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Quinupristin-Dalfopristin and Linezolid: Evidence and Opinion

  1. Louis D. Saravolatz, Section Editor
  1. George M. Eliopoulos
  1. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  1. Dr. George M. Eliopoulos, Dept. of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215 (geliopou{at}bidmc.harvard.edu).
 
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Abstract

Quinupristin-dalfopristin and linezolid demonstrate in vitro activity against a wide range of gram-positive bacteria, including many isolates resistant to earlier antimicrobials. Quinupristin-dalfopristin is inactive against Enterococcus faecalis but has been effective for treatment of infections due to vancomycin-resistant Enterococcus faecium associated with bacteremia. In comparative trials, linezolid proved to be equivalent to comparator agents, resulting in its approval for several clinical indications. The almost-complete bioavailability of linezolid permits oral administration. Each agent can cause adverse effects that may limit use in individual patients. Resistance to these drugs has been encountered infrequently among vancomycin-resistant E. faecium. Resistance to quinupristin-dalfopristin is rare among staphylococci in the United States, and resistance to linezolid is very rare. Whether there is any benefit to use of these agents in combination regimens, and whether there are circumstances in which they might be alternatives to cell-wall active antibiotics for treatment of bone or endovascular infections, are questions that deserve further study.

In anticipation of the importance of infections due to gram-positive bacteria, pharmaceutical companies committed resources to the development of antimicrobials with activity against such organisms. As a result of these efforts, 2 new antimicrobials were introduced in the United States: quinupristin-dalfopristin, in 1999, and linezolid, in 2000. Recent trends in the prevalence of antibiotic-resistant strains [1, 2] and new observations concerning their epidemiology [3] confirm that decisions to develop such compounds were both prescient and justified. The isolation of clinical strains of vancomycin-resistant Staphylococcus aureus in 2002 proves this point [4].

Quinupristin-dalfopristin and linezolid demonstrate activity in vitro against important gram-positive pathogens, including most strains that are resistant to older antibiotics. These agents may also be useful for treating many patients who are intolerant of previously available agents. The bioavailability of orally administered linezolid extends treatment options for patients who do not require parenterally administered antibiotics. For these reasons, it is appropriate to consider the potential roles of these agents in current clinical practice.

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Background

Quinupristin-dalfopristin. This antibiotic is a 30:70 mixture of quinupristin and dalfopristin, which are semisynthetic antibiotics of streptogramin groups B and A, respectively. Although the individual components are primarily bacteriostatic, the combination is often bactericidal, is more potent, and may be active even when there is resistance to 1 component. The synergistic activity of the compound is ascribed to conformational change in the bacterial ribosome after dalfopristin binding [5]. Resistance determinants for the individual components specify inactivating enzymes (e.g., vat), efflux (e.g., lsa), or target modification (e.g., erm) and can occur on transmissible elements [6–8].

The criteria of the National Committee for Clinical Laboratory Standards [9] for susceptibility, intermediate susceptibility, and resistance to quinupristin-dalfopristin are <1, 2, and ≥4 μg/mL, respectively. Surveys of isolates recovered through the year 2000 indicate that almost all strains of S. aureus (including methicillin-resistant S. aureus [MRSA]) and coagulase-negative staphylococci would be susceptible (table 1) [10–15]. Only 35 of 3052 S. aureus isolates recovered in Europe during surveillance conducted in 1997–1998 were nonsusceptible [19, 20]. Twelve of 14 strains recovered from a single hospital were related, indicating the potential for clonal spread of resistant strains [16]. Several S. aureus isolates with intermediate resistance to glycopeptides from the United States and Japan were found to be susceptible to quinupristin-dalfopristin [21]. Almost all streptococci studied have been found to be susceptible [14, 22]. Occasionally, nonsusceptible isolates are encountered [1, 2, 22–25]. In a worldwide survey for the period of 1997–2000, isolates of viridans streptococci recovered in Asia showed the lowest rate of susceptibility, at 96% [22].

Table 1
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Table 1

Representative studies of in vitro activity of quinupristin-dalfopristin and linezolid against selected bacterial species.

Quinupristin-dalfopristin is almost always inactive against Enterococcus faecalis. An efflux pump conferring resistance to dalfopristin appears to be intrinsic in this species [26]. In contrast, most isolates of vancomycin-resistant Enterococcus faecium (VREF) are susceptible to this agent. Among VREF isolates from emergency use studies, 94.3% of the first isolates recovered from any patient were found to be susceptible to quinupristin-dalfopristin [27]. More-recent surveillance has shown only slightly lower susceptibility rates (table 1). Enterococci of other species are often nonsusceptible [10]. Higher rates of nonsusceptibility among VREF and other bacterial species were reported from Taiwan [28]. Genes mediating dalfopristin inactivation have been found in resistant strains of E. faecium recovered from humans and animals [7, 29–31]. Quinupristin-dalfopristin—resistant E. faecium isolates were recovered from 58% of retail chickens [32]. However, this did not seem to be a significant source of human colonization, because quinupristin-dalfopristin—resistant strains were found in only 1% of human stool samples obtained in the same regions.

Quinupristin-dalfopristin is bactericidal against some organisms. Pneumococci may be killed <3 h after exposure to the drug at the MIC [33, 34]. For 16 strains of Streptococcus pneumoniae, killing <6 h after exposure occurred more frequently with quinupristin-dalfopristin (15 strains) than with amoxicillin, vancomycin, or levofloxacin (<6 strains) at 2 or 4 times the MIC [34]. Quinupristin-dalfopristin was not bactericidal against VREF with high levels of erythromycin resistance (MIC, >256 μg/mL) [35]. Quinupristin-dalfopristin kills some but not all staphylococci [36]. Clindamycin-susceptible (i.e., not constitutive macrolide-lincosamide—streptogramin B [MLSB]–resistant) S. aureus were killed by quinupristin-dalfopristin, whereas erythromycin- and clindamycin-resistant strains were only inhibited [37]. The significance of such in vitro observations is unclear. In some animal models, constitutive MLSB resistance predicted failure of the combination [38], whereas, in others, it did not [39]. In 90 patients treated with quinupristin-dalfopristin for MRSA infection because of intolerance to or failure of conventional therapy, MLSB phenotype did not have an obvious effect on outcome [40].

