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The Efficacy and Safety of Tigecycline for the Treatment of Bloodstream

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The Efficacy and Safety of Tigecycline for the Treatment of Bloodstream Wang et al. Ann Clin Microbiol Antimicrob (2017) 16:24 DOI 10.1186/s12941-017-0199-8 Annals of Clinical Microbiology and Antimicrobials REVIEW Open Access The efcacy and safety of tigecycline for the treatment of bloodstream infections: a systematic review and meta‑analysis Jian Wang, Yaping Pan, Jilu Shen* and Yuanhong Xu Abstract Patients with bloodstream infections (BSI) are associated with high mortality rates. Due to tigecycline has shown excellent in vitro activity against most pathogens, tigecycline is selected as one of the candidate drugs for the treatment of multidrug-resistant organisms infections. The purpose of this study was to evaluate the efectiveness and safety of the use of tigecycline for the treatment of patients with BSI. The PubMed and Embase databases were systematically searched, to identify published studies, and we searched clinical trial registries to identify completed unpublished studies, the results of which were obtained through the manufacturer. The primary outcome was mortal- ity, and the secondary outcomes were the rate of clinical cure and microbiological success. 24 controlled studies were included in this systematic review. All-cause mortality was lower with tigecycline than with control antibiotic agents, but the diference was not signifcant (OR 0.85, [95% confdence interval (CI) 0.31–2.33; P 0.745]). Clinical cure was signifcantly higher with tigecycline groups (OR 1.76, [95% CI 1.26–2.45; P 0.001]). Eradication= efciency did not dif- fer between tigecycline and control regimens, but the sample size for these= comparisons was small. Subgroup analy- ses showed good clinical cure result in bacteremia patients with CAP. Tigecycline monotherapy was associated with a OR of 2.73 (95% CI 1.53–4.87) for mortality compared with tigecycline combination therapy (6 studies; 250 patients), without heterogeneity. Five studies reporting on 398 patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae BSI showed signifcantly lower mortality in the tigecycline arm than in the control arm. The combined treatment with tigecycline may be considered the optimal option for severely ill patients with BSI. Background infections has been extensively observed worldwide and Bloodstream infections (BSI) are potentially life-threat- has become a priority issue over past decade. Tigecycline ening diseases. BSI was defned as at least 1 positive is a useful alternative to face the challenges of many MDR blood culture for a recognized pathogen and clinical organisms. Tigecycline has a large volume of distribution symptoms consistent with bacteraemia. Tey can cause of 7–10 l/kg [1], penetrating well into diferent tissues, it serious secondary infections, such as infective endocar- has been approved for the treatment of complicated skin ditis and osteomyelitis, and may result in severe sepsis. and soft-structure infections (cSSSI), complicated intra- Meanwhile, BSI due to multidrug-resistant (MDR) organ- abdominal infections (cIAI), and community-acquired isms has been associated with multiple poor outcomes, bacterial pneumonia (CAP). Tigecycline is not indicated including increased length of hospital stay, health care for treatment of diabetic foot infection or for hospital- costs and a high rate of morbidity and mortality. acquired or ventilator-associated pneumonia [2]. Te use Tigecycline is a glycylcycline with a broad spectrum of tigecycline in bacteremia is controversial because of its of antibacterial activity. Te emergence of MDR strains low serum levels with standard dosing [3]. Attention should be paid by clinicians, because tige- cycline was associated with higher mortality than *Correspondence: [email protected] comparator antibiotics [4–6]. However, a recent meta- Department of Clinical Laboratory, The First Afliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230022, Anhui, China analysis showed that the drug was not associated with © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. Ann Clin Microbiol Antimicrob (2017) 16:24 Page 2 of 10 signifcantly higher mortality than comparator antibiot- obtained during or after the antibiotic therapy. Because ics and was as efective as comparators when the analy- there are no standard criteria to assess clinical response sis was restricted to patients who received tigecycline for and adverse events, we accepted the criteria as reported approved indications [7]. A prospective study demon- in each study. strates that tigecycline plus prolonged infusion standard- All statistical analyses were performed using the com- dose imipenem/cilastatin, showed good clinical efcacy prehensive meta-analysis V2.2 (BioStat, Englewood, NJ). on VAP patients with XDR-Ab VAP bacteremia [8]. Te Among the controlled studies, the between-study het- increased mortality associated with tigecycline is not yet erogeneity was assessed using the I2 test, whereby I2 val- well understood in the treatment of BSI. Terefore, we ues >50% were defned as indicating heterogeneity. Either systemically searched and analysed the current available fxed-efects (Mantel–Haenszel method) or random- evidence to assess clinical efectiveness of tigecycline for efects (DerSimonian and Laird method) models were the treatment of BSI. used, depending on the heterogeneity result. If no het- erogeneity was found, meta-analysis was done using the Methods Mantel–Haenszel fxed-efects model. Binary outcomes Literature search from controlled studies were expressed as odds ratios Relevant studies were identifed through PubMed, (OR) with their 95% confdence intervals (CI), and con- Embase and hand-searched from inception until Octo- tinuous outcomes were expressed as the mean diference ber 2016.Te search terms were:“(tigecycline OR TGC between 2 groups. Egger regression, as well as the Begg OR tygacil) and (bacteraemia OR bacteremia OR blood- methods, was used to evaluate publication bias. All P val- stream infection OR sepsis OR septicaemia)”. No lan- ues were two-tailed, and a P value of ≤0.05 was consid- guage restrictions were applied. ered statistically signifcant. Some statistical analysis was performed by using the SPSS statistical software (version Study selection 19; SPSS Inc., Chicago, IL). Categorical variables were Any article providing the clinical outcomes of patients evaluated by using the χ2 test or 2-tailed Fisher’s exact treated for bloodstream infections caused by any etio- test, as appropriate. Subgroup analyses for mortality logical agent was considered eligible for inclusion in and clinical cure were planned for bacteraemic patients. the review. Prospective and retrospective observational Comparisons were subcategorized by the type of infec- cohort studies examining the association between tige- tion. A funnel plot was used to assess small-study efects. cycline use (on hospital admission or previous users) and the outcomes of bacteremic patients were included. Results Te outcome of interest was overall hospital mortality at Literature search results the longest follow-up at each single study. Case reports 1540 potential articles were identifed; 56 case reports and case series including fewer than 10 infected patients and clinical series including less than 10 infected patients treated with tigecycline were excluded from the review. were excluded; 41 duplicates and 18 single-arm studies were excluded; 22 studies were ruled out because they did Data extraction not present clear treatment regimens or detailed clinical Te extracted data consisted of the main characteristics outcomes; 24 articles were excluded due to few patients of a study (frst-author name, year of publication, coun- in each group. Ultimately 24 studies met the inclusion try, study period, and design), main characteristics and criteria, 24 controlled studies (1961 patients) included in underlying diseases of the study population, number of this systematic review. patients with infections BSI, the causative pathogen(s), sites of infections, and antibiotic treatment (combination Study characteristics therapy or monotherapy). Clinical outcomes (mortality, Te features of the 24 trials are described in Table 1. Five treatment failure) of patients in each treatment group of them were prospective cohort studies, 7 were retro- were recorded as well. spective studies. All of the included controlled studies had an NOS score >3. Most patients in the included stud- Statistical analysis ies were critically ill, with most of them in ICU. We chose mortality as the primary outcome, because of the high mortality rates among patients with BSI, while Mortality the secondary outcomes were: clinical response, micro- As shown in Fig. 1, no signifcant diference was noted biological response, adverse efects, and emergence of when tigecycline was compared with control groups in resistance. Microbiological response was defned as suc- terms of all-cause mortality (14 studies; 1502 patients) cessful when eradication or sterile culture results were [OR 0.841, 95% confdence interval
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