Ventriculitis due to a hetero strain of vancomycin intermediate Staphylococcus aureus (hVISA): successful treatment with linezolid in combination with intraventricular vancomycin

A 67-year male presented with relapse 14 days after treatment with vancomycin for a MRSA ventriculitis. CSF samples taken at the time of relapse grew MRSA with a MIC for vancomycin of 4 mg/L by E-test and therapy with linezolid (600 mg bd) and intraventricular vancomycin (20 mg od) was initiated. Using the macrodilution E-test, the isolate was found to have sub-populations with a MIC for vancomycin of 8 mg/L and teicoplanin of 12 mg/L and a population analysis profile almost identical to the hVISA strain MU3, indicative of a hVISA strain. Concentrations of vancomycin in the CSF over the period of therapy ranged from 25.6-192.5 mg/L after intraventricular administration and those of linezolid ranged from 3.4-6.7 mg/L after intravenous administration, exceeding the MICs for this isolate. The patient made a successful recovery, with no further episodes of ventriculitis at 1-year follow-up. We report the first case of ventriculitis due to hVISA. It was successfully treated with intrathecal vancomycin and intravenous linezolid. We also believe this to be the first documented case of clinical infection due to hVISA in South Africa.     

Randomized prospective study comparing cost-effectiveness of teicoplanin and vancomycin as second-line empiric therapy for infection in neutropenic patients

BACKGROUND AND OBJECTIVE: The current health-care philosophy dictates that new therapies should always be evaluated for their economic impact. Along with acquisition cost, the cost of delivery, monitoring, adverse effects and treatment failure must also be considered when determining the total cost of therapy. These auxiliary costs can be significant and greatly alter the overall cost of a drug treatment. We conducted a prospective randomized study to evaluate the efficacy, safety and cost of vancomycin and teicoplanin therapy in patients with neutropenia, after the failure of empirical treatment with a combination of piperacillin/tazobactam and amikacin. DESIGN AND METHODS: Seventy-six febrile episodes from 66 patients with hematologic malignancies under treatment, neutropenia (neutrophils <500/mm3) and fever (38 degrees C twice or 38.5 degrees C once) resistant to the combination piperacillin/tazobactam and amikacin were included in the study. RESULTS: Primary success of second-line therapy was obtained in 35 cases (46%) with no significant difference between vancomycin (17/38) and teicoplanin arms (18/38). No difference in renal or hepatic toxicity related to the antibiotic therapy was observed. The average cost per patient according to glycopeptide used was $450+/-180 for the teicoplanin group and $473+/-347 for the vancomycin group. Interestingly, in the teicoplanin arm, drug acquisition accounted for 97% of the total cost, while in the vancomycin arm administration and monitoring play an important role in overall costs. INTERPRETATION AND CONCLUSIONS: In conclusion, our pharmacoeconomic analysis demonstrates that teicoplanin and vancomycin can be administered in neutropenic hematologic patients with similar efficacy and direct costs.     

Vascular graft infection by Staphylococcus aureus: efficacy of linezolid,teicoplanin and vancomycin systemic prophylaxis protocols in a rat model

Objective

We investigated experimentally the in vivo prophylactic efficacies of linezolid, teicoplanin and vancomycin in subcutaneously implanted dacron graft infection caused by methicillin-resistant Staphylococcus aureus (MRSA).

Materials and methods

Dacron grafts (1 cm²) were aseptically implanted into subcutaneous pockets that were surgically prepared in the backs of 50 rats. Ten of these rats were used as the control group (group I). Grafts in the remaining 40 rats were infected by inoculation of MRSA at the concentration of 2 × 10⁷ colony-forming units (CFU)/ml. Ten of these rats constituted the contaminated, untreated group II. The other three study groups comprising 10 rats each were contaminated and then treated with linezolid (group III), teicoplanin (group IV) and vancomycin (group V), respectively. All rats were sacrificed and the grafts were removed after seven days and evaluated.

Results

The bacterial count decreased in the rats from the groups treated with linezolid, teicoplanin and vancomycin. The linezolid and teicoplanin groups, however, showed a significantly lower bacterial number than the vancomycin group (p = 0.009 and p = 0.01). The intensity of inflammation was highest in the contaminated, untreated group, as expected.

Conclusions

Single-dose linezolid, teicoplanin and vancomycin for peri-operative prophylaxis may prevent bacterial growth in vascular graft infections. The effect of linezolid and teicoplanin seemed similar and their effect was greater than that of vancomycin.     