Quinupristin-dalfopristin is approved in the United States for treatment of adults with serious infections due to VREF associated with bacteremia and for complicated skin and skin-structure infections due to group A streptococci or methicillin-susceptible S. aureus (MSSA) [41]. Patients treated for VREF infections in emergency use protocols typically had major underlying illnesses or risk factors, including organ failure or transplantation, hematologic malignancy, or diabetes [42–44]. The recommended dosage was 7.5 mg/kg given every 8 h, and patients actually received an average of ∼20 mg/kg per day [43, 44]. The overall success rate (clinical response plus bacterial eradication or presumed eradication) in the evaluable population was ∼65% (table 2). In randomized trials involving skin and soft-tissue infections in hospitalized adults, clinical success rates for evaluable patients were comparable between quinupristin-dalfopristin (7.5 mg/kg q12h) and comparators (oxacillin, cefazolin, or vancomycin; table 2). Although bacteriologic success rates were lower for quinupristin-dalfopristin, the authors thought that this could be explained in part by more frequent polymicrobial infection in this group and by assessment as presumed bacteriologic failure when treatment was changed because of an adverse effect [45]. For treatment of gram-positive nosocomial pneumonia, quinupristin-dalfopristin (7.5 mg/kg q8h) was found to be equivalent to vancomycin (table 2). Clinical success rates among the microbiologically evaluable patients infected with MRSA did not differ between the 2 treatment groups, but the rates for both treatments were lower than for patients with MSSA infection [46]. Among 19 pediatric liver transplant recipients, complete resolution of VREF infection was noted in 74% [47].

Table 2
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Table 2

Clinical outcomes reported in representative studies of quinupristin-dalfopristin therapy.

The emergence of resistance to quinupristin-dalfopristin was rare in comparative trials; in emergency use studies, resistance developed in 5 of 338 patients with VREF infection, 4 of whom had therapy failure [48]. Bacteremia due to E. faecalis, which is inherently resistant to quinupristin-dalfopristin, has occurred during its use for treatment of VREF or staphylococcal infection [49].

Safety and tolerability data from clinical trial experience have been reviewed elsewhere [50]. Quinupristin-dalfopristin significantly interferes with the metabolism of agents cleared through the cytochrome P450 (3A4) system, with important implications for drug interactions. Venous intolerance is common when the antibiotic is administered via peripheral vein. The drug is incompatible with saline, so it is given in 5% dextrose. Quinupristin-dalfopristin has been administered intrathecally or intraventricularly (together with intravenously administered therapy) to treat device-related VREF meningitis [51, 52]. These routes of administration have not been approved by the US Food and Drug Administration.

Variable numbers of patients receiving quinupristin-dalfopristin develop myalgias and/or arthralgias that may be severe. These symptoms were noted in 7%–10% of patients in noncomparative protocols, and they were noted less frequently in comparative trials [50]. In a clinical trial in which quinupristin-dalfopristin was administered together with minocycline, cases of myalgias or arthralgias were encountered in 20 (36%) of 56 oncology patients, 17 of whom had leukemia [53]. Others have reported this syndrome in ∼50% of treated patients [54].

Laboratory abnormalities have been noted during therapy, often of uncertain relationship to antibiotic therapy [50]. In comparative trials, increases in conjugated bilirubin levels to >5 times the normal level were seen in 5.5% of patients, which is significantly more frequently than the level seen in comparison patients [50]. Case reports describe reversible hyponatremia and anemia with reticulocytopenia [55, 56].

Despite these challenges, quinupristin-dalfopristin has been used successfully in the home as antibiotic therapy after initial inpatient treatment. In one study, myalgias (18.9% of patients) and arthralgias (13.5% of patients) were more common than reported in most other studies, but these symptoms did not necessitate discontinuation of therapy; nausea was also encountered more frequently in this study than in clinical trials [57].

Linezolid. Linezolid is a synthetic oxazolidinone antimicrobial that binds to the ribosome and inhibits protein synthesis [58, 59]. No cross-resistance between linezolid and drugs of other classes is exhibited [60]. Efflux accounts for resistance of gram-negative bacteria to linezolid. In gram-positive organisms, resistant mutants can be generated at low frequency in the laboratory; these have mutations involving the domain V peptidyltransferase center of 23S rRNA [61]. Resistance has been encountered among VREF isolates, and nosocomial spread of linezolid-resistant strains has been documented [62–64]. Linezolid-resistant VREF has demonstrated a G2576U mutation in 23S rRNA also seen in laboratory mutants [62, 64]. A linezolid-resistant MRSA clinical isolate demonstrated the same G2576U mutation [65].

The breakpoints of the National Committee for Clinical Laboratory Standards [9] for enterococci are as follows: susceptible, <2 μg/mL; intermediate, 4 μg/mL; resistant, ≥8 μg/mL. For staphylococci, the breakpoint for susceptibility is <4 μg/mL, and, for pneumococci and other streptococci, it is <2 μg/mL. Surveys (table 1) have shown almost 100% susceptibility among staphylococci (including MRSA), enterococci (including VREF), Streptococcus pyogenes, and pneumococci [22, 66]. Linezolid is bacteriostatic against enterococci [67]; combinations with ampicillin, gentamicin, or streptomycin are indifferent [68]. At concentrations of 4 μg/mL, linezolid demonstrated bactericidal activity at 24 h against only 1 of 14 strains of S. aureus, whereas vancomycin killed 18 of 25 strains at its breakpoint concentration [36]. In volunteers, peak serum bactericidal titers against S. aureus and E. faecalis were <1:4, even at dosages of 625 mg given 3 times per day [69]. At 4 times the MIC, linezolid killed 12 of 16 strains of pneumococci [34].

In the United States, linezolid is indicated for treatment of VREF infection; nosocomial pneumonia caused by S. aureus (including MRSA) or penicillin-susceptible S. pneumoniae; uncomplicated skin and skin-structure infections caused by MSSA or S. pyogenes; complicated skin and skin-structure infections caused by MSSA, MRSA, or streptococci of groups A or B; and community-acquired pneumonia caused by S. pneumoniae or MSSA. In adults with complicated skin or skin-structure infections who require hospitalization, linezolid, 600 mg iv q12h, followed by the same dosage given orally after initial improvement, was as effective, clinically and microbiologically, as intravenously administered oxacillin followed by orally administered dicloxacillin (table 3) [70]. In nosocomial pneumonia, the cure rates for linezolid or vancomycin were comparable for the intention-to-treat and clinically and microbiologically evaluable populations [71]. Linezolid was compared with vancomycin for treatment of MRSA infection in a randomized, open-label study [72]. Skin and skin-structure infections were the most common, but pneumonia and urinary tract infections were also represented. For evaluable patients, rates of clinical cure (73%) and microbiological success (∼60%) were similar for patients in both treatment arms.

