Days Of Vancomycin Treatment Research Articles

An Intestinal Microbiome Intervention Affects Biochemical Disease Activity in Patients with Antiphospholipid Syndrome.

Background The origin of autoantibodies in patients with antiphospholipid syndrome (APS) is unknown. The gut microbiome contributes to autoimmunity and contains peptide homologues to the main APS autoantigen, which affect disease activity in animal models. Alteration of the gut microbiota with vancomycin diminishes disease activity in mice but no data on the effect of gut microbiota alteration in APS patients are available to date. Objective To evaluate whether the gut microbiome affects disease activity in human APS. Methods This was a pre-post design intervention study in APS patients with stable disease and no gastrointestinal comorbidity. Subjects received oral vancomycin, 500 mg four times daily for 7 days, previously shown to alter gut microbiota composition without systemic effects. Disease activity was assessed at four time points by measuring a panel of clinical phenotype-related biomarkers: antiphospholipid antibodies (APLAs), complement and inflammation markers, and hemostatic parameters. The primary outcome was the composite of the biomarker panel determined by multilevel principal component analysis. Results A total of 15 subjects completed the study. The primary outcome, the first principal component of the biomarker panel data, was significantly different after 7 days of vancomycin treatment ( p = 0.03), but not at day 42. APLA titers were unaffected. Unexpectedly, 4 out of 15 patients were negative for APLAs at baseline. In a post-hoc analysis, there was a prolonged effect for subjects with positive antibodies at baseline ( p = 0.03). In subjects with negative APLAs at baseline, the intervention showed no effect. Conclusion The intestinal microbiome affects the biochemical disease activity in APS patients. The mechanism is yet unknown but appears to be APS-specific.

Resveratrol Ameliorates Vancomycin-Induced Testicular Dysfunction in Male Rats.

Background and Objectives: Numerous studies have indicated that antibiotics may adversely affect testicular and sperm function. As an alternative to penicillin, vancomycin is a glycopeptide antibiotic developed to treat resistant strains of Staphylococcus aureus. A few studies have suggested that vancomycin could cause testicular toxicity and apoptosis. Vancomycin, however, has not been investigated in terms of its mechanism of causing testicular toxicity. Materials and Methods: An experiment was conducted to investigate the effects of resveratrol (20 mg/kg, oral gavage) against vancomycin (200 mg/kg, i.p.) on the testicular function of Wistar rats for one week (7 days). There were three subgroups of animals. First, saline (i.p.) was administered to the control group. Then, in the second group, vancomycin was administered. Finally, vancomycin and resveratrol were administered in combination in the third group. Results: After seven days of vancomycin treatment, testosterone levels, sperm counts, and sperm motility were significantly reduced, but resveratrol attenuated the effects of vancomycin and restored the testosterone levels, sperm counts, and sperm motility to normal. In the presence of resveratrol, the vancomycin effects were attenuated, and the luteinizing hormone and follicular hormone levels were normalized after seven days of treatment with vancomycin. Histologically, vancomycin administration for seven days caused damage to testicular tissues and reduced the thickness of the basal lamina. However, the resveratrol administration with vancomycin prevented vancomycin's toxic effects on testicular tissue. Conclusion: Resveratrol showed potential protective effects against vancomycin-induced testicular toxicity in Wistar rats.

Comparative Genomics Identifies Novel Genetic Changes Associated with Oxacillin, Vancomycin and Daptomycin Susceptibility in ST100 Methicillin-Resistant Staphylococcus aureus.

Infections due to vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) represent a serious concern due to their association with vancomycin treatment failure. However, the underlying molecular mechanism responsible for the hVISA/VISA phenotype is complex and not yet fully understood. We have previously characterized two ST100-MRSA-hVISA clinical isolates recovered before and after 40 days of vancomycin treatment (D1 and D2, respectively) and two in vitro VISA derivatives (D23C9 and D2P11), selected independently from D2 in the presence of vancomycin. This follow-up study was aimed at further characterizing these isogenic strains and obtaining their whole genome sequences to unravel changes associated with antibiotic resistance. It is interesting to note that none of these isogenic strains carry SNPs in the regulatory operons vraUTSR, walKR and/or graXRS. Nonetheless, genetic changes including SNPs, INDELs and IS256 genomic insertions/rearrangements were found both in in vivo and in vitro vancomycin-selected strains. Some were found in the downstream target genes of the aforementioned regulatory operons, which are involved in cell wall and phosphate metabolism, staphylococcal growth and biofilm formation. Some of the genetic changes reported herein have not been previously associated with vancomycin, daptomycin and/or oxacillin resistance in S. aureus.

