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Infection and Drug Resistance 2018Sporadic studies in antimicrobial therapy have evaluated the effects of infusion rates on therapeutic and economic outcomes, and new findings may challenge the regular... (Review)
Review
BACKGROUND
Sporadic studies in antimicrobial therapy have evaluated the effects of infusion rates on therapeutic and economic outcomes, and new findings may challenge the regular infusion regimen.
METHODS
Focusing on studies comparing the outcomes of different infusion regimens, the relevant literature was identified by searching PubMed, Web of Science, and Scopus from January 1, 2013 to March 1, 2018. Papers were finally chosen using a PRISMA flowchart.
RESULTS
Antimicrobials with the superiority of prolonged infusion to standard infusion in terms of efficacy and safety include meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin. The strategy of concomitantly reducing total daily dose and prolonging infusion time may cause treatment failure (eg, imipenem). Extended infusion of piperacillin/tazobactam has pharmacoeconomic advantage over standard infusion. Prolonged infusion of voriconazole is inferior to standard infusion because of lower efficacy caused by pharmacokinetic changes. Comparable outcomes following standard infusion and continuous infusion were observed with norvancomycin and nafcillin. Factors determining whether prolonged infusion has a benefit over standard infusion include MIC of bacterial pathogens, bacterial density, diagnosis, disease severity, total daily dose, and renal function.
CONCLUSION
To maximally preserve the effectiveness of current antimicrobials, effective interventions should be implemented to enhance the application of optimal infusion strategies. For reducing nephrotoxicity, prolonged infusion of meropenem is better than conventional infusion in neonates with Gram-negative late-onset sepsis, and continuous infusion of vancomycin is superior to intermittent infusion. For increasing efficacy, prolonged or continuous infusion of time-dependent antimicrobials (eg, meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin) is an optimal choice. Nevertheless, such advantages may only be demonstrated in special clinical circumstances and special populations (eg, patients with a sequential organ failure assessment (SOFA) score≥9, respiratory tract infections, urinary or intra-abdominal infections, or infections caused by less susceptible pathogens would benefit from prolonged infusion of piperacillin/tazobactam).
PubMed: 30127628
DOI: 10.2147/IDR.S167616 -
BMC Infectious Diseases May 2022Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a growing threat. The objective of this study was to...
BACKGROUND
Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a growing threat. The objective of this study was to describe CRAB and CRPA epidemiology and identify factors associated with mortality and length of stay (LOS) post-culture.
METHODS
This was a national retrospective cohort study of Veterans with CRAB or CRPA positive cultures from 2013 to 2018, conducted at Hines Veterans Affairs Hospital. Carbapenem resistance was defined as non-susceptibility to imipenem, meropenem and/or doripenem. Multivariable cluster adjusted regression models were fit to assess the association of post-culture LOS among inpatient and long-term care (LTC) and to identify factors associated with 90-day and 365-day mortality after positive CRAB and CRPA cultures.
RESULTS
CRAB and CRPA were identified in 1,048 and 8,204 unique patients respectively, with 90-day mortality rates of 30.3% and 24.5% and inpatient post-LOS of 26 and 27 days. Positive blood cultures were associated with an increased odds of 90-day mortality compared to urine cultures in patients with CRAB (OR 6.98, 95% CI 3.55-13.73) and CRPA (OR 2.82, 95% CI 2.04-3.90). In patients with CRAB and CRPA blood cultures, higher Charlson score was associated with increased odds of 90-day mortality. In CRAB and CRPA, among patients from inpatient care settings, blood cultures were associated with a decreased LOS compared to urine cultures.
CONCLUSIONS
Positive blood cultures and more comorbidities were associated with higher odds for mortality in patients with CRAB and CRPA. Recognizing these factors would encourage clinicians to treat these patients in a timely manner to improve outcomes of patients infected with these organisms.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Retrospective Studies
PubMed: 35610601
DOI: 10.1186/s12879-022-07436-w -
Annals of Laboratory Medicine Mar 2016Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for...
