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Journal articles on the topic "NDM-Kp"

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Dobreva, Elina, Ivan Ivanov, Deyan Donchev, Krasimira Ivanova, Rumyana Hristova, Veselin Dobrinov, Veselin Dobrinov, Stefana Sabtcheva, and Todor Kantardjiev. "In vitro Investigation of Antibiotic Combinations against Multi- and Extensively Drug-Resistant Klebsiella pneumoniae." Open Access Macedonian Journal of Medical Sciences 10, B (April 5, 2022): 1308–14. http://dx.doi.org/10.3889/oamjms.2022.8934.

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Objectives: Community and hospital acquired K. pneumoniae infections have become a ubiquitous medical issue due to the limited treatment options and high mortality rate therefore the aims of this study are in vitro investigation of double antimicrobial combinations against multidrug resistant (MDR) and extensively drug resistant (XDR) isolates. Materials and Methods: Antimicrobial susceptibility of twelve isolates from eight Bulgarian hospitals was determined to study the interaction effect of selected double combinations in accordance to fractional inhibitory concentration (FIC) method. Furthermore, the isolates were subjected to genotyping by Multilocus sequence typing (MLST) and detection of carbapenemase genes by multiplex PCR. The results were assessed by groups of strains with either NDM or KPC carbapenemase. Results: Nine antimicrobial combinations: meropenem-colistin, meropenem-fosfomycin, meropenem-gentamicin, meropenem-rifampicin, meropenem-tigecycline, colistin-fosfomycin, colistin-gentamicin, colistin-rifampicin and colistin-tigecycline were tested for synergism on twelve K. pneumoniae, producing either KPC-2 (KPC-KP, 41.7%, 5/12) or NDM-1 (NDM-KP, 58.3%, 7/12). The isolates were distributed in three sequence types: ST11 (58.3%, 7/12), ST15 (25%, 3/12) and ST258 (16.7%, 2/12). All KPC-KP (ST258 and ST15) originated from three hospitals. The rest were NDM-1 carriers isolated from six hospitals and belonged to ST11. The highest synergistic effect was determined for MER-GEN (83.3%, 10/12) and COL-RIF (83.3%, 10/12). The MER-FOS combination was most efficient against NDM-KP, opposite to the KPC strains. Antagonism was not observed for any combinations. Conclusions: The evaluated joint synergistic effect of the MER-GEN and COL-RIF may facilitate the treatment options for patients infected with NDM- and KPC-KP, whereas MER-FOS is highly synergetic against NDM-KP.
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Belati, Alessandra, Davide Fiore Bavaro, Lucia Diella, Nicolò De Gennaro, Francesco Di Gennaro, and Annalisa Saracino. "Meropenem/Vaborbactam Plus Aztreonam as a Possible Treatment Strategy for Bloodstream Infections Caused by Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae: A Retrospective Case Series and Literature Review." Antibiotics 11, no. 3 (March 10, 2022): 373. http://dx.doi.org/10.3390/antibiotics11030373.

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Objectives: The aim of this study was to describe our experience of a combination treatment including meropenem/vaborbactam (M/V) plus aztreonam (ATM) for bloodstream infections (BSIs) due to ceftazidime/avibactam-resistant Klebsiella pneumoniae (CAZ/AVI-R-Kp), for which gene typing was not available at the time the blood culture (BC) results were obtained. Methods: Between 20 July and 22 August 2021, in our hospital laboratory, the molecular test for carbapenemase gene typing was not available. All Gram-negative bloodstream infections were recorded, and characteristics of patients were analysed. Among them, three patients had positive BCs for CAZ/AVI-R-Kp, and the empirical therapy was switched to M/V plus ATM pending phenotypic testing of sensitivity to M/V. Therapy was subsequently targeted on the basis of the results of this test. Results: KPC and NDM represent the most prevalent carbapenemases in our polyclinic. Three patients with CAZ/AVI-R-Kp sepsis were treated with M/V plus ATM not knowing the carbapenemase gene. Two had an NDM-Kp infection for which, upon obtaining the result of sensitivity to M/V, combination therapy was maintained. The third had KPC-Kp infection for which ATM was discontinued, after the acquisition of an antibiogram reporting full sensitivity to M/V (MIC = 0.25 mg/L). One patient with NDM-Kp infection died due to complications of the underlying disease for which he was hospitalised. Conclusions: Meropenem/vaborbactam plus ATM and subsequent de-escalation could represent a possible therapeutic strategy in severe CAZ/AVI-R-Kp infections when carbapenemase gene typing is not rapidly available.
