scholarly journals Definitive Cefazolin Therapy for Stabilized Adults with Community-Onset Escherichia coli, Klebsiella Species, and Proteus mirabilis Bacteremia: MIC Matters

2020 ◽  
Vol 9 (1) ◽  
pp. 157 ◽  
Author(s):  
Chih-Chia Hsieh ◽  
Po-Lin Chen ◽  
Chung-Hsun Lee ◽  
Chao-Yung Yang ◽  
Ching-Chi Lee ◽  
...  

Background: Cefazolin is in vitro active against wild isolates of Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP), but clinical evidence supporting the contemporary susceptibility breakpoint issued by the Clinical and Laboratory Standards Institute (CLSI) are limited. Methods: Between 2010 and 2015, adults with monomicrobial community-onset EKP bacteremia with definitive cefazolin treatment (DCT) at two hospitals were analyzed. Cefazolin minimum inhibitory concentrations (MICs) were correlated with clinical outcomes, including primary (treatment failure of DCT) and secondary (30-day mortality after bacteremia onset, recurrent bacteremia, and mortality within 90 days after the end of DCT) outcomes. Results: Overall, 466 bacteremic episodes, including 340 (76.2%) episodes due to E. coli, 90 (20.2%) Klebsiella species, and 16 (3.6%) P. mirabilis isolates, were analyzed. The mean age of these patients was 67.8 years and female-predominated (68.4%). A crude 15- and 30-day mortality rate was 0.7% and 2.2%, respectively, and 11.2% experienced treatment failure of DCT. A significant linear-by-linear association of cefazolin MICs, with the rate of treatment failure, 30-day crude mortality, recurrent bacteremia or 90-day mortality after the DCT was present (all γ = 1.00, p = 0.01). After adjustment, the significant impact of cefazolin MIC breakpoint on treatment failure and 30-day crude mortality was most evident in 2 mg/L (>2 mg/L vs. ≤2 mg/L; adjusted hazard ratio, 3.69 and 4.79; p < 0.001 and 0.02, respectively). Conclusion: For stabilized patients with community-onset EKP bacteremia after appropriate empirical antimicrobial therapy, cefazolin might be recommended as a definitive therapy for cefazolin-susceptible EKP bacteremia, based on the contemporary CLSI breakpoint.

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 112 ◽  
Author(s):  
Hyeri Seok ◽  
Ji Young Choi ◽  
Yu Mi Wi ◽  
Dae Won Park ◽  
Kyong Ran Peck ◽  
...  

We investigated fosfomycin susceptibility in Escherichia coli clinical isolates from South Korea, including community-onset, hospital-onset, and long-term care facility (LTCF)-onset isolates. The resistance mechanisms and genotypes of fosfomycin-resistant isolates were also identified. Finally, the in vitro efficacy of combinations of fosfomycin with other antibiotics were examined in susceptible or extended spectrum β-lactamase (ESBL)-producing E. coli isolates. The fosfomycin resistance rate was 6.7% and was significantly higher in LTCF-onset isolates than community-onset and hospital-onset isolates. Twenty-one sequence types (STs) were identified among 19 fosfomycin-resistant E. coli isolates, showing diverse genotypes. fosA3 was found in only two isolates, and diverse genetic variations were identified in three genes associated with fosfomycin resistance, namely, GlpT, UhpT, and MurA. Some fosfomycin-resistant E. coli isolates carried no mutations. In vitro time-kill assays showed that fosfomycin alone did not exhibit an excellent killing activity, compared with ciprofloxacin in susceptible isolates and with ertapenem in ESBL producers. However, combining fosfomycin with cefixime or piperacillin-tazobactam eradicated susceptible or ESBL-producing isolates, respectively, even with 0.5× minimum inhibitory concentrations. Overall, we found a relatively high fosfomycin resistance rate in E. coli isolates from South Korea. Based on their genotypes and resistance mechanisms, most of the fosfomycin-resistant E. coli isolates might occur independently. Antibiotic combinations with fosfomycin could be a suitable therapeutic option for infections caused by E. coli isolates.


1983 ◽  
Vol 29 (12) ◽  
pp. 1650-1652
Author(s):  
M. Coste ◽  
L. Escoula

In this work, the authors studied in vitro potential interactions between bacteria and antibiotics. Colistin and ampicillin were introduced to ampicillin-resistant Escherichia coli and ampicillin activity was measured. Two layers of agar media were used. The lower layer contained E. coli and colistin. The superficial layer was sown with indicating bacteria (ampicillin-sensitive Proteus mirabilis). Ampicillin activity was evaluated on the upper layer with impregnated disks. By this technique, it was ascertained that ampicillin degradation increased with colistin concentration. In this case, colistin may favour interactions of intracellular beta-lactamases on ampicillin.


