Let us keep you informed via our e mail news update. Click here for more information. Check the latest news now at our headline page. Discuss MRSA using the comments link at foot of stories). Discover our MRSA Watch book of the month - Visit our bookstore. We have 2,800+ stories - see list below or categories in side columns.
Link: ICAAC 2006:
Vancomycin may be overused for the treatment of hospital-acquired pneumonia, perhaps because of physicians' perceptions that patients are at high risk for methicillin-resistant Staphylococcus aureus (MRSA), according to a study by Robert H. Eng, MD, and colleagues at the Veterans Affairs New Jersey Health Care System in East Orange, NJ. The study was presented at the 45th ICAAC meeting in Washington, DC.
The researchers sought to determine whether vancomycin was used appropriately or inappropriately for the treatment of pneumonia at their institution, in accordance with guidelines developed by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS). To do so, they developed an electronic form at the point of antibiotic order to capture vancomycin prescribers' decisions and thoughts.
More at the link above
Link: Entrez PubMed.
Vancomycin, an antibiotic to which methicillin-resistant Staphylococcus aureus (MRSA) is sensitive, frequently induces hypersensitivity reactions. Lowering the vancomycin infusion rate and/or premedicating with antihistamine effectively reduce hypersensitivity in most cases. However, vancomycin desensitization is sometimes the only way to ensure safe use. Two types of desensitization protocols have been reported, and these utilize different infusion intervals; rapid desensitization and slow desensitization. We herein report a case of vancomycin hypersensitivity with methicillin-resistant Staphylococcus aureus infection. A combination of the two desensitization protocols, rapid desensitization followed by slow desensitization, effectively inhibited the hypersensitivity reaction during vancomycin infusion, and methicillin-resistant Staphylococcus aureus was successfully eradicated.
Link: Prevalence and Clinical Implications
In addition to vancomycin-intermediate Staphylococcus aureus (VISA), S. aureus with a vancomycin MIC of 4 microg/ml has been reported to be the cause of therapeutic failure. This study was designed to determine the prevalence of methicillin-resistant S. aureus (MRSA) with a vancomycin MIC of 4 microg/ml and to clarify the clinical characteristics of infections caused by these isolates. During the 8-week period from April to May, 2001, 27 hospitals participated in a nationwide surveillance program for VISA and vancomycin-resistant S. aureus (VRSA) in Korea. After screening on brain-heart infusion agar containing 4 microg/ml of vancomycin as previously described, 100 isolates with confluent growth were tested. The medical records of the patients involved were reviewed. Even though VISA or VRSA was not detected among 3,756 MRSA isolates, 18 (0.5%) had a vancomycin MIC of 4 microg/ml. The infections in 12 of these patients, excluding 5 that were colonized, were 8 chronic osteomyelitis, 1 surgical site infection, 1 pneumonia, 1 intra-abdominal infection, and 1 catheterrelated infection. Although 11 cases were exposed to glycopeptides for a long time (median 56 days), the site of infection became culture-negative in only 1 case. Two patients died of their S. aureus infections. MRSA with a vancomycin MIC of 4 microg/ml was rare. Chronic osteomyelitis was the most common type of infection, and prolonged exposure to glycopeptides was associated with reduced susceptibility to vancomycin.
Link: Potential Impact
Vancomycin as the drug of choice for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia has been called into question on the basis of therapeutic failures. In patients with MRSA pneumonia, treatment failures are probably due to the complex interplay of variables affecting the host-antimicrobial-pathogen interrelationship. However, it has been suggested that decreased penetration of vancomycin into the lungs may contribute. This review explores physiochemical and physiologic variables that affect pulmonary penetration and describes methods used in quantifying pulmonary vancomycin concentrations. Most important, findings are evaluated in the clinical context of the chemotherapeutic options available for treatment of MRSA pneumonia. The possibility of increased serum vancomycin concentrations as a method to optimize current treatment outcomes is also explored.
