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Current Drug Metabolism 2021Many antibiotics have a high potential for interactions with drugs, as a perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients.
BACKGROUND
Many antibiotics have a high potential for interactions with drugs, as a perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients.
METHODS
The aim of this review is to summarize the pharmacokinetic drug-drug interaction (DDI) of 45 antibiotics commonly used in sepsis care in China. Literature search was conducted to obtain human pharmacokinetics/ dispositions of the antibiotics, their interactions with drug-metabolizing enzymes or transporters, and their associated clinical drug interactions. Potential DDI is indicated by a DDI index ≥ 0.1 for inhibition or a treatedcell/ untreated-cell ratio of enzyme activity being ≥ 2 for induction.
RESULTS
The literature-mined information on human pharmacokinetics of the identified antibiotics and their potential drug interactions is summarized.
CONCLUSION
Antibiotic-perpetrated drug interactions, involving P450 enzyme inhibition, have been reported for four lipophilic antibacterials (ciprofloxacin, erythromycin, trimethoprim, and trimethoprim-sulfamethoxazole) and three antifungals (fluconazole, itraconazole, and voriconazole). In addition, seven hydrophilic antibacterials (ceftriaxone, cefamandole, piperacillin, penicillin G, amikacin, metronidazole, and linezolid) inhibit drug transporters in vitro. Despite no clinical PK drug interactions with the transporters, caution is advised in the use of these antibacterials. Eight hydrophilic antibiotics (all β-lactams; meropenem, cefotaxime, cefazolin, piperacillin, ticarcillin, penicillin G, ampicillin, and flucloxacillin), are potential victims of drug interactions due to transporter inhibition. Rifampin is reported to perpetrate drug interactions by inducing CYP3A or inhibiting OATP1B; it is also reported to be a victim of drug interactions, due to the dual inhibition of CYP3A4 and OATP1B by indinavir. In addition, three antifungals (caspofungin, itraconazole, and voriconazole) are reported to be victims of drug interactions because of P450 enzyme induction. Reports for other antibiotics acting as victims in drug interactions are scarce.
Topics: Anti-Bacterial Agents; Antifungal Agents; China; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Rifampin; Sepsis
PubMed: 32990533
DOI: 10.2174/1389200221666200929115117 -
Iranian Journal of Public Health Mar 2024Uropathogenic is a major cause of urinary tract infections (UTIs). This systematic review and meta-analysis was conducted to determine the prevalence of... (Review)
Review
BACKGROUND
Uropathogenic is a major cause of urinary tract infections (UTIs). This systematic review and meta-analysis was conducted to determine the prevalence of antibiotic-resistant uropathogenic among Iranian children with confirmed bacterial UTIs from 2012 to 2022.
METHODS
A systematic review was performed by searching PubMed, Scopus, Google Scholar, Web of Science, MagIran, Iranian Scientific Information Database, IranMedex, and Iranian Research Institute for Information Science and Technology. The antibiotic-specific pooled prevalence estimates were calculated by applying a random-effects model. Freeman-Tukey Double Arcsine transformation was applied. I-squared statistic, and Cochran's Q test were computed and meta-regression was conducted on latitude of sampling location.
RESULTS
The literature search retrieved 2159 articles, among which 19 articles were included. The highest antibiotic resistance was related to doxycycline, ticarcillin-clavulanic acid, cefazolin, cefuroxime, and amoxycillin-clavulanic acid, 59%, 57%, 54%, 53%, and 52%, respectively. Meta-regression on the latitude was statistically significant for nitrofurantoin (=0.05).
CONCLUSION
Resistant uropathogenic Escherichia coli strains were observed in the majority of confirmed bacterial UTIs among Iranian children. The most effective antibiotics for uropathogens were colistin, meropenem, and imipenem.
PubMed: 38919304
DOI: 10.18502/ijph.v53i3.15133 -
Antibiotics (Basel, Switzerland) Apr 2022The study aims to comparatively assess the nephrotoxicity of vancomycin when combined with piperacillin-tazobactam (V + PT) or meropenem (V + M) in adult patients...
