-
Infection and Drug Resistance 2023Antibiotic resistance represents a serious global health challenge, particularly with the emergence of strains resistant to last-resort antibiotics such as tigecycline,...
BACKGROUND
Antibiotic resistance represents a serious global health challenge, particularly with the emergence of strains resistant to last-resort antibiotics such as tigecycline, polymyxin B, and vancomycin. Urgent measures are required to alleviate this situation. To facilitate the judicious use of antibiotics, rapid and precise antimicrobial susceptibility testing (AST) is essential. Heavy water (deuterium oxide, DO)-labeled Raman spectroscopy has emerged as a promising time-saving tool for microbiological testing.
METHODS
Deuterium incorporation and experimental conditions were examined to develop and apply a Raman-based AST method to evaluate the efficacy of last-resort antibiotics, including tigecycline, polymyxin B, and vancomycin, against , and . Essential agreement and categorical agreement were used to assess the metabolism inactivation concentration based on Raman spectroscopy (R-MIC)-a new metric developed in this study-and minimum inhibitory concentration (MIC) determined via the traditional microdilution broth method. Spearman's rank correlation coefficient was employed to measure the association between R-MIC and MIC values.
RESULTS
The Raman-based AST method achieved a 100% categorical agreement (92/92) with the traditional microdilution broth method within five hours, while the traditional method required approximately 24 h. The R-MIC values shared 68.5% (63/92) consistency with the MIC values. In addition, the R-MIC and MIC values were highly correlated (Spearman's r=0.96), resulting in an essential agreement of 100%.
CONCLUSION
Our optimized experimental method and conditions indicate that Raman-based AST holds great promise as a solution to overcome the time-consuming challenges of traditional AST methods.
PubMed: 37638072
DOI: 10.2147/IDR.S404732 -
JACS Au Nov 2023Decades of antibiotic misuse have led to alarming levels of antimicrobial resistance, and the development of alternative diagnostic and therapeutic strategies to...
Decades of antibiotic misuse have led to alarming levels of antimicrobial resistance, and the development of alternative diagnostic and therapeutic strategies to delineate and treat infections is a global priority. In particular, the nosocomial, multidrug-resistant "ESKAPE" pathogens such as Gram-positive methicillin-resistant (MRSA) and vancomycin-resistant (VRE) urgently require alternative treatments. Here, we developed light-activated molecules based on the conjugation of the FDA-approved photosensitizer riboflavin to the Gram-positive specific ligand vancomycin to enable targeted antimicrobial photodynamic therapy. The riboflavin-vancomycin conjugate proved to be a potent and versatile antibacterial agent, enabling the rapid, light-mediated, killing of MRSA and VRE with no significant off-target effects. The attachment of riboflavin on vancomycin also led to an increase in antibiotic activity against and VRE. Simultaneously, we evidenced for the first time that the flavin subunit undergoes an efficient photoinduced bond cleavage reaction to release vancomycin, thereby acting as a photoremovable protecting group with potential applications in drug delivery.
PubMed: 38034955
DOI: 10.1021/jacsau.3c00369 -
European Journal of Clinical... Apr 2024To investigate the occurrence of vancomycin-variable enterococci (VVE) in a hospital in central Italy.
PURPOSE
To investigate the occurrence of vancomycin-variable enterococci (VVE) in a hospital in central Italy.
METHODS
vanA positive but vancomycin-susceptible Enterococcus faecium isolates (VVE-S) were characterized by antibiotic susceptibility tests, molecular typing (PFGE and MLST), and WGS approach. The reversion of VVE-S to a resistant phenotype was assessed by exposure to increasing vancomycin concentrations, and the revertant isolates were used in filter mating experiments. qPCR was used to analyze the plasmid copy number.