Table 3
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Table 3

Clinical outcomes reported in representative studies of linezolid therapy.

Case reports describe use of linezolid for treatment of purulent exacerbations due to MRSA in cystic fibrosis [73], hip prosthesis infection due to MRSA or VREF [74, 75], coagulase-negative staphylococcal epidural catheter infection [76], and endovascular infections due to VREF [76–78]. A preliminary report indicated that ∼85% of patients with MRSA infection who experienced treatment failure or who were intolerant of vancomycin treatment were clinically cured with linezolid [79]. Of 32 patients with definite endocarditis treated with linezolid, 50% were considered to be cured at 6 months [80]. In the latter report, 78% of the subjects were enrolled after therapy with other antibiotics had failed. Linezolid appears to penetrate well into bone, fat, and muscle in patients undergoing hip replacement [81]. Given the primarily bacteriostatic activity of linezolid against enterococci, most surprising have been several reports of successful treatment with linezolid of patients with VREF meningitis, including patients in the postoperative period, persons with infection associated with a device, and patients with infections resulting from Strongyloides hyperinfection syndrome [82–84].

The pharmacokinetics of linezolid are summarized elsewhere [41]. Orally administered linezolid is virtually completely bioavailable. One adult given a standard dosage (600 mg b.i.d. iv or po) did not achieve adequate serum concentrations [85]. Symptoms associated with linezolid, including nausea, headache, diarrhea, rash, and altered taste, have generally been mild [70, 72, 76]. Nervous system effects, including peripheral neuropathy, have been noted in a few patients [86]. Linezolid is a weak monoamine oxidase inhibitor, and, in volunteers, it can potentiate adrenergic effects of phenylpropanolamine or pseudoephedrine [41]. This appears not to have been a problem in clinical studies. Linezolid did not precipitate serotonin syndrome in volunteers receiving dextromethorphan [41], and this did not appear to be a problem in clinical studies that included patients receiving drugs that had the potential to interact with monoamine oxidase inhibitors [71, 72]. However, in patients receiving selective serotonin reuptake inhibitors with linezolid, there have been subsequent reports of confusional states involving agitation, fever, or tachycardia, which is consistent with the serotonin syndrome [87, 88].

The labeling of linezolid indicates the potential to cause reversible myelosuppression and advises monitoring of hematologic parameters in patients who receive treatment for ≥2 weeks or who might be predisposed to marrow dysfunction [89]. The hematologic effects observed during clinical studies of ∼2000 linezolid-treated patients and an equal number of subjects who received comparator agents were reviewed [90]. The percentage of patients who developed substantially low platelet counts while receiving linezolid treatment began to increase to more that seen in subjects who received comparator agents at ∼2 weeks of therapy. The cumulative percentage of patients with substantially low platelet counts was 2.4% for the linezolid arm and 1.5% for the comparator arm; the difference was not significant. Reticulocyte indices, measured in ∼600 patients in each treatment arm, were significantly decreased compared with baseline values at the end of treatment with linezolid, whereas indices increased in patients in the comparator arm. Case studies suggest that thrombocytopenia may occur earlier and in a larger proportion of patients than has been reported in the comparative trials [91, 92]. In these studies, platelet counts of <100,000 platelets/mm3 were noted in 20%–30% of treated patients. The risk of developing thrombocytopenia while receiving linezolid treatment may depend not only on total duration of therapy but also on drug exposure, reflected by the 24-h area under the curve averaged over the first few days of therapy [93].

Several articles have reported anemia, which may be associated with increases in serum iron saturation or thrombocytopenia, or both, in linezolid-treated patients [72, 92, 94–97]. Neutropenia appears to be less common [76]. Reversible pancytopenia has been reported [98]. One patient died of myelodysplastic syndrome after receiving multiple antibiotics, including linezolid [99]. Other reports document successful use of linezolid in patients who had been persistently thrombocytopenic at baseline [78] or who had previously developed thrombocytopenia while receiving chloramphenicol therapy [84].

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Opinion

The evidence above suggests that both quinupristin-dalfopristin and linezolid are effective antimicrobials, each with its own benefits and limitations. There are clearly circumstances in which one or both of these agents would be useful additions to a hospital pharmacy. MRSA infections are now common in US hospitals and have begun to appear increasingly in the community. Although vancomycin remains the standard treatment for most MRSA infections, and although it is less expensive than either new drug, treatment failures have occurred despite in vitro susceptibility of the infecting strain. Furthermore, some patients cannot tolerate this agent [76]. Although VREF are less aggressive pathogens than MRSA, they are clinically important organisms. Strains of S. aureus with intermediate resistance to glycopeptides, although uncommon at present, are a very real threat, and the appearance of vancomycin-resistant strains of S. aureus is ominous.

If one considers the properties of both agents, linezolid would be found to be the more versatile of the drugs. Its antibacterial spectrum is at least as broad as that of quinupristin-dalfopristin, and it is active against both E. faecalis and E. faecium. It can be given orally, with the potential to enhance patient comfort and decrease costs and risks of intravenous therapy. On the other hand, in some patients, myelosuppression or other effects will constrain the use of this agent, especially in long courses of treatment. In a few persons taking other medications, monoamine oxidase—inhibitory effects, however modest, may precipitate symptoms. Linezolid exhibits limited in vitro bactericidal activity against enterococci, and the time it takes to kill staphylococci can be described as “slow.” Resistance has been encountered among enterococci and in S. aureus. The former have demonstrated capacity to spread in the hospital environment. Comparative clinical studies have shown that resistance is unlikely to emerge in the patient with a straightforward infection that can be managed under optimal circumstances. However, for those occasional patients whose condition cannot be managed with optimal debridement or removal of foreign material, long courses of therapy with an orally administered antimicrobial might offer special hope. It is precisely such conditions that would favor emergence of linezolid-resistant strains.

The great majority of strains of MRSA, VREF (not, however, E. faecalis), and other common or problematic gram-positive pathogens are susceptible to quinupristin-dalfopristin. Linezolid-resistant VREF can be susceptible to quinupristin-dalfopristin, as was the linezolid-resistant MRSA strain reported elsewhere by myself and colleagues [65]. Although resistance has emerged in a few patients during therapy with quinupristin-dalfopristin, the incidence appears to be within the range observed for other antimicrobials. Resistant enterococci are found in poultry; such strains could constitute a reservoir of resistance genes for the future. Quinupristin-dalfopristin is bacteriostatic against the great majority of VREF strains but in vitro data show bactericidal potential against staphylococci that are not constitutively MLSB resistant. At present, there is a paucity of clinical information on how well this drug might work in specific infections caused by MRSA—an area of perceived need for which there is currently no US Food and Drug Administration indication. Small case studies provide tantalizing evidence that combinations of quinupristin-dalfopristin and vancomycin may be effective against MRSA infections that fail to respond to a glycopeptide alone [100, 101].

