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1.
Artigo em Inglês | MEDLINE | ID: mdl-32015048

RESUMO

Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is an emerging global public health threat that causes life-threatening pneumonia and bacteremia. Ceftazidime-avibactam (CZA) represents a promising advance for the treatment of serious infections caused by KPC-Kp We investigated the pharmacokinetics and efficacy of ceftazidime-avibactam in the treatment of experimental KPC-Kp pneumonia in persistently neutropenic rabbits. For single-dose and multidose (administration every 8 h) pharmacokinetics, rabbits received ceftazidime-avibactam intravenous infusions at 60/15, 90/22.5, and 120/30 mg/kg of body weight. Ceftazidime mean area under the concentration-time curves (AUCs) ranged from 287 to 608 µg·h/ml for a single dose and from 300 to 781 µg·h/ml for multiple doses. Avibactam AUCs ranged from 21 to 48 µg·h/ml for a single dose and from 26 to 48 µg·h/ml for multiple doses. KPC-Kp pneumonia was established by direct endotracheal inoculation. Treatments consisted of ceftazidime-avibactam at 120/30 mg/kg every 6 h, a polymyxin B (PMB) loading dose of 2.5 mg/kg followed by 1.5 mg/kg every 12 h q12h, or no treatment (untreated controls [UC]). There were significant reductions in the residual bacterial burden, lung weights, and pulmonary hemorrhage scores in CZA- and PMB-treated rabbits for a 7-day or a 14-day (P ≤ 0.01) course in comparison with those in the UC. These results corresponded to significant decreases in the bacterial burden in bronchoalveolar lavage fluid after a 7-day or a 14-day treatment (P ≤ 0.01). The outcomes demonstrated an improved response at 14 days versus that at 7 days. There was significantly prolonged survival in rabbits treated with CZA for 14 days in comparison with that in the PMB-treated or UC rabbits (P ≤ 0.05). This study demonstrates that ceftazidime-avibactam displays linear dose-proportional exposures simulating those seen from human plasma pharmacokinetic profiles, is active for the treatment of experimental KPC-Kp pneumonia in persistently neutropenic rabbits, and provides an experimental foundation for the treatment of severely immunocompromised patients with this life-threatening infection.


Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Inibidores de beta-Lactamases/uso terapêutico , Animais , Antibacterianos/farmacocinética , Compostos Azabicíclicos/farmacocinética , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Carga Bacteriana/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Ceftazidima/farmacocinética , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Testes de Sensibilidade Microbiana , Neutropenia , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Coelhos , Inibidores de beta-Lactamases/farmacocinética , beta-Lactamases/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-31358592

RESUMO

In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 µg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.


Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Bacteriemia/tratamento farmacológico , Ceftazidima/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Terapia de Salvação/métodos , Adulto , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/patologia , Carbapenêmicos/uso terapêutico , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/genética , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Enterobacteriaceae/crescimento & desenvolvimento , Enterobacteriaceae/patogenicidade , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Infecções por Enterobacteriaceae/patologia , Feminino , Expressão Gênica , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/mortalidade , Pneumonia Bacteriana/patologia , Polimixinas/uso terapêutico , Estudos Prospectivos , Análise de Sobrevida , beta-Lactamases/genética , beta-Lactamases/metabolismo
3.
New Microbiol ; 40(3): 161-164, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28513809

RESUMO

The mortality for carbapenem-resistant Klebsiella pneumoniae (KPC-Kp) infection ranges from 18 to 48% depending on the type of therapy. Mortality rates in hematologic patients are even higher, up to 85%. Gut decontamination with oral gentamicin might be an option to avoid a subsequent KPC-Kp infection in colonized patients. We treated 14 hematologic patients with oral gentamicin, 80 mg four times daily, for 7 to 25 days in order to eradicate KPC-Kp from the gut, starting oral gentamicin therapy when possible after the discontinuation of systemic antibiotic therapy. The overall decontamination rate in the entire study population was 71% (10/14). Out of the 4 patients who did not respond to oral gentamicin therapy, 1 KPC-Kp strain was gentamicin resistant and 4 patients received concomitant systemic antibiotic therapy (CSAT). One of these patients died from KPC-Kp sepsis. The decontamination rate was 90% (9/10) in patients receiving oral gentamicin only, versus 25% (1/4) in those also treated with CSAT. No new gentamicin-resistant KPC-Kp strain was isolated during oral gentamicin therapy Oral gentamicin might be useful for gut decontamination and prevention of KPC-Kp infection. This option should be considered in patients colonized by a gentamicin-susceptible KPC-Kp strain and not receiving CSAT.


Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Gentamicinas/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Feminino , Gentamicinas/farmacologia , Doenças Hematológicas/complicações , Humanos , Infecções por Klebsiella/microbiologia , Masculino , Pessoa de Meia-Idade , Reto/microbiologia
5.
Adv Exp Med Biol ; 901: 91-101, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26810235

RESUMO

In this study we report the analysis of 131 Klebsiella pneumoniae (K. pneumoniae) clinical isolates from patients hospitalized in various wards, of Perugia General Hospital, from August 2014 to January 2015. Forty two isolates (32.1 %), were resistant to at least one carbapenem antibiotic and, among these isolates, 14 (33.3 %) exhibited resistance to colistin. All isolates were carbapenemases producers and 41 (97.6 %) harboured the bla KPC gene. Carbapenem-resistant K. pneumoniae isolates (CRKPs) were, also, typed for the genotypic diversity and the results revealed the circulation of two major clusters.This surveillance study evidences the spread of CRKP isolates in Perugia General Hospital and confirms that carbapenem-resistant K. pneumoniae isolates have reached epidemic dissemination in Italy. In addition the percentage of resistance to colistin resulted to be less than that observed in other hospital laboratories across Italy. In conclusion the circulation of these isolates should be monitored and appropriate policy of surveillance must be used, in a target manner, in order to reduce the spread of carbapenem-resistant isolates.


Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Infecção Hospitalar/epidemiologia , Feminino , Humanos , Lactente , Itália/epidemiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Filogenia , Adulto Jovem
6.
Antibiotics (Basel) ; 13(5)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38786129

RESUMO

The ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella Pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) is a group of bacteria very difficult to treat due to their high ability to acquire resistance to antibiotics and are the main cause of nosocomial infections worldwide, posing a threat to global public health. Nosocomial infections with MDR bacteria are found mainly in Intensive Care Units, due to the multitude of maneuvers and invasive medical devices used, the prolonged antibiotic treatments, the serious general condition of these critical patients, and the prolonged duration of hospitalization. MATERIALS AND METHODS: During a period of one year, from January 2023 to December 2023, this cross-sectional study was conducted on patients diagnosed with sepsis admitted to the Intensive Care Unit of the Sibiu County Emergency Clinical Hospital. Samples taken were tracheal aspirate, catheter tip, pharyngeal exudate, wound secretion, urine culture, blood culture, and peritoneal fluid. RESULTS: The most common bacteria isolated from patients admitted to our Intensive Care Unit was Klebsiella pneumoniae, followed by Acinetobacter baumanii and Pseudomonas aeruginosa. Gram-positive cocci (Enterococcus faecium and Staphilococcus aureus) were rarely isolated. Most of the bacteria isolated were MDR bacteria. CONCLUSIONS: The rise of antibiotic and antimicrobial resistance among strains in the nosocomial environment and especially in Intensive Care Units raises serious concerns about limited treatment options.

