-
Clinical Pharmacokinetics Jul 2024The interstitial fluid of tissues is the effect site for antibiotics targeting extracellular pathogens. Microdialysis studies investigating these concentrations in...
BACKGROUND AND OBJECTIVE
The interstitial fluid of tissues is the effect site for antibiotics targeting extracellular pathogens. Microdialysis studies investigating these concentrations in muscle and subcutaneous tissue have reported notable variability in tissue penetration. This study aimed to comprehensively summarise the existing data on interstitial fluid penetration in these tissues and to identify potential factors influencing antibiotic distribution.
METHODS
A literature review was conducted, focusing on subcutaneous and intramuscular microdialysis studies of antibiotics in both adult healthy volunteers and patients. Random-effect meta-analyses were used to aggregate effect size estimates of tissue penetration. The primary parameter of interest was the unbound penetration ratio, which represents the ratio of the area under the concentration-time curve in interstitial fluid relative to the area under the concentration-time curve in plasma, using unbound concentrations.
RESULTS
In total, 52 reports were incorporated into this analysis. The unbound antibiotic exposure in the interstitial fluid of healthy volunteers was, on average, 22% lower than in plasma. The unbound penetration ratio values were higher after multiple dosing but did not significantly differ between muscle and subcutaneous tissue. Unbound penetration ratio values were lower for acids and bases compared with neutral antibiotics. Neither the molecular weight nor the logP of the antibiotics accounted for the variations in the unbound penetration ratio. Obesity was associated with lower interstitial fluid penetration. Conditions such as sepsis, tissue inflammation and tissue ischaemia were not significantly associated with altered interstitial fluid penetration.
CONCLUSIONS
This study highlights the variability and generally lower exposure of unbound antibiotics in the subcutaneous and intramuscular interstitial fluid compared with exposure in plasma. Future research should focus on understanding the therapeutic relevance of these differences and identify key covariates that may influence them.
PubMed: 38955946
DOI: 10.1007/s40262-024-01394-z -
Critical Care Medicine Jul 2024In sepsis treatment, antibiotics are crucial, but overuse risks development of antibiotic resistance. Recent guidelines recommended the use of procalcitonin to guide...
Benefits and Harms of Procalcitonin- or C-Reactive Protein-Guided Antimicrobial Discontinuation in Critically Ill Adults With Sepsis: A Systematic Review and Network Meta-Analysis.
OBJECTIVES
In sepsis treatment, antibiotics are crucial, but overuse risks development of antibiotic resistance. Recent guidelines recommended the use of procalcitonin to guide antibiotic cessation, but solid evidence is insufficient. Recently, concerns were raised that this strategy would increase recurrence. Additionally, optimal protocol or difference from the commonly used C-reactive protein (CRP) are uncertain. We aimed to compare the effectiveness and safety of procalcitonin- or CRP-guided antibiotic cessation strategies with standard of care in sepsis.
DATA SOURCES
A systematic search of PubMed, Embase, CENTRAL, Igaku Chuo Zasshi, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform.
STUDY SELECTION
Randomized controlled trials involving adults with sepsis in intensive care.
DATA EXTRACTION
A systematic review with network meta-analyses was performed. The Grading of Recommendations, Assessments, Developments, and Evaluation method was used to assess certainty.
DATA SYNTHESIS
Eighteen studies involving 5023 participants were included. Procalcitonin-guided and CRP-guided strategies shortened antibiotic treatment (-1.89 days [95% CI, -2.30 to -1.47], -2.56 days [95% CI, -4.21 to -0.91]) with low- to moderate-certainty evidence. In procalcitonin-guided strategies, this benefit was consistent even in subsets with shorter baseline antimicrobial duration (7-10 d) or in Sepsis-3, and more pronounced in procalcitonin cutoff of "0.5 μg/L and 80% reduction." No benefit was observed when monitoring frequency was less than half of the initial 10 days. Procalcitonin-guided strategies lowered mortality (-27 per 1000 participants [95% CI, -45 to -7]) and this was pronounced in Sepsis-3, but CRP-guided strategies led to no difference in mortality. Recurrence did not increase significantly with either strategy (very low to low certainty).
CONCLUSIONS
In sepsis, procalcitonin- or CRP-guided antibiotic discontinuation strategies may be beneficial and safe. In particular, the usefulness of procalcitonin guidance for current Sepsis-3, where antimicrobials are used for more than 7 days, was supported. Well-designed studies are needed focusing on monitoring protocol and recurrence.
