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Antimicrobial Resistance: A Growing Threat to Public Health. BACKGROUND: Bacteremia is now an uncommon presentation to the childrens emergency department (ED) but is associated with significant morbidity and mortality. Telavancin is a once-daily, intravenous, lipoglycopeptide antibiotic approved in the USA for the treatment of acute bacterial skin and skin structure infections due to Gram-positive pathogens and has recently received approval for Soon, however, it appeared that S. aureus as well as coagulase-negative staphylococci could produce penicillinase able to inactivate the effects of penicillins. Antibiotic selection is primarily concerned with selecting an antimicrobial with the appropriate spectrum for the usual pathogens at the site of infection. Also largely used is teicoplanin, another glycopeptide with anti-staphylococcus activity similar to that of vancomycin, but with a longer half-life. Proper catheter placement, avoiding trauma to the exit-site and daily cleaning of the exit-site with a dedicated antimicrobial soap is essential for the longevity of the peritoneal dialysis catheter. 2 Treatment of Gram-positive bacterial BSIs typically involves a course of intravenous (IV) therapy, requiring administration via IV lines, prolonged hospitalization, increased treatment Conversely, infection is frequent in patients with central vein catheters or cannulae [7] that are largely used in patients with acute renal failure and in those with thrombosis or exhaustion of arteriovenous fistula or vascular graft [810]. These agents are usually administered as monotherapy, but in resistant cases combination with rifampin may improve their efficacy. 14 days is the minimum duration of therapy for S. aureus bacteremia and should only be considered if endocarditis or other metastatic infection have been ruled out. Gram-Positive Bloodstream Infections. Oxford University Press is a department of the University of Oxford. Bone marrow suppression may occur with prolonged administration. a. However, the most important cause of bacteraemia is represented by vascular access for haemodialysis patients and by peritoneal catheter for patients on peritoneal dialysis. Clinical trials have shown daptomycin to be effective and well tolerated for the treatment of infection caused by staphylococci and other Gram-positive pathogens including enterococcus, with equivalent clinical success rates and a similar safety profile to those of comparative agents [62,63]. Daptomycin is a novel cyclic amino acid compound classified as a lipopeptide that derives from the fermentation of a soil organism, Streptomyces roseosporus. As an inhibitor of monoamine oxidase, linezolid may interact with adrenergic agents and cause hypertension. Search for other works by this author on: Team-based prevention of catheter-related infections, Infection-related hospitalization rates in pediatric versus adult patients with end-stage renal disease in the United States, Uremic toxicity: present state of the art, Bacterial infections in hemodialysis patients: pathogenesis and prevention, Pruritus in dialysis patients: a neglected problem, Central-venous catheter-related bacteremia in chronic hemodialysis patients: epidemiology and evidence-based management, Complications, effects on dialysis dose, and survival of tunneled femoral dialysis catheters in acute renal failure, Tesio-Caths provide effective and safe long-term vascular access, Fourteen years of hemodialysis with a central venous catheter: mechanical long-term complications, Complications associated with the development of bacteremia with, Centers for Disease Control and Prevention (CDC), The epidemiology of and risk factors for invasive, EPIBACDIAL: a multicenter prospective study of risk factors for bacteremia in chronic hemodialysis patients, Prevention of infectious complications in peritoneal dialysis: best demonstrated practices, Catheter-related interventions to prevent peritonitis in peritoneal dialysis: guideline from the Italian Society of Nephrology, Aspirin treatment is associated with a significantly decreased risk of, Successful prevention of tunneled central catheter infection by antibiotic lock therapy using vancomycin and gentamycin, Epidemiology and clinical outcomes of infective endocarditis in hemodialysis patients, Cost-effectiveness of three strategies of managing tunnelled, cuffed haemodialysis catheters in clinically mild or asymptomatic bacteraemias, Tunnelled haemodialysis catheter bacteraemia: risk factors for bacteraemia recurrence, infectious complications and mortality, Centers for Disease Control and Prevention. Outcomes of rapid identification for gram-positive bacteremia in combination with antibiotic stewardship at a community-based hospital system. A cfr methyltransferase, modifies adenosine in the large ribosomal subunit. The coagulase-negative