Several practical issues complicate use of quinupristin-dalfopristin, one of which is the limited number of approved indications. It must be given intravenously, generally by deep catheter, to avoid venous irritation. Quinupristin-dalfopristin affects clearance of medications via the cytochrome P450 system, with the potential for major drug interactions. A variable number of patients will experience myalgias and/or arthralgias that can be severe enough to require dose reduction or administration of opiate analgesics. Despite these challenges, the drug has been used successfully both in the hospital and in outpatient settings.

A number of questions remain. Particularly relevant for linezolid, which has an oral formulation, is under what circumstances this drug can be used in place of cell wall—active agents to treat serious infections requiring long courses of therapy, such as osteomyelitis, in an effort to minimize the inconvenience, risks, and costs of parenteral treatment. Would either agent prove able to prevent the development of endocarditis, infection of biomedical prostheses, or other deep infection when used to treat staphylococcal bacteremia related to intravascular catheters or other removable foci? Would combination therapies improve the bactericidal activity of either agent or prevent the emergence of resistance in challenging circumstances? Most important, can we identify patients who are at greatest risk of developing serious adverse effects associated with these agents before use, and can any steps minimize or completely avert the risk of such events?

At the moment, we await data to define the circumstances under which either drug might be superior to previously available antimicrobials for treatment of infections susceptible to both new and old agents. However, because we are faced today with organisms that are resistant to other antibiotics or with patients intolerant of or experiencing failure of therapy with older agents (despite susceptibility in vitro), these new antimicrobials offer value.

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Footnotes

  • The author has received research contract funding from, has served as a consultant for, and has spoken on behalf of the manufacturers of quinupristin-dalfopristin and linezolid, Aventis Pharmaceuticals and Pharmacia, respectively.

  • Received September 12, 2002.
  • Accepted November 7, 2002.
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References