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Wysocka, Magdalena, Roxana Zamudio, Marco R. Oggioni, Justyna Gołębiewska, Marek Bronk, and Beata Krawczyk. "Genetic Background and Antibiotic Resistance Profiles of K. pneumoniae NDM-1 Strains Isolated from UTI, ABU, and the GI Tract, from One Hospital in Poland, in Relation to Strains Nationally and Worldwide." Genes 12, no. 8 (August 22, 2021): 1285. http://dx.doi.org/10.3390/genes12081285.

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In recent years, there has been an observed increase in infections caused by carbapenem-resistant Klebsiella pneumonia (Kp) strains. The aim of this study was the phenotypic and genotypic analysis of eight K. pneumoniae NDM (Kp NDM) isolates, recovered in Poland during the years 2016 and 2018 from seven patients with urinary tract infections (UTIs), asymptomatic bacteriuria (ABU), or colonization of the gut. PCR melting profile genotyping indicated a close relationship between the strains derived from 2018, which were not related to the strain isolated in 2016. WGS results were analyzed in relation to international Kp isolates. Clonal and phylogenetic analyses were performed based on multilocus sequence typing (MLST) and single nucleotide polymorphisms (SNPs) of the core genome. The metallo-β-lactamase was assigned to the NDM-1 type and the sequence was identified as ST11. Eleven antimicrobial resistance genes were detected, mostly from plasmid contigs. Unprecedented profiles of plasmid replicons were described with the IncFII/pKPX-1 dominant replicon. In terms of the KL24 and O2v1 capsular antigen profiles, these isolates corresponded to Greek strains. Strains isolated from UTI, ABU, and colonization GI tract patients were not carrying environment-specific virulence genes. Based on the assessment of strain relationships at the genome level and their direction of evolution, the international character of the sublines was demonstrated, with a documented epidemic potential in Poland and Greece. In conclusion, some groups of patients, e.g., renal transplant recipients or those with complicated UTIs, who are frequently hospitalized and undergoing antibiotic therapy, should be monitored not only for the risk of UTI, but also for colonization by Kp NDM strains.
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Gopinath, Ramya, Patrice Savard, Karen C. Carroll, Lucy E. Wilson, B. Mark Landrum, and Trish M. Perl. "Infection Prevention Considerations Related to New Delhi Metallo-β-Lactamase Enterobacteriaceae A Case Report." Infection Control & Hospital Epidemiology 34, no. 1 (January 2013): 99–100. http://dx.doi.org/10.1086/668782.

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A 60-year-old American man who was hospitalized in India for 4 weeks after an intracranial bleed was transferred by air ambulance to a 249-bed community hospital in Maryland in January 2011. His clinical course is described elsewhere. Here, we describe the infection prevention considerations surrounding his care in the hospital. A sputum sample obtained from the patient grew a New Delhi metallo-β-lactamase-producing (NDM) Klebsiella pneumoniae (NDM-KP) strain and panresistant Acinetobacter species, among other pathogens. Two weeks later, a perirectal swab sample grew an NDM-1 Salmonella Senftenberg (NDM-SS) isolate, described elsewhere. Gut decolonization was attempted with rifaximin 300 mg every 12 hours for 12 days. The patient was discharged home 4.5 months later. He was readmitted to the hospital within 1 week and died shortly thereafter.In recognition of his epidemiological risk factors, empiric contact isolation was instituted by the infectious disease physician who was consulted when the patient experienced a fever 24 hours after hospital admission. Once the NDM-KP strain was identified, a 1:1 nursing protocol was instituted for the patient; respiratory therapists, however, continued to care for other Patients. The patient's nurses were empowered to enforce strict contact isolation. Visitors were restricted to the patient's immediate family members. The hospital implemented an intensive education and communication program for the professional staff, nurses, respiratory therapists, ancillary personnel, and the patient's family.
