Role Of Vancomycin Research Articles

Investigation of the VISA and hVISA Presence in Methicillin-Resistant Staphylococcus aureus Isolates by Various Methods

Staphylococcus aureus is an important human pathogen that causes community and hospital-acquired infections. The role of vancomycin in the treatment of methicillin-resistant S.aureus infections is indisputable. However, vancomycin intermediate susceptible S.aureus (VISA) and heterogeneously VISA (hVISA) isolates, that cause treatment failures during the use of vancomycin, cannot be detected by routine laboratory methods. The gold standard method for the detection of these isolates is the population profile analysis-area under the curve (PAP-AUC) method. In this study, it was aimed to determine the presence of mecA and mecC gene regions that cause methicillin resistance, the clonal relationship between isolates, and the presence of VISA and hVISA. A total 68 methicillin-resistant S.aureus (MRSA) strains were included in this study which were isolated in the microbiology laboratory of the hospital between 2015- 2020. Identification of the isolates were determined by matrix assisted laser desorption ionization-time of flight mass spectrophotometry (VITEK MS, BioMérieux, France). Methicillin resistance was investigated by disk diffusion method using cefoxitin (30 µg, Bioanalyse, Türkiye) disk and vancomycin MIC values were determined by broth microdilution method. mecA and mecC gene regions were investigated by polymerase chain reaction (PCR) method. The presence of VISA and hVISA were investigated by modified agar screening, macro gradient diffusion test and confirmated by PAP-AUC methods, and the clonal relationship between isolates were investigated by pulsed field gel electrophoresis method. The mecA gene region was determined in all isolates, but the mecC gene region was not found in any of the isolates. The MIC50 value of the isolates was determined as 1 μg/mL and the MIC90 value was determined as 2 μg/mL by broth microdilution method. Six VISA and four hVISA suspected strains were detected by a modified agar screening method. Among the isolates identified as suspicious by the modified agar screening method, one isolate was evaluated as VISA and one isolate was evaluated as hVISA by the gold standard PAP-AUC method. No dominant epidemic isolate has been identified by PFGE. As a result, VISA and hVISA were determined in the hospital. The increase in these isolates is a serious concern. For this reason, it is believed that it would be beneficial to investigate the VISA/hVISA ratios in MRSA isolates at certain periods, and to take necessary infection control measures to implement measures and practices to prevent the spread of these isolates in the community and hospital environment.

The concomitant use of vancomycin and piperacillin-tazobactam is associated with acute kidney injury (AKI) in extremely low birth weight infants (ELBW)

Late-onset sepsis is common in extremely low birth weight (ELBW) infants, and it leads to the use of antibiotics to cover resistant organisms, which can be nephrotoxic. Here we have investigated the role of vancomycin plus piperacillin-tazobactam on the rate of acute kidney injury (AKI). In a retrospective case-control study, medical records of all ELBW infants who were admitted to our Neonatal Intensive Care Unit (NICU) with late onset sepsis who were prescribed vancomycin plus piperacillin-tazobactam were reviewed for demographics, clinical characteristics, use of potential nephrotoxic medications and outcomes. During the study period, 264 patients were admitted, of whom 28.4%(75/264) received vancomycin plus piperacillin-tazobactam and were matched with 64 controls. There were no differences in gestational age or birth weight between cases and controls [688±160 vs. 689±162 grams (p = 0.99), and 24.7±1.8 vs. 24.7±1.6 weeks (p = 0.99) respectively]. There was no difference in the rate of sepsis between cases and controls [76%(55/72) vs. 64%(41/64) respectively, p = 0.11]. Infants exposed to vancomycin plus piperacillin-tazobactam had a higher percentage of concomitant use of vasopressors and amphotericin. To adjust for confounders, a logistic regression analysis was conducted with AKI as the dependent variable. Use of vasopressors and vancomycin plus piperacillin-tazobactam were the only risk factors associated with AKI with an adjusted OR (95%CI) of 4.08 (1.90-8.74), p < 0.001; and 2.87 (1.26-6.53), p = 0.01 respectively. The use of vancomycin plus piperacillin-tazobactam in ELBW infants is associated with an increased risk for AKI.

Single-dose bone pharmacokinetics of vancomycin in a porcine implant-associated osteomyelitis model.

