-
PloS One 2022Carbapenem-resistant Escherichia coli has emerged as a major public health issue across the world. This study was aimed to determine the virulence content and...
Carbapenem-resistant Escherichia coli has emerged as a major public health issue across the world. This study was aimed to determine the virulence content and phylogenetic groups of carbapenemase-producing E. coli isolates in southwest Iran. One hundred and fifty-two non-duplicate E. coli isolates were collected from various clinical samples. Antibiotic susceptibility and minimum inhibitory concentrations (MIC) were determined according to the Clinical and Laboratory Standards Institute (CLSI) guidelines by Kirby-Bauer disc diffusion and agar dilution methods. Phenotypic screening of carbapenemase enzymes was performed by modified Hodge test (MHT). Detection of carbapenemase genes, phylogenetic groups, and virulence-associated genes were also performed by the PCR assay. The highest and lowest resistance rates were observed against mezlocillin (70.4%) and doripenem (13.1%), respectively. Out of 28 isolates that were resistant to carbapenem antibiotics, 12 (7.9%) strains were phenotypically carbapenemase producers. The blaOXA-48 was the predominant carbapenemase gene, detected in 58.3% of isolates, followed by blaIMP (41.7%) and blaNDM (8.3%). None of the isolates harbored blaVIM and blaKPC genes. Among the twelve carbapenemase-producing strains, urinary isolates were mostly classified into B2 (41.7%) and D (25%) phylogenetic groups, while other clinical isolates belonged to B1 (25%) and A (8.3%) groups. The frequency of virulence-associated genes was also investigated in all isolates and ranged from 6.6% for hly to 75% for fimA. The emergence of carbapenemase-producing strains is a growing concern to public health. Therefore, the proper implementation of monitoring programs is crucial for limiting their dissemination.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenem-Resistant Enterobacteriaceae; Escherichia coli; Microbial Sensitivity Tests; Phylogeny; Virulence; beta-Lactamases
PubMed: 35536848
DOI: 10.1371/journal.pone.0266787 -
Journal of Clinical Medicine Research Apr 2013Most KPC-producing organisms have maintained susceptibility to polymyxins; however, development of resistance to polymyxins has been increasingly reported. One potential...
BACKGROUND
Most KPC-producing organisms have maintained susceptibility to polymyxins; however, development of resistance to polymyxins has been increasingly reported. One potential treatment modality is to optimize the use of combination therapy. Therefore, we evaluated the in vitro activity of doripenem, colistin sulfate, polymyxin B alone and in combination against KPC- producing K. pneumoniae.
METHODS
In-vitro time-kill assays were performed for four non-duplicate KPC-3 producing K. pneumoniae isolates with the following antibiotics: doripenem, polymyxin B and colistin sulfate alone and in combination. Bacterial densities were determined at 0, 4, 8, 12, 24 and 48 hours. Bactericidal activity was defined as ≥ 3-log10 CFU/mL reduction from the starting inoculum. Synergism was defined as ≥ 2-log10 reduction with the combination when compared to the most active single agent at 24 hours.
RESULTS
Minimum inhibitory concentrations (MICs) for polymyxin B and colistin sulfate ranged from 0.0625 to 0.25 µg/mL, and all isolates were resistant to doripenem (MICs ranged 16 - 32 µg/mL). Monotherapy with colistin sulfate and polymyxin B displayed bacterialcidal activity within 12 hours; however, significant re-growth occurred by 24 hours in all isolates. Monotherapy with doripenem did not show bactericidal activity in any isolate. Synergy occurred with combinations of both colistin sulfate and polymyxin B with doripenem against all isolates and was sustained at 48 hours. Combinations of colistin sulfate or polymyxin B with doripenem demonstrated rapid bactericidal activity by 4 hours in all isolates and was sustained for 24 hours.
CONCLUSION
Polymyxin B and colistin sulfate in combination with doripenem may be an important treatment modality in treating KPC-producing organisms.
PubMed: 23519391
DOI: 10.4021/jocmr1220w -
Antimicrobial Agents and Chemotherapy Jun 2012We tested two-drug combinations of doripenem, colistin, gentamicin, and doxycycline against 12 carbapenemase-producing Klebsiella pneumoniae (KPC) isolates by time-kill....