Link: HubMed Abstracts.
The clinical efficacy of Maeda's nomogram for vancomycin dosage adjustment was evaluated by comparison with a standard dosage regimen (package insert information: vancomycin dose reduced in elderly patients and patients with renal dysfunction, with Moellering's nomogram used for renal-dysfunction patients) in adult Japanese MRSA pneumonia patients. Using Maeda's nomogram, the vancomycin dose is fixed at 1,000 mg while the dosing interval is varied in accordance with individual creatinine clearance. Using a standard dosage regimen, 5 patients out of 27 (18.5%) achieved target plasma levels of vancomycin (25-40 mug/mL for peak and 5-15 mug/mL for trough) within 2-6 days. Using Maeda's nomogram, 38 patients out of 53 (71.7%) achieved target levels in that time. A higher clinical response (complete resolution of all signs and symptoms of MRSA infection) to vancomycin therapy was also obtained with Maeda's nomogram when evaluated approximately 2-weeks after discontinuation of vancomycin therapy (43.4% versus 18.5% for the standard regimen). In conclusion, the Maeda's nomogram regimen with a 1,000 mg vancomycin dose was shown to achieve target plasma levels of vancomycin at a higher rate and provide higher clinical efficacy in vancomycin therapy of MRSA pneumonia patients, as compared with the currently available standard dosage regimen.
Link: Journal of Antimicrobial Chemotherapy.
Despite the lack of development of detectable resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop vancomycin tolerance and decreased autolysis. In addition, suppression of agr function appears to end after vancomycin is stopped. Whether these changes are prerequisites for attenuated vancomycin efficacy and the development of glycopeptide resistance warrants further study. The development of vancomycin resistance may be more difficult under conditions where vancomycin serum concentrations are maintained >10 mg/L.
Link: The Annals of Pharmacotherapy.
BACKGROUND: In 2001, vancomycin replaced cefuroxime for antibiotic prophylaxis in patients undergoing cardiac surgery at our institution due to high rates of surgical site infections caused by methicillin-resistant Staphylococcus spp. However, few data supported the use of vancomycin for surgical prophylaxis. OBJECTIVE: To determine the tolerance of vancomycin for antibiotic prophylaxis and incidence of vancomycin-resistant Enterococcus (VRE) in cardiac surgery patients. METHODS: In 2 separate studies, we assessed the adverse effects in patients given perioperative vancomycin (study 1) and the incidence of VRE in patients given perioperative vancomycin (study 2). Study 1 was a prospective cohort study of patients undergoing coronary artery bypass graft (CABG) or valve replacement surgery given vancomycin (1 dose preoperatively/2 doses postoperatively) for antibiotic prophylaxis between October 2003 and December 2004. Patients were assessed for tolerance to the antibiotic regimen. In study 2, cardiac surgery patients receiving perioperative vancomycin were screened for VRE before therapy and at day 7 of hospitalization. VRE was detected using standard microbiologic procedures. RESULTS: In study 1, 1161 patients (CABG = 75%; valve = 19%; both = 6%) were evaluated. All patients but one (99.9%) were prescribed preoperative vancomycin. Therapy was changed for 34 (2.9%) patients, of which 20 changes were due to physician preference for another antibiotic. The only toxicity that required a change in the vancomycin regimen was red man's syndrome, which was experienced by 9 (0.8%) patients. Four patients did not receive a second postoperative dose due to prior renal insufficiency. Patients were most commonly switched to cefuroxime (n = 26), linezolid (n = 2), cefepime (n = 2), gatifloxacin, cefazolin, levofloxacin, or ceftriaxone (n = 1, each). In study 2, 100 patients were screened for the emergence of VRE colonization. No patient was VRE positive at baseline and 4 (4%) were positive at day 7. CONCLUSIONS: Surgical antibiotic prophylaxis with vancomycin was reasonably well tolerated in CABGnd valve replacement surgery, with a 4% incidence of VRE colonization.