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Qamar, Muhammad Usman, Hasan Ejaz, Timothy R. Walsh, Asad Ali Shah, Dunia A. Al Farraj, Roua M. Alkufeidy, Noorah A. Alkubaisi, Sidrah Saleem, and Shah Jahan. "Clonal relatedness and plasmid profiling of extensively drug-resistant New Delhi metallo-β-lactamase-producing Klebsiella pneumoniae clinical isolates." Future Microbiology 16, no. 4 (March 2021): 229–39. http://dx.doi.org/10.2217/fmb-2020-0315.

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Aim: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) particularly New Delhi metallo-β-lactamase (NDM) is a serious public health concern globally. The aim of the study to determine the molecular epidemiology of blaNDM-producing clinically isolated K. pneumoniae. Methods: Carbapenem-resistant K. pneumoniae isolates (n = 100) were collected from tertiary care hospital Lahore. Isolates were confirmed by VITEK® 2 system and MALDI-TOF. Minimum inhibitory concentration was performed by VITEK 2 and molecular characterization was done by PCR, PFGE, DNA hybridization and replicon typing. Results: Of 90 MBL-producing K. pneumoniae, 75 were NDM producers; 60 were NDM-1 and 11 NDM-5. A total of 27 K. pneumoniae belonged to ST11 and 14 to ST147. NDM-positive isolates were 100% resistant to β-lactam antibiotics except for colistin. 13.3% isolates carried blaNDM on ∼140 kb plasmids. A total of 32 (52.4%) isolates were positive for IncA/C and 18 (29.5%) IncF/II. Conclusion: The extensively resistant lineage of NDM-producing K. pneumoniae is prevalent in the clinical setting.
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Oliveira, Pâmela Maria, Célio Faria-Junior, Daniely Martins Silva, Larissa Fernandes Matos, and Alex Leite Pereira. "Clonal complexes of carbapenem-resistant Klebsiella pneumoniae recovered from community sewage." Journal of Water and Health 21, no. 1 (January 1, 2023): 94–108. http://dx.doi.org/10.2166/wh.2023.237.

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Abstract Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are life-threatening multidrug-resistant bacteria. In this study, CR-Kp strains isolated from sewage treatment plants (STPs) (n = 12) were tested for carbapenemase genes (blaKPC, blaNDM, blaIMP, blaVIM and blaOXA-48) and had their sequence types (ST) and clonal complexes (CCs) defined. A collection of clinical CR-Kp strains recovered in local hospitals was added to phylogenetic analyses along with sewage strains in order to infer clonality among CR-Kp strains. A total of 154 CR-Kp strains were isolated from raw sewage [55.8% (86/154)], treated sewage [25.3% (39/154)] and from water body downstream from STPs [18.8% (29/154)]. No CR-Kp strain was isolated from upstream water samples. blaKPC or blaNDM were detected in 143 (92.8%) strains. The occurrence of blaKPC-or-NDM CR-Kp strains was positively associated with the number of hospitalized patients in the areas serviced by STPs. Eleven STs were detected in CR-Kp strains, most of them belonging to the clinically relevant CC11 [ST11 (n = 13–28.2%) and ST340 (n = 7–15.2%)]. CCs 11, 15, 17, 147 and 2703 are shared by clinical and sewage CR-Kp strains. In conclusion, sewage harbors clinically relevant clones of CR-Kp that resist sewage treatments, contaminating water bodies downstream from STPs.