  1. ↵
    1. Jones RN,
    2. Ballow CH,
    3. Biedenbach DJ,
    4. et al
    . Antimicrobial activity of quinupristin-dalfopristin (RP 59500, Synercid) tested against over 28,000 recent clinical isolates from 200 medical centers in the United States and Canada. Diagn Microbiol Infect Dis 1998;31:437-51.
    CrossRefMedlineWeb of Science
  2. ↵
    1. Ballow CH,
    2. Jones RN,
    3. Biedenbach DJ
    . A multicenter evaluation of linezolid antimicrobial activity in North America. Diagn Microbiol Infect Dis 2002;43:75-83.
    CrossRefMedlineWeb of Science
  3. ↵
    1. Herold BC,
    2. Immergluck LC,
    3. Maranan MC,
    4. et al
    . Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA 1998;279:593-8.
    Abstract/FREE Full Text
  4. ↵
    1. Centers for Disease Control and Prevention
    . Staphylococcus aureus resistant to vancomycin—United States, 2002. MMWR Morb Mortal Wkly Rep 2002;51:565-7.
    Medline
  5. ↵
    1. Cocito C,
    2. DiGiambattista M,
    3. Nyssen E,
    4. Vannuffel P
    . Inhibition of protein synthesis by streptogramins and related antibiotics. J Antimicrob Chemother 1997;39((Suppl A)):7-13.
    Abstract/FREE Full Text
  6. ↵
    1. Allignet J,
    2. El Solh N
    . Characterization of a new staphylococcal gene, vgaB, encoding a putative ABC transporter conferring resistance to streptogramin A and related compounds. Gene 1997;202:133-8.
    CrossRefMedline
  7. ↵
    1. Thal LA,
    2. Zervos MJ
    . Occurrence and epidemiology of resistance to virginiamycin and streptogramins. J Antimicrob Chemother 1999;43:171-6.
    FREE Full Text
  8. ↵
    1. Malbruny B,
    2. Canu A,
    3. Bozdogan,
    4. et al
    . Resistance to quinupristin-dalfopristin due to mutation of L22 ribosomal protein in Staphylococcus aureus. Antimicrob Agents Chemother 2002;46:2200-7.
    Abstract/FREE Full Text
  9. ↵
    1. National Committee for Clinical Laboratory Standards
    . Performance standards for antimicrobial susceptibility testing: twelfth informational supplement. Wayne, PA: National Committee for Clinical Laboratory Standards; 2002. NCCLS document M100-S12.
  10. ↵
    1. Barrett MS,
    2. Jones RN
    . In vitro activity of quinupristin/dalfopristin (RP 59500) against a large collection of infrequently isolated or tested species. Diagn Microbiol Infect Dis 1996;25:147-9.
    CrossRefMedlineWeb of Science
    1. Mathai D,
    2. Lewis MT,
    3. Kugler KC,
    4. et al
    . Antibacterial activity of 41 antimicrobials tested against over 2773 bacterial isolates from hospitalized patients with pneumonia: I. Results from the SENTRY antimicrobial surveillance program (North America, 1998). Diagn Microbiol Infect Dis 2001;39:105-16.
    CrossRefMedlineWeb of Science
    1. von Eiff C,
    2. Reinert RR,
    3. Kresken M,
    4. et al
    . Nationwide German multicenter study on prevalence of antibiotic resistance in staphylococcal bloodstream isolates and comparative in vitro activities of quinupristin-dalfopristin. J Clin Microbiol 2000;38:2819-23.
    Abstract/FREE Full Text
    1. Lewis MT,
    2. Gales AC,
    3. Sader HS,
    4. et al
    . Frequency of occurrence and antimicrobial susceptibility patterns for pathogens isolated from Latin American patients with a diagnosis of pneumonia: results from the SENTRY antimicrobial surveillance program (1998). Diagn Microbiol Infect Dis 2000;37:63-74.
    CrossRefMedlineWeb of Science
  14. ↵
    1. Chang SC,
    2. Fang CT,
    3. Hsueh PR,
    4. et al
    . In vitro activity of quinupristin/dalfopristin against clinical isolates of common gram-positive bacteria in Taiwan. Diagn Microbiol Infect Dis 1999;33:299-303.
    CrossRefMedlineWeb of Science
  15. ↵
    1. Andrews J,
    2. Ashby J,
    3. Jevons G,
    4. Lines N,
    5. Wise R
    . Antimicrobial resistance in gram-positive pathogens isolated in the UK between October 1996 and January 1997. J Antimicrob Chemother 1999;43:689-98.
    Abstract/FREE Full Text
  16. ↵
    1. Schmitz FJ,
    2. Sadurski R,
    3. Stattfeld A,
    4. et al
    . Cross resistance analyses and molecular typing of Staphylococcus aureus and Streptococcus spp isolates resistant to quinupristin/dalfopristin. J Antimicrob Chemother 1999;44:847-55.
    FREE Full Text
    1. Henwood CJ,
    2. Livermore DM,
    3. Johnson AP,
    4. et al
    . Susceptibility of gram-positive cocci from 25 UK hospitals to antimicrobial agents including linezolid. J Antimicrob Chemother 2000;46:931-40.
    Abstract/FREE Full Text
    1. Mutnick AH,
    2. Biedenbach DJ,
    3. Turndige JD,
    4. Jones RN
    . Spectrum and potency evaluation of a new oxazolidinone, linezolid: report from the SENTRY Antimicrobial Surveillance Program, 1998–2000. Diagn Microbiol Infect Dis 2002;43:65-73.
    CrossRefMedlineWeb of Science
  19. ↵
    1. Schmitz FJ,
    2. Verhoef J,
    3. Fluit AC
    . Prevalence of resistance to MLS antibiotics in 20 European university hospitals participating in the European SENTRY surveillance programme. J Antimicrob Chemother 1999;43:783-92.
    Abstract/FREE Full Text
  20. ↵
    1. Werner G,
    2. Cuny C,
    3. Schmitz FJ,
    4. Witte W
    . Methicillin-resistant, quinupristin-dalfopristin-resistant Staphylococcus aureus with reduced sensitivity to glycopeptides. J Clin Microbiol 2001;39:3586-90.
    Abstract/FREE Full Text
  21. ↵
    1. Cohen MA,
    2. Huband MD
    . Activity of clinafloxacin, trovafloxacin, quinupristin/dalfopristin, and other antimicrobial agents versus Staphylococcus aureus isolates with reduced susceptibility to vancomycin. Diagn Microbiol Infect Dis 1999;33:43-6.
    CrossRefMedlineWeb of Science
  22. ↵
    1. Gordon KA,
    2. Beach ML,
    3. Biedenbach DJ,
    4. et al
    . Antimicrobial susceptibility patterns of β-hemolytic and viridans group streptococci: report from the SENTRY antimicrobial surveillance program (1997–2000). Diagn Microbiol Infect Dis 2002;43:157-62.
    CrossRefMedlineWeb of Science
    1. Wisplinghoff H,
    2. Reinert RR,
    3. Cornely O,
    4. Seifert H
    . Molecular relationships and antimicrobial susceptibilities of viridans group streptococci isolated from blood of neutropenic cancer patients. J Clin Microbiol 1999;37:1876-80.
    Abstract/FREE Full Text
    1. Reinert RR,
    2. vonEiff C,
    3. Kresken M,
    4. et al
    . Nationwide German multicenter study on the prevalence of antibiotic resistance in streptococcal blood isolates from neutropenic patients and comparative in vitro activities of quinupristin/dalfopristin and eight other antimicrobials. J Clin Microbiol 2001;39:1928-31.