Link: The Annals of Pharmacotherapy
BACKGROUND: Vancomycin is frequently used to manage serious resistant gram-positive infections. Neutropenia, whose epidemiology has not been well characterized, is a potentially serious adverse event associated with the use of vancomycin. OBJECTIVE: To characterize the incidence and risk factors for development of vancomycin-induced neutropenia in patients treated with home intravenous vancomycin therapy. METHODS: A retrospective chart review was conducted of adult patients receiving vancomycin therapy through the University of New Mexico Home Intravenous Infusion Clinic between January 1998 and December 2004. Data collection included demographics, comorbid conditions, dose and duration of vancomycin therapy, indications for vancomycin use, vancomycin concentrations, all concurrent medications, laboratory data, culture and susceptibility data, reasons for antibiotic alteration or discontinuations, all other recorded adverse events, management of adverse events, and outcomes of adverse events. RESULTS: A total of 372 charts of patients managed through the clinic were reviewed and 114 patients treated with vancomycin were identified. Fourteen (12%) cases of vancomycin-induced neutropenia were identified; 4 (3.5%) cases included a reduction in absolute neutrophil count to 500 cells/mm3 or less. The mean � SD duration of vancomycin therapy and time to neutropenia were 32 � 29 and 26 � 15 days, respectively. Laboratory monitoring was performed on a weekly basis and resolution of vancomycin-induced neutropenia occurred promptly after discontinuation. Total vancomycin doses used and serum concentrations were not associated with the development of neutropenia. CONCLUSIONS: Vancomycin-induced neutropenia may occur at a higher frequency than previously reported. Clinicians should monitor hematologic parameters at least weekly in patients receiving home intravenous vancomycin therapy.
Link: In vitro
Vancomycin is the preferred parenteral antibiotic for the treatment of all methicillin-resistant Staphylococcus aureus (MRSA) infections, including the newly emerging community-associated MRSA (CA-MRSA) infections. Vancomycin-intermediate nosocomial MRSA strains have developed in vitro and in vivo after exposure to vancomycin. The aim of this study was to determine whether daily serial passage of CA-MRSA strains onto vancomycin-supplemented agar selects for the development of vancomycin resistance. Twelve clinical isolates of the six commonest Australian and US strains of CA-MRSA were serially passaged daily for 25 days onto brain-heart infusion agar plates supplemented with 4mug/mL vancomycin and then subcultured for a further 15 days onto antibiotic-free agar to assess the stability of the resistance phenotype. Minimum inhibitory concentrations (MICs) were determined by standard Etest every 5 days from day 0 to day 40. Serial passaging resulted in increased MICs in all strains but the rises were modest, with an increase of <2 doubling dilutions. All strains remained vancomycin susceptible throughout the experiment according to Clinical Laboratory Standards Institute criteria.
Link: Comparative evaluation of tigecycline and vancomycin
Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis. . RESULTS: Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones. CONCLUSIONS: Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.
Link: HighWire Press -- Medline Abstract.
OBJECTIVES: To test the in vitro activity of linezolid (oxazolidinone) and other antimicrobial agents against MRSA isolates recovered from hospitalized patients. METHODS: We tested 150 MRSA isolates recovered from hospitalized patients. The minimal inhibitory concentration of vancomycin, teicoplanin, pristinamycin (quinupristin-dalforistin) and linezolid was determined by the Etest method. Susceptibility to other antibiotics was tested by the disk diffusion method. RESULTS: All isolates were sensitive to vancomycin, teicoplanin, pristinamycin, and linezolid. The MIC90 was 2.0 microg/ml for vancomycin and teicoplanin (range 0.5-2.0 microg/ml and 0.125-2.0 microg/ml, respectively), and 0.5 microg/ml for pristinamycin and linezolid (range 0.125-0.75 microg/ml and 0.125-0.5 microg/ml, respectively). Of the other antibiotics, fusidic acid showed the best in vitro activity, with 96.7% susceptibility, associated with trimethoprim/sulfamethoxazole (85.8%) and minocycline (84%). Penicillin was associated with the lowest susceptibility (1.3%), associated with ofloxacin (3%) and erythromycin (14%). An increase in the minimal inhibitory concentration value of vancomycin was associated with a significant decrease in resistance to TMP-SMZ (P < 0.01) and an apparent increase in resistance to other antibiotics. CONCLUSION: The excellent in vitro activity of linezolid and its reported in vivo effectiveness renders it an important therapeutic alternative to vancomycin in the treatment of MRSA infection.
