scholarly journals Carbapenems vs β-Lactam Monotherapy or Combination Therapy for the Treatment of Complicated Intra-abdominal Infections: Systematic Review and Meta-analysis of Randomized Controlled Trials

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Yan Li ◽  
Lingyuan Chen ◽  
Junsong Jiang ◽  
Xianshu Li ◽  
Tianguo Huang ◽  
...  

Abstract Background Complicated intra-abdominal infections (cIAIs) result in significant morbidity, mortality, and cost. Carbapenem-resistant sepsis has increased dramatically in the last decade, resulting in infections that are difficult to treat and associated with high mortality rates. To prevent further antibacterial resistance, it is necessary to use carbapenem selectively. The objective of this study was to compare the effectiveness and safety of carbapenems vs alternative β-lactam monotherapy or combination therapy for the treatment of cIAIs. Methods The PubMed, Embase, Medline (via Ovid SP), and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing carbapenems vs alternative β-lactam monotherapy or combination therapy for the treatment of cIAIs. Results Twenty-two studies involving 7720 participants were included in the analysis. There were no differences in clinical treatment success (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.71–1.05; I2 = 35%), microbiological treatment success (OR, 0.88; 95% CI, 0.71–1.09; I2 = 25%), adverse events (OR, 0.98; 95% CI, 0.87–1.09; I2 = 17%), or mortality (OR, 0.96; 95% CI, 0.68–1.35; I2 = 7%). Patients treated with imipenem were more likely to experience clinical or microbiological failure than those treated with alternative β-lactam monotherapy or combination therapy. Conclusions No differences in clinical outcomes were observed between carbapenems and noncarbapenem β-lactams in cIAIs. Patients treated with imipenem were more likely to experience clinical or microbiological failure than those treated with alternative β-lactam monotherapy or combination therapy.

2018 ◽  
Vol 7 (8) ◽  
pp. 208 ◽  
Author(s):  
I-Ling Cheng ◽  
Yu-Hung Chen ◽  
Chih-Cheng Lai ◽  
Hung-Jen Tang

This meta-analysis aims to compare intravenous colistin monotherapy and colistin-based combination therapy against carbapenem-resistant gram-negative bacteria (GNB) infections. PubMed, Embase, and Cochrane databases were searched up to July 2018. Only randomized controlled trials (RCTs) evaluating colistin alone and colistin-based combination therapy in the treatment of carbapenem-resistant GNB infections were included. The primary outcome was all-cause mortality. Five RCTs including 791 patients were included. Overall, colistin monotherapy was associated with a risk ratio (RR) of 1.03 (95% confidence interval (CI), 0.89–1.20, I2 = 0%) for all-cause mortality compared with colistin-based combination therapy. The non-significant difference was also detected in infection-related mortality (RR, 1.23, 95% CI, 0.91–1.67, I2 = 0%) and microbiologic response (RR, 0.86, 95% CI, 0.72–1.04, I2 = 62%). In addition, no significant difference was observed in the subgroup analysis—high or low dose, with or without a loading dose, carbapenem-resistant Acinetobacter baumannii infections, and in combination with rifampicin. Finally, colistin monotherapy was not associated with lower nephrotoxicity than colistin combination therapy (RR, 0.98; 95% CI, 0.84–1.21, I2 = 0%). Based on the analysis of the five RCTs, no differences were found between colistin monotherapy and colistin-based combination therapy against carbapenem-resistant GNB infections, especially for A. baumannii infections.


2019 ◽  
Author(s):  
Zhong-dong Li ◽  
Genzhu Wang ◽  
Zhikun Xun ◽  
Xiaoying Wang ◽  
Qiang Sun ◽  
...  

