间差异无统计学意义（P〉0．05）。左氧氟沙星组Hp清除率为91．3％,明显高于克拉霉素组的72．1％（P〈0．05）。B组不良反应发生率为17．7％,高于A组的7．2％,但两组间差异无统计学意义（P〉0．05）。两组费用一效果比分别为653．2元和1082．2元,A组远低于B组。结论以左氧氟沙星为基础的三联疗法治疗Hp阳性Du的愈合率与以克拉霉素为基础的三联疗法相似,但Hp清除率显著增加,不良反应发生明显减少且药物经济学效益更优。     

Comparative efficacy of azithromycin versus clarithromycin in combination with beta-lactams to treat community-acquired pneumonia in hospitalized patients: a systematic review

ObjectiveThe objective was to compare the efficacy of azithromycin and clarithromycin in combination with beta-lactams to treat community-acquired pneumonia among hospitalized adults.MethodsFive databases (PubMed, Google Scholar, Trip, Medline, and Clinical Key) were searched to identify randomized clinical trials with patients exposed to azithromycin or clarithromycin in combination with a beta-lactam. All articles were critically reviewed for inclusion in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsSeven clinical trials were included. The treatment success rate for azithromycin–beta-lactam after 10 to 14 days was 87.55% and that for clarithromycin–beta-lactam after 5 to 7 days of therapy was 75.42%. Streptococcus pneumoniae was commonly found in macrolide groups, with 130 and 80 isolates in the clarithromycin-based and azithromycin-based groups, respectively. The length of hospital stay was an average of 8.45 days for patients receiving a beta-lactam–azithromycin combination and 7.25 days with a beta-lactam–clarithromycin combination.ConclusionMacrolide inter-class differences were noted, with a higher clinical success rate for azithromycin-based combinations. However, a shorter length of hospital stay was achieved with a clarithromycin–beta-lactam regimen. Thus, a macrolide combined with a beta-lactam should be chosen using susceptibility data from the treating facility.     

单一及联合应用抗生素治疗呼吸机相关性肺炎效果Meta分析

目的 系统评价单一及联合使用抗生素治疗呼吸机相关性肺炎(ventilator-associated pneumonia,VAP)的效果.方法 应用计算机检索PubMed、EMBASE、Cochrane library、中国生物医学文献数据库、中国期刊全文数据库、万方数据库1990年1月-2014年3月发表的相关文献,对符合标准的文献,由2名评价员应用Jadad量表评价文献质量,应用Revoew Manager5.2软件进行Meta分析.结果 共纳入文献6篇,Jadad量表评分均高于4分,共1 190例患者,其中联合抗生素治疗组(联合组)624例,单一抗生素治疗组(对照组)566例;Meta分析结果显示,2组病死率(RR=0.98,95％CI:0.80～1.20,P=0.87)、治愈率(RR=1.11,95％CI:0.65～1.92,P=0.70)、ICU留治时间(MD=-0.72,95％CI:-5.23～3.78,P=0.75)、机械通气时间(MD=-0.37,95％CI:-4.15～3.42,P=0.85)差异无统计学意义.结论 对VAP患者,推荐常规选用恰当抗菌谱的单一抗生素治疗.     

多西环素可否替代大环内酯类药物用于治疗社区获得性肺炎

2007年美国感染病学会制定的社区获得性肺炎（CAP）诊治指南推荐经验性使用呼吸喹诺酮类或8内酰胺类联合大环内酯类药物治疗CAP非ICU住院患者。大环内酯类药物中的阿奇霉素因与其他药物相互作用少,服用方便和安全性高而被广泛使用。但是最近有研究报道阿奇霉素可能增加患者的心血管死亡风险。与未接受抗生素治疗的对照组相比,阿奇霉素治疗5d心血管病患者死亡和全因死亡危害比分别为2．88和1．85。     

米诺环素与阿奇霉素联用治疗儿童支原体肺炎的临床研究

目的探讨米诺环素与阿奇霉素联用治疗儿童支原体肺炎的临床效果及安全性。方法选取该院2009年1月至2012年1月收治的支原体肺炎患儿240例,采用随机数字表法分为对照组和米诺环素组,每组各120例。对照组患者采用阿奇霉素序贯治疗;米诺环素组患者使用阿奇霉素-米诺环素转换治疗。比较2组患儿临床治疗总有效率、咳嗽消失时间、发热持续时间、住院时间及肺外并发症发生率等。结果米诺环素组患儿临床治疗总有效率明显高于对照组,差异有统计学意义(P0.05);咳嗽消失、发热持续、住院时间均少于对照组,差异有统计学意义(P0.05);皮疹发生率显著低于对照组,差异有统计学意义(P0.05)。结论米诺环素与阿奇霉素联用治疗儿童支原体肺炎可显著提高疗效,缓解临床症状,缩短病程,且未增加肺外并发症发生风险。     

The role of solithromycin in the management of bacterial community-acquired pneumonia

The fluoroketolide solithromycin is 2-fold more potent in vitro than telithromycin against pneumococci (including macrolide-resistant strains) and Haemophilus influenzae and very active on pathogens causing atypical pneumonia. In contrast, it is a 30-fold less potent inhibitor of nicotinic receptors incriminated in telithromycin toxicity. In Phase II/III trials, oral solithromycin once-daily (800 mg on day 1; 400 mg on days 2-5) proved effective and safe when compared to respiratory fluoroquinolones for the treatment of community-acquired bacterial pneumonia (CABP). A Phase III intravenous trial vs. moxifloxacin has been recently completed for the same indication. Solithromycin may restore interest in ketolides as a first-line therapy for CAPB. Solithromycin safety should nevertheless be confirmed in larger populations allowing for detection of rare adverse events.