Use Of Vancomycin Research Articles

In Vitro and In Vivo Antimicrobial Activities of Vancomycin and Rifampin against Elizabethkingia anophelis

Elizabethkingia anophelis has emerged as a critical human pathogen, and a number of isolated reports have described the successful treatment of Elizabethkingia infections with vancomycin, a drug that is typically used to target Gram-positive bacteria. This study employed in vitro broth microdilution checkerboard and time-kill assays, as well as in vivo zebrafish animal models to evaluate the individual and combination antimicrobial effects of vancomycin and rifampin against E. anophelis. The minimum inhibitory concentration ranges of vancomycin and rifampin against 167 isolates of E. anophelis were 16–256 mg/L and 0.06–128 mg/L, respectively. The checkerboard assay results revealed a synergistic effect between vancomycin and rifampin in 16.8% (28/167) of the isolates. Time-kill assays were implemented for 66 isolates, and the two-drug combination had a synergistic interaction in 57 (86.4%) isolates. In vivo zebrafish studies revealed that treatment with vancomycin monotherapy, rifampin monotherapy, or vancomycin–rifampin combination therapy yielded a higher survival rate than the control group treatment with 0.9% saline. The results of this study support the use of vancomycin to treat E. anophelis infections.

1223. Utilizing Multiple Antimicrobial Stewardship Metrics to Trend Vancomycin Use in an Implementation Study

Abstract Background Inpatient IV vancomycin use is often inappropriately prolonged. Methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nares swabs have shown high negative predictive values for many infections and can guide appropriate vancomycin de-escalation. Antibiotic stewardship programs (ASPs) often monitor vancomycin use in days of therapy (DoT) per 1000 patient days present (PDP). This measure can be affected, especially for smaller facilities, by changes in bed capacity and prolonged stays and thus may not accurately reflect vancomycin use. We evaluated whether alternative metrics of vancomycin use would show different impacts during a multi-step ASP intervention to reduce inappropriate vancomycin use at Veterans Affairs Tennessee Valley Healthcare System. Figure 1 Run chart of vancomycin DoT/1000 PDP at the Tennessee Valley Healthcare System (TVHS) in two years prior to intervention. Methods In September 2021, the ASP, with multiple stakeholders, initiated use of MRSA nasal swabs to inform vancomycin de-escalation. From 7/2022 to 3/2023, we performed iterative Plan-Do-Study-Act intervention cycles including educating medicine and surgical divisions on MRSA swab result interpretation, educating nurses on timely swab collection, replacing MRSA culture swabs with PCR swabs, and adding MRSA swab orders to vancomycin order sets. In April 2022, in addition to DoT/1000 PDP, we began measuring mean, median, and mode DoT per vancomycin course initiated by start week. Results Despite multiple interventions beginning July 2022, vancomycin use in DoT/1000 PDP increased to a peak of 106 DoT/1000 PDP in September 2022. In that same period, median and mode DoT per vancomycin initiation remained steady at 2 days and 1 day, respectively. Figure 2 Run chart of vancomycin DoT/1000 PDP at the TVHS from April 2022 to March 2023. Specific ASP interventions are annotated on the dates they occur. Figure 3 Run chart of mean, median, and mode days of vancomycin therapy per vancomycin course initiated at the TVHS from April 2022 to March 2023. Specific ASP interventions are annotated on the dates they occur. Conclusion DoT/1000 PDP may not be the best metric to evaluate efforts to reduce inappropriate vancomycin use. By tracking mean, median, and mode of DoT per individual vancomycin course, we determined that most providers already practice rapid de-escalation, minimizing patient vancomycin exposure. This method also allows us to quickly detect changes in prescribing patterns and determine whether interventions were warranted. More evaluation of antibiotic use metric appropriateness based on desired outcome is needed in ASPs. Disclosures Milner Staub, MD, MPH, Gilead: Stocks/Bonds|Johnson & Johnson: Stocks/Bonds

