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1.
Medicine (Baltimore) ; 98(49): e18247, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804353

RESUMO

RATIONALE: Patients with chronic Strongyloides stercoralis infection are usually asymptomatic; therefore, their condition is easily overlooked. In immunosuppressed patients, mortality is high because of disseminated infection and hyperinfection. This report describes a fatal S stercoralis hyperinfection in a patient with nephrotic syndrome after treatment with steroids. PATIENT CONCERNS: A 70-year-old male presented with a history of progressive edema, skin infection, persistent fever, cough, intermittent abdominal pain, and progressive respiratory failure after steroid treatment. DIAGNOSIS: Nephrotic syndrome; cellulitis; S stercoralis hyperinfection; Klebsiella pneumonia. INTERVENTIONS: During the first hospital admission, the patient was administered full-dose glucocorticoid and antibiotic therapy after suffering from cellulitis. During the second admission, he was diagnosed and treated for normal digestive discomfort and a bacterial infection. The patient had progressive respiratory failure and was placed on a ventilator. He was immediately treated with albendazole when S stercoralis was found in samples of his sputum and feces. OUTCOMES: The patient died despite treatment with albendazole and antibiotic therapy. LESSONS: It is essential to consider the possibility of S stercoralis infection in immunosuppressed patients with nephrotic syndrome. Given the lack of classic manifestations and high mortality rate of advanced disease, continuous monitoring, early diagnosis, and proper treatment are imperative.


Assuntos
Infecções por Klebsiella/diagnóstico , Síndrome Nefrótica/diagnóstico , Estrongiloidíase/diagnóstico , Idoso , Animais , Doença Crônica , Coinfecção , Diagnóstico Diferencial , Evolução Fatal , Humanos , Hospedeiro Imunocomprometido , Infecções por Klebsiella/tratamento farmacológico , Masculino , Síndrome Nefrótica/tratamento farmacológico , Strongyloides stercoralis , Estrongiloidíase/tratamento farmacológico
2.
Medicine (Baltimore) ; 98(45): e17878, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702658

RESUMO

RATIONALE: Donor-derived bacterial infection is a rare cause of morbidity after solid organ transplantation (SOT) but associated with significant morbidity and mortality, deaths caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) infection account for a considerable proportion of postoperation mortality rate in liver and kidney recipients. The arterial rupture as a result of fungal arteritis is occasionally described, while the rupture of graft vascular anastomosis after SOT due to donor-derived CRKP infection is rarely reported. PATIENTS CONCERNS: We reported 1 patient with donor-derived CRKP infection following liver transplantation and 2 patients following renal transplantation (1 liver and 2 kidneys were from the same donor), who experienced sudden abdominal pain and abdominal hemorrhage almost at the same time after organ transplantation. DIAGNOSIS: The patients were diagnosed as graft arteries rupture due to corrosion caused by CRKP infection based on computed tomography scan, blood culture, laparotomy, and pulse-field gel electrophoresis. INTERVENTIONS: Anti-shock treatment, exploratory laparotomy, broad-spectrum antibiotics, and abdominal puncture and drainage were given. OUTCOMES: The liver recipient survived as well as the liver graft, still under treatment of multiple abdominal infections. The 2 renal recipients were alive after resection of the renal grafts and underwent hemodialysis. LESSONS: Rupture of graft artery should be foreseen when donor-derived CRKP infection was confirmed and broad-spectrum antibiotics and other interventions need to be considered.


Assuntos
Transplante de Rim/efeitos adversos , Infecções por Klebsiella/etiologia , Transplante de Fígado/efeitos adversos , Adulto , Antibacterianos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Feminino , Artéria Hepática/diagnóstico por imagem , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Artéria Renal/diagnóstico por imagem , Ruptura/etiologia , Doadores de Tecidos
3.
BMC Infect Dis ; 19(1): 830, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590648

