Elevated microRNA-214-3p level ameliorates neuroinflammation after spinal cord ischemia-reperfusion injury by inhibiting Nmb/Cav3.2 pathway.

BACKGROUND: Neuromedin B (Nmb) plays a pivotal role in the transmission of neuroinflammation, particularly during spinal cord ischemia-reperfusion injury (SCII). However, the detailed molecular mechanisms underlying this process remain elusive. METHODS: The SCII model was established by clamping the abdominal aorta of male Sprague-Dawley (SD) rats for 60 min. The protein expression levels of Nmb, Cav3.2, and IL-1ß were detected by Western blotting, while miR-214-3p expression was quantified by qRT-PCR. The targeted regulation between miR-214-3p and Nmb was investigated using a dual-luciferase reporter gene assay. The cellular localization of Nmb and Cav3.2 with cell-specific markers was visualized by immunofluorescence staining. The specific roles of miR-214-3p on the Nmb/Cav3.2 interactions in SCII-injured rats were explored by intrathecal injection of Cav3.2-siRNA, PD168368 (a specific NmbR inhibitor) and synthetic miR-214-3p agomir and antagomir in separate experiments. Additionally, hind-limb motor function was evaluated using the modified Tarlov scores. RESULTS: Compared to the Sham group, the protein expression levels of Nmb, Cav3.2, and the proinflammatory factor Interleukin(IL)-1ß were significantly elevated at 24 h post-SCII. Intrathecal injection of PD168368 and Cav3.2-siRNA significantly suppressed the expression of Cav3.2 and IL-1ß compared to the SCII group. The miRDB database and dual-luciferase reporter gene assay identified Nmb as a direct target of miR-214-3p. As expected, in vivo overexpression of miR-214-3p by agomir-214-3p pretreatment significantly inhibited the increases in Nmb, Cav3.2 and IL-1ß expression and improved lower limb motor function in SCII-injured rats, while antagomiR-214-3p pretreatment reversed these effects. CONCLUSIONS: Nmb protein levels positively correlated with Cav3.2 expression in SCII rats. Upregulating miR-214-3p ameliorated hind-limb motor function and protected against neuroinflammation via inhibiting the aberrant Nmb/Cav3.2 interactions and downstream IL-1ß release. These findings provide novel therapeutic targets for clinical prevention and treatment of SCII.

Eph receptor A4 regulates motor neuron ferroptosis in spinal cord ischemia/reperfusion injury in rats.

Previous studies have shown that the receptor tyrosine kinase Eph receptor A4 (EphA4) is abundantly expressed in the nervous system. The EphA4 signaling pathway plays an important role in regulating motor neuron ferroptosis in motor neuron disease. To investigate whether EphA4 signaling is involved in ferroptosis in spinal cord ischemia/reperfusion injury, in this study we established a rat model of spinal cord ischemia/reperfusion injury by clamping the left carotid artery and the left subclavian artery. We found that spinal cord ischemia/reperfusion injury increased EphA4 expression in the neurons of anterior horn, markedly worsened ferroptosis-related indicators, substantially increased the number of mitochondria exhibiting features consistent with ferroptosis, promoted deterioration of motor nerve function, increased the permeability of the blood-spinal cord barrier, and increased the rate of motor neuron death. Inhibition of EphA4 largely rescued these effects. However, intrathecal administration of the ferroptosis inducer Erastin counteracted the beneficial effects conferred by treatment with the EphA4 inhibitor. Mass spectrometry and a PubMed search were performed to identify proteins that interact with EphA4, with the most notable being Beclin1 and Erk1/2. Our results showed that inhibition of EphA4 expression reduced binding to Beclin1, markedly reduced p-Beclin1, and reduced Beclin1-XCT complex formation. Inhibition of EphA4 also reduced binding to p-Erk1/2 and markedly decreased the expression of c-Myc, transferrin receptor 1, and p-Erk1/2. Additionally, we observed co-localization of EphA4 and p-Beclin1 and of EphA4 and p-ERK1/2 in neurons in the anterior horn. In conclusion, EphA4 participates in regulating ferroptosis of spinal motor neurons in the anterior horn in spinal cord ischemia/reperfusion injury by promoting formation of the Beclin1-XCT complex and activating the Erk1/2/c-Myc/transferrin receptor 1 axis.

