scholarly journals Ceftazidime-Avibactam Therapy Versus Ceftazidime-Avibactam-Based Combination Therapy in Patients With Carbapenem-Resistant Gram-Negative Pathogens: A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Dan Li ◽  
Fan Fei ◽  
Hua Yu ◽  
Xiangning Huang ◽  
Shanshan Long ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Combination Therapy ◽  
Clinical Success ◽  
Meta Analysis ◽  
Current Evidence ◽  
Gram Negative ◽  
Beneficial Effects ◽  
Development Of Resistance ◽  
Carbapenem Resistant ◽  
Significant Difference

Objective: To systematically review and compare the efficacy and posttreatment resistance of ceftazidime-avibactam therapy and ceftazidime-avibactam-based combination therapy in patients with Gram-negative pathogens.Methods: PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases were searched from their inception up to March 31, 2021, to obtain studies on ceftazidime-avibactam therapy versus ceftazidime-avibactam-based combination therapy in patients with carbapenem-resistant Gram-negative pathogens. The primary outcome was mortality rate, and the second outcomes were microbiologically negative, clinical success, and the development of resistance after ceftazidime-avibactam treatment.Results: Seventeen studies representing 1,435 patients (837 received ceftazidime-avibactam-based combination therapy and 598 received ceftazidime-avibactam therapy) were included in the meta-analysis. The results of the meta-analysis showed that no statistically significant difference was found on mortality rate (Petos odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.79–1.34), microbiologically negative (OR = 0.99, 95% CI 0.54–1.81), and clinical success (OR =0.95, 95% CI 0.64–1.39) between ceftazidime-avibactam-based combination therapy and ceftazidime-avibactam therapy. Although there was no difference in posttreatment resistance of ceftazidime-avibactam (OR = 0.65, 95% CI 0.34–1.26) in all included studies, a trend favoring the combination therapy was found (according to the pooled three studies, OR = 0.18, 95% CI 0.04–0.78).Conclusions: The current evidence suggests that ceftazidime-avibactam-based combination therapy may not have beneficial effects on mortality, microbiologically negative, and clinical success to patients with carbapenem-resistant Gram-negative pathogens. A trend of posttreatment resistance occurred more likely in ceftazidime-avibactam therapy than the combination therapy. Due to the limited number of studies that can be included, additional high-quality studies are needed to verify the above conclusions.

scholarly journals Intravenous Colistin Monotherapy versus Combination Therapy against Carbapenem-Resistant Gram-Negative Bacteria Infections: Meta-Analysis of Randomized Controlled Trials

2018 ◽  
Vol 7 (8) ◽  
pp. 208 ◽  
Author(s):  
I-Ling Cheng ◽  
Yu-Hung Chen ◽  
Chih-Cheng Lai ◽  
Hung-Jen Tang
Keyword(s):  
Combination Therapy ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Randomized Controlled ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
All Cause Mortality

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.

scholarly journals Meropenem-Vaborbactam versus Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Infections

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Renee Ackley ◽  
Danya Roshdy ◽  
Jacqueline Meredith ◽  
Sarah Minor ◽  
William E. Anderson ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Clinical Success ◽  
Recurrent Infection ◽  
Study Drug ◽  
First Episode ◽  
Development Of Resistance ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
Enterobacteriaceae Infections ◽  
Post Hoc

ABSTRACT The comparative efficacy of ceftazidime-avibactam and meropenem-vaborbactam for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections remains unknown. This was a multicenter, retrospective cohort study of adults with CRE infections who received ceftazidime-avibactam or meropenem-vaborbactam for ≥72 hours from February 2015 to October 2018. Patients with a localized urinary tract infection and repeat study drug exposures after the first episode were excluded. The primary endpoint was clinical success compared between treatment groups. Secondary endpoints included 30- and 90-day mortality, adverse events (AE), 90-day CRE infection recurrence, and development of resistance in patients with recurrent infection. A post hoc subgroup analysis was completed comparing patients who received ceftazidime-avibactam monotherapy, ceftazidime-avibactam combination therapy, and meropenem-vaborbactam monotherapy. A total of 131 patients were included (ceftazidime-avibactam, n = 105; meropenem-vaborbactam, n = 26), 40% of whom had bacteremia. No significant difference in clinical success was observed between groups (62% versus 69%; P = 0.49). Patients in the ceftazidime-avibactam arm received combination therapy more often than patients in the meropenem-vaborbactam arm (61% versus 15%; P < 0.01). No difference in 30- and 90-day mortality resulted, and rates of AE were similar between groups. In patients with recurrent infection, development of resistance occurred in three patients that received ceftazidime-avibactam monotherapy and in no patients in the meropenem-vaborbactam arm. Clinical success was similar between patients receiving ceftazidime-avibactam and meropenem-vaborbactam for treatment of CRE infections, despite ceftazidime-avibactam being used more often as a combination therapy. Development of resistance was more common with ceftazidime-avibactam monotherapy.

