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

Author(s):  
Geneva Wilson ◽  
Margaret Fitzpatrick ◽  
Kyle Walding ◽  
Beverly Gonzalez ◽  
Marin L Schweizer ◽  
...  

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.

2020 ◽  
Vol 41 (S1) ◽  
pp. s316-s316
Author(s):  
Geneva Wilson ◽  
Margaret Fitzpatrick ◽  
Kyle Walding ◽  
Beverly Gonzalez ◽  
Charlesnika Evans

Background: Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (C/A) are new β-lactam/β-lactamase combination antibiotics that were approved by the FDA in 2014 and 2015, respectively, to treat complicated intra-abdominal and urinary tract infections. They are commonly used to treat multidrug-resistant Pseudomonas aeruginosa (MDRPA) and carbapenem-resistant Enterobacteriaceae (CRE) infections at any site. Both medications are also often used as salvage therapy when empiric therapy has failed or when the infectious organism tests resistant to all other available antibiotics. The purpose of this review is to present the clinical experience and reported clinical success rates of C/T and C/A. Methods: PubMed, EMBASE, and Google Scholar were searched from January 1, 2013, through October 1, 2019, for publications detailing clinical experience with C/T and C/A in patients with CRE and MDRPA infections. Included study designs were extended cases series and clinical observational studies. Information on infection type, bacterial agent, salvage therapy uses, clinical success, and resistance development during treatment were abstracted. Meta-regression analysis was used to determine the pooled effectiveness of C/T and C/A among included studies. Results: The literature search returned 1,645 publications. After exclusion criteria were applied, 16 publications representing 769 patients were retained. The study population was mostly male (pooled average, 62%). The major comorbidities represented in the pooled population were solid organ transplantation (20.0%), kidney disease (19.5%), cardiovascular disease (15.3%), and diabetes (15.3%). Pneumonia was the predominant infection type (41.4%) and MDRPA was the pathogen most frequently evaluated (57.7%). The pooled clinical success rate was 70.2% (95% CI, 64.5%–75.3%). Also, 10 studies explicitly evaluated C/A or C/T as salvage therapy. The pooled clinical success rate for salvage therapy studies was 75.2% (95% CI, 69.7%–80.0%). Development of resistance to C/T or C/A during or after treatment was reported for 2.0% of the population. Conclusion: Overall, these medications have a high clinical success rate in patients with severe and complicated infections and limited treatment options. Pooled clinical success rates were high (70.2%) and the medications were particularly effective as salvage therapy. Resistance rates were low, although this could have been biased by the small percentage of studies that reported on this outcome. More longitudinal studies comparing the effectiveness of C/T and C/A against other antibiotic regimens are needed.Funding: NoneDisclosures: None


Author(s):  
Geneva M. Wilson ◽  
Margaret A. Fitzpatrick ◽  
Kyle Walding ◽  
Beverly Gonzalez ◽  
Marin L. Schweizer ◽  
...  

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.


2021 ◽  
pp. 20200754
Author(s):  
Shota Yamamoto ◽  
Tomohiro Matsumoto ◽  
Satoshi Suda ◽  
Kosuke Tomita ◽  
Shunsuke Kamei ◽  
...  

Objective: We investigated the efficacy and exposure to radiation in 320-detector row computed tomography fluoroscopy-guided (CTF-guided) interventions. Methods: We analysed 231 320-detector row CTF-guided interventions (207 patients over 2 years and 6 months) in terms of technical success rates, clinical success rates, complications, scanner settings, overall radiation doses (dose–length product, mGy*cm), patient doses of peri-interventional CT series, and interventional CT (including CTF), as a retrospective cohort study. The relationships between patient radiation dose and interventional factors were assessed using multivariate analysis. Results: Overall technical success rate was 98.7% (228/231). The technical success rates of biopsies, drainages, and aspirations were 98.7% (154/156), 98.5% (66/67), and 100% (8/8), respectively. The clinical success rate of biopsies was 93.5% (146/156). All three major complications occurred in chest biopsies. The median total radiation dose was 522.4 (393.4–819.8) mGy*cm. Of the total radiation dose, 87% was applied during the pre- and post-interventional CT series. Post-interventional CT accounted for 24.4% of the total radiation dose. Only 11.4% of the dose was applied by CTF-guided intervention. Multilinear regression demonstrated that male sex, body mass index, drainage, intervention time, and helical scan as post-interventional CT were significantly associated with higher dose. Conclusion: The 320-detector row CTF interventions achieved a high success rate. Dose reduction in post-interventional CT provides patient dose reduction without decreasing the technical success rates. Advances in knowledge: This is the first study on the relationship between various interventional outcomes and patient exposure to radiation in 320-detector row CTF-guided interventions, suggesting a new perspective on dose reduction.


