scholarly journals Evaluating the clinical effectiveness of new beta-lactam/beta-lactamase inhibitor combination antibiotics: A systematic literature review and meta-analysis

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Geneva M. Wilson ◽  
Margaret A. Fitzpatrick ◽  
Kyle Walding ◽  
Beverly Gonzalez ◽  
Marin L. Schweizer ◽  
...  
Keyword(s):  
Clinical Success ◽  
Meta Analysis ◽  
Strong Association ◽  
Study Drug ◽  
Clinical Effectiveness ◽  
Multidrug Resistant ◽  
New Combination ◽  
Beta Lactam ◽  
Combination Antibiotics ◽  
Lactamase Inhibitor

Abstract Background: Ceftazidime/avibactam (C/A), ceftolozane/tazobactam (C/T), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V) combine either a cephalosporin (C/T and C/A) or a carbapenem antibiotic (M/V and I/R) with a β-lactamase inhibitor. They are used to treat carbapenem-resistant Enterobacterales (CRE) and/or multidrug-resistant Pseudomonas aeruginosa (MDRPA). Objective: We compared the pooled clinical success of these medications to older therapies. Methods: PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for C/A, C/T, I/R, and M/V studies. The main outcome was clinical success, which was assessed using random-effects models. Stratified analyses were conducted for study drug, sample size, quality, infection source, study design, and multidrug-resistant gram-negative organism (MDRGNO) population. Microbiological success and 28- and 30-day mortality were assessed as secondary outcomes. Heterogeneity was determined using I2 values. Results: Overall, 25 articles met the inclusion criteria; 8 observational studies and 17 randomized control trials. We detected no difference in clinical success comparing new combination antibiotics with standard therapies for all included organisms (pooled OR, 1.21; 95% CI, 0.96–1.51). We detected a moderate level of heterogeneity among the included studies I2 = 56%. Studies that focused on patients with CRE or MDRPA infections demonstrated a strong association between treatment with new combination antibiotics and clinical success (pooled OR, 2.20; 95% CI, 1.60–3.57). Conclusions: C/T, C/A, I/R, and M/V are not inferior to standard therapies for treating various complicated infections, but they may have greater clinical success for treating MDRPA and CRE infections. More studies that evaluate the use of these antibiotics for drug-resistant infections are needed to determine their effectiveness.

scholarly journals 1619. Meta-analysis of Randomized Control Trials Evaluating New Beta-Lactamase Combination Antibiotics

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S802-S802
Author(s):  
Geneva M Wilson ◽  
Margaret A Fitzpatrick ◽  
Kyle Walding ◽  
Beverly Gonzalez ◽  
Katie J Suda ◽  
...  
Keyword(s):  
Observational Studies ◽  
Clinical Success ◽  
Meta Analysis ◽  
New Combination ◽  
Randomized Control Trials ◽  
Beta Lactamase ◽  
Success Rates ◽  
Beta Lactam ◽  
Randomized Control ◽  
Tract Infections

Abstract Background Ceftolozane/ Tazobactam (C/T), Ceftazidime/ Avibactam (C/A), Meropenem/ Vaborbactam (M/V) and Imipenem/ Relebactam (I/R) are new combination beta-lactam/ beta-lactamase inhibitor antibiotics primarily used to treat multidrug-resistant (MDR) Gram-negative infections. This study synthesized outcomes of comparative observational studies and randomized control trials (RCTs) that evaluated clinical success of these antibiotics compared to other therapies. Methods PubMed, EMBASE, and Google Scholar were searched from January 1st, 2013 through October 1st, 2019 for comparative observational studies and RCTs of C/T, C/A, M/V and I/R in patients with pneumonia, complicated intra-abdominal and urinary tract infections. Study and patient demographics were collected along with clinical and microbiological success rates. Meta-regression analysis was used to determine the pooled effectiveness of C/T, C/A, M/V, and I/R. Heterogeneity and publication bias were assessed via I2 values and funnel plots, respectively. Results Literature search returned 1,645 results. After exclusion criteria, 21 publications representing 6,246 patients were retained: 16 RCTs (8 C/A, 3 C/T, 3 I/R, 2 M/V) and 5 comparative observational studies (3 C/A, 2 C/T). Pooled risk ratios for clinical success showed that all four antibiotics were non-inferior to comparator antibiotics (0.99 (95% CI (0.97-1.01)). Eleven of the sixteen RCTs evaluated microbiological success; pooled risk ratio was 1.08 (95% CI 1.04-1.13), indicating that older therapies were more successful at microbiological eradication than newer antibiotics. Only 6 of the included studies (3 RCTs and 2 observational studies) focused on patients with MDR infections. Limiting the analysis to MDR RCTs did not change the overall conclusions. Conclusion Although older therapies had slightly higher microbiologic clearance, pooled clinical success rates for C/A, C/T, M/V, and I/R were non-inferior to older therapies, including in studies focused on patients with MDR infections. Additional studies are needed to further evaluate these drugs’ effectiveness for treatment of MDR infections. Disclosures All Authors: No reported disclosures