scholarly journals 662. Recurrence of Infection and Emergence of Drug Resistance After Treatment with Meropenem/Vaborbactam Compared with Ceftazidime/Avibactam in Carbapenem-Resistant Enterobacteriaceae Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S303-S303 ◽  
Author(s):  
Renee Ackley ◽  
Danya Roshdy ◽  
Jacqueline Isip ◽  
Sarah B, Minor ◽  
Amanda L Elchynski ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Clinical Success ◽  
Recurrent Infection ◽  
Signs And Symptoms ◽  
Development Of Resistance ◽  
Carbapenem Resistant ◽  
Enterobacteriaceae Infections ◽  
Post Hoc ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Options for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections were historically limited to antibiotics with limited efficacy and significant toxicities. Ceftazidime/avibactam (CA) and meropenem/vaborbactam (MV) are superior to older regimens; however, a direct comparison of the agents is lacking. This study compared clinical outcomes including recurrence of infection and emergence of drug resistance in patients who received CA vs. MV for CRE infections. Methods This was a multicenter, retrospective cohort study of adults with CRE infections who received CA or MV for ≥72 hours from February 2015 to October 2018. Patients with localized urinary tract infection were excluded. The primary endpoint was clinical success (30-day survival, resolution of signs and symptoms of infection, sterilization of blood cultures within 7 days in patients with bacteremia, absence of recurrent infection). Secondary endpoints included 30- and 90-day mortality, adverse events (AE), recurrent CRE infection within 90 days, and development of resistance in patients with recurrent infection. We conducted a post hoc subgroup analysis in patients with recurrence to compare development of resistance in those who received CA monotherapy, CA combination therapy, and MV monotherapy. Results 131 patients were included (CA: 105 patients, MV: 26 patients), 40% had bacteremia. No statistical difference in clinical success was observed between groups (62% vs. 69%, respectively, P = 0.49). Patients in the CA arm received combination therapy more often than patients in the MV arm (61% vs. 15%, P < 0.01). No difference in 30- and 90-day mortality resulted among groups, but numerically higher rates of AE were observed in the CA group (38% vs. 23%, P = 0.17). In patients with recurrent infection, development of resistance occurred more often with CA monotherapy, though not statistically significant (Table 1). One case of MV resistance was observed in a patient who had received 4 prior courses of MV, but this episode was outside of the study period. Conclusion Clinical success was similar between the groups despite MV being used more often as monotherapy. Development of resistance and rates of AE were higher in the CA group compared with MV therapy. Disclosures All authors: No reported disclosures.

scholarly journals Tigecycline: Role in the Management of cIAI and cSSTI in the Indian Context

2021 ◽  
pp. 263394472110675
Author(s):  
Subramanian Swaminathan ◽  
Prithwijit Kundu
Keyword(s):  
Health Care ◽  
Mortality Rate ◽  
Combination Therapy ◽  
Broad Spectrum ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Indian Health ◽  
Carbapenem Resistant

The current millennium has witnessed an increased antimicrobial resistance which poses a mammoth challenge for public health management. This has resulted in an increase in morbidity and mortality, resulting in an increase in financial burden to the patients. A recent analysis from 10 hospitals in India reported that mortality rate increases by 1.57 times in patients suffering from multidrug resistance (MDR) bacterial infections as compared to patients infected with similar but susceptible infections. Due to the emergence of MDR and extensively drug-resistant (XDR) bacteria, most of the broad-spectrum antibiotics have been rendered ineffective. The mortality rate with Gram-negative strains is higher than with Gram-positive strains. Tigecycline is the first in class glycylcycline antibiotic with an expanded broad-spectrum activity. Tigecycline enters bacterial cells through energy-dependent pathways or via passive diffusion, to reversibly bind to the 30S ribosomal subunit. It has potent in vitro activity against Gram-negative carbapenemase producers, except Pseudomonas aeruginosa and Proteus spp. It also has good in vitro activity against Carbapenem-resistant Klebsiella pneumoniae strains. Hence, it is considered as a therapeutic option in XDR isolates. Recent meta-analyses have shown tigecycline to be as effective as its comparators with reducing mortality rates. Due to increased resistance reported in carbapenem-resistant isolates in Indian health-care settings, a colistin/polymyxin B-based combination therapy as a treatment option is being sought. A lower mortality rate has been reported with colistin-based combination therapy in Carbapenem-resistant Enterobacteriaceae-associated infections. Combinations with tigecycline, Fosfomycin, and chloramphenicol have shown to improve treatment outcomes. Tigecycline can be a good alternative in MDR and XDR complicated intra-abdominal and complicated skin and soft tissue infections. Appropriately designed clinical trials in Indian health-care setups will reinforce clinician’s confidence in using tigecycline in complex clinical situations.