Comparative Risk of Acute Kidney Injury Following Concurrent Administration of Vancomycin with Piperacillin/Tazobactam or Meropenem: A Systematic Review and Meta-Analysis of Observational Studies.
The study aims to comparatively assess the nephrotoxicity of vancomycin when combined with piperacillin-tazobactam (V + PT) or meropenem (V + M) in adult patients hospitalized in general wards or intensive care units. We searched MEDLINE, Google Scholar, and Web of Science for observational studies evaluating incidences of AKI in adult patients receiving V + PT or V + M for at least 48 h in general wards or intensive care units. The primary outcome was AKI events, while the secondary outcomes were hospital length of stay, need for renal replacement therapy (RRT), and mortality events. The odds ratio (OR), or mean difference for the hospital length of stay, with a corresponding 95% confidence interval (CI) from the inverse variance weighting random-effects model were estimated for the risk of AKI, RRT, and mortality. Of the 112 studies identified, twelve observational studies were included in this meta-analysis with a total of 14,511 patients. The odds of having AKI were significantly higher in patients receiving V + PT compared with V + M (OR = 2.31; 95%CI 1.69-3.15). There were no differences between V + PT and V + M in the hospital length of stay, RRT, or mortality outcomes. Thus, clinicians should be vigilant while using V + PT, especially in patients who are at high risk of AKI.
PubMed: 35453276
DOI: 10.3390/antibiotics11040526 -
Antibiotics (Basel, Switzerland) Dec 2023Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal... (Review)
Review
BACKGROUND
Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal complications after burn injuries, and broad-spectrum beta-lactams are the cornerstone of treatment. The aim of this study was to review the evidence for the best regimens of these antibiotics in the burn patient population.
METHODS
We performed a systematic review of evidence available on MEDLINE (from its inception to 2023) of pharmacology studies that focused on the use of 13 broad-spectrum beta-lactams in burn patients. We extracted and synthetized data on drug regimens and their ability to attain adequate PK/PD targets.
RESULTS
We selected 35 studies for analysis. Overall, studies showed that both high doses and the continuous infusion (CI) of broad-spectrum beta-lactams were needed to achieve internationally-recognized PK/PD targets, ideally with therapeutic drug monitoring guidance. The most extensive evidence concerned meropenem, but similar conclusions could be drawn about piperacillin-tazobactam, ceftazidime, cefepime, imipenem-clinastatin and aztreonam. Insufficient data were available about new beta-lactam-beta-lactamase inhibitor combinations, ceftaroline, ceftobiprole and cefiderocol.
CONCLUSIONS
Both high doses and CI of broad-spectrum beta-lactams are needed when treating burn patients due to the peculiar changes in the PK/PD of antibiotics in this population. Further studies are needed, particularly about newer antibiotics.
PubMed: 38136771
DOI: 10.3390/antibiotics12121737 -
Current Drug Safety 2017Observational studies have suggested an increased risk of nephrotoxicity when piperacillin-tazobactam is added to vancomycin, although the data are confliciting. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Observational studies have suggested an increased risk of nephrotoxicity when piperacillin-tazobactam is added to vancomycin, although the data are confliciting.
OBJECTIVE
To perform a meta-analysis of identified studies to assess if adding piperacillin-tazobactam to vancomycin increases the incidence of nephrotoxicity.
METHOD
A systematic review of PubMed, EMBASE, Cochrane Central, and Google Scholar was conducted to identify studies. Studies selected for meta-analysis were full length reports, retrospective or prospective, and designed specifically to assess if the combining piperacillin-tazobactam with vancomycin increases nephrotoxicity.
RESULTS
Six observational trials involving 963 patients were identified and analyzed. Five trials were retrospective and one was prospective. Vancomycin/piperacillin-tazobactam was compared to vancomycin alone in 2 trials, to vancomycin/cefepime in 3 trials, and vancomycin/cefepime or meropenem in one. Meta-analysis showed a statistical increase in the incidence of nephrotoxicity when piperacillin-tazobactam/vancomycin is compared to the control group (2.26 95% CI 1.41-3.63, p= 0.0007). No differences were noted between groups in patients requiring renal replacement.
