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Clinical Infectious Diseases : An... Aug 2022The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. The initial...
Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa).
BACKGROUND
The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. The initial guidance document on infections caused by extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa) was published on 17 September 2020. Over the past year, there have been a number of important publications furthering our understanding of the management of ESBL-E, CRE, and DTR-P. aeruginosa infections, prompting a rereview of the literature and this updated guidance document.
METHODS
A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections reviewed, updated, and expanded previously developed questions and recommendations about the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States.
RESULTS
Preferred and alternative treatment recommendations are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Recommendations apply for both adult and pediatric populations.
CONCLUSIONS
The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of 24 October 2021. The most current versions of IDSA documents, including dates of publication, are available at www.idsociety.org/practice-guideline/amr-guidance/.
Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Carbapenems; Cephalosporins; Child; Communicable Diseases; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; United States; beta-Lactamases
PubMed: 35439291
DOI: 10.1093/cid/ciac268 -
Frontiers in Cellular and Infection... 2022Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales... (Review)
Review
Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly , , and -like genes), CR- or MDR/XDR- (production of VIM, IMP, or NDM carbapenemases combined with porin alteration), and complex (producing mainly OXA-23, OXA-58-like carbapenemases), have gradually worsened and become a major challenge to public health because of limited antibiotic choice and high case-fatality rates. Diverse MDR/XDR-GNB isolates have been predominantly cultured from inpatients and hospital equipment/settings, but CRE has also been identified in community settings and long-term care facilities. Several CRE outbreaks cost hospitals and healthcare institutions huge economic burdens for disinfection and containment of their disseminations. Parenteral polymyxin B/E has been observed to have a poor pharmacokinetic profile for the treatment of CR- and XDR-GNB. It has been determined that tigecycline is suitable for the treatment of bloodstream infections owing to GNB, with a minimum inhibitory concentration of ≤ 0.5 mg/L. Ceftazidime-avibactam is a last-resort antibiotic against GNB of Ambler class A/C/D enzyme-producers and a majority of CR- isolates. Furthermore, ceftolozane-tazobactam is shown to exhibit excellent activity against CR- and XDR- isolates. Several pharmaceuticals have devoted to exploring novel antibiotics to combat these troublesome XDR-GNBs. Nevertheless, only few antibiotics are shown to be effective against CR/XDR- complex isolates. In this era of antibiotic pipelines, strict implementation of antibiotic stewardship is as important as in-time isolation cohorts in limiting the spread of CR/XDR-GNB and alleviating the worsening trends of resistance.
Topics: Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Microbial Sensitivity Tests
PubMed: 35372099
DOI: 10.3389/fcimb.2022.823684 -
Journal of Microbiology, Immunology,... Aug 2023The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or... (Review)
Review
The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.
Topics: Humans; Anti-Bacterial Agents; Carbapenems; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Infection Control
PubMed: 36868960
DOI: 10.1016/j.jmii.2023.01.017 -
Clinical Infectious Diseases : An... Nov 2019Antimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of... (Review)
Review
Antimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Carbapenems; Clinical Trials as Topic; Drug Resistance, Bacterial; Forecasting; Gram-Negative Bacterial Infections; Humans; Public Health
PubMed: 31724043
DOI: 10.1093/cid/ciz830 -
Microbiological Research Jan 2023Bacterial drug resistance has become a global public health threat, among which the infection of carbapenem-resistant Enterobacterales (CRE) is one of the top noticeable... (Review)
Review
Bacterial drug resistance has become a global public health threat, among which the infection of carbapenem-resistant Enterobacterales (CRE) is one of the top noticeable issues in the global anti-infection area due to limited therapy options. In recent years, the prevalence of CRE transmission around the world has increased, and the transmission of COVID-19 has intensified the situation to a certain extent. CRE resistance can be induced by carbapenemase, porin, efflux pump, penicillin-binding protein alteration, and biofilm production. Deletion, mutation, insertion, and post-transcriptional modification of corresponding coding genes may affect the sensitivity of Enterobacterales bacteria to carbapenems. Clinical and laboratory methods to detect CRE and explore its resistance mechanisms are being developed. Due to the limited options of antibiotics, the clinical treatment of CRE infection also faces severe challenges. The clinical therapies of CRE include single or combined use of antibiotics, and some new antibiotics and treatment methods are also being developed. Hence, this review summarizes the epidemiology, resistance mechanisms, screening and clinical treatments of CRE infection, to provide references for clinical prevention, control and treatment of CRE infection.
