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[Introduction] Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome., [Methods] A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed., [Results] One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin, [Conclusions] TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies., [Trial registration] This study is registered at clinicaltrials.gov, registration no. NCT03826108., This work was supported by the Innovative Medicines Initiative Joint Undertaking (grant agreement No. 115523), COMBACTE-NET consortium (European Union FP7/2007–2013 and GlaxoSmithKline Biologicals SA, as EFPIA partner). R.E, L.S, O. M, R. E-S, J. L–T, J. P, J. R-B and MD. del T are members of the Spanish Network for Research in Infectious Diseases (REIPI), supported by Plan Nacional de I + D + i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001; 0002; 0005; 0009; 0011; 0015), co‐ financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligence Growth 2014‐2020.

[Objectives] We aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions., [Methods] We performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort., [Results] In total, 130 cases and 386 controls were included. The variables independently associated with S. aureus-PJI in the preoperative period were (adjusted OR; 95% CI): body mass index >30 kg/m2 (3.0; 1.9 to 4.8), resident in a long-term care facility (2.8; 1.05 to 7.5), fracture as reason for arthroplasty (2.7; 1.4 to 5.03), skin disorders (2.5; 0.9 to 7.04), previous surgery in the index joint (2.4; 1.3 to 4.4), male sex (1.9; 1.2 to 2.9) and American Society of Anesthesiologists index score 3 to 4 (1.8; 1.2 to 2.9). The area under the receiver operating characteristic curve was 0.73 (95% CI 0.68 to 0.78). In perioperative model, the risk factors were the previous ones plus surgical antibiotic prophylaxis administered out of the first 60 minutes before incision (5.9; 2.1 to 16.2), wound drainage for >72 hours after arthroplasty (4.5; 1.9 to 19.4) and use of metal bearing material versus ceramic (1.9; 1.1 to 3.3). The area under the receiver operating characteristic curve was 0.78 (95% CI 0.72 to 0.83). The predictive scores developed were validated in the external cohort., [Discussion] Predictive scores for S. aureus-PJI were developed and validated; this information would be useful for implementation of specific preventive measures.

Background Interest in shorter antimicrobial regimens and oral treatment for osteoarticular infections is growing. The aim of this study is to assess whether there is an association between the administration of an entirely oral antibiotic therapy (OT) and the clinical outcome of native vertebral osteomyelitis (NVOs). Methods We conducted a single-center, retrospective, observational study on consecutive patients with pyogenic NVOs over a 10-year period (2008–2018). We performed multivariate logistic regression analysis to identify risk factors for clinical failure, both in the whole population and in subgroups. The impact of OT versus standard treatment (intravenous induction followed by oral treatment whenever possible) was assessed in patients with a non-multidrug-resistant microorganism (MDRO) etiology, and the impact of a rifampin-containing regimen was assessed in patients affected by NVOs caused by staphylococci or of unknown etiology. Results The study population included 249 patients, and 33 (13.3%) experienced clinical failure; the OT group consisted of 54 patients (21.7%). Multivariate regression analysis of the whole population selected Charlson comorbidity index (adjusted odds ratio [aOR], 1.291; 95% confidence interval [CI], 1.114–1.497; P = .001) and MDRO etiology (aOR, 3.301; 95% CI, 1.368–7.964; P = .008) as independent factors for clinical failure. Among patients affected by a non-MDRO NVO, OT was not associated with an increased risk of clinical failure (aOR, 0.487; 95% CI, .133–1.782; P = .271), even after adjustment for the propensity score of receiving OT. In the subgroup of patients with staphylococcal or unknown etiology, NVO rifampin was independently associated with favorable outcome (aOR, 0.315; 95% CI, .105–.949; P = .040). Conclusions An entirely oral, highly bioavailable treatment, including rifampin, may be as effective as parenteral treatment in selected patients with NVOs.

