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Antimicrobial Agents and Chemotherapy Oct 2013Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and... (Meta-Analysis)
Meta-Analysis Review
Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of ≤0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies.
Topics: Anti-Bacterial Agents; Carbapenems; Drug Synergism; Microbial Sensitivity Tests; Polymyxins
PubMed: 23917322
DOI: 10.1128/AAC.01230-13 -
The Yale Journal of Biology and Medicine Dec 2022: Antibiotic resistance in cystic fibrosis (CF) is a well-known phenomenon. However, the comprehensive epidemiological impact of antibiotic resistance in CF is not... (Meta-Analysis)
Meta-Analysis Review
: Antibiotic resistance in cystic fibrosis (CF) is a well-known phenomenon. However, the comprehensive epidemiological impact of antibiotic resistance in CF is not clearly documented. So, this meta-analysis evaluated the proportion rates of carbapenem resistance (imipenem, meropenem, and doripenem) in CF based on publication date (1979-2000, 2001-2010, and 2011-2021), continents, pathogens, and antimicrobial susceptibility testing (AST). : We searched studies in PubMed, Scopus, and Web of Science (until April 2021). Statistical analyses were conducted using STATA software (version 14.0). : The 110 studies included in the analysis were performed in 25 countries and investigated 13,324 pathogens associated with CF. The overall proportion of imipenem, meropenem, and doripenem resistance in CF were 43% (95% CI 36-49), 48% (95% CI 40-57), 28% (95% CI 23-33), and 45% (95% CI 32-59), respectively. Our meta-analysis showed that trends of imipenem, meropenem, and doripenem-resistance had gradual decreases over time (1979-2021). This could be due to the limited clinical effectiveness of these antibiotics to treat CF cases over time. Among the opportunistic pathogens associated with CF, the highest carbapenem resistance rates were shown in , spp., , and . The highest and lowest carbapenem resistance rates among in CF patients were shown against meropenem (23%) and doripenem (39%). : We showed that trends of carbapenem resistance had decreased over time (1979-2021). This could be due to the limited clinical effectiveness of these antibiotics to treat CF cases over time. Plans should be directed to fight biofilm-associated infections and prevent the emergence of mutational resistance. Systematic surveillance for carbapenemase-producing pathogens in CF by molecular surveillance is necessitated.
Topics: Humans; Meropenem; Doripenem; Carbapenems; Cystic Fibrosis; Microbial Sensitivity Tests; Anti-Bacterial Agents; Imipenem; Pseudomonas aeruginosa
PubMed: 36568834
DOI: No ID Found -
International Journal of Molecular... Apr 2015Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are β-lactam antimicrobial agents. Because carbapenems have the broadest spectra among all... (Review)
Review
Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are β-lactam antimicrobial agents. Because carbapenems have the broadest spectra among all β-lactams and are primarily used to treat infections by multi-resistant Gram-negative bacteria, the emergence and spread of carbapenemases became a major public health concern. Carbapenemases are the most versatile family of β-lactamases that are able to hydrolyze carbapenems and many other β-lactams. According to the dependency of divalent cations for enzyme activation, carbapenemases can be divided into metallo-carbapenemases (zinc-dependent class B) and non-metallo-carbapenemases (zinc-independent classes A, C, and D). Many studies have provided various carbapenemase structures. Here we present a comprehensive and systematic review of three-dimensional structures of carbapenemase-carbapenem complexes as well as those of carbapenemases. We update recent studies in understanding the enzymatic mechanism of each class of carbapenemase, and summarize structural insights about regions and residues that are important in acquiring the carbapenemase activity.
Topics: Bacterial Proteins; Drug Resistance, Microbial; Hydrolysis; Models, Molecular; Structure-Activity Relationship; Zinc; beta-Lactamases
PubMed: 25938965
DOI: 10.3390/ijms16059654 -
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 -
Antimicrobial Agents and Chemotherapy Nov 2013Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as... (Meta-Analysis)
Meta-Analysis Review
Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations.
Topics: Anti-Bacterial Agents; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Databases, Bibliographic; Doripenem; Drug Combinations; Female; Humans; Imipenem; Levofloxacin; Male; Research Design; Treatment Outcome; Urinary Tract Infections
PubMed: 23939900
DOI: 10.1128/AAC.01257-13 -
Therapeutic Drug Monitoring Feb 2018Therapeutic drug monitoring is useful in the treatment of tuberculosis to assure adequate exposure, minimize antibiotic resistance, and reduce toxicity. Salivary... (Review)
Review
BACKGROUND
Therapeutic drug monitoring is useful in the treatment of tuberculosis to assure adequate exposure, minimize antibiotic resistance, and reduce toxicity. Salivary therapeutic drug monitoring could reduce the risks, burden, and costs of blood-based therapeutic drug monitoring. This systematic review compared human pharmacokinetics of antituberculosis drugs in saliva and blood to determine if salivary therapeutic drug monitoring could be a promising alternative.
