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Treatment of gram - positive infections in critically ill patients
BMC Infectious Diseases volume 14, Article number: 92 (2014)
Gram-positive bacteria to include methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), and enterococci, to include vancomycin-resistant enterococci (VRE), display a remarkable array of resistance and virulence factors, which have contributed to their prominent role in infections of the critically ill. Over the last three decades infections with these pathogens has increased as has their overall resistance to available antimicrobial agents. This has led to the development of a number of new antibiotics for the treatment of Gram-positive bacteria. At present, it is important that clinicians recognize the changing resistance patterns and epidemiology of Gram-positive bacteria as these factors may impact patient outcomes. The increasing range of these pathogens, such as the emergence of community-associated MRSA clones, emphasizes that all specialties of physicians treating infections should have a good understanding of the infections caused by Gram-positive bacteria in their area of practice. When initiating empiric antibiotics, it is of vital importance that this therapy be timely and appropriate, as delays in treatment are associated with adverse outcomes. Although vancomycin has traditionally been considered a first-line therapy for serious MRSA infections, multiple concerns with this agent have opened the door for alternative agents demonstrating efficacy in this role. Similarly, the expansion of VRE as a pathogen in the ICU setting has required the development of agents targeting this important pathogen.
Scope of the problem
Sepsis represents a major heath care problem with half of the cases occurring in the critically ill and it is associated with a high mortality (50% for septic shock) for intensive care unit (ICU) patients [1, 2]. The administration of early appropriate antibiotics is recognized as one of the most important interventions linked to improving patient outcomes in sepsis [3–5]. The microbiology in the ICU has changed in the last 2 to 3 decades so that Gram-positive cocci (GPC) now represent one of the dominant species. A recent survey showed that GPC cause the majority of nosocomial infections with Staphylococcus aureus (16%, with more than 50% being methicillin-resistant [MRSA]) and Enterococcus species (14%, with vancomycin-resistant enterococci [VRE] accounting for approximately 3.5% of all infections) predominating . New resistance patterns are also emerging to include vancomycin - intermediate Staphylococcus aureus (VISA), increases in the Staphylococcus aureus minimum inhibitory concentration (MIC) to vancomycin without breaching the resistance threshold (i.e., MIC creep), vancomycin-resistant Staphylococcus aureus (VRSA) due to acquisition of the vanA gene, as well as daptomycin and linezolid resistance. Given these newly described resistance patterns, testing for susceptibility and adequate antibiotic dosing are of paramount importance for proper management of critically ill infected patients.
For the purpose of this review we will focus on the contribution of GPC to infections in critically ill patients emphasizing the agents available for their treatment. In the ICU, respiratory tract infections especially pneumonia, represent the most common infection and carry the highest mortality . The microbiology of pneumonia varies considerably based on the presence of risk factors for antibiotic resistance. While most community-acquired pneumonia (CAP) cases are caused by Streptococcus pneumoniae, health care associated pneumonias (HCAPs), particularly ventilator-associated pneumonia (VAP), are often caused by MRSA. Community-acquired MRSA pneumonia can also occur and accounts for 3% of bacterial pneumonia cases , usually being associated with younger patients, post-influenza, and necrotizing pneumonia. The rates of penicillin and ceftriaxone resistant strains of Streptococcus pneumoniae are relatively low in adults . However, macrolide resistance can be seen in up to 30% of strains. Risk factors for resistant pathogens appear to be identical for both CAP and HCAP and include: prior hospitalization and antibiotics, immunosuppression, non-ambulatory status, tube feeds and gastric acid suppressive agents .
With the advance of invasive devices (e.g. ventricular assisted devices, intravenous catheters) has come a rise in the incidence of bacteremia due to GPC. Along with device removal and a meticulous search for metastatic foci of infection (discitis, osteomyelitis, epidural abscess), antibiotic treatment remains the cornerstone of therapy. As will be discussed various choices are available for the treatment of bacteremia due to GPC. When Staphylococcus aureus is suspected, combination therapy with an anti-staphylocccal penicillin (nafcillin, oxacillin) and vancomycin should be considered until susceptibility results are known . Daptomycin has emerged as a good alternative agent for Staphylococcus aureus bacteremia and endocarditis . It also offers the advantage of proven efficacy in patients with MRSA bacteremia with vancomycin MIC >1 mg/L and for infections attributed to heteroresistant VISA, but not for VRSA [12, 13]. Linezolid has also been shown to have good activity as compared to vancomcyin in Staphylococcus aureus bacteremia .
Although less common than pneumonia and bacteremia, complicated skin and soft tissue infections (SSTIs) can be grave enough to warrant ICU care. Also, postsurgical site infections can complicate ICU stays. The main pathogen isolated in these infections is MRSA which makes empirical coverage mandatory . In recent years, most new drugs targeting GPC (e.g. linezolid, ceftaroline, telavancin, daptomcyin, tigecycline) have come to market by gaining indication for treatment of SSTIs. Moreover, there are now recognized subpopulations of patients with SSTIs who are at increased risk of bacteremia necessitating more aggressive and prolonged therapy [16, 17].
Usually dominated by Gram - negative rods and anaerobes, health-care associated intra-abdominal infections in debilitated patients often require empirical coverage for enterococci including VRE. The true pathogenicity of enterococci in these polymicrobial infections remains unclear, but isolation of enterococci from peritoneal fluid in severe infections was found to be an independent predictor of mortality . So far, limited data are available to formulate guideline recommendations for the coverage of GPC except for VRE coverage in certain high-risk patient populations (liver transplant recipients, post-surgical complications in patients with prior antibiotics, patients undergoing hepatobilliary surgery, patients with known VRE colonization) .
