Carbapenem-resistant <i>Klebsiella pneumoniae</i> outbreak in a COVID-19 intensive care unit; a case-control study

Ergen, Pınar; Koçoğlu, Mücahide Esra; Nural, Müge; Kuşkucu, Mert Ahmet; Aydın, Özlem; İnal, Ferda Yılmaz; Öztürk, Hande; Üçışık, Ayşe Canan; Çaşkurlu, Hülya; Güneysu, Büşra; Yildirim, Büşra; Midilli, Kenan; Çağ, Yasemin; Arslan, Ferhat; Vahaboğlu, Haluk

doi:10.1080/1120009x.2022.2064698

Cited by 4 publications

(5 citation statements)

References 27 publications

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“…For instance, the Hirszfeld Institute of Immunology or Experimental Therapy in Poland and the Eliava Institute of Bacteriophages, Microbiology, and Virology in Georgia provide phage medicine items since they support moral purposes [ 1 ]. Phages are occasionally and only in exceptional circumstances used therapeutically inside the larger EU following Article 37 (Unproven Interventions into Clinical Practice) of the Helsinki Declaration [ 4 – 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…K. pneumoniae , particularly carbapenem-resistance K. pneumonia (CRKP) infection, is the primary factor of mortality among the aged in the ICU, and its’ effect throughout the COVID-19 pandemic [ 9 ]. Because of commencing the pandemic, various authors have determined the relationship between COVID-19 and carbapenemase-producing Klebsiella pneumoniae , emphasizing that these infections may have the ability to confuse the term COVID-19 [ 10 ] critically.…”

Section: Introductionmentioning

confidence: 99%

“…International reports determined that nearly 70% of hospitalized patients with COVID-19 get antibiotics, despite a lack of evidence of bacterial coinfections [ 11 ]. With severe COVID-19 cases, the percentage of CRKP infections increased, leading to a higher mortality rate (30–70%) [ 9 ]. Conversely, the coinfections can contribute to a poor prognosis for patients with COVID-19, especially for high-risk populations such as elderly patients.…”

Section: Introductionmentioning

confidence: 99%

“…Conversely, the coinfections can contribute to a poor prognosis for patients with COVID-19, especially for high-risk populations such as elderly patients. Immunosuppressive treatments can lead to the unfavorable evolution of patients coinfected with COVID-19 and CRKP infections [ 9 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Isolation, characterization, therapeutic potency, and genomic analysis of a novel bacteriophage vB_KshKPC-M against carbapenemase-producing Klebsiella pneumoniae strains (CRKP) isolated from Ventilator-associated pneumoniae (VAP) infection of COVID-19 patients