    Abstract/FREE Full Text
  25. ↵
    1. Kugler KC,
    2. Denys GA,
    3. Wilson ML,
    4. Jones RN
    . Serious streptococcal infections produced by isolates resistant to streptogramins (quinupristin/dalfopristin): case reports from the SENTRY antimicrobial surveillance program. Diagn Microbiol Infect Dis 2000;36:269-72.
    CrossRefMedlineWeb of Science
  26. ↵
    1. Singh KV,
    2. Weinstock GM,
    3. Murray BE
    . An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin-dalfopristin. Antimicrob Agents Chemother 2002;46:1845-50.
    Abstract/FREE Full Text
  27. ↵
    1. Eliopoulos GM,
    2. Wennersten CB,
    3. Gold HS,
    4. et al
    . Characterization of vancomycin-resistant Enterococcus faecium isolates from the United States and their susceptibility in vitro to dalfopristin-quinupristin. Antimicrob Agents Chemother 1998;42:1088-92.
    Abstract/FREE Full Text
  28. ↵
    1. Luh KT,
    2. Hsueh PR,
    3. Teng LJ,
    4. et al
    . Quinupristin-dalfopristin resistance among gram-positive bacteria in Taiwan. Antimicrob Agents Chemother 2000;44:3374-80.
    Abstract/FREE Full Text
  29. ↵
    1. Werner G,
    2. Klare I,
    3. Witte W
    . Association between quinupristin/dalfopristin resistance in glycopeptide-resistant Enterococcus faecium and the use of additives in animal feed. Eur J Clin Microbiol Infect Dis 1998;17:401-2.
    MedlineWeb of Science
    1. Simjee S,
    2. McDermott PF,
    3. Wagner DD,
    4. White DG
    . Variation within the vat(E) allele of Enterococcus faecium isolates from retail poultry samples. Antimicrob Agents Chemother 2001;45:2931-2.
    Abstract/FREE Full Text
  31. ↵
    1. Hayes JR,
    2. McIntosh AC,
    3. Qaiyumi S,
    4. et al
    . High-frequency recovery of quinupristin-dalfopristin-resistant Enterococcus faecium isolates from the poultry production environment. J Clin Microbiol 2001;39:2298-9.
    Abstract/FREE Full Text
  32. ↵
    1. McDonald LC,
    2. Rossiter S,
    3. Mackinson C,
    4. et al
    . Quinupristin-dalfopristin-resistant Enterococcus faecium on chicken and in human stool specimens. N Engl J Med 2001;345:1155-60.
    CrossRefMedlineWeb of Science
  33. ↵
    1. Johnson CC,
    2. Slavoski L,
    3. Schwartz M,
    4. et al
    . In vitro activity of RP 59500 (quinupristin/dalfopristin) against antibiotic-resistant strains of Streptococcus pneumoniae and enterococci. Diagn Microbiol Infect Dis 1995;21:169-73.
    CrossRefMedlineWeb of Science
  34. ↵
    1. Peric M,
    2. Lin G,
    3. Clark CL,
    4. et al
    . Antipneumococcal activity of AZD2563, a new oxazolidinone, compared with nine other agents. J Antimicrob Chemother 2002;50:95-100.
    Abstract/FREE Full Text
  35. ↵
    1. Caron F,
    2. Gold HS,
    3. Wennersten CB,
    4. et al
    . Influence of erythromycin resistance, inoculum growth phase, and incubation time on assessment of the bactericidal activity of RP59500 (quinupristin-dalfopristin) against vancomycin-resistant Enterococcus faecium. Antimicrob Agents Chemother 1997;41:2749-53.
    Abstract/FREE Full Text
  36. ↵
    1. Fuchs PC,
    2. Barry AL,
    3. Brown SD
    . In vitro bactericidal activity of daptomycin against staphylococci. J Antimicrob Chemother 2002;49:467-70.
    Abstract/FREE Full Text
  37. ↵
    1. Fuchs PC,
    2. Barry AL,
    3. Brown SD
    . Bactericidal activity of quinupristin-dalfopristin against Staphylococcus aureus: clindamycin susceptibility as a surrogate indicator. Antimicrob Agents Chemother 2000;44:2880-2.
    Abstract/FREE Full Text
  38. ↵
    1. Carbon C
    . Quinupristin/dalfopristin: a review of its activity in experimental animal models of infection. J Antimicrob Chemother 1997;39((Suppl A)):115-9.
    Abstract/FREE Full Text
  39. ↵
    1. Batard E,
    2. Jacqueline C,
    3. Boutoille D,
    4. et al
    . Combination of quinupristin-dalfopristin and gentamicin against methicillin-resistant Staphylococcus aureus: experimental rabbit endocarditis study. Antimicrob Agents Chemother 2002;46:2174-8.
    Abstract/FREE Full Text
  40. ↵
    1. Drew RH,
    2. Perfect JR,
    3. Srinath L,
    4. et al
    . Treatment of methicillin-resistant Staphylococcus aureus infections with quinupristin-dalfopristin in patients intolerant of or failing prior therapy. J Antimicrob Chemother 2000;46:775-84.
    Abstract/FREE Full Text
  41. ↵
    1. Batts DH,
    2. Lavin BS,
    3. Eliopoulos GM
    . Quinupristin/dalfopristin and linezolid: spectrum of activity and potential roles in therapy—a status report. Curr Clin Top Infect Dis 2001;21:227-51.
    Medline
  42. ↵
    1. Winston DJ,
    2. Emmanouilides C,
    3. Kroeber A,
    4. et al
    . Quinupristin/dalfopristin therapy for infections due to vancomycin-resistant Enterococcus faecium. Clin Infect Dis 2000;30:790-7.
    Abstract/FREE Full Text
  43. ↵
    1. Moellering RC,
    2. Linden PK,
    3. Reinhardt J,
    4. et al
    . The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium. J Antimicrob Chemother 1999;44:251-61.
    Abstract/FREE Full Text
  44. ↵
    1. Linden PK,
    2. Moellering RC Jr,
    3. Wood CA,
    4. et al
    . Treatment of vancomycin-resistant Enterococcus faecium infections with quinupristin/dalfopristin. Clin Infect Dis 2001;33:1816-23.
    Abstract/FREE Full Text
  45. ↵
    1. Nichols RL,
    2. Graham DR,
    3. Barriere SL,
    4. et al
    . Treatment of hospitalized patients with complicated gram-positive skin and skin structure infections: two randomized, multicentre studies of quinupristin/dalfopristin versus cefazolin, oxacillin, or vancomycin. J Antimicrob Chemother 1999;44:263-73.
    Abstract/FREE Full Text
  46. ↵
    1. Fagon JY,
    2. Patrick H,
    3. Haas DW,
    4. et al
    . Treatment of gram-positive nosocomial pneumonia, prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Am J Respir Crit Care Med 2000;161:753-62.
    Abstract/FREE Full Text
  47. ↵
    1. Verma A,
    2. Dhawan A,
    3. Philpott-Howard J,
    4. et al
    . Glycopeptide-resistant Enterococcus faecium infections in paediatric liver transplant recipients: safety and clinical efficacy of quinupristin/dalfopristin. J Antimicrob Chemother 2001;47:105-8.
    Abstract/FREE Full Text
  48. ↵
    1. Dowzicky M,
    2. Talbot GH,
    3. Feger C,
    4. et al