1656. Evaluation of Using Oxacillin versus Vancomycin for Empiric Therapy of Late-Onset Neonatal Sepsis in NICU

Abstract Background Our Pediatric Antimicrobial Stewardship Program (PedASP) assessed methicillin-sensitive (MSSA) and methicillin-resistant S. aureus (MRSA) infections in neonatal intensive care unit (NICU) and created a NICU-specific antibiogram. Due to a rising trend of NICU MSSA infections seen in our 84-bed NICU, empiric therapy of late-onset neonatal sepsis (LONS) was modified from vancomycin to oxacillin in January 2021. We report the two-year results of using empiric oxacillin for LONS.Figure 1.Summary of S. aureus identified in LONS cases Methods We assessed MSSA versus MRSA isolated from blood and non-blood cultures in NICU between January 2019 and December 2022. Infants with weight less than 750 grams, previous MRSA infections, maternal MRSA colonization, or serious infections based on clinical judgement were advised to use empiric vancomycin. We examined the vancomycin eligibility criteria, antibiotic-pathogen mismatch rate, 30-day mortality, and frequency of peripheral intravenous (PIV) access loss after vancomycin or oxacillin administration. The cost-savings was estimated by comparing drug and lab costs associated with vancomycin and oxacillin use. Results LONS cases are summarized in Figure 1. There was no statistical difference in incidence of S. aureus bacteremia before and after protocol implementation (p=0.45). Antibiotic-pathogen mismatch rate was 0%. Cases of MRSA bacteremia increased from 0 to 3 post protocol initiation; all cases met vancomycin eligibility criteria. The 30-day mortality among MRSA infections increased from 0 to 1 case. Post protocol implementation, the PIV loss rate decreased from 4.7 to 3.3% (p=0.04), and vancomycin use decreased by 1154 doses while oxacillin use increased by 485 doses. Based on antibiotic use and 141 vancomycin levels averted, the estimated cost-savings was $140,229. Conclusion Our PedASP utilized local susceptibility data to change empiric antibiotics for LONS, reinforcing the benefit of using antibiogram to optimize antibiotic use in NICU. Implementing a NICU-specific antibiogram improved the effectiveness of antibiotic treatment and achieved significant cost savings. Disclosures All Authors: No reported disclosures

2240. Breaking Dogmas: A Single Center Evaluation of Empiric Vancomycin Use Among Intensive Care Unit Patients with Suspected Pneumonia, Bacteremia or Sepsis

Abstract Background Augmented concern for methicillin-resistant Staphylococcus aureus (SA) infections in intensive care units (ICU) has led to increased empiric vancomycin use (EVU) in patients with suspected pneumonia, bacteremia, and/or sepsis. At Tufts Medical Center, vancomycin is prescribed at clinician discretion without restrictions. We aimed to evaluate the impact of cultures on EVU and identify predictors associated with prolonged EVU among ICU patients with cultures negative (CN) for SA. Methods A retrospective study from April 2022 to January 2023 of ICU adult patients with EVU for suspected pneumonia, bacteremia, or sepsis was conducted. ICU service, length of stay (LOS), duration of EVU, blood & respiratory cultures, mechanical ventilation (MV), central line presence, and vasopressor use were collected. Prolonged EVU was defined as vancomycin use for more than 2 days despite CN for SA. The primary outcome was the rate of prolonged EVU discontinuation. Linear regression included demographics, ICU service, LOS, indication, Charlson Co-morbidity Index, lactate, MV, and 0.5 mg/dL serum creatinine change. Logistic regression included the same variables plus age, positive respiratory cultures and MV interaction. Results A total of 165 ICU patients had EVU. Of these, 132 (80%) had cultures collected before EVU vs. 33 (20%) that did not. Blood cultures were collected in 117 (88.6%); 66 (49.6%) had respiratory cultures; 51 (38.6%) had both collected. Median vancomycin duration was 2 days (1-3). Prolonged EVU was observed in 47 (46.1%) patients, while 55 (53.9%) had EVU discontinued within 2 days with CN for SA. On average Cardiac Surgery (CS) spent 2 days longer on vancomycin compared to Surgical (p=0.037) and Pulmonary (p=0.01) patients. MV among ICU patients was less likely to be associated with vancomycin discontinuation within 2 days with CN for SA (aOR [adjusted odd ratio] 0.12, 95% CI 0.03, 0.50; p=0.003). Conclusion EVU discontinuation was more likely within 2 days in ICU patients with CN for SA, but less likely for MV or CS patients. In a substantial proportion of patients, cultures were not collected. Our findings highlight the importance of diagnostic testing in ICU settings to help reduce EVU. Disclosures Maureen Campion, PharmD, Shinoigi: Speaker

