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      Review of therapeutic options for infections with carbapenem-resistant Klebsiella pneumoniae

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          Abstract

          Infections with multi-drug resistant (MDR) bacteria including carbapenem-resistant Klebsiella pneumoniae are emerging worldwide but are difficult to treat with the currently available antibiotic compounds and therefore constitute serious threats to human health. This prompted us to perform a literature survey applying the MEDLINE database and Cochrane Register of Controlled Trials including clinical trials comparing different treatment regimens for infections caused by carbapenem-resistant K. pneumoniae. Our survey revealed that a combined application of antibiotic compounds such as meropenem plus vaborbactam, meropenem plus colistin and carbapenem plus carbapenem, resulted in significantly increased clinical cure and decreased mortality rates as compared to respective control treatment. However, further research on novel antibiotic compounds, but also on antibiotic-independent molecules providing synergistic or at least resistance-modifying properties needs to be undertaken in vitro as well as in large clinical trials to provide future options in the combat of emerging life-threatening infections caused by MDR bacteria.

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          Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis

          Bradley Langford, Miranda So, Sumit Raybardhan … (2020)
          Background Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood. Aims To determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19. Sources We performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection. Content Data were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4–6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6–18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3–9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3–13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%). Implications Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment.
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            Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors

            R Podschun, U Ullmann (1998)
            Bacteria belonging to the genus Klebsiella frequently cause human nosocomial infections. In particular, the medically most important Klebsiella species, Klebsiella pneumoniae, accounts for a significant proportion of hospital-acquired urinary tract infections, pneumonia, septicemias, and soft tissue infections. The principal pathogenic reservoirs for transmission of Klebsiella are the gastrointestinal tract and the hands of hospital personnel. Because of their ability to spread rapidly in the hospital environment, these bacteria tend to cause nosocomial outbreaks. Hospital outbreaks of multidrug-resistant Klebsiella spp., especially those in neonatal wards, are often caused by new types of strains, the so-called extended-spectrum-β-lactamase (ESBL) producers. The incidence of ESBL-producing strains among clinical Klebsiella isolates has been steadily increasing over the past years. The resulting limitations on the therapeutic options demand new measures for the management of Klebsiella hospital infections. While the different typing methods are useful epidemiological tools for infection control, recent findings about Klebsiella virulence factors have provided new insights into the pathogenic strategies of these bacteria. Klebsiella pathogenicity factors such as capsules or lipopolysaccharides are presently considered to be promising candidates for vaccination efforts that may serve as immunological infection control measures.
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              β-Lactams and β-Lactamase Inhibitors: An Overview.

              Karen Bush, Patricia Bradford (2016)
              β-Lactams are the most widely used class of antibiotics. Since the discovery of benzylpenicillin in the 1920s, thousands of new penicillin derivatives and related β-lactam classes of cephalosporins, cephamycins, monobactams, and carbapenems have been discovered. Each new class of β-lactam has been developed either to increase the spectrum of activity to include additional bacterial species or to address specific resistance mechanisms that have arisen in the targeted bacterial population. Resistance to β-lactams is primarily because of bacterially produced β-lactamase enzymes that hydrolyze the β-lactam ring, thereby inactivating the drug. The newest effort to circumvent resistance is the development of novel broad-spectrum β-lactamase inhibitors that work against many problematic β-lactamases, including cephalosporinases and serine-based carbapenemases, which severely limit therapeutic options. This work provides a comprehensive overview of β-lactam antibiotics that are currently in use, as well as a look ahead to several new compounds that are in the development pipeline.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Eur J Microbiol Immunol (Bp)
                Journal ID (iso-abbrev): Eur J Microbiol Immunol (Bp)
                Journal ID (publisher-id): EUJMI
                Title: European Journal of Microbiology & Immunology
                Publisher: Akadémiai Kiadó (Budapest )
                ISSN (Print): 2062-509X
                ISSN (Electronic): 2062-8633
                Publication date (Electronic): 17 September 2020
                Publication date Collection: 14 October 2020
                Volume: 10
                Issue: 3
                Pages: 115-124
                Affiliations
                Institute of Microbiology, Infectious Diseases and Immunology, Gastrointestinal Microbiology Research Group, Charité – University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health , Berlin, Germany
                Author notes
                *Corresponding author. Department of Microbiology, Infectious Diseases and Immunology, Charité – University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, D-14195, Berlin, Germany. Tel.: +49 30 450524318 E-mail: markus.heimesaat@ 123456charite.de
                Author information
                https://orcid.org/0000-0001-6399-651X
                Article
                DOI: 10.1556/1886.2020.00022
                PMC ID: 7592515
                PubMed ID: 32946421
                SO-VID: 0cf29743-a1ed-4b17-b8c7-d9ce29adc9ee
                Copyright © © 2020, The Authors
                License:

                Open Access. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes - if any - are indicated.

                History
                Date received : 28 July 2020
                Date accepted : 25 August 2020
                Page count
                Figures: 0, Tables: 3, Equations: 0, References: 48, Pages: 10
                Categories
                Subject: Review Paper

                Keywords: antimicrobial resistance,multi-drug resistant enterobacteria,carbapenem-resistant klebsiella pneumoniae,kpc producing bacteria,novel antimicrobial therapies,nosocomial infections,randomized clinical trials,intervention studies
                Data availability:
                Keywords: antimicrobial resistance, multi-drug resistant enterobacteria, carbapenem-resistant klebsiella pneumoniae, kpc producing bacteria, novel antimicrobial therapies, nosocomial infections, randomized clinical trials, intervention studies

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