RESULTS
Eleven putative VVE-S were selected. WGS revealed two categories of vanA cluster plasmid located: the first type showed the lack of vanR, the deletion of vanS, and an intact vanH/vanA/vanX cluster; the second type was devoid of both vanR and vanS and showed a deletion of 544-bp at the 5'-end of the vanH. Strains (n = 7) carrying the first type of vanA cluster were considered VVE-S and were able to regain a resistance phenotype (VVE-R) in the presence of vancomycin, due to a 44-bp deletion in the promoter region of vanH/vanA/vanX, causing its constitutive expression. VVE-R strains were not able to transfer resistance by conjugation, and the resistance phenotype was unstable: after 11 days of growth without selective pressure, the revertants were still resistant but showed a lower vancomycin MIC. A higher plasmid copy number in the revertant strains was probably related to the resistance phenotype.
CONCLUSION
We highlight the importance of VVE transition to VRE under vancomycin therapy resulting in a potential failure treatment. We also report the first-time identification of VVE-S isolates pstS-null belonging to ST1478.
Topics: Humans; Vancomycin; Enterococcus faecium; Anti-Bacterial Agents; Multilocus Sequence Typing; Vancomycin Resistance; Microbial Sensitivity Tests; Enterococcus; Bacterial Proteins; Gram-Positive Bacterial Infections
PubMed: 38296911
DOI: 10.1007/s10096-024-04768-0 -
Frontiers in Pharmacology 2023Vancomycin remains the cornerstone antibiotic for the treatment of infective endocarditis (IE). Vancomycin has been associated with significant nephrotoxicity. However,...
Vancomycin remains the cornerstone antibiotic for the treatment of infective endocarditis (IE). Vancomycin has been associated with significant nephrotoxicity. However, vancomycin associated acute kidney injury (AKI) has not been evaluated in patients with IE. We conducted this large retrospective cohort study to reveal the incidence, risk factors, and prognosis of vancomycin-associated acute kidney injury (VA-AKI) in patients with IE. Adult patients diagnosed with IE and receiving vancomycin were included. The primary outcome was VA-AKI. In total, 435 of the 600 patients were enrolled. Of these, 73.6% were male, and the median age was 52 years. The incidence of VA-AKI was 17.01% (74). Only 37.2% (162) of the patients received therapeutic monitoring of vancomycin, and 30 (18.5%) patients had reached the target vancomycin trough concentration. Multiple logistic regression analysis revealed that body mass index [odds ratio (OR) 1.088, 95% CI 1.004, 1.179], duration of vancomycin therapy (OR 1.030, 95% CI 1.003, 1.058), preexisting chronic kidney disease (OR 2.291, 95% CI 1.018, 5.516), admission to the intensive care unit (OR 2.291, 95% CI 1.289, 3.963) and concomitant radiocontrast agents (OR 2.085, 95% CI 1.093, 3.978) were independent risk factors for VA-AKI. Vancomycin variety (Lai Kexin vs. Wen Kexin, OR 0.498, 95% CI 0.281, 0.885) were determined to be an independent protective factor for VI-AKI. Receiver operator characteristic curve analysis revealed that duration of therapy longer than 10.75 days was associated with a significantly increased risk of VA-AKI (HR 1.927). Kidney function was fully or partially recovered in 73.0% (54) of patients with VA-AKI. The incidence of VA-AKI in patients with IE was slightly higher than in general adult patients. Concomitant contrast agents were the most alarmingly nephrotoxic in patients with IE, adding a 2-fold risk of VA-AKI. In patients with IE, a course of vancomycin therapy longer than 10.75 days was associated with a significantly increased risk of AKI. Thus, closer monitoring of kidney function and vancomycin trough concentrations was recommended in patients with concurrent contrast or courses of vancomycin longer than 10.75 days.
PubMed: 38026976
DOI: 10.3389/fphar.2023.1260802 -
World Journal of Emergency Surgery :... Dec 2023Temporal changes in the microbiological resistance profile have been reported in several life-threatening infections. However, no data have ever assessed this issue in...
BACKGROUND
Temporal changes in the microbiological resistance profile have been reported in several life-threatening infections. However, no data have ever assessed this issue in postoperative peritonitis (POP). Our purpose was to assess the rate of multidrug-resistant organisms (MDROs) in POP over a two-decade period and to analyse their influence on the adequacy of empirical antibiotic therapy (EAT).