7.
Antimicrob Resist Infect Control ; 13(1): 70, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961463

RESUMO

OBJECTIVES: Genomic surveillance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is crucial for virulence, drug-resistance monitoring, and outbreak containment. METHODS: Genomic analysis on 87 KPC-Kp strains isolated from 3 Northern Italy hospitals in 2019-2021 was performed by whole genome sequencing (WGS), to characterize resistome, virulome, and mobilome, and to assess potential associations with phenotype resistance and clinical presentation. Maximum Likelihood and Minimum Spanning Trees were used to determine strain correlations and identify potential transmission clusters. RESULTS: Overall, 15 different STs were found; the predominant ones included ST307 (35, 40.2%), ST512/1519 (15, 17.2%), ST20 (12, 13.8%), and ST101 (7, 8.1%). 33 (37.9%) KPC-Kp strains were noticed to be in five transmission clusters (median number of isolates in each cluster: 5 [3-10]), four of them characterized by intra-hospital transmission. All 87 strains harbored Tn4401a transposon, carrying blaKPC-3 (48, 55.2%), blaKPC-2 (38, 43.7%), and in one case (1.2%) blaKPC-33, the latter gene conferred resistance to ceftazidime/avibactam (CZA). Thirty strains (34.5%) harbored porin mutations; of them, 7 (8.1%) carried multiple Tn4401a copies. These strains were characterized by significantly higher CZA minimum inhibitory concentration compared with strains with no porin mutations or single Tn4401a copy, respectively, even if they did not overcome the resistance breakpoint of 8 ug/mL. Median 2 (IQR:1-2) virulence factors per strain were detected. The lowest number was observed in ST20 compared to the other STs (p<0.001). While ST307 was associated with infection events, a trend associated with colonization events could be observed for ST20. CONCLUSIONS: Integration of genomic, resistance score, and clinical data allowed us to define a relative diversification of KPC-Kp in Northern Italy between 2019 and 2021, characterized by few large transmission chains and rare inter-hospital transmission. Our results also provided initial evidence of correlation between KPC-Kp genomic signatures and higher MIC levels to some antimicrobial agents or colonization/infection status, once again underlining WGS's importance in bacterial surveillance.


Assuntos
Antibacterianos , Proteínas de Bactérias , Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , beta-Lactamases/genética , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Genoma Bacteriano , Genômica , Hospitais Universitários , Itália/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/enzimologia , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma
8.
J Pharm Anal ; 11(2): 210-219, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012697

RESUMO

Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate (LNA) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). LNA alone exhibited bactericidal activity at 2.5% (V/V), and in combination with meropenem (MPM) at 1.25% (V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species (ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells.

9.
Infect Drug Resist ; 14: 237-247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33536766

RESUMO

BACKGROUND: This study was designed to characterize the dissemination mechanism and genetic context of Klebsiella pneumoniae carbapenemase (KPC) genes in carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates. METHODS: A retrospective analysis was performed on CRKP strains isolated from a teaching hospital of Wenzhou Medical University during 2015-2017. Polymerase chain reaction (PCR)-based amplification and whole-genome sequencing (WGS) were used to analyze the genetic context of the bla KPC-2 gene. Conjugation experiments were performed to evaluate the transferability of bla KPC-2-bearing plasmids. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to investigate the clonal relatedness of bla KPC-2-producing strains. RESULTS: The bla KPC-2 gene was identified from 13.61% (40/294) of clinical K. pneumoniae isolates. Three different sequence types (ST11, ST15 and ST656) and 5 PFGE subtypes (A to E) were classified among them. ST11 was the dominant sequence type (92.50%, 37/40). Plasmid-oriented antibiotic resistance genes, such as extended spectrum-ß-lactamases (ESBLs) and other antimicrobial resistance genes, were also found in KPC-positive K. pneumoniae (KPC-Kp) isolates. Mapping PCR and genomic sequencing revealed that the bla KPC-2-bearing sequence regions, which are related to different mobile elements, including Tn1721- and IS26-based transposons, were mainly located in but not restricted to IncFII-like plasmids and were structurally divergent. CONCLUSION: The bla KPC-2 genes related to divergent mobile genetic elements encoded on transferable plasmids may transfer widely, facilitating the spread of carbapenem resistance among bacteria with different genetic backgrounds. The dissemination of bla KPC-bearing plasmids that collectively carry additional multidrug resistance genes has caused widespread public concern, further limiting the antibiotics available to treat infections caused by KPC-producing pathogens.