Abstract Background Previous meta-analysis based on five randomized controlled trials (RCTs) did not display that intravenous colistin-based combination therapy is more efficacious than monotherapy against carbapenem resistant gram- negative bacterial infections. This meta-analysis aimed to further elucidate the efficacy.Methods PubMed, Embase, and Cochrane databases were searched up to March 2019 and only RCTs evaluating the combination therapy versus monotherapy against carbapenem or even colistin-resistant gram-negative bacteria infections were included. RevMan 5.3 was used to perform meta-analysis.Results Seven RCTs involving 859 patients were included. Total analysis showed that the combination therapy had a trend towards higher microbial response (RR, 1.21; 95% CI, 0.98 –1.51), lower infection-related mortality (RR, 0.75; 95% CI, 0.53–1.05), and significantly lower nephrotoxicity (RR, 0.77; 95% CI, 0.60 – 0.98) than monotherapy. Subgroup analysis on carbapenem-resistant A. baumannii infections displayed that the combination therapy had significantly higher microbiological response (RR, 1.39; P <0.001; 95% CI, 1.19–1.61). Another subgroup analysis on combination regimen for colistin plus rifampicin showed that the combination therapy had significantly higher eradication rate to carbapenem -resistant A. baumannii (RR, 1.35; 95% CI, 1.08–1.68). However, total and subgroup analysis showed no significant difference in all-cause mortality.Conclusions The present study suggests that intravenous colistin-based combination regimen, especially colistin plus rifampicin, may be superior to colistin alone against gram-negative bacterial infections, especially A. baumannii infection


Author(s):  
Haoyue Che ◽  
Jin Wang ◽  
Rui Wang ◽  
Yun Cai

Abstract Background Complicated intra-abdominal infections (cIAIs) remain a leading cause of death in surgical wards, in which antibiotic treatment is crucial. We aimed to compare the efficacy and safety of novel β-lactam/β-lactamase inhibitors (BL/BLIs) in combination with metronidazole and carbapenems in the treatment of cIAIs. Methods A comprehensive search of the randomized controlled trials (RCTs) was performed using databases of Medline, Embase and Cochrane Library, which compared the efficacy and safety of novel BL/BLIs and carbapenems for the treatment of cIAIs. Results Six RCTs consisting of 2,254 patients were included. The meta-analysis showed that novel BL/BLIs in combination with metronidazole had a lower clinical success rate (RD, -0.05; 95%CI, [-0.07, -0.02]; I2= 0%), and lower microbiological success rate (RD, -0.04; 95%CI, [-0.08, -0.00]; I2= 0%). No difference was found between two groups in the incidence of AEs (RD, 0.02; 95%CI, [-0.01, 0.06]; I2= 0%), serious adverse events (SAEs) (RD, 0.01; 95%CI, [-0.02, 0.03]; I2= 0%) and mortality (RD, 0.01; 95%CI, [-0.00, 0.02]). However, ceftazidime/avibactam had a higher risk of vomiting (RD, 0.03; 95% CI, [0.01, 0.05]; I2= 47%), and ceftolozane/tazobactam subgroup showed a higher incidence of SAEs (RD, 0.12; 95% CI, [0.01, 0.03]). Conclusions The efficacy of novel BL/BLIs in combination with metronidazole was not as good as carbapenems. Although no significant differences were found with respect to overall AEs, SAEs and mortality, the novel BL/BLIs has a higher risk of vomiting. Clinical application of new anti-infective combination still needs to be cautious. Trial registration PROSPERO ID: 42020166061


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2984
Author(s):  
Stepan M. Esagian ◽  
Christos D. Kakos ◽  
Emmanouil Giorgakis ◽  
Lyle Burdine ◽  
J. Camilo Barreto ◽  
...  

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.


Author(s):  
Rahele Tavakoly ◽  
Amir Hadi ◽  
Nahid Rafie ◽  
Behrouz Talaei ◽  
Wolfgang Marx ◽  
...  