We tested two-drug combinations of doripenem, colistin, gentamicin, and doxycycline against 12 carbapenemase-producing Klebsiella pneumoniae (KPC) isolates by time-kill. The combination of doripenem and colistin reduced the starting inocula by 2 logs for each isolate (range, 2.02 to 6.01 log(10)) and was bactericidal and synergistic against 75 and 50%, respectively. Among colistin- and pan-drug-resistant isolates, synergy was identified in 60 and 67%, respectively. All other combinations were inferior. We are currently evaluating the combination of doripenem and colistin as a frontline therapy for KPC infection.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Colistin; Doripenem; Drug Combinations; Drug Interactions; Klebsiella pneumoniae; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 22430958
DOI: 10.1128/AAC.06364-11 -
Antimicrobial Agents and Chemotherapy Jun 2014Gentamicin doses of 2 and 10 μg/ml were bactericidal against 64% and 100%, respectively, of gentamicin-susceptible KPC-2-producing Klebsiella pneumoniae strains....
Gentamicin doses of 2 and 10 μg/ml were bactericidal against 64% and 100%, respectively, of gentamicin-susceptible KPC-2-producing Klebsiella pneumoniae strains. Treatment with the combination of doripenem (8 μg/ml) plus colistin (2 μg/ml) was inferior to treatment with gentamicin (2 μg/ml), doripenem-gentamicin, gentamicin-colistin, and doripenem-gentamicin-colistin against strains with glycine and aspartic acid insertions in OpmK36 porin at amino acid (aa) positions 134 and 135 (n = 9). Doripenem-colistin was comparable to other 2- or 3-drug regimens and superior to single drugs against wild-type/minor ompK36 mutants (n = 5). An algorithm incorporating ompK36 genotypes and susceptibility to gentamicin and doripenem may predict antimicrobial activity against KPC-producing K. pneumoniae.
Topics: Algorithms; Anti-Bacterial Agents; Aspartic Acid; Bacterial Proteins; Carbapenems; Colistin; Doripenem; Drug Therapy, Combination; Genotype; Gentamicins; Glycine; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutagenesis, Insertional; Porins; beta-Lactamases
PubMed: 24566172
DOI: 10.1128/AAC.01949-13 -
Data in Brief Jun 2023The dataset reported in this article describes the adsorption isotherms of amoxicillin, ampicillin, and doripenem onto bentonite. Batch adsorption experiments were...
The dataset reported in this article describes the adsorption isotherms of amoxicillin, ampicillin, and doripenem onto bentonite. Batch adsorption experiments were carried out on single antibiotic solutions with various dosage of bentonite across temperatures from 30 to 50 °C. The adsorbent loading dataset was later obtained by measuring the concentration of antibiotic solution at adsorption equilibrium UV-Vis spectrophotometer. The dataset was also fitted using various isotherm models including Freundlich, Langmuir, Toth, Hill, and Dubinin-Radushkevich models to further analyze the adsorption behavior. On top of that, orthogonal regression was applied to avoid fitting biasness, whereby the fitting results revealed the highest adsorption capacities of 82.259 mg g for amoxicillin, 78.851 mg g for ampicillin, and 93.278 mg g for doripenem using Langmuir model, which gave an accurate representation of the adsorption isotherm dataset that was consistent with the results of Toth and Hill model.
PubMed: 37168600
DOI: 10.1016/j.dib.2023.109159 -
The Brazilian Journal of Infectious... 2015The aim of this article is to compare the efficacy and safety of doripenem for bacterial infections. (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The aim of this article is to compare the efficacy and safety of doripenem for bacterial infections.
METHODS
We included six randomized clinical trials identified from PubMed and Embase up to July 31, 2014. The included trials compared efficacy and safety of doripenem for complicated intra-abdominal infections, complicated urinary tract infection, nosocomial pneumonia, and acute biliary tract infection. The meta-analysis was carried on by the statistical software of Review Manager, version 5.2.
RESULTS
Compared with empirical antimicrobial agents on overall treatment efficacy, doripenem was associated with similar clinical and microbiological treatment success rates (for the clinical evaluable population, odds ratio [OR]=1.26, 95% confidence interval [CI] 0.93-1.69, p=0.13; for clinical modified intent-to-treatment population, OR=0.88, 95% CI 0.55-1.41, p=0.60; for microbiology evaluable population, OR=1.16, 95% CI 0.90-1.50, p=0.26; for microbiological modified intent-to-treatment (m-mITT), OR=0.98, 95% CI 0.81-1.20, p=0.87). We compared incidence of adverse events and all-cause mortality to analyze treatment safety. The outcomes suggested that doripenem was similar to comparators in terms of incidence of adverse events and all-cause mortality on modified intent-to-treatment population (for incidence of AEs, OR=1.10, 95% CI 0.90-1.35, p=0.33; for all-cause mortality, OR=1.08, 95% CI 0.77-1.51, p=0.67). In nosocomial pneumonia and ventilator-associated pneumonia treatment, doripenem was not inferior to other antibacterial agents in terms of efficacy and safety.
