scholarly journals Mutant Prevention Concentrations of Four Carbapenems against Gram-Negative Rods

2010 ◽  
Vol 54 (6) ◽  
pp. 2692-2695 ◽  
Author(s):  
Kim Credito ◽  
Klaudia Kosowska-Shick ◽  
Peter C. Appelbaum

ABSTRACT We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ß-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to ≥16. The MPC/MIC ratios for β-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 μg/ml) than those for ß-lactamase-negative strains.

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Po-Yu Liu ◽  
Yu-Lin Lee ◽  
Min-Chi Lu ◽  
Pei-Lan Shao ◽  
Po-Liang Lu ◽  
...  

ABSTRACT A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae (n = 28) and one (20%) carbapenem-resistant E. coli (n = 5) isolate harbored blaKPC (n = 17), blaOXA-48 (n = 2), and blaVIM (n = 1) genes.


2021 ◽  
Vol 10 (9) ◽  
pp. e38410918301
Author(s):  
Cleusa Wanderley de Queiroz Andrade ◽  
Katia Suely Batista Silva ◽  
Mirthes Maria Rodrigues Santana ◽  
Aline Vitória de Oliveira ◽  
Marcos Duarte Guimarães ◽  
...  

Avaliar o perfil bacteriano das amostras de aspirados traqueais e uroculturas de pacientes internados na Sala de Cuidados Intermediários do Hospital Universitário do Vale do São Francisco, Petrolina/PE. Trata-se de um estudo descritivo, quantitativo e retrospectivo envolvendo a análise do perfil microbiológico das amostras coletadas no período de janeiro a dezembro de 2020 pelo Laboratório de Análises Clínicas do Hospital Universitário. Os dados foram tabulados em planilhas do Excel®, sendo feito a análise descritiva com valores percentuais e absolutos. As identificações bacterianas e os antibiogramas foram realizados através do sistema automatizado BD Phoenix ™, seguindo a metodologia do Clinical and Laboratory Standards Institute. Foram coletados 120 aspirados traqueais, sendo 55 positivos (46%) para achados bacterianos; os patógenos mais prevalentes foram: Acinetobacter baumannii (40%), Klebsiella pneumoniae (16%) e Pseudomonas aeruginosa (11%). Em relação às uroculturas, foram realizadas 183, sendo 10 (5,46%) positivas para achados bacterianos; as bactérias mais prevalentes foram: Escherichia coli (40%) e Enterobacter cloacae (20%). A. baumannii apresentou 100% de sensibilidade à colistina e polimixina B nos aspirados traqueias, assim como a K. pneumoniae apresentou à amicacina em todas as amostras coletadas. A E. coli demonstrou certa restência às cefalospororinas, com exceção da cefoxitina, sendo sensível; além disso, teve sensibilidade parcial ao sulfametoxazol+trimetoprima no estudo. O conhecimento do perfil microbiológico das bactérias permite a elaboração de protocolos preventivos e a realização de tratamento efetivos, diminuindo as taxas de mortalidade, o tempo de internação e os custos em saúde.


2021 ◽  
Vol 24 (2) ◽  
pp. 83-86
Author(s):  
Lucian Giubelan ◽  

Objectives. Classification on multiple criteria of Gram-negative bacilli (GNBs) according to antibiotic resistance. Material and method. Retrospective study (January 2017-December 2018) carried out in the Infectious Diseases Clinic from Craiova; GNBs were identified using the Vitek 2 automated system, which subsequently established their sensitivity to antimicrobials; GNBs were classified based on an arbitrary score from 1 (minimum) to 5 (maximum) based on the multiple antibiotic resistance index (MAR), the percentage of multidrug resistant strains (MDR) and the percentage of extended resistance strains (XDR). The final classification represents the sum of the points awarded for each category considered. Results. The following GNBs were considered: Escherichia coli (n = 720), Klebsiella pneumoniae (n = 335), Pseudomonas aeruginosa (n = 139), Proteus mirabilis (n = 60) and Acinetobacter baumannii (n = 29). MAR values are: Acinetobacter baumannii (Ab) – 0.6, Proteus mirabilis (Pm) – 0.52, Pseudomonas aeruginosa (Pa) – 0.51, Klebsiella pneumoniae (Kp) - 0.37 and Escherichia coli (Ec) – 0.23. The percentage of MDR strains is: Pm – 76.67%, Kp – 68.86%, Pa - 58.71%, Ec – 51.94% and Ab – 51.72%; XDR strains were identified for Ab - 17.24% and Pa – 6.47%. The final classification of GNBs is as follows: Pa – 12p, Ab - 11 p, Pm – 7p, Kp – 6p, Ec – 3p. Conclusions. Depending on the resistance profile on multiple criteria, the classification of the studied Gram-negative bacteria is as follows: Pa, Ab, Pm, Kp, Ec.