AbstractThe possible effect of probiotic interventions on immunological markers in athletes is inconclusive. Therefore, to synthesize and quantitatively analyze the existing evidence on this topic, systematic literature searches of online databases PubMed, Scopus, Cochrane Library, and ISI Web of Sciences was carried out up to February 2021 to find all randomized controlled trials (RCTs) concerning the immunological effects of probiotics in athletes. In the random-effects model, weighted mean difference (WMD) and 95% confidence interval (CI) explained the net effect. The authors assessed the likelihood of publication bias via Egger’s and Begg’s statistics. A total of 13 RCTs (836 participants) were retrieved. Probiotic consumption reduced lymphocyte T cytotoxic count significantly (WMD=−0.08 cells×109/L; 95% CI: −0.15 to −0.01; p=0.022) with evidence of moderate heterogeneity (I 2=59.1%, p=0.044) and monocyte count when intervention duration was ≤ 4 weeks (WMD=−0.08 cells×109/L; 95% CI: −0.16 to −0.001; I 2=0.0%). Furthermore, leukocyte count was significantly elevated (WMD=0.48 cells×109/L; 95% CI: 0.02 to 0.93; I 2=0.0%) when multi-strain probiotics were used. Probiotic supplements may improve immunological markers, including lymphocyte T cytotoxic, monocyte, and leukocyte in athletes. Further randomized controlled trials using diverse strains of probiotics and consistent outcome measures are necessary to allow for evidence-based recommendations.


2020 ◽  
Vol 27 (3) ◽  
pp. 291-298
Author(s):  
Yinyin Guo ◽  
Yanxin Luo ◽  
Hui Zhao ◽  
Liangliang Bai ◽  
Juan Li ◽  
...  

Background. A substantial proportion of patients undergoing colorectal surgery receive a temporary stoma, and the timing for stoma closure remains unclear. The aim of this study was to evaluate the safety and feasibility of early stoma closure (ESC) compared with routine stoma closure (RSC) after colorectal surgery. Methods. We comprehensively searched PubMed, Embase, and the Cochrane Library for randomized controlled trials that compared ESC and RSC after colorectal surgery. Results. A total of 7 randomized controlled trials with 814 enrolled patients were identified for this meta-analysis. There were no significant differences between the ESC and RSC groups regarding the complications of stoma closure (26.8% and 16.6%, respectively; odds ratio [OR]: 1.30; 95% confidence interval [CI]: 0.89-1.90; P = .17). A subgroup analysis was conducted by Clavien-Dindo grade of complication, and no significant difference was observed in any subgroup ( P > .05). However, the ESC group had a significantly higher risk of wound complications than the RSC group (17.6% and 7.8%, respectively; OR: 2.61; 95% CI: 1.43-4.76; P = .002), and the RSC group had more cases of small bowel obstruction than the ESC group (3.1% and 8.4%, respectively; OR: 0.37; 95% CI: 0.15-0.87; P = .02). Conclusions. ESC is a safe and effective therapeutic approach in patients who have undergone colorectal surgery; it is associated with a reduced risk of bowel obstruction but a higher risk of wound complications.


2021 ◽  
Author(s):  
Seshadri Reddy Varikasuvu ◽  
Balachandar Thangappazham ◽  
Hemanth Raj

Background: Vitamin D levels have been reported to be associated with COVID-19 susceptibility, severity and mortality events.. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the use of vitamin D intervention on COVID-19 outcomes. Methods: Literature search was conducted using PubMed, Cochrane library, and ClinicalTrials.gov databases (latest search on August 5, 2021). We included RCTs reporting the use of vitamin D intervention to control/placebo group in COVID-19. Two independent researchers did literature search, abstracted data, and the risk of bias assessment. Results: A total of 6 RCTs with 551 COVID-19 patients were included. The overall collective evidence pooling all the outcomes across all RCTs indicated the beneficial use of vitamin D intervention in COVID-19 (relative risk, RR = 0.60, 95% CI 0.40 to 0.92, Z=2.33, p=0.02, I2 = 48%). However, no statistical significance was observed for individual outcomes of ICU care (RR = 0.11, 95% CI 0.15 to 1.30, Z=1.48, p=0.14, I2 = 66%) and mortality (RR = 0.78, 95% CI 0.25 to 2.40, Z=0.66, p=0.02, I2 = 33%), though decreased rates were noted. The rates of RT-CR positivity was significantly decreased in the intervention group as compared to the non-vitamin D groups (RR = 0.46, 95% CI 0.24 to 0.89, Z=2.31, p=0.02, I2 = 0%). Conclusion: COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events and RT-PCR positivity. However, no statistical significance has been achieved for individual outcomes of ICU and deaths. More RCTs and completion of ongoing trials largely needed to precisely establish the association between vitamin D use and COVID-19.