10.
Ann Lab Med ; 41(1): 86-94, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829583

RESUMO

BACKGROUND: A lineage of Klebsiella pneumoniae that produces carbapenemase-2 (KPC-2), sequence type (ST) 307, emerged in 2017. We analyzed the complete sequences of plasmids from KPC-2-producing K. pneumoniae (KPC-Kp) ST307, investigated the antimicrobial resistance conferred by this strain, and confirmed the horizontal interspecies transmission of KPC-carbapenemase-producing Enterobacteriaceae (CPE) characteristics among Enterobacteriaceae. METHODS: We performed antimicrobial susceptibility testing, PCR analysis, multilocus sequence typing, curing tests, and whole-genome sequencing to characterize plasmid-derived KPC-2-producing Enterobacteriaceae clinical isolates. RESULTS: Sequence analysis of KPC-Kp strain ST307 revealed novel plasmid-located virulence factors, including a gene cluster for glycogen synthesis. Three Enterobacteriaceae strains were identified in one patient: K. pneumoniae (CPKp1825), Klebsiella aerogenes (CPEa1826), and Escherichia coli (CPEc1827). The bla KPC-2 gene from K. pneumoniae ST307 was horizontally transmitted between these strains. The plasmids could be transferred through conjugation, because all three strains of bacteria contained the type IV secretion system, pilus genes, and tra genes for conjugal transfer. The bla KPC-2 gene was located on a truncated Tn4401 transposon. Plasmids containing the bla KPC-2 gene could not be artificially removed; thus, the three strains could not be cured. CONCLUSIONS: The ease of horizontal transfer of KPC-Kp ST307 carbapenem resistance has serious public health and epidemiological implications. This study provides a better understanding of the genetic characteristics that can contribute to the growth and spread of KPC-Kp ST307, and their association with antimicrobial resistance genes.


Assuntos
Farmacorresistência Bacteriana/genética , Klebsiella pneumoniae/genética , Plasmídeos/metabolismo , beta-Lactamases/genética , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Família Multigênica , Tipagem de Sequências Multilocus , Plasmídeos/genética , Sequenciamento Completo do Genoma , beta-Lactamases/química
11.
Ther Adv Infect Dis ; 7: 2049936120912049, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32489663

RESUMO

Carbapenemase-producing Enterobacteriaceae represent an increasing global threat worldwide and Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas. Risk stratification and rapid diagnostics laboratory workflows are of paramount importance and indication for therapy of KPC-KP infection must be individualized according to the baseline characteristics of the patient and severity of infection. The optimal treatment of infection because of KPC-KP organisms is uncertain and antibiotic options are limited. The knowledge of the patient's pathophysiology, infection site, and application of the pharmacokinetic/pharmacodynamic principles on the basis of minimum inhibitory concentration (MIC) has progressively gained major relevance. Combination therapies including high-dose meropenem, colistin, fosfomycin, tigecycline, and aminoglycosides are widely used, with suboptimal results. In the past few years, new antimicrobials targeting KPC-KP have been developed and are now at various stages of clinical research. However, their optimal use should be guaranteed in the long term for delaying, as much as possible, the emergence of resistance. Strict infection control measures remain necessary. The aim of this review is to discuss the challenges in the management and treatment of patients with infections because KPC-KP and provide an expert opinion.

13.
Infect Dis Clin North Am ; 33(2): 399-445, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31005135

RESUMO

Bacteremia (bloodstream infection) is frequent (20%-30% incidence) in the stem cell transplant and hematologic malignancy population and often occurs in the early post-transplant engraftment period. In most studies, Gram-positive bacteria occur at greater frequency than gram-negative bacteria, although some centers report that rates of gram-negative bloodstream infections have recently increased. In many centers, resistance rates among Enterococci and gram-negative bacteria, especially the Enterobacteriaceae, are extensive and associated with increased mortality. Better prediction tools, enhanced infection control, and new anti-infective agents hold promise for the treatment of highly resistant pathogens in this population.


Assuntos
Bacteriemia/microbiologia , Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Positivas/etiologia , Neoplasias Hematológicas/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Neoplasias Hematológicas/complicações , Humanos , Incidência
14.
Int J Antimicrob Agents ; 54(2): 117-124, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30885806