    . Characterization of isolates associated with emerging resistance to quinupristin/dalfopristin (Synercid) during the worldwide clinical program. Diagn Microbiol Infect Dis 2000;37:57-62.
    CrossRefMedlineWeb of Science
  49. ↵
    1. Chow JW,
    2. Davidson A,
    3. Sanford E,
    4. Zervos MJ
    . Superinfection with Enterococcus faecalis during quinupristin/dalfopristin therapy. Clin Infect Dis 1997;24:91-2.
    FREE Full Text
  50. ↵
    1. Rubinstein E,
    2. Prokocimer P,
    3. Talbot GH
    . Safety and tolerability of quinupristin/dalfopristin: administration guidelines. J Antimicrob Chemother 1999;44((Suppl A)):37-46.
    Abstract
  51. ↵
    1. Tan TY,
    2. Pitman I,
    3. Penrose-Stevens A,
    4. et al
    . Treatment of a vancomycin-resistant Enterococcus faecium ventricular drain infection with quinupristin/dalfopristin and review of the literature. J Infect 2000;41:95-7.
    MedlineWeb of Science
  52. ↵
    1. Williamson JC,
    2. Glazier SS,
    3. Peacock JE Jr
    . Successful treatment of ventriculostomy-related meningitis caused by vancomycin-resistant Enterococcus with intravenous and intraventricular quinupristin/dalfopristin. Clin Neurol Neurosurg 2002;104:54-6.
    CrossRefMedlineWeb of Science
  53. ↵
    1. Raad I,
    2. Hachem R,
    3. Hanna H,
    4. et al
    . Treatment of vancomycin-resistant enterococcal infections in the immunocompromised host: quinupristin-dalfopristin in combination with minocycline. Antimicrob Agents Chemother 2001;45:3202-4.
    Abstract/FREE Full Text
  54. ↵
    1. Olsen KM,
    2. Rebuck JA,
    3. Rupp ME
    . Arthralgias and myalgias related to quinupristin-dalfopristin administration. Clin Infect Dis 2001;32:83-6.
    CrossRef
  55. ↵
    1. Cole RP,
    2. Roberts WD,
    3. Cheng MD
    . Hyponatremia associated with quinupristin-dalfopristin. Ann Intern Med 2000;133:485.
    FREE Full Text
  56. ↵
    1. Launay O,
    2. Chemlal K,
    3. Andrieu V,
    4. Carbon C
    . Severe reversible reticulocytopenic anemia associated with quinupristin/dalfopristin RP59500 therapy. Clin Infect Dis 1997;25:156.
    FREE Full Text
  57. ↵
    1. Rehm SJ,
    2. Graham DR,
    3. Srinath L,
    4. et al
    . Successful administration of quinupristin/dalfopristin in the outpatient setting. J Antimicrob Chemother 2001;47:639-45.
    Abstract/FREE Full Text
  58. ↵
    1. Aoki H,
    2. Ke L,
    3. Poppe SM,
    4. et al
    . Oxazolidinone antibiotics target the P site on Escherichia coli ribosomes. Antimicrob Agents Chemother 2002;46:1080-5.
    Abstract/FREE Full Text
  59. ↵
    1. Champney WS,
    2. Miller M
    . Linezolid is a specific inhibitor of 50S ribosomal subunit formation in Staphylococcus aureus cells. Curr Microbiol 2002;44:350-6.
    CrossRefMedlineWeb of Science
  60. ↵
    1. Fines M,
    2. Leclercq R
    . Activity of linezolid against gram-positive cocci possessing genes conferring resistance to protein synthesis inhibitors. J Antimicrob Chemother 2000;45:797-802.
    Abstract/FREE Full Text
  61. ↵
    1. Prystowsky J,
    2. Siddiqui F,
    3. Chosay J,
    4. et al
    . Resistance to linezolid: characterization of mutations in rRNA and comparison of their occurrences in vancomycin-resistant enterococci. Antimicrob Agents Chemother 2001;45:2154-6.
    Abstract/FREE Full Text
  62. ↵
    1. Jones RN,
    2. Della-Latta P,
    3. Lee LV,
    4. Biedenbach DJ
    . Linezolid-resistant Enterococcus faecium isolated from a patient without prior exposure to an oxazolidinone: report from the SENTRY Antimicrobial Surveillance Program. Diagn Microbiol Infect Dis 2002;42:137-9.
    CrossRefMedlineWeb of Science
    1. Gonzales RD,
    2. Schreckenberger PC,
    3. Graham MB,
    4. et al
    . Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid. Lancet 2001;357:1179.
    CrossRefMedlineWeb of Science
  64. ↵
    1. Herrero IA,
    2. Issa NC,
    3. Patel R
    . Nosocomial spread of linezolid-resistant, vancomycin-resistant Enterococcus faecium. N Engl J Med 2002;346:867-9.
    CrossRefMedlineWeb of Science
  65. ↵
    1. Tsiodras S,
    2. Gold HS,
    3. Sakoulas G,
    4. et al
    . Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 2001;358:207-8.
    CrossRefMedlineWeb of Science
  66. ↵
    1. Cercenado E,
    2. García-Garrote F,
    3. Bouza E
    . In vitro activity of linezolid against multiply resistant gram-positive clinical isolates. J Antimicrob Chemother 2001;47:77-81.
    Abstract/FREE Full Text
  67. ↵
    1. Eliopoulos GM,
    2. Wennersten CB,
    3. Gold HS,
    4. Moellering RC Jr
    . In vitro activities in new oxazolidinone antimicrobial agents against enterococci. Antimicrob Agents Chemother 1996;40:1745-7.
    Abstract/FREE Full Text
  68. ↵
    1. Bostic GD,
    2. Perri MB,
    3. Thal LA,
    4. Zervos MJ
    . Comparative in vitro and bactericidal activity of oxazolidinone antibiotics against multidrug-resistant enterococci. Diagn Microbiol Infect Dis 1998;30:109-12.
    CrossRefMedlineWeb of Science
  69. ↵
    1. Schaadt RD,
    2. Batts DH,
    3. Daley-Yates PT,
    4. et al
    . Serum inhibitory titers and serum bactericidal titers for human subjects receiving multiple doses of the antibacterial oxazolidinones eperezolid and linezolid. Diagn Microbiol Infect Dis 1997;28:201-4.
    CrossRefMedlineWeb of Science
  70. ↵
    1. Stevens DL,
    2. Smith LG,
    3. Bruss JB,
    4. et al
    . Randomized comparison of linezolid (PNU-100766) versus oxacillin-dicloxacillin for treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother 2000;44:3408-13.
    Abstract/FREE Full Text
  71. ↵
    1. Rubinstein E,
    2. Cammarata SK,
    3. Oliphant TH,
    4. Wunderink RG
    . Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study. Clin Infect Dis 2001;32:402-12.
    Abstract/FREE Full Text
  72. ↵
    1. Stevens DL,
    2. Herr D,
    3. Lampiris H,
    4. et al
    . Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 2002;34:1481-90.
    CrossRefMedlineWeb of Science
  73. ↵
    1. Ferrin M,
    2. Zuckerman JB,
    3. Meagher A,
    4. Blumberg EA
    . Successful treatment of methicillin-resistant Staphylococcus aureus pulmonary infection with linezolid in a patient with cystic fibrosis. Pediatr Pulmonol 2002;33:221-3.
    CrossRefMedlineWeb of Science
  74. ↵
    1. Till M,
    2. Wixson RL,
    3. Pertel PE
    . Linezolid treatment for osteomyelitis due to vancomycin-resistant Enterococcus faecium. Clin Infect Dis 2002;34:1412-4.
    CrossRefMedlineWeb of Science
  75. ↵