RESUMO

BACKGROUND: Many gaps in the burden of resistant pathogens exist in endemic areas of low- and middle-income economies, especially those endemic for carbapenem resistance. The aim of this study is to evaluate risk factors for carbapenem-resistance, to estimate the association between carbapenem-resistance and all-cause 30-day mortality and to examine whether mortality is mediated by inappropriate therapy. METHODS: A case-control and a cohort study were conducted in one tertiary-care hospital in Medellín, Colombia from 2014 to 2015. Phenotypic and genotypic characterization of isolates was performed. In the case-control study, cases were defined as patients infected with carbapenem-resistant K. pneumoniae (CRKP) and controls as patients infected with carbapenem-susceptible K. pneumoniae (CSKP). A risk factor analysis was conducted using logistic regression models. In the cohort study, the exposed group was defined as patients infected with CRKP and the non-exposed group as patients infected with CSKP. A survival analysis using an accelerated failure time model with a lognormal distribution was performed to estimate the association between carbapenem resistance and all-cause 30-day-mortality and to examine whether mortality is mediated by inappropriate therapy. RESULTS: A total of 338 patients were enrolled; 49 were infected with CRKP and 289 with CSKP. Among CRKP isolates CG258 (n = 29), ST25 (n = 5) and ST307 (n = 4) were detected. Of importance, every day of meropenem (OR 1.18, 95%CI 1.10-1.28) and cefepime (OR 1.22, 95%CI 1.03-1.49) use increase the risk of carbapenem resistance. Additional risk factors were previous use of ciprofloxacin (OR 2.37, 95%CI 1.00-5.35) and urinary catheter (OR 2.60, 95%CI 1.25-5.37). Furthermore, a significant lower survival time was estimated for patients infected with CRKP compared to CSKP (Relative Times 0.44, 95%CI 0.24-0.82). The strength of association was reduced when appropriate therapy was included in the model (RT = 0.81 95%CI 0.48-1.37). CONCLUSION: Short antibiotic courses had the potential to reduce the selection and transmission of CRKP. A high burden in mortality occurred in patients infected with CRKP in a KPC endemic setting and CRKP leads to increased mortality via inappropriate antibiotic treatment. Furthermore, dissemination of recognized hypervirulent clones could add to the list of challenges for antibiotic resistance control.


Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos , Doenças Endêmicas , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/genética , Meropeném/uso terapêutico , Idoso , Antibacterianos/efeitos adversos , Estudos de Casos e Controles , Cefepima/efeitos adversos , Cefepima/uso terapêutico , Ciprofloxacino/efeitos adversos , Ciprofloxacino/uso terapêutico , Colômbia , Farmacorresistência Bacteriana Múltipla , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Klebsiella pneumoniae/isolamento & purificação , Modelos Logísticos , Masculino , Meropeném/efeitos adversos , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Cateteres Urinários/efeitos adversos
4.
Turk J Pediatr ; 61(1): 40-43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31559720

RESUMO

Zhu Y, Xu F. The pathogens and curative effects analysis of perianal abscess of infants under 3 months. Turk J Pediatr 2019; 61: 40-43. In order to guide clinical treatment for perianal abscess of young infants, the characteristics of pathogens and curative effects analysis were conducted. Bacterial culture results, antibiotics susceptibility tests and curative effects of abscess incision were retrospectively analyzed in 66 cases of perianal abscess of infants under 3 months. There were 48 cases of Klebsiella pneumoniae, 7 cases of Staphylococcus, 6 cases of Escherichia coli, 5 cases of Proteus in the pathogen culture results. Klebsiella pneumoniae, the predominant pathogen, was susceptible to most antibiotics, especially to imipenem, cefoperazonesulbactam and amikacin with low drug resistance rates. However, high drug resistance rates were found to ampicillin and nitrofurantion. After abscess incision, the complication rate of anal fistula was 6.6% in infants under 3 months and 60.3% in the adult group. There was significant difference P<0.01. In conclusion, Klebsiella pneumoniae was the most common pathogen in perianal abscess of infants under 3 months and was commonly resistant to ampicillin and nitrofurantion. Since perianal abscess of infants under 3 months is a self-limited disorder, simple surgical intervention and synchronous sensitive antibiotic administration are suggested as the optimal management.


