Aminoglycosides for Treatment of Bacteremia Due to Carbapenem-Resistant Klebsiella pneumoniae

ABSTRACTAminoglycoside treatment of carbapenem-resistant (CR)Klebsiella pneumoniaebacteremia was associated with a 70% rate (23/33) of 30-day survival. Successful treatment was associated with sources of bacteremia amenable to reliable aminoglycoside pharmacokinetics (P= 0.037), acute physiology and chronic health evaluation II (APACHE II) scores of <20 (P= 0.16), and nonfatal underlying diseases (P= 0.015). Success rates were 78% and 100% if ≥2 and all 3 factors were present, respectively. Clinicians may consider the use of aminoglycosides against CRK. pneumoniaebacteremia if strains are susceptible and the sources of infection are amenable to reliable pharmacokinetics.

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Successful Treatment of Carbapenemase-Producing Pandrug-Resistant Klebsiella pneumoniae Bacteremia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00655-15 ◽

2015 ◽

Vol 59 (10) ◽

pp. 5903-5908 ◽

Cited By ~ 34

Author(s):

Jose F. Camargo ◽

Jacques Simkins ◽

Thiago Beduschi ◽

Akin Tekin ◽

Laura Aragon ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Successful Treatment ◽

Resistant Isolate ◽

Content Type ◽

Carbapenem Resistant ◽

Prolonged Hospitalization ◽

Intestinal Transplant

ABSTRACTNew antibiotic options are urgently needed for the treatment of carbapenem-resistantEnterobacteriaceaeinfections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate ofKlebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.

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Prognostic Value of Charlton’s Weighted Index of Capabilities Combined with Chronic Health Evaluation II Score in COVID-19：a retrospective cohort study

10.21203/rs.3.rs-22479/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Yali Qian ◽

Zhuo Li ◽

Ziqiang Du ◽

Yanfang Zhu ◽

Hongjun Miao

Keyword(s):

Hospital Mortality ◽

Characteristic Curve ◽

Chronic Health Evaluation ◽

Apache Ii ◽

P Value ◽

Health Evaluation ◽

Joint Detection ◽

Chronic Health ◽

Weighted Index ◽

Underlying Diseases

Abstract Background: Since December 2019, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across the world. Age and underlying diseases have been reported as predictors of mortality in 2019-nCoV infection. Charlson's weighted index of comorbidities (WIC) and acute physiology and chronic health evaluation (APACHE) II are two frequently-used measures of comorbidity. In this study, we have assessed the performance of WIC and APACHE II in predicting the mortality of COVID-19 patients.Methods: A total of 76 adult patients with COVID-19 were admitted to a designated hospital in Huangshi province from 1 January 2020 to 29 February 2020. Clinical data including age, gender, underlying diseases, and hospital mortality were collected. The APACHE II and WIC scores were assessed within the first 24 hours of admission. Univariate and multiple logistic regression analyses were used to compare the performance of WIC, APACHE II, and joint detection. The area under the receiver operating characteristic curve (AUC) was used to predict the hospital mortality. Results: Of the 76 enrolled patients, 57 patients survived, and 19 died. The surviving patients had significantly lower WIC and APACHE II than the non-surviving patients (p-value < 0.05). The AUC for the hospital mortality was 0.814 (95% confidence interval (CI) 0.705-0.923) of WIC, 0.854 (95% CI 0.705-0.956) of APACHE II and 0.891(95% CI 0.830-0.966) for the joint detection. The diagnostic value of the joint detection was found to be better than that of WIC (p-value= 0.002) or APACHE II (p-value = 0.042). Conclusions: The WIC and APACHE II scores might serve as independent determinants for the hospital mortality associated with COVID-19 patients. The combined use of WIC and APACHE II is more predictive than individuals．

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Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00883-17 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 146

Author(s):

Ryan K. Shields ◽

M. Hong Nguyen ◽

Liang Chen ◽

Ellen G. Press ◽

Brian A. Potoski ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Clinical Success ◽

Severity Of Illness ◽

Content Type ◽

Treatment Groups ◽

Treatment Regimens ◽

Carbapenem Resistant ◽

Underlying Diseases

ABSTRACT There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success (P = 0.006) and survival (P = 0.01) than other regimens. Across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics (97% produced K. pneumoniae carbapenemase). Aminoglycoside- and colistin-containing regimens were associated with increased rates of nephrotoxicity (P = 0.002).

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Emergence of OXA-232 Carbapenemase-Producing Klebsiella pneumoniae That Carries a pLVPK-Like Virulence Plasmid among Elderly Patients in China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02246-18 ◽

2018 ◽

Vol 63 (3) ◽

Cited By ~ 14

Author(s):

Lingbin Shu ◽

Ning Dong ◽

Jun Lu ◽

Zhiwei Zheng ◽

Jie Hu ◽

...