2014 ◽  
Vol 53 (3) ◽  
pp. 1031-1033 ◽  
Author(s):  
Baixing Ding ◽  
Fupin Hu ◽  
Yang Yang ◽  
Qinglan Guo ◽  
Jinwei Huang ◽  
...  

Carbapenem-resistantEscherichia coli,Klebsiella pneumoniae,Enterobacter aerogenes, andAcinetobacter baumanniiwere isolated from a single patient, each producing different carbapenemases (NDM-1, KPC-2, IMP, and OXA-23, respectively). The NDM-1-producingE. colistrain was preceded by a clonally related carbapenem-susceptible strain a month earlier, suggestingin vivoacquisition ofblaNDM-1.


2021 ◽  
Vol 1 (1) ◽  
pp. 67-76
Author(s):  
Gabriela Ramos Gonçalves  ◽  
Kátia Suely Batista Silva ◽  
Ricardo Santana Lima  ◽  
CARINE FREITAS E SILVA ◽  
Samuel Ricarte de Aquino ◽  
...  

As infecções hospitalares são aquelas adquiridas 48 horas após a admissão hospitalar ou que se manifestam até 3 dias após a alta e que estejam associadas a cuidados em saúde. Este trabalho teve como objetivo analisar o perfil bacteriano de uroculturas coletadas em pacientes internados em um Hospital Universitário. Trata-se de um estudo retrospectivo, descritivo e documental, realizado a partir de planilhas disponibilizadas pelo Laboratório de Análises Clínicas/Setor Microbiologia do Hospital Universitário, provenientes de resultados dos exames realizados no período de janeiro de 2017 a dezembro de 2018. No primeiro ano foram coletadas 242 uroculturas, destas, 12% apresentaram crescimento bacteriano. Em 2018 foram 256, com 15% de positividade. As bactérias mais isoladas foram: Klebsiella pneumoniae, Enterococcus sp., Pseudomonas aeruginosa, Escherichia coli e Acinetobacter baumannii. Klebsiella pneumoniae apresentou resistência a amicacina, imipenem, piperacilia + tazobactam, sendo sensível a linezolida.  O Enterococcus sp. em 2017, foi resistente à ampicilina, ciprofloxacino, vancomicina e nitrofurantoína, porém em 2018 foram sensíveis a estes. A P. aeruginosa foi resistente à ceftazidima, cefepime, imipenem, piperacilina + tazobactam, quinolonas e amicacina e sensível a colistina. A E. coli foi resistente a ampicilina + sulbactam, as quinolonas e sulfametoxazol + trimetoprima, sendo sensível a amoxicilina + clavulonato, nitrofurantoina e piperacilina + tazobactam, cefalosporinas de 2ª geração, aminoglicosídeos e carbapenêmicos. O A. baumannii apresentou resistência para amicacina, gentamicina, imipenem, meropenem, piperacilina + tazobactam e colistina, não apresentando 100% de sensibilidade a nenhum dos antibióticos testados. O conhecimento do perfil bacteriano nas uroculturas é de grande importância, pois poderá nortear o tratamento medicamentoso, contribuindo na desaceleração da seleção de bactérias resistentes.


2021 ◽  
Vol 14 (4) ◽  
pp. 370
Author(s):  
Le Phuong Nguyen ◽  
Chul Soon Park ◽  
Naina Adren Pinto ◽  
Hyunsook Lee ◽  
Hyun Soo Seo ◽  
...  

The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB10-0200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB10-0200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC- producing E. coli and K. pneumoniae, while LCB10-0200 alone was active against ADC-, OXA-, and VIM- producing A. baumannii and P. aeruginosa. Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP- and NDM- producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli, K. pneumoniae.


Author(s):  
Andrea Miró-Canturri ◽  
Rafael Ayerbe-Algaba ◽  
Raquel del Toro ◽  
Jerónimo Pachón ◽  
Younes Smani