In Vitro Interactions of Antibiotic Combinations of Colistin, Tigecycline, and Doripenem Against Extensively Drug-Resistant and Multidrug-Resistant Acinetobacter baumannii.
BACKGROUND
Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii.
METHODS
Time-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 μg/mL, doripenem 8 μg/mL) and achievable tissue levels (tigecycline 2 μg/mL) for each antibiotic were used in this study.
RESULTS
The colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, the-doripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bactericidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination.
CONCLUSIONS
The colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropriate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Tigecycline; beta-Lactamases
PubMed: 26709259
DOI: 10.3343/alm.2016.36.2.124 -
Antimicrobial Agents and Chemotherapy Nov 2013Doripenem-colistin exerts synergy against some, but not all, Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains in vitro. We determined if...
Doripenem-colistin exerts synergy against some, but not all, Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains in vitro. We determined if doripenem MICs and/or ompK36 porin gene mutations impacted the responses of 23 sequence type 258 (ST258), KPC-2-producing strains to the combination of doripenem (8 μg/ml) and colistin (2 μg/ml) during time-kill assays. The median doripenem and colistin MICs were 32 and 4 μg/ml. Doripenem MICs did not correlate with KPC-2 expression levels. Five and 18 strains had wild-type and mutant ompK36, respectively. The most common mutations were IS5 promoter insertions (n = 7) and insertions encoding glycine and aspartic acid at amino acid (aa) positions 134 and 135 (ins aa134-135 GD; n = 8), which were associated with higher doripenem MICs than other mutations or wild-type ompK36 (all P values ≤ 0.04). Bactericidal activity (24 h) was achieved by doripenem-colistin against 12%, 43%, and 75% of ins aa134-135 GD, IS5, and wild-type/other mutants, respectively (P = 0.04). Doripenem-colistin was more active in time-kill studies than colistin at 12 and 24 h if the doripenem MIC was ≤8 μg/ml (P = 0.0007 and 0.09, respectively), but not if the MIC was >8 μg/ml (P = 0.10 and 0.16). Likewise, doripenem-colistin was more active at 12 and 24 h against the wild type/other mutants than ins aa134-135 GD or IS5 mutants (P = 0.007 and 0.0007). By multivariate analysis, the absence of ins aa134-135 GD or IS5 mutations was the only independent predictor of doripenem-colistin responses at 24 h (P = 0.002). In conclusion, ompK36 genotypes identified ST258 KPC-K. pneumoniae strains that were most likely to respond to doripenem-colistin.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; Carbapenems; Colistin; Doripenem; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Gene Expression; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Multivariate Analysis; Mutation; Porins; Promoter Regions, Genetic; beta-Lactamases
PubMed: 23939888
DOI: 10.1128/AAC.01069-13 -
Antimicrobial Agents and Chemotherapy Oct 2012Multidrug-resistant (MDR) Klebsiella pneumoniae may require combination therapy. We systematically investigated bacterial killing with colistin and doripenem mono- and...
The combination of colistin and doripenem is synergistic against Klebsiella pneumoniae at multiple inocula and suppresses colistin resistance in an in vitro pharmacokinetic/pharmacodynamic model.