scholarly journals Meta-analysis of Clinical Outcomes Using Ceftazidime/Avibactam, Ceftolozane/ Tazobactam, and Meropenem/ Vaborbactam for the Treatment of Multidrug Resistant Gram-Negative Infections

2021 ◽  
Author(s):  
Geneva Wilson ◽  
Margaret Fitzpatrick ◽  
Kyle Walding ◽  
Beverly Gonzalez ◽  
Marin L Schweizer ◽  
...  
Keyword(s):  
Success Rate ◽  
Clinical Success ◽  
Infection Type ◽  
Meta Analysis ◽  
Treatment Options ◽  
Clinical Success Rate ◽  
Multidrug Resistant ◽  
Success Rates ◽  
Beta Lactam ◽  
Review Reports

Abstract Ceftolozane-tazobactam (C/T), Ceftazidime-avibactam (C/A), and Meropenem/vaborbactam (M/V) are new beta-lactam/beta-lactamase combination antibiotics commonly used to treat multi-drug resistant Pseudomonas aeruginosa (MDRPA) and carbapenem-resistant Enterobacteriaceae (CRE) infections. This review reports the clinical success rates for C/T, C/A., and M/V. PubMed and EMBASE were searched from January 1 st, 2012 through September 2 nd, 2020 for publications detailing use of C/T, C/A, and M/V. Meta-analysis determined the pooled effectiveness of C/T, C/A, and M/V. The literature search returned 1,950 publications, 29 publications representing 1,620 patients were retained. Pneumonia was the predominant infection type (49.8%). MDRPA was the major pathogen treated (65.3%). The pooled clinical success rate was 73.3% (95% CI 68.9%-77.5%). C/T, C/A, or M/V resistance was reported in 8.9% of the population. These antibiotics had a high clinical success rate in patients with complicated infections and limited treatment options. Larger studies comparing C/T, C/A, and M/V against other antibiotic regimens are needed.

scholarly journals Use of Ceftolozane/Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Pneumonia in a Pediatric Patient with Combined Immunodeficiency (CID): A Case Report from a Tertiary Hospital in Saudi Arabia

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 67 ◽  
Author(s):  
Ahmed Zikri ◽  
Kamal El Masri
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pediatric Patient ◽  
Pediatric Population ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Combined Immunodeficiency ◽  
Beta Lactam ◽  
Pharmacokinetic Profiles ◽  
Lactamase Inhibitor

Infections, with multidrug-resistant Pseudomonas aeruginosa, are a major concern in the pediatric intensive care unit, especially in immunocompromised patients. Some of these strains are resistant to all beta-lactams, including carbapenems, leaving very limited treatment options remaining. These options include aminoglycosides and colistin, both of which have poor pharmacokinetic profiles with significant toxicities. Newer beta-lactam/beta-lactamase inhibitor combinations offer additional novel options to treat such infections, given their good pharmacokinetic profiles and activity against multi-drug resistant strains. Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination approved in 2014. The drug demonstrates good activity against multidrug-resistant P. aeruginosa strains, including those resistant to all other antibiotics. Ceftolozane/tazobactam is currently approved in adult patients 18 years and older only. There are very limited data on its pharmacokinetic profile and clinical utility in the pediatric population. We report the use of ceftolozane/tazobactam to successfully treat pneumonia caused by multidrug-resistant P. aeruginosa in a pediatric patient with combined immunodeficiency syndrome.

