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Clinical Pharmacokinetics Feb 2023Pharmacokinetics (PK) are severely altered in pregnant women due to changes in volume of distribution (Vd) and/or drug clearance (CL), affecting target attainment of...
BACKGROUND AND OBJECTIVE
Pharmacokinetics (PK) are severely altered in pregnant women due to changes in volume of distribution (Vd) and/or drug clearance (CL), affecting target attainment of antibiotics in pregnant women. This review is part of a series that reviews literature on the description of PK and target attainment of antibiotics in pregnant women with specific focus on penicillins.
METHODS
A systematic literature search was carried out in PubMed. Articles were labelled as relevant when information on PK of penicillins in pregnant women was available.
RESULTS
Thirty-two relevant articles were included, 8 of which discussed amoxicillin (with and without clavulanic acid), 15 ampicillin, 4 benzylpenicillin, 1 phenoxymethylpenicillin, and 4 piperacillin (with and without tazobactam). No studies were found on pheneticillin and flucloxacillin in pregnant women. Ten out of 32 articles included information on both Vd and CL. During the second and third trimester of pregnancy, a higher CL and larger Vd was reported than in non-pregnant women and in pregnant women during first trimester. Reduced target attainment was described in second and third trimester pregnant women. Only 7 studies reported dosing advice, 4 of which were for amoxicillin.
CONCLUSION
The larger Vd and higher CL in second and third trimester pregnant women might warrant a higher dosage or shortening of the dosing interval of penicillins to increase target attainment. Studies frequently fail to provide dosing advice for pregnant women, even if the necessary PK information was available.
Topics: Pregnancy; Female; Humans; Penicillins; Anti-Bacterial Agents; Amoxicillin; Ampicillin; Piperacillin
PubMed: 36662480
DOI: 10.1007/s40262-023-01211-z -
Journal of Clinical and Experimental... Oct 2022Patients with odontogenic infections are commonly prescribed antimicrobials on an experiential base without knowing the precise microorganisms implicated. The aim of... (Review)
Review
BACKGROUND
Patients with odontogenic infections are commonly prescribed antimicrobials on an experiential base without knowing the precise microorganisms implicated. The aim of this systematic scoping review is to evaluate the prevalence and proportions of antimicrobial-resistant species in patients with odontogenic infections.
MATERIAL AND METHODS
A systematic scoping review of scientific evidence was accomplished involving different databases.
RESULTS
Eight randomized clinical trials and 13 prospective observational studies were included. These investigations analyzed 1506 patients. The species that showed higher levels of resistance included aerobic and facultative anaerobe such as , and . In obligate anaerobes sampled were Peptostreptococcos spp., Bacteroides spp., and Prevotella spp. Staphylococcus showed resistance to ampicillin, piperacillin, clindamycin, amoxicillin, metronidazole, and penicillin. Streptococcus had resistance to metronidazole, clindamycin, doxycycline, penicillin, and amoxicillin. Peptostreptococcus spp. presented resistance to penicillin, amoxicillin, erythromycin, and cefalexin. Gram-negative microorganisms had resistance to tetracycline, ciprofloxacin, azithromycin, amoxicillin, erythromycin, and penicillin. Bacteroides spp. exhibited resistance to penicillin, erythromycin, and gentamicin. Prevotella spp. showed resistance to penicillin, amoxicillin, erythromycin, clindamycin, levofloxacin, and imipenem. Finally, Klebsiella spp. displayed resistance to ampicillin, amoxicillin, moxifloxacin, and cefalexin. Interestingly, one clinical trial showed that after therapy there was a reduction in sensitivity of 18% for azithromycin and 26% for spiramycin.
CONCLUSIONS
Most of the microorganisms had resistance to diverse groups of antimicrobials. Suitable antimicrobials must be prescribed founded on the microbial samples, culture susceptibility, and clinical progression of the odontogenic infection. Furthermore, it was observed high levels of resistance to antimicrobials that have been used in local and systemic therapy of oral cavity infections. A preponderance of anaerobic microorganisms over aerobic ones was observed. Antibiotic resistance, odontogenic infections, efficacy, microorganisms, scoping review.