Advances in the management of patients with neurologic disorders and injuries have also resulted in increasing occurrence of infections at these sites, particularly with MRSA . Although microbiology varies depending on type of intervention and antibiotic prophylaxis, more than two thirds of the cases are due to Staphylococcus species (approximately half of them Staphylococcus aureus), with this percentage increasing over the last two decades [21, 22]. As with bacteremias and intravascular infections, it is imperative to remove foreign devices such as shunts and intraventricular catheters. Treatment should include vancomycin and/or ceftriaxone at doses that will insure adequate penetration into the central nervous system (CNS). Linezolid has also emerged as an alternative agent especially when vancomcyin is not an option due to unachievable trough levels or renal toxicity, due to excellent CNS penetration of linezolid even in the absence of inflamed meninges. Ceftaroline also appears to be an acceptable agent for Streptococcus pneumoniae meningitis based on animal data, but human studies are lacking. The following section will focus on the available agents to treat infections caused by GPC in critically ill patients.
Linezolid is an oxazolidinone antibiotic that blocks assembly of the initiation complex required for protein synthesis providing broad activity against Gram-positive bacteria with little to no Gram-negative activity . Linezolid has high oral bioavailability (approximately 100%) with toxicity primarily being myelosuppression, peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome . Linezolid is indicated in the US for vancomycin-resistant Enterococcus faecium (VRE) infections, including bacteremia; nosocomial pneumonia caused by Staphylococcus aureus (MSSA and MRSA), or Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP]); complicated and uncomplicated SSTIs; and CAP caused by Streptococcus pneumoniae (including MDRSP) and MSSA.
The greatest utility of linezolid seems to be for the treatment of Staphylococcus aureus infections, especially nosocomial pneumonia [24–26]. This is especially true for isolates with MICs > 1.0 mg/mL where linezolid appears to be a superior agent [26–28]. Linezolid is also indicated for the treatment of necrotizing pneumonia due to MSSA and MRSA strains secreting the Panton–Valentine leukocidin (PVL) virulence factor given its ability to block toxin production  and has been extensively studied for SSTIs, outperforming vancomycin in terms of clinical cures [30–35]. Linezolid has successfully been used off label for the treatment of secondary MRSA bacteremia [36, 37], endocarditis [38, 39], and central nervous system infections [40–42]. The greater efficacy of linezolid over vancomycin observed in some of the above noted clinical studies may be due to the upward drifting MICs of MSSA ansd MRSA to vancomycin as well as the presence of heteroresistance to vancomycin, although not all studies are consistent in demonstrating greater mortality with the presence of heteroresistance [43–50].
Like all other antibiotics, resistance to linezolid has emerged and is a concern given the drug’s potent activity for difficult to treat infections caused by GPC . However, several new oxazolidinone antibiotics are in development, including tedizolid in phase three clinical trials, that offer advantages over linezolid to include coverage of linezolid-resistant isolates and once daily dosing [52, 53].
Daptomycin is a bactericidal concentration-dependent lipopeptide that promotes the efflux of potassium out of bacterial cells, leading to cell death. It is indicated for the treatment of SSTIs (6 mg/kg) and Staphylococcus aureus bloodstream infections (8 mg/kg) including right-sided infective endocarditis, and it has been used off label for the treatment of difficult central nervous system infections caused by Gram-positive bacteria . Daptomycin should not be used for patients with pneumonia due to the inability to establish non-inferiority to ceftriaxone in a clinical trial, in large part due to the inhibition of daptomycin by surfactant [54, 55]. The main toxicities of daptomycin include eosinophilic pneumonia and skeletal muscle injury.
Guidelines from the Infectious Diseases Society of America (IDSA) for the treatment of MRSA recommend consideration of high-dose (10 mg/kg) daptomycin in patients with persistent MRSA bacteremia associated with vancomycin failure and possibly endocarditis . These recommendations are grounded on the concentration-dependent pharmacokinetic (PK)–pharmacodynamic (PD) profile of daptomycin . Suboptimal daptomycin area under the concentration-time curve (AUC) values indexed to the minimum inhibitory concentration (MIC), or AUC/MIC, have been linked to clinical failure, whereas trough (Cmin) concentrations are correlated with skeletal muscle toxicity [57, 58]. Recently, investigators observed high daptomycin clearance among critically ill patients and significantly lower drug exposures with the use of standard doses . These investigators suggest that daptomycin doses of 750 mg/day may be more effective then the 6 to 8 mg/kg dosing, especially early on when creatinine clearance and volume of distribution may be augmented, especially in septic patients .
Several large multicenter observational case series have documented the safety of high-dose daptomycin, to include the treatment of VRE bacteremia which is also an off label indication for its use [60–63]. Moreover, combination with a beta-lactam, trimethoprim/sulfamethoxazole, rifampin or gentamicin have been recommended along with higher dose daptomycin to avoid the emergence of resistance when used as salvage therapy for vancomycin treatment failures . Clinicians should also be aware that recurrent or breakthrough bacteremia following prolonged treatment of Staphylococcus aureus or enterococcal infection, to include endocarditis, may signal the emergence of daptomycin resistance, necessitating a change in therapy [11, 64].
Vancomycin is a glycopeptides antibiotic with a number of labeled indications for use in the US against GPC, primarily MRSA, to include catheter-related infections, Clostridium difficile-associated diarrhea (oral), complicated infections in seriously ill patients, enterocolitis due to Staphylococcus aureus (oral), Group B streptococcus (neonatal prophylaxis), meningitis (with third-generation cephalosporin for penicillin-resistant Streptococcus pneumonia), pneumonia, prophylaxis against infective endocarditis, and susceptible (MIC ≤1 mcg/mL) Gram-positive infections. There are also many off-label indications where vancomycin is frequently used as first line therapy to include bacteremia, central nervous system infections due to MRSA (brain abscess, subdural empyema, spinal epidural abscess), endocarditis (native valve or prosthetic valve due to Enterococcus with vancomycin MIC ≤4 mg/L, streptococci with penicillin MIC >0.5 mg/L or patient intolerance to penicillin, or MRSA), endophthalmitis, SSTIs, prosthetic joint infections, and surgical prophylaxis. The main toxicities of vancomycin for concern in critically ill patients include hypersensitivity reactions, renal toxicity and cytopenias.
