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Frontiers in Medicine 2023Carbapenem-resistant (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment...
, and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant and multidrug-resistant isolates or infections: a scoping review.
INTRODUCTION
Carbapenem-resistant (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 , 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 , 7 and 20 clinical studies were evaluated. 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 or 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.
PubMed: 37727767
DOI: 10.3389/fmed.2023.1249030 -
Antibiotics (Basel, Switzerland) May 2023Infections by multi-drug-resistant (MDR) organisms are sharply increasing in newborns worldwide. In low and middle-income countries, a disproportionate amount of... (Review)
Review
BACKGROUND
Infections by multi-drug-resistant (MDR) organisms are sharply increasing in newborns worldwide. In low and middle-income countries, a disproportionate amount of neonatal sepsis caused by MDR Gram negatives was recently reported. Newborns with infections by MDR organisms with limited treatment options may benefit from novel antimicrobials.
METHODS
We performed a literature search investigating the use in newborns, infants and children of novel antimicrobials for the treatment of MDR Gram negatives, namely ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, meropenem/vaborbactam, imipenem/relebactam, and Gram positives with resistance of concern, namely ceftaroline and dalbavancin. PubMed, EMBASE, and Web of Science were searched.
RESULTS
A total of 50 records fulfilled the inclusion criteria. Most articles were case reports or case series, and ceftazidime/avibactam was the most studied agent. All studies showed favorable efficacy and safety profile in newborns and across different age cohorts.
CONCLUSIONS
novel antibiotics may be considered in newborns for the treatment of MDR Gram negatives with limited treatment options and for Gram positives with resistance concerns. Further studies are needed to address their effectiveness and safety in newborns.
PubMed: 37370275
DOI: 10.3390/antibiotics12060956 -
Diagnostic Microbiology and Infectious... Aug 2023Antibiotic resistance surveillance may be essential to identify patterns of antibiotic resistance and guide treatment choices. Therefore, this systematic review and... (Meta-Analysis)
Meta-Analysis Review
Antibiotic resistance surveillance may be essential to identify patterns of antibiotic resistance and guide treatment choices. Therefore, this systematic review and meta-analysis aimed to evaluate amikacin resistance and susceptibility in children with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). From inception to September 5, 2022, relevant studies were searched via PubMed, Embase, Cochrane Library, and Web of Science databases. A network meta-analysis was conducted to explore the sequencing of resistance rates in amikacin and other antibiotics. Totally, 26 studies with 2582 clusters of bacterial isolates were included. The resistance rate of amikacin in children with ESBL-PE was 10.1%, higher than the resistance rate of tigecycline (0.0%), ertapenem (0.4%), meropenem (0.7%), and imipenem (3.0%). For the drug susceptibility rate in children with ESBL-PE, the susceptibility rate of amikacin (89.7%) was lower than tigecycline (99.6%), imipenem (96.8%), meropenem (97.3%), and ertapenem (95.6%). Amikacin showed a low drug resistance and a high drug resistance in children with ESBL-PE infection, making it a good option for the treatment of the infection caused by ESBL-PE.
Topics: Child; Humans; Amikacin; Ertapenem; Meropenem; Tigecycline; Escherichia coli; Klebsiella pneumoniae; Anti-Bacterial Agents; Imipenem; beta-Lactamases; Drug Resistance; Microbial Sensitivity Tests
PubMed: 37290259
DOI: 10.1016/j.diagmicrobio.2023.115956 -
Antibiotics (Basel, Switzerland) Apr 2023While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects,... (Review)
Review
While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects, differences in antimicrobial pharmacokinetics between Asian and non-Asian patients with severe pathologic conditions require further investigation. For the purpose of describing the potential differences in antimicrobial pharmacokinetics between Asian and non-Asian populations, a systematic review was performed using six journal databases and six theses/dissertation databases (PROSPERO record CRD42018090054). The pharmacokinetic data of healthy volunteers and non-critically ill and critically ill patients were reviewed. Thirty studies on meropenem, imipenem, doripenem, linezolid, and vancomycin were included in the final descriptive summaries. In studies recruiting hospitalised patients, inconsistent differences in the volume of distribution (V) and drug clearance (CL) of the studied antimicrobials between Asian and non-Asian patients were observed. Additionally, factors other than ethnicity, such as demographic (e.g., age) or clinical (e.g., sepsis) factors, were suggested to better characterise these pharmacokinetic differences. Inconsistent differences in pharmacokinetic parameters between Asian and non-Asian subjects/patients may suggest that ethnicity is not an important predictor to characterise interindividual pharmacokinetic differences between meropenem, imipenem, doripenem, linezolid, and vancomycin. Therefore, the dosing regimens of these antimicrobials should be adjusted according to patients' demographic or clinical characteristics that can better describe pharmacokinetic differences.