1209. Let’s take a time-out: Implementing a standardized process to assess the clinical use of vancomycin for pharmacists

Abstract Background Vancomycin is often started empirically for its reliability with gram-positive pathogens, particularly Methicillin Resistant Staph aureus (MRSA). Consequently, it is often over-prescribed. Antimicrobial stewardship programs (ASP) have used time-outs to ensure therapies are tailored to the patient with proper indication and coverage. This study aims to evaluate the impact of a standardized vancomycin time-out to optimize utilization and safety. Methods This is a pre-/post-implementation study conducted at a community teaching hospital. The study was separated into a pre-implementation phase (July-September 2022), implementation/teaching phase (October 2022), and post-implementation phase (November 2022-February 2023). Study subjects included inpatient adults on vancomycin for longer than 48 hours. Patients who are immunocompromised, hospice, or on a vancomycin regimen prior to admission were excluded. Primary outcomes include (1) percent appropriate vancomycin continued after time-out, (2) percent inappropriate vancomycin discontinued during time-out, and (3) time to de-escalation. Additional outcomes include vancomycin days of therapy (DOT) per 1000 patient days, hospital length of stay, and acute kidney injury (AKI) incidence rate. This study looked at 182 patients in the retrospective arm and 214 patients in the prospective arm. Preliminary data was initially presented at the Illinois Pharmacy Residency Conference when only 195 total patients had been reviewed. Results There was a statistically significant difference seen in percent appropriate vancomycin continued after time-out, with 57% and 40.2% seen in the prospective and retrospective arm respectively. The percent inappropriate vancomycin discontinued during time-out was also statistically significant with 69.9% and 38.8% respectively. With a time-out, average days to discontinuation for continued inappropriate regimens, and overall vancomycin DOT were decreased. There was no significant difference seen in safety outcomes including AKI incidence rates. Conclusion Pharmacy driven time-outs are useful for promoting antimicrobial stewardship and can contribute to decreased vancomycin use, Disclosures All Authors: No reported disclosures

1319. Microbiology and Epidemiology of Pediatric Ventriculoperitoneal Shunt Infections

Abstract Background Infections complicate approximately 10% of ventriculoperitoneal (VP) shunts in children, with considerable associated morbidity and mortality. Recent guidelines for empiric treatment of VP shunt infections recommend use of vancomycin combined with an anti-pseudomonal beta-lactam, but are based on low-quality evidence. We aimed to further characterize and update the microbiology of pediatric VP shunt infections using the U.S. Military Health System database. Methods Department of Defense beneficiaries less than 22 years-of-age admitted for VP shunt infection between Oct 1, 2008 and Sep 30, 2019 were included. VP shunt infection was defined using a combination of ICD-9-CM and ICD-10-CM codes, CPT codes for removal or replacement of a shunt (Table 1), and positive cultures from a normally sterile site (cerebrospinal fluid, blood, catheter tip, and peritoneum). Demographic data on age, sex, and year of admission were collected for each patient, as was microbiologic data including organism and specimen source. Results There were 32 qualifying admissions among 30 patients for VP shunt infection over the 10-year study period, with no discernable year-to-year trend identified. Half of all VP shunt infections occurred in patients less than 12 months of age (Table 2). Sixty-one unique positive cultures were identified among the 30 patients, 38 (62%) from CSF samples, and the remaining 23 (38%) from blood, peritoneum, and catheter tips (Figure 1). Coagulase-negative Staphylococcus (28%), Staphylococcus aureus (15%), and Enterococcus spp. (10%) were the leading causative pathogens (Figure 2). Enteric gram-negative rods accounted for 21% of positive cultures. Pseudomonas spp. were rarely isolated (3%), however, strict anaerobic pathogens made up 8% of positive cultures. Conclusion Empiric antibiotic treatment of VP shunt infections in children should cover gram-positive cocci and enteric gram-negative rods but need not cover Pseudomonas spp. Existing guidelines do not recommend anaerobic coverage, however, these data indicate empiric anaerobic coverage is prudent, especially when an intra-abdominal VP shunt infection is suspected. Disclosures All Authors: No reported disclosures