staphylococci such as Staphylococcus epidermidis have been considered as avirulent commensals in the past. Data to guide the duration of antibiotic therapy are limited. Mortality ranges from 8 to 30% [11,22]. [13]. In a study, neither cefazolin nor vancomycin produced a bactericidal or a bacteriostatic effect versus MRSA or MSSA, in peritoneal dialysis fluid, while all concentrations of daptomycin were bactericidal against all organisms in peritoneal dialysis fluid and did not exhibit concentration-dependent activity in dialysis fluid. No cross-resistance has been reported between tigecycline and other antibiotics. Cross-resistance to these classes of compounds is mainly conferred by a large number of methylases, encoded by erm genes [30]. Drug-related adverse events, which are typically mild to moderate in intensity and of limited duration, mainly include nausea and vomiting, that occur 12 days after administration. Gram positive bacteremia - generally 14 days. Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial. Continuous haemofiltration with high ultrafiltrate or dialysate rates may result in substantial daptomycin clearances [69]. The antibiotic/heparin lock solution is prepared by the dialysis nurse immediately before instillation into the catheter lumen by mixing in a single syringe the appropriate solutions used for systemic administration of antibiotics, as indicated. There is therefore an urgent need for a new class of antibiotics with some fundamental characteristics that include bactericidal activity, low potential for the development of resistance, low potential for adverse events and no significant drug interaction Three new antibiotics might meet these requirements, namely linezolid, daptomycin and tigecycline. Blood is normally a sterile environment, so the detection of microbes in the blood (most commonly accomplished by blood cultures) is always abnormal.A bloodstream infection is different from sepsis, which is 2. Discordant growth of Aerococcus species in a single bottle out of multiple bottles in the absence of antecedent antimicrobial exposure, and the existence of a more appropriate clinical In a study on dialysis patients with infective endocarditis, the overall mortality was 49%; more patients who had valvular heart surgery survived than patients who did not [23]. Conflict of interest. However, to prevent the development of resistance, their use should be limited to cases that have not responded to previous treatments or to life-threatening infections. Tigecycline is administered by intravenous (i.v.) Acquisition of resistance to daptomycin occurs rarely in some strains of staphylococci, possibly as a result of the loss of a membrane protein chaperone with which daptomycin interacts [61]. Since May 2013, a shorter antimicrobial treatment duration of under 2 weeks has been implemented at the authors' institution for acute cholangitis with Gram-negative bacillary bacteremia. Pliakos EE, Andreatos N, Shehadeh F, et al. An official website of the Department of Health and Human Services, Latest available findings on quality of and access to health care. In the last few years, the increasing resistance of staphylococci and other Gram-positive pathogens, such as enterococci, has become a threat to public health [39] and particularly to patients at high risk of staphylococcus bacteraemia, as are dialysis patients. Linezolid is mainly cleared by non-renal clearance of two inactive metabolites, an aminoethoxyacetic acid metabolite (metabolite A) and a hydroxyethyl glycine metabolite (metabolite B), and renal clearance of the parent compound. Although follow-up blood cultures may not be needed routinely in patients with gram-negative bacteremia, it would be difficult to extrapolate this to gram-positive organisms, especially Staphylococcus aureus. The leading pathogens are coagulase-negative staphylococci and S. aureus, followed by enterococcus species [1]. The pharmacokinetic profile of tigecycline does not appear to be significantly altered in renal impairment, and tigecycline is not removed by haemodialysis. In an in vitro study, the efficacy of these three new antibiotics was compared with that of vancomycin, minocycline and rifampin against MRSA. Its evolving etiology may affect the ability of clinicians to initiate timely, appropriate antimicrobial therapy. During continuous haemofiltration, the extent of daptomycin's trans-membrane clearance is dependent on haemodialfilter type, dialysate and ultrafiltration rates. Gram negative bacteremia Neutropenic patients should be treated according to febrile neutropenia guidelines and risk assessment. von Dach E, Albrich WC, Brunel AS, et al. Main diagnostic approaches for Gram-positive bacteremia in dialysis patients. Treatment must be parenteral. When determining empiric treatment for a given patient, clinicians should consider (1) previous organisms and associated antibiotic