PubMed: 37237706
DOI: 10.3390/antibiotics12050803 -
Blood Purification 2023The optimal meropenem dosing regimens in critically ill patients receiving continuous renal replacement therapy (CRRT) based on pharmacokinetic and pharmacodynamic (PD)...
INTRODUCTION
The optimal meropenem dosing regimens in critically ill patients receiving continuous renal replacement therapy (CRRT) based on pharmacokinetic and pharmacodynamic (PD) concepts are not well established. This study aimed to (1) gather the available published pharmacokinetic studies conducted in septic patients receiving CRRT and (2) to define the optimal meropenem dosing regimens in these populations via Monte Carlo simulations.
METHODS
We used Medical Subject Headings "meropenem," "continuous renal replacement therapy," and "pharmacokinetics" or related terms to identify studies for systematic review. A one-compartment pharmacokinetic model was conducted to predict meropenem levels for the initial 48 h of therapy. The PD targets were 40% of free drug above a threshold of 1 times the minimum inhibitory concentration (MIC) (40% fT > MIC), 4 times the MIC (40% fT > 4MIC), and an additional target of free drug level above 1 times MIC 100% of the time (fT > MIC). The dose that achieved at least 90% of the probability of target attainment (PTA) was defined as an optimal dose.
RESULTS
Twenty-one articles were included for our systematic review. The necessary pharmacokinetic parameters such as volume of distribution and CRRT clearance were cited in 90.5 and 71.4% of articles, respectively. None of the published studies reported completed necessary parameters. A regimen of 750 mg q 8 h was found to be the optimal dose for pre-dilution continuous venovenous hemofiltration and continuous venovenous hemodialysis modality using two effluent rates (25 and 35 mL/kg/h) which achieved the PD target of 40% fT > 4MIC.
CONCLUSION
None of the published studies showed the necessary pharmacokinetic parameters. PD target significantly contributed to meropenem dosage regimens in these patients. Differing effluent rates and types of CRRT shared similar dosing regimens. Clinical validation of the recommendation is suggested.
Topics: Humans; Meropenem; Continuous Renal Replacement Therapy; Anti-Bacterial Agents; Monte Carlo Method; Critical Illness; Renal Replacement Therapy
PubMed: 37231811
DOI: 10.1159/000529694 -
Medicina (Kaunas, Lithuania) Mar 2023: Vancomycin combined with piperacillin/tazobactam (vancomycin + piperacillin/tazobactam) has a higher risk of acute kidney injury (AKI) than vancomycin combined with... (Meta-Analysis)
Meta-Analysis Review
Evaluating the Nephrotoxicity of Area-under-the-Curve-Based Dosing of Vancomycin with Concomitant Antipseudomonal Beta-Lactam Antibiotics: A Systematic Review and Meta-Analysis.
: Vancomycin combined with piperacillin/tazobactam (vancomycin + piperacillin/tazobactam) has a higher risk of acute kidney injury (AKI) than vancomycin combined with cefepime or meropenem. However, it is uncertain if applying area under the curve (AUC)-based vancomycin dosing has less nephrotoxicity than trough-based dosing in these combinations. : We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to December 2022. We examined the odds ratio (OR) of AKI between vancomycin + piperacillin/tazobactam and the control group. The control group was defined as vancomycin combined with antipseudomonal beta-lactam antibiotics, except for piperacillin-tazobactam. : The OR for AKI is significantly higher in vancomycin + piperacillin/tazobactam compared with the control group (3 studies, 866 patients, OR of 3.861, 95% confidence interval of 2.165 to 6.887, < 0.05). In the sample population of patients who received vancomycin + piperacillin/tazobactam (2 studies, 536 patients), the risk of AKI (OR of 0.715, 95% CI of 0.439 to 1.163, = 0.177) and daily vancomycin dose (standard mean difference-0.139, 95% CI-0.458 to 0.179; = 0.392) are lower by AUC-based dosing than trough-based dosing, although it is not statistically significant. : Nephrotoxicity is higher when combined with piperacillin/tazobactam than other antipseudomonal beta-lactam antibiotics (cefepime or meropenem) using the AUC-based dosing. However, applying the AUC-based dosing did not eliminate the risk of AKI or significantly reduce thedaily vancomycin dose compared with the trough-based dosing in the available literature.
Topics: Humans; Vancomycin; Anti-Bacterial Agents; Cefepime; Meropenem; Drug Therapy, Combination; Retrospective Studies; Piperacillin, Tazobactam Drug Combination; Monobactams; Acute Kidney Injury
PubMed: 37109649
DOI: 10.3390/medicina59040691 -
BMC Infectious Diseases Apr 2023Which antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Which antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains unclear but is paramount in the context of evolving antimicrobial resistance. Therefore, updated meta-analyses on this issue are warranted.
