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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 -
The Annals of Pharmacotherapy Jan 2024Several studies have shown that vancomycin combined with piperacillin/tazobactam (VPT) increased the risk of acute kidney injury (AKI) compared with other antibiotics in... (Review)
Review
BACKGROUND
Several studies have shown that vancomycin combined with piperacillin/tazobactam (VPT) increased the risk of acute kidney injury (AKI) compared with other antibiotics in children. However, the epidemiology of VPT-associated AKI in children is unknown.
OBJECTIVE
To evaluate the incidence and risk factors of VPT-associated AKI in children.
DATA SOURCES
Literature databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and China Biology Medicine Disc were searched from inception to November 2023. References of included studies were also manually checked.
STUDY SELECTION AND DATA EXTRACTION
Two independent reviewers selected studies, extracted data, and quality assessment. Meta-analyses were performed to quantify the incidence and risk factors of VPT-associated AKI in children.
DATA SYNTHESIS
Sixteen cohort studies were identified. Overall, the incidence of VPT-associated AKI in children was 24.3% (95% CI: 17.9%-30.6%). The incidence of VPT-associated AKI in critically ill children (26.6%) was higher than that in noncritically ill children (10.9%). Moreover, higher serum vancomycin trough concentration (>15 mg/L), use of vasopressors, combination of nephrotoxins and intensive care unit admission were risk factors for VPT-associated AKI in children ( < 0.05).
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Identifying high-risk groups and determining safer treatments is critical to reducing the incidence of VPT-associated AKI in children.
CONCLUSIONS
The incidence of VPT-associated AKI in children is high, especially in critically ill children. Medication regimens should be personalized based on the presence of individual risk factors. Moreover, renal function was regularly assessed throughout treatment with VPT.
PubMed: 38279799
DOI: 10.1177/10600280231220379 -
Thorax Oct 2021The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate and (2) mortality rate in hospitalised patients with community acquired pneumonia (CAP) .
METHOD
Inclusion criteria: (1) adult patients (>16 years old) diagnosed with CAP that required hospitalisation; (2) randomised to at least two different Em-ATBs, (3) that report cure rate and (4) are written in English or Spanish.
EXCLUSION CRITERIA
(1) ambiguous antibiotics protocol and (2) published exclusively in abstract or letter format.
DATA SOURCES
Medline, Embase, Cochrane and citation reviews from 1 January 2000 to 31 December 2018. Risk of bias: Cochrane's tool. Quality of the systematic review (SR): A MeaSurement Tool to Assess systematic Reviews-2. Certainity of the evidence: Grading of Recommendations Assessment, Development and Evaluation.
STATISTICAL ANALYSES
frequentist method performed with the 'netmeta' library, R package.
RESULTS
27 randomised controlled trials (RCTs) from the initial 41 307 screened citations were included. Regarding the risk of bias, more than one quarter of the studies presented low risk and no study presented high risk in all domains. The SR quality is moderate. two networks were constructed. Thus, two Em-ATBs have the HPBB: cetaroline 600 mg (two times a day) and piperacillin 2000 mg (two times a day). three networks were constructed. Thus, three Em-ATBs have the HPBB: ceftriaxone 2000 mg (once a day) plus levofloxacin 500 (two times a day), ertapenem 1000 mg (two times a day) and amikacin 250 mg (two times a day) plus clarithromycin 500 mg (two times a day). The certainity of evidence for each results is moderate.
CONCLUSION
For cure rate, ceftaroline and piperaciline are the options with the HPBB. However, for mortality rate, the options are ceftriaxone plus levofloxacin, ertapenem and amikacin plus clarithromycin. It seems necessary to conduct an RCT that compares treatments with the HPBB for each event (cure or mortality) (CRD42017060692).
Topics: Adolescent; Adult; Anti-Bacterial Agents; Community-Acquired Infections; Humans; Network Meta-Analysis; Pneumonia
PubMed: 33723019
DOI: 10.1136/thoraxjnl-2019-214054 -
Open Forum Infectious Diseases Apr 2021In hospital settings, restriction of selected classes of antibiotics is usually believed to contribute to containment of resistance development. We performed a...
BACKGROUND
In hospital settings, restriction of selected classes of antibiotics is usually believed to contribute to containment of resistance development. We performed a systematic review and meta-analysis to assess the effect of restricting the use of specific antibiotic classes on the prevalence of resistant bacterial pathogens.
