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Antibiotics (Basel, Switzerland) Feb 2022Antimicrobial resistance to treatments for infection (CDI) poses a significant threat to global health. is widely thought to be susceptible to oral vancomycin, which... (Review)
Review
Antimicrobial resistance to treatments for infection (CDI) poses a significant threat to global health. is widely thought to be susceptible to oral vancomycin, which is increasingly the mainstay of CDI treatment. However, clinical labs do not conduct susceptibility testing, presenting a challenge to detecting the emergence and impact of resistance. In this systematic review, we describe gene determinants and associated clinical and laboratory mechanisms of vancomycin resistance in , including drug-binding site alterations, efflux pumps, RNA polymerase mutations, and biofilm formation. Additional research is needed to further characterize these mechanisms and understand their clinical impact.
PubMed: 35203860
DOI: 10.3390/antibiotics11020258 -
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 -
International Journal of Antimicrobial... Nov 2019Ceftaroline fosamil is a fifth-generation cephalosporin with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. It has been approved by the EMA and FDA... (Review)
Review
Ceftaroline fosamil is a fifth-generation cephalosporin with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. It has been approved by the EMA and FDA for the treatment of adults and children with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). However, ceftaroline fosamil has a broad spectrum of activity, and a good safety and tolerability profile, so is frequently used off-label. The aim of this systematic review was to summarize the safety and efficacy of off-label use of ceftaroline. The review was conducted according to PRISMA guidelines. MEDLINE, EMBASE and CENTRAL databases (2010-2018) were searched using as the main term ceftaroline fosamil and its synonyms in combination with names of infectious diseases of interest. A total of 21 studies with 1901 patients were included: the most common off-label indications for ceftaroline use were bacteremia (n=595), endocarditis (n=171), osteoarticular infections (n=368), hospital-acquired pneumonia (n=115) and meningitis (n=23). The most common reasons for off-label use were persistent or recurrent infection after standard treatment or non-susceptibility to vancomycin and daptomycin. Clinical success was evaluated in 933 patients, and 724 (77%) of these reached this positive outcome. Incidence of adverse events (AEs) was reported in 11 studies. In 83 (9%) cases there were AEs related to the use of ceftaroline; the most common reported AEs were nausea, vomiting, diarrhea, rash and neutropenia. The review results show that ceftaroline may be used in clinical settings other than those currently approved; however, the use of ceftaroline in these contexts deserves further investigation.
Topics: Anti-Bacterial Agents; Bacteremia; Cephalosporins; Community-Acquired Infections; Cross Infection; Endocarditis, Bacterial; Healthcare-Associated Pneumonia; Humans; Meningitis; Off-Label Use; Ceftaroline
PubMed: 31279152
DOI: 10.1016/j.ijantimicag.2019.06.025 -
Frontiers in Pharmacology 2023Dose optimization of vancomycin plays a substantial role in drug pharmacokinetics because of the increased incidence of obesity worldwide. This systematic review was...
Dose optimization of vancomycin plays a substantial role in drug pharmacokinetics because of the increased incidence of obesity worldwide. This systematic review was aimed to highlight the current dosing strategy of vancomycin among obese patients. This systematic review was in concordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The literature search was carried out on various databases such as Scopus, PubMed/MEDLINE, ScienceDirect and EMBASE using Keywords and MeSH terms related to vancomycin dosing among obese patients. Google Scholar was also searched for additional articles. The English language articles published after January, 2000 were included in this study. The quality of the study was assessed using different assessment tools for cohort, and case reports. A total of 1,029 records were identified. After screening, 18 studies were included for the final review. Of total, twelve studies are retrospective and remaining six are case-control studies. A total of eight studies were conducted in pediatrics while remaining studies were conducted in adult population. Most of the studies reported the dosing interval every 6-8 h. Differences in target trough concentration exist with respect to target ranges. The administration of loading dose (20-25 mg/kg) followed by maintenance dose (15-25 mg/kg) of vancomycin is recommended in adult patients to target therapeutic outcomes. Moreover, a dose of 40-60 mg/kg/day appears appropriate for pediatric patients. The initial dosing of vancomycin based on TBW could be better predictor of vancomycin trough concentration. However, the clinical significance is uncertain. Therefore, more studies are needed to evaluate the dosing strategy of vancomycin in overweight or obese patients.