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Pons, Maria J., Marta Marí-Almirall, Barbara Ymaña, Jeel Moya-Salazar, Laura Muñoz, Sharon Sauñe, Richard Salazar-Hernández, Jordi Vila, and Ignasi Roca. "Spread of ST348 Klebsiella pneumoniae Producing NDM-1 in a Peruvian Hospital." Microorganisms 8, no. 9 (September 11, 2020): 1392. http://dx.doi.org/10.3390/microorganisms8091392.

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The aim of this study was to characterize carbapenem-resistant Klebsiella pneumoniae (CR-Kp) isolates recovered from adults and children with severe bacteremia in a Peruvian Hospital in June 2018. Antimicrobial susceptibility was determined by disc/gradient diffusion and broth microdilution when necessary. Antibiotic resistance mechanisms were evaluated by PCR and DNA sequencing. Clonal relatedness was assessed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Plasmid typing was performed with a PCR-based method. Thirty CR-Kp isolates were recovered in June 2018. All isolates were non-susceptible to all β-lactams, ciprofloxacin, gentamicin and trimethoprim-sulfamethoxazole, while mostly remaining susceptible to colistin, tigecycline, levofloxacin and amikacin. All isolates carried the blaNDM-1 gene and were extended spectrum β-lactamase (ESBL) producers. PFGE showed four different pulsotypes although all isolates but two belonged to the ST348 sequence type, previously reported in Portugal. blaNDM-1 was located in an IncFIB-M conjugative plasmid. To our knowledge, this is the first report of an New Delhi metallo-β-lactamase (NDM)-producing K. pneumoniae recovered from both children and adults in Lima, Peru, as well as the first time that the outbreak strain ST348 is reported in Peru and is associated with NDM. Studies providing epidemiological and molecular data on CR-Kp in Peru are essential to monitor their dissemination and prevent further spread.
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Taing, Meng-Wong, Jean-Thomas Pierson, Paul N. Shaw, Ralf G. Dietzgen, Sarah J. Roberts-Thomson, Michael J. Gidley, and Gregory R. Monteith. "Mango Fruit Extracts Differentially Affect Proliferation and Intracellular Calcium Signalling in MCF-7 Human Breast Cancer Cells." Journal of Chemistry 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/613268.

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The assessment of human cancer cell proliferation is a common approach in identifying plant extracts that have potential bioactive effects. In this study, we tested the hypothesis that methanolic extracts of peel and flesh from three archetypal mango cultivars, Irwin (IW), Nam Doc Mai (NDM), and Kensington Pride (KP), differentially affect proliferation, extracellular signal-regulated kinase (ERK) activity, and intracellular calcium ([Ca2+]I) signalling in MCF-7 human breast cancer cells. Mango flesh extracts from all three cultivars did not inhibit cell growth, and of the peel extracts only NDM reduced MCF-7 cell proliferation. Mango cultivar peel and flesh extracts did not significantly change ERK phosphorylation compared to controls; however, some reduced relative maximal peak[Ca2+]Iafter adenosine triphosphate stimulation, with NDM peel extract having the greatest effect among the treatments. Our results identify mango interfruit and intrafruit (peel and flesh) extract variability in antiproliferative effects and[Ca2+]Isignalling in MCF-7 breast cancer cells and highlight that parts of the fruit (such as peel and flesh) and cultivar differences are important factors to consider when assessing potential chemopreventive bioactive compounds in plants extracts.
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Krapp, Fiorella, Catherine Amaro, Karen Ocampo, Lizeth Astocondor, Noemi Hinostroza, Maribel Riveros, and Coralith Garcia. "1189. A Comprehensive Characterization of the Emerging Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates From a Public Hospital in Lima, Peru." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S359—S360. http://dx.doi.org/10.1093/ofid/ofy210.1022.

