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BioRxiv : the Preprint Server For... Oct 2023is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to...
is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment, particularly when they are caused by Methicillin-Resistant (MRSA). Antibiotic tolerance, the ability for bacteria to persist despite normally lethal doses of antibiotics, is responsible for most antibiotic treatment failure in MRSA infections. To understand how antibiotic tolerance is induced, biofilms exposed to multiple anti-MRSA antibiotics (vancomycin, ceftaroline, delafloxacin, and linezolid) were examined using both quantitative proteomics and transposon sequencing. These screens indicated that arginine metabolism is involved in antibiotic tolerance within a biofilm and led to the hypothesis that depletion of arginine within communities can induce antibiotic tolerance. Consistent with this hypothesis, inactivation of the final gene in the arginine synthesis pathway, induces antibiotic tolerance under conditions in which the parental strain is susceptible to antibiotics. Arginine restriction was found to induce antibiotic tolerance via inhibition of protein synthesis. Finally, although fitness in a mouse skin infection model is decreased in an mutant, its ability to survive during antibiotic treatment with vancomycin is enhanced, highlighting the relationship between arginine metabolism and antibiotic tolerance during infection. Uncovering this link between arginine metabolism and antibiotic tolerance has the potential to open new therapeutic avenues targeting previously recalcitrant infections.
PubMed: 37873095
DOI: 10.1101/2023.10.12.561972 -
Iranian Journal of Kidney Diseases Jul 2023Central venous catheters, frequently used in patients undergoing hemodialysis, place the patients at high risk of catheter-related infections. Therefore, it is essential... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Central venous catheters, frequently used in patients undergoing hemodialysis, place the patients at high risk of catheter-related infections. Therefore, it is essential to select the optimal prevention protocol for these infections. This study aims to compare the efficacy of the Taurolock solution and antibiotic lock in preventing tunneled catheter (permcath) related infections.
METHODS
This multicenter study was conducted between June 2020 and July 2021 on 86 hemodialysis patients with a central venous catheter from four dialysis centers in Tehran, Iran. The patients were randomly assigned into two groups. The first group received Taurolock, and the second group received antibiotic lock (a combination of vancomycin and heparin) at the end of each dialysis session. Peripheral blood and catheter blood samples were collected once before the intervention and monthly thereafter, for up to six months, and blood culture performed for detection of various bacterial strains.
RESULTS
The findings showed no significant difference in the infection rate (positive peripheral blood or catheter cultures) between the Taurolock and vancomycin groups (P > .05). Additionally, there was no significant difference in the duration of catheter implantation in individuals with positive and negative cultures (P > .05). Furthermore, no significant correlation was found between comorbidities and catheter-related infection in patients of the two groups (P > .05).
CONCLUSION
There was no significant difference between the two groups in the rate of catheter-related infection. Therefore, vancomycin lock solutions can be good alternatives to Taurolock solution for preventing catheter-related infections. DOI: 10.52547/ijkd.7615.
Topics: Humans; Vancomycin; Catheter-Related Infections; Iran; Anti-Bacterial Agents; Central Venous Catheters; Renal Dialysis
PubMed: 37634248
DOI: No ID Found -
PloS One 2024In the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs), vancomycin stands as the prevalent therapeutic agent. Daptomycin... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness of daptomycin versus vancomycin among patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections: A systematic literature review and meta-analysis.
BACKGROUND
In the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs), vancomycin stands as the prevalent therapeutic agent. Daptomycin remains an alternative antibiotic to treat MRSA BSIs in cases where vancomycin proves ineffective. However, studies have conflicted on whether daptomycin is more effective than vancomycin among patients with MRSA BSI.
OBJECTIVE
To compare the effectiveness of daptomycin and vancomycin for the prevention of mortality among adult patients with MRSA BSI.
METHODS
Systematic searches of databases were performed, including Embase, PubMed, Web of Science, and Cochrane Library. The Newcastle Ottawa Scale (NOS) and Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) were used to assess the quality of individual observational and randomized control studies, respectively. Pooled odd ratios were calculated using random effects models.
RESULTS
Twenty studies were included based on a priori set inclusion and exclusion criteria. Daptomycin treatment was associated with non-significant lower mortality odds, compared to vancomycin treatment (OR = 0.81; 95% CI, 0.62, 1.06). Sub-analyses based on the time patients were switched from another anti-MRSA treatment to daptomycin demonstrated that switching to daptomycin within 3 or 5 days was significantly associated with 55% and 45% decreased odds of all-cause mortality, respectively. However, switching to daptomycin any time after five days of treatment was not significantly associated with lower odds of mortality. Stratified analysis based on vancomycin minimum inhibitory concentration (MIC) revealed that daptomycin treatment among patients infected with MRSA strains with MIC≥1 mg/L was significantly associated with 40% lower odds of mortality compared to vancomycin treatment.