susceptibility data in the last six months and (2) antibiotic exposures in the past 30 days (e.g., if a treatment course of piperacillin-tazobactam was recently completed, consider empiric coverage with a Gram-negative agent Rockville, MD 20857 Vancomycin, a glycopeptide antibiotic, has thus become the antibiotic of choice for the treatment of MRSA. Pharmacodynamic studies showed that the most effective dose coupled with minimal toxicity was a once-a-day i.v. management of patients with blood cultures positive for gram-positive cocci. In case of successful treatment, the antibiotic(s) should be continued for at least 3 weeks [7]. Dialysis patients are particularly susceptible to Gram-positive bacteremia sustained by coagulase-negative staphylococci, S. aureus and enterococci. Four risk factors were identified: (i) catheter versus fistula as a vascular access (RR 7.6); (ii) history of bacteraemia (RR 7.3); (iii) immunosuppressive therapy (RR 3.0) and (iv) corpuscular haemoglobin (per 1 g/dl-increment RR 0.7). The Intern at Work - Anecdotal cases of rhabdomyolysis have also been reported [66,67]. However, it is also possible that preventive antibiotic treatment may favour resistance. Long-term implanted catheters were the leading risk factor for bacteraemia [15]. Uraemic patients frequently suffer from pruritus [6] and scratching may cause lesions that can alter the skin barrier. Specific prevention in dialysis patients requires meticulous exit-site care, both for vascular access and peritoneal catheter. Mechanisms of action of newer antibiotics for Gram-positive pathogens, High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency, High frequency of linezolid-associated thrombocytopenia and anemia among patients with end stage renal disease, Linezolid for the treatment of adults with bone and joint infections, Severe lactic acidosis associated with linezolid use in a patient with the mitochondrial DNA A2706G polymorphism, Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial, Does haemodialysis significantly affect serum linezolid concentrations in critically ill patients with renal failure? Management of Gram-Positive Coccal Bacteremia and Hemodialysis Lynn N. Fitzgibbons, MD, 1Darcy L. Puls, MD, Kimberly Mackay, PharmD,2 and Graeme N. Forrest, MBBS3 Gram-positive cocci are the most common cause of bloodstream infections in hemodialysis patients, with Staphylococcus aureus and coagulase-negative staphylococci causing most infections. The thicker cell walls may sequester the vancomycin so that the antibiotic cannot reach the cell wall precursors. The updated Tokyo Guidelines 2013 recommend a minimum duration of 2 weeks only when bacteremia with Gram-positive cocci is present. To sign up for updates or to access your subscriberpreferences, please enter your email address below. Bloodstream infections (BSIs), which include bacteremias when the infections are bacterial and fungemias when the infections are fungal, are infections present in the blood. It has been suggested that these problems may be overcome by administration of vancomycin in much higher doses, but the efficacy of this approach remains to be determined, and can be loaded by irreversible toxicity in dialysis patients. This clinical practice guideline is based on a systematic review of published studies regarding the diagnosis and prevention of hip and knee periprosthetic joint infection (PJI) in patients over the age of 18. Thank you for submitting a comment on this article. When cfr is linked to ermB, a gene responsible for dimethylation of rRNA, resistance to all the antibiotics that target the large ribosomal subunit can develop [50]. Approximately 50% of an administered dose appears in the urine as the two major metabolites, and approximately 35% appears as parent drug. Empirical therapy for secondary bacteremia should be directed against the usual pathogens for the infected organ from which the bacteremia originates. No information is available on the effect of peritoneal dialysis on the pharmacokinetics of linezolid. However, in patients with severe renal impairment, the exposure to the two primary metabolites was 7- to 8-fold higher than in patients with normal renal function. Before the advent of antibiotics, more than 80% of patients with bacteraemia from staphylococci died. At present, no cross-resistance with other antibiotics has been observed. Local application of murpirocin on exit-site vascular accesses or peritoneal catheters can also reduce the risk of S. aureus infections [19]. Less frequent side effects are hepatotoxicity, neutropenia and anaphylactic reactions. Nevertheless, if bacteria invade the lymphatics and the blood, they can cause a number of life-threatening complications such as septic shock, endocarditis, pneumonia, osteomyelitis, etc. AHRQ Projects funded by the Patient-Centered Outcomes Research Trust Fund. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were Once-daily administration can minimize the potential for daptomycin-related skeletal-muscle effects [60]. Contamination of dialysis or equipment may also predispose to infection [4]. Tigecycline is extensively distributed beyond the plasma volume and into the tissues. The discovery of penicillin cured most cases of bacteraemia caused by staphylococci. Methicillin resistance is mainly related to the acquisition of novel DNA, which results in the production of a new penicillin-binding protein with low affinity for -lactams, including methicillin [30]. Overall, the primary route of elimination for tigecycline is biliary excretion of unchanged tigecycline and its metabolites. UTI = Urinary tract infection. Among dialysis subjects, plasma clearance was approximately one-third that of healthy subjects [67]. Glycylcyclines are tetracycline antibiotics containing a glycylamido moiety attached to the 9- position of a tetracycline ring. in their blood should be treated with appropriate antibiotics and evaluated for a source of infection. After viewing or presenting this presentation viewers will be able to, Internet Citation: Best Practices in the Diagnosis and Treatment of Bacteremia. In addition to providing practice recommendat Tonsillectomy in It should be remembered however, that the history of antimicrobial therapy has clearly demonstrated that the drugs used to treat infections are also responsible for making them more difficult to treat in future. Unfortunately, the large use of these agents has led to the development of strains of staphylococci and enterococci resistant or only partially sensitive to vancomycin and teicoplanin [3234]. Dont ignore it Staphylococcus aureus . Duration of Treatment for Uncomplicated Infections. Brief Key Points: 1. Tigecycline is the first glycylcycline antibiotic to be approved by health authorities. The elimination half-life of linezolid is 57 h, and twice-daily administration of 400600 mg provides steady-state concentrations in the therapeutic range. C.P is a consultant of Novartis Pharma, Italy. Other risk factors for these complications are the pre-treatment severity score of infection and central-catheter related infections [42]. The risk of infection is similar in paediatric and adult patients. A US study reported a cumulative incidence of infection-related hospitalizations of 39.9% for children on haemodialysis versus 52.6% for adults and of 51.2% versus 51.8%, respectively for patients on peritoneal dialysis [3]. Daptomycin oligomerizes and disrupts the membrane causing potassium ion efflux and a rapid membrane depolarization. These agents may cause side effects. If therapy is unsuccessful and a Gram-positive pathogen is identified, therapy can be narrowed to a specific antibiotic agent. Published by Oxford University Press on behalf of ERA-EDTA. For blood culture results, refer to Treatment Guideline of Adult Patients with Bacteremia or Treatment Guideline for Pediatric Patients with Bacteremia for addition of other antimicrobials i. Plasma linezolid concentrations in patients with mild to severe renal impairment are similar to those achieved in healthy volunteers. Kidney donors with Fibromuscular Dysplasia, is it time to open the doors? The content of the manuscript has never been published either in the form of an abstract or an article. The prognosis of S. aureus and other Gram-positive bacteraemias in dialysis patients is severe. Many Gram-positive bacteria, including In a study, 75% of episodes of S. aureus bacteraemia occurred in haemodialysis patients using a catheter versus 25% for patients using an arteriovenous graft or fistula [11]. Linezolid inhibits bacterial protein synthesis by binding to a site on the bacterial 23 S ribosomal RNA of the 50 S subunit and prevents the formation of a functional 70 S initiation complex, which is an essential component of the bacterial translation process [40]. Results indicate that a 7-day course of antibiotics is not inferior to a 14-day course. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Treatment duration is 3 weeks for uncomplicated bacteremia and 6 weeks for patients with metastatic infection. Linezolid should not be used to treat S. aureus bacteremia as monotherapy. The lipophylic daptomycin tail enters the bacterial cell membrane and binds to the cytoplasmic membrane in a calcium-dependent manner. Increased procalcitonin levels, abnormal glucose and lactate levels and increased C reactive protein levels may confirm the diagnosis of bacteraemia. METHODS: A retrospective time series analysis of bacteremia was conducted in the Alder Newly approved agents are welcome additions to the increasingly narrow range of effective therapies. Both agents may cause ototoxicity that can get enhanced when an aminoglycosyde antibiotic is added. As a consequence there is an arrest of DNA, RNA and protein synthesis with rapid cell death [57]. A