The major current problem associated with increasing vancomycin usage over the last several decades is the increasing occurrence of treatment failures due to drug resistance. Rising MICs to vancomycin appears to be the main mechanism associated with these treatment failures . Although uncommon, horizontal transfer of the vanA operon from VRE has led to VRSA, while repeated exposure to vancomycin has allowed staphylococci to adapt under selective pressure leading to the emergence of both VISA and heterogeneous-resistant VISA (hVISA) [66, 67]. Surveillance studies have reported the prevalence of hVISA among clinical MRSA isolates to be between zero and 74% [68–73]. The true prevalence of hVISA is difficult to determine since many institutions do not routinely screen for it and there are no standardized methods for rapid detection of hVISA as the ‘gold standard’ population analysis is labor intensive to perform.
Given the emerging resistance of GPC, especially MRSA, to vancomycin, the IDSA has recommended that vancomycin be administered according to body weight (15–20 mg/kg/dose, actual body weight) every 8–12 hours, not to exceed 2 g per dose, in patients with normal renal function (56). However, in seriously ill patients (eg, those with sepsis, meningitis, pneumonia, or infective endocarditis) with suspected MRSA infection, a loading dose of 25–30 mg/kg (actual body weight) may be considered. Vancomycin trough concentrations should be monitored in such patients and maintained between 15–20 μg/mL. Unfortunately, clinical studies do not support an association between greater vancomycin trough levels and improved clinical outcomes supporting the use of alternative agents when suspected or proven infection with high MIC isolates is encountered [26, 33, 74, 75]. Moreover, the MIC test method has a significant impact on vancomycin AUC/MIC estimation . Clinicians should be aware that the current target AUC/MIC of ≥400 for vancomycin was derived using the reference broth microdilution method and does not apply to the use of other automated methods .
Ceftaroline is an anti-MRSA cephalosporin that was approved by the FDA in 2010 for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and soft structure infections (ABSSSI). Ceftaroline works by binding to penicillin-binding proteins (PBPs) inhibiting their ability to function as transpeptidases in cell wall synthesis. However, it is unique for its affinity for PBP2a and PBP2x providing activity against MRSA and MDRSP including ceftriaxone resistant strains . The approved indications for ceftaroline include SSTIs and CAP at a dose of 600 mg every 12 hours. However, it is important to note that the CAP trials only enrolled patients who were not critically ill [77, 78]. It is not clear whether the approved dose of ceftaroline is adequate for critically ill patients with augmented creatinine clearance and volumes of distribution. In critically ill patients with normal or augmented renal function 600 mg every 8 hours should be considered until more data become available in this population.
Despite ceftaroline having activity against MRSA, little data is available for its use in severe infections caused by Gram-positive bacteria such as infective endocarditis or osteomyelitis. However, a number of case series have recently appeared suggesting that ceftaroline alone, or in combination with another agent, can be used to treat such infections attributed to MRSA or Enterococcus faecalis[79–83]. Though limited clinical data supporting ceftaroline for hVISA, VISA or daptomycin non-susceptible Staphylococcus aureus infections is currently available, positive in vitro data exists to support such off label use [84–86].
Tigecycline is a glycylcycline, an analog of tetracyclines with an extended spectrum of activity to include resistant Gram-positive organisms such as MRSA, specific resistant Gram-negative bacteria, to include the extended-spectrum β-lactamase producing Enterobacteriaceae, and as salvage therapy for susceptible strains of Acinetobacter and other multi-drug resistant (MDR) pathogens. Tigecycline is approved for use by the FDA and European Medicines Agency (EMA) for adults with complicated intra-abdominal infections (cIAIs) and SSTIs as well as for CAP [87–89]. Tigecycline has also been used off label for hospital-acquired pneumonia (HAP) and VAP, diabetic foot infections, urinary tract infections (UTIs), and refractory Clostridium difficile infection .
A major concern with the use of tigecycline in critically ill patients has to do with the current dosing which is half of the originally planned dosing. This change was made due to perceived unacceptable nausea and emesis at the higher dose. Possibly as a result of this dosing issue several meta-analyses have found the incidence of death to be greater for tigecycline compared to the comparator antibiotics, this was most evident in the nosocomial pneumonia studies [91–93]. However, this mortality excess seems to be driven by infections with Gram-negative bacteria, possible because standard tigecycline doses provide serum concentrations that are below the MICs of most Gram-negative pathogens. Moreover, Ambrose et al. have proposed a tigecycline breakpoint of 0.25 mg/L for Staphylococcus aureus and streptococci classifying more isolates as resistant . The use of tigecycline in critically ill patients should be carefully considered in light of the available clinical outcomes data regarding its use.
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 the treatment of HAP caused by these pathogens. Unlike other glycopeptides, telavancin maintains its antimicrobial activity against pathogens with decreased susceptibility to glycopeptides, including VISA and hVISA strains, and exhibits more rapid concentration-dependent bactericidal activity against susceptible organisms .
In two clinical trials of HAP due to Gram-positive pathogens, particularly MRSA, treatment with telavancin achieved higher cure rates in patients with monomicrobial Staphylococcus aureus infection and cure rates comparable to vancomycin in patients with MRSA infection . In patients with mixed Gram-positive/Gram-negative infections, cure rates were higher in the vancomycin group. Incidence and types of adverse events were comparable between the treatment groups. Mortality rates for telavancin-treated versus vancomycin-treated patients were 21.5% versus 16.6% and 18.5% versus 20.6% for the two trials. Increases in serum creatinine level were more common in the telavancin group (16% vs 10%) .
Due to updated FDA guidance  for future antibiotic clinical trials of bacterial nosocomial pneumonia that recommend using diagnostic criteria from the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines , and using a primary end point of 28-day all-cause mortality, a post-hoc reanalysis of the two HAP studies was undertaken . Clinical cure rates at final follow-up were determined in the refined all-treated (AT) and clinically-evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively) and the exploratory end point of 28-day survival was evaluated in the ATS/IDSA-AT group. Non-inferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%, respectively) and ATS/IDSA-CE groups (83% versus 80%, respectively). Cure rates favored telavancin in ATS/IDSA-CE patients where Staphylococcus aureus was the sole pathogen (86% versus 75%). Overall, 28-day survival was similar in the telavancin (76%) and vancomycin (77%) groups, but lower in telavancin-treated patients with pre-existing moderate-to-severe renal impairment (CLCR <50 ml/min). The FDA approval indicates that telavancin should only be administered to patients with moderate-to-severe renal impairment if treatment benefit outweighs risk, or if no suitable alternatives are available.