万古霉素等十种抗生素对耐苯唑西林葡萄球菌的体外活性比较

为了比较万古霉素等１０种抗生素对１９９５年分离的９５株耐苯唑西林的金黄色葡萄球菌和７２株凝固酶阴性葡萄球菌的体外活性，用ＮＣＣＬＳ颁布的琼脂稀释法测ＭＩＣ。结果受检的１０种抗生素中万古霉素的活性最好，其ＭＩＣ５０及ＭＩＣ９０分别为１ｍｇ／Ｌ及２ｍｇ／Ｌ，平均值为１２４ｍｇ／Ｌ；耐药率为０％。其次为壁霉素，其ＭＩＣ５０及ＭＩＣ９０分别为２ｍｇ／Ｌ及８ｍｇ／Ｌ，平均值为２５１ｍｇ／Ｌ；耐药率为２％。利福平ＭＩＣ５０及ＭＩＣ９０分别为０１２５ｍｇ／Ｌ及３２ｍｇ／Ｌ，平均值为０２２ｍｇ／Ｌ；耐药率为１４％。其它依ＭＩＣ９０的大小排序，为氧氟沙星，甲氧苄啶，红霉素，庆大霉素，磷霉素，磺胺甲恶唑等。用柱状图显示了前三种药的ＭＩＣ值的分离，万古霉素具有良好的分散性，全部落在敏感区，且为单峰。结果表明万古霉素对ＭＲＳＡ和ＭＲＳＣｏＮ有良好的抗菌活性。     

Treatment of infective endocarditis caused by methicillin-resistant Staphylococcus aureus: teicoplanin versus vancomycin in a retrospective study

Infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) is increasing. Vancomycin and teicoplanin are 2 intravenous glycopeptides appropriate for its treatment. There is no human study comparing teicoplanin and vancomycin for the treatment of MRSA endocarditis. Between 1996 and 2006, 51 MRSA endocarditis patients were treated at the authors' hospital. There were 29 patients with nosocomial infection; 15 were treated with teicoplanin. Teicoplanin was used as the first therapeutic agent in 3 patients because of renal insufficiency. Vancomycin was used as the first therapeutic agent in 12 patients. Treatment was changed to teicoplanin because of adverse reactions in 10 and persistent bacteremia in 2 patients. Early operation was performed in 2 patients because of persistent MRSA bacteremia. Overall, 7 patients died in hospital. There was no statistically significant difference in hospital mortality rate (42% vs 47%) and bacteriologic failure rate (34% vs 40%) between 36 patients treated with vancomycin and 15 patients treated with teicoplanin. Teicoplanin can be an alternative therapy of MRSA infective endocarditis.     

Nosocomial infection caused by multidrug-resistant Staphylococcus aureus with reduced susceptibility to vancomycin and teicoplanin.--Yamagata Prefecture, Japan; May 2004-Jun 2005

Nosocomial infection caused by methicillin-resistant Staphylococcus aureus (MRSA) occurred at a major in Yamagata prefecture hospital between May 2004 and June 2005. We studied pulsed-field gel electrophoresis patterns, antimicrobial susceptibility patterns, and bacteriological features, such as coaglase type for eight isolates, including two of methicillin-resistant Staphylococcus epidermidis (MRSE). Our results suggest that this case was caused by a single strain of multidrug-resistant S. aureus. These 8 clinical isolates indicated reduced susceptibility to vancomycin and teicoplanin. PCR assay results for detection of the staphylococcal vanA, vanB, and vanC gene were all negative as all isolates. In transmission electron microscopy, cell walls appeared thicker than those of a susceptible strain from food poisoning. MRSA with reduced susceptibility to glycopeptide antibiotics may not be treated successfully with vancomycin or teicoplanin, making it important to closely observe MRSA with reduced susceptibility to glycopeptide antibiotics.     