METHODS
We conducted a systematic literature search in Embase and PubMed/OVID MEDLINE. We included studies until June 4, 2020 in which a restrictive antibiotic policy was applied and prevalence of resistance and use of antibiotics were reported. We calculated the overall effect of antimicrobial resistance between postintervention versus preintervention periods using pooled odds ratios (ORs) from a mixed-effects model. We stratified meta-analysis by antibiotic-pathogen combinations. We assessed heterogeneity between studies using the I statistic and sources of heterogeneity using meta-regression.
RESULTS
We included 15 individual studies with an overall low quality of evidence. In meta-analysis, significant reductions in resistance were only observed with nonfermenters after restricting fluoroquinolones (OR = 0.77, 95% confidence interval [CI] = 0.62-0.97) and piperacillin-tazobactam (OR = 0.81, 95% CI = 0.72-0.92). High degrees of heterogeneity were observed with studies restricting carbapenem (Enterobacterales, I = 70.8%; nonfermenters, I = 81.9%), third-generation cephalosporins (nonfermenters, I = 63.3%), and fluoroquiolones (nonfermenters, I = 64.0%). Results were comparable when excluding studies with fewer than 50 bacteria. There was no evidence of publication bias for any of the antibiotic-pathogen combinations.
CONCLUSIONS
We could not confirm that restricting carbapenems or third-generation cephalosporins leads to decrease in prevalence of antibiotic resistance among Enterobacterales, nonfermenters, or Gram-positive bacteria in hospitalized patients. Nevertheless, reducing fluoroquinolone and piperacilline-tazobactam use may decrease resistance in nonfermenters.
PubMed: 33880388
DOI: 10.1093/ofid/ofab070 -
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 -
Antimicrobial Agents and Chemotherapy Sep 2019Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this...
Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Out of 1381 non-duplicate studies, 10 met our inclusion criteria. We performed a random effects meta-analysis, based on crude odds ratios, and we accounted for both quality of included studies and publication bias. In primary analysis, concomitant vancomycin and TZP use yielded a statistically significant association with the development of AKI. More specifically, children with AKI had higher odds to have been exposed to vancomycin plus TZP, in comparison with vancomycin monotherapy (OR 8.15; 95% CI: 3.49-18.99), or vancomycin plus any other beta-lactam antibiotic (OR 3.48; 95% CI: 2.71-4.46). Based on the results of the Newcastle Ottawa Scale quality assessment, a secondary analysis including only higher quality studies (6 out of 10 studies) yielded again higher odds of exposure to vancomycin plus TZP, compared to vancomycin plus another beta-lactam antibiotic (OR 3.76; 95% CI: 2.56-5.51). Notably, even after controlling for possible publication bias our results remained statistically significant (OR 3.09; 95% CI: 2.30-4.14). In conclusion, the concomitant use of vancomycin and TZP could be associated with AKI development and the clinical significance of this potential association needs to be studied further in the pediatric population.
PubMed: 31591125
DOI: 10.1128/AAC.01572-19 -
Frontiers in Public Health 2023(), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated... (Review)
Review
BACKGROUND
(), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated with diverse diseases. The diagnostic trajectory for -related diseases encounters delays, often with severe consequences, including fatality, attributed to the absence of symptom specificity and challenges in culture. The absence of a consensus on the diagnostic and therapeutic approaches to exacerbates the complexity of addressing associated conditions. This study aims to elucidate and scrutinize the clinical manifestations linked to , drawing insights from an extensive literature review of pertinent case reports.
CASE PRESENTATION
A 53-year-old male sought medical attention at our institution presenting with recurrent hemoptysis. Empirical treatment was initiated while awaiting pathogen culture results; however, the patient's symptoms persisted. Subsequent metagenomic next-generation sequencing (mNGS) analysis revealed a pulmonary infection attributable to . Resolution of symptoms occurred following treatment with piperacillin sulbactam sodium and moxifloxacin hydrochloride. A comprehensive literature review, utilizing the PubMed database, was conducted to assess case reports over the last decade where was identified as the causative agent.
CONCLUSION
The literature analysis underscores the predilection of for immunocompromised populations afflicted by cardiovascular diseases, diabetes, orthopedic conditions, and tumors. Risk factors, including oral and periodontal hygiene, smoking, and alcohol consumption, were found to be associated with infections. Clinical manifestations encompassed fever, cough, sputum production, and back pain, potentially leading to severe outcomes such as Spondylodiscitis, septic arthritis, lung abscess, bacteremia, sepsis, and mortality. While conventional bacterial culture remains the primary diagnostic tool, emerging technologies like mNGS offer alternative considerations. In terms of treatment modalities, β-lactam antibiotics and nitroimidazoles predominated, exhibiting recovery rates of 56.10% (46/82) and 23.17% (19/82), respectively. This case report and literature review collectively aim to enhance awareness among clinicians and laboratory medicine professionals regarding the intricacies of -associated infections.