The rise in infections attributed to GPC in critically ill patient mandates that clinicians treating these individuals be familiar with the pathogen types, virulence factors, and susceptibilities of GPC in their local practice areas. Moreover, the availability of MICs, especially for vancomycin and daptomycin in MRSA, should help direct the use of these agents, as well as the new antimicrobials targeting GPC. This is especially important in potentially life-threatening infections or infections associated with foreign bodies. Moreover, there is a need for the development of non-traditional agents such as vaccines and monoclonal antibodies directed against GPC such as MRSA in order to help prevent these infections and improve their outcomes .
MHK holds the Virginia E. and Sam J. Golman Chair in Respiratory Intensive Care Medicine and is full professor At Washington University.
Acute bacterial skin and soft structure infections
American Thoracic Society
Area under the curve
Community-acquired bacterial pneumonia
Complicated intra-abdominal infection
Central nervous system
Heteroresistant vancomycin-intermediate Staphylococcus aureus
Intensive care unit
Infectious Disease Society of America
Multidrug-resistant Streptococcus pneumoniae
Minimum inhibitory concentration
Meticillin-susceptible Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus
Penicillin binding protein
Skin and soft tissue infections
Urinary tract infection
Vancomycin intermediate Staphylococcus aureus
Vancomycin-resistant Staphylococcus aureus
Martin GS, Mannino DM, Eaton S, Moss M: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003, 348 (16): 1546-1554. 10.1056/NEJMoa022139.
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR: Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001, 29 (7): 1303-1310. 10.1097/00003246-200107000-00002.
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M: Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006, 34 (6): 1589-1596. 10.1097/01.CCM.0000217961.75225.E9.
Kollef MH, Sherman G, Ward S, Fraser VJ: Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999, 115 (2): 462-474. 10.1378/chest.115.2.462.
Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH: Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest. 2002, 122 (1): 262-268. 10.1378/chest.122.1.262.
Sievert DM, Ricks P, Edwards JR, Schneider A, Patel J, Srinivasan A, Kallen A, Limbago B, Fridkin S: National Healthcare Safety Network (NHSN) Team and Participating NHSN Facilities: Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009–2010. Infect Control Hosp Epidemiol. 2013, 34 (1): 1-14. 10.1086/668770.
Hageman JC, Uyeki TM, Francis JS, Jernigan DB, Wheeler JG, Bridges CB, Barenkamp SJ, Sievert DM, Srinivasan A, Doherty MC, McDougal LK, Killgore GE, Lopatin UA, Coffman R, MacDonald JK, McAllister SK, Fosheim GE, Patel JB, McDonald LC: Severe community-acquired pneumonia due to Staphylococcus aureus, 2003–04 influenza season. Emerg Infect Dis. 2006, 12 (6): 894-899. 10.3201/eid1206.051141.
Centers for Disease Control and Prevention (CDC): Effects of new penicillin susceptibility breakpoints for Streptococcus pneumoniae--United States, 2006–2007. MMWR Morb Mortal Wkly Rep. 2008, 57 (50): 1353-1355.
Shindo Y, Ito R, Kobayashi D, Ando M, Ichikawa M, Shiraki A, Goto Y, Fukui Y, Iwaki M, Okumura J, Yamaguchi I, Yagi T, Tanikawa Y, Sugino Y, Shindoh J, Ogasawara T, Nomura F, Saka H, Yamamoto M, Taniguchi H, Suzuki R, Saito H, Kawamura T, Hasegawa Y: Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2013, 188 (8): 985-995. 10.1164/rccm.201301-0079OC.
McConeghy KW, Bleasdale SC, Rodvold KA: The empirical combination of vancomycin and a beta-Lactam for staphylococcal bacteremia. Clin Infect Dis. 2013, 57 (12): 1760-1765. 10.1093/cid/cit560.
Fowler VG, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, DeMeyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, Fätkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE: S. aureus endocarditis and bacteremia study group: daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006, 355: 653-665. 10.1056/NEJMoa053783.
Murray KP, Zhao JJ, Davis SL, Kullar R, Kaye KS, Lephart P, Rybak MJ: Early use of daptomycin versus vancomycin for methicillin-resistant Staphylococcus aureus bacteremia with vancomycin minimum inhibitory concentration >1 mg/L: a matched cohort study. Clin Infect Dis. 2013, 56 (11): 1562-1569. 10.1093/cid/cit112.
Cui L, Tominaga E, Neoh HM, Hiramatsu K: Correlation between reduced daptomycin susceptibility and vancomycin resistance in vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother. 2006, 50 (3): 1079-1082. 10.1128/AAC.50.3.1079-1082.2006.
Shorr AF, Kunkel MJ, Kollef M: Linezolid versus vancomycin for Staphylococcus aureus bacteraemia: pooled analysis of randomized studies. J Antimicrob Chemother. 2005, 56 (5): 923-929. 10.1093/jac/dki355.
Awad SS, Elhabash SI, Lee L, Farrow B, Berger DH: Increasing incidence of methicillin-resistant Staphylococcus aureus skin and soft-tissue infections: reconsideration of empiric antimicrobial therapy. Am J Surg. 2007, 194 (5): 606-610. 10.1016/j.amjsurg.2007.07.016.
Lipsky BA, Kollef MH, Miller LG, Sun X, Johannes RS, Tabak YP: Predicting bacteremia among patients hospitalized for skin and skin-structure infections: derivation and validation of a risk score. Infect Control Hosp Epidemiol. 2010, 31 (8): 828-837. 10.1086/654007.
Micek ST, Hoban AP, Pham V, Doherty JA, Zilberberg MD, Shorr AF, Kollef MH: Bacteremia increases the risk of death among patients with soft-tissue infections. Surg Infect (Larchmt). 2010, 11 (2): 169-176. 10.1089/sur.2009.007.
