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Journal of Global Antimicrobial... Mar 2023Antimicrobial resistance (AMR) is a global concern among infectious diseases. Bloodstream infections can potentially become life-threatening if they become untreatable... (Review)
Review
OBJECTIVES
Antimicrobial resistance (AMR) is a global concern among infectious diseases. Bloodstream infections can potentially become life-threatening if they become untreatable with conventional antimicrobials. This review aims to provide an understanding of the AMR prevalence and trends of common bacteremic pathogens, namely Escherichia coli and Staphylococcus aureus in the World Health Organization (WHO) Africa region.
METHODS
PubMed and Google Scholar were searched using relevant keywords for published human studies (excluding case reports and reviews) reporting bacteremic AMR data on the pathogens of interest between 2008 and 2019. Two reviewers independently screened the articles against a pre-defined eligibility criterion. Data extraction and analysis were achieved with different platforms: Covidence, Excel, R version 3.6.3, and QGIS v3.4.5. The pooled prevalence, 95% confidence intervals, and I index (a measure of heterogeneity) were calculated for the various pathogen-antibiotic combinations.
RESULTS
Five hundred sixty-two papers were retrieved, with 27 papers included in the final analysis. Only 23.4% (11/47) of member states of the WHO African region had reports on AMR in bacteremia. The Clinical and Laboratory Standards Institute (CLSI) (78.5%) was the most common standard used in the region. For E. coli, the pooled resistance was: cefotaxime (42%), imipenem (4%), meropenem (0%), and colistin (0%). For S. aureus, the calculated pooled resistance was cloxacillin (34%), oxacillin (12%), and vancomycin (0%). There was a high degree of variation across studies (I > 90%).
CONCLUSION
The pooled resistance rates indicate a concerning degree of methicillin-resistant and Extended Spectrum-ß-lactamase-producing pathogens. The paucity of AMR data also presents challenges for a comprehensive understanding of the situation in the region. Continent-wide and standardized surveillance efforts therefore need strengthening.
Topics: Humans; Staphylococcus aureus; Anti-Bacterial Agents; Escherichia coli; Prevalence; Drug Resistance, Bacterial; Staphylococcal Infections; Bacteremia; Africa
PubMed: 36526264
DOI: 10.1016/j.jgar.2022.11.016 -
Antibiotics (Basel, Switzerland) Nov 2022Shigellosis remains one of the leading causes of morbidity and mortality worldwide and is the second leading cause of diarrheal mortality among all age groups. However,... (Review)
Review
Shigellosis remains one of the leading causes of morbidity and mortality worldwide and is the second leading cause of diarrheal mortality among all age groups. However, the global emergence of antimicrobial-resistant strains, limiting the choice of effective drugs for shigellosis, has become the major challenge in the treatment of infections. The aim of this systematic review and meta-analysis was to provide an updated picture of the prevalence of antimicrobial-resistant species in Asia. A comprehensive and systematic search was performed on three electronic databases (PubMed, ScienceDirect and Scopus), in which 63 eligible studies published between 2010 and 2022 were identified. From our meta-analysis of proportions using a random-effects model, the overall prevalence of spp. in Asian patients was estimated to be 8.0% (95% CI: 5.5-10.5). The pooled prevalence rates of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing strains were 68.7% (95% CI: 59.9-77.5) and 23.9% (95% CI: 12.9-34.8), respectively. Concerning recommended antimicrobial drugs for , the prevalence of resistance was highest for ciprofloxacin (29.8%) and azithromycin (29.2%), followed by ceftriaxone (23.8%), in spite of their importance as first- and second-line treatments for shigellosis. In contrast, resistance to carbapenems, such as ertapenem (0.0%), imipenem (0.1%) and meropenem (0.0%), was almost non-existent among the 49 tested antibiotics. The significantly high prevalence estimation suggests that the multidrug-resistant is a pressing threat to public health worthy of careful and justified interventions. Effective antibiotic treatment strategies, which may lead to better outcomes for the control and treatment of shigellosis in Asia, are essential.
PubMed: 36421297
DOI: 10.3390/antibiotics11111653 -
International Journal of Microbiology 2022Carbapenems are the last-line therapy for multidrug-resistant (MDR) infections caused by including those caused by species. However, the recent emergence of...
BACKGROUND
Carbapenems are the last-line therapy for multidrug-resistant (MDR) infections caused by including those caused by species. However, the recent emergence of carbapenem-resistant (CR) and extended-spectrum -lactamase (ESBL)-producing pathogens, which are resistant to nearly all antibiotics, has raised concerns among international healthcare organizations. Hence, because there is no comprehensive data in Iran, the current study aimed to evaluate the prevalence of antibiotic resistance among species, especially CR and ESBL-producing strains, in Iran.