Selection for vancomycin resistance in clinical isolates of Staphylococcus haemolyticus

Killing curves were used to characterize Staphylococcus haemolyticus isolates previously reported to contain subpopulations showing increased resistance to vancomycin. Results suggested that vancomycin and teicoplanin were ineffective at a concentration of 8 micrograms/ml and growth was seen between 24 and 48 h. Conversely, the lipopeptide antibiotic daptomycin at the same concentration rapidly killed tested strains by 6 h. Various staphylococcal strains were examined to determine if vancomycin resistance could be selected in all strains of staphylococci, was specie(s) restricted, or was unique to this patient's clinical isolates. About 1 x 10(8) colony-forming units were added to melted brain-heart infusion agar plates containing 12 micrograms/ml of vancomycin. Plates were examined after 48 h for presence of resistant clones. Results indicated that selection for vancomycin resistance was restricted to S. haemolyticus strains. Further, all S. haemolyticus isolates that displayed a double zone of growth around imipenem agar diffusion discs (Impdz) contained stably resistant subpopulations. Vancomycin resistance could not be selected in imipenem-sensitive derivative clones. Impdz isolates that were recovered from geographically distinct locations displayed nearly identical SDS-PAGE protein profiles. It appears that a characteristic susceptibility pattern displayed by clinical isolates of S. haemolyticus may provide a marker for those strains that contain subpopulations having increased resistance to vancomycin.     

Reporting antimicrobial susceptibilities and phenotypes of resistance to vancomycin in vancomycin-resistant Enterococcus spp. clinical isolates: A nationwide proficiency study

IntroductionThe ability of Spanish microbiology laboratories to (a) determine antimicrobial susceptibility (AS), and (b) correctly detect the vancomycin resistance (VR) phenotype in vancomycin-resistant Enterococcus spp. (VRE) was evaluated.MethodsThree VRE isolates representing the VanA (E. faecium), VanB (E. faecium) and VanC (E. gallinarum) VR phenotypes were sent to 52 laboratories, which were asked for: (a) AS method used; (b) MICs of ampicillin, imipenem, vancomycin, teicoplanin, linezolid, daptomycin, ciprofloxacin, levofloxacin and quinupristin–dalfopristin, and high-level resistance to gentamicin and streptomycin; (c) VR phenotype.Results(a) The most frequently used system was MicroScan; (b) according to the system, the highest percentage of discrepant MICs was found with gradient strips (21.3%). By antimicrobial, the highest rates of discrepant MICs ranged 16.7% (imipenem) to 0.7% (linezolid). No discrepant MICs were obtained with daptomycin or levofloxacin. Mayor errors (MEs) occurred with linezolid (1.1%/EUCAST) and ciprofloxacin (5.0%/CLSI), and very major errors (VMEs) with vancomycin (27.1%/EUCAST and 33.3%/CLSI) and teicoplanin (5.7%/EUCAST and 2.3%/CLSI). For linezolid, ciprofloxacin, and vancomycin, discrepant MICs were responsible for these errors, while for teicoplanin, errors were due to a misassignment of the clinical category. An unacceptable high percentage of VMEs was obtained using gradient strips (14.8%), especially with vancomycin, teicoplanin and daptomycin; (c) 86.4% of the centers identified VanA and VanB phenotypes correctly, and 95.0% the VanC phenotype.ConclusionMost Spanish microbiology laboratories can reliably determine AS in VRE, but there is a significant percentage of inadequate interpretations (warning of false susceptibility) for teicoplanin in isolates with the VanB phenotype.     

异质性万古霉素中介的金黄色葡萄球菌感染发生率及相关危险因素分析

  目的 调查复旦大学附属中山医院（中山医院）异质性万古霉素中介的金黄色葡萄球菌(hVISA)的发生率,了解hVISA菌群对新型抗生素的敏感性,研究下呼吸道hVISA感染的危险因素和影响病死率的相关因素。方法 收集2008年1月至2010年11月中山医院临床分离的甲氧西林耐药的金黄色葡萄球菌（MRSA）菌株,采用脑心浸出液琼脂（BHIA）筛选平板和宏量Etest试条检测法（macroEtest,MET）进行hVISA的筛选,改良菌群分析策略-曲线下面积(PAP-AUC) 确证hVISA。肉汤稀释法测定MRSA对万古霉素、替考拉宁和利奈唑胺的最小抑菌浓度（MIC）,用SPSS16.0比较hVISA和万古霉素敏感的金黄色葡萄球菌（VSSA）在不同MIC区间的分布差异。通过病例调查表收集筛选的hVISA病例和VSSA组的临床信息,使用t检验、Mann-Whitney检验、χ²检验及Fisher精确检验进行相关危险因素。结果 从457株MRSA菌株中经含5 mg/L替考拉宁的BHIA （BHIA5T）、含6 mg/L万古霉素的BHIA（BHIA6V）法筛选的hVISA为105株(23.0%),MET法筛选出23株hVISA(5.0%),PAP-AUC法确证的hVISA为21株(4.6%)。hVISA对万古霉素和利奈唑胺均敏感,hVISA和VSSA对万古霉素的MIC分别为（1.76±0.16） mg/L 和（1.09±0.07） mg/L（P<0.01）,hVISA和VSSA在不同MIC区间的分布差异无统计学意义（P>0.05）。单因素分析发现,hVISA组合并慢性阻塞性肺疾病者（5/11）明显高于VSSA组（14.3%,P< 0.05),但未发现hVISA感染与临床病死率相关。结论 中山医院hVISA的总体发生率为4.6%,血标本中hVISA的发生率高达12.5%。hVISA对万古霉素和利奈唑胺均为敏感,但hVISA的万古霉素MIC高于VSSA者。下呼吸道内发生hVISA感染与慢性阻塞性肺疾病可能有关。        