scholarly journals Beta-Lactam/Beta-Lactamase Inhibitor Therapy for Potential AmpC-Producing Organisms: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Matthew P Cheng ◽  
Robyn S Lee ◽  
Alexandre P Cheng ◽  
Samuel De L’étoile-Morel ◽  
Koray Demir ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Bloodstream Infections ◽  
Optimal Treatment ◽  
Inhibitor Therapy ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Significant Difference ◽  
Lactamase Inhibitor

Abstract The optimal treatment for potential AmpC-producing Enterobacteriaceae, including Serratia, Providencia, Citrobacter, Enterobacter, and Morganella species, remains unknown. An updated systematic review and meta-analysis of studies comparing beta-lactam/beta-lactamase inhibitors with carbapenems in the treatment of bloodstream infections with these pathogens found no significant difference in 30-day mortality (OR, 1.13; 95% CI, 0.58 – 2.20).

REVERSION OF ANTIBIOTIC RESISTANCE WITH BETA-LACTAMASE INHIBITOR FROM MEDICINAL PLANTS

2017 ◽  
Vol 10 (10) ◽  
pp. 204
Author(s):  
Sneha Arora ◽  
Shoma Paul Nandi
Keyword(s):  
Antibiotic Resistance ◽  
Medicinal Plants ◽  
Ethyl Acetate ◽  
Ethyl Acetate Extract ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Lactamase Inhibitor

  Objective: Screening of medicinal plants for the presence of beta-lactamase inhibitor identified three plants; Terminalia chebula, Terminalia bellirica, and Ocimum tenuiflorum, extracts of which inhibit beta-lactamase enzyme in vitro. The objective of this study was to evaluate and compare beta-lactamase inhibiting potential of these plant extracts.Methods: Extracts of these plants were prepared with 6 solvents of different polarity. Beta-lactamase inhibition study was performed using antibiotic-resistant bacteria in bioassay and by micro-iodometric assay. Multidrug-resistant clinical strains of Escherichia coli and laboratory strain with plasmid carrying beta-lactamase gene as positive control were used.Results: Our results from bioassay, as well as micro-iodometric assay for enzyme activity, confirmed the presence of beta-lactamase inhibitor in these plant extracts. Among the extracts made by different solvents, hexane and ethyl acetate extract of T. chebula, hexane extract of T. bellirica, and all extracts of O. tenuiflorum except dichloromethane, possessed beta-lactamase inhibitor. Multidrug-resistant clinical isolate of E. coli AIIMS-1 could be reverted by applying 50 μg/μl of extract of all the medicinal plants. The micro-iodometric result showed highest beta-lactamase inhibition with O. tenuiflorum extracts. Comparative evaluation of the O. tenuiflorum extracts with increasing concentration of inhibitor suggests that ethyl acetate extract of O. tenuiflorum contains the highest inhibition potential, which is comparable with clavulanic acid.Conclusion: The results demonstrated that the ethyl acetate extract of O. tenuiflorum contain the highest level of beta-lactamase inhibitor, which in the future can be used as an alternative to synthetic beta-lactamase inhibitors that are presently being used to control beta-lactam antibiotic resistance

scholarly journals Evaluation of Ceftolozane/Tazobactam, Ceftazidime/Avibactam and Meropenem/Vaborbactam Against Multidrug-Resistant (MDR) Pseudomonas

2021 ◽  
Vol 1 (S1) ◽  
pp. s69-s70
Author(s):  
Haider Shamsulddin ◽  
Jeffrey Lin ◽  
Julie Ribes ◽  
Thein Myint
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Patient Outcomes ◽  
Kidney Injury ◽  
Multidrug Resistant ◽  
New Combination ◽  
Control Group ◽  
Retrospective Case ◽  
University Of Kentucky ◽  
Combination Antibiotics ◽  
The Impact