Fra-1 induces apoptosis and neuroinflammation by targeting S100A8 to modulate TLR4 pathways in spinal cord ischemia/reperfusion injury.

Spinal cord ischemia/reperfusion injury (SCII) is a severe complication driven by apoptosis and neuroinflammation. An increase in the expression of c-Fos, a member of the AP-1 family, is known as a neuronal activation marker in SCII. The AP-1 family is composed of Jun, Fos, and is associated with the regulation of cytokines expression and apoptosis. Fra-1 is a member of the Fos family, however, the contribution of Fra-1 to SCII is still unclear. In our study, Fra-1 was highly upregulated especially in neurons and microglia and promoted apoptosis by changing the expression of Bax/Bcl-2 after SCII. Furthermore, we found that Fra-1 directly regulated the transcription expression of S100A8. We demonstrated that knockdown of Fra-1 alleviated S100A8 mediated neuronal apoptosis and inflammatory factor release, thus improved motor function after SCII. Interestingly, we showed that administration of TAK-242, the TLR4 inhibitor, to the ischemia/reperfusion (I/R) injury induced rats suppressed the activation of the ERK and NF-κB pathways, and further reduced Fra-1 expression. In conclusion, we found that Fra-1-targeted S100A8 was expressed the upstream of Fra-1, and the Fra-1/S100A8 interaction formed a feedback loop in the signaling pathways activated by SCII.

Case report: Reducing the duration of positive-pressure ventilation for large mediastinal masses.

Large mediastinal masses (MMs) are rare and present some challenges in hemodynamic and airway management under general anesthesia. Multiple studies have reported cardiopulmonary collapse during general anesthesia. Maintenance of spontaneous ventilation, avoidance of muscle relaxants, and awake-intubation were usually recommended during general anesthesia for high-risk patients with large MMs. However, the recent notion challenged the classic teaching that maintaining spontaneous ventilation is superior to positive-pressure ventilation (PPV). In our case reports, we present two patients with large MMs during general anesthesia. In the first case, a 21-year-old male was administered a muscle relaxant during induction, followed by PPV, but his blood oxygen saturation decreased to 40% after 20 min. Finally, his oxygen saturation was restored by a sternotomy rather than by cardiopulmonary bypass (CPB) by femoral vascular intubation. In the second case, a 33-year-old male was also administered a muscle relaxant during induction followed by PPV, but for him, sternotomy was immediately performed, with stable blood oxygen saturation. Both patients recovered well and were discharged from hospital a week after surgery. Therefore, we present a recommendation that patients with large MMs could undergo PPV after the administration of a muscle relaxant during induction, but the cardiothoracic surgeon should immediately cleave the sternum.

CDGSH iron sulfur domain 2 mitigates apoptosis, oxidative stress and inflammatory response caused by oxygen-glucose deprivation/reoxygenation in HT22 hippocampal neurons by Akt-Nrf2-activated pathway.

CDGSH iron sulfur domain 2 (Cisd2) is known as a key determinant factor in maintaining cellular homeostasis. However, whether Cisd2 contributes to the mediation of neuronal injury during ischemic stroke has not been well stressed. This work focuses on investigating the role of Cisd2 in regulating neuronal injury caused by oxygen-glucose deprivation/reoxygenation (OGD/R). The dramatic down-regulation of Cisd2 was observed in hippocampal neurons suffering from OGD/R injury. In Cisd2-overexpressed neurons, OGD/R-induced neuronal apoptosis, oxidative stress and inflammation were prominently mitigated. Further investigation uncovered that the forced expression of Cisd2 reinforced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in OGD/R-exposed neurons. Moreover, the overexpression of Cisd2 enhanced Akt activation, and the restraint of Akt abolished Cisd2-induced Nrf2 activation. Importantly, restraint of Nrf2 reversed Cisd2-conferred neuroprotective effects in OGD/R-exposed neurons. Taken together, our findings indicate that Cisd2 is able to protect neurons from OGD/R-induced injuries by strengthening Nrf2 activation via Akt. Our work identifies Cisd2 as a potential determinant factor for neuronal injury during cerebral ischemia/reperfusion injury.

The roles of microRNAs in spinal cord ischemia-reperfusion injury.