METHODS
On December 2, 2016, PubMed and the Institute for Scientific Information Web of Knowledge were searched for pharmacokinetic studies reporting human salivary and blood concentrations of antituberculosis drugs. Data on study population, study design, analytical method, salivary Cmax, salivary area under the time-concentration curve, plasma/serum Cmax, plasma/serum area under the time-concentration curve, and saliva-plasma or saliva-serum ratio were extracted. All included articles were assessed for risk of bias.
RESULTS
In total, 42 studies were included in this systematic review. For the majority of antituberculosis drugs, including the first-line drugs ethambutol and pyrazinamide, no pharmacokinetic studies in saliva were found. For amikacin, pharmacokinetic studies without saliva-plasma or saliva-serum ratios were found.
CONCLUSIONS
For gatifloxacin and linezolid, salivary therapeutic drug monitoring is likely possible due to a narrow range of saliva-plasma and saliva-serum ratios. For isoniazid, rifampicin, moxifloxacin, ofloxacin, and clarithromycin, salivary therapeutic drug monitoring might be possible; however, a large variability in saliva-plasma and saliva-serum ratios was observed. Unfortunately, salivary therapeutic drug monitoring is probably not possible for doripenem and amoxicillin/clavulanate, as a result of very low salivary drug concentrations.
Topics: Antitubercular Agents; Drug Monitoring; Humans; Saliva
PubMed: 29120971
DOI: 10.1097/FTD.0000000000000462 -
Infectious Diseases & Clinical... Sep 2023This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes. (Review)
Review
OBJECTIVE
This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes.
MATERIALS AND METHODS
It was conducted according to the preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by using the keywords "Pancrea AND carbapenem OR imipenem OR ertapenem OR meropenem OR doripenem." Primer outcomes were mortality, surgical intervention, and pancreatic and non-pancreatic infection. Subgroup analyses were also performed to reduce the risk of bias.
RESULTS
Ten studies with 4038 patients were included in the meta-analyses. While eight of ten were randomized controlled trials, two were observational studies. The prophylactic use of carbapenems had no statistically significant effect on mortality (OR=0.82, 95% CI=0.65-1.04, I²=0%) and surgical intervention. (OR=0.81, 95% CI=0.57-1.17, I²=0%). However, the real impact of prophylaxis on reducing the incidence of mortality and surgical intervention was uncertain due to the insufficient sample size. The prophylactic use of carbapenems was significantly associated with a lower risk of peripancreatic (OR=0.37, 95% CI=0.25-0.55, I²=61%) and non-pancreatic infection risk (OR=0.60, 95% CI=0.46-0.78, I²=65%). The definitions of infection in the articles were not clear, and the diagnostic approach to infection was based on subjective criteria. In addition, there was inadequate collateral damage and safety assessments. In high-quality studies with a low risk of bias, prophylactic carbapenems had no effect on peripancreatic infection (RR=1.54, 95% CI=0.65-3.47, I²=0%) and non-pancreatic infection (RR=0.72, 95% CI=0.48-1.07, I²=0%).
CONCLUSION
Although there is a reduction in the infection risk, routine carbapenem use in acute pancreatitis cases should not be recommended based on current evidence. Cooperation with Infectious Disease specialists and developing diagnostic algorithms are required instead of routine prophylaxis to prevent infection, especially non-pancreatic infection.
PubMed: 38633556
DOI: 10.36519/idcm.2023.239 -
Annals of Clinical Microbiology and... Mar 2024Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most appropriate antibiotic to treat S. maltophilia infection is a major challenge.
AIM
The current meta-analysis aimed to investigate the global prevalence of antibiotic resistance among S. maltophilia isolates to the develop more effective therapeutic strategies.
METHOD
A systematic literature search was performed using the appropriate search syntax after searching Pubmed, Embase, Web of Science and Scopus databases (May 2023). Statistical analysis was performed using Pooled and the random effects model in R and the metafor package. A total of 11,438 articles were retrieved. After a thorough evaluation, 289 studies were finally eligible for inclusion in this systematic review and meta-analysis.