Introduction: We aim to evaluate the use of silver (PorAg®) coated compared to uncoated prosthesis in two-stage revision for prosthetic joint infection (PJI) of distal femur and proximal tibia megaprosthesis in oncological patients. Materials and methods: In total, 68 patients were retrospectively evaluated. Median age was 30years (range 14–83). In total, 29 patients were re-implanted with PorAg® prosthesis and 39 with uncoated prosthesis (Megasystem C®, Waldemar Link GmbH & Co. KG, Hamburg, Germany). All patients had PJI confirmed according to Musculoskeletal Infection Society (MSIS) criteria. In 10 cases, no microorganism was identified at the time of first-stage revision, but all had a sinus communicating with the prosthesis. Successful eradication of the infection was defined by the absence of clinical/serologic evidence of infection at 6months after the second stage or at latest follow-up. Infection was again defined according to the MSIS criteria. Results: At 3-year follow-up, estimated reinfection rate in the silver group was slightly lower than in uncoated EPR (10.3% vs. 17.5%, p = 0.104). Among reinfected patients, only one out of three patients (33%) in the silver group required an amputation compared to 80% in the nonsilver group (p = 0.047). Conclusions: Our results show the efficacy of PorAg® coating in the two-stage revision of knee EPR. PorAg®-coated EPR may have possible advantages over this traditional strategy, in particular when applied to patients with a higher risk of reinfection.

We thank Baklouti et al. (1) for commenting on our population pharmacokinetic study of dalbavancin for optimal treatment of adult patients with staphylococcal osteoarticular infections (2) and for suggesting that our model tends to underestimate the concentrations observed in a group of French patients (French group).….

Imaging is needed for the diagnosis of bone and joint infections, determining the severity and extent of disease, planning biopsy, and monitoring the response to treatment. Some radiological features are pathognomonic of bone and joint infections for each modality used. However, imaging diagnosis of these infections is challenging because of several overlaps with non-infectious etiologies. Interventional radiology is generally needed to verify the diagnosis and to identify the microorganism involved in the infectious process through imaging-guided biopsy. This narrative review aims to summarize the radiological features of the commonest orthopedic infections, the indications and the limits of different modalities in the diagnostic strategy as well as to outline recent findings that may facilitate diagnosis.

Dalbavancin is gaining interest in the treatment of complex osteoarticular (OA) infections. We aimed to conduct a population pharmacokinetic analysis of dalbavancin in a prospective cohort of adult patients with OA infections caused by Gram-positive organisms and to identify optimal dosing regimens for long-term treatment. Nonlinear mixed-effects modeling was performed with Monolix. Monte Carlo simulations were performed with six dalbavancin regimens (1,500 mg at day 1; 1,000 mg at day 1 plus 500 mg at day 8; 1,500 mg at days 1 and 8; and 1,500 mg at days 1 and 8 plus 500, 1,000, or 1,500 mg at day 36) to assess the probability of target attainment (PTA) of three pharmacodynamic targets of area under the concentration-time curve for the free, unbound fraction of a drug at 24 h/MIC (fAUC(24h)/MIC) against Staphylococcus aureus (>27.1, 53.3, and 111.1). The cumulative fraction of response (CFR) was calculated against the MIC distribution of both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). Desirable PTAs and CFRs were ≥90%. Fifteen patients provided 120 plasma concentrations. Most (73.3%) had prosthetic joint infections. The clinical cure rate was 87%. A two-compartment model with linear elimination well described the data. No covariate was retained in the final model. Pharmacokinetic dalbavancin estimates were 0.106 liter/h for total body clearance (CL) and 36.4 liter for volume of distribution at steady state(V(ss)). The tested dosing regimens granted desirable CFRs against S. aureus at the most effective pharmacokinetic/pharmacodynamic (PK/PD) target for a period ranging 3 to 9 weeks. Giving a regimen of two 1,500-mg doses of dalbavancin 1 week apart may ensure efficacy against both MSSA and MRSA up to 5 weeks in patients with OA infections. Clinical assessment at that time may allow for considering whether an additional dose should be administered for prolonging effective treatment.

Background The treatment of shoulder prosthetic joint infections (PJIs) requiring removal of the prosthesis is not well defined. This article aims to systematically review and compare the results of the literature in single-stage and two-stage protocols in the treatment of shoulder PJI. Methods An in-depth search on PubMed/Scopus/Web of Science databases and cross-referencing search was carried out concerning the articles reporting detailed data on the topic. Results A total of 486 shoulder PJIs were included: 137 treated with single-stage and 349 with two-stage procedure. A similar distribution between early and not-early infections (19.1% vs 80.9%) was found between the two groups. The overall rate of success in terms of PJI eradication was significantly higher in the single-stage group (95.6% vs 85.7%, p Discussion The single-phase protocol showed a higher success rate in eradicating the infection and a lower complication rate. However, the low number of patients included, the low quality of the articles, the lack of data on clinical severity and bacteriological virulence suggest caution in conclusions.