1706. Risk factors for infections caused by extended spectrum beta lactamase (ESBL) producing and Carbapenem-resistant Enterobacterales (CRE) in pediatric critical care settings: A case control study

Abstract Background Infections due to Gram negative resistant bacterial pathogens are a major concern in intensive care units. The purpose of this study is to determine the risk factors for developing ESBL-producing and CRE infections in pediatric patients in critical care settings (PICU and NICU). Methods A retrospective case control study of infections due to ESBL-producing and CRE during a 5-year period (2016-2021) at Children’s Hospital of Michigan, Detroit. All patients had positive cultures during their PICU/NICU stay. Control cases were matched for age, infection site and year of infection but their cultures grew Enterobacterales that were non-ESBL or carbapenemase producers. Results A total of 58 patients with ESBL/Carbapenemase-producing Enterobacterales (cases) and 59 control patients were included. Majority of organisms were E. coli and Klebsiella species recovered from respiratory tract. There was no difference in both groups in regards to age, gender, race or length of hospital stay (p >0.3). There was no difference in prior hospital admission, PICU or NICU stay during the previous 6 months, indwelling devices, comorbid conditions, or surgery in the last 6 months (p >0.3). However, the presence of gastrostomy tube was more frequent in the cases group (29.3%) than the control group (15.3%) (p=0.078). Risk factors by univariate analysis included history of antibiotic use in last 6 months (93% in cases vs 73% in controls; p=0.006), cephalosporins use > 14 days (67% vs 31.2%; p=0.006),Trimethoprim/Sulfamethoxazole treatment duration > 14 days (11.1% vs 0%; p=0.012), carbapenem treatment duration > 14 days (14% vs 1.9%; p=0.027), and vancomycin use > 14 days (43.6% vs 21.6%; p=0.053). However, multivariate logistic regression analysis showed that antibiotic usage in the last 6 months was the single best predictor for cases with odds ratio of 5.02-fold (95% CI 1.56-16.13) (p=0.007). Conclusion Prior broad spectrum antibiotic usage was significantly associated with acquisition of ESBL and carbapenemase producing Enterobacterales. The study further underscores the need for optimizing antimicrobial stewardship practices to limit unnecessary and prolonged use of antibiotics to prevent the emergence of resistant pathogens. Disclosures All Authors: No reported disclosures

160. Measuring the Impact of PCR-based MRSA Nares Screening on Vancomycin Use and Duration of Vancomycin Among Pneumonia Patients at an Academic Medical Center

Abstract Background The benefits of PCR-based MRSA nares screening for de-escalation of pneumonia therapy are well-established. In late 2022, UNCMC introduced a PCR-based MRSA nares screen for inpatient use, replacing a chromogenic culture-based screen. The improved turnaround time of the PCR-based test was hypothesized to increase adoption of screening for empirical de-escalation. This project assessed adoption of this diagnostic and measured impact on patients with pneumonia who comprise a cohort followed by the ASP using a visualization dashboard. Methods A report was generated of patients with admission ICD-10 codes compatible with pneumonia for January-March of 2022 (pre-PCR) and 2023 (PCR). Electronic medical records of included encounters were reviewed to collect respiratory culture data, validate vancomycin exposure days within the context of the patient’s renal function, and confirm presence of clinical pneumonia. For 2022 data, MRSA screen results were manually collected from the medical record, while for 2023 data, encounters were matched with MRSA PCR results. Fisher’s exact was used to analyze categorical data. Results 46 and 68 patients, respectively, were included for 2022 and 2023. There was a trend increase in the percentage of patients who were screened for MRSA (28% to 51%, p = 0.68; Table 1). Median turnaround time decreased from 2,022 min to 112 min. The frequency of respiratory sputum cultures, MRSA positivity, and empiric vancomycin therapy were similar. Median duration of vancomycin exposure decreased among all vancomycin recipients (3 to 2 days; Table 2). The percentage of vancomycin recipients who received just one day of coverage increased from 22% to 46%, a trend observed regardless of MRSA screening (Figure 1). Conclusion The PCR-based MRSA nares screen for inpatients with pneumonia has trended toward wider adoption compared to the prior screening method, and PCR has been associated with decreased durations of vancomycin therapy. However, similar trends were present in patients who did and did not undergo MRSA screening, suggesting both the new MRSA screen and broader institutional factors have contributed to a shift away from empirical anti-MRSA coverage for pneumonia. Disclosures All Authors: No reported disclosures