PubMed: 38949476
DOI: 10.1097/CCM.0000000000006366 -
World Journal of Experimental Medicine Jun 2024Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity, that negatively affect the patients' quality of...
BACKGROUND
Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity, that negatively affect the patients' quality of life. Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation. Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features. Despite the advances in experimental protocols and techniques, designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.
AIM
To review current state of the art for experimental protocols in high-risk anastomosis in rats.
METHODS
This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. To identify eligible studies, a comprehensive literature search was performed in the electronic databases PubMed (MEDLINE) and Scopus, covering the period from conception until 18 October 2023.
RESULTS
From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis. Methods of assessing anastomotic healing were extracted and were individually appraised.
CONCLUSION
Anastomotic healing studies have evolved over the last decades, but the findings are yet to be translated into human studies. There is a need for high-quality, well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.
PubMed: 38948424
DOI: 10.5493/wjem.v14.i2.94135 -
Mycopathologia Jun 2024Candidemia, a bloodstream infection predominantly affecting critically ill patients, poses a significant global health threat especially with the emergence of... (Review)
Review
INTRODUCTION
Candidemia, a bloodstream infection predominantly affecting critically ill patients, poses a significant global health threat especially with the emergence of non-albicans Candida species, including drug-resistant strains. In Brazil, limited access to advanced diagnostic tools and trained microbiologists hampers accurate identification of Candida species and susceptibility to antifungals testing hindering surveillance efforts.
METHODS
We conducted a systematic review spanning publications from 2017 to 2023 addressing Candida species distribution and antifungal susceptibility among Brazilian patients with candidemia.
RESULTS
Despite initially identifying 7075 records, only 16 met inclusion criteria providing accurate information of 2305 episodes of candidemia. The predominant species were C. albicans, C. parapsilosis, and C. tropicalis, followed by notable proportions of Nakaseomyces glabratus. Limited access to diagnostic tests was evident as only 5 out of 16 studies on candidemia were able to report antifungal susceptibility testing results. In vitro resistance to echinocandins was rare (only 6/396 isolates, 1,5%). In counterpart, fluconazole exhibited resistance rates ranging from 0 to 43%, with great heterogeneity among different studies and species of Candida considered.
CONCLUSION
Our review underscores the critical need for enhanced surveillance and research efforts to address the evolving landscape of candidemia and antifungal resistance in Brazil. Despite some limitations, available data suggest that while resistance to echinocandins and amphotericin B remains rare, there is a growing concern regarding resistance to fluconazole among Candida species.
Topics: Candidemia; Brazil; Humans; Antifungal Agents; Candida; Drug Resistance, Fungal; Microbial Sensitivity Tests
PubMed: 38940953
DOI: 10.1007/s11046-024-00867-w -
The Cochrane Database of Systematic... Jun 2024Peripherally inserted central catheters (PICCs) facilitate diagnostic and therapeutic interventions in health care. PICCs can fail due to infective and non-infective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripherally inserted central catheters (PICCs) facilitate diagnostic and therapeutic interventions in health care. PICCs can fail due to infective and non-infective complications, which PICC materials and design may contribute to, leading to negative sequelae for patients and healthcare systems.
OBJECTIVES
To assess the effectiveness of PICC material and design in reducing catheter failure and complications.