Keyword(s):

Multidrug Resistance ◽

Klebsiella Pneumoniae ◽

Elderly Patients ◽

Active Surveillance ◽

Antimicrobial Therapy ◽

Sequence Type ◽

Virulence Plasmid ◽

Content Type ◽

Carbapenem Resistant ◽

Underlying Diseases

ABSTRACT This study reported the clonal dissemination of OXA-232-producing sequence type 15 (ST15) carbapenem-resistant Klebsiella pneumoniae among elderly patients in China. All patients were immunocompromised, suffered from multiple underlying diseases, and were hospitalized for a prolonged period; however, they slowly recovered on antimicrobial therapy. The blaOXA-232 gene was in a 6.1-kb ColKP3-type nonconjugative plasmid. The strains displayed a multidrug resistance phenotype and were not hypervirulent despite harboring a virulence plasmid. Active surveillance should be enforced to control further transmission.

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Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Chromosomal Integration of Plasmid DNA

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00404-17 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 2

Author(s):

Astrid V. Cienfuegos-Gallet ◽

Liang Chen ◽

Barry N. Kreiswirth ◽

J. Natalia Jiménez

Keyword(s):

Klebsiella Pneumoniae ◽

Plasmid Dna ◽

Clonal Expansion ◽

Genetic Alterations ◽

Sequence Type ◽

Chromosomal Integration ◽

Colistin Resistance ◽

Content Type ◽

Carbapenem Resistant ◽

Single Locus Variant

ABSTRACT Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB. Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting that the colistin resistance is mediated by chromosomal integration of plasmid DNA.

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Análise de eventos adversos em pacientes internados em unidade de terapia intensiva

Acta Paulista de Enfermagem ◽

10.1590/1982-0194201700026 ◽

2017 ◽

Vol 30 (2) ◽

pp. 168-173

Author(s):

Daniela Benevides Ortega ◽

Maria D’Innocenzo ◽

Lucia Marta Giunta da Silva ◽

Elena Bohomol

Keyword(s):

Chronic Health Evaluation ◽

Apache Ii ◽

Health Evaluation ◽

Chronic Health ◽

Terapia Intensiva

Resumo Objetivo Avaliar a incidência de eventos adversos e associá-los com a carga de trabalho de enfermagem, o dimensionamento da equipe de enfermagem e o perfil de gravidade do paciente. Métodos Foi realizado um estudo transversal, prospectivo, com abordagem quantitativa, em 304 pacientes consecutivos internados em Unidade de Terapia Intensiva geral de um hospital privado, admitidos entre setembro e dezembro de 2013 (quatro meses). Resultados Ocorreram 39 eventos adversos sendo a lesão por pressão a mais prevalente. Os pacientes que apresentaram algum evento tiveram maior média de idade, maior prevalência de internações clínicas, internações mais prolongadas, maior escala Acute Physiology and Chronic Health Evaluation (APACHE) II, maior pontuação do Nursing Activities Score (NAS), menor escore na escala de Braden e menor escala de Glasgow e não tiveram diferenças significantes em relação ao dimensionamento da equipe de enfermagem. Conclusão Houve maior incidência de eventos adversos em pacientes que exibiram um perfil de maior risco e gravidade identificados por meio de escalas preditoras.

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Impacto de la bacteriemia en una cohorte de pacientes con neumonía neumocócica

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37132012000400003 ◽

2012 ◽

Vol 38 (4) ◽

pp. 422-430 ◽

Cited By ~ 7

Author(s):

Ileana Palma ◽

Ricardo Mosquera ◽

Carmen Demier ◽

Carlos Vay ◽

Angela Famiglietti ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Pneumonia Severity Index ◽

Severity Index ◽

Chronic Health Evaluation ◽

Apache Ii ◽

Health Evaluation ◽

Pneumonia Severity ◽

Chronic Health

OBJETIVO: Bacteriemia es la forma invasiva más común de neumonía adquirida en la comunidad (NAC) por Streptococcus pneumoniae. Investigamos si la bacteriemia en NAC neumocócica empeora los resultados y si ella guarda relación con la vacunación antineumocócica (VAN). MÉTODOS: Análisis secundario de una cohorte de pacientes con NAC neumocócica confirmada por cultivo de sangre o esputo o antígeno urinario. Se registraron datos demográficos, clínicos, radiográficos y de laboratorio, escores Acute Physiology and Chronic Health Evaluation II (APACHE II) y pneumonia severity index (PSI), comorbilidades y antecedente de VAN. Se compararon pacientes con NAC neumocócica bacteriémica (NNB) vs. no bacteriémica (NNNB). RESULTADOS: Cuarenta y siete pacientes tenían NNB y 71 NNNB (45 por cultivo de esputo y 26 por antígeno urinario); 107 tenían alguna indicación de VAN. Ningún paciente con NNB, pero 9 con NNNB, habían recibido VAN (p = 0,043). Los pacientes con NNB eran mayores (76,4 ± 11,5 vs. 67,5 ± 20,9 años), tenían mayor APACHE II (16,4 ± 4,6 vs. 14,1 ± 6,5) y PSI (129,5 ± 36 vs. 105,2 ± 45), más frecuentemente cardiopatía e insuficiencia renal crónica e internación en UTI (42,5% vs. 22,5%) y menor hematocrito (35,7 ± 5,8 vs. 38,6 ± 6,7%) y sodio plasmático (133,9 ± 6,0 vs. 137,1 ± 5,5 mEq/L). La mortalidad fue similar (29,8% vs. 28,2%). CONCLUSIONES: Los niveles de VAN (8,4%) en esta población con alto riesgo de NAC por S. pneumoniae fueron extremadamente bajos. Los pacientes con NNB estaban más graves, pero la mortalidad fue similar entre los dos grupos. La VAN reduce la incidencia de NNB y es razonable incrementar el nivel de vacunación de la población en riesgo.

