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    Initial Concentration-Time Profile of Gentamicin Determines Efficacy against Enterobacter cloacae ATCC 13047
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    Abstract:
    In vitro studies were designed to investigate the influence of peak drug concentration (Cmax), the area under the concentration-time curve (AUC), and, consequently, the trough concentration on the bactericidal effects of gentamicin against Enterobacter cloacae (MIC, 0.5 mg/liter) by simulating bolus versus infusion administration and bolus dosing with altered drug clearance. Bacteria in the lag phase were exposed to gentamicin concentration-time profiles modelling either bolus or infusion dosing (AUC constant, Cmax changing) with 30-min postdose peak concentrations (Cpeak30) of 4, 6, 8, and 10 mg/liter or bolus dosing with normal and double drug clearance (Cmax constant, AUC changing) corresponding to normal clearance profiles with Cpeak30 of 6 and 8 mg/liter. Exposure to gentamicin caused early bactericidal effects apparent by 2 h, followed by variable bacteriostatic and recovery phases. Exposure to bolus profiles resulted in greater bactericidal activity than the corresponding infusion profile up to a Cpeak30 of 8 mg/liter. At a Cpeak30 of 10 mg/liter, there were no differences in bactericidal effect. Double clearance profiles had a reduced bactericidal effect at 6 mg/liter compared to the corresponding normal clearance profile, but no differences in bactericidal effect were observed for 8-mg/liter double and normal clearance profiles. These results suggest that the initial exposure (i.e., 0 to 30 min) is a more important determinant for bacterial killing than the AUC or trough concentration for this bacterium. Subject to confirmation of these findings with other gram-negative bacteria, to optimize aminoglycoside efficacy the initial exposure (Cmax) should be maximized by giving higher doses or bolus administration at intervals which may not produce detectable trough concentrations. Clinical trials with a broad range of patients, especially those with higher clearance, would confirm these in vitro observations and define optimal dosing recommendations.
    Keywords:
    Liter
    Enterobacter cloacae
    Bolus (digestion)
    Pharmacodynamics
    This paper study the ability of Enterobacter cloacae for degrading crude oil in contaminated water. Six isolates of E. cloacae were isolated from hydrocarbon contaminated soil and water of different sites. The isolate E. cloacae E1 showed the highest emulsification index (E24%) reached 62% thus it was chosen for further study. Biosurfactant produced by E. cloacae E1 reduced the surface tension of the medium from 64 to 36 mN/m. pH range 6.5 – 7 and temperature range 30˚C - 35˚C were the optimal conditions for maximum degradation. After 30 days of incubation, E. cloacae E1 degraded 70.00 ± 0.40% of the crude oil. GC-MS analysis revealed that E. cloacae E1 was able to degrade aromatic compounds. This study proved that E. cloacae E1 consider being an efficient in crude oil degradation.
    Enterobacter cloacae
    Degradation
    Citations (20)
    In vitro studies were designed to investigate the influence of peak drug concentration (Cmax), the area under the concentration-time curve (AUC), and, consequently, the trough concentration on the bactericidal effects of gentamicin against Enterobacter cloacae (MIC, 0.5 mg/liter) by simulating bolus versus infusion administration and bolus dosing with altered drug clearance. Bacteria in the lag phase were exposed to gentamicin concentration-time profiles modelling either bolus or infusion dosing (AUC constant, Cmax changing) with 30-min postdose peak concentrations (Cpeak30) of 4, 6, 8, and 10 mg/liter or bolus dosing with normal and double drug clearance (Cmax constant, AUC changing) corresponding to normal clearance profiles with Cpeak30 of 6 and 8 mg/liter. Exposure to gentamicin caused early bactericidal effects apparent by 2 h, followed by variable bacteriostatic and recovery phases. Exposure to bolus profiles resulted in greater bactericidal activity than the corresponding infusion profile up to a Cpeak30 of 8 mg/liter. At a Cpeak30 of 10 mg/liter, there were no differences in bactericidal effect. Double clearance profiles had a reduced bactericidal effect at 6 mg/liter compared to the corresponding normal clearance profile, but no differences in bactericidal effect were observed for 8-mg/liter double and normal clearance profiles. These results suggest that the initial exposure (i.e., 0 to 30 min) is a more important determinant for bacterial killing than the AUC or trough concentration for this bacterium. Subject to confirmation of these findings with other gram-negative bacteria, to optimize aminoglycoside efficacy the initial exposure (Cmax) should be maximized by giving higher doses or bolus administration at intervals which may not produce detectable trough concentrations. Clinical trials with a broad range of patients, especially those with higher clearance, would confirm these in vitro observations and define optimal dosing recommendations.