SEARCH METHODS
The University of Queensland and Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the WHO ICTRP and ClinicalTrials.gov trials registers to 16 May 2023. We aimed to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, as well as relevant systematic reviews, meta-analyses, and health technology assessment reports. We contacted experts in the field to ascertain additional relevant information.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating PICC design and materials.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were venous thromboembolism (VTE), PICC-associated bloodstream infection (BSI), occlusion, and all-cause mortality. Secondary outcomes were catheter failure, PICC-related BSI, catheter breakage, PICC dwell time, and safety endpoints. We assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 12 RCTs involving approximately 2913 participants (one multi-arm study). All studies except one had a high risk of bias in one or more risk of bias domain. Integrated valve technology compared to no valve technology for peripherally inserted central catheter design Integrated valve technology may make little or no difference to VTE risk when compared with PICCs with no valve (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.19 to 2.63; I² = 0%; 3 studies; 437 participants; low certainty evidence). We are uncertain whether integrated valve technology reduces PICC-associated BSI risk, as the certainty of the evidence is very low (RR 0.20, 95% CI 0.01 to 4.00; I² = not applicable; 2 studies (no events in 1 study); 257 participants). Integrated valve technology may make little or no difference to occlusion risk when compared with PICCs with no valve (RR 0.86, 95% CI 0.53 to 1.38; I² = 0%; 5 studies; 900 participants; low certainty evidence). We are uncertain whether use of integrated valve technology reduces all-cause mortality risk, as the certainty of evidence is very low (RR 0.85, 95% CI 0.44 to 1.64; I² = 0%; 2 studies; 473 participants). Integrated valve technology may make little or no difference to catheter failure risk when compared with PICCs with no valve (RR 0.80, 95% CI 0.62 to 1.03; I² = 0%; 4 studies; 720 participants; low certainty evidence). We are uncertain whether integrated-valve technology reduces PICC-related BSI risk (RR 0.51, 95% CI 0.19 to 1.32; I² = not applicable; 2 studies (no events in 1 study); 542 participants) or catheter breakage, as the certainty of evidence is very low (RR 1.05, 95% CI 0.22 to 5.06; I² = 20%; 4 studies; 799 participants). Anti-thrombogenic surface modification compared to no anti-thrombogenic surface modification for peripherally inserted central catheter design We are uncertain whether use of anti-thrombogenic surface modified catheters reduces risk of VTE (RR 0.67, 95% CI 0.13 to 3.54; I² = 15%; 2 studies; 257 participants) or PICC-associated BSI, as the certainty of evidence is very low (RR 0.20, 95% CI 0.01 to 4.00; I² = not applicable; 2 studies (no events in 1 study); 257 participants). We are uncertain whether use of anti-thrombogenic surface modified catheters reduces occlusion (RR 0.69, 95% CI 0.04 to 11.22; I² = 70%; 2 studies; 257 participants) or all-cause mortality risk, as the certainty of evidence is very low (RR 0.49, 95% CI 0.05 to 5.26; I² = not applicable; 1 study; 111 participants). Use of anti-thrombogenic surface modified catheters may make little or no difference to risk of catheter failure (RR 0.76, 95% CI 0.37 to 1.54; I² = 46%; 2 studies; 257 participants; low certainty evidence). No PICC-related BSIs were reported in one study (111 participants). As such, we are uncertain whether use of anti-thrombogenic surface modified catheters reduces PICC-related BSI risk (RR not estimable; I² = not applicable; very low certainty evidence). We are uncertain whether use of anti-thrombogenic surface modified catheters reduces the risk of catheter breakage, as the certainty of evidence is very low (RR 0.15, 95% CI 0.01 to 2.79; I² = not applicable; 2 studies (no events in 1 study); 257 participants). Antimicrobial impregnation compared to non-antimicrobial impregnation for peripherally inserted central catheter design We are uncertain whether use of antimicrobial-impregnated catheters reduces VTE risk (RR 0.54, 95% CI 0.05 to 5.88; I² = not applicable; 1 study; 167 participants) or PICC-associated BSI risk, as the certainty of evidence is very low (RR 2.17, 95% CI 0.20 to 23.53; I² = not applicable; 1 study; 167 participants). Antimicrobial-impregnated catheters probably make little or no difference to occlusion risk (RR 1.00, 95% CI 0.57 to 1.74; I² = 0%; 2 studies; 1025 participants; moderate certainty evidence) or all-cause mortality (RR 1.12, 95% CI 0.71 to 1.75; I² = 0%; 2 studies; 1082 participants; moderate certainty evidence). Antimicrobial-impregnated catheters may make little or no difference to risk of catheter failure (RR 1.04, 95% CI 0.82 to 1.30; I² = not applicable; 1 study; 221 participants; low certainty evidence). Antimicrobial-impregnated catheters probably make little or no difference to PICC-related BSI risk (RR 1.05, 95% CI 0.71 to 1.55; I² = not applicable; 2 studies (no events in 1 study); 1082 participants; moderate certainty evidence). Antimicrobial-impregnated catheters may make little or no difference to risk of catheter breakage (RR 0.86, 95% CI 0.19 to 3.83; I² = not applicable; 1 study; 804 participants; low certainty evidence).
AUTHORS' CONCLUSIONS
There is limited high-quality RCT evidence available to inform clinician decision-making for PICC materials and design. Limitations of the current evidence include small sample sizes, infrequent events, and risk of bias. There may be little to no difference in the risk of VTE, PICC-associated BSI, occlusion, or mortality across PICC materials and designs. Further rigorous RCTs are needed to reduce uncertainty.