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Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States

mBio ◽

10.1128/mbio.02881-20 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Victor I. Band ◽

Sarah W. Satola ◽

Richard D. Smith ◽

David A. Hufnagel ◽

Chris Bower ◽

...

Keyword(s):

United States ◽

Klebsiella Pneumoniae ◽

Diagnostic Testing ◽

Cladistic Analysis ◽

The United States ◽

Clinical Diagnostics ◽

Infection Model ◽

Content Type ◽

Carbapenem Resistant ◽

Clinical Diagnostic

ABSTRACT Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States. IMPORTANCE Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance to colistin was more common than conventional resistance and was overwhelmingly misclassified as susceptibility by clinical diagnostic testing. Higher proportions of colistin heteroresistance observed in certain Enterobacter species and clustering among heteroresistant Klebsiella pneumoniae strains may inform colistin treatment recommendations. Overall, the rate of colistin nonsusceptibility was more than double the level detected by clinical diagnostics, suggesting that the prevalence of colistin nonsusceptibility among CRE may be higher than currently appreciated in the United States.

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Epigenomics, genomics, resistome, mobilome, virulome and evolutionary phylogenomics of carbapenem-resistant Klebsiella pneumoniae clinical strains

Microbial Genomics ◽

10.1099/mgen.0.000474 ◽

2020 ◽

Vol 6 (12) ◽

Author(s):

Katlego Kopotsa ◽

Nontombi M. Mbelle ◽

John Osei Sekyere

Keyword(s):

Klebsiella Pneumoniae ◽

Multidrug Resistant ◽

Type I ◽

Bacteriophage Therapy ◽

Content Type ◽

Carbapenem Resistant ◽

Plasmid Replicon ◽

Size Number ◽

Plasmid Size ◽

Epidemiological Trends

Carbapenem-resistant Klebsiella pneumoniae (CRKP) remains a major clinical pathogen and public health threat with few therapeutic options. The mobilome, resistome, methylome, virulome and phylogeography of CRKP in South Africa and globally were characterized. CRKP collected in 2018 were subjected to antimicrobial susceptibility testing, screening by multiplex PCR, genotyping by repetitive element palindromic (REP)-PCR, plasmid size, number, incompatibility and mobility analyses, and PacBio’s SMRT sequencing (n=6). There were 56 multidrug-resistant CRKP, having bla OXA-48-like and bla NDM-1/7 carbapenemases on self-transmissible IncF, A/C, IncL/M and IncX3 plasmids endowed with prophages, traT, resistance islands, and type I and II restriction modification systems (RMS). Plasmids and clades detected in this study were respectively related to globally established/disseminated plasmids clades/clones, evincing transboundary horizontal and vertical dissemination. Reduced susceptibility to colistin occurred in 23 strains. Common clones included ST307, ST607, ST17, ST39 and ST3559. IncFIIk virulent plasmid replicon was present in 56 strains. Whole-genome sequencing of six strains revealed least 41 virulence genes, extensive ompK36 mutations, and four different K- and O-loci types: KL2, KL25, KL27, KL102, O1, O2, O4 and O5. Types I, II and III RMS, conferring m6A (G A TC, G A TGNNNNNNTTG, CA A NNNNNNCATC motifs) and m4C (C C WGG) modifications on chromosomes and plasmids, were found. The nature of plasmid-mediated, clonal and multi-clonal dissemination of blaOXA-48-like and blaNDM-1 mirrors epidemiological trends observed for closely related plasmids and sequence types internationally. Worryingly, the presence of both bla OXA-48 and bla NDM-1 in the same isolates was observed. Plasmid-mediated transmission of RMS, virulome and prophages influence bacterial evolution, epidemiology, pathogenicity and resistance, threatening infection treatment. The influence of RMS on antimicrobial and bacteriophage therapy needs urgent investigation.

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