The main use of<unk>  is the treatment of severe infections caused by aerobic Gram-positive bacteria that are resistant to other antibiotics; it should not be used against bacteria that are sensitive to drugs with a narrower spectrum of activity, such as penicillins and cephalosporins. In both the popular press and the scientific literature,<unk>  has been called a "reserve antibiotic"—one that should be used sparingly so that it will remain effective as a drug of last resort against potentially intractable infections. In the United States, the indications for<unk>  use approved by the U.S. Food and Drug Administration (FDA) are the treatment of vancomycin-resistant Enterococcus faecium infections, with or without bacterial invasion of the bloodstream; nosocomial pneumonia (hospital-acquired) and community-acquired pneumonia caused by S. aureus or S. pneumoniae; complicated skin and skin structure infections (cSSSI) caused by susceptible bacteria, including diabetic foot infection, unless complicated by osteomyelitis (infection of the bone and bone marrow); and uncomplicated skin and soft tissue infections caused by S. pyogenes or S. aureus. The manufacturer advises against the use of<unk>  for community-acquired pneumonia or uncomplicated skin and soft tissue infections caused by MRSA. In the United Kingdom, pneumonia and cSSSIs are the only indications noted in the product labeling.<unk>  appears to be as safe and effective for use in children and newborns as it is in adults. Skin and soft tissue infections A large meta-analysis of randomized controlled trials found<unk>  to be more effective than glycopeptide antibiotics (such as vancomycin and teicoplanin) and beta-lactam antibiotics in the treatment of skin and soft tissue infections (SSTIs) caused by Gram-positive bacteria, and smaller studies appear to confirm its superiority over teicoplanin in the treatment of all serious Gram-positive infections. In the treatment of diabetic foot infections,<unk>  appears to be cheaper and more effective than vancomycin. In a 2004 open-label study, it was as effective as ampicillin/sulbactam and amoxicillin/clavulanic acid, and far superior in patients with foot ulcers and no osteomyelitis, but with significantly higher rates of adverse effects. A 2008 meta-analysis of 18 randomized controlled trials, however, found that<unk>  treatment failed as often as other antibiotics, regardless of whether patients had osteomyelitis. Some authors have recommended that combinations of cheaper or more cost-effective drugs (such as co-trimoxazole with rifampicin or clindamycin) be tried before<unk>  in the treatment of SSTIs when susceptibility of the causative organism allows it. Pneumonia No significant difference appears in treatment success rates between<unk> , glycopeptides, or appropriate beta-lactam antibiotics in the treatment of pneumonia. Clinical guidelines for the treatment of community-acquired pneumonia developed by the American Thoracic Society and the Infectious Diseases Society of America recommend that<unk>  be reserved for cases in which MRSA has been confirmed as the causative organism, or when MRSA infection is suspected based on the clinical presentation. The guidelines of the British Thoracic Society do not recommend it as first-line treatment, but rather as an alternative to vancomycin.<unk>  is also an acceptable second-line treatment for community-acquired pneumococcal pneumonia when penicillin resistance is present. U.S. guidelines recommend either<unk>  or vancomycin as the first-line treatment for hospital-acquired (nosocomial) MRSA pneumonia. Some studies have suggested that<unk>  is better than vancomycin against nosocomial pneumonia, particularly ventilator-associated pneumonia caused by MRSA, perhaps because the penetration of<unk>  into bronchial fluids is much higher than that of vancomycin. Several issues in study design have been raised, however, calling into question results that suggest the superiority of<unk> . Regardless,<unk> 's advantages include its high oral bioavailability—which allows easy switching to oral therapy—and the fact that poor kidney function is not an obstacle to use. In contrast, achieving the correct dosage of vancomycin in patients with kidney failure is very difficult. Other echocardiogram shows vegetations on the tricuspid valve (white arrow) caused by infective endocarditis. The patient received conventional treatment, with ampicillin, imipenem, and glucocorticoids, and recovered fully after heart surgery.|alt=Side-by-side echocardiogram cross-sections of a human heart. In the second image a white arrow points at a mass on the tricuspid valve. It is traditionally believed that so-called "deep" infections—such as osteomyelitis or infective endocarditis—should be treated with bactericidal antibiotics, not bacteriostatic ones. Nevertheless, preclinical studies were conducted to assess the efficacy of<unk>  for these infections, and the drug has been used successfully to treat them in clinical practice.