RESUMO

OBJECTIVES: The aim of this study was to investigate the spread of the blaKPC-2 gene among Klebsiella pneumoniae and to illustrate the mechanism of dissemination of K. pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) ST11 in China. METHODS: A total of 354 K. pneumoniae isolates were collected from four hospitals in China and were characterized by multilocus sequence typing (MLST). Mobile genetic elements (MGEs) and pulsed-field gel electrophoresis (PFGE) analysis were used to identify the subtypes of K. pneumoniae ST11. Polymerase chain reaction (PCR)-based amplification and sequencing were performed to analyse Tn1721 transposons and IncFII-like plasmids. Electroporation experiments and whole-genome sequencing (WGS) were used to reveal the genetic environment of the blaKPC-2 gene. RESULTS: As the primary type (87.1%) of KPC-Kp, K. pneumoniae ST11 was not predominant in non-KPC-Kp (3.1%). ST11 KPC-Kp was clonally heterogeneous and could be further classified into 11 MGE types and 14 PFGE subtypes. Five Tn1721-blaKPC-2 variants were identified on IncFII-like plasmids. The detection rate of IncFII-like plasmids was much higher in ST11 KPC-Kp (100%) compared with non-ST11 KPC-Kp (16.0%) and the non-KPC-Kp group (7.5%). Moreover, the IncFII plasmid (with IIa replicon) was primarily detected on the MGE-F type (61.7%). The IncFIIk plasmid (with IIk replicon) was clustered into two subtypes: MGE-A (28.3%) and -F (41.5%). The detection of the IncFII and IncFIIk plasmids on MGE-A was 57.1% (20/35) and 42.9% (15/35), respectively. CONCLUSIONS: A close correlation was shown between ST11 KPC-Kp and IncFII-like plasmids. Horizontal transfer mediated by IncFII-like plasmids plays an important role in the pandemic expansion of blaKPC-2 among K. pneumoniae ST11 in China.


Assuntos
Transferência Genética Horizontal , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Plasmídeos/análise , beta-Lactamases/genética , China/epidemiologia , Eletroforese em Gel de Campo Pulsado , Humanos , Sequências Repetitivas Dispersas , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/isolamento & purificação , Tipagem de Sequências Multilocus , Pandemias , Plasmídeos/classificação , Reação em Cadeia da Polimerase
15.
Pathog Immun ; 1(2): 352-370, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-30993245

RESUMO

BACKGROUND: During the last decade, the spread of Klebsiella pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) has increased dramatically worldwide. In this scenario, growing interest has been addressed to genotyping of KPC-Kp strains, which emerged as an important tool for a better understanding of the epidemiological and clinical characteristics of the outbreaks. METHODS: We performed a retrospective cohort study on patients infected with KPC-Kp during a 28-month outbreak period (January 2010-April 2012) at San Gerardo Hospital (Monza, Italy), investigating KPC-Kp genotypes by means of repetitive element sequence-based polymerase chain reaction (Rep-PCR). RESULTS: We enrolled 97 patients infected with KPC-Kp. Rep-PCR analysis identified 5 distinct clone types, with different distribution over time. During the first 12 months of the outbreak period, only 1 clone was detected (clone A, in 47 patients), while the 4 other clones were identified over the remaining 16 months (clones C, E, and F/L in 23, 24, and 3 patients respectively). Mechanical ventilation was less frequent in patients infected with clones C/E/F/L (OR = 0.14; 95% CI: 0.05-0.37) compared to clone A, and the Charlson comorbidity index (CI) was more likely to have a score >5 in patients infected with clones C/E/F/L (OR = 7.21; 95% CI: 2.24-23.14) compared to clone A.Overall mortality was higher in patients infected with clones C/E/F/L (13/20 patients, 65%) compared to those infected with clone A (7/20, 35%). Mortality in patients infected with clones C/E/F/L remained significantly higher even after adjusting for the potential confounding effect of comorbidities (ie, CI), with a hazard ratio (HR) of 4.65 (95% CI: 1.83-11.89). CONCLUSIONS: Our results suggested a close relationship between strain genotype and clinical outcome.