Impact of Vancomycin Treatment on Human Mesenchymal Stromal Cells During Osteogenic Differentiation.

Vancomycin is frequently applied locally to the operative site during foot and ankle procedures to help prevent infection. Although the efficacy of locally applied vancomycin has been demonstrated in spine surgery, there is no consensus on dosing and indication within foot and ankle surgery. Osteogenic differentiation of human mesenchymal stromal cells (hMSCs) is key to healing of both fractures and arthrodesis. The purpose of this research was to determine the impact of vancomycin on human hMSCs during the process of osteogenic differentiation. hMSCs were cultured in osteogenic differentiation media to promote osteogenic differentiation. Cells were treated with vancomycin at differing concentrations of 0, 50, 500, and 5000 µg/mL. Viability and cell growth were assessed via LIVE/DEAD viability/cytotoxicity kit (Invitrogen, Waltham, MA) after 1, 3, and 7 days of vancomycin treatment. Differentiation and mineralization was assessed via alizarin red staining after 21 days of treatment. Mean cell viability, cell number, and mineralization were compared between treatment groups using 1-way analysis of variance and the Tukey-Kramer method for post hoc pairwise comparisons. At the highest concentrations of vancomycin, there was a significant reduction in cell viability and proliferation after 3 days compared with all other treatment groups. Mineralization was also significantly decreased with higher doses of vancomycin. At high concentrations, vancomycin may impair hMSC viability and osteogenic differentiation. Surgeons should exercise caution and consider the limited soft tissue envelope when applying vancomycin locally during foot and ankle surgery, especially during arthrodesis procedures.

Novel Mutation Sites in the Development of Vancomycin- Intermediate Resistance in Staphylococcus aureus.

Increased use of vancomycin has led to the emergence of vancomycin-intermediate Staphylococcus aureus (VISA). To investigate the mechanism of VISA development, 39 methicillin-susceptible strains and 3 MRSA strains were treated with vancomycin to induce non-susceptibility, and mutations in six genes were analyzed. All the strains were treated with vancomycin in vitro for 60 days. MICs were determined by the agar dilution and E-test methods. Vancomycin was then removed to assess the stability of VISA strains and mutations. Following 60 days of vancomycin treatment in vitro, 29/42 VISA strains were generated. The complete sequences of rpoB, vraS, graR, graS, walK, and walR were compared with those in the parental strains. Seven missense mutations including four novel mutations (L466S in rpoB, R232K in graS, I594M in walk, and A111T in walR) were detected frequently in strains with vancomycin MIC ≥ 12 μg/mL. Jonckheere-Terpstra trend test indicated these mutations might play an important role during VISA evolution. After the vancomycin treatment, strains were passaged to vancomycin-free medium for another 60 days, and the MICs of all strains decreased. Our results suggest that rpoB, graS, walk, and walR are more important than vraS and graR in VISA development.

A Rare Cause of Peritonitis in a Patient on Continuous Ambulatory Peritoneal Dialysis: Kytococcus Sedentarius

A 27-year-old male patient on CAPD presented to our clinic with a 2-day history of nausea, abdominal pain and cloudy peritoneal fluid. Intraperitoneal (ip) ceftazidime and vancomycin were empirically initiated based on the diagnosis of peritonitis. Microbiological examination of peritoneal fluid showed that Kytococcus sedentarius was the causative agent. On day 3, ceftazidime was discontinued. After 14 days of vancomycin treatment the patient was discharged with complete recovery.