Systemic absorption of oral vancomycin in patients with Clostridium difficile infection

Oral vancomycin is utilized in the treatment of severe Clostridium difficile infection (CDI). We prospectively measured serum vancomycin concentrations (SVC) in patients treated with oral vancomycin. The SVC was measured by immunoassay prior to, and at least 3 days after, the administration of oral vancomycin 125 mg every 6 h. Patients treated with intravenous vancomycin were excluded. Fifty-seven patients with a mean age of 74 y (± 18) were enrolled. There was no detectable SVC in 56 patients (98%); 1 patient had a transient SVC of 6.7 μg/ml that was not detectable on subsequent testing. The severity of the CDI and/or renal failure did not have an effect on SVC. Orally administered vancomycin at 125 mg 4 times daily was not absorbed from the gastrointestinal tract.     

Successful treatment of right-sided native valve methicillin-resistant Staphylococcus aureus endocarditis and septicaemia with teicoplanin and rifampicin: a case report

Vancomycin is the drug of choice in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. However, the presence of certain clinical complications like renal failure alters vancomycin pharmacokinetics, leading to drug accumulation and toxicity. This highlights the need to identify an effective substitute for treating MRSA infections when vancomycin cannot be used. We report the case of a 57-y-old Indian male diagnosed with tricuspid valve endocarditis with septicaemia and a right upper lobe cavity caused by MRSA. The patient also presented with renal failure, which precluded the use of vancomycin for treatment. A 6-week regimen of teicoplanin and rifampicin was used instead, and the infection was successfully treated. This case report provides evidence of the effectiveness of teicoplanin and rifampicin in the treatment of MRSA bacteraemia in situations where the use of vancomycin is contraindicated.     

Release of Vancomycin and Teicoplanin from a Plasticized and Resorbable Gelatin Sponge: in Vitro Investigation of a New Antibiotic Delivery System with Glycopeptides

Abstract Background: The aim of this study was to evaluate the efficacy of sustained release of vancomycin and teicoplanin from a resorbable gelatin glycerol sponge, in order to establish a new delivery system for local anti-infective therapy. Materials and Methods: 60 plasticized glycerol gelatin sponges containing either 10 or 20% gelatin (w/v) were incubated in vancomycin or teicoplanin solution at 20 °C for either 1 or 24 h. In vitro release properties of the sponges were investigated over a period of 1 week by determining the levels of vancomycin and teicoplanin eluted in plasma using fluorescent polarization immunoassay. The rate constant and the half-life for the antibiotic release of each group were calculated by linear regression assuming first order kinetics. Results: Presoaking for 24 h was associated with a significant increase in the total antibiotic release in all groups opposed to 1 h of incubation, except for the 10% sponges presoaked in teicoplanin. Doubling the gelatin content of the sponges from 10 to 20% significantly increased the total release of antibiotic load only in teicoplanin-containing sponges after 24 h incubation. In all corresponding groups investigated, release of vancomycin was more prolonged compared to teicoplanin, which allowed a gradual release beyond 5 days. The half-life (h ± SEM) of both types of vancomycin-containing sponges was significantly prolonged by 24 h incubation in comparison to 1 h incubation (29.1 ± 5.9 vs 5.9 ± 1.0; p < 0.001, 30.0 ± 2.1 vs 11.1 ± 1.9; p < 0.001). However, neither doubling the gelatin content of the sponges nor a prolonged incubation was associated with a significantly prolonged delivery of teicoplanin. Conclusion: This study demonstrated a better diffusion-controlled release of vancomycin-impregnated glycerol gelatin sponges compared to those pretreated with teicoplanin. The plasticized glycerol gelatin sponge may be a promising carrier for the application of vancomycin to infected wounds for local anti-infective therapy.     