CONCLUSION
From this meta-analysis, we can conclude that doripenem is as valuable and well-tolerated than empirical antimicrobial agents for complicated intra-abdominal infections, complicated urinary tract infection, acute biliary tract infection and nosocomial pneumonia treatment.
Topics: Acute Disease; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cholangitis; Cross Infection; Doripenem; Humans; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Randomized Controlled Trials as Topic; Urinary Tract Infections
PubMed: 25636188
DOI: 10.1016/j.bjid.2014.10.010 -
The Canadian Journal of Infectious... 2018Evaluation of the in vitro interaction of doripenem and amikacin against , , and was done by classifying them into four groups: doripenem and amikacin sensitive...
Evaluation of the in vitro interaction of doripenem and amikacin against , , and was done by classifying them into four groups: doripenem and amikacin sensitive (DOR-S/AMK-S), doripenem sensitive and amikacin resistant (DOR-S/AMK-R), doripenem resistant and amikacin sensitive (DOR-R/AMK-S), and both doripenem and amikacin resistant (DOR-R/AMK-R). The MIC of each antibiotic and their combination was obtained using the Etest method. The fractional inhibitory concentration index was calculated to classify the results as synergistic, additive, indifferent, or antagonistic interaction. In the DOR-S/AMK-S class, 1 isolate of showed synergy and the other 5 showed additive results, 5 isolates of showed additive and 1 isolate showed indifferent result, and 2 isolates of showed additive and the other 4 showed indifferent results. In the DOR-S/AMK-R class, 3 isolates of showed additive and the other 3 showed indifferent results, 2 isolates of showed indifferent results, and 1 isolate of showed additive and the other 5 showed indifferent results. In the DOR-R/AMK-S class, 1 isolate of showed additive and the other 5 showed indifferent results, 1 isolate of showed additive and the other 5 showed indifferent results, and 4 isolates of showed additive and the other 2 showed indifferent results. In the DOR-R/AMK-R class, 6 isolates of showed indifferent results, 1 isolate of showed additive and the other 5 showed indifferent results, and 1 isolate of showed additive and the other 5 showed indifferent results. Synergy occurred in only 1 (1.5%) isolate. Additive interaction occurred in 24 (35.3%) isolates, and indifferent interaction occurred in 43 (63.2%) isolates. Doripenem sensitive combined with amikacin sensitive reduced MIC significantly in all bacterial isolates when compared to single MIC of each antibiotic.
PubMed: 30065794
DOI: 10.1155/2018/1047670 -
Revista Da Sociedade Brasileira de... 2020Consumption of carbapenem has increased due to extended-spectrum beta-lactamase-producing bacteria spreading. Ertapenem has been suggested as a not carbapenem-resistance... (Review)
Review
Consumption of carbapenem has increased due to extended-spectrum beta-lactamase-producing bacteria spreading. Ertapenem has been suggested as a not carbapenem-resistance inducer. We performed a scoping review of carbapenem-sparing stewardship with ertapenem and its impact on the antibiotic resistance of Gram-negative bacilli. We searched PubMed for studies that used ertapenem as a strategy to reduce resistance to carbapenems and included epidemiologic studies with this strategy to evaluate susceptibility patterns to cephalosporins, quinolones, and carbapenems in Gram-negative-bacilli. The search period included only studies in English, up to February 2018. From 1294 articles, 12 studies were included, mostly from the Americas. Enterobacteriaceae resistance to quinolones and cephalosporins was evaluated in 6 studies and carbapenem resistance in 4 studies. Group 2 carbapenem (imipenem/meropenem/doripenem) resistance on A. baumannii was evaluated in 6 studies. All studies evaluated P. aeruginosa resistance to Group 2 carbapenem. Resistance profiles of Enterobacteriaceae and P. aeruginosa to Group 2 carbapenems were not associated with ertapenem consumption. The resistance rate of A. baumannii to Group 2 carbapenems after ertapenem introduction was not clear due to a lack of studies without bias. In summary, ertapenem as a strategy to spare use of Group 2 carbapenems may be an option to stewardship programs without increasing resistance of Enterobacteriaceae and P. aeruginosa. More studies are needed to evaluate the influence of ertapenem on A. baumannii.
Topics: Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Ertapenem; Microbial Sensitivity Tests; beta-Lactams
PubMed: 33174959
DOI: 10.1590/0037-8682-0413-2020 -
Frontiers in Cellular and Infection... 2018Enterobacteriaceae cause different types of community- and hospital-acquired infections. Moreover, the spread of multidrug-resistant Enterobacteriaceae is a public...
Activity of Pentamidine Alone and in Combination With Aminoglycosides, Tigecycline, Rifampicin, and Doripenem Against Clinical Strains of Carbapenemase-Producing and/or Colistin-Resistant Enterobacteriaceae.