Topics: Humans; Carbapenem-Resistant Enterobacteriaceae; Enterobacteriaceae; Enterobacteriaceae Infections; COVID-19; Carbapenems; Anti-Bacterial Agents
PubMed: 36356348
DOI: 10.1016/j.micres.2022.127249 -
Journal of Clinical Laboratory Analysis Dec 2022Klebsiella pneumoniae is a notorious bacterium in clinical practice. Virulence, carbapenem-resistance and their convergence among K. pneumoniae are extensively discussed... (Review)
Review
Klebsiella pneumoniae is a notorious bacterium in clinical practice. Virulence, carbapenem-resistance and their convergence among K. pneumoniae are extensively discussed in this article. Hypervirulent K. pneumoniae (HvKP) has spread from the Asian Pacific Rim to the world, inducing various invasive infections, such as pyogenic liver abscess, endophthalmitis, and meningitis. Furthermore, HvKP has acquired more and more drug resistance. Among multidrug-resistant HvKP, hypervirulent carbapenem-resistant K. pneumoniae (Hv-CRKP), and carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) are both devastating for their extreme drug resistance and virulence. The hypervirulence of HvKP is primarily attributed to hypercapsule, macromolecular exopolysaccharides, or excessive siderophores, although it has many other factors, for example, lipopolysaccharides, fimbriae, and porins. In contrast with classical determination of HvKP, that is, animal lethality test, molecular determination could be an optional and practical method after improvement. HvKP, including Hv-CRKP and CR-HvKP, has been progressing. R-M and CRISPR-Cas systems may play pivotal roles in such evolutions. Hv-CRKP and CR-HvKP, in particular the former, should be of severe concern due to their being more and more prevalent.
Topics: Animals; Klebsiella pneumoniae; Klebsiella Infections; Carbapenems; Virulence; Virulence Factors; Anti-Bacterial Agents
PubMed: 36347819
DOI: 10.1002/jcla.24743 -
Antimicrobial Agents and Chemotherapy Nov 2011In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently... (Review)
Review
In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as "slow substrates" or inhibitors of β-lactamases, and still target penicillin binding proteins. This "value-added feature" of inhibiting β-lactamases serves as a major rationale for expansion of this class of β-lactams. We describe the initial discovery and development of the carbapenem family of β-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.
Topics: Anti-Bacterial Agents; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Doripenem; Drug Combinations; Ertapenem; Humans; Imipenem; Thienamycins; beta-Alanine; beta-Lactams
PubMed: 21859938
DOI: 10.1128/AAC.00296-11 -
Clinical Microbiology and Infection :... Jan 2015The aim of this study was to determine whether ertapenem, being highly protein bound, is less effective than other carbapenems in the presence of hypoalbuminemia. In a...