PubMed: 37033643
DOI: 10.3389/fphar.2023.965284 -
Antimicrobial Agents and Chemotherapy Aug 2022To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases,... (Meta-Analysis)
Meta-Analysis
To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases, including PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, the Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED), were comprehensively searched to obtain research articles on vancomycin use in children from inception through December 2021. All studies were screened and evaluated using the Cochrane systematic review method. Then, the feature information was extracted for meta-analysis. The evaluated results included clinical efficacy, vancomycin-associated nephrotoxicity, hepatotoxicity, ototoxicity, mortality, and microbial clearance. A total of 35 studies involving 4820 children were included in the analysis. The meta-analysis showed that compared with children with vancomycin trough concentrations <10 μg/mL, those with vancomycin trough concentrations ≥10 μg/mL had a higher clinical efficacy rate [OR: 2.23, 95% CI: 1.29 to 3.84, = 0.004] and higher incidences of nephrotoxicity [OR: 2.76, 95% CI: 1.51 to 5.07, = 0.001], ototoxicity [OR: 1.87, 95% CI: 1.08 to 3.23, = 0.02] and microbial clearance [OR: 2.36, 95% CI: 1.53 to 3.64, = 0.0001]. All-cause mortality [OR: 1.07, 95% CI: 0.45 to 2.53, = 0.88] and hepatotoxicity [OR: 0.84, 95% CI: 0.46 to 1.53, = 0.57] were similar between the two groups. Subgroup analysis showed that compared with children with vancomycin trough concentrations of 10 to 15 μg/mL, those with vancomycin trough concentrations >15 μg/mL had a higher incidence of nephrotoxicity [OR: 2.64, 95% CI: 1.28 to 5.43, = 0.008], but there was no significant difference in clinical efficacy [OR: 0.85, 95% CI: 0.30 to 2.44, = 0.76]. A vancomycin trough concentration of 10 to 15 μg/mL can improve clinical efficacy in children. Additionally, avoidance of trough concentrations >15 μg/mL can reduce the incidence of adverse reactions.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Child; Humans; Ototoxicity; Renal Insufficiency; Retrospective Studies; Vancomycin
PubMed: 35862741
DOI: 10.1128/aac.00138-22 -
The Annals of Pharmacotherapy Dec 2022To assess the success rates of off-label uses of ceftaroline for infections caused by methicillin-resistant (MRSA) and evaluate emerging ceftaroline resistance. (Review)
Review
OBJECTIVE
To assess the success rates of off-label uses of ceftaroline for infections caused by methicillin-resistant (MRSA) and evaluate emerging ceftaroline resistance.
DATA SOURCES
We queried PubMed/MEDLINE, with the search term "Ceftaroline." Articles were restricted to the English language and year of publication (January 1, 2009-January 31, 2022).
STUDY SELECTION AND DATA EXTRACTION
Clinical trials, observational studies, and case reports that reported efficacy, safety, pharmacokinetics, use in MRSA infections other than acute bacterial skin infection and community-acquired pneumonia, and ceftaroline resistance were selected.
DATA SYNTHESIS
The search pooled 103 publications and all abstracts were reviewed. Forty-six articles that reported efficacy, safety, pharmacokinetics, or off-label use in multiple patients and 7 articles on ceftaroline resistance are used in this review. Ceftaroline has been approved for treatment of acute skin/soft tissue infection and community-acquired pneumonia. Ceftaroline's efficacy in off-label infections ranged from 66.7% to 87.3% depending on the types of infection. There were 14 documented cases of ceftaroline resistance associated with PBP2a changes.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Case series and observational studies have documented success with ceftaroline alone or in combination with vancomycin or daptomycin for treatment of MRSA bone and joint, endovascular, diabetic foot infections, and bacteremia from other causes.
CONCLUSION
Despite the lack of randomized controlled trials, ceftaroline is used as salvage therapy for different MRSA infections. The data from case series and observational studies are promising but ceftaroline should be used judiciously as ceftaroline-resistant MRSA begin to emerge.
Topics: Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Daptomycin; Drug Resistance; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Vancomycin; Ceftaroline
PubMed: 35300514
DOI: 10.1177/10600280221082326 -
Therapeutic Drug Monitoring Jun 2020Studies comparing the clinical outcomes between vancomycin intermittent infusion (InI) and continuous infusion (CoI) treated patients are generally underpowered....