Assuntos
Abscesso , Doenças do Ânus , Infecções por Escherichia coli , Infecções por Klebsiella , Klebsiella pneumoniae/isolamento & purificação , Infecções Estafilocócicas , Abscesso/diagnóstico , Abscesso/tratamento farmacológico , Abscesso/microbiologia , Abscesso/cirurgia , Adulto , Antibacterianos/uso terapêutico , Doenças do Ânus/diagnóstico , Doenças do Ânus/tratamento farmacológico , Doenças do Ânus/microbiologia , Doenças do Ânus/cirurgia , Terapia Combinada , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/cirurgia , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/cirurgia , Resultado do Tratamento
5.
Nat Commun ; 10(1): 3957, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477712

RESUMO

Carbapenem-resistance in Klebsiella pneumoniae (KP) sequence type ST258 is mediated by carbapenemases (e.g. KPC-2) and loss or modification of the major non-selective porins OmpK35 and OmpK36. However, the mechanism underpinning OmpK36-mediated resistance and consequences of these changes on pathogenicity remain unknown. By solving the crystal structure of a clinical ST258 OmpK36 variant we provide direct structural evidence of pore constriction, mediated by a di-amino acid (Gly115-Asp116) insertion into loop 3, restricting diffusion of both nutrients (e.g. lactose) and Carbapenems. In the presence of KPC-2 this results in a 16-fold increase in MIC to Meropenem. Additionally, the Gly-Asp insertion impairs bacterial growth in lactose-containing medium and confers a significant in vivo fitness cost in a murine model of ventilator-associated pneumonia. Our data suggests that the continuous selective pressure imposed by widespread Carbapenem utilisation in hospital settings drives the expansion of KP expressing Gly-Asp insertion mutants, despite an associated fitness cost.


Assuntos
Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/genética , Porinas/genética , Sequência de Aminoácidos , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Cristalografia por Raios X , Feminino , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/patogenicidade , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Mutação , Porinas/química , Porinas/metabolismo , Homologia de Sequência de Aminoácidos , Virulência/genética
6.
Int J Infect Dis ; 86: 208-211, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402295

RESUMO

BACKGROUND: The aim of this study was to determine the effect of colistin resistance and other predictors on fatality among patients with Klebsiella pneumoniae bloodstream infections (Kp-BSI) and to describe the effect of amikacin and tigecycline on the outcome in an OXA-48 dominant country. METHOD: This was a retrospective study performed among patients >16 years of age in a tertiary hospital with 465 beds. All cases had ≥1 positive blood culture for K. pneumoniae 48 h after admission. RESULTS: Among 210 patients with Kp-BSI, the 30-day mortality rate after isolation of the microorganism was 58%. The rate of carbapenem resistance was higher (64% vs. 38%, p < 0.001) and the colistin minimum inhibitory concentration (MIC) was elevated (7 vs. 4, p < 0.029) among the patients who died. Among the colistin-resistant K. pneumoniae, the rates of OXA-48, ST101, and NDM-1 were 78%, 67%, and 35%, respectively. Amikacin was added to the treatment of 13 patients with carbapenem and colistin-resistant Kp-BSI and 77% survived (p < 0.001). Tigecycline was added to the treatment of 24 patients with carbapenem and colistin-resistant Kp-BSI, and the 30-day mortality rate was 71% (p = 0.576). In the multivariate analysis, carbapenem resistance (odds ratio (OR) 5.2, 95% confidence interval (CI) 2.47-10.9, p < 0.001) and increasing APACHE II score (OR 1.19, 95% CI 1.12-1.26, p < 0.001) were significantly associated with 30-day mortality. The addition of amikacin to the treatment regimen (OR 0.05, 95% CI 0.01-0.23, p < 0.001) was significantly beneficial. CONCLUSIONS: Carbapenem resistance, increasing MIC of colistin, and the lungs as the source of the infection were significantly associated with 30-day mortality. The empirical use of combined active aminoglycosides was found to be beneficial in the treatment of colistin-resistant K. pneumoniae infections.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Colistina/farmacologia , Farmacorresistência Bacteriana , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amicacina/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Carbapenêmicos/farmacologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Tigeciclina/farmacologia , Adulto Jovem , beta-Lactamases/análise
7.
BMC Surg ; 19(1): 111, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412850

RESUMO

BACKGROUND: Bacteraemia of the donor is not considered to be contraindication of organ procurement. On the other hand, infection of solid organ transplant recipients remains to be a major cause of their morbidity and mortality. When using organs from bacteraemic donors, individual risks need to be assessed and the appropriate antibiotic treatment applied. CASE PRESENTATION: In this case series we report several serious donor-derived infectious complications in four out of five recipients of different organs from one single donor in the early posttransplant period. Donor-transmitted multi-drug resistant strains of Escherichia coli and Klebsiella pneumonia was confirmed by both serologic and molecular testing. CONCLUSIONS: To prevent donor-derived infections, careful microbiological screening followed by targeted antibiotic treatment is essential. Although such complications can never by completely prevented, a high index for potential bacterial infection in organ donors and transplant recipients should be routinely employed.