METHODS
This retrospective monocentric analysis (1999-2019) addressed the changes over time in microbiologic data, including the emergence of MDROs and the adequacy of EAT for all intensive care unit adult patients treated for POP. The in vitro activities of 10 antibiotics were assessed to determine the most adequate EAT in the largest number of cases among 17 antibiotic regimens in patients with/without MDRO isolates. Our primary endpoint was to determine the frequency of MDRO and their temporal changes. Our second endpoint assessed the impact of MDROs on the adequacy of EAT per patient and their temporal changes based on susceptibility testing. In this analysis, the subgroup of patients with MDRO was compared with the subgroup of patients free of MDRO.
RESULTS
A total of 1,318 microorganisms were cultured from 422 patients, including 188 (45%) patients harbouring MDROs. The growing proportions of MDR Enterobacterales were observed over time (p = 0.016), including ESBL-producing strains (p = 0.0013), mainly related to Klebsiella spp (p < 0.001). Adequacy of EAT was achieved in 305 (73%) patients. Decreased adequacy rates were observed when MDROs were cultured [p = 0.0001 vs. MDRO-free patients]. Over the study period, decreased adequacy rates were reported for patients receiving piperacillin/tazobactam in monotherapy or combined with vancomycin and imipenem/cilastatin combined with vancomycin (p < 0.01 in the three cases). In patients with MDROs, the combination of imipenem/cilastatin + vancomycin + amikacin or ciprofloxacin reached the highest adequacy rates (95% and 91%, respectively) and remained unchanged over time.
CONCLUSIONS
We observed high proportions of MDRO in patients treated for POP associated with increasing proportions of MDR Enterobacterales over time. High adequacy rates were only achieved in antibiotic combinations involving carbapenems and vancomycin, while piperacillin/tazobactam is no longer a drug of choice for EAT in POP in infections involving MDRO.
Topics: Adult; Humans; Retrospective Studies; Vancomycin; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Cilastatin, Imipenem Drug Combination; Peritonitis; Piperacillin; Tazobactam
PubMed: 38115142
DOI: 10.1186/s13017-023-00528-1 -
Saudi Pharmaceutical Journal : SPJ :... Dec 2023is a Gram-positive bacterium that can cause various infections. The has been used as a preliminary test for infection model. The study aimed to evaluate the...
BACKGROUND
is a Gram-positive bacterium that can cause various infections. The has been used as a preliminary test for infection model. The study aimed to evaluate the effectiveness of as a microbiome model and compare the efficacy of vancomycin and antimicrobial activity of (NS) on the gut flora.
METHODS
larvae were subjected to metagenomic analysis. The larvae's guts were collected, homogenized in phosphate-buffered saline (PBS), and the gut contents isolated for bacterial DNA extraction. Larvae were assigned into the following groups: negative control (PBS only); positive control (MRSA only); vancomycin treated group; NS oil treated group and combination (vancomycin and NS oil) treated group. Larvae were cultured, inoculated with , and treated with vancomycin and NS oil. Larval activity, cocoon formation, growth, melanization, and survival were monitored. The toxicity of vancomycin and NS oil was tested, and burden and natural microbiota were determined. Hemocyte density was measured. Statistical analysis was conducted using R.
RESULTS
related species dominated approximately 90 % of the gastrointestinal tract of the larvae. The survival rate following treatment was 85 % with vancomycin, 64 % with NS oil, and 73 % with a combination of both. The count of Colony Forming Units (CFUs) was significantly lower in the vancomycin treatment group (8.14E+04) compared to those treated with NS oil (1.97E+06) and the combination treatment (8.95E+05). Furthermore, the burden was found to be lower in the NS oil (1.04E+06) and combination treatment groups (9.02E+05) compared to the vancomycin treatment group (3.38E+06). Hemocyte densities were significantly higher in the NS oil (8.29E+06) and combination treatment groups (8.18E+06) compared to the vancomycin treatment group (4.89E+06).
