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systematically searched, to identify published studies, and we searched clinical trial registries to identify completed unpublished studies, the results of which were obtained through the manufacturer.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 (CI) 0.517–1.367; Wang et al. Ann Clin Microbiol Antimicrob (2017) 16:24 Page 3 of 10 - - of colistin base 8 divided over or 12 h lowed by 2 g by lowed per 12 h van - plus comycin aztreonam followed by by followed 600 mg per 12 h vanco plus mycin linezolid and merope nem every 8 h, 5 mg/kg gentamicin and amikacin once daily by 500 mg per by 6 h combined imipenem and cilastatin 2.5–5 mg/kg/d Na - 1 g per 12 h fol 1 g per 12 h Na 1 g imipenem Na mg followed 500 mg followed - regi Control men dose mg, of 100 mg, by followed 50 mg every 12 h of tigecycline mg, of 100 mg, by followed 50 mg every 12 h mg, of 100 mg, by followed 50 mg every 12 h the total daily the total dose was 100–200 mg administered in two divided dosages mg, of 100 mg, by followed 50 mg every 12 h Initial dose Standard dose Standard Initial dose Initial dose Na For tigecycline For Na Initial dose Tigecycline Tigecycline dose - - enem aztreonam linezolid tam + imipe nem/cilastatin noglycoside noglycoside carbapenem cilastatin Colistin carbapColistin Na Vancomycin plus Vancomycin Vancomycin or Vancomycin Sulbac - Colistin ami - Colistin Na Imipenem Compatator - - sulbactam sulbactam levofoxacin ceftazidime cilasta noglycoside noglycoside carbapenem Colistin Ampicillin- None None Ipipenem/ Colistin ami - Colistin Na None Concomitant Concomitant antibiotics administere din tigecy cline group 29/55 17/65 8/22 14/20 28/56 94/81 162/163 14/27 Sample size(no.of tigecycline/ control patients) after the last dose At discharge At At 14 days At Overall days 12–37 days At At 14 days At At 28 days At Overall Undetermined Mortality assessed XDR-Ab Acinetobacter XDR-Ab MRSA VRE XDR-Ab CP-Kp Mix Mix Causative Causative pathogen(s) - - - bacteremia bacteremia remia remia Bacteremia Secondary cSSSI with Bacteremia VAP with bacte VAP BSI Bacteremia cIAI with bacte Type of infec Type tion double-blind, phase 3 phase 3 studies, phase studies, 3 and 4 double-blind phase 3 Prospective Retrospective Randomized, Randomized, Double-blind, Prospective Retrospective Comparative Comparative Prospective, Prospective, Type of study Type Taiwan Taiwan Multicenter Multicenter Taiwan Greece USA Multicenter Location 2010–13 2007–13 Na 2003–05 2013 2009–10 2001–08 Na Study years Study Characteristics of included studies Characteristics al. [ 25 ] et al. [ 24 ] al. [ 11 ] et al. al. [ 27 ] Cheng et al. al. [ 26 ] Liou et al. Sacchidanand al. et al. Florescu al. [ 8 ] Jean et al. al. [ 23 ] Daikos et al. McGovern al. [ 22 ] Oliva et al. 1 Table Reference Wang et al. Ann Clin Microbiol Antimicrob (2017) 16:24 Page 4 of 10 cin plus 2 g per aztreonam 12 h - lin/tazobac tam every 8 h for a total a total for daily dose of 6,000,000– 9,000,000 IU colistin; 4–5 mg/kg every 24 h gentamicin; 2 g every 8 h meropenem - 24 h levofoxa cin - 1 g vancomy Na Na 4.5 g piperacil - Na Every 8–12 h 500 mg every - regi Control men dose mg, of 100 mg, by followed 50 mg every 12 h mg, of 100 mg, by followed 50 mg every 12 h (100–200 mg/ day) mg, of 100 mg, by followed 50 mg every 12 h Initial dose Na Na Initial dose Na Every 12 h Initial dose Tigecycline Tigecycline dose - aztreonam tamicin bactam gentamicin carbapenem gentamicin meropenem Vancomycin- Na Colistin gen - Colistin Piperacillin/tazo Colistin Colistin Colistin Colistin Levofoxacin Compatator - - tamicin tazobactam gentamicin carbapenem amikacin gentamicin meropenem None Na Colistin gen - Colistin Piperacillin/ Colistin Colistin Colistin Colistin None Concomitant Concomitant antibiotics administere din tigecy cline group 15/10 91/79 27/9 86/94 22/13 70/48 22/40 Sample size(no.of tigecycline/ control patients) after the last dose Overall Na