Search for Staphylococcus aureus heterogeneously resistant to vancomycin (hetero-VRSA) in MRSA strains isolated from clinical samples during 1990s

Hetero-VRSA was studied in 978 MRSA strains isolated from clinical samples during 1991 to 1998. Although no VRSA was detected, 23 strains (2.4%) were identified as hetero-VRSA by the vancomycin-resistance using MU3 agar plate. The frequency of hetero-VRSA was not increased in the course of time. MIC of the hetero-VRSA to vancomycin and teicoplanin was 1-2 micrograms/ml and 0.5-12 micrograms/ml, respectively. All of the hetero-VRSA strains were confirmed as a heterogeneous strain by a population analysis. Although 43% of the hetero-VRSA strains were coagulase type II, positive for TSST-1, and enterotoxin type C, others were various in the characteristics. In the gene analysis by pulse field gelelectrophoresis (PFGE), 4 sets of 2 strains were found to be identical among the 23 strains but the other 15 strains were genetically different. We speculate that hetero-VRSA strains were generated in 1991 secondary possibly by use of beta-lactam antibiotics.     

Enhanced killing of methicillin-resistantStaphylococcus aureus in human macrophages by liposome-entrapped vancomycin and teicoplanin

Summary The antibacterial effects of liposomal vancomycin and teicoplanin against intracellular methicillin-resistantStaphylococcus aureus (MRSA) were evaluated using a macrophage infection model. Human blood-derived monocytes were cultured for 7 days to obtain adherent macrophages. Uptake of each drug by macrophages was markedly enhanced by liposomal encapsulation. Following phagocytosis and removal of residual extracellular MRSA, the infected macrophages were exposed to clinically achievable concentrations of teicoplanin and vancomycin. The free (untrapped) and liposome-entrapped forms of each drug were used at the same concentration. The number of intracellularly surviving bacteria was determined by colony counts after lysis of the macrophages at different time intervals following drug treatment. Intracellular antimicrobial effect of each drug was significantly (p<0.001) increased by entrapment in liposomes. Also, the efficacies of the free and liposomal forms of both drugs were correspondingly comparable (p>0.05). It is, therefore, concluded that liposomal encapsulation of vancomycin and teicoplanin results in an increased availability of the antibiotics for efficient elimination of intracellular MRSA infection.

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Liposomen-verkapseltes Vancomycin und Teicoplanin erhöhen die Abtötung methicillinresistenter Staphylokokken in menschlichen Makrophagen

Zusammenfassung In einem Makrophagen-Infektionsmodell wurde der antibakterielle Effekt von liposomalem Vancomycin und Teicoplanin gegen intrazelluläre methicillinresistente Stämme vonStaphylococcus aureus untersucht. Adhärente Makrophagen wurden durch 7-Tage-Kulturen von menschlichen Blutmonozyten gewonnen. Durch Liposomenverkapselung erhöhte sich die Aufnahme der beiden Antibiotika in Makrophagen erheblich. Nach Phagozytose und Entfernung der verbliebenen extrazellulären methicillinresistenten Staphylokokken wurden die Makrophagen klinisch erreichbaren Konzentrationen von Teicoplanin und Vancomycin ausgesetzt. Die freie und liposomale Form der Substanzen wurde jeweils in der gleichen Konzentration verwendet. Nach Lyse der Makrophagen in unterschiedlichen Zeitabständen nach Antibiotikabehandlung wurden die Koloniebildnerzahlen intrazellulär überlebender Bakterien bestimmt. Bei beiden Antibiotika führte die Liposomenverkapselung zu einer signifikanten Erhöhung (p < 0,001) des intrazellulären antimikrobiellen Effektes. Die Aktivität der Antibiotika in freier und liposomaler Form war folglich vergleichbar (p > 0,05). Wir folgern aus diesen Beobachtungen, daß die Verkapselung von Vancomycin oder Teicoplanin in Liposomen die intrazelluläre Verfügbarkeit und Elimination der intrazellulären Infektion mit methicillinresistenten Staphylokokken erhöht.