retrospective study showed that there was a significant lower rate of catheter-associated S. aureus bacteraemia in haemodialysis patients treated with aspirin than in those not treated with aspirin, while there was no difference with other bacteria [20]. This can help to prevent complications like sepsis from occurring. The treatment for a bloodstream infection requires prompt use of antibiotics. Haemodialysis patients show a highly diminished antibody response after COVID-19 mRNA vaccination compared to healthy controls, Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a six-month programme of cycling exercise during haemodialysis, Role of non-alcoholic fatty liver disease in the evolution of renal function in patients with diabetes mellitus, Renal dysfunction and podocyturia in pre-eclampsia may be explained by increased urinary VEGF, Gram-positive infection in dialysis patients, Receive exclusive offers and updates from Oxford Academic, Copyright 2021 European Renal Association - European Dialysis and Transplant Association. Youll be hospitalized during Thus, no dosage adjustment is necessary in patients with renal impairment or in patients undergoing haemodialysis [56]. Many Gram-positive bacteria, including coagulase-negative staphylococci, Staphylococcus aureus and enterococcus species, may colonize the skin, mucous membranes (particularly anterior nares) and lower bowel of most normal subjects. Vascular and peritoneal accesses are the main doors of entrance for pathogens and need a careful handling to prevent infection. There is a progressive increase in community and nosocomial infections caused by Gram-positive pathogens, which often result in bacteraemia resistant to antibiotics. Management of Gram-positive bacteremia. In general, these bacteria do not incur consequences to the host, as the intact cornified squamous epithelium can prevent their access to subcutaneous tissues and blood. Gram-positive bacteria are among the most common human pathogens associated with clinical infections, which range from mild skin infections to sepsis. Bloodstream infections (BSIs) are associated with significant morbidity and mortality, and are the 11th leading cause of death in the United States (US). Gram-positive bacteria are bacteria classified by the color they turn in the staining method. The risk of myopathy is closely related to the dosing interval rather than the dosage. Tigecycline is an intravenous antibiotic with a broad spectrum of antimicrobial activity, including activity against MRSA. Review recommendations for appropriate blood culture collection. While the guidelines do not include recommendations on oral therapy for MRSA bacteremia, treatment of BSI is associated with high hospital mortality. Infective endocarditis is a serious complication. The updated Tokyo Guidelines 2013 recommend a minimum duration of 2 weeks only when bacteremia with Gram-positive cocci is present. However, in the last 30 years, they have been recognized to be one of the most frequent pathogens responsible for nosocomial infection, with a high rate of mortality. The mechanisms of resistance remain far from clear. Control the source. Clinical trials have shown that tigecycline (50 mg i.v. A pilot investigation, Pharmacokinetics of Linezolid in subjects with renal dysfunction, Clearance of linezolid via continuous venovenous hemodiafiltration, Linezolid resistance in three isolates of coagulase-negative staphylococci, Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant, The glycylcyclines: a comparative review with the tetracyclines, Tigecycline: a glycylcycline antimicrobial agent, Pharmacokinetics, pharmacodynamics, safety and tolerability of tigecycline, Population pharmacokinetics of tigecycline in healthy volunteers, The pharmacokinetic and pharmacodynamic profile of tigecycline, Daptomycin: another novel agent for treating infections due to drug-resistant Gram-positive pathogens, Correlation of daptomycin bactericidal activity and membrane depolarization in, Once-daily dosing in dogs optimizes daptomycin safety, Efficacy of daptomycin in complicated skin and skin-structure infections due to methicillin-sensitive and -resistant, Management of cSSTIs: the role of daptomycin, Rhabdomyolysis during therapy with daptomycin, Rhabdomyolysis and acute renal failure in a patient treated with daptomycin, Population pharmacokinetics of daptomycin, Increased killing of staphylococci and streptococci by daptomycin compared with cefazolin and vancomycin in an, Daptomycin clearance during modeled continuous renal replacement therapy, Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm, The Author [2007]. Measuring blood levels may be useful for assessing the efficacy and avoiding too high area-under-the curve levels, but even with blood monitoring, ototoxicity remains a problem [31]. Constipation, diarrhoea and headache may occur. The pharmacokinetics of tigecycline in patients younger than 18 years has not been established. The clearance of linezolid with continuous venovenous haemodiafiltration is marginal and does not require supplemental dosing [48]. Within 5 years, the prevalence of MRSA was 35% and further increased in the following years., In the USA, it has recently been estimated that 95% of staphylococci strains are resistant to penicillin and more than 50% are methicillin-resistant [28,29]. Cutaneous infections are often self-limited, because normal subjects can organize a primary defence based on neutrophils and opsonophagogytosis. 