Spinal cord ischemia/reperfusion injury is a devastating medical disorder with poor prognosis that is associated with several pathophysiological conditions. However, multiple stimuli can trigger SCII, so the underlying mechanism of this pathology has not yet been fully established. MicroRNAs (miRNAs) are a class of non-coding RNAs that mediate a variety of nervous system diseases and regulate numerous physiological functions, including apoptosis, autophagy, inflammation, and blood-spinal cord barrier damage. miRNA expression profiles are known to be altered after spinal cord ischemia/reperfusion injury. Therefore, gaining a better understanding of the significant roles that miRNAs play in spinal cord ischemia/reperfusion injury could help develop potential preventive and therapeutic strategies for spinal cord ischemia/reperfusion injury. This review summarizes the current state of our knowledge about the relationship between miRNAs and spinal cord ischemia/reperfusion injury, as well as potential miRNAs that could be targeted to treat spinal cord ischemia/reperfusion injury.

Antimicrobial Stewardship in Surgery: A Literature Bibliometric Analysis.

Background: Antimicrobial resistance and the dwindling antibiotic development pipeline have resulted in a looming post-antibiotic era. Research related to antimicrobial stewardship (AMS) has grown rapidly in the past decade, especially in the field of surgery. We conducted a bibliometric analysis of these publications. In addition, we aimed to identify research hotspots and infer future research trends. Methods: We screened global publications on AMS in the surgical field over ten years (between 2011 and 2020) from the Web of Science core collection database. The keywords "antimicrobial or antibiotic", "stewardship", "management", "management strategies", "programme", "surgery" and "surgical" were used to search for related papers. VOS viewer, R software, and other machine learning and visualization tools were used to conduct the bibliometric analysis of the publications. Results: We identified 674 publications on AMS in surgical fields; "antimicrobial stewardship" (with total link strength of 1,096) was the most frequent keyword, and had strong links to "antimicrobial resistance" and "guidelines". The top 100 most cited papers had a mean citation count of 47.21 (range: 17-1155) citations, which were cited by survey research studies, clinical trials, and observational studies. The highest-ranking and most cited journal was Clinical Infectious Diseases with eight publications. Jason G. Newland from Washington University wrote seven papers and was cited 1,282 times. The University of Washington published 17 papers and was cited 1,258 times, with the largest number of publications by author and organization. The USA published 198 papers and cooperated with 21 countries, mainly partnering with Italy, the UK, and Canada. Published articles mainly focused on the current clinical situation regarding surgical AMS management, antibiotic prescription, and antibiotic resistance. Conclusions: Publications on surgical AMS management have increased in recent decades, with the USA being the most prolific. Epidemiological investigations of surgical-related infections, antibiotic prescriptions, and antibiotic resistance are fast-developing research trends. However, further improvements are still needed according to the recommendations gained from the bibliometric analysis.

Inhibiting the aberrant PACT-p53 axis activation ameliorates spinal cord ischaemia-reperfusion injury in rats.

Spinal cord ischaemia-reperfusion injury (SCII) induces multiple molecular and cellular changes, resulting in dyskinesia. Recently, it is reported that the p53 network plays a vital role in SCII. However, the roles of the PACT/PRKRA (interferon-inducible double-stranded RNA-dependent protein kinase activator A)-p53 axis in SCII are still unclear. The aim of this study was to elucidate the roles of the PACT-p53 axis in SCII. A Sprague-Dawley rat model of SCII was established by subjecting rats to a 14-min occlusion of the aortic arch. The Tarlov criteria, Western blotting, double immunofluorescence staining, haematoxylin and eosin (HE) staining, and transferase dUTP nick end labelling (TUNEL) assay were performed after SCII. Here, spinal cord ischaemia-reperfusion (SCI) caused hindlimb motor functional deficits as assessed by the Tarlov criteria. The protein expression of PACT was substantially upregulated at 48 h after SCII. Increased PACT fluorescence was mainly localized to neurons. Si-PACT pretreatment improved hindlimb motor function, ameliorated histological changes, and attenuated cell apoptosis after SCII. Si-PACT pretreatment reduced the protein expression of PACT, p53, Caspase-8 and IL-1ß and the number of double-labelled PACT and p53. Taken together, inhibiting the aberrant PACT-p53 axis activation by si-PACT pretreatment ameliorates SCI-induced neuroapoptosis and neuroinflammation in rats. Silencing PACT expression is promising new therapeutic strategy for SCII.

