Epidemiology of an outbreak of antibiotic-resistant Klebsiella pneumoniae at a tertiary care medical center

Filozov, Alina; Visintainer, Paul; Carbonaro, Carol A.; Agüero-Rosenfeld, Maria E.; Wormser, Gary P.; Montecalvo, Marisa A.

doi:10.1016/j.ajic.2009.02.006

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…Treatment of K. pneumoniae infections has become increasingly difficult because of the predominance of multiple-antibiotic-resistant strains. 1,2) Increasing antibiotic resistance has led to an urgent need for new therapeutic approaches.…”

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confidence: 99%

High Mobility Group Nucleosomal Binding Domain 2 Protein Protects Bladder Epithelial Cells from Klebsiella pneumoniae Invasion

Cao

Fan

et al. 2011

Biological & Pharmaceutical Bulletin

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Due to the predominance of multiple-antibiotic-resistant Klebsiella pneumoniae strains, the search for new approaches for the prevention of K. pneumoniae infections is now under intensive investigation. The objective of the present study was to investigate the effects of high mobility group nucleosomal binding domain 2 (HMGN2) protein, which acts on the bladder epithelial cells T 24, on the invasion of K. pneumoniae 03183 and explore its possible mechanisms. Pretreatment with HMGN2 significantly reduced K. pneumoniae 03183 uptake by T 24 cells. In T 24 cells, there were no detectable cytotoxic effects of HMGN2 at any concentration between 32 and 256 m mg/ml after 2 h incubation. HMGN2 exhibited no appreciable antibacterial activity against K. pneumoniae 03183. Fluorescence microscopy and flow cytometry analysis revealed that HMGN2 blocked K. pneumoniae 03183-induced actin polymerization. K. pneumoniae 03183-induced phosphorylation of extracellular signal-regulated kinase (ERK) and cofilin were prevented by pretreatment with HMGN2. These results indicated that pretreatment with HMGN2 inhibited cofilin phosphorylation and then induced actin disruption which may block ERK phosphorylation. These changes led to inhibition of K. pneumoniae 03183 invasion of T 24 bladder epithelial cells.Key words high mobility group nucleosomal binding domain 2; actin; Klebsiella pneumoniae; extracellular signal-regulated kinase; cofilin Biol. Pharm. Bull. 34(7) 1065-1071 (2011) © 2011 Pharmaceutical Society of Japan * To whom correspondence should be addressed. e-mail: huangpanxiaoxiao@sina.com tein Assay Kit (Pierce, U.S.A.) and the purity was confirmed by Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting with a primary antibody mouse anti-His monoclonal antibody (Roche, U.K.).Invasion Assay For the invasion assay, T 24 cells were seeded at 5ϫ10 4 cells per well in 24-well plates. Cells were preincubated with substances (rHMGN2 or cytochalasin B or latrunculin B or Y27632 or PD98059) for 2 h prior to bacterial infection in order to study the cell structures and processes involved in internalization. The monolayers were washed twice with PBS to remove any substances prior to infection with K. pneumoniae 03183. In each well of a 24-well cell culture cluster, about 5ϫ10 6 mid-log-phase K. pneumoniae 03183 (OD 600 ϭ0.4-0.6) were added to epithelial cells per well. Invasion was allowed to occur for 2 h at 37°C in 5% CO 2 . Before a second 2 h incubation (kill) period under the same conditions but with fresh medium containing 100 mg of gentamicin per ml, monolayers were washed once with PBS (pH 7.4). During the kill period, all extracellular K. pneumoniae 03183 were killed but the viability of internalized bacteria was not affected. Finally, monolayers were washed twice with PBS and lysed with 0.1% Triton X-100 and the released intracellular bacteria were enumerated by plate count. The number of intracellular K. pneumoniae 03183 after invasion in the presence of an inhibitor was divided b...