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Abstract Background In contrast with other countries in Latin America, Peru had been notoriously spared by the global dissemination of carbapenem-resistant Klebsiella pneumoniae (CR-Kp), until recently. Even though, isolated cases of KPC-producing K. pneumoniae had been reported since 2013, it was not until 2016 that the first outbreak of NDM- producing K. pneumoniae was described in Peru. By 2017, rapid emergence of CR-Kp took place in Hospital Cayetano Heredia (HCH), a tertiary care hospital in Lima. Here, we provide a description of clinical, microbiological and molecular characteristics of CR-Kp isolates recovered at HCH. Methods Retrospective review of all CR-Kp clinical isolates recovered at HCH until December 2017. Antibiotic susceptibility data were obtained during routine care (Vitek or disc diffusion) and was assessed using CLSI breakpoints. DNA extraction was performed by heat shock, and PCR was performed to assess carriage of blaNDM gene. String test was performed to detect hypermucoviscosity. Results The first case of CR-Kp in HCH dated from July 2015. Since then, a total of 69 CR-Kp clinical isolates, from 60 patients have been recovered until December 2017. A significant increase in the number of cases was observed during 2017 (Figure 1). The average age of patients was 55. Urinary, and respiratory sources of infection or colonization were the most common ones (35% and 30%, respectively), followed by blood stream (17%) and intraabdominal (10%) infections. Isolate recovery and DNA extraction was achieved in 40 cases. Of these, 15 (38%) had a positive PCR for blaNDM carbapenemase gene (Figure 2). Antibiotic susceptibility testing revealed that amikacin was the most effective antimicrobial with the rest of antimicrobials having extremely high rates of resistance (Figure 3). String test was positive in two of these isolates, suggesting that hypervirulent CR-KP might be emerging in this region. Conclusion An epidemic of CR-Kp has established in our hospital, representing the first one reported in Peru. The different mechanisms of carbapenem resistance found suggest a polyclonal expansion. Amikacin remains the only active antimicrobial within the routinely tested antibiotics, highlighting the need to add other antimicrobials to the routine panel. Disclosures All authors: No reported disclosures.
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Khan, Ayesha, Blake Hanson, An Dinh, Audrey Wanger, Luis Ostrosky-Zeichner, William Miller, and Cesar Arias. "705. Four Superbugs Isolated From a Single Patient in the United States: E. coli (EC) and K. pneumoniae (KP) Harboring NDM-5, P. aeruginosa (PA) Harboring NDM-1 and Candida auris." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S254. http://dx.doi.org/10.1093/ofid/ofy210.712.

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Abstract Background The spread of carbapenem resistance in Enterobacteriacae (CRE) and PA is an urgent public health concern. Candida auris (CA) is also an emerging threat, with the epicenter of US cases on the East Coast. Transcontinental spread of multi-drug-resistant (MDR) organisms has the potential to change local susceptibility patterns via dissemination of resistance determinants or high-risk clones. Here, we report and characterize MDR-isolates of EC, KP, PA and CA, all isolated from a single patient admitted to an ICU in Houston, Texas after complications from plastic surgery in India. Methods CRE were isolated from the urine, PA from respiratory cultures and CA from wound cultures. Antimicrobial susceptibility testing was performed on Vitek 2 or by Etest. Synergy testing was done by Aztreonam (ATM) E-test on Mueller-Hinton agar supplemented with 2.2 µg/mL avibactam. Bacterial isolates underwent whole genome sequencing on an Illumina MiSeq, and resistance determinants (Abricate using CARD), plasmid replicon types (PlasmidFinder 1.3) and sequence type (Tseemann MLSTtool) were identified. Genes were verified by PCR. Results The CRE were resistant to all β-lactams, including ceftazidime/avibactam (CZA) and ceftolozane/tazobactam. Synergy testing with CZA+ATM reduced the ATM MICs of the EC from >256 to 0.5 µg/mL and the KP from >256 to .094 µg/mL, while the PA ATM MIC was 4 µg/mL irrespective of the presence of avibactam. WGS indicated that the EC and KP shared the blaNDM-5, blaTEM-4, and blaCTX-M-15 β-lactamase genes, as well as IncFII and IncX3 plasmid replicon types. In addition, the EC harbored blaCMY-59, blaOXA-181, qnrS1 and two additional IncB and IncY plasmid replicon types. The PA isolate harbored blaNDM-1, qnrVC1, several aminoglycoside resistance genes and a type 1 integrase. The CA isolate had a fluconazole MIC of >256 µg/mL and a micafungin MIC of 0.125 µg/mL. Conclusion Here we report the identification of 4 MDR organisms, including the first reported isolate of CA in Houston, in one patient. The pattern of resistance determinants suggests horizontal transmission of blaNDM-5 between the CRE isolates. Prompt recognition of MDR organisms is imperative to prevent healthcare-associated spread. Disclosures W. Miller, Merck: Investigator, Research support. C. Arias, Merck & Co., Inc.: Grant Investigator, Research support. MeMed: Grant Investigator, Research support. Allergan: Grant Investigator, Research support.