2020 ◽  
Vol 08 (07) ◽  
pp. E861-E868
Author(s):  
Naosuke Kuraoka ◽  
Kazuo Hara ◽  
Nozomi Okuno ◽  
Takamichi Kuwahara ◽  
Nobumasa Mizuno ◽  
...  

Abstract Background and study aims Endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CDS) is an alternative therapy for percutaneous transhepatic biliary drainage. Outcomes of EUS-CDS for distal biliary tract obstruction with a covered self-expandable metallic stent (SEMS) as a primary drainage technique are unclear because there are few relevant reports. This study aimed to determine outcomes in patients undergoing EUS-CDS using SEMS as the primary drainage technique for malignant distal biliary duct obstruction. Patients and methods This retrospective study was conducted at Aichi Cancer Center Hospital, from January 2010 to July 2018, using data from our database. Results EUS-CDS was performed as a primary drainage technique for 92 patients. The technical success rate was 92.8 %, and the clinical success rate was 91.6 %. The overall incidence of adverse events was 15.7 %. The median stent patency time for the EUS-CDS was 396 days. Nineteen patients required re-intervention because of cholangitis or jaundice. Conclusion EUS-CDS as a primary drainage technique using SEMS has high technical and clinical success rates. It should be considered an effective drainage method with respect to long-term stent patency, low re-intervention rates, and absence of severe complications.


2021 ◽  
Author(s):  
Ruanmei Sheng ◽  
Xuemin Wang ◽  
Yanqiang Hou ◽  
Jun Liu ◽  
Zhiwen Yang

Abstract Carbapenem-resistant gram-negative bacteria constitute a serious threat to public health worldwide. However, as a result of the complexities of clinical therapy, antibiotic options against carbapenem-resistant pathogens have not yet been fully standardized. Here, we conducted a retrospective study in 65,000 inpatients over a 2-year period that involved a total of 86 patients from whom carbapenem-resistant gram-negative bacteria were isolated. Monotherapy using trimethoprim/ sulfamethoxazole, amikacin, meropenem, and/or doxycycline in our hospital exhibited a clinical success rate of 83.3% for carbapenem-resistant Klebsiella pneumoniae, monotherapy using moxifloxacin, piperacillin/tazobactam, cefepime, and/or ceftazidime for carbapenem-resistant Pseudomonas aeruginosa exhibited a clinical success rate of 77.7%, and monotherapy using cefoperazone/sulbactam or combination therapy with tigecycline and cefoperazone/sulbactam for carbapenem-resistant Acinetobacter baumannii exhibited a clinical success rate of 62.1%. Our findings highlight the clinical strategies used in our hospital to successfully treat carbapenem-resistant gram-negative bacterial infections.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S802-S802
Author(s):  
Geneva M Wilson ◽  
Margaret A Fitzpatrick ◽  
Kyle Walding ◽  
Beverly Gonzalez ◽  
Katie J Suda ◽  
...  

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


2019 ◽  
Vol 103 (11-12) ◽  
pp. 605-612
Author(s):  
Bünyamin Gürbulak ◽  
Esin Kabul Gürbulak ◽  
Hasan Bektaş ◽  
İsmail Ethem Akgün ◽  
Hızır Yakup Akyildiz ◽  
...  

We aimed to review our experiences to evaluate the practicality, safety, and effectiveness of endoscopic stent placement for the palliation of malignant obstructions of the upper gastrointestinal system (GIS) and the treatment of postoperative complications such as failure of anastomoses and fistulae. Endoscopic stent placement is increasingly used in the upper GIS for the management of both high grade malignancies causing obstruction and benign pathologies such as anastomosis failures, gastrointestinal fistulae, and strictures. Hospital records, clinical data, and endoscopy reports of 61 patients who had undergone endoscopic stenting between the years 2012 and 2015 were analyzed retrospectively. For all patients, self-expandable metal covered stents were used. Data involving technical and clinical success rates, complication, morbidity, and mortality rates of the endoscopic stenting procedure was collected and simple statistical analyses were made. Endoscopic stenting was successful in 60 of 61 patients (98.3%). Overall technical success rate was found to be 98.3%; clinical success rate, 86.6%; complication rate, 4.9%. No stent related mortality was observed in our series. Endoscopic stents can be effectively and safely used in the treatment of various lesions of the upper GIS.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16261-e16261
Author(s):  
Hamid Ehsan ◽  
Muhammad Nadeem Yousaf ◽  
Ahsan Wahab ◽  
Karun Neupane ◽  
Muhammad Khawar Sana ◽  
...  