At 30 days At Overall Overall At 30 days At days 7–23 days At Mortality assessed pneumoniae Mix Mix KPC-Kp Mix KPC-Kp KPC-Kp Streptococcus Streptococcus Causative Causative pathogen(s) - bacteremia teremia cSSSI with Bacteremia BSI Bacteremia BSI BSI CAP with bac - Type of infec Type tion double-blind, phase 3 randomized, 7 randomized, double-blind and 1 open- phase 3 label, observational study open-label double-blind, phase 3 Randomized, Randomized, Retrospective, Retrospective, Single-centre Prospective, Prospective, Observational Retrospective Randomized, Randomized, Type of study Type Multicenter Multicenter Greece Multicenter Greece Italy Multicenter Location 2002–03 Na Na 2008–10 2008–10 2010–11 2003–05 Study years Study continued [ 19 ] al. et al. Olivgeris [ 32 ] [ 31 ] [ 30 ] al. [ 29 ] et al. al. [ 28 ] et al. al. [ 33 ] et al. Breedt al. et al. Gardiner Papadimitriou- al. et al. Bucaneve Zarkotou et al. Tumbarello Tumbarello Tanaseanu Tanaseanu 1 Table Reference Wang et al. Ann Clin Microbiol Antimicrob (2017) 16:24 Page 5 of 10 - - ertape nem ± vanco mycin or per 12 h levofoxacin by 500 mg per by 6 h combined imipenem and cilastatin cin plus 2 g per aztreonam 12 h by 500 mg per by 6 h combined imipenem and cilastatin Na Na Na 1 g once-daily Na 500 mg per 24 h mg followed 500 mg followed - 1 g vancomy mg followed 500 mg followed - regi Control men dose 12 h mg, of 100 mg, by followed 50 mg every 12 h once-daily tigecycline mg, of 100 mg, by followed 50 mg every 12 h mg, of 100 mg, by followed 50 mg every 12 h mg, of 100 mg, by followed 50 mg every 12 h mg, of 100 mg, by followed 50 mg every 12 h Na 50 mg every Initial dose 150 mg Na Initial dose Initial dose Initial dose Initial dose Tigecycline Tigecycline dose - - - - polymyxin polymyxin aminoglyco side aminoglyco side nem ± vanco mycin gentamicin et al. cefepime cilastatin aztreonam cilastatin Carbapenem Vancomycin Polymyxin b Polymyxin Ertape Carbapenem Levofoxacin Imipenem- Vancomycin- Imipenem- Compatator - - - - polymyxin polymyxin aminoglyco side antibiotic aminoglyco side Carbapenem Na Beta-lactam None Carbapenem None None None None Concomitant Concomitant antibiotics administere din tigecy cline group 15/62 8/23 26/42 7/14 11/23 32/31 26/23 23/24 40/50 Sample size(no.of tigecycline/ control patients) At 30 days At Na At 30 days At Na At 28 days At Overall Na Overall Overall Mortality assessed teriaceae - KPC-Enterobac CVC-CoNS CR-Kp Mix KPC-Kp Mix Mix Mix Mix Causative Causative pathogen(s) - - - remia bacteremia remia Bacteremia Bacteremia BSI Bacteremia Bacteremia CAP with bacteremia cIAI with bacte cSSSI with cIAI with bacte Type of infec Type tion double-blind, phase 3 phase 3 phase 3 double-blind, phase 3 double-blind, phase 3 Retrospective Prospective Retrospective Randomized, Randomized, Retrospective Double-blind, Double-blind, Randomized, Randomized, Randomized, Randomized, Type of study Type Brazil USA USA Multicenter USA Multicenter Multicenter Multicenter Multicenter Location 2009–13 2007 2006–13 2006–09 2005–09 Na Na 2001–04 2002–04 Study years Study continued [ 42 ] al. monds et al. [ 40 ] [ 38 ] [ 37 ] al. [ 35 ] et al. al. [ 34 ] et al. al. et al. Oliveira Maki [ 41 ] et al. Gomez-Sim - al. [ 39 ] Lauf et al. al. et al. Qureshi Dartois et al. 36 ] [ et al. Fomin Ellis-Grosse Babinchak Reference 1 Table K. carbapenem-resistant pneumoniae ; CVC- pneumonia; CR-Kp, community-acquired skin cSSSI, complicated infections; and skin-structure intra-abdominal CAP, infections; infection; cIAI, complicated BSI, bloodstream Klebsiella pneumoniae carbapenemase-producing KPC-Kp, ; Na, not available; aureus K. coagulase-negative Staphylococcus staphylococcal; pneumoniae ; MRSA, methicillin-resistant catheter-related venous central CoNS, baumannii Acinetobacter drug-resistant extensively XDR-Ab, enterococci; vancomycin-resistant VRE, pneumonia; ventilator-associated VAP, Wang et al. Ann Clin Microbiol Antimicrob (2017) 16:24 Page 6 of 10