METHODS
We systematically searched four major electronic databases from their inception through October 2022. Randomized controlled trials examining antimicrobial agents for cIAI treatment were included. Two reviewers independently assessed the quality of included studies utilizing the Cochrane Collaboration's risk of bias tool as described in the updated version 1 of the Cochrane Collaboration Handbook and extracted data from all manuscripts according to a predetermined list of topics. All meta-analyses were conducted using R software. The primary outcome was clinical success rate in patients with cIAIs.
RESULTS
Forty-five active-controlled trials with low to medium methodological quality and involving 14,267 adults with cIAIs were included in the network meta-analyses. The vast majority of patients with an acute physiology and chronic health evaluation II score < 10 had low risk of treatment failure or death. Twenty-one regimens were investigated. In the network meta-analyses, cefepime plus metronidazole was more effective than tigecycline and ceftolozane/tazobactam plus metronidazole (odds ratio [OR] = 1.96, 95% credibility interval [CrI] 1.05 ~ 3.79; OR = 3.09, 95% CrI 1.02 ~ 9.79, respectively). No statistically significant differences were found among antimicrobial agents regarding microbiological success rates. Cefepime plus metronidazole had lower risk of all-cause mortality than tigecycline (OR = 0.22, 95% CrI 0.05 ~ 0.85). Statistically significant trends were observed favoring cefotaxime plus metronidazole, which exhibited fewer discontinuations because of adverse events (AEs) when compared with eravacycline, meropenem and ceftolozane/tazobactam plus metronidazole (OR = 0.0, 95% CrI 0.0 ~ 0.8; OR = 0.0, 95% CrI 0.0 ~ 0.7; OR = 0.0, 95% CrI 0.0 ~ 0.64, respectively). Compared with tigecycline, eravacycline was associated with fewer discontinuations because of AEs (OR = 0.17, 95% CrI 0.03 ~ 0.81). Compared with meropenem, ceftazidime/avibactam plus metronidazole had a higher rate of discontinuation due to AEs (OR = 2.09, 95% CrI 1.0 ~ 4.41). In pairwise meta-analyses, compared with ceftriaxone plus metronidazole, ertapenem and moxifloxacin (one trial, OR = 1.93, 95% CI 1.06 ~ 3.50; one trial, OR = 4.24, 95% CI 1.18 ~ 15.28, respectively) were associated with significantly increased risks of serious AEs. Compared with imipenem/cilastatin, tigecycline (four trials, OR = 1.57, 95%CI 1.07 ~ 2.32) was associated with a significantly increased risk of serious AEs. According to the surface under the cumulative ranking curve, Cefepime plus metronidazole was more likely to be optimal among all treatments in terms of efficacy and safety, tigecycline was more likely to be worst regimen in terms of tolerability, and eravacycline was more likely to be best tolerated.
CONCLUSION
This study suggests that cefepime plus metronidazole is optimal for empirical treatment of patients with cIAIs and that tigecycline should be prescribed cautiously considering the safety and tolerability concerns. However, it should be noted that data currently available on the effectiveness, safety, and tolerability of antimicrobial agents pertain mostly to lower-risk patients with cIAIs.
Topics: Adult; Humans; Metronidazole; Meropenem; Network Meta-Analysis; Tigecycline; Cefepime; Anti-Bacterial Agents; Intraabdominal Infections; Tazobactam; Anti-Infective Agents
PubMed: 37085768
DOI: 10.1186/s12879-023-08209-9 -
Frontiers in Pharmacology 2023Cholera is a challenging ancient disease caused by (. Antibiotics that prevent cell wall synthesis are among the first known antibiotic groups. Due to its high... (Review)
Review
Cholera is a challenging ancient disease caused by (. Antibiotics that prevent cell wall synthesis are among the first known antibiotic groups. Due to its high consumption, has developed resistance to the majority of antibiotics in this class. Resistance to recommended antibiotics for the treatment of has also increased. In light of the decrease in consumption of certain antibiotics in this group that inhibit cell wall synthesis and the implementation of new antibiotics, it is necessary to determine the antibiotic resistance pattern of and to employ the most effective treatment antibiotic. An comprehensive systematic search for relevant articles was conducted in PubMed, Web of Science, Scopus, and EMBASE through October 2020. Stata version 17.1 utilized the Metaprop package to execute a Freeman-Tukey double arcsine transformation in order to estimate weighted pooled proportions. A total of 131 articles were included in the meta-analysis. Ampicillin was the most investigated antibiotic. The prevalence of antibiotic resistance was in order aztreonam (0%), cefepime (0%), imipenem (0%), meropenem (3%), fosfomycin (4%), ceftazidime (5%), cephalothin (7%), augmentin (8%), cefalexin (8%), ceftriaxone (9%), cefuroxime (9%), cefotaxime (15%), cefixime (37%), amoxicillin (42%), penicillin (44%), ampicillin (48%), cefoxitin (50%), cefamandole (56%), polymyxin-B (77%), carbenicillin (95%) respectively. Aztreonam, cefepime, and imipenem are the most efficient cell wall synthesis inhibitors. There has been an increase in resistance to antibiotics such as cephalothin, ceftriaxone, amoxicillin, and meropenem. Over the years, resistance to penicillin, ceftazidime, and cefotaxime, has decreased.