Mohammadi

Saffari

Siadat

et al. 2023

Ann Clin Microbiol Antimicrob

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Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant clinical problem, given the lack of therapeutic options. The CRKP strains have emerged as an essential worldwide healthcare issue during the last 10 years. Global expansion of the CRKP has made it a significant public health hazard. We must consider to novel therapeutic techniques. Bacteriophages are potent restorative cases against infections with multiple drug-resistant bacteria. The Phages offer promising prospects for the treatment of CRKP infections. Objective In this study, a novel K. pneumoniae phage vB_KshKPC-M was isolated, characterized, and sequenced, which was able to infect and lyse Carbapenem-resistant K. pneumoniae host specifically. Methods One hundred clinical isolates of K. pneumoniae were collected from patients with COVID-19 associated with ventilator-associated acute pneumonia hospitalized at Shahid Beheshti Hospital, Kashan, Iran, from 2020 to 2021. Initially, all samples were cultured, and bacterial isolates identified by conventional biochemical tests, and then the ureD gene was used by PCR to confirm the isolates. The Antibiotic susceptibility test in the disc diffusion method and Minimum inhibitory concentrations for Colistin was done and interpreted according to guidelines. Phenotypic and molecular methods determined the Carbapenem resistance of isolates. The blaKPC, blaNDM, and blaOXA-23 genes were amplified for this detection. Biofilm determination of CRKP isolates was performed using a quantitative microtiter plate (MTP) method. The phage was isolated from wastewater during the summer season at a specific position from Beheshti Hospital (Kashan, Iran). The sample was processed and purified against the bacterial host, a CRKP strain isolated from a patient suffering from COVID-19 pneumoniae and resistance to Colistin with high potency for biofilm production. This isolate is called Kp100. The separated phages were diluted and titration by the double overlay agar plaque assay. The separate Phage is concentrated with 10% PEG and stored at −80 °C until use. The phage host range was identified by the spot test method. The purified phage morphology was determined using a transmission electron microscope. The phage stability tests (pH and temperature) were analyzed. The effect of cationic ions on phage adsorption was evaluated. The optimal titer of bacteriophage was determined to reduce the concentration of the CRKP strain. One-step growth assays were performed to identify the purified phage burst’s latent cycle and size. The SDS-PAGE was used for phage proteins analysis. Phage DNA was extracted by chloroform technique, and the whole genome of lytic phage was sequenced using Illumina HiSeq technology (Illumina, San Diego, CA). For quality assurance and preprocessing, such as trimming, Geneious Prime 2021.2.2 and Spades 3.9.0. The whole genome sequence of the lytic phage is linked to the GenBank database accession number. RASTtk—v1.073 was used to predict and annotate the ORFs. Prediction of ORF was performed using PHASTER software. ResFinder is used to assess the presence of antimicrobial resistance and virulence genes in the genome. The tRNAs can-SE v2.0.6 is used to determine the presence of tRNA in the genome. Linear genome comparisons of phages and visualization of coding regions were performed using Easyfig 2.2.3 and Mauve 2.4.0. Phage lifestyles were predicted using the program PHACTS. Phylogenetic analysis and amino acid sequences of phage core proteins, such as the major capsid protein. Phylogenies were reconstructed using the Neighbor-Joining method with 1000 bootstrap repeat. HHpred software was used to predict depolymerase. In this study, GraphPad Prism version 9.1 was used for the statistical analysis. Student’s t-test was used to compare the sets and the control sets, and the significance level was set at P ≤ 0.05. Results Phage vB_KshKPC-M is assigned to the Siphoviridae, order Caudovirales. It was identified as a linear double-stranded DNA phage of 54,378 bp with 50.08% G + C content, had a relatively broad host range (97.7%), a short latency of 20 min, and a high burst size of 260 PFU/cell, and was maintained stable at different pH (3–11) and temperature (45–65 °C). The vB_KshKPC-M genome contains 91 open-reading frames. No tRNA, antibiotic resistance, toxin, virulence-related genes, or lysogen-forming gene clusters were detected in the phage genome. Comparative genomic analysis revealed that phage vB_KshKPC-M has sequence similarity to the Klebsiella phages, phage 13 (NC_049844.1), phage Sushi (NC_028774.1), phage vB_KpnD_PeteCarol (OL539448.1) and phage PWKp14 (MZ634345.1). Conclusion The broad host range and antibacterial activity make it a promising candidate for future phage therapy applications. The isolated phage was able to lyse most of the antibiotic-resistant clinical isolates. Therefore, this phage can be used alone or as a phage mixture in future studies to control and inhibit respiratory infections caused by these bacteria, especially in treating respiratory infections caused by resistant strains in sick patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Isolation, characterization, therapeutic potency, and genomic analysis of a novel bacteriophage vB_KshKPC-M against carbapenemase-producing Klebsiella pneumoniae strains (CRKP) isolated from Ventilator-associated pneumoniae (VAP) infection of COVID-19 patients