Fig. 1 Mortality with tigecycline versus other antibiotics therapy

P = 0.485]. Because statistical heterogeneity existed tigecycline combination therapy group in terms of among studies (X­ 2 32.76, df 13, (P 0.002), mortality (6 studies; 250 patients) (OR 2.733, [95% CI 2 = = = 2 ­I = 60.3%), a random-efects model of analysis was 1.533–4.873; P = 0.001]; ­I = 8.7%). A signifcantly higher used. No publication bias was detected by Egger regres- mortality was noted in the monotherapy group than in sion (t = −0.39; df = 12.0; P = 0.701) or Begg (z = 0.55; the combination therapy group in cases of blood stream df = 12.0; P = 0.584). infection. Te mortality in the combination of tigecycline Table 2 shows the subgroup analysis of the controlled plus colistin based group was not signifcantly lower than studies. A signifcant diference was observed between that in the other antibiotics combination group (OR 0.68, 2 the tigecycline monotherapy therapy group and the [95% CI 0.407–1.135; P = 0.14]; ­I = 0.0%).

Table 2 Subgroup analysis of overall mortality with tigecycline versus other antibiotics for treatment of bloodstram infections in controlled studies Variables Studies, no. Mortality of tigecycline compared Heterogeneity of studies (patients, no.) with control OR (95% CI); P

Monotherapy vs combination 6 (250) 2.733 (1.533–4.873); 0.001 X2 5.47, df 5, (P 0.361), ­I2 8.7% = = = = Tigecycline plus polymyxins based vs 5 (289) 0.680 (0.407–1.135); 0.140 X2 2.88, df 4, (P 0.578), ­I2 0.0% other antibiotics combination = = = = Kp BSI 6 (466) 0.678 (0.457–1.006); 0.054 X2 3.95, df 5, (P 0.556), ­I2 0.0% = = = = KPC-Kp BSI 5 (398) 0.636 (0.417–0.971); 0.036 X2 3.31, df 4, (P 0.507), ­I2 0.0% = = = = Acinetobacter BSI 3 (221) 0.967 (0.096–9.759); 0.978 X2 23.76, df 2, (P 0.001), ­I2 91.6% = = = = CI, confdence interval; OR, odds ratio Wang et al. Ann Clin Microbiol Antimicrob (2017) 16:24 Page 7 of 10

2 In the patients infected with Klebsiella pneumoniae cSSSI (OR 0.71, [95% CI 0.26–1.90; P = 0.494]; ­I = 0.0%; (Kp) BSI, tigecycline seemed to have a lower mortal- [P = 0.821]), but in trials assessing patients with CAP, ity than comparator drugs, but the diference was not for the rate of clinical cure, the efcacy of tigecycline signifcant (OR 0.678, [95% CI 0.457–1.006; P 0.054]; was better than that of comparator regimens (OR 2.44, 2 = 2 ­I = 0.0%; [P = 0.556]). Five studies (398 patients) [95% CI 1.20–4.94; P = 0.013]; ­I = 0.0%; [P = 0.821]). As reported data on carbapenemase-producing Kp BSI, and shown in Fig. 2. a signifcant diference with respect to overall mortality was observed between the tigecycline therapy group and Microbiological response the controls (OR 0.636, [95% CI 0.417–0.971; P 0.036]; As shown in Fig. 2, tigecycline group did not difer sig- 2 = ­I = 0.0%; [P = 0.507]). Tree controlled studies (221 nifcantly compared with the comparators in the rate of patients) reported Acinetobacter BSI, no diference was microbiological success (OR 2.07, [95% CI 0.56–7.70; 2 seen between patients who received tigecycline as ther- P = 0.279]; ­I = 0.0%; [P = 0.854]) (Fig. 2). apy and others in mortality (OR 0.967, [95% CI 0.096– 2 Adverse efects 0.759; P = 0.978]; ­I = 91.6%; [P = 0.001]). Tere were not sufciently efective data to be recoded, Clinical cure so that the common adverse efects of tigecycline (nau- Tere was a signifcant diferences were observed sea, vomiting, and diarrhea) could not be extracted in any between the tigecycline and control groups in this regard of the studies. (OR 1.76, [95% CI 1.26–2.45; P 0.001]; ­I2 29.2%; = = Discussion [P = 0.159]; Fig. 2). Clinical cure was signifcantly higher in the tigecycline population. In the subgroup analysis, We conducted this systematic review and meta-analysis for analysis by type of infection, without statistical sig- to investigate the efectiveness and safety of tigecycline nifcance was found in patients with cIAI (OR 0.97, [95% for the treatment of BSI. Numerous studies have estab- 2 CI 0.52–1.80; P = 0.919]; ­I = 0.0%; [P = 0.953]) and lished bacteremia as a marker of severe infection and a