Enterobacteriaceae cause different types of community- and hospital-acquired infections. Moreover, the spread of multidrug-resistant Enterobacteriaceae is a public health problem and the World Health Organization pointed them among the pathogens in which the search of new antibiotics is critical. The objective of this study was to analyze the activity of pentamidine alone and in combination with gentamicin, tobramycin, amikacin, tigecycline, rifampicin, or doripenem against eight clinical strains of carbapenemase-producing and/or colistin-resistant Enterobacteriaceae: five carbapenemase-producing , one carbapenemase-producing , and two colistin-resistant . MIC and MBC were determined following standard protocols. MIC results were interpreted for all the antibiotics according to the EUCAST breakpoints but for rifampicin in which the French FSM breakpoint was used. Bactericidal and synergistic activity of pentamidine alone and in combination with antibiotics at concentrations of 1xMIC was measured by time-kill curves. For one selected strain, OXA-48/CTX-M-15 time-kill curves were performed also at 1/2xMIC of pentamidine. All studies were performed in triplicate. Pentamidine MIC range was 200-800 μg/mL. The 50, 12.5, 62.5, 87.5, and 62.5% of the strains were susceptible to gentamicin, tobramycin, amikacin, tigecycline, and doripenem, respectively. Only the two strains were susceptible to rifampicin. Pentamidine alone at 1xMIC showed bactericidal activity against all strains, except for the 32 strain. The bactericidal activity of pentamidine alone was also observed in combination. The combinations of pentamidine were synergistic against 32 with amikacin and tobramycin at 24 h and with tigecycline at 8 h. Pentamidine plus rifampicin was the combination that showed synergistic activity against more strains (five out of eight). Pentamidine plus doripenem did not show synergy against any strain. At 1/2xMIC, pentamidine was synergistic with all the studied combinations against the K. pneumoniae OXA-48/CTX-M-15 strain. In summary, pentamidine alone and in combination shows activity against carbapenemase-producing and/or colistin-resistant Enterobacteriaceae. Pentamidine appears to be a promising option to treat infections caused by these pathogens.
Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Drug Resistance, Bacterial; Drug Synergism; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Microbial Viability; Pentamidine
PubMed: 30406040
DOI: 10.3389/fcimb.2018.00363 -
BMC Microbiology Aug 2020Interest in carbapenems has been rising in the last few years due to the emergence of drug resistant tuberculosis. Ertapenem (ETP), given once a day parenteral, and... (Comparative Study)
Comparative Study
BACKGROUND
Interest in carbapenems has been rising in the last few years due to the emergence of drug resistant tuberculosis. Ertapenem (ETP), given once a day parenteral, and faropenem (FAR), oral, have a better administration profile than meropenem (MEM), imipenem (IPM) and doripenem (DOR). The addition of amoxicillin-clavulanate (AMC) inhibits the hydrolysis by the carbapenemase present in Mycobacterium tuberculosis (MTB). The aim of this study was to determine the in vitro activity of ETP and FAR against susceptible and resistant clinical MTB strains by two widely use methodologies, the BACTEC960 MGIT and microdilution.
RESULTS
19 clinical isolates with different susceptibility profiles and H37Rv were included. Minimal inhibitory concentration (MIC) testing was performed using two methods of different concentrations of ETP and FAR with and without AMC. MIC50 was 2 and 8 for FAR with and without AMC by both methods. MIC90 was > 16 and > 8 by microdilution and MGIT respectively and did not change after AMC addition. 18/20 samples were resistant to the highest concentration of ETP, with and without AMC. Half of the samples had some susceptibility to FAR; addition of AMC further reduced the MIC level in seven isolates. 10/20 isolates showed susceptibility to FAR and the addition of AMC further reduced the MIC in 7 isolates. However, most of the MICs were near the limit of effectiveness (8 μg/mL). Resistance to FAR was associated with resistance to MEM (p = 0.04) but not to resistance profiles of other drugs, including M/XDR status.
CONCLUSIONS
The lack of ETP activity may be associated with its degradation, independent of carbapenemase, during incubation. No susceptibility pattern to traditional drugs can predict susceptibility to FAR and susceptibility testing is not routinely available. PK/PD studies are needed as reaching the concentrations tested in these experiments may be challenging. This work highlighted some of the limitations of carbapenem use. More evidence is needed to clarify their true impact in TB treatment and outcome, considering the financial burden, complications and microbiota changes associated with their use.
Topics: Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; Drug Resistance, Bacterial; Ertapenem; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Multidrug-Resistant; beta-Lactams
PubMed: 32867678
DOI: 10.1186/s12866-020-01954-w