PubMed: 37021056
DOI: 10.3389/fphar.2023.1027277 -
Journal of Global Antimicrobial... Jun 2023Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing... (Meta-Analysis)
Meta-Analysis
Clinical efficacy of ertapenem vs. other carbapenems for the treatment of extended-spectrum-β-lactamase-producing Enterobacterales infection: A systematic review and meta-analysis.
OBJECTIVE
Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales infection. However, whether ertapenem is as effective as other carbapenems for ESBL-producing Enterobacterales remains unclear. Therefore, this meta-analysis was conducted to compare the clinical efficacy of ertapenem versus other carbapenems in the treatment of ESBL-producing Enterobacterales infection.
METHODS
PubMed, Web of Science, and Cochrane Library were searched from their inception to 29 November 2022. Only studies comparing ertapenem and other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections were included.
RESULTS
A total of six studies meeting selection criteria were identified. Overall, ertapenem was associated with a significantly lower 30-d mortality when compared with other carbapenems (10.7% [46/431] vs. 17.7% [104/586]; risk ratio [RR], 0.61; 95% CI: 0.40-0.91). The ertapenem group exhibited a significantly shorter length of hospital stay than the other carbapenem groups (mean differences, -6.02 d; 95% CI, -9.39 to -2.64). No significant differences were noted between ertapenem and other carbapenem groups in terms of rates of clinical cure or improvement (RR, 1.11; 95% CI: 0.97-1.25) and microbiological eradication (RR, 1.01; 95% CI: 0.97-1.06).
CONCLUSIONS
Ertapenem could be as effective as other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections.
Topics: Humans; Ertapenem; Carbapenems; Anti-Bacterial Agents; beta-Lactams; beta-Lactamases; Treatment Outcome; Gammaproteobacteria
PubMed: 36944409
DOI: 10.1016/j.jgar.2023.03.003 -
The Yale Journal of Biology and Medicine Dec 2022: Antibiotic resistance in cystic fibrosis (CF) is a well-known phenomenon. However, the comprehensive epidemiological impact of antibiotic resistance in CF is not... (Meta-Analysis)
Meta-Analysis Review
: Antibiotic resistance in cystic fibrosis (CF) is a well-known phenomenon. However, the comprehensive epidemiological impact of antibiotic resistance in CF is not clearly documented. So, this meta-analysis evaluated the proportion rates of carbapenem resistance (imipenem, meropenem, and doripenem) in CF based on publication date (1979-2000, 2001-2010, and 2011-2021), continents, pathogens, and antimicrobial susceptibility testing (AST). : We searched studies in PubMed, Scopus, and Web of Science (until April 2021). Statistical analyses were conducted using STATA software (version 14.0). : The 110 studies included in the analysis were performed in 25 countries and investigated 13,324 pathogens associated with CF. The overall proportion of imipenem, meropenem, and doripenem resistance in CF were 43% (95% CI 36-49), 48% (95% CI 40-57), 28% (95% CI 23-33), and 45% (95% CI 32-59), respectively. Our meta-analysis showed that trends of imipenem, meropenem, and doripenem-resistance had gradual decreases over time (1979-2021). This could be due to the limited clinical effectiveness of these antibiotics to treat CF cases over time. Among the opportunistic pathogens associated with CF, the highest carbapenem resistance rates were shown in , spp., , and . The highest and lowest carbapenem resistance rates among in CF patients were shown against meropenem (23%) and doripenem (39%). : We showed that trends of carbapenem resistance had decreased over time (1979-2021). This could be due to the limited clinical effectiveness of these antibiotics to treat CF cases over time. Plans should be directed to fight biofilm-associated infections and prevent the emergence of mutational resistance. Systematic surveillance for carbapenemase-producing pathogens in CF by molecular surveillance is necessitated.
Topics: Humans; Meropenem; Doripenem; Carbapenems; Cystic Fibrosis; Microbial Sensitivity Tests; Anti-Bacterial Agents; Imipenem; Pseudomonas aeruginosa
PubMed: 36568834
DOI: No ID Found