Fig. 2 The efcacy of tigecycline, as compared with other antibiotics, in treating infections caused by BSI Wang et al. Ann Clin Microbiol Antimicrob (2017) 16:24 Page 8 of 10

risk for adverse outcomes in multiple treatment settings diference was found when tigecycline was compared [9, 10], but there were some positive elements about the with the comparators. treatment of BSI with tigecycline. Previous studies have shown that the most common To our knowledge, this was the frst systematic review adverse efects of tigecycline had increased incidence in to assess the efcacy of tigecycline in treating BSI. the tigecycline group, such as nausea, vomiting, and diar- Although all-cause mortality was lower with tigecycline rhea [13, 14]. According to a recently published review, than with the control regimens, the diference was not tigecycline induces acute pancreatitis, indicating that signifcant. Tigecycline seemed to be better than levo- surveillance for adverse events from the digestive system foxacin for treatment of community-acquired pneumo- is needed during treatment [15]. But lack of data from all nia, and worse than control regimens for cIAI and cSSSI, trials results can not be obtained about adverse events but these diferences were not signifcant. However, outcomes in our meta-analysis. drug safety guidelines published by the FDA refer to an Small non-comparative series have reported relatively increased mortality risk associated with intravenous tige- poor clinical and microbiological outcomes with tigecy- cycline compared with other drugs used to treat serious cline for tigecycline-susceptible CR-Ab bacteremia [16– infections (risk diference = 0.6%, 95% CI 0.1–1.2) [2]. 18]. Te high severity of illness and the notable delays Tis result has been confrmed by a study that associ- in initiation of efective antimicrobial therapy could also ated the increased risk mortality with resistant patho- explain these results. In a pooled, retrospective data anal- gens, hospital-acquired pneumonia, and increased age ysis of phase 3 clinical trials, 91 patients being treated of patients [11]. However the type of serious infections with tigecycline had secondary bacteremia detected, tige- didn’t include BSI. We used the same efect metric to cycline appeared safe and well tolerated in the treatment assess our results, and noted that the risk diference of of secondary bacteremia associated with cSSSI, cIAI, all-cause mortality was not signifcant ( 3.5%, 95% CI and CAP; cure rates were similar to comparative stand- 2 − −13 to −6; ­I = 85.4%, P = 0.001). ard therapies [19]. Recently, a high-dose regimen (load- Although the overall mortality did not difer between ing dose 200 mg followed by 100 mg every 12 h) has been tigecycline and the control groups, subgroup analysis successfully and safely used in critically ill patients with found the mortality was signifcantly lower in the tigecy- severe infections due to multi drug resistant bacteria cline combination group than in the tigecycline mono- although the number of primary bacteremia was anecdo- therapy therapy group. Tigecycline in combination with tal [20]. colistin, carbapenem in combination with colistin, and Several potential limitations should be taken into con- tigecycline in combination with gentamicin were the sideration when interpreting the present results. Firstly, commonly administered antibiotic treatment regimens the number of subjects included was not large enough. among the included studies and might result in lower We would have preferred to contact researchers directly mortality than other combinations of antibiotics. Te for missing data, but this approach was not attempted most common combination was tigecycline with colistin because of time constraints. Secondly, in some subgroup in tigecycline combination therapy group, yet this data analyses, the sample size was small, which may have did not necessarily predict tigecycline plus polymyxins reduced the power of the statistical analysis. Another based therapy was signifcantly better than other antibi- important issue is that the administrations of the antibi- otics combination therapy. For the patients with KPC-Kp otics difered among the studies with regard to the dura- BSI, antibiotic therapy with tigecycline was associated tion of infusion or the total daily dose. Tirdly, due to the with lower mortality. included studies did not provide relevant data, we were With regard to clinical response, the evidence that we unable to assess the impact of tigecycline on adverse drug could compile from studies was that tigecycline therapy reactions. Accordingly, these diferences might infuence may have no clinical advantage over comparator therapy, the clinical outcomes. Last, the matter of the emergence but may result in better clinical cure in treatment of CAP of resistance during therapy was not raised by any of the presenting with bacteremia. included studies. Tigecycline had good eradication ability for most In conclusion, based on a review of published cases, pathogens recorded at baseline, as a novel glycylcy- tigecycline appears to have produced some favourable cline antibiotic, it has a broad spectrum of antimicro- clinical and microbiological outcomes in patients with bial activity, ranging from aerobic to anaerobic bacteria, BSI, even when used as monotherapy. Tis research and gram-positive, gram-negative (exceptions of Pseu- was needed to clarify whether tigecycline was suit- domonas aeruginosa and Proteus mirabilis), and atypi- able for treatment such infections when other antibiot- cal organisms [12]. Eradication was better than with ics fail, especially because indications for increased risk control regimens in all cases, although no signifcant of all-cause mortality have been reported in patients Wang et al. Ann Clin Microbiol Antimicrob (2017) 16:24 Page 9 of 10

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