CONCLUSIONS
The study supported the use of model as a preliminary test to assess the effect of different antimicrobials against and gut microbiota. NS oil showed more selectivity against and protectiveness for the natural gut flora.
PubMed: 37965487
DOI: 10.1016/j.jsps.2023.101824 -
International Journal of Molecular... Sep 2023Combining pentamidine with Gram-positive-targeting antibiotics has been proven to be a promising strategy for treating infections from Gram-negative bacteria (GNB)....
Combining pentamidine with Gram-positive-targeting antibiotics has been proven to be a promising strategy for treating infections from Gram-negative bacteria (GNB). However, which antibiotics pentamidine can and cannot synergize with and the reasons for the differences are unclear. This study aimed to identify the possible mechanisms for the differences in the synergy of pentamidine with rifampicin, linezolid, tetracycline, erythromycin, and vancomycin against GNB. Checkerboard assays were used to detect the synergy of pentamidine and the different antibiotics. To determine the mechanism of pentamidine, fluorescent labeling assays were used to measure membrane permeability, membrane potential, efflux pump activity, and reactive oxygen species (ROS); the LPS neutralization assay was used to evaluate the target site; and quantitative PCR was used to measure changes in efflux pump gene expression. Our results revealed that pentamidine strongly synergized with rifampicin, linezolid, and tetracycline and moderately synergized with erythromycin, but did not synergize with vancomycin against , , , and . Pentamidine increased the outer membrane permeability but did not demolish the outer and inner membranes, which exclusively permits the passage of hydrophobic, small-molecule antibiotics while hindering the entry of hydrophilic, large-molecule vancomycin. It dissipated the membrane proton motive force and inactivated the efflux pump, allowing the intracellular accumulation of antimicrobials that function as substrates of the efflux pump, such as linezolid. These processes resulted in metabolic perturbation and ROS production which ultimately was able to destroy the bacteria. These mechanisms of action of pentamidine on GNB indicate that it is prone to potentiating hydrophobic, small-molecule antibiotics, such as rifampicin, linezolid, and tetracycline, but not hydrophilic, large-molecule antibiotics like vancomycin against GNB. Collectively, our results highlight the importance of the physicochemical properties of antibiotics and the specific mechanisms of action of pentamidine for the synergy of pentamidine-antibiotic combinations. Pentamidine engages in various pathways in its interactions with GNB, but these mechanisms determine its specific synergistic effects with certain antibiotics against GNB. Pentamidine is a promising adjuvant, and we can optimize drug compatibility by considering its functional mechanisms.
Topics: Linezolid; Vancomycin; Rifampin; Pentamidine; Escherichia coli; Reactive Oxygen Species; Anti-Bacterial Agents; Gram-Negative Bacteria; Tetracycline; Erythromycin
PubMed: 37762115
DOI: 10.3390/ijms241813812 -
World Journal of Orthopedics Aug 2023Periprosthetic joint infection (PJI) is a rare but terrible complication in hip and knee arthroplasty, and the use of topical vancomycin powder (VP) has been... (Review)
Review
Periprosthetic joint infection (PJI) is a rare but terrible complication in hip and knee arthroplasty, and the use of topical vancomycin powder (VP) has been investigated as a tool to potentially reduce its incidence. However, there remains no consensus on its efficacy. Therefore, the aim of this review is to provide an overview on the application of topical vancomycin in orthopaedic surgery focusing on the recent evidence and results in total joint arthroplasty. Several systematic reviews and meta-analyses on topical VP in hip and knee arthroplasty have been recently published reporting sometimes conflicting results. Apart from all being limited by the quality of the included studies (mostly level III and IV), confounding variables are often included potentially leading to biased conclusions. If taken into consideration the exclusive use of VP in isolation, the available data, although very limited, suggest that it does not reduce the infection rate in routine primary hip and knee arthroplasty. Therefore, we still cannot advise for a routinary application. A properly powered randomized-controlled trial would be necessary to clarify the role of VP in hip and knee arthroplasty. Based on the analysis of the current evidence, the use of topical VP appears to be safe when used locally in terms of systemic adverse reactions, hence, if proven to be effective, it could bring great benefits due to its low cost and accessibility.