CONCLUSION
Compared with vancomycin, an early switch from vancomycin to daptomycin was significantly associated with lower odds of mortality. In contrast, switching to daptomycin at any time only showed a trend towards reduced mortality, with a non-significant association. Therefore, the efficacy of early daptomycin use over vancomycin against mortality among MRSA BSIs patients may add evidence to the existing literature in support of switching to daptomycin early over remaining on vancomycin. More randomized and prospective studies are needed to assess this association.
Topics: Adult; Humans; Vancomycin; Daptomycin; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Bacteremia; Treatment Outcome; Retrospective Studies; Anti-Bacterial Agents; Sepsis; Microbial Sensitivity Tests
PubMed: 38381737
DOI: 10.1371/journal.pone.0293423 -
Journal of Biomedical Science Aug 2023Beyond the development of resistance, the effects of antibiotics on bacteria and microbial communities are complex and far from exhaustively studied. In the context of... (Review)
Review
Beyond the development of resistance, the effects of antibiotics on bacteria and microbial communities are complex and far from exhaustively studied. In the context of the current global antimicrobial resistance crisis, understanding the adaptive and physiological responses of bacteria to antimicrobials is of paramount importance along with the development of new therapies. Bacterial dependence on antibiotics is a phenomenon in which antimicrobials instead of eliminating the pathogens actually provide a boost for their growth. This trait comprises an extreme example of the complexities of responses elicited by microorganisms to these drugs. This compelling evolutionary trait was readily described along with the first wave of antibiotics use and dependence to various antimicrobials has been reported. Nevertheless, current molecular characterizations have been focused on dependence on vancomycin, linezolid and colistin, three critically important antibiotics frequently used as last resource therapy for multi resistant pathogens. Outstanding advances have been made in understanding the molecular basis for the dependence to vancomycin, including specific mutations involved. Regarding linezolid and colistin, the general physiological components affected by the dependence, namely ribosomes and membrane function respectively, have been established. Nonetheless the implications of antibiotic dependence in clinically relevant features, such as virulence, epidemics, relationship with development of resistance, diagnostics and therapy effectiveness require clarification. This review presents a brief introduction of the phenomenon of bacterial dependence to antibiotics and a summary on early and current research concerning the basis for this trait. Furthermore, the available information on the effect of dependence in key clinical aspects is discussed. The studies performed so far underline the need to fully disclose the biological and clinical significance of this trait in pathogens to successfully assess its role in resistance and to design adjusted therapies.
Topics: Anti-Bacterial Agents; Vancomycin; Linezolid; Colistin; Poisons; Bacteria; Microbial Sensitivity Tests; Drug Resistance, Bacterial
PubMed: 37574554
DOI: 10.1186/s12929-023-00963-x -
Antimicrobial Resistance and Infection... Nov 2023Vancomycin-resistant enterococcus (VRE) was the fastest growing pathogen in Europe in 2022 (+ 21%) but its clinical relevance is still unclear. We aim to identify risk...
BACKGROUND
Vancomycin-resistant enterococcus (VRE) was the fastest growing pathogen in Europe in 2022 (+ 21%) but its clinical relevance is still unclear. We aim to identify risk factors for acquired VRE rectal colonization in hematological patients and evaluate the clinical impact of VRE colonization on subsequent infection, and 30- and 90-day overall mortality rates, compared to a matched control group.
METHODS
A retrospective, single center, case-control matched study (ratio 1:1) was conducted in a hematological department from January 2017 to December 2020. Case patients with nosocomial isolation of VRE from rectal swab screening (≥ 48 h) were matched to controls by age, sex, ethnicity, and hematologic disease. Univariate and multivariate logistic regression compared risk factors for colonization.
RESULTS
A total of 83 cases were matched with 83 controls. Risk factors for VRE colonization were febrile neutropenia, bone marrow transplant, central venous catheter, bedsores, reduced mobility, altered bowel habits, cachexia, previous hospitalization and antibiotic treatments before and during hospitalization. VRE bacteraemia and Clostridioides difficile infection (CDI) occurred more frequently among cases without any impact on 30 and 90-days overall mortality. Vancomycin administration and altered bowel habits were the only independent risk factors for VRE colonization at multivariate analysis (OR: 3.53 and 3.1; respectively).
CONCLUSIONS
Antimicrobial stewardship strategies to reduce inappropriate Gram-positive coverage in hematological patients is urgently required, as independent risk factors for VRE nosocomial colonization identified in this study include any use of vancomycin and altered bowel habits. VRE colonization and infection did not influence 30- and 90-day mortality. There was a strong correlation between CDI and VRE, which deserves further investigation to target new therapeutic approaches.