The increasing incidence of orthopaedic methicillin-resistant Staphylococcus aureus (MRSA) infections represents a significant therapeutic challenge. Being effective against MRSA, the role of vancomycin may become more important in the orthopaedic setting in the years to come. Nonetheless, vancomycin bone and soft tissue penetration during infection remains unclear. In eight pigs, implant-associated osteomyelitis was induced on day 0, using a Staphylococcus aureus strain. Following administration of 1,000 mg of vancomycin on day 5, vancomycin concentrations were obtained with microdialysis for 8 h in the implant bone cavity, in cancellous bone adjacent to the implant cavity, in subcutaneous adipose tissue (SCT) adjacent to the implant cavity, and in healthy cancellous bone and healthy SCT in the contralateral leg. Venous blood samples were also obtained. The extent of infection and inflammation was evaluated by post-mortem computed tomography scans, C-reactive protein serum levels and cultures of blood and swabs. In relation to all the implant cavities, bone destruction was found. Ranging from 0.20 to 0.74, tissue penetration, expressed as the ratio of the area under the concentration-time curve from 0 to the last measured value, was incomplete for all compartments except for healthy SCT. The lowest penetration was found in the implant cavity. In conclusion, Staphylococcus aureus implant-associated osteomyelitis was found to reduce vancomycin bone penetration, especially in the implant cavity. These findings suggest that it may be unsafe to rely solely on vancomycin therapy when treating acute osteomyelitis. Particularly when metaphyseal cavities are present, surgical debridement seems necessary. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1093-1098, 2018.

The role of vancomycin in addition with colistin and meropenem against colistin-sensitive multidrug resistant Acinetobacter baumannii causing severe infections in a Paediatric Intensive Care Unit.

BackgroundAcinetobacter baumannii has been associated with high morbidity and mortality rates, even in pediatric patients. Therapeutic options are limited, especially when the strain is multidrug resistant.MethodsClinical and microbiological analyses of 4 cases of systemic infections caused by multi drug resistant A. baumannii treated with colistin/vancomycin combination at a Pediatric Intensive Care Unit were performed in order to explore the potential synergistic activity of colistin plus vancomycin. All the patients were treated with colistin, meropenem and vancomycin.ResultsFour severe infections due to MDR A. baumannii were observed. All patients treated with colistin/vancomycin combination had a positive outcome with no infection relapses. Most importantly, no significant adverse events related to the simultaneous administration of COL plus VAN were observed. In our in-vitro experiments, the synergistic effect of the combination COL plus VAN showed an early bactericidal activity even at VAN concentration of 16 mg/L, which reflects the serum trough concentrations obtained in patients.DiscussionAn antimicrobial strategy based on the activity of colistin plus vancomycin was in-vitro and in-vivo effective in life-threatening infections caused by multidrug-resistant A. baumannii in a Pediatric Intensive Care Unit, in the absence of adverse effects. Colistin plus vancomycin were highly synergic and bactericidal against carbapenem-resistant, colistin sensitive A. baumannii whereas the addition of meropenem did not enhance the in-vitro activity of colistin plus vancomycin.ConclusionsOur results confirm existing data on the potential synergistic activity of a therapeutic strategy including colistin plus vancomycin and provide important new clinical information for its potential use as a therapeutic option against MDR A. baumannii infections, especially in the pediatric population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1133-3) contains supplementary material, which is available to authorized users.

The Role of Vancomycin and Metronidazole for the Treatment of Clostridium difficile–Associated Diarrhea

For the treatment of Clostridium difficile–associated diarrhea (CDAD), metronidazole and vancomycin remain the most commonly used agents. The major advantage of metronidazole is its low cost, while the advantage of oral vancomycin is a more favorable pharmacokinetic profile. The epidemiology and clinical severity of CDAD have changed due to the emergence of a hypervirulent strain (BI/NAP1/027). In 2010, the Infectious Diseases Society of America/Society for Health Care Epidemiology of America expert panel defined severe CDAD and recommended oral vancomycin to treat these patients. Metronidazole remains the preferred agent for treatment of mild to moderate CDAD.