PubMed: 37662663
DOI: 10.5312/wjo.v14.i8.589 -
World Journal of Orthopedics Oct 2023Vancomycin flushing syndrome (VFS), also known as red man syndrome, is an allergic reaction to vancomycin. It typically presents as a rash on the face, neck, and upper...
BACKGROUND
Vancomycin flushing syndrome (VFS), also known as red man syndrome, is an allergic reaction to vancomycin. It typically presents as a rash on the face, neck, and upper torso after intravenous administration of vancomycin. VFS is blamed on rapid intravenous infusion of vancomycin during management and rarely happens after local use. A review of the literature showed that in the last 23 years, 4 such cases have been reported. Here, we add another case of VFS developed after slow local absorption of vancomycin in cement beads.
CASE SUMMARY
A 44-year-old male with a known case of hypertension, no history of allergies to medications, and a history of chronic osteomyelitis of the right tibia with discharging sinus over the anterolateral aspect of the leg. The pus culture grew , which was sensitive to clindamycin and vancomycin. The patient underwent irrigation and debridement with the placement of vancomycin cement beads made from 4 g of vancomycin powder and 40 g of polymethyl methacrylate. Three hours postoperatively, the patient developed a pruritic, erythematous, macular rash predominantly on his face, neck, chest, and lower extremities and to a lesser extent his upper extremities. A diagnosis of VFS was made and was successfully treated with cetirizine (10 mg, oral) and methylprednisolone sodium succinate (125 mg, intravenous). The patient continued to have itching with a facial rash for 12 h with gradual improvement. A decision was made to not remove the beads as the patient continued to improve. Gradually, the rash disappeared after 96 h with no further sequela.
CONCLUSION
VFS can occur not only after rapid intravenous injection of vancomycin but also with local release, as in our case. As orthopaedic surgeons routinely use vancomycin with polymethyl methacrylate in chronic osteomyelitis and revision arthroplasty, they should be aware of such a complication occurring.
PubMed: 37970623
DOI: 10.5312/wjo.v14.i10.771 -
Southern African Journal of Infectious... 2023Antimicrobial stewardship principles guide the clinical use of antimicrobials, including vancomycin, but paediatric vancomycin prescribing practices have not been...
BACKGROUND
Antimicrobial stewardship principles guide the clinical use of antimicrobials, including vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa.
OBJECTIVES
To document the use, prescribing practices and monitoring of intravenous vancomycin and the spectrum of bacteria isolated on microbiological culture in children treated with intravenous vancomycin during a 12-month period at Red Cross War Memorial Children's Hospital (RCWMCH).
METHOD
A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019 was performed.
RESULTS
All 158 vancomycin prescription episodes for 143 children were included. Overall usage of intravenous vancomycin was 63 days of therapy per 1000 patient days (interquartile range [IQR]: 38-72). The median starting dose was 15 mg/kg per dose (IQR: 14-15) and median daily dose was 45 mg/kg per day (IQR: 43-60). Vancomycin was prescribed as empiric (127/158, 80%) and directed (31/158, 20%) treatment. The median duration of treatment for the directed group (7 days) was longer than the empiric group (4 days) ( = 0.001). Vancomycin serum trough concentrations were performed in 65/98 (66%) episodes where vancomycin treatment exceeded 3 days, with only 16/65 (25%) of these samples obtained before the fourth dose. Prolonged antibiotic treatment of 14 days or more was not associated with Gram-positive bacteria on culture (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 0.17-4.2).
CONCLUSION
Dosing errors, prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions.
CONTRIBUTION
The study identified multiple opportunities for improved vancomycin prescribing and monitoring. Further research and implementation of improved prescribing practices could contribute to the preservation of vancomycin as an effective antibiotic.
PubMed: 38058658
DOI: 10.4102/sajid.v38i1.528