MicroRNA-101a-3p mimic ameliorates spinal cord ischemia/reperfusion injury.

miR-101a-3p is expressed in a variety of organs and tissues and plays a regulatory role in many diseases, but its role in spinal cord ischemia/reperfusion injury remains unclear. In this study, we established a rat model of spinal cord ischemia/reperfusion injury by clamping the aortic arch for 14 minutes followed by reperfusion for 24 hours. Results showed that miR-101a-3p expression in L4-L6 spinal cord was greatly decreased, whereas MYCN expression was greatly increased. Dual-luciferase reporter assay results showed that miR-101a-3p targeted MYCN. MYCN immunoreactivity, which was primarily colocalized with neurons in L4-L6 spinal tissue, greatly increased after spinal cord ischemia/reperfusion injury. However, intrathecal injection of an miR-101a-3p mimic within 24 hours before injury decreased MYCN, p53, caspase-9 and interleukin-1ß expression, reduced p53 immunoreactivity, reduced the number of MYCN/NeuN-positive cells and the number of necrotic cells in L4-L6 spinal tissue, and increased Tarlov scores. These findings suggest that the miR-101a-3p mimic improved spinal ischemia/reperfusion injury-induced nerve cell apoptosis and inflammation by inhibiting MYCN and the p53 signaling pathway. Therefore, miR-101a-3p mimic therapy may be a potential treatment option for spinal ischemia/reperfusion injury.

Delayed aortoesophageal and tracheoesophageal fistulas secondary to foreign body ingestion: a case report.

Ingestion of a foreign body (FB) is a common condition with a few potentially life-threatening complications, including esophageal perforation (EP), aortoesophageal fistula (AEF), mediastinal infection, and tracheoesophageal fistula (TEF). In this case, a patient who accidentally ingested a duck bone gradually experienced all of the above complications. To resolve the symptom of difficulty swallowing, the patient underwent emergency treatment for removal of the esophageal FB via endoscopic surgery. Under endoscopy, esophageal mucosal injuries were present, but no other abnormalities, such as active bleeding, were observed. However, the patient returned to our hospital a week later with symptoms of vomiting and black stool and received the diagnosis of EP, AEF and mediastinal infection. Two days later, he vomited 1,000-2,000 mL of blood after experiencing sudden severe chest pain. Then, thoracic endovascular aortic repair (TEVAR) and mediastinal drainage with video-assisted thoracoscopic surgery (VATS) were performed under emergency general anesthesia. Additionally, the patient underwent esophageal stent implantation when TEF was confirmed by tracheal computed tomography (CT). The patient was treated with anti-infective therapy throughout the treatment process. Finally, he recovered and was able to tolerate a liquid diet. Comprehensive evaluation and multidisciplinary cooperation are all very important for the treatment of esophageal foreign bodies and complications.

Reduction in antimicrobial use associated with a multifaceted antimicrobial stewardship programme in a tertiary teaching hospital in Shanghai: a segmented regression analysis.

BACKGROUND: Rational use of antibiotics received great attention in China, therefore the multifaceted antimicrobial stewardship (MAMS) is urgently required in hospital management. We conducted this study to assess the impact of a MAMS programme on antimicrobial use in a tertiary teaching hospital in Shanghai. METHODS: This retrospective observational study was conducted at a tertiary teaching hospital in Shanghai. The MAMS programme involved multifaceted interventions consisting of a quality premium with financial incentives, antibiotic restriction, audit and feedback, and education. Data were extracted from the electronic medical records of inpatients to analyse monthly and annual antibiotic consumption and the percentage of antibiotic prescriptions during 2017-2020. Segmented regression analysis of the interrupted time series was used to contrast antimicrobial use during 2019-2020, with non-MAMS data from the 2017-2018 period as the historical control. RESULTS: With MAMS implementation, antibiotic consumption decreased from 63.3 (59.3, 67.2) defined daily doses (DDDs) per 100 patient-days (PD) to 43.3 (39.0, 49.8) DDDs/100 PD (P<0.001), and the percentage of antibiotic prescriptions decreased from 44.8% (44.1%, 45.4%) to 43.3% (42.2%, 44.3%) (P<0.001). Segmented regression models suggested a reduction in antibiotic consumption (coefficient = -12.537, P<0.001) and indicated a downward trend in the percentage of antibiotic prescriptions (coefficient =-0.165, P=0.049). Neither antibiotic consumption nor the percentage of antibiotic prescriptions was influenced by the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: This study suggests that MAMS plays an important role in reducing antibiotic use and is not affected by special circumstances such as the COVID-19 pandemic. This novel intervention, consisting of a quality premium and multidisciplinary cooperation, should be prioritized by policy and decision makers, where rational management of antimicrobial use is urgently needed.