Targeted Use of Vancomycin as Perioperative Prophylaxis Reduces Periprosthetic Joint Infection in Revision TKA

The role of vancomycin in surgical antimicrobial prophylaxis and high-risk patients who are most likely to benefit remains unclear. We determined the impact of targeted use of vancomycin on (1) the incidence of periprosthetic joint infection (PJI); and (2) the incidence of PJI from methicillin-resistant organisms in patients undergoing revision total knee arthroplasty (TKA) at our institution. In an effort to reduce PJI rates, we added vancomycin to cefazolin as surgical antimicrobial prophylaxis for patients undergoing revision TKA in October 2010. Internal data indicated a high rate of PJI in revision TKA and in particular PJI resulting from methicillin-resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). We retrospectively reviewed infection control surveillance data on 414 revision TKAs performed between July 2008 and June 2012 (fiscal years 2009-2012). The overall rate of PJI in fiscal years 2009-2010 among 190 patients undergoing revision TKA was 7.89%. After the change in surgical antimicrobial prophylaxis, there was a significant reduction in PJI among patients undergoing revision TKA in fiscal years 2011-2012 to 3.13% (p = 0.046). In particular, we observed a reduction in PJI resulting from methicillin-resistant organisms over this same time period, from 4.21% to 0.89% (p = 0.049). Targeted use of vancomycin in patients undergoing revision TKA was effective in reducing the rate of PJI and PJI resulting from methicillin-resistant organisms in an institution with a high baseline rate of PJI due to MRSA and MRSE. Identification of high-risk subgroups of patients within a surgical population can help target infection prevention strategies to those who are most likely to benefit and thus minimize potential risks (eg, selection of resistant organisms, adverse drug events) associated with broader application of such an intervention.

Current and novel antibiotics against resistant Gram-positive bacteria

The challenge posed by resistance among Gram-positive bacteria, epitomized by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and vancomycin-intermediate and -resistant S. aureus (VISA and VRSA) is being met by a new generation of antimicrobials. This review focuses on the new β-lactams with activity against MRSA (ceftobiprole and ceftaroline) and on the new glycopeptides (oritavancin, dalbavancin, and telavancin). It will also consider the role of vancomycin in an era of existing alternatives such as linezolid, daptomycin and tigecycline. Finally, compounds in early development are described, such as iclaprim, friulimicin, and retapamulin, among others.

The Role of Vancomycin in the Treatment Paradigm

Vancomycin was introduced in the United States in 1956 as a possible treatment for infections due to penicillin-resistant Staphylococcus aureus, but it was not used widely because of toxicity and the nearly simultaneous development of semisynthetic antibiotics and cephalosporins. Thus, its main indication was the treatment of serious gram-positive infections in penicillin-allergic patients. For susceptible strains of S. aureus, vancomycin was more rapidly bactericidal than penicillin, nafcillin, or cefazolin, and, in a rabbit model of S. aureus endocarditis, sterilization of vegetations was more rapid with vancomycin. In clinical practice, however, nafcillin remained the treatment of choice for staphylococcal bacteremia, largely because it had failure rates of only 4%. With the appearance of methicillin-resistant S. aureus and coagulase-negative staphylococci, vancomycin became the drug of choice for these infections. Recently, the efficacy of vancomycin has been questioned because of vancomycin's increasing minimum inhibitory concentrations among staphylococci, poor tissue penetration, and apparently slower bacterial killing than previously was recognized.

The role of vancomycin in the persistence or recurrence of Staphylococcus aureus bacteraemia

Persistence and recurrence of Staphylococcus aureus bacteraemia (SAB) have been linked primarily with difficult-to-eradicate foci of infection such as endocarditis, osteomyelitis or abscess formation. Although vancomycin therapy has been suggested as a predictor of relapse of SAB, it has never been shown to be associated with persistent SAB. The purpose of this study was to examine the possible association of vancomycin therapy and persistence of SAB. Two groups of patients were retrospectively studied. One group consisted of 124 patients who completed > or =10 d of appropriate anti-staphylococcal therapy (from among a total of 284 patients with SAB during 2 y, 1997-8). In this group, persistence of SAB (methicillin resistant and susceptible combined) for >3 d while on therapy, occurred in 11 (22%) of 55 vancomycin recipients and in none of 52 cloxacillin recipients (p = 0.002). When calculated for methicillin susceptible SAB alone, the numbers were 3 of 13 vs 0 of 52, respectively (p = 0.007). The second study group included all patients with persistence and/or relapse of SAB while on appropriate anti-staphylococcal therapy during 4 y (1997-2000). In this group, the persistence occurred while on vancomycin therapy, in 32 (94%) of 34 patients with >3 d of persistence of SAB. In the majority of these patients a secondary focus of infection serving as the site of persistence was identified in addition to the primary focus (or portal of entry). It was concluded that vancomycin is inferior to cloxacillin therapy in terminating SAB and therefore may predispose to prolonged bacteraemia and secondary seeding of infection during therapy.

Vancomycin for Staphylococcus aureus therapy of respiratory tract infections: the end of an era?

