Multidrug-resistant<i>Klebsiella pneumoniae</i>: challenges for treatment, prevention and infection control

Bassetti, Matteo; Righi, Elda; Carnelutti, Alessia; Graziano, Elena; Russo, Alessandro

doi:10.1080/14787210.2018.1522249

Cited by 160 publications

(113 citation statements)

References 131 publications

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“…Instead, in infections like nosocomial pneumonia (HAP, VAP) or abdominal infection (Table 4) fosfomycin was most often combined with a carbapenem. This combination is supported by synergistic effects and has recently been recommended, especially if MDR GN pathogens are involved [26,[33][34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Current clinical use of intravenous fosfomycin in ICU patients in two European countries

et al. 2019

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Purpose In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. Methods Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). Results Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community-(CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. Conclusion Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

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Section: Discussionmentioning

confidence: 99%

Current clinical use of intravenous fosfomycin in ICU patients in two European countries

et al. 2019

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“…The common practice of routine administration of broad-spectrum antibiotics to treat an infection before identification of the specific pathogen responsible for an infection has proven to be an ill-advised practice. By removing the normal bacterial microflora, antibiotics actually provide an opportunistic niche for the emergence of antibiotic-resistant bacterial strains which no longer have to compete with the normal bacterial populations present in the body [71,72]. Klebsiella pneumoniae is a Gram negative, facultative anaerobic commensal microorganism that can cause chronic urinary tract and soft tissue infections, pneumonia, and sepsis, and mostly occurs in immunocompromised patients [73].…”

Section: Commercial Development Of Antibioticsmentioning

confidence: 99%

The Glucosinolates: A Sulphur Glucoside Family of Mustard Anti-Tumour and Antimicrobial Phytochemicals of Potential Therapeutic Application

Melrose

2019

Biomedicines

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This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and antimicrobial properties. Sinigrin and glucoraphanin are converted by the β-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant “priority pathogens” and also act as anti-cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.

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“…Treatment options for CRKP infections are usually limited to aminoglycosides, tigecycline, fosfomycin, and colistin. Novel β-lactam-β-lactamase inhibitors combinations, such as ceftazidime-avibactam and meropenem-vaborbactam, have represented a major breakthrough for treatment of some CRKP (e.g., those producing KPC-type and OXA-48-like enzymes), but unfortunately they do not cover strains producing metallocarbapenemases (Bassetti et al, 2018). Colistin, despite its nephrotoxicity and neurotoxicity, remains a key component of some anti-CRKP regimens (Karaiskos et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Genomic Epidemiology of Carbapenem- and Colistin-Resistant Klebsiella pneumoniae Isolates From Serbia: Predominance of ST101 Strains Carrying a Novel OXA-48 Plasmid

et al. 2020

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Klebsiella pneumoniae is a major cause of severe healthcare-associated infections and often shows MDR phenotypes. Carbapenem resistance is frequent, and colistin represents a key molecule to treat infections caused by such isolates. Here we evaluated the antimicrobial resistance (AMR) mechanisms and the genomic epidemiology of clinical K. pneumoniae isolates from Serbia. Consecutive non-replicate K. pneumoniae clinical isolates (n = 2,298) were collected from seven hospitals located in five Serbian cities and tested for carbapenem resistance by disk diffusion. Isolates resistant to at least one carbapenem (n = 426) were further tested for colistin resistance with Etest or Vitek2. Broth microdilution (BMD) was performed to confirm the colistin resistance phenotype, and colistin-resistant isolates (N = 45, 10.6%) were characterized by Vitek2 and whole genome sequencing. Three different clonal groups (CGs) were observed: CG101 (ST101, N = 38), CG258 (ST437, N = 4; ST340, N = 1; ST258, N = 1) and CG17 (ST336, N = 1). mcr genes, encoding for acquired colistin resistance, were not observed, while all the genomes presented mutations previously associated with colistin resistance. In particular, all strains had a mutated MgrB, with MgrB C28S being the prevalent mutation and associated with ST101. Isolates belonging to ST101 harbored the carbapenemase OXA-48, which is generally encoded by an IncL/M plasmid that was no detected in our isolates. MinION sequencing was performed on a representative ST101 strain, and the obtained long reads were assembled together with the Illumina high quality reads to decipher the bla OXA-48 genetic background.

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Multidrug-resistantKlebsiella pneumoniae: challenges for treatment, prevention and infection control

Cited by 160 publications

References 131 publications

Current clinical use of intravenous fosfomycin in ICU patients in two European countries

Current clinical use of intravenous fosfomycin in ICU patients in two European countries

The Glucosinolates: A Sulphur Glucoside Family of Mustard Anti-Tumour and Antimicrobial Phytochemicals of Potential Therapeutic Application

Genomic Epidemiology of Carbapenem- and Colistin-Resistant Klebsiella pneumoniae Isolates From Serbia: Predominance of ST101 Strains Carrying a Novel OXA-48 Plasmid

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