RESULT
Present analysis indicated that the highest incidences of resistance were associated with doripenem (97%), cefoxitin (96%), imipenem and cefuroxime (95%), ampicillin (94%), ceftriaxone (92%), aztreonam (91%) and meropenem (90%) which resistance to Carbapenems is intrinsic. The lowest resistance rates were documented for minocycline (3%), cefiderocol (4%). The global resistance rate to TMP-SMX remained constant in two periods before and after 2010 (14.4% vs. 14.6%). A significant increase in resistance to tigecycline and ceftolozane/tazobactam was observed before and after 2010.
CONCLUSIONS
Minocycline and cefiderocol can be considered the preferred treatment options due to low resistance rates, although regional differences in resistance rates to other antibiotics should be considered. The low global prevalence of resistance to TMP-SMX as a first-line treatment for S. maltophilia suggests that it remains an effective treatment option.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Minocycline; Stenotrophomonas maltophilia; Microbial Sensitivity Tests; Anti-Bacterial Agents; Cefiderocol; Drug Resistance, Microbial; Gram-Negative Bacterial Infections
PubMed: 38504262
DOI: 10.1186/s12941-024-00685-4 -
Journal of Global Antimicrobial... Jun 2023Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing... (Meta-Analysis)
Meta-Analysis
Clinical efficacy of ertapenem vs. other carbapenems for the treatment of extended-spectrum-β-lactamase-producing Enterobacterales infection: A systematic review and meta-analysis.
OBJECTIVE
Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales infection. However, whether ertapenem is as effective as other carbapenems for ESBL-producing Enterobacterales remains unclear. Therefore, this meta-analysis was conducted to compare the clinical efficacy of ertapenem versus other carbapenems in the treatment of ESBL-producing Enterobacterales infection.
METHODS
PubMed, Web of Science, and Cochrane Library were searched from their inception to 29 November 2022. Only studies comparing ertapenem and other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections were included.
RESULTS
A total of six studies meeting selection criteria were identified. Overall, ertapenem was associated with a significantly lower 30-d mortality when compared with other carbapenems (10.7% [46/431] vs. 17.7% [104/586]; risk ratio [RR], 0.61; 95% CI: 0.40-0.91). The ertapenem group exhibited a significantly shorter length of hospital stay than the other carbapenem groups (mean differences, -6.02 d; 95% CI, -9.39 to -2.64). No significant differences were noted between ertapenem and other carbapenem groups in terms of rates of clinical cure or improvement (RR, 1.11; 95% CI: 0.97-1.25) and microbiological eradication (RR, 1.01; 95% CI: 0.97-1.06).
CONCLUSIONS
Ertapenem could be as effective as other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections.
Topics: Humans; Ertapenem; Carbapenems; Anti-Bacterial Agents; beta-Lactams; beta-Lactamases; Treatment Outcome; Gammaproteobacteria
PubMed: 36944409
DOI: 10.1016/j.jgar.2023.03.003 -
European Journal of Medical Research Nov 2010Severe infections with multiresistant bacteria (MRB) are a medical challenge and a financial burden for hospitals. The adequate antibiotic therapy is a key issue in... (Review)
Review
UNLABELLED
Severe infections with multiresistant bacteria (MRB) are a medical challenge and a financial burden for hospitals. The adequate antibiotic therapy is a key issue in multiresistant bacteria management. Several major cost drivers have been identified. Remarkably drug acquisition costs are not necessarily included. Most significant are the length of stay in hospital, the hours of mechanical ventilation and the time treated on an intensive care unit. - In a systematic review of the literature the following aspects were investigated: - Do generic treatment strategies contribute in cost savings? - Are there specific results for recent antibiotics? - Early adequate and effective antimicrobial treatment, switch from i.v. to oral therapy, adjusted duration of therapy and adherence to guidelines have been found to be successful strategies. - Looking at specific antibiotics, the best evidence for cost-effectiveness is found for Linezolid in treatment of cSSTI as well as in HAP. Daptomycin shows good economic results in bloodstream infections, so possibly being a cost-effective alternative to vancomycin. Looking at tigecycline the published data show neither higher costs nor savings compared to imipeneme. Doripenem as one of the newest therapy options has proven to be highly cost-saving in HAP when compared with imipenem. However, most analyses are based on pharmacoeconomic modelling rather than on directly analysing trial data or real life clinical populations. -
CONCLUSION
Using modern antibiotics in whole is not more expensive than using established therapies. Modern antibiotics are cost-effective and sometimes even cost-saving. This is especially true if an effective therapy is initiated as early as possible.
Topics: Acetamides; Anti-Bacterial Agents; Carbapenems; Daptomycin; Doripenem; Drug Resistance, Microbial; Drug Resistance, Multiple; Economics, Pharmaceutical; Linezolid; Minocycline; Oxazolidinones; Tigecycline
PubMed: 21163732
DOI: 10.1186/2047-783x-15-12-571