Multidrug-resistant (MDR) Klebsiella pneumoniae may require combination therapy. We systematically investigated bacterial killing with colistin and doripenem mono- and combination therapy against MDR K. pneumoniae and emergence of colistin resistance. A one-compartment in vitro pharmacokinetic/pharmacodynamic model was employed over a 72-h period with two inocula (∼10(6) and ∼10(8) CFU/ml); a colistin-heteroresistant reference strain (ATCC 13883) and three clinical isolates (colistin-susceptible FADDI-KP032 [doripenem resistant], colistin-heteroresistant FADDI-KP033, and colistin-resistant FADDI-KP035) were included. Four combinations utilizing clinically achievable concentrations were investigated. Microbiological responses were examined by determining log changes and population analysis profiles (for emergence of colistin resistance) over 72 h. Against colistin-susceptible and -heteroresistant isolates, combinations of colistin (constant concentration regimens of 0.5 or 2 mg/liter) plus doripenem (steady-state peak concentration [C(max)] of 2.5 or 25 mg/liter over 8 h; half-life, 1.5 h) generally resulted in substantial improvements in bacterial killing at both inocula. Combinations were additive or synergistic against ATCC 13883, FADDI-KP032, and FADDI-KP033 in 9, 9, and 14 of 16 cases (4 combinations at 6, 24, 48, and 72 h) at the 10(6)-CFU/ml inoculum and 14, 11, and 12 of 16 cases at the 10(8)-CFU/ml inoculum, respectively. Combinations at the highest dosage regimens resulted in undetectable bacterial counts at 72 h in 5 of 8 cases (4 isolates at 2 inocula). Emergence of colistin-resistant subpopulations in colistin-susceptible and -heteroresistant isolates was virtually eliminated with combination therapy. Against the colistin-resistant isolate, colistin at 2 mg/liter plus doripenem (C(max), 25 mg/liter) at the low inoculum improved bacterial killing. This investigation provides important information for optimization of colistin-doripenem combinations.
Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Synergism; Klebsiella pneumoniae; Microbial Sensitivity Tests
PubMed: 22802247
DOI: 10.1128/AAC.01064-12 -
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 -
Antibiotics (Basel, Switzerland) Sep 2022In the context of difficult-to-treat carbapenem-resistant infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven...
In the context of difficult-to-treat carbapenem-resistant infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing isolates. According to the widespread global distribution of high-risk clones and carbapenemases, four representative isolates were selected: ST175 (OXA-2/VIM-20), ST175 (VIM-2), ST235 (GES-5), and ST111 (IMP-33), for efficacy studies using a sepsis murine model. Minimum inhibitory concentration (mg/L) ranges were 64-256 for imipenem and 16-128 for meropenem and doripenem. In vitro, imipenem plus meropenem was synergistic against 72% of isolates and doripenem plus meropenem or imipenem against 55% and 45%, respectively. All combinations were synergistic against the ST175, ST235, and ST155 clones. In vivo, meropenem diminished the spleen and blood bacterial concentrations of four and three isolates, respectively, with better efficacy than imipenem or doripenem. The combinations did not show efficacy compared with the more active monotherapies, except for imipenem plus meropenem, which reduced the ST235 bacterial spleen concentration. Mortality decreased with imipenem plus meropenem or doripenem for the ST175 isolate. Results suggest that carbapenem combinations are not an alternative for severe infections by carbapenemase-producing . Meropenem monotherapy showed in vivo efficacy despite its high MIC, probably because its dosage allowed a sufficient antimicrobial exposure at the infection sites.
PubMed: 36139991
DOI: 10.3390/antibiotics11091212 -
Antimicrobial Agents and Chemotherapy Mar 2012To compare the antipseudomonal efficacy of doripenem and imipenem as well as their abilities to restrict the enrichment of resistant Pseudomonas aeruginosa,... (Comparative Study)
Comparative Study
To compare the antipseudomonal efficacy of doripenem and imipenem as well as their abilities to restrict the enrichment of resistant Pseudomonas aeruginosa, multiple-dosing regimens of each drug were simulated at comparable values of the cumulative percentages of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (T(>MIC)) and ratios of the 24-hour area under the curve (AUC(24)) to the MIC. Three clinical isolates of ciprofloxacin-resistant P. aeruginosa (MIC of doripenem, 1 μg/ml; MICs of imipenem, 1, 2, and 2 μg/ml) were exposed to thrice-daily doripenem or imipenem for 3 days at AUC(24)/MIC ratios of from 50 to 170 h (doripenem) and from 30 to 140 h (imipenem). The antimicrobial effects for susceptible and resistant subpopulations of bacteria were expressed by the areas between control growth and time-kill curves (I(E)s) and areas under the bacterial mutant concentration curves (AUBC(M)s), respectively. With each antibiotic, the I(E) and AUBC(M) versus log AUC(24)/MIC relationships were bacterial strain independent. At similar AUC(24)/MIC ratios, doripenem was slightly less efficient than imipenem against susceptible and resistant subpopulations of bacteria. However, doripenem appeared to be somewhat more efficient than imipenem at clinically achievable AUC(24)s related to the means of the MICs for the three studied strains and had higher antimutant potentials for two of the three strains.