2016 ◽  
Vol 11 (38) ◽  
pp. 1-12 ◽  
Author(s):  
Débora Monteiro dos Santos Alves ◽  
Marcos Krahe Edelweiss ◽  
Lúcio José Botelho

Objetivo: Determinar a frequência de isolamento dos uropatógenos e avaliar o perfil de sensibilidade antimicrobiana in vitro das bactérias isoladas em uroculturas de pacientes ambulatoriais atendidos em Florianópolis no ano de 2014, correlacionando tais dados com sexo e idade do paciente. Métodos: Estudo observacional, descritivo do tipo transversal, que incluiu uroculturas positivas de pacientes ambulatoriais realizadas em um único laboratório seguindo a mesma metodologia. Realizaram-se análises de estatísticas descritivas e testes de associação entre as variáveis classificatórias: sexo, idade, agente etiológico e sensibilidade aos antimicrobianos. Resultados: Foram registradas 1035 uroculturas positivas, das quais 89,66% de pacientes femininas. Microrganismos Gram-negativos foram os patógenos mais isolados, com destaque para a Escherichia coli (77,10%), principal agente causal. Proteus mirabilis foi significativamente mais prevalente no sexo masculino e o principal microrganismo isolado nas uroculturas dos meninos de 1 a 5 anos. A E. coli foi significativamente mais prevalente no sexo feminino e apresentou o perfil mais amplo de resistência. Evidenciaram-se diferenças estatisticamente significativas nas resistências às fluoroquinolonas entre os gêneros, com maiores prevalências de resistência em homens e entre as faixas etárias, com maior resistência entre idosos. Conclusões: Idade e sexo são variáveis determinantes na frequência de isolamento dos uropatógenos e na prevalência da susceptibilidade antimicrobiana; e os microrganismos mais prevalentes já não respondem satisfatoriamente a parte dos antimicrobianos amplamente utilizados. É fundamental que o médico considere tais informações no momento da decisão terapêutica e preze pelo uso racional dos antimicrobianos, sobretudo aqueles de largo espectro como as fluoroquinolonas.


2015 ◽  
Vol 8 (3) ◽  
pp. 493
Author(s):  
Renata Soares Da Silva ◽  
Karla Maria Santos De Oliveira ◽  
Giani Maria Cavalcante

Úlceras crônicas são suscetíveis à infecção devido à perda estéril da função de barreira inata da pele e dos anexos cutâneos, facilitando o desenvolvimento de comunidades microbianas. O objetivo do estudo foi investigar a suscetibilidade de bactérias associadas a úlceras crônicas aos extratos brutos de Prosopis juliflora. Os testes in vitro foram realizados com extratos brutos das folhas e casca do caule contra as estirpes de Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923) e Proteus mirabilis (ATCC 7002), por meio de ensaio de difusão em agar com poço e determinação da Concentrações Inibitórias Mínimas (MIC). Os resultados mostraram que as estirpes de E. coli, P. aeruginosa, S. aureus e P. mirabilis foram mais susceptíveis aos extratos brutos da folha, com diâmetro de zona de inibição de 21,0; 33,0; 20,0; 21,0 mm, respectivamente, enquanto, E. coli e S. aureus foram mais susceptíveis aos extratos brutos da casca do caule, com diâmetro da zona de inibição de 21,5 e 20,0 mm, respectivamente. Os melhores valores de CIM foram registrados para EBF de P. juliflora. Estudo químico para a extração e o isolamento de compostos ativos é recomendado para realização de ensaios in vitro para investigar a atividade antimicrobiana destes compostos.


2008 ◽  
Vol 29 (1) ◽  
pp. 80-82 ◽  
Author(s):  
Anucha Apisarnthanarak ◽  
Patarachai Kiratisin ◽  
Piyawan Saifon ◽  
Rungrueng Kitphati ◽  
Surang Dejsirilert ◽  
...  

A matched case-control study was performed to identify predictors of mortality among patients (n = 46) with community-onset infections due to extended-spectrum β-lactamase-producing Escherichia coli in Thailand. The crude mortality rate was 30%. By multivariable analysis, community-onset bloodstream infection due to extended-spectrum β-lactamase-producing E. coli was the sole predictor of mortality (adjusted odds ratio, 41.3 [95% confidence interval, 4.3-69.4]; P = .001).