e16261 Background: Endoscopic ultrasound-guided ablation therapy (EUS-A) is a minimally invasive technique increasingly used for the management of surgically unresectable pancreatic cancer. The data on the efficacy and clinical outcome of EUS-A for unresectable pancreatic cancer is lacking. We conducted this systematic review and meta-analysis to evaluate the safety, technical and clinical success of EUS-A therapies specifically for unresectable pancreatic cancer. Methods: Studies were identified with a comprehensive search for EUS-A and pancreatic cancer on PubMed, Google Scholar, Web of Science and Embase data search as of October 2020. The technical and clinical success rates of EUS-A were primary outcomes while adverse events (AEs) rate was secondary outcome. We defined technical success as successful placement of probe within tumor and able to perform ablation regardless of tumor outcome. Clinical success was defined as symptomatic improvement and/or any reduction in tumor size or evidence of necrosis on radiological imaging after EUS-A. A compute pooled analysis was performed using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.0.2) using random effect model. Results: Nineteen studies including 192 patients (54% females) were included. Common pancreatic tumors were nonfunctional neuroendocrine tumor (NNET) 43.5% (97), followed by locally advanced pancreatic ductal adenocarcinoma (LAPDAC) 27.3% (61), insulinoma 17.9% (40), cystic neoplastic lesions 8.5% (19). The pancreatic head was the most common site of tumor 49.8% (111), followed by body, neck and tail 44.8% (100). EUS-RFA was the most commonly used ablative therapy 63% (12/19 studies), followed by EUS-EA (ethanol ablation) 26% (5/19 studies) while EUS-A using laser and lauromacrogol injection was used in one study each. The mean number of ablation sessions per patient was 1.4 based on the total 243 sessions in 176 patients. The pooled technical success rate of EUS-A was 99.5% [95% CI = 0.90-0.97, I2 = 0%]. The pooled clinical success rate calculated out of total number of pancreatic lesions was 91.1% [95% CI = 0.79-0.92, I2 = 16%]. Clinical improvement in symptoms was reported in 11 studies and a complete resolution or decrease in tumor size was reported in 16 studies. The pooled AEs rate was 22.9% [95% CI = 0.17-0.37, I2 = 43%]. Common AEs were abdominal pain 7.8% (15), pancreatitis 5.2% (10) and pancreatic pseudocyst 2.1% (4). The median follow-up was 9.5 months. Conclusions: EUS-A is a safe and promising modality in the management of unresectable pancreatic cancer with a high technical and clinical success rate. Large prospective studies and clinical trials are required for comparison of clinical outcome of different EUS-A therapies and its widespread application for unresectable pancreatic cancer.


Author(s):  
Akhil Baby ◽  
Danny Joy ◽  
Nihar R. Dash ◽  
Sujoy Pal ◽  
Deep N. Srivastava ◽  
...  

Abstract Introduction This article assesses the safety and utility of transhepatic drainage of deep seated postoperative intra-abdominal collections under computed tomography (CT) guidance in a short series. Materials and Methods This retrospective study included five patients (mean age: 45.8 years; 3 males, 2 females) who underwent CT-guided transhepatic drainage of postoperative abdominal abscess in our department between April 2019 and December 2020. The clinical and surgical details and the details of the transhepatic drainage procedure were evaluated along with success rates and complications. Results The surgical procedures were Whipple's pancreaticoduodenectomy in four patients and gastrectomy in one patient. Four out of five abscesses were drained through the right lobe of liver, while one was through the left lobe with a technical success rate of 100%. The mean total time for catheter drainage procedure including patient positioning and preparation was 29.2 minutes. None of the patients had procedure-related complications. Mean duration of catheter drainage was 12 days. All patients had complete resolution of symptoms after drainage and the clinical success rate was 100%. Conclusion Transhepatic approach is safe and effective for the drainage of inaccessible postoperative abdominal collections or abscesses where a standard percutaneous approach is not possible.


1977 ◽  
Vol 5 (5) ◽  
pp. 313-321 ◽  
Author(s):  
J Sjövall

In an open multicentre study of bacampicillin (Penglobe®), a new orally well absorbed prodrug of ampicillin, 516 patients with acute exacerbations of chronic bronchitis or pneumonia were treated by a group of Belgian pneumologists or internists. Bacampicillin was given in a dosage regimen of 400 mg or 800 mg three times daily. In patients with acute exacerbations of chronic bronchitis the clinical success rate was high, over 95% in both groups. A n improvement in the sputum purulence score was seen in 93% of the patients with an initially purulent sputum and 69% had a normal mucoid sputum at follow-up. The clinical success rate in patients with pneumonia was also similar in both dosage groups with success rates over 96%. The total number of patients with adverse reactions was not more than 5·4%, of which the majority were considered mild or moderate. Each type of side-effect occurred in a frequency of 1·2% or less. There were no differences between the two dosage regimens as regards the frequency of side-effects which indicates a remarkably good tolerance of bacampicillin also with the higher dosage.


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