Fosfomycin is gaining interest in the treatment of complex osteoarticular infections (OI) due to multidrug-resistant (MDR) pathogens. Our aims were to conduct population pharmacokinetics of fosfomycin in a cohort of OI patients receiving 16 g daily by intermittent (II) or continuous (CI) infusion and to carry out Monte Carlo simulations for dosage optimization in the treatment of these infections. Patients underwent blood sampling on day 5 of therapy (2 to 3 serial samples). Population pharmacokinetics and Monte Carlo simulations were performed to define the probability of target attainment (PTA) of 70% T>MIC and the cumulative fraction of response (CFR) against common OI pathogens with dosages of 8, 12, 16, and 20 g/day administered by II, extended infusion (EI), or CI. Forty-eight patients were recruited. A two-compartment open model with infusion input and first-order elimination was developed. Estimated creatinine clearance (CL(CR)) was included as a covariate in the final model. Monte Carlo simulations showed that optimal PTAs and CFRs (≥90%) can be achieved in three different classes of renal function by administering a daily dosage of 2 g every 6 h (q6h) by II against Staphylococcus aureus, Escherichia coli, expanded-spectrum beta-lactamase (ESBL)-producing E. coli, and methicillin-resistant S. aureus; 8 g by CI against coagulase-negative staphylococci, K. pneumoniae, and ESBL-producing K. pneumoniae; 12 g by CI against P. aeruginosa; and 16 g by CI against KPC-producing K. pneumoniae. Our study provides a strong rationale for considering fosfomycin dosages of 8 to 16 g daily by CI in several clinical scenarios for OI patients. The feasibility of administration by CI in an elastomeric pump makes fosfomycin a candidate for OPAT programs.

Purpose (1) To evaluate the diagnostic testing performance of the synovial white blood cell (WBC) count, polymorphonuclear cell percentage, and synovial glucose, synovial protein, synovial lactate dehydrogenase, and synovial C-reactive protein levels as diagnostic markers for the diagnosis of septic arthritis after anterior cruciate ligament (ACL) reconstruction; (2) to define the ideal thresholds of the aforementioned tests, leading to the optimal sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy; and (3) to define the sensitivity of synovial fluid culture and synovial tissue sample culture, as well as determine whether previous antibiotic treatment may affect the accuracy of these tests. Methods We performed a retrospective analysis of all patients readmitted from January 2009 to September 2019 with signs suggestive of septic arthritis and undergoing a knee aspiration for synovial fluid analysis and culture. The receiver operating characteristic curve and the associated area under the curve were constructed for the aforementioned synovial markers. Sensitivity, specificity, PPV, NPV, and accuracy were calculated for the obtained optimal values. Sensitivity was also calculated for synovial fluid culture and synovial tissue sample culture, and the influence of previous antibiotic treatments on culture sensitivity was evaluated. Results Among 3,408 cases of ACL reconstruction, after the exclusion of 13 patients not meeting the inclusion criteria, 24 infected and 14 uninfected patients were reviewed and included in the analysis. The diagnosis was confirmed by the presence of 2 positive culture findings with the same isolated microorganism or at least 3 of the 4 following criteria: elevated serum C-reactive protein level and erythrocyte sedimentation rate, positive results of histologic analysis of synovial tissue, macroscopic evidence of purulence, and 1 positive culture finding. The receiver operating characteristic curve analysis showed that the most reliable marker for the diagnosis of septic arthritis after ACL reconstruction was the synovial WBC count (area under the curve, 0.89). A cutoff value of 28,100 cells/mL presented the highest accuracy (0.85), highest PPV (0.94), and highest NPV (0.76); moreover, with the threshold set at 40,000 cells/mL, postoperative infection could be diagnosed with 100% specificity. The sensitivity of synovial fluid culture was significantly lower than the sensitivity of synovial tissue sample culture (0.63 vs 0.96, P = .0045); moreover, the sensitivity further decreased if patients took antibiotics before aspiration (0.44 vs 0.73), although this decrease was not statistically significant. Conclusions The synovial WBC count is the most reliable test for the diagnosis of septic arthritis after ACL reconstruction. Although the sensitivity of synovial fluid culture is affected by previous antibiotic treatment, the synovial WBC count is not influenced and proves to be useful in the diagnosis of this uncommon complication. Level of Evidence Level II, diagnostic study.

Objectives: We aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19). Methods: We performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: SpO2 30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, β-coefficients were used to develop a risk score. Trial Registration NCT04316949. Results: We analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66–4.50), obesity (OR 4.62; 95% CI 2.78–7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30–2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01–7.01), lymphocytes ≤900 cells/mm3 (OR 2.69; 95% CI 1.60–4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59–3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88–7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11–5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86–0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%–79%), 89.1% (86%–92%), 74% (67%–80%) and 89% (85%–91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81–0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%–85%), 76% (70%–81%), 69% (60%–74%) and 85% (80%–89%), respectively. Conclusion: PREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.