In 1991, Karchmer [1] raised several key issues related to the pathogenesis and optimal treatment of Staphylococcus aureus infections. The main issue concerned the role of vancomycin in treating serious or invasive methicillin-sensitive S. aureus ( MSSA) and methicillinresistant S. aureus (MRSA) infections. He recognized and envisaged the current global epidemic of MRSA infections in hospitals [2], and to a lesser extent the community [3], and concluded that ‘there is an urgent need for effective alternatives to vancomycin for the treatment of MRSA infections’. Since then we have emerging evidence, a recent meta-analysis, that in patients with S. aureus -related bacteraemia, MRSA is an independent risk factor for higher mortality compared with MSSA bacteraemia [4]. This adds further support to the ongoing debate about the virulence of MRSA infections compared with MSSA and the need for optimal antibiotics at the onset of treatment. The reality, a decade later, is the occurrence of a broad range of serious and invasive MRSA infections, often in vulnerable patients in ‘high risk’ clinical settings [5]. The need to treat many of these patients empirically with a view to ‘covering’ the most likely offending pathogens is perceived to be high if the critical therapeutic window of opportunity for optimal antibiotic therapy is not to be missed. The undesirable consequences of not getting the ‘right drug, to the right patient, in the right dose at the right time’ are clear [6]. The rapid laboratory and clinical capability of predicting patients likely to be infected with MRSA continues to improve but is by no means ideal [7,8]. Additionally, we are witnessing the concurrent rise in S. aureus strains that exhibits glycopeptide-intermediate susceptibility from several countries including Japan, France and US that has been subject to recent review [9]. For example, strains with MIC to vancomycin of 4 mg/l have caused clinical infections that failed to respond to vancomycin therapy. Traditionally, when the effectiveness of an antimicrobial agent in serious infections is considered, there has been an overemphasis on the need for bactericidal activity as a pre-requisite for a good outcome. Many of us now accept that local tissue penetration should be considered of equal importance. This is particularly important when looking at treatment options for staphylococcal infections, especially in tissues such as lung or the endovascular lining. Vancomycin is still regarded as the ‘gold-standard’ therapy for serious or invasive MRSA infections. Considering Karchmer’s concerns of a decade ago, we examine what more have we learnt about vancomycin treatment and summarize the emerging evidence for new or combination therapies. Vancomycin is bactericidal and appears to exert its effect by binding to the precursor units of peptidoglycan synthesis inhibiting the transpeptidase reaction. It exhibits concentration-independent bactericidal action against susceptible bacteria and is more bactericidal in aerobic conditions. This effect is exerted without a lag period but acts only on multiplying organisms and with a post-antibiotic effect of about 2 h. Against MSSA, it is a less active agent than b-lactams [1,10 /12] by virtue of being more slowly and incompletely bactericidal compared with equivalent concentrations of a b-lactam. A recent illustration of this phenomenon in clinical practice was demonstrated by Tam et al. [13] in haemodialysis patients with MSSA bacteraemia. This study revealed that persistent bacteraemia 24 h after therapy was significantly greater (37% vs. 25%, P /0.05) in patients initially treated with vancomycin compared with those with a b-lactam. Additionally, in patients with MSSA endocarditis and related bacteraemia, there * Corresponding author. Tel.: /44-1382-660-111; fax: /44-1382816-178. E-mail address: dilip.nathwani@tuht.scot.nhs.uk (D. Nathwani). International Journal of Antimicrobial Agents 21 (2003) 521 /524

Preoperative vancomycin prophylaxis decreases incidence of postoperative hemodialysis vascular access infections

The role of vancomycin in the treatment of infected arteriovenous chronic dialysis access is well established. However, the role of preoperative vancomycin administration in preventing infection in newly placed, revised, or surgically thrombectomized grafts has not been determiend. We performed a prospective randomized study to examine whether vancomycin prophylaxis can decrease the incidence of postoperative graft infections. Over a 5-year period, 206 patients undergoing 408 permanent vascular access procedures were randomized into two groups. Group 1 (206 procedures) received a single intravenous dose of 750 mg of vancomycin approximately 6 to 12 hours before vascular access placement procedures, while group 2 (202 procedures) did not. Patients were evaluated for access infection within the following 30 days and before use of the access for chronic dialysis. Access infection developed in two patients (1%) in group 1 and in 12 patients (6%) in group 2 (P = 0.006. All 14 infections occurred in upper extremity polytetrafluoroethylene grafts. We conclude that the use of preoperative single-dose intravenous vancomycin prophylaxis for hemodialysis vascular graft procedures reduces the risk of postoperative access infection.