METHODS
The literature search was performed up to June 21, 2021, in national and international databases using MeSH-extracted keywords, i.e., , antibiotic resistance, carbapenem, ESBL, and Iran. Study selection was done based on the predefined inclusion and exclusion criteria, and data analysis was carried out using the Comprehensive Meta-Analysis (CMA) software.
RESULTS
The pooled prevalence of species resistant to various antibiotics is as follows: imipenem 16.6%, meropenem 16.2%, aztreonam 40.9%, ciprofloxacin 35.3%, norfloxacin 31%, levofloxacin 48%, gentamicin 42.1%, amikacin 30.3%, tobramycin 37.2%, tetracycline 50.1%, chloramphenicol 25.7%, trimethoprim/sulfamethoxazole 52%, nalidixic acid 49.1%, nitrofurantoin 43%, ceftriaxone 49.3%, cefixime 52.4%, cefotaxime 52.7%, ceftazidime 47.9%, cefepime 43.6%, and ceftizoxime 45.5%. The prevalence rates of MDR and ESBL-producing species in Iran were 63.1% and 32.8%, respectively.
CONCLUSION
In accordance with the warning of international organizations, our results revealed a high prevalence of ESBL-producing species in Iran, which is probably associated with the high prevalence of species resistant to most of the assessed antibiotics, especially MDR strains. However, the resistance rate to carbapenems was relatively low, and these drugs can still be considered as drugs of choice for the treatment of infections in Iran. Nevertheless, continuous monitoring of drug resistance along with antibiotic therapy based on the local data and evaluation of the therapeutic efficacy of new antibiotics or combination therapeutic strategies, such as ceftazidime/avibactam, meropenem/vaborbactam, plazomicin, and eravacycline, is recommended.
PubMed: 36312785
DOI: 10.1155/2022/8367365 -
Pathogens (Basel, Switzerland) Sep 2022Background: Among gram-negative bacteria, Klebsiella pneumoniae is one of the most common causes of healthcare-related infection. Bloodstream infections (BSIs) caused by... (Review)
Review
Background: Among gram-negative bacteria, Klebsiella pneumoniae is one of the most common causes of healthcare-related infection. Bloodstream infections (BSIs) caused by Klebsiella pneumoniae are notorious for being difficult to treat due to resistance to commonly used antimicrobials. Klebsiella pneumoniae isolates from bloodstream infections are becoming increasingly resistant to carbapenems. In the fight against carbapenem-resistant Klebsiella pneumoniae, colistin [polymyxin E] is the antimicrobial of choice and is thus widely used. Objective: This study aimed to determine the global prevalence of colistin resistance amongst Klebsiella pneumoniae isolates from bloodstream infections. Methods: PubMed, Medline, Scopus, and the Cochrane Library were searched for published articles without restricting the search period. Studies meeting the predefined inclusion and exclusion criteria were included, and quality was assessed using Joanna Briggs Institute Checklist. We used a statistical random effect model to analyze data with substantial heterogeneity (I2 > 50%) in the meta-analysis. Results: A total of 10 studies out of 2873 search results that met the inclusion criteria were included in the final synthesis for this study. A pooled prevalence of colistin resistance was 3.1%, 95% CI (1.5−4.7%). The highest colistin resistance pooled prevalence was recorded in isolates studied in 2020 and beyond 12.90% (4/31), while Klebsiella pneumoniae isolates studied in 2015 and before and in 2016−2019 showed a pooled colistin resistance rate of 2.89% (48/1661) and 2.95% (28/948), respectively. The highest colistin resistance was found in Klebsiella pneumoniae isolates from Thailand (19.2%), while the least pooled resistance was in Klebsiella pneumoniae from South Korea (0.8%). The pooled prevalence of the multidrug-resistant (MDR) of Klebsiella pneumoniae from bloodstream infection ranged from 80.1%, 95% CI (65.0−95.2%), and the resistance prevalence of other antibiotics by Klebsiella pneumoniae from bloodstream infections were as follows; ciprofloxacin (45.3%), ertapenem (44.4%), meropenem (36.1%), imipenem (35.2%), gentamicin (33.3%), amikacin (25.4%) and tigecycline (5.1%). Klebsiella pneumoniae recovered from the intensive care unit (ICU) showed higher colistin resistance, 11.5% (9/781%), while non-ICU patients showed 3.03% (80/2604) pooled colistin resistance. Conclusion: This study showed low colistin resistance in Klebsiella pneumoniae isolates from global bloodstream infections. However, significant colistin resistance was observed in isolates collected from 2020 and beyond. Significant colistin resistance was also observed in Klebsiella pneumoniae isolates in bloodstream infections from the intensive care unit (ICU) compared to those from non-ICUs. As a result, there is a need to institute colistin administration stewardship in the ICU in clinical settings.
