-
Clinical Microbiology and Infection :... Apr 2022These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant...
European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine).
SCOPE
These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy.
METHODS
An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak).
RECOMMENDATIONS
The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.
Topics: Anti-Bacterial Agents; Carbapenems; Communicable Diseases; Critical Care; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans
PubMed: 34923128
DOI: 10.1016/j.cmi.2021.11.025 -
Antibiotics (Basel, Switzerland) Aug 2021Infections caused by metallo-β-lactamase (MBL)-producing and are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither... (Review)
Review
Infections caused by metallo-β-lactamase (MBL)-producing and are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing , 85% of and 6% of MBL-producing . Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially , much less for ) while waiting for new antimicrobials.
PubMed: 34439062
DOI: 10.3390/antibiotics10081012 -
Clinical Microbiology and Infection :... Mar 2023COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises.
OBJECTIVE
We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings.
DATA SOURCE
A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022.
STUDY ELIGIBILITY
Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted.
METHODS
Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed.
RESULTS
Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40).
CONCLUSION
The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Methicillin-Resistant Staphylococcus aureus; COVID-19; Carbapenems
PubMed: 36509377
DOI: 10.1016/j.cmi.2022.12.006 -
Antimicrobial Resistance and Infection... 2020Antibiotics are the most common medicines prescribed to children in hospitals and the community, with a high proportion of potentially inappropriate use. Antibiotic... (Review)
Review
BACKGROUND
Antibiotics are the most common medicines prescribed to children in hospitals and the community, with a high proportion of potentially inappropriate use. Antibiotic misuse increases the risk of toxicity, raises healthcare costs, and selection of resistance. The primary aim of this systematic review is to summarize the current state of evidence of the implementation and outcomes of pediatric antimicrobial stewardship programs (ASPs) globally.
METHODS
MEDLINE, Embase and Cochrane Library databases were systematically searched to identify studies reporting on ASP in children aged 0-18 years and conducted in outpatient or in-hospital settings. Three investigators independently reviewed identified articles for inclusion and extracted relevant data.
RESULTS
Of the 41,916 studies screened, 113 were eligible for inclusion in this study. Most of the studies originated in the USA (52.2%), while a minority were conducted in Europe (24.7%) or Asia (17.7%). Seventy-four (65.5%) studies used a before-and-after design, and sixteen (14.1%) were randomized trials. The majority (81.4%) described in-hospital ASPs with half of interventions in mixed pediatric wards and ten (8.8%) in emergency departments. Only sixteen (14.1%) studies focused on the costs of ASPs. Almost all the studies (79.6%) showed a significant reduction in inappropriate prescriptions. Compliance after ASP implementation increased. Sixteen of the included studies quantified cost savings related to the intervention with most of the decreases due to lower rates of drug administration. Seven studies showed an increased susceptibility of the bacteria analysed with a decrease in extended spectrum beta-lactamase producers and a reduction in the rate of carbapenem resistance subsequent to an observed reduction in the rate of antimicrobial days of therapy; and, in two studies set in outpatient setting, an increase in erythromycin-sensitive following a reduction in the use of macrolides.
CONCLUSIONS
Pediatric ASPs have a significant impact on the reduction of targeted and empiric antibiotic use, healthcare costs, and antimicrobial resistance in both inpatient and outpatient settings. Pediatric ASPs are now widely implemented in the USA, but considerable further adaptation is required to facilitate their uptake in Europe, Asia, Latin America and Africa.
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Asia; Bacteria; Bacterial Infections; Child; Drug Resistance, Bacterial; Europe; Global Health; Humans; Inappropriate Prescribing; Pediatrics; Prescription Drug Misuse; United States
PubMed: 31911831
DOI: 10.1186/s13756-019-0659-3 -
Antibiotics (Basel, Switzerland) May 2022Cefiderocol appears promising, as it can overcome most β-lactam resistance mechanisms (including β-lactamases, porin mutations, and efflux pumps). Resistance is... (Review)
Review
Cefiderocol appears promising, as it can overcome most β-lactam resistance mechanisms (including β-lactamases, porin mutations, and efflux pumps). Resistance is uncommon according to large multinational cohorts, including against isolates resistant to carbapenems, ceftazidime/avibactam, ceftolozane/tazobactam, and colistin. However, alarming proportions of resistance have been reported in some recent cohorts (up to 50%). A systematic review was conducted in PubMed and Scopus from inception to May 2022 to review mechanisms of resistance, prevalence of heteroresistance, and in vivo emergence of resistance to cefiderocol during treatment. A variety of mechanisms, typically acting in concert, have been reported to confer resistance to cefiderocol: β-lactamases (especially NDM, KPC and AmpC variants conferring resistance to ceftazidime/avibactam, OXA-427, and PER- and SHV-type ESBLs), porin mutations, and mutations affecting siderophore receptors, efflux pumps, and target (PBP-3) modifications. Coexpression of multiple β-lactamases, often in combination with permeability defects, appears to be the main mechanism of resistance. Heteroresistance is highly prevalent (especially in ), but its clinical impact is unclear, considering that in vivo emergence of resistance appears to be low in clinical studies. Nevertheless, cases of in vivo emerging cefiderocol resistance are increasingly being reported. Continued surveillance of cefiderocol's activity is important as this agent is introduced in clinical practice.