Global trends and hotspots in research of carbapenem-resistant Enterobacteriaceae (CRE): a bibliometric analysis from 2010 to 2020.

BACKGROUND: Infectious disease caused by carbapenem-resistant Enterobacteriaceae (CRE) has become one of the most serious challenges due to its high morbidity and mortality and research on it has aroused great concern worldwide in the last decade. Thus, a bibliometric analysis of relevant publications is needed to identify the situation of current investigations and prioritize the future research areas. METHODS: The current study retrieved articles related to CRE published between 2010 and 2020 from the Web of Science core collection database. The search strategy syntax included "carbapenem-resistant Enterobacteriaceae", "carbapenem-resistant Klebsiella pneumoniae", "carbapenemase producing Enterobacteriaceae" and "carbapenemase producing Klebsiella pneumoniae" which were searched in both Medical Subject Headings (MeSH) and titles. A bibliometric analysis was conducted using VOSviewer, Bibliographic Item Co-Occurrence Matrix Builder, gCLUTO and other machine learning tools. Key words, subject terms, contributions as well as collaborations were assessed. Moreover, hot off the press and future research trends were demonstrated. RESULTS: A total of 1,671 publications on CRE were finally included in the bibliometric analysis and 5 related theme clusters were identified which mainly focused on epidemiology, resistance mechanisms, antibiotics treatment and infection control. A total of 142 keywords occurred more than 5 times and the most frequent keyword was "carbapenem-resistant Enterobacteriaceae" with 247 occurrences and a total link strength of 559. The output on CRE has gradually increased during the last decade, and the USA has made the greatest contribution due to the 533 research papers. Agents that act against CRE, especially ceftazidime-avibactam (occurrences, 85; average publication year, 2018.26), and the early detection of CRE by genome sequencing techniques (occurrences, 97; average publication year, 2017.94) were emerging hot topics which would probably attract future research interest. CONCLUSIONS: The bibliometric analysis revealed that development of antibacterial agents, early etiological detection and genome sequencing techniques were the hotspots and would probably direct the future research directions which would also facilitate a better understanding of the epidemiology of drug-resistant bacteria and implementing the antibiotic stewardship program.

Bioinformatics-Based Analysis of the lncRNA-miRNA-mRNA Network and TF Regulatory Network to Explore the Regulation Mechanism in Spinal Cord Ischemia/Reperfusion Injury.

BACKGROUND: Spinal cord ischemia/reperfusion injury (SCII) is a catastrophic complication involved with cardiovascular, spine, and thoracic surgeries and can lead to paraplegia. Nevertheless, the molecular mechanism of SCII remain ill-defined. METHODS: Expression profiling (GSE138966) data were obtained from GEO database. Then, differentially expressed (DE) lncRNAs and DEmRNAs were screened out with p < 0.05, and | fold change| > 1.5. Aberrant miRNAs expression in SCII was obtained from PubMed. Functional enrichment analysis of overlapping DEmRNAs between predicted mRNAs in miRDB database and DEmRNAs obtained from GSE138966 was performed using cluster Profiler R package. The lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was established in light of ceRNA theory. The key lncRNAs in the ceRNA network were identified by topological analysis. Subsequently, key lncRNAs related ceRNA-pathway network and transcription factors (TFs)-mRNAs network were constructed. Simultaneously, the expression levels of hub genes were measured via qRT-PCR. RESULTS: The results in this study indicated that 76 miRNAs, 1373 lncRNAs, and 4813 mRNAs were differentially expressed in SCII. A SCII-related ceRNA network was constructed with 154 ncRNAs, 139 mRNAs, and 51 miRNAs. According topological analysis, six lncRNAs (NONRATT019236.2, NONRATT009530.2, NONRATT026999.2, TCONS_00032391, NONRATT023112.2, and NONRATT021956.2) were selected to establish the ceRNA-pathway network, and then two candidate hub lncRNAs (NONRATT009530.2 and NONRATT026999.2) were identified. Subsequently, two lncRNA-miRNA-mRNA regulatory axes were identified. NONRATT026999.2 and NONRATT009530.2 might involve SCII via miR-20b-5p/Map3k8 axis based on the complex ceRNA network. SP1 and Hnf4a acting as important TFs might regulate Map3k8. Furthermore, qRT-PCR results showed that the NONRATT009530.2, NONRATT026999.2, Map3k8, Hfn4a, and SP1 were significantly upregulated in SCII of rats, while the miR-20b-5p was downregulated. CONCLUSION: Our results offer a new insight to understand the ceRNA regulation mechanism in SCII and identify highlighted lncRNA-miRNA-mRNA axes and two key TFs as potential targets for prevention and treatment of SCII.