Dupont H, Friggeri A, Touzeau J, Airapetian N, Tinturier F, Lobjoie E, Lorne E, Hijazi M, Regimbeau JM, Mahjoub Y: Enterococci increase the morbidity and mortality associated with severe intra-abdominal infections in elderly patients hospitalized in the intensive care unit. J Antimicrob Chemother. 2011, 66 (10): 2379-2385. 10.1093/jac/dkr308.
Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG, Bartlett JG: Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010, 50 (2): 133-164. 10.1086/649554.
Lyke KE, Obasanjo OO, Williams MA, O'Brien M, Chotani R, Perl TM: Ventriculitis complicating use of intraventricular catheters in adult neurosurgical patients. Clin Infect Dis. 2001, 33 (12): 2028-2033. 10.1086/324492.
Korinek AM, Baugnon T, Golmard JL, van Effenterre R, Coriat P, Puybasset L: Risk factors for adult nosocomial meningitis after craniotomy: role of antibiotic prophylaxis. Neurosurgery. 2008, 62 (Suppl 2): 532-539.
Conen A, Walti LN, Merlo A, Fluckiger U, Battegay M, Trampuz A: Characteristics and treatment outcome of cerebrospinal fluid shunt-associated infections in adults: a retrospective analysis over an 11-year period. Clin Infect Dis. 2008, 47 (1): 73-82. 10.1086/588298.
Watkins RR, Lemonovich TL, File TM: An evidence-based review of linezolid for the treatment of methicillin-resistant Staphylococcus aureus (MRSA): place in therapy. Core Evid. 2012, 7: 131-143.
Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef MH: Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2003, 124: 1789-1797.
Kollef MH, Rello J, Cammarata SK, Croos-Dabrera RV, Wunderink RG: Clinical cure and survival in Gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin. Intensive Care Med. 2004, 30: 388-394. 10.1007/s00134-003-2088-1.
Wunderink RG, Niederman MS, Kollef MH, Shorr AF, Kunkel MJ, Baruch A, McGee WT, Reisman A, Chastre J: Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis. 2012, 54: 621-629. 10.1093/cid/cir895.
Haque NZ, Zuniga LC, Peyrani P, Reyes K, Lamerato L, Moore CL, Patel S, Allen M, Peterson E, Wiemken T, Cano E, Mangino JE, Kett DH, Ramirez JA, Zervos MJ, Improving Medicine through Pathway Assessment of Critical Therapy of Hospital-Acquired Pneumonia (IMPACT-HAP) Investigators: Relationship of vancomycin minimum inhibitory concentration to mortality in patients with methicillin-resistant Staphylococcus aureus hospital-acquired, ventilator-associated, or health-care-associated pneumonia. Chest. 2010, 138: 1356-1362. 10.1378/chest.09-2453.
Choi EY, Huh JW, Lim CM, Koh Y, Kim SH, Choi SH, Kim YS, Kim MN, Hong SB: Relationship between the MIC of vancomycin and clinical outcome in patients with MRSA nosocomial pneumonia. Intensive Care Med. 2011, 37: 639-647. 10.1007/s00134-011-2130-7.
Micek ST, Dunne M, Kollef MH: Pleuropulmonary complications of Panton-Valentine leukocidin-positive community-acquired methicillin-resistant Staphylococcus aureus: importance of treatment with antimicrobials inhibiting exotoxin production. Chest. 2005, 128: 2732-2738. 10.1378/chest.128.4.2732.
Weigelt J, Kaafarani HM, Itani KM, Swanson RN: Linezolid eradicates MRSA better than vancomycin from surgical-site infections. Am J Surg. 2004, 188: 760-766. 10.1016/j.amjsurg.2004.08.045.
Weigelt J, Itani K, Stevens D, Lau W, Dryden M, Knirsch C, Linezolid CSSTI Study Group: Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother. 2005, 49: 2260-2266. 10.1128/AAC.49.6.2260-2266.2005.
Sharpe JN, Shively EH, Polk HC: Clinical and economic outcomes of oral linezolid versus intravenous vancomycin in the treatment of MRSA-complicated, lower-extremity skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. Am J Surg. 2005, 189: 425-428. 10.1016/j.amjsurg.2005.01.011.
Itani KM, Dryden MS, Bhattacharyya H, Kunkel MJ, Baruch AM, Weigelt JA: Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus aureus. Am J Surg. 2010, 199: 804-816. 10.1016/j.amjsurg.2009.08.045.
Duane TM, Weigelt JA, Puzniak LA, Huang DB: Linezolid and vancomycin in treatment of lower-extremity complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus in patients with and without vascular disease. Surg Infect (Larchmt). 2012, 13: 147-153. 10.1089/sur.2011.062.
Lipsky BA, Itani K, Norden C, Linezolid Diabetic Foot Infections Study Group: Treating foot infections in diabetic patients: a randomized, multicenter, open-label trial of linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate. Clin Infect Dis. 2004, 38: 17-24. 10.1086/380449.
Shorr AF, Kunkel MJ, Kollef M: Linezolid versus vancomycin for Staphylococcus aureus bacteraemia: pooled analysis of randomized studies. J Antimicrob Chemother. 2005, 56: 923-929. 10.1093/jac/dki355.
Park HJ, Kim SH, Kim MJ, Lee YM, Park SY, Moon SM, Park KH, Chong YP, Lee SO, Choi SH, Woo JH, Kim YS: Efficacy of linezolid-based salvage therapy compared with glycopeptide-based therapy in patients with persistent methicillin-resistant Staphylococcus aureus bacteremia. J Infect. 2012, 65: 505-512. 10.1016/j.jinf.2012.08.007.
Lauridsen TK, Bruun LE, Rasmussen RV, Arpi M, Risum N, Moser C, Johansen HK, Bundgaard H, Hassager C, Bruun NE: Linezolid as rescue treatment for left-sided infective endocarditis: an observational, retrospective, multicenter study. Eur J Clin Microbiol Infect Dis. 2012, 31: 2567-2574. 10.1007/s10096-012-1597-7.