PubMed: 35740130
DOI: 10.3390/antibiotics11060723 -
Frontiers in Cellular and Infection... 2023To analyze the mortality rate of patients with bacteremia (KPB) and the impact of extended spectrum beta-lactamase (ESBL) producing or carbapenem-resistance (CR) KP on... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To analyze the mortality rate of patients with bacteremia (KPB) and the impact of extended spectrum beta-lactamase (ESBL) producing or carbapenem-resistance (CR) KP on the mortality rate among patients with bacteremia.
METHODS
EMbase, Web of Science, PubMed, and The Cochrane Library were searched up to September 18, 2022. Two reviewers independently extracted data and evaluated risk of bias of included studies by ROBINS-I tool. A meta-regression analysis was conducted using a mixed-effects model to explore possible sources of heterogeneity. A random-effects model was used for pooled analysis in case of significant heterogeneity (I>50%). Otherwise, the fixed-effects model was performed.
RESULTS
A total of 157 studies (37,915 enrolled patients) were included in the meta-analysis. The pooled death proportions of KPB were 17% (95% CI=0.14-0.20) at 7-day, 24% (95% CI=0.21-0.28) at 14-day, 29% (95% CI=0.26-0.31) at 30-day, 34% (95% CI=0.26-0.42) at 90-day, and 29% (95% CI=0.26-0.33) in hospital, respectively. Heterogeneity was found from the intensive care unit (ICU), hospital-acquired (HA), CRKP, and ESBL-KP in the meta-regression analysis. More than 50% of ICU, HA, CRKP, and ESBL-KP were associated with a significant higher 30-day mortality rates. The pooled mortality odds ratios (ORs) of CRKP . non-CRKP were 3.22 (95% CI 1.18-8.76) at 7-day, 5.66 (95% CI 4.31-7.42) at 14-day, 3.87 (95% CI 3.01-3.49) at 28- or 30-day, and 4.05 (95% CI 3.38-4.85) in hospital, respectively.
CONCLUSIONS
This meta-analysis indicated that patients with KPB in ICU, HA-KPB, CRKP, and ESBL-KP bacteremia were associated with a higher mortality rate. The high mortality rate caused by CRKP bacteremia has increased over time, challenging the public health.
Topics: Humans; Anti-Bacterial Agents; Klebsiella pneumoniae; Klebsiella Infections; Hydrolases; Bacteremia; Retrospective Studies; beta-Lactamases; Risk Factors
PubMed: 37153146
DOI: 10.3389/fcimb.2023.1157010 -
Clinical Microbiology and Infection :... Jan 2014Healthcare-associated infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) are a leading cause of morbidity and mortality worldwide. These... (Review)
Review
Healthcare-associated infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) are a leading cause of morbidity and mortality worldwide. These evidence-based guidelines have been produced after a systematic review of published studies on infection prevention and control interventions aimed at reducing the transmission of MDR-GNB. The recommendations are stratified by type of infection prevention and control intervention and species of MDR-GNB and are presented in the form of 'basic' practices, recommended for all acute care facilities, and 'additional special approaches' to be considered when there is still clinical and/or epidemiological and/or molecular evidence of ongoing transmission, despite the application of the basic measures. The level of evidence for and strength of each recommendation, were defined according to the GRADE approach.
Topics: Anti-Infective Agents, Local; Bacterial Typing Techniques; Chlorhexidine; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hand Hygiene; Health Knowledge, Attitudes, Practice; Humans; Infection Control; Risk Factors
PubMed: 24329732
DOI: 10.1111/1469-0691.12427 -
Clinical Microbiology and Infection :... Jul 2019The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all...
SCOPE
The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings.
METHODS
These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations.