2020 ◽  
Vol 24 (19) ◽  
pp. 2272-2282
Author(s):  
Vu Ngoc Toan ◽  
Nguyen Minh Tri ◽  
Nguyen Dinh Thanh

Several 6- and 7-alkoxy-2-oxo-2H-chromene-4-carbaldehydes were prepared from corresponding alkyl ethers of 6- and 7-hydroxy-4-methyl-2-oxo-2H-chromen-2-ones by oxidation using selenium dioxide. 6- and 7-Alkoxy-4-methyl-2H-chromenes were obtained with yields of 57-85%. Corresponding 4-carbaldehyde derivatives were prepared with yields of 41-67%. Thiosemicarbazones of these aldehydes with D-galactose moiety were synthesized by reaction of these aldehydes with N-(2,3,4,6-tetra-O-acetyl-β-Dgalactopyranosyl) thiosemicarbazide with yields of 62-74%. These thiosemicarbazones were screened for their antibacterial and antifungal activities in vitro against bacteria, such as Staphylococcus aureus, Escherichia coli, and fungi, such as Aspergillus niger, Candida albicans. Several compounds exhibited strong inhibitory activity with MIC values of 0.78- 1.56 μM, including 8a (against S. aureus, E. coli, and C. albicans), 8d (against E. coli and A. niger), 9a (against S. aureus), and 9c (against S. aureus and C. albicans).


1998 ◽  
Vol 64 (12) ◽  
pp. 4862-4869 ◽  
Author(s):  
Jörg F. Rippmann ◽  
Michaela Klein ◽  
Christian Hoischen ◽  
Bodo Brocks ◽  
Wolfgang J. Rettig ◽  
...  

ABSTRACT Recently it has been demonstrated that L-form cells ofProteus mirabilis (L VI), which lack a periplasmic compartment, can be efficiently used in the production and secretion of heterologous proteins. In search of novel expression systems for recombinant antibodies, we compared levels of single-chain variable-fragment (scFv) production in Escherichia coliJM109 and P. mirabilis L VI, which express four distinct scFvs of potential clinical interest that show differences in levels of expression and in their tendencies to form aggregates upon periplasmic expression. Production of all analyzed scFvs in E. coli was limited by the severe toxic effect of the heterologous product as indicated by inhibition of culture growth and the formation of insoluble aggregates in the periplasmic space, limiting the yield of active product. In contrast, the L-form cells exhibited nearly unlimited growth under the tested production conditions for all scFvs examined. Moreover, expression experiments with P. mirabilis L VI led to scFv concentrations in the range of 40 to 200 mg per liter of culture medium (corresponding to volume yields 33- to 160-fold higher than those with E. coli JM109), depending on the expressed antibody. In a translocation inhibition experiment the secretion of the scFv constructs was shown to be an active transport coupled to the signal cleavage. We suppose that this direct release of the newly synthesized product into a large volume of the growth medium favors folding into the native active structure. The limited aggregation of scFv observed in the P. mirabilis L VI supernatant (occurring in a first-order-kinetics manner) was found to be due to intrinsic features of the scFv and not related to the expression process of the host cells. The P. mirabilis L VI supernatant was found to be advantageous for scFv purification. A two-step chromatography procedure led to homogeneous scFv with high antigen binding activity as revealed from binding experiments with eukaryotic cells.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaitlin S. Witherell ◽  
Jason Price ◽  
Ashok D. Bandaranayake ◽  
James Olson ◽  
Douglas R. Call

AbstractMultidrug-resistant bacteria are a growing global concern, and with increasingly prevalent resistance to last line antibiotics such as colistin, it is imperative that alternative treatment options are identified. Herein we investigated the mechanism of action of a novel antimicrobial peptide (CDP-B11) and its effectiveness against multidrug-resistant bacteria including Escherichia coli #0346, which harbors multiple antibiotic-resistance genes, including mobilized colistin resistance gene (mcr-1). Bacterial membrane potential and membrane integrity assays, measured by flow cytometry, were used to test membrane disruption. Bacterial growth inhibition assays and time to kill assays measured the effectiveness of CDP-B11 alone and in combination with colistin against E. coli #0346 and other bacteria. Hemolysis assays were used to quantify the hemolytic effects of CDP-B11 alone and in combination with colistin. Findings show CDP-B11 disrupts the outer membrane of E. coli #0346. CDP-B11 with colistin inhibits the growth of E. coli #0346 at ≥ 10× lower colistin concentrations compared to colistin alone in Mueller–Hinton media and M9 media. Growth is significantly inhibited in other clinically relevant strains, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In rich media and minimal media, the drug combination kills bacteria at a lower colistin concentration (1.25 μg/mL) compared to colistin alone (2.5 μg/mL). In minimal media, the combination is bactericidal with killing accelerated by up to 2 h compared to colistin alone. Importantly, no significant red blood hemolysis is evident for CDP-B11 alone or in combination with colistin. The characteristics of CDP-B11 presented here indicate that it can be used as a potential monotherapy or as combination therapy with colistin for the treatment of multidrug-resistant infections, including colistin-resistant infections.


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