     

Adverse effect of staphylococci slime on in vitro activity of glycopeptides

Adhesion to biomaterial is assumed to be a crucial step in the development of staphylococcal foreign body infections. Production of extracellular slime has major implications for the development and implementation of therapeutic strategies. The effect of extracted slime was investigated on the activity of vancomycin, teicoplanin, linezolid, quinupristin/dalfopristin, rifampicin and ranbezolid against 10 clinical and 4 ATCC staphylococcal isolates. The slime extract caused a 2- to 16-fold increase in the MICs of vancomycin and teicoplanin, with a shift in the MIC(90) from 2 to 32 (vancomycin) and 2 to 16 (teicoplanin), whereas the MICs of linezolid and quinupristin/dalfopristin were only moderately affected. In time-kill studies, a significant decrease in bacterial killing (>3 log(10) cfu/ml) was observed with vancomycin and teicoplanin (4 x MIC) after addition of slime (5 and 20 mg/ml), whereas the effect of killing by linezolid and quinupristin/dalfopristin was very modest. The rifampicin and ranbezolid MICs and kill curves were not influenced by the addition of slime. The present study thus indicated that slime interferes with the antimicrobial effect of glycopeptide drugs (vancomycin, teicoplanin), and that for effective prevention and treatment of prosthetic device-related infections, appropriate and newer antibiotics such as ranbezolid should be considered.     

Emergence of teicoplanin resistance during therapy of Staphylococcus aureus endocarditis

Serial isolates of Staphylococcus aureus showing two- to eightfold increases in teicoplanin minimum inhibitory concentrations (MICs) and twofold or less increases in MICs of other glycopeptides were recovered from the blood of a patient with endocarditis in whom drug therapy was unsuccessful. Comparable resistance emerged during teicoplanin treatment of rabbits with endocarditis caused by the original susceptible parent strain. For the parent strain, spontaneous resistance to teicoplanin at concentrations of 2-10 times the MIC was detected in vitro at frequencies of 10(-7) to 10(-9). Similar results were found for isolates of S. aureus from other geographic locations. Resistance was constitutive and not plasmid mediated, and its acquisition was not associated with changes in cytoplasmic membrane proteins. Teicoplanin was less effective than vancomycin at inhibiting peptidoglycan synthesis in resistant strains, suggesting that there is differential interference with the access of teicoplanin to or interaction with its target(s). Alternatively, teicoplanin and vancomycin may differ in some detail(s) of their mechanism of action against S. aureus.     

Sterilization of Ommaya reservoir by instillation of vancomycin

We describe the management of a patient with a Staphylococcus epidermidis infection of an Ommaya reservoir that was being used for the treatment of carcinomatous meningitis. Intravenous vancomycin failed to eradicate the organism. We treated our patient successfully with parenteral antibiotics and local instillation of vancomycin (25 μg/ml) without removing the reservoir. The patient tolerated the intraventricular vancomycin well. We recommend this approach in the treatment of infected Ommaya reservoirs in patients who have diseases with extremely poor prognoses and who wish to be discharged from the hospital early.     

Vancomycin-induced neutropenia resolves after substitution with teicoplanin.

Neutropenia is an uncommon adverse effect associated with prolonged vancomycin therapy. Neutrophil counts normally recover after discontinuation of vancomycin in this situation, but treatment options are needed for those patients who require ongoing antibiotic therapy. We describe a case of vancomycin-induced neutropenia in which the neutropenia resolved after vancomycin was replaced by the structurally related compound teicoplanin.     

Severe staphylococcal knee arthritis responding favourably to linezolid, after glycopeptide-rifampicin failure: a case report and literature review

A puzzling case report of a septicaemic post-surgical staphylococcal knee arthritis which did not respond to long-term courses of associated rifampicin and teicoplanin or vancomycin, despite apparently favourable in vitro susceptibility assays, but which rapidly resolved after i.v. followed by oral administration of linezolid is presented, and discussed in the context of the most recent literature evidence. The lack of response to a 14-d-long course of glycopeptides does not find explanation from the in vitro minimum inhibitory concentrations (MIC90) of involved organisms, which showed full susceptibility of Staphylococcus aureus to vancomycin and teicoplanin, and sensitivity of an accompanying Staphylococcus epidermidis isolated from blood cultures to vancomycin and rifampicin, with borderline 'intermediate' values found for teicoplanin. Since neither bone involvement nor abscess formation was of concern, effective glycopeptide and rifampicin penetration into infectious tissue should have been assured. From a clinical viewpoint, the introduction of a 2-week i.v. linezolid followed by 1 further week of oral linezolid led to complete clinical and microbiological cure, and an unexpected functional success.