CONCLUSION
Adding piperacillin-tazobactam to vancomycin increases the risk of nephrotoxicity when compared to vancomycin alone or vancomycin with either cefepime or meropenem.
Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Kidney Diseases; Observational Studies as Topic; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Retrospective Studies; Vancomycin
PubMed: 27784223
DOI: 10.2174/1574886311666161024164859 -
Annals of Intensive Care Apr 2024Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial...
BACKGROUND
Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP.
METHODS
We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events.
RESULTS
Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17-0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19-3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00-2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03-2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02-2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin.
CONCLUSIONS
This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria. Registration PROSPERO CRD42021226603.
PubMed: 38662091
DOI: 10.1186/s13613-024-01291-5 -
Pathogens and Global Health Feb 2020The present study was conducted to investigate the antimicrobial susceptibility profiles of serotypes, especially fluoroquinolone-resistant strains, recovered from... (Meta-Analysis)
Meta-Analysis
The present study was conducted to investigate the antimicrobial susceptibility profiles of serotypes, especially fluoroquinolone-resistant strains, recovered from clinical samples in Iran. A full electronic search using related keywords was conducted in Persian and English languages in ISI Web of Knowledge, PubMed, Scopus, Google Scholar and the Scientific Information Database (SID) search engines to find papers published between 1983 and 1 July 2019. According to the inclusion and exclusion criteria, 46 eligible articles were selected for the final analysis out of the initial 13,186 studies retrieved. The pooled prevalence of quinolone-resistant serotypes in clinical specimens in Iran was 2.9% to ciprofloxacin and 48.1% to nalidixic acid. Additional data on antibiotic resistance was as follows: 54.3% to tetracycline, 50.6% to ceftizoxime, 50.2% to streptomycin, 37.9% to ampicillin, 36.5% to kanamycin, 33.5% to trimethoprim-sulfamethoxazole, 27.2% to chloramphenicol, 19.1% to cephalothin, 8.8% to ceftriaxone, 7.6% to cefotaxime, 7.4% to aztreonam, 7.2% to gentamicin, 7% to cefepime, 6.8% to ceftazidime, 5.8% to cefixime, 2.7% to imipenem and 2.2% to meropenem. Findings of the present study showed a rising trend of resistance to the drugs of choice for the treatment of infections, i.e. ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole in Iran. However, ciprofloxacin, third-generation cephalosporins and carbapenems are still effective antibiotics especially against multi-drug resistant strains in Iran.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Iran; Salmonella; Salmonella Infections
PubMed: 32013798
DOI: 10.1080/20477724.2020.1719701 -
Antimicrobial Stewardship & Healthcare... 2021Ceftazidime/avibactam (C/A), ceftolozane/tazobactam (C/T), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V) combine either a cephalosporin (C/T and C/A) or a...
BACKGROUND
Ceftazidime/avibactam (C/A), ceftolozane/tazobactam (C/T), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V) combine either a cephalosporin (C/T and C/A) or a carbapenem antibiotic (M/V and I/R) with a β-lactamase inhibitor. They are used to treat carbapenem-resistant Enterobacterales (CRE) and/or multidrug-resistant (MDRPA).
OBJECTIVE
We compared the pooled clinical success of these medications to older therapies.
METHODS
PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for C/A, C/T, I/R, and M/V studies. The main outcome was clinical success, which was assessed using random-effects models. Stratified analyses were conducted for study drug, sample size, quality, infection source, study design, and multidrug-resistant gram-negative organism (MDRGNO) population. Microbiological success and 28- and 30-day mortality were assessed as secondary outcomes. Heterogeneity was determined using I values.
RESULTS
Overall, 25 articles met the inclusion criteria; 8 observational studies and 17 randomized control trials. We detected no difference in clinical success comparing new combination antibiotics with standard therapies for all included organisms (pooled OR, 1.21; 95% CI, 0.96-1.51). We detected a moderate level of heterogeneity among the included studies I = 56%. Studies that focused on patients with CRE or MDRPA infections demonstrated a strong association between treatment with new combination antibiotics and clinical success (pooled OR, 2.20; 95% CI, 1.60-3.57).