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High Mobility Group Nucleosomal Binding Domain 2 Protein Protects Bladder Epithelial Cells from Klebsiella pneumoniae Invasion

Cao

Fan

et al. 2011

Biological & Pharmaceutical Bulletin

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“…The neurorehabilitation setting is also known to be characterized by a higher prevalence of MDRO; patients undergoing the most invasive treatments are more likely to be colonized, increasing the risk of prolonged hospital stays, exposure to antibiotic therapies and morbidity [10]. Rehabilitation units represent a challenge for infection control, also due to the dependency of patients and the environment that encourages socialization [11].…”

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Impact of Multidrug-Resistant Organisms on Severe Acquired Brain Injury Rehabilitation: An Observational Study

Castellani,

Maietti,

Colombo

et al. 2024

Microorganisms

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Healthcare-associated infections (HAIa) and antimicrobial resistance are expected to be the next threat to human health and are most frequent in people with severe acquired brain injury (SABI), who can be more easily colonized by multidrug-resistant organisms (MDROs). The study’s aim is to investigate the impact of MDRO colonizations and infections on SABI rehabilitation outcomes. This retrospective observational study was performed in a tertiary referral specialized rehabilitation hospital. The main outcomes were the presence of carbapenemase-producing Enterobacteriaceae (CPE) colonization, type and timing of HAI and MDRO HAI, and the number of CPE transmissions. We included 48 patients, 31% carrying CPE on admission and 33% colonized during the hospitalization. A total of 101 HAI were identified in 40 patients, with an overall incidence of 10.5/1000 patient days. Some 37% of patients had at least one MDRO infection, with a MDRO infection incidence of 2.8/1000 patient days. The number of HAIs was significantly correlated with the length of stay (LOS) (r = 0.453, p = 0.001). A significant correlation was found between colonization and type of hospital room (p = 0.013). Complications and HAI significantly affected LOS. We suggest that CPE carriers might be at risk of HAI and worse outcomes compared with non-CPE carriers.

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“…Clonally-related isolates are often detected among patients residing in the same healthcare facilities and geographical regions [ 17 ]. During an outbreak situation, Gram-negative bacteria acquired ESBL genes through clonal dissemination [ 18 ]. Even during endemic periods, clonally-unrelated strains can harbor identical ESBL-carrying plasmids through horizontal gene transfer between the same Enterobacterales species, as well as between E. coli and K. pneumoniae [ 19 ].…”

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confidence: 99%

Pharmacokinetic/Pharmacodynamic Evaluation of Aztreonam/Amoxicillin/Clavulanate Combination against New Delhi Metallo-β-Lactamase and Serine-β-Lactamase Co-Producing Escherichia coli and Klebsiella pneumoniae

Zhang

Diao

et al. 2023

Pharmaceutics

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This study aimed to examine specific niches and usage for the aztreonam/amoxicillin/clavulanate combination and to use population pharmacokinetic simulations of clinical dosing regimens to predict the impact of this combination on restricting mutant selection. The in vitro susceptibility of 19 New-Delhi metallo-β-lactamase (NDM)-producing clinical isolates to amoxicillin/clavulanate and aztreonam alone and in co-administration was determined based on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). The fractions of a 24-h duration that the free drug concentration was within the mutant selection window (fTMSW) and above the MPC (fT>MPC) in both plasma and epithelial lining fluid were determined from simulations of 10,000 subject profiles based on regimens by renal function categories. This combination reduced the MIC of aztreonam and amoxicillin/clavulanate to values below their clinical breakpoint in 7/9 K. pneumoniae and 8/9 E. coli, depending on the β-lactamase genes detected in the isolate. In the majority of the tested isolates, the combination resulted in fT>MPC > 90% and fTMSW < 10% for both aztreonam and amoxicillin/clavulanate. Clinical dosing regimens of aztreonam and amoxicillin/clavulanate were sufficient to provide mutant restriction coverage for MPC and MIC ≤ 4 mg/L. This combination has limited coverage against NDM- and extended-spectrum β-lactamase co-producing E. coli and K. pneumoniae and is not effective against isolates carrying plasmid-mediated AmpC and KPC-2. This study offers a potential scope and limitations as to where the aztreonam/amoxicillin/clavulanate combination may succeed or fail.

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Epidemiology of an outbreak of antibiotic-resistant Klebsiella pneumoniae at a tertiary care medical center

Cited by 6 publications

References 30 publications

High Mobility Group Nucleosomal Binding Domain 2 Protein Protects Bladder Epithelial Cells from Klebsiella pneumoniae Invasion

High Mobility Group Nucleosomal Binding Domain 2 Protein Protects Bladder Epithelial Cells from Klebsiella pneumoniae Invasion

Impact of Multidrug-Resistant Organisms on Severe Acquired Brain Injury Rehabilitation: An Observational Study

Pharmacokinetic/Pharmacodynamic Evaluation of Aztreonam/Amoxicillin/Clavulanate Combination against New Delhi Metallo-β-Lactamase and Serine-β-Lactamase Co-Producing Escherichia coli and Klebsiella pneumoniae

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