In vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa isolates or infections: a scoping review

IntroductionCarbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment costs. We aimed to evaluate in vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam (CZA) combination regimens with CZA alone against CRE and/or MDR-PA isolates or infections.MethodsWe systematically reviewed the relevant literature in CINAHL/MEDLINE, Pubmed, Cochrane, Web of Science, Embase, and Scopus until December 1, 2022. Review articles, grey literature, abstracts, comments, editorials, non-peer reviewed articles, non-English articles, and in vitro synergy studies conducted on single isolates were excluded.Results22 in vitro, 7 in vivo and 20 clinical studies were evaluated. In vitro studies showed reliable synergy between CZA and aztreonam against metallo-β-lactamase (MBL)-producing isolates. Some studies indicated good in vitro synergy between CZA and amikacin, meropenem, fosfomycin and polymyxins against CRE isolates. For MDR-PA isolates, there are comparatively fewer in vitro or in vivo studies. In observational clinical studies, mortality, clinical cure, adverse events, and development of CZA resistance after exposure were generally similar in monotherapy and combination therapy groups. However, antibiotic-related nephrotoxicity and infection relapses were higher in patients receiving CZA combination therapies.DiscussionThe benefit, if any, of CZA combination regimens in MDR-PA infections is elusive, as very few clinical studies have included these infections. There is no currently documented clinical benefit for the use of CZA combination regimens rather than CZA monotherapy. CZA combined with aztreonam for serious infections due to MBL producers should be evaluated by randomized controlled trials.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278552, CRD42021278552

Cutibacterium acnes in shoulder surgery : a scoping review of strategies for prevention, diagnosis, and treatment

Background: Cutibacterium acnes is a commensal, gram-positive, facultatively anaerobic bacillus that resides in the dermis. Historically thought to be a contaminant when identified on cultured specimens, recent advances in diagnostic technology have now implicated it as the most common organism responsible for postoperative shoulder infections. Despite a recognition of the role of this organism and a significant research interest in recent years, there is clear lack of consensus guideline on strategies to prevent, diagnose, and treat postoperative shoulder infection. Method: The electronic databases PubMed, MEDLINE, CINAHL, Scopus, and Web of Science were searched in March 2020. All experimental and nonexperimental studies that investigate C acnes in shoulder surgery were included. Inclusion was limited to articles published after 2000 and written in English; reviews, gray literature, or abstracts were excluded. A total of 70 studies were included in this review. This scoping review was performed in accordance with the Extended Preferred Reporting Items of Systematic Reviews and Meta-Analyses Statement for Scoping Reviews (PRISMA-ScR). Results: Standard surgical prophylactic regimens such as intravenous antibiotics and topical chlorhexidine are ineffective at removing C acnes from the deep layer of the dermis, and there is a shift toward using topical benzoyl peroxide with significantly improved efficacy. An improved understanding of the bacteria has demonstrated that a prolonged culture time of up to 14 days is needed, especially in cases of established infection. Advances in diagnostics such as sonication and molecular-based testing are promising. Although usually thought to be susceptible to a broad range of antibiotics, resistance is emerging to clindamycin. An improved understanding of its ability to form a biofilm highlights the difficulty in treating an established infection. Conclusion: The role of C acnes causing postoperative infection following shoulder surgery is being increasingly recognized. Strategies for prevention, diagnosis, and treatment have been outlined from both an antimicrobial and surgical perspective. A number of these strategies are emerging and require further research to demonstrate efficacy before implementation into clinical guidelines.</p

In vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa isolates or infections: a scoping review

Introduction: Carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment costs. We aimed to evaluate in vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam (CZA) combination regimens with CZA alone against CRE and/or MDR-PA isolates or infections. Methods: We systematically reviewed the relevant literature in CINAHL/MEDLINE, Pubmed, Cochrane, Web of Science, Embase, and Scopus until December 1, 2022. Review articles, grey literature, abstracts, comments, editorials, non-peer reviewed articles, non-English articles, and in vitro synergy studies conducted on single isolates were excluded. Results: 22 in vitro, 7 in vivo and 20 clinical studies were evaluated. In vitro studies showed reliable synergy between CZA and aztreonam against metallo-β-lactamase (MBL)-producing isolates. Some studies indicated good in vitro synergy between CZA and amikacin, meropenem, fosfomycin and polymyxins against CRE isolates. For MDR-PA isolates, there are comparatively fewer in vitro or in vivo studies. In observational clinical studies, mortality, clinical cure, adverse events, and development of CZA resistance after exposure were generally similar in monotherapy and combination therapy groups. However, antibiotic-related nephrotoxicity and infection relapses were higher in patients receiving CZA combination therapies. Discussion: The benefit, if any, of CZA combination regimens in MDR-PA infections is elusive, as very few clinical studies have included these infections. There is no currently documented clinical benefit for the use of CZA combination regimens rather than CZA monotherapy. CZA combined with aztreonam for serious infections due to MBL producers should be evaluated by randomized controlled trials. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278552, CRD42021278552