Background: Data on the patient outcomes for newer β-lactam–β-lactamase inhibitor (BLBI) drugs compared to carbapenem-containing combination antibiotics for multidrug-resistant (MDR)–Pseudomonas aeruginosa infections are limited. Methods: This retrospective, case–control observational study was based on chart review of the patients managed at the University of Kentucky. Results: In total, 143 patients with MDRO Pseudomonas aeruginosa infections were identified and divided into 2 groups: 1 group received newer BLBI combinations with or without aminoglycosides or polymyxins, for at least 72 hours, and the control group received carbapenem containing combination antibiotics or other antibiotics. Baseline characteristics and patient outcomes are shown in Table 1. Discussion: The newer BLBI combinations group consisted of 60.8% MDR Pseudomonas bacteremia, whereas the control group had 68.4% of MDR Pseudomonas respiratory cultures. Overall, the use of newer BLBI combinations such as ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam was associated with lower rates of acute kidney injury (AKI), shorter LOS, and lower mortality rates compared to the control group, and these differences were statistically significant. Because the 2 populations of patient differed significantly based on the site of infection (sepsis vs pneumonia), the data were reanalyzed to evaluate the impact of therapy on the occurrence of AKI, LOS, and mortality based on the site of infection. Only those patients with sepsis who received the newer combination drugs had significantly better rates of AKI, lower LOS, and had lower rates of mortality. The 2 treatment arms were not statistically different when comparing patients with pneumonia. Additionally, the use of these new combination therapies did not make a difference regarding readmission rates or duration of bacteremia for the patients included in the study.Funding: NoDisclosures: None

scholarly journals EUS-guided gastroenterostomy versus enteral stenting for gastric outlet obstruction: Systematic review and meta-analysis

2021 ◽  
Vol 09 (03) ◽  
pp. E496-E504
Author(s):  
Saurabh Chandan ◽  
Shahab R. Khan ◽  
Babu P. Mohan ◽  
Aun R. Shah ◽  
Mohammad Bilal ◽  
...  
Keyword(s):  
Gastric Outlet Obstruction ◽  
Safety Profile ◽  
Clinical Success ◽  
Meta Analysis ◽  
Surgical Techniques ◽  
Outlet Obstruction ◽  
Final Analysis ◽  
Clinical Effectiveness ◽  
Morbidity Rate ◽  
Technical Success

Abtract Background and study aims Endoscopic and surgical techniques have been utilized for palliation of gastric outlet obstruction (GOO). Enteral stenting (ES) is an established technique with high clinical success and low morbidity rate. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a novel approach that aims to provide sustained palliation of GOO. We conducted a comprehensive review and meta-analysis to evaluate the effectiveness in terms of clinical and technical success, as well as the safety profile of EUS-GE and ES. Methods We searched multiple databases from inception through July 2020 to identify studies that reported on safety and effectiveness of EUS-GE in comparison to ES. Pooled rates of technical success, clinical success, and adverse events (AEs) were calculated. Study heterogeneity was assessed using I2% and 95 % confidence interval. Results Five studies including 659 patients were included in our final analysis. Pooled rate of technical and clinical success for EUS-GE was 95.2 % (CI 87.2-.98.3, I2 = 42) and 93.3 % (CI 84.4–97.3, I2 = 59) while for ES it was 96.9 % (CI 90.9–99, I2 = 64) and 85.6 % (CI 73–92.9, I2 = 85), respectively. Pooled rate of re-intervention was significantly lower with EUS-GE i. e. 4 % (CI 1.8–8.7, I2 = 35) compared to ES, where it was 23.6 % (CI 17.5–31, I2 = 35), p = 0.001. Pooled rates of overall and major AEs were comparable between the two techniques. Conclusion EUS-GE is comparable in terms of technical and clinical effectiveness and has a similar safety profile when compared to ES for palliation of GOO.

scholarly journals Intravenous colistin use for infections due to multidrug-resistant gram-negative bacilli in critically ill paediatric patients: a systematic review and meta-analysis

2018 ◽  
Author(s):  
Spyridon A. Karageorgos ◽  
Hamid Bassiri ◽  
George Siakallis ◽  
Michael Miligkos ◽  
Constantinos Tsioutis
Keyword(s):  
Systematic Review ◽  
Critically Ill ◽  
Meta Analysis ◽  
Age Groups ◽  
Clinical Effectiveness ◽  
Multidrug Resistant ◽  
Loading Dose ◽  
Gram Negative ◽  
Paediatric Patients ◽  
Tract Infections