Link: Journal of Pharmacy Practice.
Surveillance data demonstrate that the majority of gram-positive bacterial isolates obtained in the intensive care unit (ICU) setting are staphylococci and enterococci. Staphylococci, mainly Staphylococcus aureus and coagulase-negative staphylococci, compose the majority of clinical isolates. Data from 25 North American ICUs reported methicillin-resistant Saureus (MRSA) in more than 50% of the Saureus organisms isolated mainly from a respiratory source. In addition to MRSA, Saureus with reduced susceptibility to vancomycin has been reported. Enterococci are typically considered opportunistic pathogens, infecting immunocompromised hosts. Resistance of enterococci to vancomycin, along with the newer gram-positive antimicrobials, is an increasing problem. Investigators have demonstrated that nearly 30% of enterococci isolated in the ICU are resistant to vancomycin. The high level of resistance and limited therapeutic options make treating resistant gram-positive organisms such as MRSA and vancomycin-resistant enterococci particularly problematic. While vancomycin has long been considered the gold standard for the treatment of resistant gram-positive infections, newer agents (eg, quinupristin-dalfopristin, linezolid, and daptomycin) offer therapeutic alternatives.
Link: BBC NEWS.
This story begs several questions. Click the link above for the whole story. Is Vancomycin the only drug used in the UK? Linzelolid is believed to be more effective as we will suggest in an article next week. Why is not used more in the UK? Could it be a budget issue
Deaths from the hospital superbug MRSA could double over the next five years, experts have warned. UK scientists say the methicillin-resistant Staphylococcus aureus bacteria is becoming increasingly resistant to the antibiotic vancomycin. Around 5,000 Britons die each year from infections acquired in hospital. But the researchers, whose study is published in Emerging Infectious Diseases, say more lives will be lost if vancomycin can no longer be used. If we lose vancomycin completely as a treatment, we could see a doubling in deaths over the next five years Dr Mark Enright, University of Bath It had been thought that vancomycin-resistance was only a problem in one strain of MRSA - seen in the US and Japan. But scientists from the University of Bath, University of Bristol and Southmead Hospital say all five major types of MRSA - including those seen in the UK - show signs of resistance to vancomycin.
Link: HighWire Press -- Medline Abstract.
We report the first case of ventriculitis due to hVISA. It was successfully treated with intrathecal vancomycin and intravenous linezolid. We also believe this to be the first documented case of clinical infection due to hVISA in South Africa.
Link: HighWire Press -- Medline Abstract.
One of the cell wall-synthesizing enzymes (known as PBP2') of this pathogen has low affinity to beta-lactams, and therefore the bacterial cells continue to grow even under high concentrations of the agents. However, this drug resistance does not seem to be total. They seem to have some weak spots and several substances are known to sensitize strains of MRSA to beta-lactams. This review discusses the ability of polyoxotungstates (POTs) to sensitize MRSA to beta-lactams by reducing the expression of PBP2'. It is also possible that the sensitization is a type of stress response of MRSA to POTs. This idea may provide a hint for the development of a new antimicrobial agent.
Link: HighWire Press -- Medline Abstract.