2232. Comparison of Empiric Vancomycin Prescribing in Response to Gram Positive Cocci Alerts on Blood Cultures Between Primary and Overnight Physicians on General Medicine Services: A Retrospective Study

Abstract Background Blood culture contamination is associated with unnecessary antibiotic use, increased length of stay, and increased costs. Assessing the likelihood of true bacteremia versus contamination requires consideration of clinical context and microbiologic data. This may be more difficult for covering physicians overnight, who typically cover more patients and may not know patients’ clinical history as well. We compared rates of vancomycin (VAN) initiation in response to microbiology alerts for gram-positive cocci (GPC) in blood cultures during primary team shifts versus overnight. Methods We queried the University of Virginia Clinical Data Repository for blood culture results positive for GPC from 07/01/2021 to 12/30/2022 in inpatient general medicine patients. Cultures were stratified by time of the initial positive gram stain alert, which is called as a critical result to the team. All new positive blood cultures are run on a rapid molecular diagnostic (ePlex GenMark Diagnostics) with speciation results passively entered into the chart 2 hours after gram stain. Results were excluded if the patient was already on VAN or daptomycin at the time of gram stain or if the gram stain resulted during hours when the physician coverage (primary vs covering) was not consistent. The primary outcome was the rate of VAN initiation within 2 hours of gram stain with GPCs. Secondary outcomes were number of repeat blood cultures, length of stay (LOS), and incidence of acute kidney injury (AKI). Results 320 instances of positive blood cultures were reviewed. 141 were excluded. Of 179 included instances, there was no significant difference in VAN initiation by overnight physicians compared to primary teams (21% vs 26%; p=0.418). There was no significant difference in repeat cultures or incidence of AKI. Comparison of primary and overnight physicians Blood culture speciation Conclusion There was no difference in VAN use, repeat blood cultures, or AKI when positive gram stain alerts were received by overnight physicians versus primary teams. Stewardship interventions targeting VAN prescribing in the setting of a rapid diagnostic workflow may not need to be specifically adapted to covering physicians or teams. Disclosures Amy Mathers, MD, D(ABMM), Merck: Advisor/Consultant

Maternal Group B Streptococcus Prophylaxis Improvement using an Electronic Medical Record Dynamic Order Set.

To develop and implement a Group B Streptococcal (GBS) dynamic order set to improve adherence to the American College of Obstetricians and Gynecologists/Centers for Disease Control and Prevention (ACOG/CDC) guidelines. A team of information technology and clinical experts developed a dynamic order block. The content was patterned after the CDC "Prevent GBS" mobile app. It was then embedded in the labor and delivery/induction order set and piloted at a single high-volume obstetric unit. Following the pilot and incorporation of the 2019 ACOG update of the CDC guidelines, the order set was rolled out in five additional hospitals within a region of a large health system. Information on GBS prophylaxis performance before and after implementation was available for the pilot site and four of the additional hospitals. Information before implementation was obtained electronically from electronic medical record (EMR) laboratory and pharmacy data and supplemented by manual chart review. Postimplementation data were obtained from discrete order set EMR data elements. Adherence to the guidelines before and after were compared using chi-squared test. There were 7,114 deliveries before implementation and 4,502 after implementation. Preterm delivery occurred in 6.8 and 6.9%, respectively. There was an increase in appropriate treatment of preterm patients (positive and unknown GBS) delivering after implementation (88.7-99.1%, p < 0.001). More patients were reported to have a penicillin allergy before implementation than after implementation (14.7 vs. 11.1%, respectively, p = 0.01). Associated changes in therapy noted after implementation included a nonsignificant decrease in the proportion reporting a high-risk allergy (50.3 vs. 41.9%, p = 0.18), an increase in the appropriate use of clindamycin and vancomycin (64.4 vs. 92.3%, p < 0.001) and a decrease in clindamycin use in those without sensitivity testing. Routine universal use of a dynamic admission labor/induction order set was associated with high and improved adherence to GBS prophylaxis guidelines. · Lapses in GBS prophylaxis are associated with early-onset GBS disease.. · Preterm delivery and penicillin allergic patients are commonly associated with lapses in prophylaxis.. · Dynamic EMR order set use can improve adherence to clinical guidelines..