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Dissertations / Theses on the topic "NDM-Kp"

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CONA, ANDREA. "HOSPITAL-ACQUIRED BACTERIAL INFECTIONS IN SARS-COV-2 INFECTED PATIENTS. WASN¿T COVID-19 COMPLICATED ENOUGH? PROSPECTIVE STUDY ON NOSOCOMIAL BLOODSTREAM INFECTIONS AND DESCRIPTION OF NDM-1-PRODUCING KLEBSIELLA PNEUMONIAE OUTBREAK IN COVID-19 UNITS." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/885836.

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Introduzione. È ormai noto come il decorso clinico dei pazienti ospedalizzati per infezione da SARS-CoV-2 possa essere complicato da sovra-infezioni batteriche. Tuttavia, la reale incidenza, le caratteristiche cliniche e le conseguenze di tali complicazioni batteriche sull’esito del ricovero non sono ancora del tutto chiariti. In questa dissertazione verranno esposti due studi clinici condotti durante gli anni di studio del corso di dottorato in Ricerca Clinica. Il primo studio si pone come obiettivo quello di valutare il burden e le caratteristiche cliniche e microbiologiche delle infezioni del circolo ematico acquisite in ospedale (acronimo in inglese HA-BSI) nei pazienti ricoverati per polmonite COVI-19. In particolare, sono stati analizzati i fattori di rischio per queste infezioni e l’impatto sull’outcome clinico in termini di mortalità e lunghezza di degenza. Nel secondo studio viene descritto un outbreak intraospedaliero di infezioni sostenute da Klebsiella pneumoniae produttrice di metallo-betalattamasi di tipo New Delhi (NDM-Kp) che ha coinvolto alcuni reparti COVID compresa la terapia intensiva. Verranno descritte le caratteristiche cliniche ed epidemiologiche dei casi e la caratterizzazione fenotipica e molecolare dei ceppi. Infine, verranno discusse le misure di Infection Control messe in atto per limitare l’outbreak. Materiali e metodi. Il primo è uno studio osservazionale di coorte prospettico condotto presso l’Ospedale San Paolo di Milano. Tutti i pazienti ricoverati per infezione da SARS-CoV-2 sintomatica dal 24 febbraio 2020 al 31 marzo 2021 sono stati inclusi nello studio. Le HA-BSI sono state definite come infezioni insorte almeno 48 ore dopo l’ingresso in ospedale. L’incidenza è stata stimata come il numero di episodi di HA-BSI su 1000 giornate di ospedalizzazione con il 95% di intervallo di confidenza calcolato tramite Poisson. I fattori associati con lo sviluppo di HA-BSI sono stati analizzati tramite modelli di regressione uni e multivariati. L’impatto delle HA-BSI sull’outcome clinico è stato analizzato tramite analisi competitiva del rischio dopo aver selezionato per età, sesso e ricovero in ICU 100 pazienti che non hanno sviluppato batteriemia (non-BSI) (controlli) comparati con i 100 pazienti HA-BSI (casi) con