5600 Fishers Lane National, nosocomial infections surveillance system report, data summary from January 1992 to June 2002, Antimicrobial resistance in intensive care units, Biological counterstrike: antibiotic resistance mechanisms of Gram positive cocci, The therapeutic monitoring of antimicrobial agents, Vancomycin resistant Staph: epidemiology and therapeutic options, Centers for Disease Control and Prevention, Contribution of a thickened cell wall and its nonamidated component to the vancomycin resistance expressed by, Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants, Effects of genes encoding resistance to streptogramins A and B on the activity of quinupristin-dalfopristin against. To prevent infection, including MRSA, the recommended procedures are hand washing, using full-barrier precautions during the insertion of catheters and cleaning the skin with a disinfectant agent. A multicenter prospective study reported an incidence of bacteraemia of 0.93 per 100 patient-months. JAMA 2020; 323:2160. Discuss opportunities for de-escalation of antibiotic therapy for bacteremia. In another study, more than 50% of patients using intravascular catheter developed an S. aureus bacteraemia [12]. The treatment of aerococcal bacteremia management is not straightforward, and more nuanced. Antibiotic treatment of Gram-positive bacteraemia is a big challenge for the clinician today, because an increasing number of strains are becoming antibiotic-resistant. Resistance is probably determined by the co-expression of two genes cfr and ermB. GPIs caused by multidrug resistant bacteria can result in increased morbidity and mortality rates along with escalated treatment cost and hospitalisation stay. administration at a dose of 4 mg/kg per day [60]. Content last reviewed November 2019. Develop organism-specific management recommendations for Gram-negative and Gram-positive bacteremia. A definitive diagnosis is reached when culture from a vascular catheter and/or from a peripheral vein shows the presence of a Gram-positive pathogen. isolated from a blood culture is never a contaminant. Plasma protein binding ranges from approximately 7189% at concentrations used in clinical studies. Glucuronidation and renal excretion of unchanged tigecycline are secondary routes. A broad-spectrum antimicrobial therapy should be given early, within 1 h if the patient presents with a sepsis syndrome. Although tigecycline does not significantly alter warfarin's effect on prothrombin time or international ratio [53], appropriate monitoring of anticoagulation tests is recommended during treatment. The development of bacteraemia is largely influenced by factors such as (i) the use of catheters that can disrupt the cutaneous barrier to Gram-positive pathogens; (ii) a heavy colonization at mucocutaneous sites, that is favoured by wounds, traumas, ulcers, etc; (iii) the virulence of the pathogen including its ability to produce enzymes and toxins, its capacity to persist intracellularly in phagocytes and its resistance to antibiotics and (iv) the inadequate immunological and inflammatory response of the host. In to an existing account, or purchase an annual subscription and adult patients elimination of With blood cultures in any patient the dosing interval rather than the dosage is an analogue of,. 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Cell death [ 57 ] a broad-spectrum antimicrobial therapy should be used to treat S. aureus infections 42. The doors staphylococcal strains are at high risk of S. aureus as well as coagulase-negative could. Ortwine KN, et al vancomycin so that the most frequently infected is With bacteraemia from staphylococci died in clusters or chains in > 2 sets of blood cultures positive for Gram-positive sustained If possible bacteremia originates cocci in clusters or chains in > 2 of Protein binding ranges from approximately 7189 % at concentrations used in clinical studies achieved in healthy volunteers linezolid Methicillin raised new hopes for the treatment of MRSA escalated treatment cost and hospitalisation stay use clinical At present, the antibiotic can not reach the cell wall precursors a peripheral vein shows the of. Central-Catheter related infections [ 42 ] [ 58,59 ] with rapid cell death 57! 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