Comparative proteomic analysis of vancomycin-sensitive and vancomycin-intermediate resistant Staphylococcus aureus.

The extensive use of vancomycin has led to the development of Staphylococcus aureus strains with varying degrees of resistance to vancomycin. The present study aimed to explore the molecular causes of vancomycin resistance by conducting a proteomics analysis of subcellular fractions isolated from vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-sensitive S. aureus (VSSA) strains. We conducted proteomics analysis of subcellular fractions isolated from 2 isogenic S. aureus strains: strain 11 (VSSA) and strain 11Y (VISA). We used an integrated quantitative proteomics approach assisted by bioinformatics analysis, and comprehensively investigated the proteome profile. Intensive bioinformatics analysis, including protein annotation, functional classification, functional enrichment, and functional enrichment-based cluster analysis, was used to annotate quantifiable targets. We identified 128 upregulated proteins and 21 downregulated proteins in strain 11Y as compared to strain 11. The largest group of differentially expressed proteins was composed of enzymatic proteins associated with metabolic and catalytic activity, which accounted for 32.1% and 50% of the total proteins, respectively. Some proteins were indispensable parts of the regulatory networks of S. aureus that were altered with vancomycin treatment, and these proteins were related to cell wall metabolism, cell adhesion, proteolysis, and pressure response. Our proteomics study revealed regulatory proteins associated with vancomycin resistance in S. aureus. Some of these proteins were involved in the regulation of cell metabolism and function, which provides potential targets for the development of strategies to manage vancomycin resistance in S. aureus.

Randomized trial of shunt infection rates comparing intraoperative Vancomycin versus Gentamicin in ventriculoperitoneal shunt system preparation

BackgroundVentriculoperitoneal (VP) shunt is the mainstay of surgical management of patients with hydrocephalus. The insertion of ventriculoperitoneal shunt may be accompanied by many potentially life-threatening complications including shunt infection. Concerted efforts have been made to reduce shunt infection rates, including use of saline- antibiotic solutions containing antibiotics such as Gentamicin, mixture of Gentamicin and Vancomycin in shunt system preparation. We therefore set out to determine the infection rates following the use of intraoperative Gentamicin and Vancomycin in ventriculoperitoneal shunt system preparation and compare the infection rates. Therefore, a randomized single blind comparative study was carried out for a period of seventeen months, among 56 patients that presented to 2 tertiary health centers in Nigeria diagnosed of hydrocephalus. Patients were randomized into Vancomycin- and Gentamicin-shunt preparation groups. The outcome measure was postoperative shunt infection rates. Statistical analysis was performed using SPSS software (version) 21. Group comparisons were made using the Student's t-test for numerical variables, and chi-square test or fisher’s exact test for categorical variables. Statistical significance was inferred at p-value < 0.05.ResultFifty-six patients were included in the study. One patient was lost to follow-up in Vancomycin group. Another patient died in Gentamicin group of sudden death without the patient exhibiting symptoms of shunt infection leaving a total of 54 for analysis. All the patients included in the study were followed up for six months. Their mean ages were between 1688.5 ± 665.3 (days) for Vancomycin group and 10,222 ± 6635.8 (days) for Gentamicin group. There was male preponderance of 55.6% as against female of 44.4%. Majority of the hydrocephalus were of congenital cause accounting for 64.8%. There was one shunt infection in the Gentamicin group giving rise to an infection rate of 1.9% which was not statistically significant (P –value—0.313). The organism isolated was Pseudomonas species.ConclusionVentriculoperitoneal shunt infection rates can be reduced to the barest minimum if standard concentration of antibiotics is used to prepare the shunt hardware employing a standard surgical technique.