un match 1:1. Obiettivi principali dello studio: (i) descrizione delle caratteristiche cliniche e microbiologiche delle HA-BSI; (ii) valutare l’incidenza delle HA-BSI; (iii) valutare dei fattori di rischio associati; (iv) valutare l’impatto sulla mortalità ospedaliera e la lunghezza di degenza. Risultati. Tra i 1950 pazienti ricoverati per COVID-19, sono stati osservati 121 episodi di HA-BSI in 101 (5.2%) pazienti. L’incidenza è stata di 3.5/1000patient-days (95%CI 2.3–4.3). Clinicamente, il 55% dei pazienti è stato trattato con terapia steroidea e solo il 5% con terapia immunomodulante. Dal punto di vista del supporto respiratorio, 29% dei pazienti è stato trattato con casco C-PAP, il 7% tramite NIMV e il 5.5% dei pazienti sono stati sottoposto a ventilazione meccanica invasiva (IMV). All’analisi multivariata, fattori di rischio indipendenti per lo sviluppo di HA-BSI sono risultati essere l’uso di NIMV/CPAP (aOR 1.82, 95%CI 1.15–2.90, p=0.010), di IMV (aOR 4.75, 95%CI 2.32–9.72, p<0.001) e la terapia corticosteroidea (aOR 2.15, 95%CI 1.27–3.65, p=0.005). Per quanto concerne l’esito clinico, i pazienti con HA-BSI hanno avuto una degenza più lunga (28 contro 10 giorni, p<0.001) ed una maggiore ma non significativa mortalità (33% contro 25%, p=0.091). All’analisi competitiva del rischio, è stato osservato un aumento del rischio di morte nei pazienti con HA-BSI; tuttavia, all’analisi multivariata si è confermato un trend verso un aumento di mortalità ma non statisticamente significativo (aSHR 1.80, 95%CI 0.98-3.30, p=0.057). Mentre, è stato confermato l’aumento della lunghezza di degenza nei casi rispetto ai controlli (incidenza di dimissione ospedaliera 54% in HA-BSI vs 75% in non-BSI; aSHR 0.65, 95%CI 0.43-0.85, p=0.003). L’outbreak di NDM-Kp descritto nel secondo studio è stato osservato da febbraio a marzo 2021 presso l’Ospedale San Carlo Borromeo di Milano. Ha coinvolto complessivamente 4 reparti COVID, compresa la terapia intensiva, per un totale di 12 pazienti. 5 di questi hanno sviluppato un’infezione sostenuta dal ceppo in questione mentre 7 sono risultati essere solamente colonizzati. 7 pazienti sono deceduti. L’analisi molecolare ha confermato che i casi erano dovuti al ceppo ST-945. L’outbreak è stato controllato grazie all’implementazione di misure aggiuntive di Infection Control. Conclusioni. Nella nostra coorte l’incidenza di infezioni del circolo ematico ospedaliere è stata relativamente bassa. Tuttavia, è risultata essere associate ad un aumento dei tempi di degenza. I pazienti tratti con terapia steroidea hanno avuto un rischio aumentato di sviluppare tale infezione. Per quanto riguarda l’outbreak di NDM-Kp, l’implementazione di misure di Infection Control aggiuntive, oltre a quelle già in atto, ha permesso il contenimento del cluster.