PubMed: 36320675
DOI: 10.4317/jced.59830 -
Frontiers in Pharmacology 2022β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing...
β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of β-lactams. Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of β-lactams are included in this study. A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used β-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses.
PubMed: 36210807
DOI: 10.3389/fphar.2022.964005 -
Frontiers in Medicine 2022Eravacycline is a novel, fully synthetic fluorocycline antibiotic for the treatment of adults with complicated intra-abdominal infections (cIAIs). However, the efficacy...
The efficacy and safety of eravacycline compared with current clinically common antibiotics in the treatment of adults with complicated intra-abdominal infections: A Bayesian network meta-analysis.
BACKGROUND
Eravacycline is a novel, fully synthetic fluorocycline antibiotic for the treatment of adults with complicated intra-abdominal infections (cIAIs). However, the efficacy and safety of eravacycline compared with current clinically common antibiotics remain unknown.
OBJECTIVE
This study aims to compare the efficacy and safety of eravacycline and other clinically common antibiotics in China, including tigecycline, meropenem, ertapenem, ceftazidime/avibactam+metronidazole, piperacillin/tazobactam, imipenem/cilastatin, and ceftriaxone+metronidazole, for the treatment of adults with cIAIs and to provide a reference for clinical choice.
METHODS
The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were electronically searched to collect clinical randomized controlled studies (RCTs) comparing different antibiotics in the treatment of patients with cIAIs from inception to June 1, 2021. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies.
RESULTS
A total of 4050 articles were initially retrieved, and 25 RCTs were included after screening, involving eight treatment therapies and 9372 patients. The results of network meta-analysis showed that in the intention-to-treat (ITT) population, the clinically evaluable (CE) population, and the microbiologically evaluable (ME) population, the clinical response rate of eravacycline was not significantly different from that of the other 7 therapies ( > 0.05). In terms of microbiological response rate, eravacycline was significantly better than tigecycline [tigecycline vs. eravacycline: RR = 0.82, 95%CI (0.65,0.99)], and there was no significant difference between the other 6 regimens and eravacycline ( > 0.05). In terms of safety, the incidence of serious adverse events, discontinuation rate, and all-cause mortality of eravacycline were not significantly different from those of the other 7 treatment therapies ( > 0.05).
CONCLUSION
Based on the evidence generated by the current noninferiority clinical trial design, the efficacy and safety of eravacycline for the treatment of adults with cIAIs are not significantly different from those of the other 7 commonly used clinical antibiotics in China. In terms of microbiological response rate, eravacycline was significantly better than tigecycline. In view of the severe multidrug-resistant situation in China, existing drugs have difficulty meeting the needs of clinical treatment, and the new antibacterial drug eravacycline may be one of the preferred options for the treatment of cIAIs in adults.
PubMed: 36186801
DOI: 10.3389/fmed.2022.935343 -
British Journal of Clinical Pharmacology Sep 2022This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence. (Meta-Analysis)
Meta-Analysis Review
AIMS
This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence.
METHODS
This study assessed risk factors for vancomycin-associated AKI in adult patients by searching studies from PubMed, the Cochrane Library and Embase. Random effect models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Fifty-three studies were included in our meta-analysis. For patient factors, black race (OR 1.47, 95% CI: 1.16-1.87), Caucasian (OR 0.72, 95% CI: 0.58-0.90) and obesity (OR 1.46, 95% CI: 1.12-1.90) were associated with an increase in vancomycin-associated AKIs. In terms of vancomycin-related factors, longer treatment duration (>14 d; OR 1.73, 95% CI: 1.06-2.83), serum vancomycin trough level >15 μg/mL (OR 2.10, 95% CI: 1.43-3.07) and vancomycin trough level >20 μg/mL (OR 2.84, 95% CI: 1.48-5.44) increased the risks of vancomycin-associated AKI. For comorbidities and clinical factors, renal disease (OR 2.19, 95% CI: 1.51-3.17) showed the highest odds of vancomycin-associated AKI, followed by hepatic disease, intensive care unit admission, heart failure, sepsis, coronary heart disease and diabetes mellitus. For concomitant nephrotoxic drugs, amphotericin B (OR 5.21, 95% CI: 3.44-7.87) showed the highest odds of vancomycin-associated AKI, followed by acyclovir (OR 3.22, 95% CI: 1.39-7.46), vasopressors, loop diuretics, piperacillin-tazobactam and aminoglycoside. The use of any concomitant nephrotoxic agent (OR 1.74, 95% CI: 1.17-2.58) increased the odds of vancomycin-associated AKI.