Vancomicina versus teicoplanina en la profilaxis antibiótica quirúrgica

Vancomicina versus teicoplanina en la profilaxis antibiótica quirúrgica

Vancomycin resistant enterococcus risk factors for hospital colonization in hematological patients: a matched case-control study

BackgroundVancomycin-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.MethodsA 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.ResultsA 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).ConclusionsAntimicrobial 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.

Experimental Evaluation of the Hypersensitivity Reactions of a New Glycopeptide Antibiotic Flavancin in Animal Models.

Glycopeptide antibiotics are still in demand in clinical practice for treating infections caused by resistant gram-positive pathogens; however, their use is limited due to severe adverse reactions. Their predominant types of side effects are immunoglobulin E-mediated or nonmediated hypersensitivity reactions. Therefore, the development of new glycopeptide antibiotics with improved toxicity profiles remains an important objective in advancing modern antimicrobial agents. We investigated a new eremomycin aminoalkylamide flavancin, its anaphylactogenic properties, influence on histamine levels in blood plasma, pseudoallergic inflammatory reaction on concanavalin A and the change in the amount of flavancin in the blood plasma after administration. It has been shown that flavancin does not demonstrate anaphylactogenic properties. The injection of flavancin resulted in a level of histamine in the blood three times lower than that caused by vancomycin. The therapeutic dose of vancomycin led to a statistically significant increase in the concanavalin A response index compared to flavancin (54% versus 3.7%). Thus, flavancin does not cause a pseudo-allergic reaction. The rapid decrease in flavancin concentration in the blood and the low levels of histamine in the plasma lead us to assume that any pseudoallergic reactions resulting from flavancin application, if they do occur in clinical practice, will be significantly less compared to the use of vancomycin.

A descriptive study of vancomycin use at Red Cross War Memorial Children's Hospital, Cape Town.

Antimicrobial stewardship principles guide the clinical use of antimicrobials, including vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa. 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). A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019 was performed. 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) (p = 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). Dosing errors, prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions. 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.

The use of intra-articular vancomycin is safe in primary hip and knee arthroplasty

BackgroundThe use of a single dose of intra-articular antibiotic (IAA) has been reported in reducing the rate of prosthetic joint injection after total hip and knee arthroplasty. We examine the safety of IAA in primary hip and knee replacement surgery and the blood levels and joint fluid levels of vancomycin utilising this technique. MethodsFrom August to October 2021, 68 patients undergoing primary total joint arthroplasty (THA & TKA) were given 1g vancomycin intra-articularly (IA)after closure of the fascia. All patients received 2g cefazolin intravenously (IV) 30 min prior to the procedure as is our standard prophylaxis, and 21 of the patients (IA + IV) were also administered an additional 1 gm vancomycin IV. Post-operative blood vancomycin, creatinine land eGFR level monitoring was performed d1 and d3. To determine the post-operative intra-articular vancomycin levels, surgical drain fluid was sampled at day 1 and 2, in 10 patients. ResultsAll patients had serum vancomycin levels measured on day 1 and 3. In the group where vancomycin was injected after fascial closure, the average blood vancomycin level day 1 was 5.2 μg/ml (range 2.0–10.9) and day 3 was <1.4 μg/ml. The average pre-op creatinine levels were 69.4 μmol/L (56.1–82.6) compared to 70.2 μmol/L (57.0–83.4) on day 1 and 66.1 μmol/L (52.6–79.6) on day 3, (p = 0.663). The average pre-op eGFR levels (ml/min/1.73 m2) were 82.2 (76.0–88.3) compared to 81.7 (75.6–87.8) on day 1 and 83.0 (76.8–89.2) on day 3 (p = 0.736). Samples of joint fluid aspirated from surgical drains on day 1 and day 2 showed average vancomycin levels of 224 μg/ml and 51 μg/ml respectively, significantly higher than the MIC for Staph aureus. ConclusionsThe use of intra-articular vancomycin is safe in primary TJA, with no renal damage and delivers levels within the joint which are highly therapeutic for at least 48 h post injection.