    Bassetti M, DiBiagio A, Cenderello G, et al. Linezolid treatment of prosthetic hip infections due to methicillin-resistant Staphylococcus aureus (MRSA) J Infect 2001;43:148-57.
  76. ↵
    1. Chien JW,
    2. Kucia ML,
    3. Salata RA
    . Use of linezolid, an oxazolidinone, in the treatment of multidrug-resistant gram-positive bacterial infections. Clin Infect Dis 2000;30:146-51.
    Abstract/FREE Full Text
    1. Babcock HM,
    2. Ritchie DJ,
    3. Christiansen E,
    4. et al
    . Successful treatment of vancomycin-resistant Enterococcus endocarditis with oral linezolid. Clin Infect Dis 2001;32:1373-5.
    Abstract/FREE Full Text
  78. ↵
    1. McNeil SA,
    2. Clarke NM,
    3. Chandrasekar PH,
    4. Kauffman CA
    . Successful treatment of vancomycin-resistant Enterococcus faecium bacteremia with linezolid after failure of treatment with Synercid (quinupristin/dalfopristin). Clin Infect Dis 2000;30:403-4.
    FREE Full Text
  79. ↵
    1. Moise PA,
    2. Birmingham MC,
    3. Forrest A,
    4. Schentag JJ
    . Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (Toronto). Washington, DC: American Society for Microbiology; 2000. Linezolid use in patients who are intolerant to or fail vancomycin [abstract 2233].
  80. ↵
    1. Dresser LD,
    2. Birmingham MC,
    3. Karchmer AW,
    4. et al
    . Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (Toronto). Washington, DC: American Society for Microbiology; 2000. Results of treating infective endocarditis with linezolid [abstract 2239].
  81. ↵
    1. Lovering AM,
    2. Zhang J,
    3. Bannister GC,
    4. et al
    . Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement. J Antimicrob Chemother 2002;50:73-7.
    Abstract/FREE Full Text
  82. ↵
    1. Hachem R,
    2. Afif C,
    3. Gokaslan Z,
    4. Raad I
    . Successful treatment of vancomycin-resistant Enterococcus meningitis with linezolid. Eur J Clin Microbiol Infect Dis 2001;20:432-4.
    CrossRefMedlineWeb of Science
    1. Steinmetz MP,
    2. Vogelbaum MA,
    3. DeGeorgia MA,
    4. et al
    . Successful treatment of vancomycin-resistant enterococcus meningitis with linezolid: case report and review of the literature. Crit Care Med 2001;29:2383-5.
    CrossRefMedlineWeb of Science
  84. ↵
    1. Zeana C,
    2. Kubin CJ,
    3. Della-Latta P,
    4. Hammer SM
    . Vancomycin-resistant Enterococcus faecium meningitis successfully managed with linezolid: case report and review of the literature. Clin Infect Dis 2001;33:477-82.
    Abstract/FREE Full Text
  85. ↵
    1. Sperber SJ,
    2. Levine JF,
    3. Gross PA
    . Proceedings of the 39th Annual Meeting of the Infectious Diseases Society of America (San Francisco). Alexandria, VA: Infectious Diseases Society of America; 2001. Low serum linezolid levels in a patient with persistent MRSA bacteremia [abstract 465].
  86. ↵
    1. Brown-Elliott BA,
    2. Wallace RJ Jr,
    3. Griffith DE,
    4. et al
    . Proceedings of the 40th Annual Meeting of the Infectious Diseases Society of America (Chicago). Alexandria, VA: Infectious Diseases Society of America; 2002. Safety and tolerance of long-term therapy of linezolid for mycobacterial and nocardial disease with a focus on once daily therapy [abstract 609].
  87. ↵
    1. Wigen CL,
    2. Goetz MB
    . Serotonin syndrome and linezolid. Clin Infect Dis 2002;34:1651-2.
    Abstract/FREE Full Text
  88. ↵
    1. Hicks K,
    2. Hachem RY,
    3. Huen A,
    4. Raad II
    . Proceedings of the 39th Annual Meeting of the Infectious Diseases Society of America (San Francisco). Alexandria, VA: Infectious Diseases Society of America; 2001. Myelosuppression and serotonin syndrome associated with linezolid and selective serotonin re-uptake inhibitors (SSRIs) [abstract 467].
  89. ↵
    88A Zyvox [package insert]. Kalamazoo, MI: Pharmacia & Upjohn; 2002.
  90. ↵
    1. Gerson SL,
    2. Kaplan SL,
    3. Bruss JB,
    4. et al
    . Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother 2002;46:2723-6.
    Abstract/FREE Full Text
  91. ↵
    1. Orrick JJ,
    2. Johns T,
    3. Janelle J,
    4. Ramphal R
    . Thrombocytopenia secondary to linezolid administration: what is the risk? Clin Infect Dis 2002;35:348-9.
    FREE Full Text
  92. ↵
    1. Attassi K,
    2. Hershberger E,
    3. Alam R,
    4. Zervos M
    . Thrombocytopenia associated with linezolid therapy. Clin Infect Dis 2002;34:695-8.
    Abstract/FREE Full Text
  93. ↵
    1. Forrest A,
    2. Rayner CR,
    3. Meagher A,
    4. et al
    . Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (Toronto). Washington, DC: American Society for Microbiology; 2000. Pharmacostatistical modelling of hematologic effects of linezolid in seriously ill patients [abstract 283].
  94. ↵
    1. Green SL,
    2. Maddox JC,
    3. Huttenbach ED
    . Linezolid and reversible myelosuppression. JAMA 2001;285:1291.
    FREE Full Text
    1. Abena PA,
    2. Mathieux VG,
    3. Scheiff JM,
    4. et al
    . Linezolid and reversible myelosuppression. JAMA 2001;286:1973.
    FREE Full Text
    1. Green SL,
    2. Maddox JC
    . Linezolid and reversible myelosuppression. JAMA 2001;286:1974.
    FREE Full Text
  97. ↵
    1. Monson T,
    2. Schichman SA,
    3. Zent CS
    . Linezolid-induced pure red blood cell aplasia. Clin Infect Dis 2002;35:29-31.
    CrossRef
  98. ↵
    1. Halpern M
    . Linezolid-induced pancytopenia. Clin Infect Dis 2002;35:347-8.
    FREE Full Text
  99. ↵
    1. Patron RL
    . Proceedings of the 39th Annual Meeting of the Infectious Diseases Society of America (San Francisco). Alexandria, VA: Infectious Diseases Society of America; 2001. Myelodisplasia and severe fatal pancytopenia associated with linezolid treatment [abstract 466].
  100. ↵
    1. Sgarabotto D,
    2. Cusinato R,
    3. Narne E,
    4. et al
    . Synercid plus vancomycin for the treatment of severe methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococcal infections: evaluation of 5 cases. Scand J Infect Dis 2002;34:122-6.
    CrossRefMedlineWeb of Science
  101. ↵
    1. Moise-Broder PA,
    2. Forrest A,
    3. Jagodzinski LM,
    4. Schentag JJ
    . Proceedings of the 40th Annual Meeting of the Infectious Diseases Society of America (Chicago). Alexandria, VA: Infectious Diseases Society of America; 2002. Methicillin-resistant Staphylococcus aureus bloodstream infections failing vancomycin (Vm): results of increasing Vm versus adding quinupristin-dalfopristin to Vm [abstract 182].
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