Assuntos
Bacteriemia , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/microbiologia , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/microbiologia , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos , Adulto , Antibacterianos/uso terapêutico , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Obtenção de Tecidos e Órgãos , Transplantados
8.
Indian J Med Res ; 149(4): 528-538, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31411177

RESUMO

Background & objectives: The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is an emerging clinical problem. Hence, in this study, the plausible role of extended-spectrum beta-lactamases (ESBLs)/carbapenemases, OmpC/Ompk36, acrB and their combinations was explored among CRE. Methods: The minimum inhibitory concentration (MIC) of meropenem, enzyme-phenotypes (ESBLs/IR and metallo-beta-lactamase (MBL)/non-MBL carbapenemase), genotypes (blaTEM, blaSHV and blaCTX-M; blaNDM and blaVIM; blaKPC and blaOXA-48-like variants), acrB and outer membrane protein (OMP) expressions were analyzed with a total of 101 non-duplicate clinical isolates, obtained from various samples of patients visiting two tertiary care units of Eastern India during May 2013 - October 2016. This included Escherichia coli (n=36) and Klebsiella pneumoniae (n=65), categorized into two groups, namely Group I (resistant to all carbapenems; n=93; E. coli=34 and Klebsiella spp.=59) and Group II (non-resistant to all the carbapenems; n=8; E. coli=2 and Klebsiella spp.=6). Results: Though 88.17 per cent of Group I isolates exhibited ESBL property, the presence of carbapenemase activity (70.96%) and that of blaNDM gene (42/66: 63.63%) indicated their contributions towards the emergence of CRE. Further, porin loss and/or efflux pump activation among ESBL/carbapenemase-producing isolates heightened the MIC of meropenem from 64 to 256 mg/l (range exhibited by only ESBL/carbapenemase-producing isolates) to >256 mg/l. Interpretation & conclusions: These findings implied the major contribution of porin loss and/or efflux pump activation over the presence of ESBLs/carbapenemases in imparting carbapenem resistance in pathogenic bacteria.


Assuntos
Proteínas de Bactérias/genética , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Porinas/genética , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/enzimologia , Escherichia coli/genética , Escherichia coli/patogenicidade , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Infecções por Klebsiella/genética , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidade , Masculino , beta-Lactamases/genética
9.
Indian J Med Microbiol ; 37(1): 34-41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424008

RESUMO

Introduction: Carbapenem resistance (CR) in Klebsiella pneumoniae is mainly mediated by bla NDM and bla OXA-48 carbapenemases. Newer Food and Drug Administration-approved antimicrobial ceftazidime/avibactam (C/A) has a potent activity against bla OXA-48-like producers. However, its activity is limited in organisms co-producing bla NDM and bla OXA-48-like. Addition of aztreonam (ATM) to C/A potentially expands the spectrum of coverage for carbapenemase co-producers. With this, we aimed to determine the synergistic activity of combination of C/A plus ATM against bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48-like producing CR Klebsiella pneumoniae (CRKp). Materials and Methods: A total of 12 isolates of CRKp-harbouring genes encoding bla NDM and bla OXA-48-like were tested. Minimum inhibitory concentrations (MICs) were determined for several antimicrobial agents, including C/A (0.5-8 µg/ml) by broth microdilution method. Checkerboard assay was performed for the combination of C/A plus ATM at varying concentrations. Fold differences in the MIC of C/A with and without addition of ATM were determined to infer synergistic effects. Results: MIC of C/A and ATM ranged from 0.5 to >8 µg/ml and 64 to 2048 µg/ml, respectively. Two isolates were susceptible to C/A with MIC of 0.5 and 1 µg/ml, while others were resistant with MIC of >8 µg/ml. Synergistic effects of >8-fold MIC difference in C/A MIC were noted with addition of ATM at 4 µg/ml. This was observed for all CRKp with profiles of bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48-like genes, which was a promising effect. Notably, all five of the colistin-resistant CRKp were inhibited with >8-fold MIC difference in the combination of C/A plus ATM at 4 µg/ml. Conclusion: With the increasing burden of CRKp, the use of C/A with ATM combination seems to be very promising, especially for bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48like carbapenemases.