Tascini C, Bongiorni MG, Doria R, Polidori M, Iapoce R, Fondelli S, Tagliaferri E, Soldati E, Di Paolo A, Leonildi A, Menichetti F: Linezolid for endocarditis: a case series of 14 patients. J Antimicrob Chemother. 2011, 66: 679-682. 10.1093/jac/dkq506.
Kessler AT, Kourtis AP: Treatment of meningitis caused by methicillin-resistant Staphylococcus aureus with linezolid. Infection. 2007, 35: 271-274. 10.1007/s15010-007-6211-z.
Naesens R, Ronsyn M, Druwé P, Denis O, Ieven M, Jeurissen A: Central nervous system invasion by community-acquired meticillin-resistant Staphylococcus aureus. J Med Microbiol. 2009, 58: 1247-1251. 10.1099/jmm.0.011130-0.
Sipahi OR, Bardak S, Turhan T, Arda B, Pullukcu H, Ruksen M, Aydemir S, Dalbasti T, Yurtseven T, Zileli M, Ulusoy S: Linezolid in the treatment of methicillin-resistant Staphylococcal post-neurosurgical meningitis: a series of 17 cases. Scand J Infect Dis. 2011, 43: 757-764. 10.3109/00365548.2011.585177.
Soriano A, Marco F, Martínez JA, Pisos E, Almela M, Dimova VP, Alamo D, Ortega M, Lopez J, Mensa J: Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2008, 46: 193-200. 10.1086/524667.
Lodise TP, Graves J, Evans A, Graffunder E, Helmecke M, Lomaestro BM, Stellrecht K: Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother. 2008, 52: 3315-3320. 10.1128/AAC.00113-08.
Sancak B, Ercis S, Menemenlioglu D, Colakoglu S, Hasçelik G: Methicillin-resistant Staphylococcus aureus heterogeneously resistant to vancomycin in a Turkish university hospital. J Antimicrob Chemother. 2005, 56: 519-523. 10.1093/jac/dki272.
Krause KM, Blais J, Lewis SR, Lunde CS, Barriere SL, Friedland HD, Kitt MM, Benton BM: In vitro activity of telavancin and occurrence of vancomycin heteroresistance in isolates from patients enrolled in phase 3 clinical trials of hospital-acquired pneumonia. Diagn Microbiol Infect Dis. 2012, 74: 429-431. 10.1016/j.diagmicrobio.2012.08.010.
Charles PG, Ward PB, Johnson PD, Howden BP, Grayson ML: Clinical features associated with bacteremia due to heterogeneous vancomycin-intermediate Staphylococcus aureus. Clin Infect Dis. 2004, 38: 448-451. 10.1086/381093.
Khatib R, Jose J, Musta A, Sharma M, Fakih MG, Johnson LB, Riederer K, Shemes S: Relevance of vancomycin-intermediate susceptibility and heteroresistance in methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother. 2011, 66: 1594-1599. 10.1093/jac/dkr169.
Satola SW, Lessa FC, Ray SM, Bulens SN, Lynfield R, Schaffner W, Dumyati G, Nadle J, Patel JB, Active Bacterial Core surveillance (ABCs) MRSA Investigators: Clinical and laboratory characteristics of invasive infections due to methicillin-resistant Staphylococcus aureus isolates demonstrating a vancomycin MIC of 2 micrograms per milliliter: lack of effect of heteroresistant vancomycin-intermediate S. aureus phenotype. J Clin Microbiol. 2011, 49: 1583-1587. 10.1128/JCM.01719-10.
van Hal SJ, Jones M, Gosbell IB, Paterson DL: Vancomycin heteroresistance is associated with reduced mortality in ST239 methicillin-resistant Staphylococcus aureus blood stream infections. PLoS One. 2011, 6: e21217-10.1371/journal.pone.0021217.
Morales G, Picazo JJ, Baos E, Candel FJ, Arribi A, Peláez B, Andrade R, de la Torre MA, Fereres J, Sánchez-García M: Resistance to linezolid is mediated by the cfr gene in the first report of an outbreak of linezolid-resistant Staphylococcus aureus. Clin Infect Dis. 2010, 50: 821-825. 10.1086/650574.
Rybak JM, Barber KE, Rybak MJ: Current and prospective treatments for multidrug-resistant gram-positive infections. Expert Opin Pharmacother. 2013, 14: 1919-1932. 10.1517/14656566.2013.820276.
Thomson KS, Goering RV: Activity of tedizolid (TR-700) against well-characterized methicillin-resistant Staphylococcus aureus strains of diverse epidemiological origins. Antimicrob Agents Chemother. 2013, 57: 2892-2895. 10.1128/AAC.00274-13.
Pertel PE, Bernardo P, Fogarty C, Matthews P, Northland R, Benvenuto M, Thorne GM, Luperchio SA, Arbeit RD, Alder J: Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin Infect Dis. 2008, 46: 1142-1151. 10.1086/533441.
Silverman JA, Mortin LI, VanPraagh AD, Li T, Alder J: Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. J Infect Dis. 2005, 191: 2149-2152. 10.1086/430352.
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, Rybak M J, Talan DA, Chambers HF: Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011, 52: 285-292. 10.1093/cid/cir034.
Eisenstein BI, Oleson FB, Baltz RH: Daptomycin: from the mountain to the clinic, with essential help from Francis Tally, MD. Clin Infect Dis. 2010, 50: S10-S15. 10.1086/647938.
Bhavnani SM, Rubino CM, Ambrose PG, Drusano GL: Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis. Clin Infect Dis. 2010, 50: 1568-1574. 10.1086/652767.
Falcone M, Russo A, Venditti M, Novelli A, Pai MP: Considerations for higher doses of daptomycin in critically ill patients with methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2013, 57: 1568-1576. 10.1093/cid/cit582.
Kullar R, Davis SL, Levine DP, Zhao JJ, Crank CW, Segreti J, Sakoulas G, Cosgrove SE, Rybak MJ: High-dose daptomycin for treatment of complicated gram-positive infections: a large, multicenter, retrospective study. Pharmacotherapy. 2011, 31: 527-536. 10.1592/phco.31.6.527.