AbstractThe development of new strategic therapies for multidrug-resistant bacteria, like the use of non-antimicrobial approaches and/or drugs repurposing to be used as monotherapies or in combination with clinically relevant antibiotics, has become an urgent need. A therapeutic alternative for infections by multidrug-resistant Gram-negative bacilli (MDR-GNB) is immune system modulation to improve the infection clearance. We showed that immunocompetent mice infected by Acinetobacter baumannii, Pseudomonas aeruginosa or Escherichia coli in peritoneal sepsis models and treated with tamoxifen at 80 mg/kg/d for three days reduced the release of MCP-1 and its signalling pathway IL-18 and phosphorylated ERK1/2. This reduction of MCP-1 induced the reduction of migration of inflammatory monocytes and neutrophils from bone marrow to blood. Indeed, the treatment with tamoxifen in murine peritoneal sepsis models reduced the bacterial load in tissues and blood; and increased the mice survival from 0% to 60-100%. Tamoxifen treatment of neutropenic mice infected by these pathogens increased mice survival up to 20-60%. Furthermore, susceptibility and time-kill assays showed that the metabolites of tamoxifen, N-desmethyltamoxifen, hydroxytamoxifen and endoxifen, the three together exhibited MIC90 values of 16 mg/L and were bactericidal against clinical isolates of A. baumannii and E. coli. This antimicrobial activity of tamoxifen metabolites parallels’ an increased membrane permeability of A. baumannii and E. coli without affecting their outer membrane proteins profiles. Together, these data showed that tamoxifen present a therapeutic efficacy against MDR A. baumannii, P. aeruginosa and E. coli in experimental models of infections and can be repurposed as new treatment for GNB infections.ImportanceAntimicrobial resistance in Gram-negative bacilli (GNB) is a global health treat. Drug repurposing, a novel approach involving the search of new indications for FDA approved drugs is gaining interest. Among them, we found the anti-cancer drug tamoxifen, which presents very promising therapeutic efficacy. The current study showed that tamoxifen presents activity in animal models of infection with MDR Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli by modulating the traffic of innate immune system cells and the antibacterial activity presented by its three major metabolites produced in vivo against these GNB. Our results offer a new candidate to be repurposed to treat severe infections caused by these pathogens.


2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Alexander J. Lepak ◽  
Miao Zhao ◽  
Brian VanScoy ◽  
Daniel S. Taylor ◽  
Evelyn Ellis-Grosse ◽  
...  

ABSTRACT Fosfomycin is a broad-spectrum agent with activity against Gram-positive and Gram-negative bacteria, including drug-resistant strains, such as extended-spectrum-beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Gram-negative rods. In the present study, the pharmacokinetic/pharmacodynamic (PK/PD) activity of ZTI-01 (fosfomycin for injection) was evaluated in the neutropenic murine thigh infection model against 5 Escherichia coli, 3 Klebsiella pneumoniae, and 2 Pseudomonas aeruginosa strains, including a subset with ESBL and CR phenotypes. The pharmacokinetics of ZTI-01 were examined in mice after subcutaneous administration of 3.125, 12.5, 50, 200, 400, and 800 mg/kg of body weight. The half-life ranged from 0.51 to 1.1 h, area under the concentration-time curve (AUC0–∞) ranged from 1.4 to 87 mg · h/liter, and maximum concentrations ranged from 0.6 to 42.4 mg/liter. Dose fractionation demonstrated the AUC/MIC ratio to be the PK/PD index most closely linked to efficacy (R 2 = 0.70). Net stasis and bactericidal activity were observed against all strains. Net stasis was observed at 24-h AUC/MIC ratio values of 24, 21, and 15 for E. coli, K., pneumoniae and P. aeruginosa, respectively. For the Enterobacteriaceae group, stasis was noted at mean 24-h AUC/MIC ratio targets of 23 and 1-log kill at 83. Survival in mice infected with E. coli 145 was maximal at 24-h AUC/MIC ratio exposures of 9 to 43, which is comparable to the stasis exposures identified in the PK/PD studies. These results should prove useful for the design of clinical dosing regimens for ZTI-01 in the treatment of serious infections due to Enterobacteriaceae and Pseudomonas.


10.21149/8767 ◽  
2018 ◽  
Vol 60 (2,mar-abr) ◽  
pp. 151
Author(s):  
Consuelo Velázquez-Acosta ◽  
Patricia Cornejo-Juárez ◽  
Patricia Volkow-Fernández

Objetivo. Describir la tendencia de cepas multidrogorre­sistentes (MDR) aisladas en hemocultivos de pacientes con cáncer durante el periodo de 2005 a 2015. Material y métodos. Análisis retrospectivo en el que se procesaron 33 127 hemocultivos. La identificación y la sensibilidad antimicro­bianas se realizaron a través de métodos automatizados WaLK away (Siemens Laboratory Diagnostics) y BD Phoenix (Becton, Dickinson and Company). Se determinaron cepas resistentes de acuerdo con la concentración mínima inhibitoria, según los pa­rámetros del Clinical and Laboratory Standards Institute (CLSI). Resultados. 5 604 (16.9%) aislamientos fueron positivos, con 6 397 aislamientos, 3 732 (58.4%) bacilos gramnegativos, 2 355 (36.9%) cocos grampositivos, 179 (2.7%) levaduras y 126 (1.9%) bacilos grampositivos. Escherichia coli (n=1 591, 24.5%) fue la bacteria más frecuente, 652 (41%) productoras de beta-lactamasas de espectro-extendido (BLEE); Enterococ­cus faecium 143 (2.1%), 45 (31.5%) resistente a vancomicina; Staphylococcus aureus 571 (8.7%), 121 (21.2%) resistentes a meticilina (SARM); Klebsiella pneumoniae 367 (5.6%), 41 (11.2%) BLEE, Acinetobacter baumannii 96 (1.4%), 23 (24%) MDR; Pseudomonas aeruginosa 384 (5.6%), 43 (11.2%) MDR. Las cepas MDR se aislaron más frecuentemente en pacientes con neoplasias hematológicas en comparación con tumores sólidos; SARM (RM=4.48, IC95% 2.9-6.8); E. coli BLEE (RM=1.3, IC95% 1.10-1.65) y A. baumannii-MDR (RM=3.2, IC95% 1.2-8.3). Conclusiones. Se observó un aislamiento significativamente mayor de cepas E-ESKAPE MDR en pacientes con neoplasias hematológicas.