Assuntos
Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Aztreonam/farmacologia , Ceftazidima/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/genética , Sinergismo Farmacológico , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , beta-Lactamases/metabolismo
10.
Emerg Infect Dis ; 25(9): 1632-1638, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31441424

RESUMO

We aimed to provide updated epidemiologic data on carbapenem-resistant Klebsiella pneumoniae in Portugal by characterizing all isolates (N = 46) recovered during 2013-2018 in a 123-bed hospital in Lisbon. We identified blaKPC-3 (n = 36), blaOXA-181 (n = 9), and blaGES-5 (n = 8) carbapenemase genes and observed co-occurrence of blaKPC-3 and blaGES-5 in 7 isolates. A single GES-5-producing isolate co-produced the extended-spectrum ß-lactamase BEL-1; both corresponding genes were co-located on the same ColE1-like plasmid. The blaOXA-181 gene was always located on an IncX3 plasmid, whereas blaKPC-3 was carried on IncN, IncFII, IncFIB, and IncFIIA plasmid types. The 46 isolates were distributed into 13 pulsotypes and 9 sequence types. All isolates remained susceptible to ceftazidime/avibactam, but some exhibited reduced antimicrobial susceptibility (MIC = 3 mg/L).


Assuntos
Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Hospitais , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Testes de Sensibilidade Microbiana , Portugal/epidemiologia , beta-Lactamases/metabolismo
11.
Biomed Res Int ; 2019: 6736897, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467906

RESUMO

The aim of this study was to investigate the mechanisms responsible for resistance to antimicrobials in a collection of enterobacterial isolates recovered from two hospitals in Saudi Arabia. A total of six strains isolated from different patients showing high resistance to carbapenems was recovered in 2015 from two different hospitals, with four being Klebsiella pneumoniae and two Enterobacter cloacae. All isolates except one K. pneumoniae were resistant to tigecycline, but only one K. pneumoniae was resistant to colistin. All produced a carbapenemase according to the Carba NP test, and all were positive for the EDTA-disk synergy test for detection of MBL. Using PCR followed by sequencing, the four K. pneumoniae isolates produced the carbapenemase NDM-1, while the two E. cloacae isolates produced the carbapenemase VIM-1. Genotyping analysis by Multilocus Sequence Typing (MLST) showed that three out of the four K. pneumoniae isolates were clonally related. They had been recovered from the same hospital and belonged to Sequence Type (ST) ST152. In contrast, the fourth K. pneumoniae isolate belonged to ST572. Noticeably, the NDM-1-producing K. pneumoniae additionally produced an extended-spectrum ß-lactamase (ESBL) of the CTX-M type, together with OXA-1 and TEM-1. Surprisingly, the three clonally related isolates produced different CTX-M variants, namely, CTX-M-3, CTX-M-57, and CTX-M-82, and coproduced QnrB, which confers quinolone resistance, and the 16S rRNA methylase RmtC, which confers high resistance to all aminoglycosides. The AAC(6')-Ib acetyltransferase was detected in both K. pneumoniae and E. cloacae. Mating-out assays using Escherichia coli as recipient were successful for all isolates. The bla NDM-1 gene was always identified on a 70-kb plasmid, whereas the bla VIM-1 gene was located on either a 60-kb or a 150-kb plasmid the two E. cloacae isolates, respectively. To the best of our knowledge, this is the first report of the coexistence of an MBL (NDM-1), an ESBL (CTX-M), a 16S rRNA methylase (RmtC), an acetyltransferase (AAC[6']-Ib), and a quinolone resistance enzyme (QnrB) in K. pneumoniae isolates recovered from different patients during an outbreak in a Saudi Arabian hospital.