CONCLUSION
Our results may help predict the risk of vancomycin-associated AKI in the clinical setting.
Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Retrospective Studies; Risk Factors; Vancomycin
PubMed: 35665530
DOI: 10.1111/bcp.15429 -
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 -
Infection & Chemotherapy Mar 2022The use of antibiotics in diabetic foot ulcer infections (DFUI) is essential in reducing morbidity. Optimal administration of antibiotics can improve clinical outcomes...
BACKGROUND
The use of antibiotics in diabetic foot ulcer infections (DFUI) is essential in reducing morbidity. Optimal administration of antibiotics can improve clinical outcomes and reduce the risk of antibiotic resistance. This study aims to review the efficacy, in terms of clinical cure, of various regimens and the duration of antibiotic administration in DFUI patients, based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The efficacy based on microbiological response is also reviewed as the secondary outcome.
MATERIALS AND METHODS
We used three databases, namely PubMed, Scopus, and ScienceDirect, to search for randomized controlled trials (RCTs) in patients with DFUI who required antibiotics.
RESULTS
A total of 16 studies were included in the systematic review. The study locations and bacterial patterns varied, with the most common pathogen being . Most studies did not demonstrate a significant difference in clinical cure and pathogen eradication, either in the comparison between systemic and topical antibiotics or in the duration of administration. Some studies had similar characteristics and were analyzed to conclude. These studies showed that ertapenem had comparable efficacy to piperacillin/tazobactam. Similar results were also conducted from studies of piperacillin-tazobactam+amoxicillin-clavulanic acid moxifloxacin.
CONCLUSION
Most studies have heterogeneous characteristics, possibly due to differences in research location. Therefore, there is no strong evidence to recommend a specific antibiotic with the highest efficacy. However, since all included studies are RCTs, this review provides a good summary in considering antibiotic choices when treating DFUI patients.
PubMed: 35384424
DOI: 10.3947/ic.2021.0144 -
Medicine Dec 2021Antipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric...
BACKGROUND
Antipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric patients remain unclear. The aim of this study was to comprehensively compare the efficacy and side effects of optional antipseudomonal β-lactams for pediatric FN.
METHODS
PubMed, Embase, Medline, and Cochrane Library were systematically searched from their inception to December 18, 2020. Eligible randomized controlled trials in which pediatric FN patients were treated with an empiric monotherapy of antipseudomonal β-lactams were selected. Data synthesis was performed using WinBUGS 14.0 software and meta packages implemented in R 3.6.2. Random-effects network meta-analysis was performed, and dichotomous data were pooled as odds ratios with 95% confidence intervals. The primary outcome was treatment success without modification; the secondary outcomes were adverse events (AEs), all-cause mortality, and new infections. The GRADE tool was used to assess the quality of the evidence. The protocol was registered with PROSPERO ID CRD42021226763.
RESULTS
Eighteen studies with 2517 patients were included. The results showed no statistically significant difference between the optional antipseudomonal β-lactams in the outcomes of treatment success without modification, all AEs, all-cause mortality, and new infections for pediatric FN. Based on the results of Bayesian rank probability, meropenem was ranked highest among all the treatment options with regard to treatment success without modification benefit; ceftazidime and meropenem were associated with a lower risk of AEs; cefoperazone/sulbactam and piperacillin/tazobactam were associated with a lower risk of mortality, and piperacillin/tazobactam and meropenem were associated with a lower risk of new infections. The quality of evidence was moderate.
CONCLUSIONS
Meropenem and piperacillin/tazobactam were found to be better with regard to treatment success without modification, with a comparable safety profile. Therefore, our findings support the use of meropenem and piperacillin/tazobactam as a treatment option for pediatric FN patients.