Topics: Anti-Bacterial Agents; Area Under Curve; Carbapenems; Ciprofloxacin; Doripenem; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Humans; Imipenem; Microbial Sensitivity Tests; Models, Biological; Mutation; Predictive Value of Tests; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 22203591
DOI: 10.1128/AAC.05964-11 -
Critical Care (London, England) 2008The US Institute of Medicine's focus on patient safety has motivated hospital administrators to facilitate a culture of safety. As a result, subcommittees of the... (Review)
Review
The US Institute of Medicine's focus on patient safety has motivated hospital administrators to facilitate a culture of safety. As a result, subcommittees of the pharmacy and therapeutics committee have emerged in many hospitals to focus on adverse events and patient safety. Antimicrobial harms have gained the attention of practicing clinicians and hospital formulary committees, because they top the list of drugs that are associated with adverse events and because of certain serious harms that have ultimately led to the withdrawal of some antimicrobial agents. In the near future, several antimicrobials in the late phase of development will become available for clinical use (ceftobiprole, ceftaroline, and telavancin), and others (doripenem and dalbavancin) have recently joined the armamentarium. Because new antimicrobials will become part of the treatment armamentarium, it is important to discuss our current understanding of antimicrobial harms in general. Although not thought of as traditional adverse events, Clostridium difficile infection and development of resistance during therapy are adverse events that occur as a result of antimicrobial exposure and therefore are discussed. In addition, a distillation of our current understanding of beta-lactam specific adverse events will be provided. Finally, new methods of administration are being evaluated that may influence peak concentration-related antimicrobial adverse events.
Topics: Carbapenems; Central Nervous System Diseases; Clostridioides difficile; Clostridium Infections; Drug Resistance, Bacterial; Drug Resistance, Multiple; Glucose Metabolism Disorders; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Heart Diseases; Humans
PubMed: 18495060
DOI: 10.1186/cc6819 -
Antibiotics (Basel, Switzerland) Apr 2023While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects,... (Review)
Review
While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects, differences in antimicrobial pharmacokinetics between Asian and non-Asian patients with severe pathologic conditions require further investigation. For the purpose of describing the potential differences in antimicrobial pharmacokinetics between Asian and non-Asian populations, a systematic review was performed using six journal databases and six theses/dissertation databases (PROSPERO record CRD42018090054). The pharmacokinetic data of healthy volunteers and non-critically ill and critically ill patients were reviewed. Thirty studies on meropenem, imipenem, doripenem, linezolid, and vancomycin were included in the final descriptive summaries. In studies recruiting hospitalised patients, inconsistent differences in the volume of distribution (V) and drug clearance (CL) of the studied antimicrobials between Asian and non-Asian patients were observed. Additionally, factors other than ethnicity, such as demographic (e.g., age) or clinical (e.g., sepsis) factors, were suggested to better characterise these pharmacokinetic differences. Inconsistent differences in pharmacokinetic parameters between Asian and non-Asian subjects/patients may suggest that ethnicity is not an important predictor to characterise interindividual pharmacokinetic differences between meropenem, imipenem, doripenem, linezolid, and vancomycin. Therefore, the dosing regimens of these antimicrobials should be adjusted according to patients' demographic or clinical characteristics that can better describe pharmacokinetic differences.
PubMed: 37237706
DOI: 10.3390/antibiotics12050803