Assuntos
Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , beta-Lactamases/genética , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/genética , Enterobacter cloacae/patogenicidade , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Infecções por Klebsiella/genética , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidade , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Arábia Saudita/epidemiologia
12.
Int J Antimicrob Agents ; 54(4): 442-448, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377343

RESUMO

External validation of the INCREMENT-CPE risk score (ICS) for 30-day all-cause mortality is needed. There is also scarce information about whether colistin resistance influences the prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKp) bacteraemia. In this study, the ability of ICS to predict all-cause mortality in the KAPECOR cohort was calculated using the area under the receiver operating characteristic (AUROC) curve. The association of colistin resistance with mortality was studied. The ICS showed an AUROC curve of 0.77 (95% CI 0.68-0.86). A cut-off of 8 points showed 96.8% sensitivity and 50.7% specificity. Mortality of low-risk patients was not different in those treated with monotherapy versus combination therapy. However, mortality of high-risk patients treated with combination therapy (37.8%) was significantly lower than in those treated with monotherapy (68.4%) (P = 0.008). To study the prognostic significance of colistin resistance, 83 selected cases of bacteraemia due to colistin-susceptible CRKp were obtained from the INCREMENT cohort for comparison. Colistin resistance could not be shown to be associated with higher mortality in either the high-risk ICS group [adjusted odds ratio (aOR) = 1.56, 95% CI 0.69-3.33; P = 0.29] or in 37 ICS-matched pairs (aOR = 1.38, 95% CI 0.55-3.42; P = 0.49), or in a sensitivity analysis including only KPC isolates (aOR = 1.81, 95% CI 0.73-4.57; P = 0.20), but the precision of estimates was low. These results validate ICS for all-cause mortality and to optimise targeted therapy for CRKp bacteraemia. Colistin resistance was not clearly associated with increased mortality.


Assuntos
Bacteriemia/mortalidade , Bacteriemia/patologia , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/isolamento & purificação , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Colistina/farmacologia , Farmacorresistência Bacteriana , Feminino , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Análise de Sobrevida
13.
Zhonghua Nei Ke Za Zhi ; 58(8): 566-571, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31365977

RESUMO

Objective: To evaluate the efficacy and safety of different antimicrobial regimens in patients with bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: The clinical date of patients with CRKP bloodstream infections were retrospectively analyzed at the First Affiliated Hospital of Zhejiang University Medical College between January 2017 and January 2018. All subjects were separated into three groups based on antibiotics regimens over 72 hours, including meropenem 2.0 g every 8 hours, tigecycline 200 mg as initial dose and 100 mg every 12 hours, and polymyxin B 1.25 mg/kg every 12 hours as salvage treatment of tigecycline. Results: A total of 86 patients were finally recruited, including 14, 52 and 20 patients in groups of meropenem, tigecycline and polymyxin B salvage, respectively. All of the strains were resistant to meropenem and susceptible to tigecycline and polymyxin B initially, while 2 of them became resistant to tigecycline during treatment. The 28-day mortality was significantly higher in meropenem group (13/14) than that in tigecycline group and polymyxin B salvage group (61.5%, 32/52) and (12/20), respectively (P<0.01), while as no significant difference was seen in the last two groups (χ(2)=0.014, P>0.05). The incidences of hepatic impairment [3.8%(2/52) vs. 1/20] and renal dysfunction (0 vs. 1/20) between tigecycline group and polymyxin B salvage group were both comparable (P>0.05). Conclusion: The meropenem-based therapy is not recommended for CRKP-related bloodstream infections. Tigecycline-based therapy is still disappointing despite salvage use of polymyxin B after 72 hours. Hepatic and nephretic toxicities caused by additional polymyxin B are acceptable.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Meropeném/uso terapêutico , Polimixinas/uso terapêutico , Tigeciclina/uso terapêutico , Antibacterianos/administração & dosagem , Bacteriemia/mortalidade , China/epidemiologia , Farmacorresistência Bacteriana Múltipla , Humanos , Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Resultado do Tratamento , Resistência beta-Lactâmica
14.
Nat Commun ; 10(1): 3517, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388008