Topics: Humans; Randomized Controlled Trials as Topic; Catheterization, Peripheral; Catheter-Related Infections; Equipment Failure; Equipment Design; Venous Thromboembolism; Catheter Obstruction; Central Venous Catheters; Cause of Death; Bias; Catheterization, Central Venous; Bacteremia
PubMed: 38940297
DOI: 10.1002/14651858.CD013366.pub2 -
American Journal of Infection Control Jun 2024Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a significant healthcare-associated infection carrying substantial mortality. We aimed to assess the...
BACKGROUND
Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a significant healthcare-associated infection carrying substantial mortality. We aimed to assess the clinical impact of active screening cultures for CRAB.
METHODS
A systematic review and meta-analysis, aiming to answer two questions: 1. Does screening vs no screening improve clinical outcomes? 2. Does positive screening ("CRAB carrier") predict CRAB infections? We searched MEDLINE, Cochrane library, Web of Science, and conferences, until January 2024, comparative studies reporting clinical outcomes (mortality, invasive CRAB infections).
RESULTS
Of 5,407 screened publications, 9 studies (10,865 individuals) were included for study question #2. Invasive CRAB infection rate was significantly higher among CRAB carriers (odds ratio [OR] 11.14, 95% confidence interval [CI] 4.95-25.05, with substantial heterogeneity stemming from size rather than direction of the effect). Negative predictive value (NPV) of non-carriage for invasive infection was 97%. CRAB bloodstream infections rate was significantly higher among carriers (OR 16.23, 95% CI 2.9-110.08). No significant difference was demonstrated between the two groups CRAB ventilator-associated pneumonia, length of stay, and mortality. Only one study reported outcomes for the screening vs no screening (study question #1).
CONCLUSIONS
Data to support active CRAB screening are scarce regarding its clinical benefit for patients. Positively screened patients are at significantly higher risk for invasive CRAB infections, with high NPV for non-carriage. This did not translate to reduced mortality.
PubMed: 38936479
DOI: 10.1016/j.ajic.2024.06.017 -
Medical Mycology Jun 2024The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and...
The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and Web of Science were used to find studies published from 1 January 2011 to 18 February 2021, reporting on predefined criteria including: mortality, morbidity (i.e., hospitalization and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. Thirty-seven studies were included in the final analysis. The overall and 30-day mortality rates associated with C. auris candidaemia ranged from 29% to 62% and 23% to 67%, respectively. The median length of hospital stay was 46-68 days, ranging up to 140 days. Late-onset complications of C. auris candidaemia included metastatic septic complications. Resistance rates to fluconazole were as high as 87%-100%. Susceptibility to isavuconazole, itraconazole, and posaconazole varied with MIC90 values of 0.06-1.0 mg/l. Resistance rates to voriconazole ranged widely from 28% to 98%. Resistance rates ranged between 8% and 35% for amphotericin B and 0%-8% for echinocandins. Over the last ten years, outbreaks due to C. auris have been reported in in all WHO regions. Given the outbreak potential of C. auris, the emergence and spread of MDR strains, and the challenges associated with its identification, and eradication of its environmental sources in healthcare settings, prevention and control measures based on the identified risk factors should be evaluated for their effectiveness and feasibility. Global surveillance studies could better inform the incidence rates and distribution patterns to evaluate the global burden of C. auris infections.
Topics: Humans; Antifungal Agents; Drug Resistance, Fungal; World Health Organization; Candidiasis; Candida auris; Microbial Sensitivity Tests; Candidemia; Disease Outbreaks; Candida; Incidence
PubMed: 38935900
DOI: 10.1093/mmy/myae042 -
Antibiotics (Basel, Switzerland) Jun 2024The issue of bacterial infections in COVID-19 patients has received increasing attention. Scant data are available on the impact of bacterial superinfection and... (Review)
Review
The issue of bacterial infections in COVID-19 patients has received increasing attention. Scant data are available on the impact of bacterial superinfection and antibiotic administration on the outcome of hospitalized COVID-19 patients. We conducted a literature review from 1 January 2022 to 31 March 2024 to assess the current burden of bacterial infection and the evidence for antibiotic use in hospitalized COVID-19 patients. Published articles providing data on antibiotic use in COVID-19 patients were identified through computerized literature searches with the search terms [(antibiotic) AND (COVID-19)] or [(antibiotic treatment) AND (COVID-19)]. PubMed and SCOPUS databases were searched from 1 January 2022 to 31 March 2024. No attempt was made to obtain information about unpublished studies. English language restriction was applied. The quality of the included studies was evaluated by the tool recommended by the Joanna Briggs Institute. Both quantitative and qualitative information were summarized by means of textual descriptions. Five hundred fifty-one studies were identified, and twenty-nine studies were included in this systematic review. Of the 29 included studies, 18 studies were on the prevalence of bacterial infection and antibiotic use in hospitalized COVID-19 patients; 4 studies reported on the efficacy of early antibiotic use in COVID-19; 4 studies were on the use of sepsis biomarkers to improve antibiotic use; 3 studies were on the efficacy of antimicrobial stewardship programs and predictive models among COVID-19-hospitalized patients. The quality of included studies was high in 35% and medium in 62%. High rates of hospital-acquired infections were reported among COVID-19 patients, ranging between 7.5 and 37.7%. A high antibiotic resistance rate was reported among COVID-19 patients developing hospital-acquired infections, with a high in-hospital mortality rate. The studies evaluating multi-faceted antimicrobial stewardship interventions reported efficacy in decreasing antibiotic consumption and lower in-hospital mortality.