BACKGROUND
Studies comparing the clinical outcomes between vancomycin intermittent infusion (InI) and continuous infusion (CoI) treated patients are generally underpowered. Moreover, due to large differences in the design and efficacy end points in these studies, a meta-analysis of the currently available data is not feasible. Therefore, this systematic review aimed to compare the exposure variability and target attainment with vancomycin during InI and CoI.
PATIENTS AND METHODS
A literature search was performed, and clinical studies reporting on vancomycin-treated populations were selected. After exclusion of reviews, case reports, and articles not published in the English language, 505 articles were screened for reported data on vancomycin serum concentrations. A total of 34 studies were included in the review. Relative standard deviations reported in the included studies were assessed, and vancomycin serum concentration variability and target attainment were compared between vancomycin InI and CoI.
RESULTS
The variability in serum concentrations was significantly larger for InI than for CoI (relative standard deviations 46.5% and 32.1%, respectively; P = 0.001). Notably, variability appeared to be independent of the study population or design. Studies directly comparing target attainment between both modes of administration denoted higher and faster target attainment with CoI in all instances.
CONCLUSIONS
In conclusion, CoI was associated with lower variabilities in the serum concentration and favorable target attainment rates compared with InI. These findings are important because vancomycin exposure is considered a major predictor of the patients' clinical outcomes. However, the role of lower serum concentration variability and higher target attainment rates in achieving better clinical outcomes needs to be evaluated in patients treated with vancomycin CoI compared with InI.
Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Drug Administration Schedule; Drug Monitoring; Healthy Volunteers; Humans; Infusions, Intravenous; Intensive Care Units; Vancomycin
PubMed: 32432845
DOI: 10.1097/FTD.0000000000000755 -
Microbial Drug Resistance (Larchmont,... Aug 2021Several and studies demonstrated that adding a β-lactam to vancomycin (VAN) or daptomycin (DAP) can provide synergy against methicillin-resistant (MRSA). However,... (Meta-Analysis)
Meta-Analysis
Several and studies demonstrated that adding a β-lactam to vancomycin (VAN) or daptomycin (DAP) can provide synergy against methicillin-resistant (MRSA). However, the results from clinical studies were controversial. The objective of this systematic review and meta-analysis was to compare the efficacy and safety of using VAN or DAP plus a β-lactam (combination therapy) and using VAN or DAP alone (monotherapy) in MRSA bloodstream infections. We included randomized controlled trials and observational studies evaluating whether combination therapy can improve clinical and microbiological outcomes and safety compared to monotherapy with VAN or DAP in MRSA-related bacteremia. Literature search identified 3 randomized clinical trials and 10 observational studies involving at least 1,796 patients. There were no significant associations between the combination therapy and risk of mortality within 30 days (risk ratios [RRs], 1.10, 95% confidence interval [CI], 0.82-1.46), in-hospital mortality (RR, 0.59, 95% CI, 0.31-1.13) and mortality within 60-90 days (RR, 0.91, 95% CI, 0.64-1.29). There was also no evidence that there was a difference in length of hospital stay between the combination therapy and monotherapy (mean difference, -0.41 days, 95% CI, -3.41 to 2.59). However, compared with monotherapy, combination therapy seemed to have a shorter duration of bacteremia(mean difference, -1.06 days, 95% CI, -1.53 to -0.60), a lower risk of persistent bacteremia (RR, 0.63, 95% CI, 0.51-0.79) and a lower risk of bacteremia recurrence within 60-90 days (RR, 0.61, 95% CI, 0.40-0.92). There were no statistically significant differences in the total number of adverse events, including acute kidney injury (AKI) (RR, 1.52, 95% CI, 0.84-2.73), thrombocytopenia (RR, 1.13, 95% CI, 0.74-1.73), and diarrhea (RR, 1.36, 95% CI, 0.70-2.65), between patients with combination therapy and monotherapy. In subgroup analysis, when the analysis was limited to the studies comparing using DAP plus ceftaroline with monotherapy, we found that the former had a lower risk of mortality within 30 days. In addition, a subgroup analysis limited to randomized clinical trials showed that the combination therapy was associated with a higher risk of AKI compared with using VAN or DAP alone. Although adding a β-lactam to standard therapy seemed to experience a higher clearance compared with monotherapy in patients with MRSA bacteremia, the combination therapy did not increase survival benefits. Based on the available evidence, the combination therapy was not supported as the routine management of MRSA-related bacteremia, and both its harms and benefits should be taken into account.