RESUMO

New Delhi metallo-ß-lactamase-1 (NDM-1) is the most prevalent type of metallo-ß-lactamase and hydrolyzes almost all clinically used ß-lactam antibiotics. Here we show that the antimicrobial peptide thanatin disrupts the outer membrane of NDM-1-producing bacteria by competitively displacing divalent cations on the outer membrane and inducing the release of lipopolysaccharides. In addition, thanatin inhibits the enzymatic activity of NDM-1 by displacing zinc ions from the active site, and reverses carbapenem resistance in NDM-1-producing bacteria in vitro and in vivo. Thus, thanatin's dual mechanism of action may be useful for combating infections caused by NDM-1-producing pathogens.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Parede Celular/efeitos dos fármacos , Resistência beta-Lactâmica/efeitos dos fármacos , beta-Lactamases/metabolismo , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Carbapenêmicos/farmacologia , Domínio Catalítico/efeitos dos fármacos , Modelos Animais de Doenças , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Concentração Inibidora 50 , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Zinco/metabolismo
16.
BMC Infect Dis ; 19(1): 611, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299943

RESUMO

BACKGROUND: Bloodstream infections (BSI) due to Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) have become an important problem and they are associated with a high mortality rate. The aim of our study was to evaluate the clinical and epidemiological characteristics of KPC-Kp from BSIs. METHODS: In this retrospective cohort study, conducted in a tertiary referral center in Italy, 112 patients with KPC-Kp BSIs diagnosed between February 2011 and December 2015 were identified. We evaluated the mortality at 30 days from the first positive blood culture. Survivor and non-survivor subgroups were compared to identify predictors of mortality. RESULTS: The overall crude mortality was 35%. APACHE II score ≥ 15, septic shock at BSI onset, immunosuppressive therapy during the 30 days before the BSI onset, and the lack of a combination therapy with at least 2 active drugs emerged as independent predictors of mortality. Excluding patients with inadequate therapy, the mortality decreased to 25% while an APACHE II score ≥ 15 and the presence of septic shock remained independently associated with a negative outcome. Two different pulsotypes were identified: pulsotype A belonged to ST512 and carried KPC-3 and pulsotype B belonged to ST307 and carried KPC-2. CONCLUSIONS: This study confirmed a high mortality rate of KPC-Kp BSIs. The outcome is heavily influenced by the patient's clinical conditions. A therapeutic approach including a combination with at least two active drugs in vitro can improve the prognosis, unless patients received an appropriate therapy.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae/enzimologia , beta-Lactamases/metabolismo , Adulto , Idoso , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Feminino , Humanos , Itália/epidemiologia , Estimativa de Kaplan-Meier , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Choque Séptico/complicações , Choque Séptico/diagnóstico , Centros de Atenção Terciária
18.
Eur J Clin Microbiol Infect Dis ; 38(10): 1925-1931, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31278562

RESUMO

Combination therapies are frequently used in the treatment of multidrug-resistant Klebsiella pneumoniae infection without consensus regarding which combination is the most effective. We compared bactericidal titres from sera collected from critically ill patients receiving meropenem plus tigecycline (n = 5), meropenem plus colistin (n = 5), or meropenem, colistin and tigecycline (n = 5) against K. pneumoniae isolates that included ESBL-producing (n = 7) and KPC-producing strains (n = 14) with varying sensitivity patterns to colistin and tigecycline. Meropenem concentrations (Cmin) were measured in all samples by LC-MS/MS, and indexed to respective pathogen MICs to explore differences in patterns of bactericidal activity for two versus three drug combination regimens. All combination regimens achieved higher SBTs against ESBL (median reciprocal titre 128, IQR 32-256) versus KPC (4, IQR 2-32) strains. Sera from patients treated with meropenem-colistin yielded higher median SBTs (256, IQR 64-512) than either meropenem-tigecycline (32, IQR 8-256; P < 0.001). The addition of tigecycline was associated with a lower probability of achieving a reciprocal SBT above 8 when meropenem concentrations were below the MIC (P = 0.04). Although the clinical significance is unknown, sera from patients receiving tigecycline-based combination regimens produce lower serum bactericidal titres against ESBL or KPC-producing K. pneumoniae. SBTs may represent a useful complimentary endpoint for comparing pharmacodynamics of combinations regimens for MDR Enterobacteriaceae.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Meropeném/administração & dosagem , Meropeném/farmacocinética , beta-Lactamases/metabolismo , Idoso , Cromatografia Líquida , Colistina/administração & dosagem , Estado Terminal , Quimioterapia Combinada/métodos , Feminino , Humanos , Klebsiella pneumoniae/enzimologia , Masculino , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Pessoa de Meia-Idade , Soro/química , Espectrometria de Massas em Tandem , Tigeciclina/administração & dosagem
19.
Pol Merkur Lekarski ; 46(276): 251-256, 2019 Jun 28.
Artigo em Polonês | MEDLINE | ID: mdl-31260434