Topics: Humans; Vancomycin; Case-Control Studies; Retrospective Studies; Gram-Positive Bacterial Infections; Vancomycin Resistance; Risk Factors; Vancomycin-Resistant Enterococci; Hospitals; Cross Infection
PubMed: 37957773
DOI: 10.1186/s13756-023-01332-x -
International Journal of Infectious... Nov 2023To investigate the preventive effect of intraarticularly administered vancomycin on acute postoperative periprosthetic joint infection (PJI) in total joint arthroplasty...
Intraarticular vancomycin decreased the risk of acute postoperative periprosthetic joint infection without increasing complication in primary total joint arthroplasty-a prospective study.
OBJECTIVES
To investigate the preventive effect of intraarticularly administered vancomycin on acute postoperative periprosthetic joint infection (PJI) in total joint arthroplasty (TJA).
METHODS
Consecutive patients who underwent unilateral primary TJA were prospectively enrolled. The patients were divided into vancomycin group and control group according to whether 1 g of vancomycin powder suspended in 30 ml normal saline was intraarticularly administered after arthrotomy closure. Acute postoperative PJI and aseptic wound complication were evaluated within 3 months postoperatively. Vancomycin-associated toxicity including acute renal failure, ototoxicity and anaphylaxis was also evaluated.
RESULTS
In terms of demographic parameters and comorbidities, no significant difference was found between the two groups. Intra-articular vancomycin significantly lowered the risk of acute postoperative PJI after primary TJA (P = 0.015) and primary total knee arthroplasty (P = 0.031). However, for patients who underwent total hip arthroplasty, the PJI rate was comparable between the two groups. Overall, the risk of aseptic wound complication between the two groups was also similar. Vancomycin-associated acute renal injury, ototoxicity, or anaphylaxis was not observed.
CONCLUSIONS
Intra-articular injection of 1 g of vancomycin suspension after arthrotomy closure during TJA lowered the risk of acute postoperative PJI without increasing the risk of aseptic wound complication and vancomycin-associated systemic toxicity.
Topics: Humans; Vancomycin; Prospective Studies; Prosthesis-Related Infections; Ototoxicity; Retrospective Studies; Arthroplasty, Replacement, Knee; Arthritis, Infectious; Acute Kidney Injury
PubMed: 37714404
DOI: 10.1016/j.ijid.2023.09.004 -
BMJ Open Sep 2023infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence of infection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial.
INTRODUCTION
infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT.
METHODS AND ANALYSIS
We will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group).
ETHICS AND DISSEMINATION
Ethical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital '12 de Octubre' (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.
TRIAL REGISTRATION NUMBER
NCT05320068.
Topics: Adult; Humans; Vancomycin; Anti-Bacterial Agents; Clostridium Infections; Secondary Prevention; Hospitals, University
PubMed: 37709311
DOI: 10.1136/bmjopen-2023-072121 -
Heliyon May 2024The main aim of this study was to compare the clinical outcomes of patients attended in our area with infection (CDI) (sustained cure, recurrence or death) in relation...
OBJECTIVES
The main aim of this study was to compare the clinical outcomes of patients attended in our area with infection (CDI) (sustained cure, recurrence or death) in relation to treatment to normal or hypervirulent as a risk factor and to describe the resistance profile to metronidazole and vancomycin antibiotics in our hospital over a one-year period.
METHODS
A retrospective, cross-sectional and observational study was conducted between June 2022 and June 2023 to compare the clinical cure and/or recurrence of CDI in adult patients treated in a Spanish secondary Hospital depending on the prescribed antibiotic treatment. In addition, we performed an antimicrobial susceptibility study to vancomycin and metronidazole in all isolated in bacterial culture.
RESULTS
Out of 194 selected patients the treatments were as follow: 43.81 % vancomycin, 21.65 % metronidazole, 8.25 % a combination of both, 6.70 % fidaxomicin and 19.59 % were untreated. Vancomycin and fidaxomicin patients had higher odds ratio of prolonged hospitalization ( = 0.041 and = 0.040, respectively). Fidaxomicin had increased odds of suffering another episode of ( = 0.009) and it was inferior to metronidazole for recurrent CDI (rCDI) ( = 0.035).Resistance profile for was 4.07 % for vancomycin and 3.49 % for metronidazole. Hypervirulent was identified in 17 (8.76 %) patients with 29.41 % of mortality (5/17; p > 0.05).
CONCLUSION
Fidaxomicin treated patients had statistically increased odds of rCDI. Compared to other treatments, fidaxomicin was inferior to metronidazole for rCDI in our cohort;Hypervirulent was not associated with death.Vancomycin resistance of statistically decreased, whereas metronidazole resistance did not vary during the studied period.