Hall AD, Steed ME, Arias CA, Murray BE, Rybak MJ: Evaluation of standard- and high-dose daptomycin versus linezolid against vancomycin-resistant Enterococcus isolates in an in vitro pharmacokinetic/pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother. 2012, 56: 3174-3180. 10.1128/AAC.06439-11.
Mohr JF, Friedrich LV, Yankelev S, Lamp KC: Daptomycin for the treatment of enterococcal bacteraemia: results from the Cubicin Outcomes Registry and Experience (CORE). Int J Antimicrob Agents. 2009, 33: 543-548. 10.1016/j.ijantimicag.2008.12.007.
Moise PA, Amodio-Groton M, Rashid M, Lamp KC, Hoffman-Roberts HL, Sakoulas G, Yoon MJ, Schweitzer S, Rastogi A: Multicenter evaluation of the clinical outcomes of daptomycin with and without concomitant β-lactams in patients with Staphylococcus aureus bacteremia and mild to moderate renal impairment. Antimicrob Agents Chemother. 2013, 57: 1192-1200. 10.1128/AAC.02192-12.
Gasch O, Camoez M, Domínguez MA, Padilla B, Pintado V, Almirante B, Martín C, López-Medrano F, de Gopegui ER, Blanco JR, García-Pardo G, Calbo E, Montero M, Granados A, Jover A, Dueñas C, Pujol M, on behalf of the REIPI/GEIH Study Groups: Emergence of resistance to daptomycin in a cohort of patients with methicillin-resistant Staphylococcus aureus persistent bacteraemia treated with daptomycin. J Antimicrob Chemother. 2013, Oct 30 [Epub ahead of print]
van Hal SJ, Lodise TP, Paterson DL: The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis. 2012, 54: 755-771. 10.1093/cid/cir935.
Howden BP: Recognition and management of infections caused by vancomycin-intermediate Staphylococcus aureus (VISA) and heterogenous VISA (hVISA). Int Med J. 2005, 35: S136-S140. 10.1111/j.1444-0903.2005.00986.x.
Liu C, Chambers HF: Staphylococcus aureus with heterogeneous resistance to vancomycin: epidemiology, clinical significance, and critical assessment of diagnostic methods. Antimicrob Agents Chemother. 2003, 47: 3040-3045. 10.1128/AAC.47.10.3040-3045.2003.
Sader HS, Jones RN, Rossi KL, Rybak MJ: Occurrence of vancomycin-tolerant and heterogeneous vancomycin-intermediate strains (hVISA) among Staphylococcus aureus causing bloodstream infections in nine USA hospitals. J Antimicrob Chemother. 2009, 64: 1024-1028. 10.1093/jac/dkp319.
Pitz AM, Yu F, Hermsen ED, Rupp ME, Fey PD, Olsen KM: Vancomycin susceptibility trends and prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus in clinical methicillin-resistant S. aureus isolates. J Clin Microbiol. 2011, 49: 269-274. 10.1128/JCM.00914-10.
Sievert DM, Rudrik JT, Patel JB, McDonald LC, Wilkins MJ, Hageman JC: Vancomycin-resistant Staphylococcus aureus in the United States, 2002–2006. Clin Infect Dis. 2008, 46: 668-674. 10.1086/527392.
Fridkin SK, Hageman J, McDougal LK, Mohammed J, Jarvis WR, Perl TM, Tenover FC: Vancomycin-Intermediate Staphylococcus aureus Epidemiology Study Group. Epidemiological and microbiological characterization of infections caused by Staphylococcus aureus with reduced susceptibility to vancomycin, United States, 1997–2001. Clin Infect Dis. 2003, 36: 429-439. 10.1086/346207.
Rybak MJ, Leonard SN, Rossi KL, Cheung CM, Sader HS, Jones RN: Characterization of vancomycin-heteroresistant Staphylococcus aureus from the metropolitan area of Detroit, Michigan, over a 22-year period (1986 to 2007). J Clin Microbiol. 2008, 46: 2950-2954. 10.1128/JCM.00582-08.
Sun W, Chen H, Liu Y, Zhao C, Nichols WW, Chen M, Zhang J, Ma Y, Wang H: Prevalence and characterization of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates from 14 cities in China. Antimicrob Agents Chemother. 2009, 53: 3642-3649. 10.1128/AAC.00206-09.
Jeffres MN, Isakow W, Doherty JA, McKinnon PS, Ritchie DJ, Micek ST, Kollef MH: Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices. Chest. 2006, 130: 947-955. 10.1378/chest.130.4.947.
Patel N, Pai MP, Rodvold KA, Lomaestro B, Drusano GL, Lodise TP: Vancomycin: we can't get there from here. Clin Infect Dis. 2011, 52: 969-974. 10.1093/cid/cir078.
Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O'Sullivan MV, Anderson TL, Roberts SA, Warren SJ, Gao W, Howden BP, Johnson PD: Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2013, 57: 1654-1663. 10.1128/AAC.01485-12.
Low DE, File TM, Eckburg PB, Talbot GH, David Friedland H, Lee J, Llorens L, Critchley IA, Thye DA, FOCUS 2 Investigators: FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011, 66: iii33-iii44. 10.1093/jac/dkr121.
File TM, Low DE, Eckburg PB, Talbot GH, Friedland HD, Lee J, Llorens L, Critchley IA, Thye DA, FOCUS 1 Investigators: FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011, 66: iii19-iii32.
Sakoulas G, Nonejuie P, Nizet V, Pogliano J, Crum-Cianflone N, Haddad F: Treatment of high-level gentamicin-resistant Enterococcus faecalis endocarditis with daptomycin plus ceftaroline. Antimicrob Agents Chemother. 2013, 57: 4042-4045. 10.1128/AAC.02481-12.
Jongsma K, Joson J, Heidari A: Ceftaroline in the treatment of concomitant methicillin-resistant and daptomycin-non-susceptible Staphylococcus aureus infective endocarditis and osteomyelitis: case report. J Antimicrob Chemother. 2013, 68: 1444-1445. 10.1093/jac/dkt009.