Evaluation of a dosing regimen for continuous vancomycin infusion in critically ill patients: An observational study in intensive care unit patients

PurposeWe aimed to evaluate a dosing algorithm for continuous vancomycin administration in intensive care unit patients. Materials and MethodsThis observational study was conducted in a medical intensive care unit (German university hospital; June 2012-February 2013). Following a loading dose of 20 mg per kg actual body weight, vancomycin was administered continuously (20 or 30 mg of vancomycin per kg actual body weight over 24 hours depending on renal function). The vancomycin infusion rate was adjusted to achieve a target serum vancomycin concentration of 20-30 mg/L. ResultsVancomycin was administered for a median (interquartile range) of 7 (5-9) days. The median vancomycin dose given as an initial bolus was 1750 (1400-2000) mg. The median daily vancomycin dose ranged from 480 (180–960) mg (day 6) to 3.120 (2596-3980) mg (day 1). Altogether, the achieved median serum vancomycin concentration was 29.0 (25.2-33.2) mg/L. On treatment days 1 to 7, we observed target serum vancomycin levels (20-30 mg/L) in 48%, 39%, 33%, 26%, 43%, 57%, and 69% of patients. Supra-therapeutic serum vancomycin concentrations (>30 mg/L) were observed in 36%, 52%, 61%, 63%, 39%, 19%, and 15% of patients on treatment days 1 to 7. ConclusionsThe evaluated vancomycin dosing regimen for continuous infusion allowed rapid achievement of sufficient vancomycin serum levels. However, we frequently observed supra-therapeutic serum vancomycin concentrations in the first days of vancomycin treatment.

Intravenous Immunoglobulin in the Treatment of Vancomycin-Induced Toxic Epidermal Necrolysis = الغلوبيولين المناعي الوريدي في علاج إنحلال البشرة السمي الناتج عن الفانكوميسين

Toxic epidermal necrolysis (TEN), an uncommon but potentially life-threatening skin reaction, is frequently induced by drugs. The mucocutaneous reaction is characterised by bullous detachment of the epidermis and mucous membranes. We present a 9-month-old male with methylmalonic acidaemia, generalised hypotonia, and global developmental delay. He presented with a 3-day history of fever, cough, shortness of breath, and vomiting. Eruption appeared after 5 days of vancomycin treatment. The eruption involved almost 60% of the total body surface area and both eyes. He was successfully treated with intravenous immunoglobulin (IVIG), antibiotics, and appropriate wound management and made a full recovery with negligible sequelae despite the severity of his disease. Important components of successful treatment include early recognition, intensive care, prompt withdrawal of the causative agent, early administration of IVIG, appropriate fluid resuscitation, and control of infection. IVIG might be beneficial in the treatment of TEN; however, controlled studies are needed to evaluate IVIG compared to other modalities.

Positron emission tomography in the diagnosis of disseminated pyomyositis due to PVL-negative methicillin-resistant Staphylococcus aureus

A 55-year-old woman with myelodysplastic syndrome was admitted because of pyrexia and bilateral lower limb muscle pain. The creatine kinase (CK) was 1152 U/l (reference range: 40–161 U/l). Urine for myoglobin was positive. Blood culture grew methicillin-resistant Staphylococcus aureus (MRSA), sensitive to vancomycin, fusidic acid, clindamycin and erythromycin. She was treated with intravenous vancomycin (1 g every 12 h). Computed tomography (CT) of pelvis and lower limbs showed inflammatory changes in the thighs. She was discharged after 7 days of vancomycin treatment, with the CK normal and blood culture negative. She was re-admitted a week later because of recurrent pyrexia. There were multiple indurated lesions over her right lateral thigh, right forearm, left calf and the …

Outcomes and Costs Associated With a History of Vancomycin Exposure in Patients With MRSA-Related Complicated Bacteremia and Infective Endocarditis