scholarly journals Intravenous colistin combination is superior to monotherapy against carbapenem-resistant gram-negative bacterial infections: evidence from seven randomized controlled trials

2019 ◽  
Author(s):  
Zhong-dong Li ◽  
Genzhu Wang ◽  
Zhikun Xun ◽  
Xiaoying Wang ◽  
Qiang Sun ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Randomized Controlled Trials ◽  
Subgroup Analysis ◽  
Bacterial Infections ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Combination Regimen ◽  
Gram Negative ◽  
Randomized Controlled ◽  
Carbapenem Resistant

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

scholarly journals Effects of n-3 Polyunsaturated Fatty Acid Supplementation in the Prevention and Treatment of Depressive Disorders—A Systematic Review and Meta-Analysis

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1070
Author(s):  
Maike Wolters ◽  
Annkathrin von der Haar ◽  
Ann-Kristin Baalmann ◽  
Maike Wellbrock ◽  
Thomas L. Heise ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Treatment Duration ◽  
Depressive Disorders ◽  
Meta Analysis ◽  
Pufa Supplementation ◽  
Depressive Symptomology ◽  
Beneficial Effects ◽  
Randomized Controlled ◽  
Significant Difference

N-3 polyunsaturated fatty acids (PUFAs) have been suggested to affect depressive disorders. This review aims to determine the effect of n-3 PUFAs on depressive symptoms in people with or without diagnosed depression. Medline, PsycINFO, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) assessing the association between n-3 PUFAs and depressive symptoms or disorders as outcomes. A random-effects meta-analysis of standardized mean difference (SMD) with 95% confidence intervals (CI) was performed. Twenty-five studies (7682 participants) were included. Our meta-analysis (20 studies) indicated that n-3 PUFA supplementation lowered depressive symptomology as compared with placebo: SMD = −0.34, 95% CI: −0.55, −0.12, I2 = 86%, n = 5836, but a possible publication bias cannot be ruled out. Subgroup analyses indicated no statistically significant difference by treatment duration of <12 vs. ≥12 weeks, presence of comorbidity, or severity of depressive symptoms. Nevertheless, beneficial effects were seen in the subgroups of studies with longer treatment duration and with no depression and mild to moderate depression. Subgroup analysis by eicosapentaenoic acid (EPA) dosage revealed differences in favor of the lower EPA dosage. Sensitivity analysis including studies with low risk of bias seems to confirm the overall result. Supplementation of n-3 PUFA appears to have a modest beneficial effect on depressive symptomology, although the quality of evidence is still insufficient.

scholarly journals Kinesio Taping for Balance Function after Stroke: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Yijuan Hu ◽  
Dongling Zhong ◽  
Qiwei Xiao ◽  
Qiang Chen ◽  
Juan Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Treatment Duration ◽  
Meta Analysis ◽  
Current Evidence ◽  
Cochrane Library ◽  
Clinical Effects ◽  
Balance Function ◽  
Balance Impairment ◽  
Kinesio Taping ◽  
Significant Difference

Objective. With the increasing social and economic burdens of balance impairment after stroke, the treatment for balance impairment after stroke becomes a major public health problem worldwide. Kinesio taping (KT) as a part of clinical practice has been used widely in the treatment of balance impairment after stroke. However, the clinical effects of KT for balance function have not been confirmed. The objective of this study is to investigate the effects and safety of KT for balance impairment after stroke. Methods. We conducted a systematic review (SR) and meta-analysis of randomized controlled trials (RCTs) on the effects of KT for balance impairment after stroke. We searched the following databases: (1) English databases: EMBASE (via Ovid), MEDLINE (via Ovid), the Cochrane library, PubMed, and PEDro; (2) Chinese databases: China Biology Medicine (CBM), Wan Fang database, China National Knowledge Infrastructure (CNKI), and VIP. Besides, hand searches of relevant references were also conducted. We systematically searched from the inception to December 2018, using the keywords (Kinesio, Kinesio Tape, tape, or Orthotic Tape) and (stroke, hemiplegia, or hemiplegic paralysis) and (balance or stability). The search strategies were adjusted for each database. The reference lists of included articles were reviewed for relevant trials. For missing data, we contacted the authors to get additional information. Results. 22 RCTs involved 1331 patients, among which 667 patients in the experimental group and 664 patients in the control group were included. Results of meta-analysis showed that, compared with conventional rehabilitation (CR), there was significant difference in Berg Balance Scale (BBS) (MD=4.46, 95%CI 1.72 to 7.19, P=0.001), Time Up and Go Test (TUGT) (MD=-4.62, 95%CI -5.48 to -3.79, P < 0.00001), functional ambulation category scale (FAC) (MD=0.53, 95%CI 0.38 to 0.68, P < 0.00001), Fugl-Meyer assessment (FMA-L) (MD=4.20, 95%CI 3.17 to 5.24, P < 0.00001), and Modified Ashworth Scale (MAS) (MD=-0.38, 95%CI -0.49 to -0.27, P < 0.00001). The results of subgroup analysis showed that there was no significant difference between KT and CR with ≤4 weeks treatment duration (< 4 weeks: MD=5.03, 95%CI -1.80 to 11.85, P=0.15; =4 weeks: MD=4.33, 95%CI -1.50 to 10.15, P=0.15), while there was significant difference with more than 4-week treatment duration (MD=4.77, 95%CI 2.58 to 6.97, P < 0.0001). Conclusions. Based on current evidence, KT was more effective than CR for balance function, lower limb function, and walking function in poststroke patients. Longer treatment duration may be associated with better effects. However, more well-conducted RCTs are required in the future.