Rose WE, Schulz LT, Andes D, Striker R, Berti AD, Hutson PR, Shukla SK: Addition of ceftaroline to daptomycin after emergence of daptomycin-nonsusceptible Staphylococcus aureus during therapy improves antibacterial activity. Antimicrob Agents Chemother. 2012, 56: 5296-5302. 10.1128/AAC.00797-12.
Lin JC, Aung G, Thomas A, Jahng M, Johns S, Fierer J: The use of ceftaroline fosamil in methicillin-resistant Staphylococcus aureus endocarditis and deep-seated MRSA infections: a retrospective case series of 10 patients. J Infect Chemother. 2013, 19: 42-49. 10.1007/s10156-012-0449-9.
Ho TT, Cadena J, Childs LM, Gonzalez-Velez M, Lewis JS: Methicillin-resistant Staphylococcus aureus bacteraemia and endocarditis treated with ceftaroline salvage therapy. J Antimicrob Chemother. 2012, 67: 1267-1270. 10.1093/jac/dks006.
Steed M, Vidaillac C, Rybak MJ: Evaluation of ceftaroline activity versus daptomycin (DAP) against DAP-nonsusceptible methicillin-resistant Staphylococcus aureus strains in an in vitro pharmacokinetic/ pharmacodynamic model. Antimicrob Agents Chemother. 2011, 55: 3522-3526. 10.1128/AAC.00347-11.
Bhalodi AA, Hagihara M, Nicolau DP, Kuti JL: In vitro pharmacodynamics of human simulated ceftaroline and daptomycin against MRSA, hVISA, and VISA with and without prior vancomycin exposure. Antimicrob Agents Chemother. 2013, [Epub ahead of print]
Werth BJ, Steed ME, Kaatz GW, Rybak MJ: Evaluation of ceftaroline activity against heteroresistant vancomycin-intermediate Staphylococcus aureus and vancomycin-intermediate methicillin-resistant S. aureus strains in an in vitro pharmacokinetic/pharmacodynamic model: exploring the "seesaw effect". Antimicrob Agents Chemother. 2013, 57: 2664-2668. 10.1128/AAC.02308-12.
Babinchak T, Ellis-Grosse E, Dartois N, Rose GM, Loh E, Tigecycline 301 Study Group: The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis. 2005, 41: S354-S367. 10.1086/431676.
Ellis-Grosse EJ, Babinchak T, Dartois N, Rose G, Loh E, Tigecycline 300 cSSSI Study Group: The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam. Clin Infect Dis. 2005, 41: S341-S353. 10.1086/431675.
Tanaseanu C, Bergallo C, Teglia O, Jasovich A, Oliva ME, Dukart G, Dartois N, Cooper CA, Gandjini H, Mallick R, 308 Study Group: Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia. Diagn Microbiol Infect Dis. 2008, 61: 329-338. 10.1016/j.diagmicrobio.2008.04.009.
Stein GE, Babinchak T: Tigecycline: an update. Diagn Microbiol Infect Dis. 2013, 75: 331-336. 10.1016/j.diagmicrobio.2012.12.004.
Cai Y, Wang R, Liang B, Bai N, Liu Y: Systematic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infectious disease. Antimicrob Agents Chemother. 2011, 55: 1162-1172. 10.1128/AAC.01402-10.
McGovern PC, Wible M, El-Tahtawy A, Biswas P, Meyer RD: All-cause mortality imbalance in the tigecycline phase 3 and 4 clinical trials. Int J Antimicrob Agents. 2013, 41: 463-467. 10.1016/j.ijantimicag.2013.01.020.
Prasad P, Sun J, Danner RL, Natanson C: Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis. 2012, 54: 1699-1709. 10.1093/cid/cis270.
Ambrose PG, Meagher AK, Passarell JA, Van Wart SA, Cirincione BB, Bhavnani SM, Ellis-Grosse E: Application of patient population-derived pharmacokinetic-pharmacodynamic relationships to tigecycline breakpoint determination for staphylococci and streptococci. Diagn Microbiol Infect Dis. 2009, 63: 155-159. 10.1016/j.diagmicrobio.2008.10.011.
Nannini EC, Corey GR, Stryjewski ME: Telavancin for the treatment of hospital-acquired pneumonia: findings from the ATTAIN studies. Expert Rev Anti Infect Ther. 2012, 10: 847-854. 10.1586/eri.12.81.
Rubinstein E, Lalani T, Corey GR, Kanafani ZA, Nannini EC, Rocha MG, Rahav G, Niederman MS, Kollef MH, Shorr AF, Lee PC, Lentnek AL, Luna CM, Fagon JY, Torres A, Kitt MM, Genter FC, Barriere SL, Friedland HD, Stryjewski ME, ATTAIN Study Group: Telavancin versus vancomycin for hospital-acquired pneumonia due to gram-positive pathogens. Clin Infect Dis. 2011, 52: 31-40. 10.1093/cid/ciq031.
U.S. Department of Health and Human Services: Guidance for Industry. Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia: Developing drugs for treatment. [http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM234907.pdf
American Thoracic Society: Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005, 171: 388-416.
Corey GR, Kollef MH, Shorr AF, Rubenstein E, Stryjewski ME, Hopkins A, Barriere SL: Telavancin for hospital-acquired pneumonia: clinical response and 28-day survival. Antimicrob Agents Chemother. 2013, in press
Daum RS, Spellberg B: Progress toward a Staphylococcus aureus vaccine. Clin Infect Dis. 2012, 54: 560-567. 10.1093/cid/cir828.
The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/14/92/prepub
The authors thank Rebecca Light for her assistance in preparing this manuscript.
Dr. Kollef’s effort was supported by the Barnes-Jewish Hospital Foundation.
MHK served as an advisory board member for Cubist and received honoraria for lectures from Cubist. Dr. Kollef’s effort was supported by the Barnes-Jewish Hospital Foundation.
All authors agreed on the focus and structure of the paper. MHK and CVG conducted the literature search, drafted the first version of the manuscript, and contributed substantially to the final version.
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Vazquez-Guillamet, C., Kollef, M.H. Treatment of gram - positive infections in critically ill patients. BMC Infect Dis 14, 92 (2014) doi:10.1186/1471-2334-14-92
- Gram-positive cocci
- Staphylococcus aureus