RESUMO

Klebsiella pneumoniae belongs to the Enterobacteriaceae family and is responsible for 70% of human infections. From 20 to 80% strains of Klebsiella pneumoniae reveal resistance to first line antibiotics, including cephalosporins, fluoroquinolones and aminoglycosides, as well as carbapenems. Due to the resistance found in MDR (multidrug resistant) Klebsiella pneumoniae is classified according to the sequence types (ST), which are defined on the basis of the nucleotide sequence in the 7 loci (mdh, infB, tonB, gapA, phoE, pgi, and rpoB). Klebsiella pneumoniae uses several methods to protect against the effects of the human immune system. It affects receptors that recognize patterns expressed on epithelial cells and the immune system that are responsible for initiating signal cascades and phagocytic influences, including Toll-like receptors (TLRs) 2 and 4. Activates interleukins (IL) 12 (IL-12) and IL-23p40 by natural stimulation and leads to a decrease in the level of activation of interferon gamma (IFN-γ), IL-17, tumor necrosis factor (TNF-α) and IL-1ß, resulting in neutrophil and macrophage inflow and induction of humoral and cellular responses. Capsular polysaccharides and other components of the bacterial cell membrane protect it from the natural mechanisms of resistance, making it resistant to beta-defensins against bacteria. Increased virulence of Klebsiella pneumoniae is related to the protein structure associated with the capsule, especially in strains with increased virulence (HV - hypervirulent), lipopolysaccharides (LPS), siderophores and cilia (fimbriae). Today, two main types of Klebsiella pneumoniae strains are distinguished depending on the mechanism of resistance to antibiotics: strains that express beta-lactamases with extended spectrum (ESBL - extended spectrum beta-lactamases) that are resistant to cephalosporins and monobactams and strains that reveal the expression of carbapenemases, which they show resistance to available beta-lactams, including carbapenes. Polymyxins are useful in the treatment of patients infected with Klebsiella pneumoniae NDM (New Delhi metallo-beta-lactamase), where the effectiveness of therapy is greater when colistin is used together with carbapenem or rifampicin or tigecycline. The introduced abivactam in combination with ceftazidime is a promising therapeutic combination in severe infections. Similar clinical assessments were obtained with sulbactam, especially in combination with meropenem and colistin.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Antibacterianos , Carbapenêmicos , Humanos , Infecções por Klebsiella/complicações , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana
20.
Diagn Microbiol Infect Dis ; 95(1): 84-88, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31256940

RESUMO

This study aimed to assess the predictive factors of bacteremia due to hypermucoviscous Klebsiella pneumoniae (hvKP), as well as the mortality. The medical records of 114 patients with K. pneumoniae bacteremia who were divided into the hvKP (n = 24) and non-hvKP (n = 90) groups and were retrospectively reviewed. The male-to-female ratio, age, and underlying disease did not differ between the 2 groups. Mortality was higher among patients in the hvKP bacteremia group than in the non-hvKP bacteremia group (29.2% vs 6.7%). Multivariate analysis showed that the independent predictors associated with hvKP bacteremia were abscess (P = 0.01) and no antibiotic exposure (P = 0.02); thus, early assessment of these conditions is important. For patients with a history of abscess and no antibiotic exposure, it is necessary to administer treatment while keeping the risk of hvKP in mind.


Assuntos
Bacteriemia/epidemiologia , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/fisiologia , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Feminino , Humanos , Japão/epidemiologia , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidade , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Fatores de Virulência/genética
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