16.
Clin Microbiol Infect ; 22(5): 444-50, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26850826

RESUMO

The aim of this study was to identify factors associated with mortality in intensive care unit patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) septic shock. A retrospective analysis of intensive care unit patients with KPC-Kp infection and septic shock observed in a large teaching hospital from November 2010 to December 2014 was performed. A total of 111 patients were included in the study. The most frequent source of infection was unknown-focus bacteraemia in 53 patients (47.7%). The rate of resistance to colistin was 51.3%; 30-day mortality was reported for 44 patients (39.6%). Surviving patients were more frequently treated with an initial therapy (within 24 hours) including two or more antibiotics displaying in vitro activity against the isolated KPC-Kp strain (41.8 vs. 18.1%, p 0.01) and were also more likely to receive a definitive therapy including two or more in vitro active antibiotics (85.1 vs. 15.9%, p <0.001). Cox regression analysis revealed that a colistin-containing antibiotic regimen (hazard ratio (HR) 0.21, confidence interval (CI) 95% 0.05-0.72, p <0.001), use of two or more in vitro active antibiotics as definite therapy (HR 0.08, CI 95% 0.02-0.21, p <0.001) and control of removable source of infection (HR 0.14, CI 95% 0.04-0.25, p <0.001) were associated with favourable outcome; colistin resistance (HR 8.09, CI 95% 3.14-11.23, p 0.001) and intra-abdominal source of infection (HR 2.92, CI 95% 2.11-4.12, p 0.002) were associated with death. In conclusion, use of a definitive therapy with at least two antibiotics displaying in vitro activity against the KPC-Kp isolates was the most important determinant of favourable outcome, whilst isolation of colistin-resistant strains was associated with death in septic patients with KPC-Kp infection.


Assuntos
Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/enzimologia , Choque Séptico/tratamento farmacológico , Choque Séptico/mortalidade , beta-Lactamases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais de Ensino , Humanos , Unidades de Terapia Intensiva , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Choque Séptico/microbiologia , Análise de Sobrevida , Resultado do Tratamento
17.
Future Microbiol ; 10(5): 743-61, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26000649

RESUMO

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae strains (KPC-Kp) are emerging worldwide causing different nosocomial infections including those of the urinary tract, lung or skin wounds. For these strains, the antibiotic treatment is limited to only few choices including colistin, whose continuous use led to the emergence of carbapenem-resistant KPC-Kp strains resistant also to this treatment (KPC-Kp Col-R). AIM: Very little is known about the capacity of the different strains of KPC-Kp to invade the epithelial cells in vitro. To verify if the acquisition of carbapenem-resistant and the colistin-resistant phenotypes are correlated with a different ability to infect a series of epithelial cell lines of various tissutal origin and with a different capacity to induce cellular death. MATERIALS & METHODS: We used Klebsiella pneumoniae (KP), KPC-Kp and KPC-Kp Col-R strains, isolated from different patients carrying various tissue-specific infections, to infect a series of epithelial cell lines of different tissutal origin. The invasive capacity of the strains and the extent and characteristics of the cell damage and death induced by the bacteria were evaluated and compared. CONCLUSION: Our results show that both KPC-Kp and KPC-Kp Col-R display a greater ability to infect the epithelial cells, with respect to KP, and that the bacterial cell invasion results in a nonprogrammed cell death.


Assuntos
Morte Celular , Endocitose , Células Epiteliais/microbiologia , Células Epiteliais/fisiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/fisiologia , Resistência beta-Lactâmica , Linhagem Celular , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação
18.
Future Microbiol ; 10(2): 283-94, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25689539

RESUMO

The wide dissemination of carbapenemase producing K. pneumoniae (KPC-Kp) has caused a public health crisis of global dimensions, due to the serious infections in hospitalized patients associated with high mortality. In 2014, we aim to review clinical data on KPC-Kp at a time when a pro-active strategy (combating the problem before it is established) is no longer useful, focusing on epidemiology, patient risk profile, infection control, digestive tract colonization and treatment issues such as the role of carbapenems or carbapenem sparing strategies, colistin and resistance, dual carbapenem administration and the role of tigecycline. All these issues are illustrated prospectively to provide a forum for a Consensus strategy when not only intensive care units but also medical and surgical wards are affected by the epidemics.


Assuntos
Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Controle de Infecções , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Proteínas de Bactérias/biossíntese , Colistina/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Quimioterapia Assistida por Computador , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Minociclina/análogos & derivados , Minociclina/uso terapêutico , Fatores de Risco , Tigeciclina , beta-Lactamases/biossíntese
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