Mohammadi

Saffari

Siadat

et al. 2023

Ann Clin Microbiol Antimicrob

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“…Another study by Sun Jin L. and Fisher D. [ 9 ] stated that due to the lack of MDRO infection control measures and the irrational use of antibacterial drugs, MDRO infection outbreaks have also occurred during COVID-19. A study showed that during the COVID-19 epidemic from 12 November to 19 December 2020, a CRKP outbreak occurred in the ICU of a tertiary hospital, and the risk factors of CRKP outbreak were analyzed related to invasive procedures [ 10 ]; the drug resistance and virulence analysis of an outbreak of KPC Klebsiella pneumoniae ST15 strain in a tertiary hospital in China found that there was high drug resistance and CRKP should be strictly monitored [ 11 ]. CRKP infection outbreak necessitates a large number of medical and social resources [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Application Effect of Transparent Supervision Based on Informatization in Prevention and Control of Carbapenem-Resistant Klebsiella pneumoniae Nosocomial Infection

Feng

et al. 2022

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Objective. To explore the effect of transparent supervision model on the prevention and control of carbapenem-resistant Klebsiella pneumoniae (CRKP) nosocomial infection and the value of the autoregressive integrated moving average (ARIMA) model in predicting the incidence of CRKP infection. Methods. A total of 46,873 inpatients from Jiawang District People’s Hospital of Xuzhou between January 2019 and December 2019 (prior to COVID-19 prevention and control) were selected as the preintervention group and 45,217 inpatients from January 2020 to December 2020 (after the COVID-19 prevention and control) as the postintervention group. We performed transparent supervision on CRKP patients detected by the real-time monitoring system for nosocomial infection. Incidence and detection rate of CRKP, utilization rate of special grade hydrocarbon enzyme alkene antibiotics, hand hygiene compliance rate, qualified rate of ATP tests on surface of environmental objects, and execution rate of CRKP core prevention and control were compared between the two groups. Results. Transparent supervision of CRKP-infected patients was conducted daily from January to December 2020, which resulted in the following: (a) the infection rate of CRKP decreased in a fluctuating manner, and the actual value of hydrocarbon alkene use rate was basically the same as the predicted value with an overall decreasing trend; (b) after the intervention, hand hygiene compliance rate increased from 53.30% to 70.24% ( P < 0.001 ) and the ATP qualified rate increased from 53.77% to 92.24% ( P < 0.001 ); (c) the fitted value of the ARIMA model was in good agreement with the actual value. The incidence of CRKP infection and the utilization rate of carbene antibiotics were also in good agreement with the predicted value. The average relative errors were 11% and 10.78%. Conclusions. During the COVID-19 outbreak in 2020, the ARIMA model effectively fit and predicted the CRKP infection rate, thereby providing scientific guidance for the prevention and control of CRKP infection. In addition, the transparent supervision intervention model improved the hand hygiene compliance and environmental hygiene qualification rates of medical staff, effectively reducing CRKP cross-infection in the hospital.

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Sobreinfecciones intrahospitalarias y su relación con la mortalidad en pacientes obesos o diabéticos con COVID-19 críticamente enfermos

Osorio-Rodríguez,

Aldana-Roa,

Patiño-Patiño

et al. 2024

Acta Colombiana de Cuidado Intensivo

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Carbapenem-resistant Klebsiella pneumoniae outbreak in a COVID-19 intensive care unit; a case-control study

Cited by 4 publications

References 27 publications

Isolation, characterization, therapeutic potency, and genomic analysis of a novel bacteriophage vB_KshKPC-M against carbapenemase-producing Klebsiella pneumoniae strains (CRKP) isolated from Ventilator-associated pneumoniae (VAP) infection of COVID-19 patients

Isolation, characterization, therapeutic potency, and genomic analysis of a novel bacteriophage vB_KshKPC-M against carbapenemase-producing Klebsiella pneumoniae strains (CRKP) isolated from Ventilator-associated pneumoniae (VAP) infection of COVID-19 patients

Application Effect of Transparent Supervision Based on Informatization in Prevention and Control of Carbapenem-Resistant Klebsiella pneumoniae Nosocomial Infection

Sobreinfecciones intrahospitalarias y su relación con la mortalidad en pacientes obesos o diabéticos con COVID-19 críticamente enfermos

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