2017 ◽  
Vol 1 (2) ◽  
pp. 48-60
Author(s):  
A.G. Salmanov ◽  
A.V. Rudenko

Мета роботи — вивчити резистентність до антибіотиків бактеріальних збудників інфекцій сечових шляхів (ІСШ), виділених у пацієнтів урологічного стаціонару в м. Києві. Матеріали і методи. Досліджено 1612 штамів бактерій, виділених із сечі хворих з ІСШ (цистит, уретрит, пієлонефрит), госпіталізованих в урологічне відділення ДУ «Інститут урології НАМН України» у м. Києві протягом 2016 р. Серед пацієнтів переважали жінки — 1201 (74,5 %). Вік хворих становив від 17 до 74 років. Для збору даних використано медичну документацію лікарні. Мікробіологічні дослідження виконано у лабораторії мікробіології ДУ «Інститут урології НАМН України». Аналізували результати культурального дослідження зразків сечі, зібраних за наявності клінічних ознак ІСШ. Дослідження клінічного матеріалу та інтерпретацію отриманих результатів проводили загальноприйнятими методами. Вивчено чутливість уропатогенів до 31 антибіотика дискодифузійним методом відповідно до рекомендацій Інституту клінічних та лабораторних стандартів США (Clinical and Laboratory Standards Institute (CLSI)). Результати та обговорення. Аналіз мікробного спектра сечі виявив домінування серед уропатогенів штамів Escherichia coli (32,0 %), Enterococcus faecalis (19,5 %), Klebsiella pneumoniae (10,9 %), Staphylococcus epidermidis (8,9 %), S. haemolyticus (6,5 %) та Pseudomonas aeruginosa (6,4 %). Частка Enterococcus faecium, Enterobacter aerogenes і Streptococcus viridans становила відповідно 2,5, 2,2 і 1,6 %, Enterobacter cloacae, Klebsiella oxytoca, Acinetobacter baumannii, Proteus vulgaris та Providencia rettgeri — менше 1,0 %. У більшості випадків (69,7 %) мікроорганізми виділено у монокультурі, у решті випадків — у мікробних асоціа- ціях. Високу резистентність до тестованих антибіотиків виявили штами E. aerogenes (45,1 %), E. cloacae (45,7 %), E. faecium (40,9 %), E. faecalis (40,7 %), E. coli (39,9 %), P. aeruginosa (34,0 %), K. pneumoniae (28,6 %). Найбільш активними до уропатогенів були іміпенем (E. coli — 87,6 %, P. aeruginosa — 75,7 %, E. cloacae — 67,3 %, E. aerogenes — 72,6 %, K. pneumoniae — 93,2 %), меропенем (E. coli — 89,1 %, P. aeruginosa — 76,7 %, K. pneumoniae — 82,6 %), лефлоцин (E. coli — 74,5 %, ентерококи — 78,7 %, P. aeruginosa — 76,7 %, E. cloacae — 73,9 %, E. aerogenes — 80,4 %, K. pneumoniae — 83,5 %), амоксицилін/клавуланат (ентерококи — 84,6 %), фурагін (ентерококи — 82,6 %), цефоперазон (K. pneumoniae — 89,2 %, P. aeruginosa — 73,8 %), цефтріаксон (K. pneumoniae — 80,1 %). Висновки. Антибіотикорезистентність збудників ІСШ — важлива терапевтична проблема. Найбільшою активністю до уропатогенів характеризуються іміпенем, меропенем, лефлоцин, амоксицилін/ клавуланат, фурагін, цефоперазон, цефтріаксон, які можна розглядати як препарат вибору для призначення стартової терапії ІСШ. Необхідно здійснювати постійний моніторинг за резистентністю до дії антибіотиків. Політику використання антибіотиків у кожному стаціонарі слід визначати залежно від локальних даних щодо резистентності до протимікробних препаратів.


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