<unk>  appears to be a reasonable therapeutic option for infective endocarditis caused by multi-resistant Gram-positive bacteria, despite a lack of high-quality evidence to support this use. Results in the treatment of enterococcal endocarditis have varied, with some cases treated successfully and others not responding to therapy. Low- to medium-quality evidence is also mounting for its use in bone and joint infections, including chronic osteomyelitis, although adverse effects are a significant concern when long-term use is necessary. In combination with other drugs,<unk>  has been used to treat tuberculosis. The optimal dose for this purpose has not been established. In adults, daily and twice-daily dosing have been used to good effect. Many months of treatment are often required, and the rate of adverse effects is high regardless of dosage. There is not enough reliable evidence of efficacy and safety to support this indication as a routine use.<unk>  has been studied as an alternative to vancomycin in the treatment of febrile neutropenia in cancer patients when Gram-positive infection is suspected. It is also one of few antibiotics that diffuse into the vitreous humor, and may therefore be effective in treating endophthalmitis (inflammation of the inner linings and cavities of the eye) caused by susceptible bacteria. Again, there is little evidence for its use in this setting, as infectious endophthalmitis is treated widely and effectively with vancomycin injected directly into the eye. Infections of the central nervous system In animal studies of meningitis caused by Streptococcus pneumoniae,<unk>  was found to penetrate well into cerebrospinal fluid, but its effectiveness was inferior to that of other antibiotics. There does not appear to be enough high-quality evidence to support the routine use of<unk>  to treat bacterial meningitis. Nonetheless, it has been used successfully in many cases of central nervous system infection—including meningitis—caused by susceptible bacteria, and has also been suggested as a reasonable choice for this indication when treatment options are limited or when other antibiotics have failed. The guidelines of the Infectious Diseases Society of America recommend<unk>  as the first-line drug of choice for VRE meningitis, and as an alternative to vancomycin for MRSA meningitis.<unk>  appears superior to vancomycin in treating community-acquired MRSA infections of the central nervous system, although very few cases of such infections have been published (). Catheter-related infections In March 2007, the FDA reported the results of a randomized, open-label, phase III clinical trial comparing<unk>  to vancomycin in the treatment of catheter-related bloodstream infections. Patients treated with vancomycin could be switched to oxacillin or dicloxacillin if the bacteria that caused their infection was found to be susceptible, and patients in both groups<unk>  and vancomycin) could receive specific treatment against Gram-negative bacteria if necessary. The study itself was published in January 2009.<unk>  was associated with significantly greater mortality than the comparator antibiotics. When data from all participants were pooled, the study found that 21.5% of those given<unk>  died, compared to 16% of those not receiving it. The difference was found to be due to the inferiority of<unk>  in the treatment of Gram-negative infections alone or mixed Gram-negative/Gram-positive infections. In participants whose infection was due to Gram-positive bacteria alone,<unk>  was as safe and effective as vancomycin. In light of these results, the FDA issued an alert reminding healthcare professionals that<unk>  is not approved for the treatment of catheter-related infections or infections caused by Gram-negative organisms, and that more appropriate therapy should be instituted whenever a Gram-negative infection is confirmed or suspected. Specific populations In adults and children over the age of 12,<unk>  is usually given every 12 hours, whether orally or intravenously. In younger children and infants, it is given every eight hours. No dosage adjustments are required in the elderly, in people with mild-to-moderate liver failure, or in those with impaired kidney function. In people requiring hemodialysis, care should be taken to give<unk>  after a session, because dialysis removes 30–40% of a dose from the body; no dosage adjustments are needed in people undergoing continuous hemofiltration, although more frequent administration may be warranted in some cases. According to one study,<unk>  may need to be given more frequently than normal in people with burns affecting more than 20% of body area, due to increased nonrenal clearance of the drug.<unk>  is in U.S. pregnancy category C, meaning there have been no adequate studies of its safety when used by pregnant women, and although animal studies have shown mild toxicity to the fetus, the benefits of using the drug may outweigh its risks. It also passes into breast milk, although the clinical significance of this (if any) is unknown. Spectrum of activity<unk>  is effective against all clinically important Gram-positive bacteria—those whose cell wall
Linezolid
Meropenem
Teicoplanin
Vancomycin
Resistin
Daptomycin
Ertapenem
Colistin