Topics: Anti-Bacterial Agents; Bacteremia; Daptomycin; Drug Therapy, Combination; Humans; Length of Stay; Methicillin-Resistant Staphylococcus aureus; Observational Studies as Topic; Randomized Controlled Trials as Topic; Staphylococcal Infections; Vancomycin; beta-Lactams
PubMed: 33728980
DOI: 10.1089/mdr.2020.0350 -
Journal of Ophthalmic Inflammation and... Nov 2022The goal of this study is to determine if certain aspects of endophthalmitis prophylaxis strategies are superior to others.
PURPOSE
The goal of this study is to determine if certain aspects of endophthalmitis prophylaxis strategies are superior to others.
DESIGN
This investigation is a systematic review and meta-analysis.
METHODS
All studies specifying a type of prophylaxis strategy and resulting rates of endophthalmitis were included. Time course, method of administration, and antibiotic regimen, and confounding factors were collected and included for meta-regression.
RESULTS
Time courses greater than 24 h did not significantly improve outcomes. Likewise, intraocular and/or intravenous antibiotic administration methods did not significantly outperform oral administration. No antibiotic regimens performed differently from vancomycin/ ≥ 3 generation cephalosporin except for ciprofloxacin monotherapy which yielded significantly worse outcomes.
CONCLUSIONS
Future antibiotic strategies should strongly consider the risks of antibiotic treatment > 24 h and administration methods other than the oral antibiotic forms. In addition, providers should be wary of using ciprofloxacin monotherapy for endophthalmitis prophylaxis when treating open globe injuries.
PubMed: 36396863
DOI: 10.1186/s12348-022-00317-y -
Expert Review of Anti-infective Therapy Nov 2022To know the efficacy of different doses of dalbavancin in acute bacterial skin and skin-structure infections (ABSSSIs) and versus other antibiotics. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To know the efficacy of different doses of dalbavancin in acute bacterial skin and skin-structure infections (ABSSSIs) and versus other antibiotics.
METHODS
We performed a systematic review of dalbavancin efficacy for ABSSSIs. We selected 10 clinical trials from MEDLINE and Cochrane databases for qualitative review. Of these, five trials compared one or two doses of dalbavancin versus other antibiotics such as vancomycin or linezolid.
RESULTS
Treatment outcomes with other antibiotics were not significantly different versus two doses of dalbavancin (OR 1.13; 95% CI 0.75-1.71; p = 0.55) or single dose dalbavancin (OR 0.98; 95% CI 0.19-5.17; p = 0.98). One dose versus two doses of dalbavancin did not show significant differences in any of the treatment groups. In contrast, the global microbiological assessment results indicated a favorable outcome for two doses of dalbavancin compared to the single dose of dalbavancin (OR 2.96; 95% CI 1.19-7.39; p = 0.02) in both methicillin-resistant and methicillin-susceptible .
CONCLUSION
Either single dose or two dose dalbavancin treatment is as clinically effective as other antibiotics such as vancomycin and linezolid for the treatment of ABSSSIs.: acute bacterial skin and skin-structure infection; AUC: area under the concentration-time curve; CE: clinical evaluable; CI: confidence interval; EOT: end of treatment; ITT: intention-to-treat; LOS: length of stay; MIC: minimum inhibitory concentration; MIC: minimum concentration to inhibit growth of 90% of isolates; MR: methicillin resistant; MRSA: methicillin-resistant ; MS: methicillin susceptible; MSSA: methicillin-susceptible OPAT: Outpatient Parenteral Antimicrobial Therapy; OR: odds ratio; PI: penicillin intermediate; PR: penicillin resistant; PS penicillin susceptible; SIRS: systemic inflammatory response syndrome; SSTI: skin and soft tissue infection; TOC: test of cure; VR: vancomycin resistant; VS: vancomycin susceptible.
Topics: Humans; Vancomycin; Linezolid; Methicillin-Resistant Staphylococcus aureus; Methicillin; Anti-Bacterial Agents; Skin Diseases, Bacterial; Staphylococcus aureus; Penicillins; Anti-Infective Agents
PubMed: 32981375
DOI: 10.1080/14787210.2021.1828865