RECOMMENDATIONS
The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Pseudomonas aeruginosa; Stenotrophomonas maltophilia
PubMed: 30708122
DOI: 10.1016/j.cmi.2019.01.005 -
International Journal of Microbiology 2021Antimicrobial resistance especially caused by extended-spectrum -lactamase-producing (ESBL-PE) has become a global public health concern. Globally, these isolates have... (Review)
Review
BACKGROUND
Antimicrobial resistance especially caused by extended-spectrum -lactamase-producing (ESBL-PE) has become a global public health concern. Globally, these isolates have remained the most important causes of several infections and associated mortality. Their rapid spread in Ethiopia is associated with a lack of regular surveillance and antibiotic stewardship programs. Isolates of ESBL-PE from different regions of Ethiopia were searched exhaustively. However, published data regarding the pooled estimate of ESBL-PE are not conducted in Ethiopia. For this reason, we systematically reviewed laboratory-based studies to summarize the overall pooled prevalence of the isolates recovered from various human specimens.
METHODS
An exhaustive literature search was carried out using the major electronic databases including PubMed, Web of Science, MEDLINE, EMBASE, CINAHL, Google Scholar, Cochrane Library, Scopus, and Wiley Online Library to identify potentially relevant studies without date restriction. Original articles which address the research question were identified, screened, and included using the PRISMA follow diagram. Data extraction form was prepared in Microsoft Excel, and data quality was assessed by using 9-point Joanna Briggs Institute critical appraisal tools. Then, data were exported to STATA 16.0 software for analyses of pooled estimation of outcome measures. Estimation of outcome measures at 95% confidence interval was performed using Der-Simonian-Laird's random-effects model. Finally, results were presented via text, figures, and tables.
RESULTS
A comprehensive electronic database literature search has yielded a total of 86 articles. Among the total, 68 original articles were excluded after the review process. A total of 18 studies with 1191 bacterial isolates recovered from 7919 various clinical samples sizes were included for systematic review and meta-analysis. In this study, the pooled prevalence of ESBL-PE was 18% (95% CI: 9-26). Nine out of the total (50%) reviewed articles were studied using the combination disk test. Likewise, and . (50% both) were the predominant isolates of ESBL-PE in addition to other isolates such as spp. and spp.
CONCLUSION
This meta-analysis has shown a low pooled estimate of ESBL-PE in Ethiopia.
PubMed: 33859697
DOI: 10.1155/2021/6669778 -
Journal of Infection and Public Health Mar 2023There is paucity of data describing the impact of COVID-19 pandemic on antimicrobial resistance. This review evaluated the changes in the rate of multidrug resistant... (Review)
Review
BACKGROUND
There is paucity of data describing the impact of COVID-19 pandemic on antimicrobial resistance. This review evaluated the changes in the rate of multidrug resistant gram negative and gram positive bacteria during the COVID-19 pandemic.
METHODS
A search was conducted in PubMed, Science Direct, and Google Scholar databases to identify eligible studies. Studies that reported the impact of COVID-19 pandemic on carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum beta-lactamase inhibitor (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CPE) were selected. Studies published in English language from the start of COVID-19 pandemic to July 2022 were considered for inclusion.
RESULTS
Thirty eligible studies were selected and most of them were from Italy (n = 8), Turkey (n = 3) and Brazil (n = 3). The results indicated changes in the rate of multidrug resistant bacteria, and the changes varied between the studies. Most studies (54.5%) reported increase in MRSA infection/colonization during the pandemic, and the increase ranged from 4.6 to 170.6%. Five studies (55.6%) reported a 6.8-65.1% increase in VRE infection/colonization during the pandemic. A 2.4-58.2% decrease in ESBL E. coli and a 1.8-13.3% reduction in ESBL Klebsiella pneumoniae was observed during the pandemic. For CRAB, most studies (58.3%) reported 1.5-621.6% increase in infection/colonization during the pandemic. Overall, studies showed increase in the rate of CRE infection/colonization during the pandemic. There was a reduction in carbapenem-resistant E. coli during COVID-19 pandemic, and an increase in carbapenem-resistant K. pneumoniae. Most studies (55.6%) showed 10.4 - 40.9% reduction in the rate of CRPA infection during the pandemic.
CONCLUSION
There is an increase in the rate of multidrug resistant gram positive and gram negative bacteria during the COVID-19 pandemic. However, the rate of ESBL-producing Enterobacteriaceae and CRPA has decrease during the pandemic. Both infection prevention and control strategies and antimicrobial stewardship should be strengthen to address the increasing rate of multidrug resistant gram positive and gram negative bacteria.
Topics: Humans; Anti-Bacterial Agents; Pandemics; Gram-Negative Bacteria; Escherichia coli; Methicillin-Resistant Staphylococcus aureus; Gram-Positive Bacteria; COVID-19; Enterobacteriaceae; Klebsiella pneumoniae; Carbapenems; Microbial Sensitivity Tests
PubMed: 36657243
DOI: 10.1016/j.jiph.2022.12.022