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Antimicrobial Resistance and Infection... 2019Antimicrobial resistance is an increasingly serious threat to public health, and the increased occurrence of multidrug-resistant (MDR) bacteria is a concern in both... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antimicrobial resistance is an increasingly serious threat to public health, and the increased occurrence of multidrug-resistant (MDR) bacteria is a concern in both high-income and low- and middle-income countries. The purpose of this systematic review was to identify and critically appraise current antimicrobial treatment options for infections with MDR Gram-negative bacteria.
METHODS
A literature search for treatment of MDR extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, and was conducted in MEDLINE in January 2019. Relevant studies published in English, German, and French that evaluated clinical success, microbiological success, and 30-day mortality outcomes were included. The population of interest was adult patients.
RESULTS
Of 672 studies, 43 met the inclusion criteria. Carbapenems are the most common antibiotics used for the treatment of ESBL-producing Enterobacteriaceae The clinical and microbiological success was similar for group 1 carbapenems (imipenem, meropenem, or doripenem), group 2 carbapenems (ertapenem), and non-carbapenem antibiotics. Mortality data were contradictory for group 1 carbapenems compared to group 2 carbapenems. The most common treatment option for and infections was intravenous colistin, regardless of infection site. Clinical success and mortality were similar in infections treated with colistin combination therapy vs. colistin monotherapy, whereas heterogeneous results were found with respect to microbiological success. Monotherapy and colistin combination therapy were used against with clinical and microbiological success (70-100%) depending on the infection site and severity, and the antibiotic used. Ceftazidime-avibactam therapy for ESBL-producing Enterobacteriaceae and showed good clinical success in one study.
CONCLUSION
We did not find robust evidence for antibiotic treatment of any infection with MDR Gram-negative bacteria, including ESBL-producing Enterobacteriaceae, and that would lead to a firm recommendation for one specific antibiotic over another or for monotherapy over combination therapy. The choice of antibiotic treatment should be based on susceptibility testing balancing the expected clinical success rate against the risk of development of antibiotic resistance and the risk of severe side effects.
Topics: Anti-Bacterial Agents; Clinical Decision-Making; Disease Management; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Prognosis; Publication Bias; Treatment Outcome; beta-Lactamases
PubMed: 31709047
DOI: 10.1186/s13756-019-0624-1 -
Medicine Oct 2019Complicated intra-abdominal infections (cIAIs) are common in clinical practice, caused by a mixture of aerobic and anaerobic bacteria, increase the risk of mortality.... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Complicated intra-abdominal infections (cIAIs) are common in clinical practice, caused by a mixture of aerobic and anaerobic bacteria, increase the risk of mortality. Carbapenems and tigecycline (TGC) are recommended for antimicrobial therapies for cIAIs.
OBJECTIVE
To compare the effectiveness and safety of different carbapenems vs TGC for the treatment of cIAIs.
METHODS
PubMed, Embase, Medline (via Ovid SP) and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing different carbapenems vs TGC for the treatment of cIAIs. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. We estimated summary ORs using pairwise and network meta-analysis with random effects.
RESULTS
Fifteen studies involving 6745 participants were included in the analysis. Five different carbapenems and TGC were ultimately evaluated in this study. Although, the efficacy of carbapenems and TGC by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that clinical treatment success from best to worst was doripenem (DOPM), meropenem (MEPM), imipenem/cilastatin (IC), biapenem (BAPM), TGC and imipenem/cilastatin/relebactam (ICRB); microbiological treatment success from best to worst was DOPM, MEPM, IC, BAPM, ICRB and TGC. As for the risk of adverse events (AEs), TGC showed higher risk of AEs compared with IC (OR = 1.53, 95% CrI = 1.02-2.41), the remain antibiotic agents from lower to higher was MEPM, IC, BAPM, DOPM, ICRB and TGC. The risk of mortality from lower to higher was BAPM, DOPM, MEPM, IC, TGC and ICRB.
CONCLUSION
No differences in clinical and microbiological outcomes were observed between different carbapenems and TGC. Balancing the evidence for drug efficacy and side effects, DOPM appears to be the best available treatment for cIAIs. Therefore, it is reasonable to consider that DOPM is one of the best carbapenem monotherapy for cIAIs. MEPM and IC was also associated with higher rates of clinical and microbiological treatment success following DOPM. Empiric antimicrobial treatment of patients with cIAIs should be selected in light of the local bacterial epidemiology and patterns of resistance.