Identification of the biological function of miR-9 in spinal cord ischemia-reperfusion injury in rats.

Spinal cord ischemia-reperfusion injury (SCII) is still a serious problem, and the mechanism is not fully elaborated. In the rat SCII model, qRT-PCR was applied to explore the altered expression of miR-9 (miR-9a-5p) after SCII. The biological function of miR-9 and its potential target genes based on bioinformatics analysis and experiment validation in SCII were explored next. Before the surgical procedure of SCII, miR-9 mimic and inhibitor were intrathecally infused. miR-9 mimic improved neurological function. In addition, miR-9 mimic reduced blood-spinal cord barrier (BSCB) disruption, inhibited apoptosis and decreased the expression of IL-6 and IL-1ß after SCII. Gene Ontology (GO) analysis demonstrated that the potential target genes of miR-9 were notably enriched in several biological processes, such as "central nervous system development", "regulation of growth" and "response to cytokine". The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the potential target genes of miR-9 were significantly enriched in several signaling pathways, including "Notch signaling pathway", "MAPK signaling pathway", "Focal adhesion" and "Prolactin signaling pathway". We further found that the protein expression of MAP2K3 and Notch2 were upregulated after SCII while miR-9 mimic reduced the increase of MAP2K3 and Notch2 protein. miR-9 mimic or MAP2K3 inhibitor reduced the release of IL-6 and IL-1ß. miR-9 mimic or si-Notch2 reduced the increase of cleaved-caspase3. Moreover, MAP2K3 inhibitor and si-Notch2 reversed the effects of miR-9 inhibitor. In conclusion, overexpression of miR-9 improves neurological outcomes after SCII and might inhibit BSCB disruption, neuroinflammation, and apoptosis through MAP2K3-, or Notch2-mediated signaling pathway in SCII.

Efficacy and safety of tigecycline for complicated urinary tract infection: a systematic review.

BACKGROUND: Facing the global threat of emerging resistance to antibiotics, tigecycline, a novel glycylcycline antibiotic, is developed to against multidrug-resistant pathogens, but not recommended for the treatment of complicated urinary tract infection (cUTI). We performed a summary of the literatures to characterize and evaluate the efficacy and safety of tigecycline in patients with cUTI. METHODS: We searched PubMed, EMBASE, Cochrane and Clinical Trials using appropriate syntax to retrieve potential articles up to Jan 2020. General information, pathogen, medication regimen, comorbidities of patients from eligible literatures were recorded. Univariate logistic regression analysis was used to detect the potential factors associated with clinical cure. RESULTS: Nineteen articles comprising 31 cases were included. The subpopulation with transplantation (25.8% of the patients) was the most common comorbidity, and cUTIs were mainly caused by Klebsiella pneumoniae (K. pneumoniae) (48.28%) in our research. Tigecycline 100 mg per day as monotherapy was most common. Clinical cure was reported as majority (77.4%), and microbiological eradication cases accounted for the most (65.2%) among the clinical cure cases. Univariate analysis showed that K. pneumoniae caused cUTI and tigecycline as a single treatment have significant meaning to clinical outcomes (P=0.044 and P=0.034, respectively). CONCLUSIONS: Clinical and microbiological outcomes of tigecycline treatment revealed high rate of successful response. Tigecycline monotherapy may have a role in the treatment of cUTI except that caused by the pathogen K. pneumoniae. Further randomized controlled trials was still needed to evaluate tigecycline monotherapy for cUTI.