Aims: To investigate whether dehydroepiandosterone (DHEA), an androgen present throughout life, alters the response of Staphylococcus aureus clinical isolates to vancomycin. Methods and Results: DHEA in physiologically relevant concentrations (0.1, 0.5, 1.0 and 5.0 mumol l(-1)) was tested for its effect on methicillin-sensitive S. aureus (MSSA, n = 53) and methicillin-resistant S. aureus (MRSA, n = 73) response to vancomycin using standard protocols. Mutant selection was determined by serial transfer of selected isolates (n = 5). DHEA-mediated at least a fourfold increase in vancomycin MIC for 42% of MSSA and 21% of MRSA. For five of the isolates (0.1 and 0.5 mumol l(-1) DHEA) the MIC was increased to levels (8 mug ml(-1)) defined as vancomycin-intermediate resistance. Conclusion: Resistance was detected only in the presence of DHEA, and was not related to altered generation time, indicating induction of phenotypic resistance. Significance and Impact of the Study: These findings require further investigation to determine what role DHEA plays in clinical vancomycin treatment failure that has been reported in the absence of vancomycin genotypic resistance or heteroresistance.
Link: Journal of Antimicrobial Chemotherapy.
It is not entirely surprising, therefore, that despite more than 40 years of clinical use and the interim appearance of bacterial strains resistant to this drug class, there remains continued interest in the development of newer members of the glycopeptide antibiotic class. This paper is intended to provide a global overview of the efficacy and safety of glycopeptide antibiotics currently in use, as background to understanding the need for and potential roles of new agents of this class.
Link: Antimicrobials Are Used Properly Only About Half the Time.
Antimicrobial medications intended to prevent surgical site infections are appropriately administered to patients (within one hour before incision) only 55.7 percent of the time, according to a study published in the February 2005 issue of Archives of Surgery. Surgical site infections (SSIs) are a major contributor to patient injury, mortality and health care costs, increasing mortality rates by two to three times, length of hospital stay by an average of seven days and charges by approximately $3,000, according to background information in the article.
"Most (92.6 percent) of the patients in this assessment received a prophylactic antimicrobial regimen consistent with current guidelines,” according to the study. “However, only 78.7 percent received regimens that were limited to the recommended agents, suggesting that a substantial amount of antimicrobials are used unnecessarily.” “The results of this study raise additional concerns regarding antimicrobial resistance. Our data suggest that vancomycin continues to be used excessively for surgical prophylaxis,” the authors write. “In addition, 59.3 percent of patients received prophylaxis for more than 24 hours after the end of surgery.” There is evidence that use of new, broad spectrum antimicrobials and prolonged use of antimicrobials can promote antimicrobial-resistant bacteria and increase the incidence of antibiotic-associated complications, according to the article.
Link: Journal of Bone and Joint Surgery - British Volume.
Bone allografts can store and release high levels of vancomycin. We present our results of a two-stage treatment for infected hip arthroplasty with acetabular and femoral impaction grafting using vancomycin-loaded allografts. We treated 29 patients (30 hips) by removal of the implants, meticulous debridement, parenteral antibiotic therapy and second-stage reconstruction using vancomycin-supplemented impacted bone allografts and a standard cemented Charnley femoral component. The mean follow-up was 32.4 months (24 to 60). Infection control was obtained in 29 cases (re-infection rate of 3.3%; 95% confidence interval 0.08 to 17) without evidence of progressive radiolucent lines, demarcation or graft resorption. One patient had a further infection ten months after revision caused by a different pathogen. Associated post-operative complications were one traumatic periprosthetic fracture at 14 months, a single dislocation in two hips and four displacements of the greater trochanter. Vancomycin-supplemented allografts restored bone stock and provided sound fixation with a low incidence of further infection.
A short introduction from Dave Roberts
This 12 minute introduction will help you grasp the key facts and the key issues surrounding drug resistant staph aureus (mersa, mursa)