Topics: Anti-Bacterial Agents; Ceftazidime; Child; Drug Therapy, Combination; Febrile Neutropenia; Female; Humans; Imipenem; Male; Meropenem; Network Meta-Analysis; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Treatment Outcome; beta-Lactams
PubMed: 34918626
DOI: 10.1097/MD.0000000000027266 -
Revista Chilena de Infectologia :... Aug 2021Febrile neutropenia in children with onco-hematological diseases is an important cause of morbidity and mortality and requires early and adequate empirical treatment.... (Meta-Analysis)
Meta-Analysis
[Efficacy and safety of empirical treatment with piperacillin/tazobactan as monotherapy in episodes of neutropenia and fever in children with cancer: systematic review and meta-analysis].
BACKGROUND
Febrile neutropenia in children with onco-hematological diseases is an important cause of morbidity and mortality and requires early and adequate empirical treatment. This systematic review was conducted to evaluate if piperacillin/ tazobactan (PTZ) monotherapy leads to a lower incidence of therapeutic failures than comparators.
METHODS
A literature search was carried out in Embase, and MEDLINE databases using the search terms ('febrile neutropenia' OR hemato oncology OR haemato oncology OR 'immunocompromised host' OR 'immunocompromised patient' OR 'chemotherapy-induced febrile neutropenia') AND (piperacillin OR tazobactam OR 'piperacillin plus tazobactam' OR 'piperacillin/tazobactam' OR 'piperacillin-tazobactam' OR tazocin OR 'piperacillin-tazobactam drug combination')), Efficacy endpoint was treatment failure rate. The safety end-point was absence of any adverse effects (AE).
RESULTS
Eleven studies were included. No heterogeneity was detected ( I 2 0%). The risk of failure was not superior for piperacillin/tazobactan to comparators (Global RR: 0.94; IC95% 0.83 a 1.07). Rates of adverse events were similar among studies. No publication bias was detected (p 0.36).
CONCLUSIONS
This systematic review and meta-analysis showed that treating episodes of febrile neutropenia in oncology pediatric patients, the risk of failure for PTZ was not superior to comparators. Adverse events were similar to the comparators.
Topics: Anti-Bacterial Agents; Child; Drug Therapy, Combination; Humans; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin
PubMed: 34652393
DOI: 10.4067/S0716-10182021000400488 -
Revista Do Instituto de Medicina... 2021The aim of this study was to establish an evidence-based guideline for the antibiotic treatment of Corynebacterium striatum infections. Several electronic databases were...
The aim of this study was to establish an evidence-based guideline for the antibiotic treatment of Corynebacterium striatum infections. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with systemic inflammatory response syndrome, harboring C. striatum isolated from body fluids or tissues in which it is not normally present. C. striatum had to be identified as the only causative agent of the invasive infection, and its isolation from blood, body fluids or tissues had to be confirmed by one of the more advanced diagnostic methods (biochemical methods, mass spectrometry and/or gene sequencing). This systematic review included 42 studies that analyzed 85 individual cases with various invasive infections caused by C. striatum. More than one isolate of C. striatum exhibited 100% susceptibility to vancomycin, linezolid, teicoplanin, piperacillin-tazobactam, amoxicillin-clavulanate and cefuroxime. On the other hand, some strains of this bacterium showed a high degree of resistance to fluoroquinolones, to the majority majority of β-lactams, aminoglycosides, macrolides, lincosamides and cotrimoxazole. Despite the antibiotic treatment, fatal outcomes were reported in almost 20% of the patients included in this study. Gene sequencing methods should be the gold standard for the identification of C. striatum, while MALDI-TOF and the Vitek system can be used as alternative methods. Vancomycin should be used as the antibiotic of choice for the treatment of C. striatum infections, in monotherapy or in combination with piperacillin-tazobactam. Alternatively, linezolid, teicoplanin or daptomycin may be used in severe infections, while amoxicillin-clavulanate may be used to treat mild infections caused by C. striatum.
Topics: Aminoglycosides; Anti-Bacterial Agents; Corynebacterium; Corynebacterium Infections; Humans; Microbial Sensitivity Tests
PubMed: 34161555
DOI: 10.1590/S1678-9946202163049