scholarly journals The Comparison of Hypomethylating Agents (HMA) Monotherapy with HMA Combined with Intensive Chemotherapy for Intermediate / High-Risk MDS or AML

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3903-3903
Author(s):  
Jiang Ji ◽  
Zhao Wang ◽  
Bing Han
Keyword(s):  
High Risk ◽  
Combination Therapy ◽  
Death Rate ◽  
Therapy Group ◽  
Meta Analysis ◽  
Combination Group ◽  
Combination Therapy Group ◽  
Hypomethylating Agents ◽  
Monotherapy Group ◽  
Significant Difference

Introduction: Hypomethylating agents (HMA) azacitidine and decitabine were the first-line therapy for intermediate/ higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients unsuitable for hematopoietic cell transplantation (HSCT). HMA combined with chemotherapy was recently used to achieve for a better outcome. However, few studies were carried out to compare the HMA monotherapy to the HMA and chemotherapy combination therapy. This meta-analysis aimed to compare the efficacy, survival benefit and safety of HMA monotherapy and combination therapy (with chemotherapy) in patients with intermediate/high-risk MDS or AML. Methods: Related articles published between January 2009 and April 2019 were selected and patients were separated as monotherapy group and combination group for meta-analysis. To further eliminate the potential influence of differences in patients' baseline characteristic between the two groups, subgroups with similar patients' baseline characteristics were selected for further analysis. Complete response (CR) rate, overall response (ORR) rate, 1-year overall survival (OS) rate, 1-month death rate and the proportion of adverse event (AE) were pooled and compared. Results: 13 RCT or cohort studies with 997 patients (790 in monotherapy group, 207 in HMA combination group) were selected for meta-analysis. For the pooled data, there was no significant difference in sex and cytogenetic risk between the 2 groups, but the age of combination therapy group was significantly younger than that of the monotherapy group (61.3±13.2 year-old vs 67.7±10.2 year-old, p=0.000). The CR and ORR rate were significantly higher in combination therapy group (53% vs 17%, p=0.000 for CR and 67% vs 44%, p=0.000 for ORR). However, the 1-year OS (56% for combination therapy vs 51% for HMA monotherapy group, p=0.282) and 1-month death rate (5% for combination therapy vs 4% for HMA monotherapy group, p=0.965) were similar between the two groups. The incidence of CTCAE grade 3-4 infection and bleeding were significantly higher (infection: 50% for combination therapy vs 25.7% for monotherapy group, p=0.003; bleeding: 27.5%% for combination therapy vs 7.8% for monotherapy group, p=0.004) in combination group. In subgroup analysis, 117 and 179 patients were included in combination group and HMA monotherapy group, respectively. There was no significant difference in age (69.5±4.6 vs 69.0±6.8 years old, p=0.451) and proportion of favorable/intermediate cytogenetic risk (62% vs 71%, p=0.114) between the two groups, but a significantly lower proportion of male was found in combination therapy group (57% vs 74%, p=0.003). Although combination group had a higher CR rate (49% vs 17%, p=0.000), it had similar ORR rate (58% vs 49%, p=0.140) to monotherapy group. Meanwhile, combination therapy came with higher 1-month death rate (12% vs 3%, p=0.008) and lower 1-year OS (54% vs 68%, p=0.013) compared with monotherapy group. Conclusions: HMA combined with chemotherapy could increase CR rate in all patients and ORR rate in younger patients, but could not improve OS. For patients with similar older age, combination therapy could result in higher 1-month death rate and less 1-year OS. Disclosures No relevant conflicts of interest to declare.

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