PubMed: 36297149
DOI: 10.3390/pathogens11101092 -
Antibiotics (Basel, Switzerland) Sep 2022Diarrhea is one of the leading causes of morbidity and mortality in developing countries. Diarrheagenic (DEC) is an important bacterial agent for diarrhea in infants,... (Review)
Review
Diarrhea is one of the leading causes of morbidity and mortality in developing countries. Diarrheagenic (DEC) is an important bacterial agent for diarrhea in infants, children, and international travelers, and accounts for more than 30% of diarrheal cases in children less than 5 years old. However, the choices of antimicrobial agents are now being limited by the ineffectiveness of many first-line drugs, in relation to the emergence of antimicrobial-resistant strains. The aim of this systematic review and meta-analysis was to provide an updated prevalence of antimicrobial-resistant DEC in Asia. A comprehensive systematic search was conducted on three electronic databases (PubMed, ScienceDirect, and Scopus), where 40 eligible studies published between 2010 and 2022 were identified. Using meta-analysis of proportions and a random-effects model, the pooled prevalence of DEC in Asian diarrheal patients was 22.8% (95% CI: 16.5-29.2). The overall prevalence of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing DEC strains was estimated to be 66.3% (95% CI: 58.9-73.7) and 48.6% (95% CI: 35.1-62.1), respectively. Considering antimicrobial drugs for DEC, the resistance prevalence was highest for the penicillin class of antibiotics, where 80.9% of the DEC isolates were resistant to amoxicillin and 73.5% were resistant to ampicillin. In contrast, resistance to carbapenems such as imipenem (0.1%), ertapenem (2.6%), and meropenem (7.9%) was the lowest. The relatively high prevalence estimation signifies that the multidrug-resistant DEC is a public health threat. Effective antibiotic treatment strategies, which may lead to better outcomes for the control of infections in Asia, are necessary.
PubMed: 36289991
DOI: 10.3390/antibiotics11101333 -
Antibiotics (Basel, Switzerland) Sep 2022Adjusting dosing regimens based on measurements of carbapenem levels may improve carbapenem exposure in patients. This systematic review aims to describe the effect... (Review)
Review
Adjusting dosing regimens based on measurements of carbapenem levels may improve carbapenem exposure in patients. This systematic review aims to describe the effect carbapenem therapeutic drug monitoring (TDM) has on health outcomes, including the emergence of antimicrobial resistance (AMR). Four databases were searched for studies that reported health outcomes following adjustment to dosing regimens, according to measurements of carbapenem concentration. Bias in the studies was assessed with risk of bias analysis tools. Study characteristics and outcomes were tabulated and a narrative synthesis was performed. In total, 2 randomised controlled trials (RCTs), 17 non-randomised studies, and 19 clinical case studies were included. Significant variation in TDM practice was seen; consequently, a meta-analysis was unsuitable. Few studies assessed impacts on AMR. No significant improvement on health outcomes and no detrimental effects of carbapenem TDM were observed. Five cohort studies showed significant associations between achieving target concentrations and clinical success, including suppression of resistance. Studies in this review showed no obvious improvement in clinical outcomes when TDM is implemented. Optimisation and standardisation of carbapenem TDM practice are needed to improve intervention success and enable study synthesis. Further suitably powered studies of standardised TDM are required to assess the impact of TMD on clinical outcomes and AMR.
PubMed: 36289971
DOI: 10.3390/antibiotics11101311 -
Frontiers in Pharmacology 2022β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing...
β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of β-lactams. Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of β-lactams are included in this study. A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used β-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses.
PubMed: 36210807
DOI: 10.3389/fphar.2022.964005 -
Frontiers in Medicine 2022Eravacycline is a novel, fully synthetic fluorocycline antibiotic for the treatment of adults with complicated intra-abdominal infections (cIAIs). However, the efficacy...
The efficacy and safety of eravacycline compared with current clinically common antibiotics in the treatment of adults with complicated intra-abdominal infections: A Bayesian network meta-analysis.