Background Methicillin-resistant Staphylococcus aureus (MRSA) is the primary cause of complicated bacteremia (CB) and infective endocarditis (IE). Studies have compared the costs of treatment with vancomycin to those of other agents, as well as the efficacy and tolerability of these treatments. However, a literature search found no published studies of the effects of vancomycin exposure on outcomes and hospital costs in patients with CB or IE due to MRSA. Objective The aim of this study was to determine whether there is a quantitative relationship between the duration of vancomycin treatment or cumulative vancomycin exposure and outcomes or costs in patient with CB or IE due to MRSA. Methods Electronic medical records of confirmed cases of MRSA-related CB or IE from July 1, 2006, to June 30, 2008, were retrospectively reviewed to identify patients with a history of vancomycin exposure or no vancomycin exposure. Those who received vancomycin were stratified by the amount of drug administered or the duration of treatment to determine the relationship between treatment and outcomes. Data collected included demographic information, treatment information, attributable mortality, MIC data, and hospital costs. Classification and regression tree analysis (CART) was used to determine whether a history of vancomycin exposure was associated with treatment failure, attributable mortality, or both. The Mann-Whitney U test and the Fisher exact test were used for univariate analyses, and logistic regression was used for multivariate modeling. Results Data from 50 patients were evaluated (CB, 32; IE, 18). Overall rates of failure and attributable mortality were 32% and 16%, respectively. No significant differences were observed between the variables and costs. The CART break points for failure were ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years; for attributable mortality, the CART break points were ≥45 g and ≥31 days. In the final multivariate model for failure, ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years were predictors of failure (both, P = 0.002). Acute Physiology and Chronic Health Evaluation (APACHE) II score ( P = 0.04), ≥45 g ( P = 0.002), and ≥31 days of treatment ( P = 0.002) in the previous 3 years were predictors of attributable mortality after adjustment for all covariates. Conclusions Using the present model, cumulative vancomycin amount and duration were associated with attributable mortality and clinical failure but not with costs.

Successful treatment of methicillin-resistant Staphylococcus aureus endocarditis with telavancin

Sir, Within our institution, we have recently seen an increase in bloodstream infections due to methicillin-resistant Staphylococcus aureus (MRSA) having decreased responsiveness to glycopeptides. Testing has revealed that these isolates are neither vancomycin intermediate nor heterogeneous vancomycin intermediate. Patients continue to be bacteraemic despite therapeutic levels of vancomycin. In September 2009, the FDA approved telavancin for the treatment of complicated skin and soft-tissue infections. To date, there have been no reports of the use of telavancin in bacteraemic patients. Here we report the successful use of telavancin for MRSA bacteraemia and right-sided endocarditis. A patient with a history of hepatitis C and intravenous drug use presented with fevers and chills. Blood cultures grew MRSA (vancomycin MIC≤0.5 mg/L, daptomycin MIC≤1 mg/L) and he was begun on 15 mg/kg vancomycin every 12 h. He was found to have septic pulmonary emboli and a pleural effusion. A transoesophageal echocardiogram showed severe tricuspid valve regurgitation with a large tricuspid valve vegetation. Blood cultures remained positive through 8 days of vancomycin treatment with documented trough levels of 15–20 mg/L. Treatment was changed to 10 mg/kg telavancin intravenously every 24 h. Blood cultures became negative within 1 day of the start of telavancin. The patient’s creatinine was monitored and remained stable from admission. The patient underwent a tricuspid valve repair for severe tricuspid regurgitation 1 month after his initial positive culture. He completed 4 weeks of telavancin and was discharged home in a stable condition 6 weeks after his admission. At follow-up 6 weeks after completing treatment, the patient was afebrile with documented negative blood cultures. To our knowledge, this is the first case of persistent MRSA bacteraemia treated successfully with telavancin. Telavancin is a lipoglycopeptide with a mechanism of action similar to that of the glycopeptides but with an added mechanism that interferes with cell membrane function. It is reportedly rapidly bactericidal against S. aureus, thus having potential for use in bacteraemic patients. The study of telavancin in MRSA bacteraemia has been completed in murine models with the comparator being vancomycin. In this model, telavancin demonstrated greater killing activity than vancomycin, and a statistically significant difference in survival was found between the two groups with 0% survival for vancomycin and 93% for telavancin. These results have been attributed to the dual mechanism of action of telavancin as well as a longer post-antibiotic effect. With the increasing frequency of persistent MRSA bacteraemia with decreased responsiveness to vancomycin and failures reported with daptomycin after vancomycin use, new therapeutic options are desirable. Clinical studies will be necessary to determine whether telavancin offers advantages over other currently available antibiotics.