Is ceftazidime/avibactam an option for serious infections due to ESBL and AmpC producing Enterobacterales?: A systematic review and meta-analysis

Carbapenem sparing regimens are needed for the treatment of ESBL/AmpC producing Enterobacterales infections. We sought to compare the clinical efficacy of ceftazidime/avibactam and carbapenems against ESBL/AmpC producing Enterobacterales spp. A systematic review and meta-analysis of randomized controlled trials comparing ceftazidime/avibactam with carbapenems for the treatment of ESBL/AmpC producing Enterobacterales was conducted. Five RCTs with ESBLs/AmpC specific outcome data were compiled. Of the 246 patients infected with an ESBL producing microorganism in the ceftazidime/avibactam arm, 224 (91%) had a clinical response at TOC versus 240 of 271 (89%) patients in the carbapenem arm (RR 1.02, 95% CI 0.97–1.08, P=0.45, I2=0%). Clinical response for AmpC producers in the ceftazidime/avibactam and carbapenem arms were 32/40 (80%) and 37/42 (88%), respectively (RR 0.91, 95% CI 0.76–1.10, P=0.35, I2=0%). Microbiological response and mortality rates were not reported specifically for ESBL/AmpC producers. Ceftazidime/avibactam may be a carbapenem-sparing option for the treatment of mild to moderate complicated urinary tract and intraabdominal infections caused by ESBL producing Enterobacterales spp. and the data are limited to provide any conclusive recommendations for the AmpC producers. Care should be taken before extrapolating this to severe infections, given that the representation of this population in the reviewed studies was negligible. Ceftazidime/avibactam is a costly drug active against carbapenem resistant microorganisms, and should be used judiciously to preserve its activity against these

Efficacy and safety of carbapenems versus new antibiotics for treatment of adult patients with complicated urinary tract infections: a systematic review and meta-analysis

This systematic review and meta-analysis evaluated the clinical efficacy and safety of carbapenems for the treatment of complicated urinary tract infections (cUTIs) with the comparators being new antibiotics evaluated for this indication. We searched 13 electronical databases for published randomised controlled trials (RCTs) and completed and/or ongoing trials. The search terms were developed by using the PICOS framework. Pooled efficacy estimates of composite cure (clinical success and microbiological eradication) favour the new antibiotic groups, although this is not statistically significant [risk ratio (RR)=0.91; 95% confidence interval (CI); 0.79-1.04]. A pooled estimate examining clinical response alone showed no difference between treatment arms (RR=1.00; 95% CI: 0.96-1.05), however, new antibiotic treatments were superior to carbapenems for microbiological response (RR=0.85; 95% CI: 0.79-0.91). New antibiotic treatments demonstrated a superior microbiological response compared to carbapenems in clinical trials of cUTI, despite an absence of carbapenem resistance. However, it is noteworthy that the clinical response and safety profile of new antibiotics were not different from carbapenems

Efficacy and Safety of Carbapenems vs New Antibiotics for Treatment of Adult Patients With Complicated Urinary Tract Infections: A Systematic Review and Meta-analysis

This systematic review and meta-analysis evaluated the clinical efficacy and safety of carbapenems for the treatment of complicated urinary tract infections (cUTIs), with the comparators being new antibiotics evaluated for this indication. We searched 13 electronic databases for published randomized controlled trials (RCTs) and completed and/or ongoing trials. The search terms were developed using the Population, Intervention, Comparison, Outcomes, and Study framework. Pooled efficacy estimates of composite cure (clinical success and microbiological eradication) favored the new antibiotic groups, although this was not statistically significant (risk ratio [RR], 0.91; 95% CI, 0.79-1.04). A pooled estimate examining clinical response alone showed no difference between treatment arms (RR, 1.00; 95% CI, 0.96-1.05), however, new antibiotic treatments were superior to carbapenems for microbiological response (RR, 0.85; 95% CI, 0.79-0.91). New antibiotic treatments demonstrated a superior microbiological response compared with carbapenems in clinical trials of cUTI, despite an absence of carbapenem resistance. However, it is noteworthy that the clinical response and safety profile of new antibiotics were not different from those of carbapenems.© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America