BACKGROUND
Eravacycline is a novel, fully synthetic fluorocycline antibiotic for the treatment of adults with complicated intra-abdominal infections (cIAIs). However, the efficacy and safety of eravacycline compared with current clinically common antibiotics remain unknown.
OBJECTIVE
This study aims to compare the efficacy and safety of eravacycline and other clinically common antibiotics in China, including tigecycline, meropenem, ertapenem, ceftazidime/avibactam+metronidazole, piperacillin/tazobactam, imipenem/cilastatin, and ceftriaxone+metronidazole, for the treatment of adults with cIAIs and to provide a reference for clinical choice.
METHODS
The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were electronically searched to collect clinical randomized controlled studies (RCTs) comparing different antibiotics in the treatment of patients with cIAIs from inception to June 1, 2021. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies.
RESULTS
A total of 4050 articles were initially retrieved, and 25 RCTs were included after screening, involving eight treatment therapies and 9372 patients. The results of network meta-analysis showed that in the intention-to-treat (ITT) population, the clinically evaluable (CE) population, and the microbiologically evaluable (ME) population, the clinical response rate of eravacycline was not significantly different from that of the other 7 therapies ( > 0.05). In terms of microbiological response rate, eravacycline was significantly better than tigecycline [tigecycline vs. eravacycline: RR = 0.82, 95%CI (0.65,0.99)], and there was no significant difference between the other 6 regimens and eravacycline ( > 0.05). In terms of safety, the incidence of serious adverse events, discontinuation rate, and all-cause mortality of eravacycline were not significantly different from those of the other 7 treatment therapies ( > 0.05).
CONCLUSION
Based on the evidence generated by the current noninferiority clinical trial design, the efficacy and safety of eravacycline for the treatment of adults with cIAIs are not significantly different from those of the other 7 commonly used clinical antibiotics in China. In terms of microbiological response rate, eravacycline was significantly better than tigecycline. In view of the severe multidrug-resistant situation in China, existing drugs have difficulty meeting the needs of clinical treatment, and the new antibacterial drug eravacycline may be one of the preferred options for the treatment of cIAIs in adults.
PubMed: 36186801
DOI: 10.3389/fmed.2022.935343 -
Antimicrobial Stewardship & Healthcare... 2021Ceftazidime/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...
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 (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 I 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 I = 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.
PubMed: 36168482
DOI: 10.1017/ash.2021.217 -
Frontiers in Pediatrics 2022Dosing recommendations for anti-infective medicines in children with pre-existing kidney dysfunction are derived from adult pharmacokinetics studies and adjusted to...
BACKGROUND
Dosing recommendations for anti-infective medicines in children with pre-existing kidney dysfunction are derived from adult pharmacokinetics studies and adjusted to kidney function. Due to neonatal/pediatric age and kidney impairment, modifications in renal clearance and drug metabolism make standard anti-infective dosing for children and neonates inappropriate, with a risk of drug toxicity or significant underdosing. The aim of this study was the systematic description of the use of anti-infective medicines in pediatric patients with pre-existing kidney impairment.
METHODS
A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The EMBASE, Medline and Cochrane databases were searched on September 21st, 2021. Studies in all languages reporting data on pre-defined outcomes (pharmacokinetics-PK, kidney function, safety and efficacy) regarding the administration of anti-infective drugs in children up to 18 years with pre-existing kidney dysfunction were included.
RESULTS
29 of 1,792 articles were eligible for inclusion. There were 13 case reports, six retrospective studies, nine prospective studies and one randomized controlled trial (RCT), reporting data on 2,168 pediatric patients. The most represented anti-infective class was glycopeptides, with seven studies on vancomycin, followed by carbapenems, with five studies, mostly on meropenem. Antivirals, aminoglycosides and antifungals counted three articles, followed by combined antibiotic therapy, cephalosporins, lipopeptides with two studies, respectively. Penicillins and polymixins counted one study each. Nine studies reported data on patients with a decreased kidney function, while 20 studies included data on kidney replacement therapy (KRT). Twenty-one studies reported data on PK. In 23 studies, clinical outcomes were reported. Clinical cure was achieved in 229/242 patients. There were four cases of underdosing, one case of overdosing and 13 reported deaths.
CONCLUSION
This is the first systematic review providing evidence of the use of anti-infective medicines in pediatric patients with impaired kidney function or requiring KRT. Dosing size or interval adjustments in pediatric patients with kidney impairment vary according to age, critical illness status, decreased kidney function and dialysis type. Our findings underline the relevance of population PK in clinical practice and the need of developing predictive specific models for critical pediatric patients.
PubMed: 35558367
DOI: 10.3389/fped.2022.868513