2020 ◽  
Author(s):  
YongCheng Su ◽  
XiaoGang Zheng

Abstract BACKGROUND: Poly(ADP–ribose) polymerase (PARP) inhibitors are new class of drugs that are currently being studied in several malignancies. However, datas about the efficacy and safety of the PARP inhibitors are limited. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) in patients with breast cancer.METHODS: Pubmed/Medline, Embase, Cochrane Library, and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018.Summary incidences and the RR, HR with 95% confidence intervals, were calculated by using a random-effects or fixed-effects model.RESULTS: The summary HR indicated PARPi was not associated with OS (HR=0.83, 95%CI 0.66–1.06, Z=1.49, P=0.14), while it could significantly improve PFS ande time to deterioration (TTD) of global health status/quality of life(GHS/QoL) as compared with traditional standard therapy, the HR was 0.60(95%CI 0.50-0.72; Z=5.52, P<0.00001) and 0.4 (95%CI 0.29–0.54,z=5.80 ,p=0.000),respectively.The RR of grade 3 or more anemia ,fatigue and headache was 3.02 (95% CI, 0.69–13.17;p = 0.14,,I2=90%),0.77 (95%CI, 0.34–1.73;p=0.52,I2=7%) and 1.13 (95% CI,0.30–4.18;p=0.86,I2=0%),respectively.CONCLUSION: The findings of this meta-analysis showed that PARPi has no significant effect on OS, while it could significantly improve in PFS and TTD of GHS/QoL for patients with advanced or metastatic breast cancer.Furthermore,our findings also demonstrated that the PARPi treatment is connected with an increased risk of grade 3 or more anemia adverse events.


2020 ◽  
Vol 2;23 (4;2) ◽  
pp. 135-148
Author(s):  
Zifeng Xu

Background: The pain control effect of ketamine versus control in women during cesarean operation is not well determined. Objectives: The present meta-analysis aimed to evaluate the clinical efficacy of ketamine versus control in cesarean section anesthesia for reducing the postoperative pain and analgesia. Study Design: We used meta-analysis to address this concern. Setting: Meta-analysis-based study. Methods: The databases PubMed, Embase, and the Cochrane Library were systematically searched to identify the relevant randomized controlled trials (RCTs) of ketamine versus control in controlling pain after cesarean section from inception to August 2018. Based on the Cochrane Handbook, the combined analysis was performed using Revman 5.3 software. Results: A total of 20 RCTs with 1,737 patients who underwent cesarean section were included. Meta-analysis showed that the pain score in the ketamine group was less than that of the control group (mean difference [MD], –1.10; 95% confidence interval [CI], –1.61, –0.59; P < 0.0001). Application of ketamine during cesarean section also resulted in decreased consumption of morphine when compared with the control group (MD, –6.11 mg; 95% CI, –9.93, –2.29; P = 0.002). In addition, the first time required for analgesia was significantly longer in the ketamine group than that of the control group (MD, 72.48 minutes; 95% CI, 50.85, 94.11; P < 0.00001). Limitations: Limited patients were included with moderate strength. Conclusions: Ketamine supplementation during cesarean section reduces pain and morphine consumption and prolongs the postoperative analgesia. Key words: Ketamine, cesarean section, randomized controlled trials, meta-analysis


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