PubMed: 38803946
DOI: 10.1016/j.heliyon.2024.e30742 -
BMC Nephrology Sep 2023Few drug dosing recommendations for patients receiving home hemodialysis (HHD) have been published which has hindered the adoption of HHD. HHD regimens vary widely and...
BACKGROUND
Few drug dosing recommendations for patients receiving home hemodialysis (HHD) have been published which has hindered the adoption of HHD. HHD regimens vary widely and differ considerably from conventional, thrice weekly, in-center hemodialysis in terms of treatment frequency, duration and blood and dialysate flow rates. Consequently, vancomycin and daptomycin clearances in HHD are also likely to be different, consequently HHD dosing regimens must be developed to ensure efficacy and minimize toxicity when these antibiotics are used. Many HHD regimens are used clinically, this study modeled ten common HHD regimens and determined optimal vancomycin and daptomycin dosing for each HHD regimen.
METHODS
Monte Carlo simulations using pharmacokinetic data derived from the literature and demographic data from a large HHD program treating patients with end stage kidney disease were incorporated into a one-compartment pharmacokinetic model. Virtual vancomycin and daptomycin doses were administered post-HHD and drug exposures were determined in 5,000 virtual patients receiving ten different HHD regimens. Serum concentration monitoring with subsequent dose changes was incorporated into the vancomycin models. Pharmacodynamic target attainment rates were determined for each studied dose. The lowest possible doses that met predefined targets in virtual patients were chosen as optimal doses.
RESULTS
HHD frequency, total dialysate volumes and HHD durations influenced drug exposure and led to different dosing regimens to meet targets. Antibiotic dosing regimens were identified that could meet targets for 3- and 7-h HHD regimens occurring every other day or 4-5 days/week. HHD regimens with 3-day interdialytic periods required higher doses prior to the 3-day period. The addition of vancomycin serum concentration monitoring allowed for calculation of necessary dosing changes which increased the number of virtual subjects meeting pharmacodynamic targets.
CONCLUSIONS
Doses of vancomycin and daptomycin that will meet desired pharmacodynamic targets in HHD are dependent on patient and HHD-specific factors. Doses used in conventional thrice weekly hemodialysis are unlikely to meet treatment goals. The antibiotic regimens paired with the HHD parameters studied in this analysis are likely to meet goals but require clinical validation.
Topics: Humans; Vancomycin; Daptomycin; Hemodialysis, Home; Monte Carlo Method; Anti-Bacterial Agents; Dialysis Solutions
PubMed: 37710245
DOI: 10.1186/s12882-023-03314-y -
Journal of Korean Neurosurgical Society Sep 2023Surgical site infection is the most detrimental complication following cranioplasty. In other surgical fields, intrawound vancomycin powder application has been...
OBJECTIVE
Surgical site infection is the most detrimental complication following cranioplasty. In other surgical fields, intrawound vancomycin powder application has been introduced to prevent surgical site infection and is widely used based on results in multiple studies. This study evaluated the effect of intrawound vancomycin powder in cranioplasty compared with the conventional method without topical antibiotics.
METHODS
This retrospective study included 580 patients with skull defects who underwent cranioplasty between August 1, 1998 and December 31, 2021. The conventional method was used in 475 (81.9%; conventional group) and vancomycin powder (1 g) was applied on the dura mater and bone flap in 105 patients (18.1%; vancomycin powder group). Surgical site infection was defined as infection of the incision, organ, or space that occurred after cranioplasty. Surgical site infection within 1-year surveillance period was compared between the conventional and vancomycin powder groups with logistic regression analysis. Penalized likelihood estimation method was used in logistic regression to deal with zero events. All local and systemic adverse events associated with topical vancomycin application were also evaluated.
RESULTS
Surgical site infection occurred in 31 patients (5.3%) and all were observed in the conventional group. The median time between cranioplasty and detection of surgical site infection was 13 days (range, 4-333). Staphylococci were the most common organisms and identified in 25 (80.6%) of 31 cases with surgical site infections. The surgical site infection rate in the vancomycin powder group (0/105, 0.0%) was significantly lower than that in the conventional group (31/475, 6.5%; crude odds ratio [OR], 0.067; 95% confidence interval [CI], 0.006-0.762; adjusted OR, 0.068; 95% CI, 0.006-0.731; p=0.026). No adverse events associated with intrawound vancomycin powder were observed during the follow-up.
CONCLUSION
Intrawound vancomycin powder effectively prevented surgical site infections following cranioplasty without local or systemic adverse events. Our results suggest that intrawound vancomycin powder is an effective and safe strategy for patients undergoing cranioplasty.
PubMed: 37032483
DOI: 10.3340/jkns.2023.0024