CONCLUSIONS
C/T, C/A, I/R, and M/V are not inferior to standard therapies for treating various complicated infections, but they may have greater clinical success for treating MDRPA and CRE infections. More studies that evaluate the use of these antibiotics for drug-resistant infections are needed to determine their effectiveness.
PubMed: 36168482
DOI: 10.1017/ash.2021.217 -
Expert Opinion on Drug Safety Jan 2024Most of the safety data of clobazam came from well-designed clinical trials, while the real-world information is insufficient.
BACKGROUND
Most of the safety data of clobazam came from well-designed clinical trials, while the real-world information is insufficient.
RESEARCH DESIGN AND METHODS
We performed a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database through OpenVigil 2 and conducted a systematic review of case reports regarding adverse drug reactions (ADR) linked to clobazam.
RESULTS
The analysis of FAERS identified 595 ADR signals. Nervous system disorders cantains the most positive signals among all system organ classes (SOCs). Except for seizure ( = 1696) and somnolence ( = 813), drug interactions ( = 492) were the most frequently reported positive signals. A total of 502 unique citations were initially retrieved and 31 individual cases from 28 publications were included. Skin reactions were the most reactions ( = 9), containing three types of severe reactions not alerted in the instruction. Five cases were caused by interactions between clobazam and other antiepileptic drugs, etravirine-based antiretroviral therapy, omeprazole, or meropenem. One patient died of aspiration pneumonia.
CONCLUSIONS
Clinicians must pay attention to severe skin reactions and monitor the signs of suspicious respiratory infections/inflammations and central sedation. Patients with skin reactions will benefit from the withdrawal of clobazam and the treatment with glucocorticoids. The drug reactions between clobazam with severe or moderate cytochrome P450 (CYP) 3A4 or CYP2C19 inhibitors or other antiepileptic drugs should also be alerted.
Topics: Humans; Clobazam; Anticonvulsants; Adverse Drug Reaction Reporting Systems; Drug-Related Side Effects and Adverse Reactions; Drug Interactions
PubMed: 37070461
DOI: 10.1080/14740338.2023.2204227 -
Medicine Oct 2020Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment.
METHODS
To compare the effectiveness and safety of carbapenems versus β-lactams for FN. PubMed, Medline (Ovid SP), Cochrane CENTRAL, and Embase were searched up to March 2019. FN in patients due to undergoing chemotherapy and treated with carbapenems and β-lactams were included. Odds ratio (OR) and 95% confidence interval (CI) were estimated.
RESULTS
Fifty randomized controlled trials (RCTs) studies involving 10,995 participants were included. Carbapenems were more likely to experience treatment success without modification (OR = 1.34, 95% CI = 1.24-1.46) compared with β-lactams. Meropenem (OR = 1.36, 95% CI = 1.18-1.56; OR = 1.24, 95% CI = 1.01-1.53), imipenem/cilastatin (OR = 1.40, 95% CI = 1.19-1.65; OR = 1.31, 95% CI = 1.04-1.67) showed higher effectiveness from that by β-lactams monotherapy or in combination with aminoglycoside, respectively. Carbapenems-aminoglycoside combination therapy does not provide an advantage over carbapenems alone. Meropenem showed similar risk of adverse events (AEs) versus β-lactams. Imipenem/cilastatin was related to higher risk of AEs compared with β-lactams. There was no significant difference between carbapenems and β-lactams monotherapy or in combination.
CONCLUSION
Meropenem and imipenem/cilastatin monotherapy appears to be available treatment for FN compared with β-lactams. Imipenem/cilastatin was related to higher risk of AEs. Balancing the evidence for drug efficacy and side effects, meropenem monotherapy appears to be available treatment for FN. Individual centers should select the best matching therapy regimens according to local epidemiology and susceptibility patterns.
Topics: Anti-Bacterial Agents; Carbapenems; Drug Therapy, Combination; Febrile Neutropenia; Humans; Randomized Controlled Trials as Topic; beta-Lactams
PubMed: 33120768
DOI: 10.1097/MD.0000000000022725