The aim of this study was to determine whether ertapenem, being highly protein bound, is less effective than other carbapenems in the presence of hypoalbuminemia. In a prospective cohort study, we included adults with clinically and microbiologically documented infections caused by carbapenem-susceptible Enterobacteriaceae who were hospitalized in a tertiary medical center from March 2010 to September 2012. We tested whether hypoalbuminemia (serum albumin <2.5 g/dL) had a larger effect on 30-day mortality in subjects treated with ertapenem compared to those treated with meropenem or imipenem (I/M). Logistic regression analysis was used to identify independent risk factors for death including the carbapenem drug and the interaction between albumin and the carbapenem. Of 279 individual subjects included, 173 were treated with ertapenem and 106 with I/M. The odds ratio (OR) for 30-day mortality with hypoalbuminemia was 4.6 (95% confidence interval (CI) 2.1-10.1) among subjects with ertapenem versus 1.2 (95% CI 0.5-2.70) with I/M (p = 0.02 for difference between groups). In the regression model, the interaction between carbapenem type and albumin levels was significant (p = 0.03); for ertapenem lower albumin levels were associated with increased 30-day mortality (OR 2.45, 95% CI 1.19-5.05), while for I/M the change was not significant (OR 0.67, 95% CI 0.31-1.41). The model suggests that the risk of death for ertapenem-treated subjects quintupled when albumin was 2 g/dL compared to 4 g/dL. Hypoalbuminemia was associated with mortality significantly more among subjects treated with ertapenem compared to subjects treated with I/M. The effectiveness of current dosing schemes of ertapenem in subjects with significant hypoalbuminemia should be revisited.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Humans; Hypoalbuminemia; Israel; Middle Aged; Prospective Studies; Risk Factors; beta-Lactams
PubMed: 25636928
DOI: 10.1016/j.cmi.2014.08.003 -
Frontiers in Cellular and Infection... 2022Infections by Gram-negative multi-drug resistant (MDR) bacterial species are difficult to treat using available antibiotics. Overuse of carbapenems has contributed to... (Review)
Review
Infections by Gram-negative multi-drug resistant (MDR) bacterial species are difficult to treat using available antibiotics. Overuse of carbapenems has contributed to widespread resistance to these antibiotics; as a result, carbapenem-resistant Enterobacterales (CRE), (CRAB), and (CRPA) have become common causes of healthcare-associated infections. Carbapenems, tigecycline, and colistin are the last resource antibiotics currently used; however, multiple reports of resistance to these antimicrobial agents have been documented worldwide. Recently, new antibiotics have been evaluated against Gram-negatives, including plazomicin (a new aminoglycoside) to treat CRE infection, eravacycline (a novel tetracycline) with activity against CRAB, and cefiderocol (a synthetic conjugate) for the treatment of nosocomial pneumonia by carbapenem-non-susceptible Gram-negative isolates. Furthermore, combinations of known β-lactams with recently developed β-lactam inhibitors, such as ceftazidime-avibactam, ceftolozane-tazobactam, ceftazidime-tazobactam, and meropenem-vaborbactam, has been suggested for the treatment of infections by extended-spectrum β-lactamases, carbapenemases, and AmpC producer bacteria. Nonetheless, they are not active against all carbapenemases, and there are reports of resistance to these combinations in clinical isolates.This review summarizes and discusses the and clinical evidence of the recently approved antibiotics, β-lactam inhibitors, and those in advanced phases of development for treating MDR infections caused by Gram-negative multi-drug resistant (MDR) bacterial species.
Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporins; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Tazobactam
PubMed: 35669117
DOI: 10.3389/fcimb.2022.884365 -
The Yale Journal of Biology and Medicine Dec 2022Worldwide, remains a leading nosocomial pathogen that is difficult to treat and constitutes a challenging menace to healthcare systems. shows increased and alarming... (Review)
Review
Worldwide, remains a leading nosocomial pathogen that is difficult to treat and constitutes a challenging menace to healthcare systems. shows increased and alarming resistance to carbapenems, long acknowledged as last-resort antibiotics for treatment of resistant infections. Varied and recalcitrant pathways of resistance to carbapenems can simultaneously occur in , including the production of carbapenemases, broadest spectrum types of β-lactamases that hydrolyze virtually almost all β-lactams, including carbapenems. The organism can produce chromosomal, plasmid-encoded, and integron- or transposon-mediated carbapenemases from different molecular classes. These include Ambler class A (KPC and some types of GES enzymes), class B (different metallo-β-lactamases such as IMP, VIM, and NDM), and class D (oxacillinases with carbapenem-hydrolyzing capacity like OXA-198) enzymes. Additionally, derepression of chromosomal AmpC cephalosporinases in contributes to carbapenem resistance in the presence of other concomitant mechanisms such as impermeability or efflux overexpression. Epidemiologic and molecular evidence of carbapenemases in has been long accumulating, and reports of their existence in different geographical areas of the world currently exist. Such reports are continuously being updated and reveal emerging varieties of carbapenemases and/or new genetic environments. This review summarizes carbapenemases of importance in , highlights their genetic profile, and presents current knowledge about their global epidemiology.
Topics: Humans; Pseudomonas aeruginosa; Genetic Profile; beta-Lactamases; Anti-Bacterial Agents; Carbapenems; Microbial Sensitivity Tests
PubMed: 36568831
DOI: No ID Found