Intraosseous regional prophylaxis in total knee arthroplasty.

Prophylactic antibiotics are important in reducing the risk of periprosthetic joint infection (PJI) following total knee arthroplasty. Their effectiveness depends on the choice of antibiotic and the optimum timing of their administration, to ensure adequate tissue concentrations. Cephalosporins are typically used, but an increasing number of resistant organisms are causing PJI, leading to the additional use of vancomycin. There are difficulties, however, with the systemic administration of vancomycin including its optimal timing, due to the need for prolonged administration, and potential adverse reactions. Intraosseous regional administration distal to a tourniquet is an alternative and attractive mode of delivery due to the ease of obtaining intraosseous access. Many authors have reported the effectiveness of intraosseous prophylaxis in achieving higher concentrations of antibiotic in the tissues compared with intravenous administration, providing equal or enhanced prophylaxis while minimizing adverse effects. This annotation describes the technique of intraosseous administration of antibiotics and summarizes the relevant clinical literature to date.

Vancomycin vs metronidazole use for the treatment of Clostridioides difficile infection in a tertiary care hospital in Saudi Arabia

BackgroundThe 2017 Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) guidelines recommendation for oral vancomycin as preferred treatment was based on studies conducted in North America, Australia, and Europe. According to recent published data, metronidazole remains a reasonable option. No studies have been conducted in Saudi Arabia to compare prescribing patterns before and after the release of the guidelines. Due to low CDI burden in Saudi Arabia, the aim is to assess the effectiveness and outcomes of vancomycin vs metronidazole treatment options. MethodsThis was a retrospective cohort study conducted in a tertiary care hospital in Jeddah which was approved by the Institutional Review Board (IRB 2020–53). Data was collected from January 2017 to April 2020. Eligible patients were adults (>18 years old) diagnosed with CDI who either received oral metronidazole (500 mg 3 times daily) or oral vancomycin (125–500 mg 4 times daily). Patients who received a combination of treatment or who were diagnosed with fulminant CDI were excluded. Demographic data were collected. The primary outcome was to assess treatment response to initial therapy with oral metronidazole versus oral vancomycin. Secondary outcomes included assessing early treatment response, time to discharge after diagnosis, proportion of patients with a positive VRE surveillance culture within 6 months of diagnosis, 30-day recurrence and 30-day all-cause mortality. Chi-square or Fisher's exact test were used to examine differences in categorical variables while student t-test or Mann–Whitney test, were used to examine differences in continuous variables. P value < 0.05 was considered as significant. ResultsA total of 166 patients were included in the analysis. Demographic characteristics were not significantly different between the two groups. There was no difference in treatment response between vancomycin and metronidazole (96.4 % versus 94.3 %, p = 0.682). However, compared with metronidazole, vancomycin treatment was significantly associated with better early response (94.0 % versus 77.8 %, p = 0.008). Other outcomes were not significantly different between the two drug groups for time to discharge after diagnosis (P = 0.522), 30-day recurrence (P > 0.99) and 30-day all-cause mortality (P = 0.782). Of note, the vancomycin versus metronidazole use before the 2017 IDSA guidelines (26 % versus 74 %) was completely reversed after the release of the guidelines (83.3 % versus 16.7 %), p < 0.001). ConclusionThe results of this study demonstrate that vancomycin and metronidazole have comparable outcomes in regards to treatment response for non-fulminant CDI. The study also reveals the high and quick impact of international guidelines on local prescription patterns. Further studies are needed in Saudi Arabia to guide the treatment of CDI.

Use of vancomycin and gentamicin-impregnated calcium sulfate beads for the prevention of surgical site infection in adult spinal deformity

Use of vancomycin and gentamicin-impregnated calcium sulfate beads for the prevention of surgical site infection in adult spinal deformity