PubMed: 38927211
DOI: 10.3390/antibiotics13060545 -
Archives of Disease in Childhood. Fetal... Jun 2024There is increasing evidence that probiotic supplementation in very preterm infants decreases the risk of necrotising enterocolitis (NEC), sepsis and mortality. The...
OBJECTIVE
There is increasing evidence that probiotic supplementation in very preterm infants decreases the risk of necrotising enterocolitis (NEC), sepsis and mortality. The underlying mechanisms, including effects on the gut microbiota, are largely unknown. We aimed to systematically review the available literature on the effects of probiotic supplementation in very preterm infants on gut microbiota development.
DESIGN
A systematic review in Medline, Embase, Cochrane Library, CINAHL and Web of Science.
SETTING
Neonatal intensive care unit.
PATIENTS
Premature infants.
INTERVENTION
Probiotic supplementation.
MAIN OUTCOME MEASURES
Gut microbiota.
RESULTS
A total of 1046 articles were screened, of which 29 were included. There was a large heterogeneity in study design, dose and type of probiotic strains, timepoints of sample collection and analysing techniques. Bifidobacteria and lactobacilli were the most used probiotic strains. The effects of probiotics on alpha diversity were conflicting; however, beta diversity was significantly different between probiotic-supplemented infants and controls in the vast majority of studies. In most studies, probiotic supplementation led to increased relative abundance of the supplemented strains and decreased abundance of genera such as , , and .
CONCLUSIONS
Probiotic supplementation to preterm infants seems to increase the relative abundance of the supplemented strains with a concurrent decrease of potentially pathogenic species. These probiotic-induced microbial alterations may contribute to the decreased risk of health complications such as NEC. Future trials, including omics technologies to analyse both microbiota composition and function linked to health outcomes, are warranted to identify the optimal mixture and dosing of probiotic strains.
PROSPERO REGISTRATION NUMBER
CRD42023385204.
PubMed: 38925919
DOI: 10.1136/archdischild-2023-326691 -
Minerva Urology and Nephrology Jun 2024Artificial intelligence and machine learning are the new frontier in urology; they can assist the diagnostic work-up and in prognostication bring superior to the...
INTRODUCTION
Artificial intelligence and machine learning are the new frontier in urology; they can assist the diagnostic work-up and in prognostication bring superior to the existing nomograms. Infectious events and in particular the septic risk, are one of the most common and in some cases life threatening complication in patients with urolithiasis. We performed a scoping review to provide an overview of the current application of AI in prediction the infectious complications in patients affected by urolithiasis.
EVIDENCE ACQUISITION
A systematic scoping review of the literature was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Scoping Reviews (PRISMA-ScR) guidelines by screening Medline, PubMed, and Embase to detect pertinent studies.
EVIDENCE SYNTHESIS
A total of 467 articles were found, of which nine met the inclusion criteria and were considered. All studies are retrospective and published between 2021 and 2023. Only two studies performed an external validation of the described models. The main event considered is urosepsis in four articles, urinary tract infection in two articles and diagnosis of infection stones in three articles. Different AI models were trained, each of which exploited several types and numbers of variables. All studies reveal good performance. Random forest and artificial neural networks seem to have higher AUC, specificity and sensibility and perform better than the traditional statistical analysis.
CONCLUSIONS
Further prospective and multi-institutional studies with external validation are needed to better clarify which variables and AI models should be integrated in our clinical practice to predict infectious events.
Topics: Humans; Urolithiasis; Artificial Intelligence; Urinary Tract Infections; Risk Assessment; Sepsis; Machine Learning
PubMed: 38920010
DOI: 10.23736/S2724-6051.24.05686-6