Topics: Humans; Male; Middle Aged; Base Composition; Firmicutes; Hemoptysis; Phylogeny; Piperacillin; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Gram-Positive Bacterial Infections
PubMed: 38389952
DOI: 10.3389/fpubh.2023.1307902 -
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 -
Frontiers in Pediatrics 2020This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future...
This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future pharmacology studies. We systematically searched the databases MEDLINE, CINAHL, and Embase from earliest publication until November 2018 using a controlled vocabulary and keywords related to "ECMO" and "pharmacokinetics," "pharmacology," "drug disposition," "dosing," and "pediatrics." Inclusion criteria were as follows: study population aged <18 years, supported on ECMO for any indications, received any medications while on ECMO, and reported pharmacokinetic data. Clearance and/or volume of distribution values were extracted from included studies. Forty-one studies (total patients = 574) evaluating 23 drugs met the inclusion criteria. The most common drugs studied were antimicrobials ( = 13) and anticonvulsants ( = 3). Twenty-eight studies (68%) were conducted in children <1 year of age. Thirty-three studies (80%) were conducted without intra-study comparisons to non-ECMO controls. Increase in volume of distribution attributable to ECMO was demonstrated for nine (56%) drugs: cefotaxime, gentamicin, piperacillin/tazobactam, fluconazole, micafungin, levetiracetam, clonidine, midazolam, and sildenafil (range: 23-345% increase relative to non-ECMO controls), which may suggest the need for higher initial dosing. Decreased volume of distribution was reported for two drugs: acyclovir and ribavirin (50 and 69%, respectively). Decreased clearance was reported for gentamicin, ticarcillin/clavulanate, bumetanide, and ranitidine (range: 26-95% decrease relative to non-ECMO controls). Increased clearance was reported for caspofungin, micafungin, clonidine, midazolam, morphine, and sildenafil (range: 25-455% increase relative to non-ECMO controls). There were substantial pharmacokinetic alterations in 70% of drugs studied in children on ECMO. However, studies evaluating pharmacokinetic changes of many drug classes and those that allow direct comparisons between ECMO and non-ECMO patients are still lacking. Systematic evaluations of pharmacokinetic alterations of drugs on ECMO that incorporate multidrug opportunistic trials, physiologically based pharmacokinetic modeling, and other methods are necessary for definitive dose recommendations. : CRD42019114881.
PubMed: 32670992
DOI: 10.3389/fped.2020.00260 -
APMIS : Acta Pathologica,... Feb 2024The objectives of this study were to perform a systematic review of publications between 2010 and 2021 on the antibiotic resistance of Pseudomonas aeruginosa and...
The objectives of this study were to perform a systematic review of publications between 2010 and 2021 on the antibiotic resistance of Pseudomonas aeruginosa and Acinetobacter baumannii from urinary tract infections and to analyze changes over time in hospital urine cultures from 2016 through 2021. The literature was searched, and a retrospective cross-sectional descriptive study was performed in the hospital. Out of 21 838 positive urine cultures, 3.86% were due to P. aeruginosa and 0.44% were due to A. baumannii. For P. aeruginosa, lower resistance rates were observed to virtually all tested antibiotics than were obtained in the systematic review, and the present series of hospital samples showed an in vitro resistance rate <10% to ceftazidime, cefepime, meropenem, piperacillin-tazobactam, amikacin, tobramycin, and colistin. For A. baumannii, the resistance rates to almost all antibiotics were higher in the present series than in the systematic review, being lowest to colistin (10%). Both microorganisms show reduced in vitro susceptibility to some antibiotics during the years of the COVID-19 pandemic in comparison to previous years. In our setting, both piperacillin-tazobactam and meropenem can be recommended for the empirical treatment of UTIs by P. aeruginosa, whereas only colistin can be recommended for UTIs by A. baumannii.
Topics: Humans; Pseudomonas aeruginosa; Meropenem; Acinetobacter baumannii; Spain; Colistin; Cross-Sectional Studies; Retrospective Studies; Pandemics; Anti-Bacterial Agents; Pseudomonas Infections; Piperacillin, Tazobactam Drug Combination; Urinary Tract Infections; Drug Resistance, Multiple, Bacterial; Hospitals; Microbial Sensitivity Tests
PubMed: 37971152
DOI: 10.1111/apm.13360