Introduction Bacterial superinfections may complicate the clinical course of hospitalized SARS-CoV2 infected patients. However, the exact burden of bacterial complications and their impact on mortality in COVID-19 is not fully understood yet. Aim of the first study included in this dissertation is to evaluate the burden and epidemiology of hospital-acquired bloodstream infections (HA-BSIs) in patients hospitalized with COVID-19 pneumonia, exploring in particular risk factors associated with HA-BSIs and impact of HA-BSI on mortality. In the second study it will be described an outbreak due to NDM-1-producing Klebsiella pneumoniae (NDM-Kp) involving SARS-CoV-2 infected patients in ICU and non-ICU Units. Epidemiological and clinical characteristics of the outbreak, including molecular characterization of the micro-organism, will be discussed as well as the infection control measures implemented to control the outbreak. Methods Prospective observational cohort study conducted at San Paolo Hospital in Milan, Italy. All patients admitted to hospital for symptomatic SARS-CoV-2 infection from 24 February 2020 to 31 March 2021 were included in the study. HA-BSI defined as infections occurring ≥48 hours after hospital admission. Incidence of HA-BSI was estimated as the numbers of HA-BSI episodes over 1000 patients-day of hospitalization with 95% confidence interval calculated by Poisson distribution. Factors associated with the development of HA-BSI were analysed using an unadjusted and adjusted logistic regression model. The impact of HA-BSI on in-hospital mortality and hospital discharge has been evaluated with a 1:1 matching nested study using competing-risk analysis. The main objectives of the study were: (i) description of microbiological and clinical characteristics of HA-BSIs; (ii) assessment of the incidence and prevalence of HA-BSIs; (iii) evaluation of risk factors for the development of HA-BSIs; (iv) evaluation of the impact of HA-BSIs on length of stay and in-hospital mortality. Results Among 1,950 consecutive patients hospitalised with COVID-19, 121 episodes of HA-BSI were observed in 101 (5.2%) patients. The incidence rate of HA-BSI was 3.5/1000patient-days (95%CI 2.3–4.3). 1,077/1,950 (55%) patients received corticosteroid therapy and 93/1,950 (5%) immunomodulators. 29% and 7% received continuous positive airway pressure (C-PAP) or non-invasive mechanical ventilation (NIMV) while 5.5% of patients received invasive mechanical ventilation (IMV). No difference in the distribution of therapies and oxygen support was noted between the HA-BSI and non-BSI groups except for a higher consumption of steroids (73% vs 54%, p=0.001) and higher use of NIMV/IMV (44% vs 12%, p<0.001) in the HA-BSI group. At multivariate analysis, NIMV/CPAP (aOR 1.82, 95%CI 1.15–2.90, p=0.010), IMV (aOR 4.75, 95%CI 2.32–9.72, p<0.001) and corticosteroid treatment (aOR 2.15, 95%CI 1.27–3.65, p=0.005) were confirmed as independent factors associated with HA-BSI. Concerning clinical outcomes, patients with HA-BSI compared to no-BSI groups, had a longer hospital stay (28 vs 10 days, p<0.001) but a similar in-hospital mortality (HA-BSI 33% vs non-BSI 25%, p=0.091). At competing-risk analysis, an increased risk of death in patients with HA-BSI was observed (p=0.030). However, after fitting a multivariable competing-risk regression model, a trend toward an increased risk of death in patients with HA-BSI was observed even tough statistical significance was not reached (aSHR 1.80, 95%CI 0.98-3.30, p=0.057). Regarding length of stay, the 30 days cumulative incidence of hospital discharge was 54% and 75% in patients with and without HA-BSI, respectively (p=0.019); this finding was confirmed after multivariable competing-risk regression model adjusted (aSHR 0.65, 95%CI 0.43-0.85, p=0.003). The outbreak of NDM-Kp described in the second study was observed from February 2021 to March 2021 at the San Carlo Hospital. It involved 4 Units, including COVID-ICU, for a total of 12 patients. Five of these patients developed an infection caused by NDM-Kp while the rest of them had an asymptomatic colonization. 7 out of 12 patients died. Genomic sequencing has confirmed that all the cases were due to the same strain, ST-945. The outbreak was controlled thanks to the implementation of additional infection control measures. Conclusions In our cohort the incidence of HA-BSI was relatively low. Development of HA-BSI did not significantly affect mortality but was associated with a longer hospital stay. Patients treated with corticosteroid therapy had double the risk of developing BSI. Concerning the outbreak, the additional infection control measures implemented, in association with those already in force, made possible the containment of the NDM-Kp outbreak. No more cases have been reported; recently few more cases of NDM-Kp have been identified in non-COVID-19 patients; epidemiological and molecular analysis are currently ongoing.
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