Topics: Anti-Bacterial Agents; Bayes Theorem; Carbapenems; Humans; Intraabdominal Infections; Network Meta-Analysis; Tigecycline
PubMed: 31577763
DOI: 10.1097/MD.0000000000017436 -
The Annals of Pharmacotherapy May 2018To present systematic recommendations for carbapenem-sparing therapy against extended-spectrum β-lactamases (ESBLs) Enterobacteriaceae bloodstream infections (BSIs)...
Is It Time to Rethink the Notion of Carbapenem-Sparing Therapy Against Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Bloodstream Infections? A Critical Review.
OBJECTIVE
To present systematic recommendations for carbapenem-sparing therapy against extended-spectrum β-lactamases (ESBLs) Enterobacteriaceae bloodstream infections (BSIs) derived from a critical review of clinical data.
DATA SOURCES
A systematic literature search using PubMed and MEDLINE databases (January 1, 2012, to June 30, 2017) was performed using key MESH terms: ESBL or extended-spectrum β-lactamases and bacteremia or bloodstream infection with piperacillin/tazobactam, ciprofloxacin, levofloxacin, cefepime, cephamycins, carbapenem, doripenem, meropenem, and ertapenem. References within articles of interest were also evaluated.
STUDY SELECTION AND DATA EXTRACTION
All English language trials were considered, and results were limited to clinical efficacy trials. Articles were screened by title and abstract for inclusion.
DATA SYNTHESIS
Studies comparing noncarbapenem versus carbapenem therapy for ESBL BSIs were critically analyzed to identify heterogeneity among studies. Data abstracted included empirical or definitive therapy, patient population, dosing, source of infection and severity, infectious etiology, and outcome.
CONCLUSIONS
Completely sparing carbapenem therapy cannot be justified among patients with ESBL BSIs. Determining the source of infection is critical to identify patients for whom carbapenem-sparing therapy is appropriate.
Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cefepime; Enterobacteriaceae; Enterobacteriaceae Infections; Fluoroquinolones; Humans; beta-Lactamases
PubMed: 29239220
DOI: 10.1177/1060028017748943 -
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 -
Infection Apr 2018Ceftazidime-avibactam is an antimicrobial association active against several Enterobacteriaceae species, including those resistant to carbapenem. Considering the... (Review)
Review
PURPOSE
Ceftazidime-avibactam is an antimicrobial association active against several Enterobacteriaceae species, including those resistant to carbapenem. Considering the importance of this drug in the current panorama of multidrug-resistant bacteria, we performed a systematic review about ceftazidime-avibactam with emphasis on clinical and pharmacological published data.
METHODS
A systematic search of the medical literature was performed. The databases searched included MEDLINE, EMBASE and Web of Science (until September 2017). The search terms used were 'avibactam', 'NXL104' and 'AVE1330A'. Bibliographies from those studies were also reviewed. Ceftazidime was not included as a search term, once relevant studies about avibactam in association with other drugs could be excluded. Only articles in English were selected. No statistical analysis or quality validation was included in this review.
RESULTS
A total of 151 manuscripts were included. Ceftazidime-avibactam has limited action against anaerobic bacteria. Avibactam is a potent inhibitor of class A, class C, and some class D enzymes, which includes KPC-2. The best pharmacodynamic profile of ceftazidime-avibactam is ƒT > MIC, validated in an animal model of soft tissue infection. Three clinical trials showed the efficacy of ceftazidime-avibactam in patients with intra-abdominal and urinary infections. Ceftazidime-avibactam has been evaluated versus meropenem/doripenem in hospitalized adults with nosocomial pneumonia, neutropenic patients and pediatric patients.
CONCLUSION
Ceftazidime-avibactam has a favorable pharmacokinetic profile for severe infections and highly active against carbapenemases of KPC-2 type.
Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Drug Combinations; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Urinary Tract Infections; beta-Lactam Resistance
PubMed: 29110143
DOI: 10.1007/s15010-017-1096-y -
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