SynopsisBackgroundData are limited regarding the clinical effectiveness and safety of intravenous colistin for treatment of infections by multidrug-resistant gram-negative bacilli (MDR-GNB) in the paediatric intensive care unit (PICU).MethodsSystematic review of intravenous colistin use in critically ill paediatric patients with MDR-GNB infection in PubMed, Scopus and Embase (through January 31st, 2018).ResultsOut of 1,181 citations, 7 studies were included on the use of intravenous colistin for 405 patients in PICU. Majority of patients were diagnosed with lower respiratory tract infections, with Acinetobacter baumannii being the predominant pathogen. Colistin dosages ranged between 2.6-18 mg/kg/day, with none but one case reporting a loading dose. Emergence of colistin-resistance during treatment was reported in two cases. Nephrotoxicity and neurotoxicity were reported in 6.1% and 0.5% respectively, but concomitant medications and severe underlying illness limited our ability to definitively associate use of colistin with nephrotoxicity. Crude mortality was 29.5% (95%CI 21.7-38.1%), whereas infection-related mortality was 16.6% (95%CI 12.2-21.5%).ConclusionsWhile the reported incidence of adverse events related to colistin were low, reported mortality rates for infections by MDR-GNB in PICU were notable. In addition to severity of disease and comorbidities, inadequate daily dosage and the absence of a loading dose may have contributed to mortality. As the use of colistin for treatment of MDR-GNB infections increases, it is imperative to understand whether optimal dosing of colistin in paediatric patients differs across different age groups. As such, future studies to establish the pharmacokinetic properties of colistin in different paediatric settings are warranted.

scholarly journals Clarithromycin versus Amoxicillin alone or with Clavulanate in Acute Maxillary Sinusitis: A Meta-analysis of Clinical Trials

2021 ◽  
Vol 13 (1) ◽  
pp. 1-9
Author(s):  
Daryl J. Hoban ◽  
Jos Nauta
Keyword(s):  
Drug Treatment ◽  
Clinical Success ◽  
Maxillary Sinusitis ◽  
Meta Analysis ◽  
Study Drug ◽  
Total Daily Dose ◽  
Success Rates ◽  
Rate Difference ◽  
Daily Dose ◽  
Cure Rates

Objective: A meta-analysis was performed to explore the relative effects of clarithromycin and amoxicillin (with or without clavulanate potassium) in the treatment of acute maxillary sinusitis. Methods: Six studies were identified in the peer-reviewed literature. All were randomized single-blind (investigator-blind) or open-label trials in outpatients diagnosed with acute maxillary sinusitis. A total of 1580 patients were enrolled, of whom 1194 were clinically evaluable. The total daily dose of clarithromycin was 1000 mg; the total daily dose of amoxicillin (with or without clavulanate potassium) was either 1500 or 2000 mg. The duration of study drug treatment varied from 8 to 14 days. Endpoints comprised clinical and radiological success within 48 h of the end of study drug treatment plus bacteriologic cure and eradication. Success and cure rate differences were analyzed using fixed- and random-effect models. The absence of between-study heterogeneity was tested using Cochran’s Q-test. Results: Clinical success rates varied between 85.8% and 97.9% for clarithromycin and between 84.2% and 96.8% for amoxicillin. The combined rate difference in clinical success rates between clarithromycin and amoxicillin was +1.9% (P=0.14). Radiological success rates (four studies) varied from 78.2% to 94.0% for clarithromycin and 79.7% to 95.0% for amoxicillin, with a combined rate difference of zero (P=1.00). Bacteriologic cure rates (four studies) were 87.1–94.6% for clarithromycin, compared with 89.8–98.1% for amoxicillin, with a combined difference in cure rates of –3.2% (P=0.16). Overall bacterial eradication rates were comparable between the two treatments (clarithromycin, 89.3%; amoxicillin, 92.1%). Conclusion: These data, with their limitations properly acknowledged, identify clarithromycin as a valid and viable alternative to amoxicillin for the treatment of acute maxillary sinusitis in adults.

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