Genomic Analysis Reveals a Point Mutation in the Two-Component Sensor Gene graS That Leads to Intermediate Vancomycin Resistance in Clinical Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA), once restricted to hospitals, is spreading rapidly through the wider community. Resistance to vancomycin, the principal drug used to treat MRSA infections, has only recently emerged, is mainly low level, and characteristically appears during vancomycin therapy (vancomycin-intermediate S. aureus [VISA] and hetero-resistant VISA). This phenomenon suggests the adaptation of MRSA through mutation, although defining the mutations leading to resistance in clinical isolates has been difficult. We studied a vancomycin-susceptible clinical MRSA isolate (MIC of 1 microg/ml) and compared it with an isogenic blood culture isolate from the same patient, despite 42 days of vancomycin treatment (MIC of 4 microg/ml). A whole-genome sequencing approach allowed the nearly complete assembly of the genome sequences of the two isolates and revealed only six nucleotide substitutions in the VISA strain compared with the parent strain. One mutation occurred in graS, encoding a putative two-component regulatory sensor, leading to a change from a polar to a nonpolar amino acid (T136I) in the conserved histidine region of the predicted protein. Replacing the graS allele of the vancomycin-susceptible parent strain with the graS allele from the VISA derivative resulted in increased vancomycin resistance at a level between those of the vancomycin-susceptible S. aureus and VISA clinical isolates, confirming a role for graRS in VISA. Our study suggests that MRSA is able to develop clinically significant vancomycin resistance via a single point mutation, and the two-component regulatory system graRS is a key mediator of this resistance. However, additional mutations are likely required to express the full VISA phenotype.

Methicillin-resistant Staphylococcus aureus on orthopaedic wards

We examined the rates of infection and colonisation by methicillin-resistant Staphylococcus aureus (MRSA) between January 2003 and May 2004 in order to assess the impact of the introduction of an MRSA policy in October 2003, which required all admissions to be screened. Emergency admissions were treated prophylactically and elective beds ring-fenced. A total of 5,594 admissions were cross-referenced with 22,810 microbiology results. The morbidity, mortality and cost of managing MRSA-carrying patients, with a proximal fracture of the femur were compared, in relation to age, gender, American Society of Anaesthesiologists grade and residential status, with a group of matched controls who were MRSA-negative. In 2004, we screened 1795 of 1,796 elective admissions and MRSA was found in 23 (1.3%). We also screened 1,122 of 1,447 trauma admissions and 43 (3.8%) were carrying MRSA. All ten ward transfers were screened and four (40%) were carriers (all p < 0.001). The incidence of MRSA in trauma patients increased by 2.6% per week of inpatient stay (r = 0.97, p < 0.001). MRSA developed in 2.9% of trauma and 0.2% of elective patients during that admission (p < 0.001). The implementation of the MRSA policy reduced the incidence of MRSA infection by 56% in trauma patients (1.57% in 2003 (17 of 1,084) to 0.69% in 2004 (10 of 1,447), p = 0.035). Infection with MRSA in elective patients was reduced by 70% (0.56% in 2003 (7 of 1,257) to 0.17% in 2004 (3 of 1,806), p = 0.06). The cost of preventing one MRSA infection was 3,200 pounds. Although colonisation by MRSA did not affect the mortality rate, infection by MRSA more than doubled it. Patients with proximal fractures of the femur infected with MRSA remained in hospital for 50 extra days, had 19 more days of vancomycin treatment and 26 more days of vacuum-assisted closure therapy than the matched controls. These additional costs equated to 13,972 pounds per patient. From this experience we have been able to describe the epidemiology of MRSA, assess the impact of infection-control measures on MRSA infection rates and determine the morbidity, mortality and economic cost of MRSA carriage on trauma and elective orthopaedic wards.

ORAL VANCOMYCIN FOR ANTIBIOTIC-ASSOCIATED PSEUDOMEMBRANOUS COLITIS

Nine patients with antibiotic-associated pseudomembranous colitis were treated with oral vancomycin. All had severe diarrhœa, tissue-culture evidence of a clostridial toxin in stool, and typical lesions on sigmoidoscopic examination, despite discontinuation of all antimicrobials for periods of 10 days to 8 weeks. Oral vancomycin was given in doses of 2 g daily. All patients showed a good clinical response with gradual resolution of diarrhœa over 7 days and a rapid decrease in concentrations of the toxin in stools. Follow-up sigmoidoscopies in seven patients showed major improvement or complete clearing of lesions after 7-10 days of vancomycin treatment. The mean concentration of vancomycin in twenty-five stools obtained during treatment was 3100 μg/g, levels in serum being very low. These results suggest a role for oral vancomycin treatment of antibiotic-associated pseudomembranous colitis which persists for extended periods despite discontinuation of the incriminated antimicrobial.