    Liter
    Enterobacter cloacae
    Bolus (digestion)
    Pharmacodynamics
    Citations (4)
    Objective To investigate the clinical characteristics of the infantnewborn enterobacter cloacae septicaemia and the characteristics of its drug sensitivity to find out the basis for the early diagnose and treatment.Methods Through history analysis of the clinical data and the results of the drug sensitivity of 29 infantnewborn diagnosed as enterobacter cloacae septicaemia from May 2005 to August 2007 in our hospital.Results Enterobacter cloacae septicaemia can cause the damage to the function of visceras,and the sensitivity of enterobacter cloacae to imipenem、amikacinand ciprofloxacin is up to 100%;All the Enterobacter cloacae were severely resistant to majority of cephalosporins Ⅲ,and 82.8% of them were susceptible to cephalosporins Ⅳ,32.4% of them were ESBLs which can produce Enterobacter cloacae.Conclusion Enterobacter cloacae septicaemia cases have the tendancy to increase,most of which are infected in the hospital and not sensitive to the common antibiotics.The carbapenem antibiotics like imipenem and cefepime are suggested to be the first option for the enterobacter cloacae infection.Enterobacter cloacae septicaemia can be treated with satisfactory effectiveness by prompt using sensitive antibiotics.
    Enterobacter cloacae
    Cefepime
    Carbapenem
    Citations (0)
    The ampR gene and its regulation of AmpC β-lactamase synthesis were investigated for Enterobacter cloacae 1194E, a wild-type strain producing a group A (pI 8.7) enzyme. Expression of the cloned E. cloacae 1194E ampR-ampC region was examined initially in Escherichia coli HB101. However, transformants showed only constitutive β-lactamase expression. For study of enzyme expression in a more closely related host, the cloned E. cloacae 1194E ampR-ampC region was transformed into E. cloacae 55, a wild-type strain producing a group B (pI 7.8) enzyme. Results indicated a functional E. cloacae 1194E ampR gene that could not be transcomplemented by E. cloacae 55. A comparative analysis of ampR nucleotide and amino acid-sequence data from E. cloacae 1194E and E. cloacae MHN1 revealed related but divergent genes. Thermal induction studies of AmpC β-lactamase also indicated a difference between E. cloacae 1194E and E. cloacae 55 in ampR-ampC interaction. Thus, it appears that, in at least some strains of Enterobacter, significant intraspecies divergence of ampR has occurred. This heterogeneity in ampR would not have been detected with β-lactamase expression studies conducted exclusively in E. coli.
    Enterobacter cloacae
    Enterobacteriaceae Infections
    Pathogenic organism
    Citations (4)
    MICs of DU-6859a, a novel fluoroquinolone, for 18 Klebsiella pneumoniae isolates and 21 Enterobacter cloacae isolates with altered GyrA or altered GyrA and ParC ranged from < or =0.025 to 6.25 microg/ml and from 0.1 to 3.13 microg/ml, respectively. Based on the MICs at which 90% of the isolates were inhibited for these strains of K. pneumoniae and E. cloacae, DU-6859a exhibited 16- to 256-fold-greater activity than currently available fluoroquinolones.
    Enterobacter cloacae
    Quinolone
    Citations (16)
    Objective To establish a rapid and effective way to analyze whether Enterobacter cloacae(E.cloacae) isolates produce AmpC enzyme. Methods 58 clinical isolates of E.cloacae were analyzed by disk double inhibitor parallel inhibit test(DDIST).E.coli(ATCC 25922),K.pneumoniae (ATCC 700603),E.cloacae(029),E.cloacae(029M) and E.cloacae(1194E) were used as β-lactamase negative controls,ESBLs controls,common E.cloacae control,AmpC enzyme over producers controls and AmpC enzyme over producer controls by inducing them respectively.In order to confirm the results obtained by DDIST,three-dimensional extract test was used to detect the overproduced AmpC enzyme. Results In E.cloacae,21 of 58 isolates were positive for overproduced AmpC enzyme by three-dimensional extract test;18 of 58 isolates were positive for overproduced AmpC enzyme by DDIST;6 of 58 isolates were positive for overproducing AmpC enzyme by DDIST. Conclusions DDIST is a rapid and effective way to analyze AmpC enzyme in E. cloacae isolates.
    Enterobacter cloacae
    Citations (0)
    About 70% of all Enterobacter cloacae strains tested possessed one of two species-specific beta-lactamases. These enzymes, E. cloacae beta-lactamase A and E. cloacae beta-lactamase B, with isoelectric points of 8.8 and 7.8, respectively, had the same pH and temperature optima. Both showed similar enzyme kinetics and were inhibited by cloxacillin but not by p-chloromercuribenzoate. E. cloacae beta-lactamase B appeared to be identical with the enzyme of E. cloacae P99. By a mutation in a regulatory gene, inducible enzyme production could be converted into constitutive expression. In E. cloacae, both enzymes did not hydrolyze third-generation cephalosporins, but they were solely responsible for resistance toward these drugs. This was demonstrated by the characterization of Escherichia coli strains expressing an identical resistance pattern after transfer of the corresponding Enterobacter gene.
    Enterobacter cloacae
    Citations (154)
    Objective:To investigate the the genotyping of β-Lactamases(bla) in Enterobacter cloacae.Methods:44 strains of Enterobacter cloacae were isolated from hospitalized patients,and the bla genes were detected by PCR.Results: The positive rates of genes of TEM,DHA and ACT-1 were 54.5%,11.4% and 79.5%.The other genes were not found in all 44 isolates tested.Conclusion: There were very high positive percentages of TEM,DHA and ACT-1 genes in Enterobacter cloacae isolated clinically.
    Enterobacter cloacae
    Citations (0)