As shown by the studies of Gustilo–Anderson, infections are one of the most frequent complications in open fractures, owing to the heavy contamination of tissue during the trauma. Therefore, an immediate antibiotic prophylaxis capable of covering the majority of microbes involved in this type of contamination is needed. In this paper we address this need by proposing a diagnostic-therapeutic protocol.

We aim to evaluate the use of silver (PorAgIn total, 68 patients were retrospectively evaluated. Median age was 30 years (range 14-83). In total, 29 patients were re-implanted with PorAgAt 3-year follow-up, estimated reinfection rate in the silver group was slightly lower than in uncoated EPR (10.3% vs. 17.5%, p = 0.104). Among reinfected patients, only one out of three patients (33%) in the silver group required an amputation compared to 80% in the nonsilver group (p = 0.047).Our results show the efficacy of PorAg

The original version of this article unfortunately contained a mistake. The correct information is given below.

Urinary tract infections (UTIs) are the most common bacterial infections and represent a significant problem both from an epidemiological and clinical point of view. Moreover, they place a substantial financial burden on society. UTIs can be asymptomatic or symptomatic and are characterized by a wide spectrum of symptoms ranging from mild irritative voiding to bacteremia, sepsis, severe sepsis or septic shock. They may occur in a normal genitourinary tract with no prior instrumentation (uncomplicated infections) or in genitourinary tracts with structural or functional abnormalities, or in patients with specific risk factors (complicated infections). In the hospital setting bacterial and fungal UTIs are strongly related to the use and misuse of indwelling urinary catheters. Catheter-related UTIs increase morbidity, mortality and costs and constitute an efficient reservoir for multidrug-resistant bacteria.

BJECTIVES: Prolonged treatment with linezolid may cause toxicity. The purpose of this study was to define pharmacodynamic thresholds for improving safety outcomes of linezolid. METHODS: We performed a retrospective study of patients who had trough (C(min)) and peak (C(max)) plasma levels measured during prolonged linezolid treatment. Dosage adjustments were performed when C(min) ≥10 mg/L and/or AUC₂₄ ≥400 mg/L · h. Patients were divided into two subgroups according to the absence or presence of co-treatment with rifampicin (the linezolid group and the linezolid + rifampicin group, respectively). Data on demographic characteristics, disease, microbiology and haematochemical parameters were collected and outcomes in relation to drug exposure were compared between groups. RESULTS: A total of 45 patients were included. Dosage adjustments were needed in 40% versus 0% of patients in the linezolid group (n = 35) versus the linezolid + rifampicin group (n = 10), respectively. Patients in the linezolid group had either significantly higher C(min) [3.71 mg/L (1.43-6.38) versus 1.37 mg/L (0.67-2.55), P

Antibiotic therapy in patients affected by discitis is often empirical. Therefore, early evaluation of response to therapy is important. In many patients inflammatory indexes are low during all the phases of the diseases or are altered by concomitant diseases. The aim of the study was to assess the possible role of FDG PET/CT for the early evaluation of response to therapy in patients affected by infective discitis, in comparison to C-reactive protein (CRP) serum levels.Enrolled in the study were 38 patients diagnosed with haematogenous infective discitis. Of the 38 patients, 7 had tubercular infection, 1 fungal infection and 30 pyogenic discitis. Four patients were excluded because the second PET/CT scan was not performed. Thus 34 patients (18 women, mean age 64 years) were analysed. All the patients included underwent a FDG PET/CT scan and determination of CRP level at baseline and again 2 to 4 weeks after the start of therapy. The PET results in terms of SUV of the first and second scans (SUV1 and SUV2) and delta-SUVmax were compared to the inflammatory indexes and clinical status during therapy.The mean SUVmax at diagnosis was 8.6 ± 3.7. The mean CRP level at diagnosis was 3.8 ± 3.8 mg/dl. A progressive clinical response was seen in 26 patients and 8 patients showed no response. SUV1 was not correlated with the baseline CRP level (CRP1, p = 0.7) and SUV2 was not correlated with the CRP level at the time of the second scan (CRP2, p = 0.4). In responders, SUV2 and CRP2 were significantly lower than SUV1 and CRP1 (p < 0.0001 and p = 0.001, respectively). ROC curves for delta-SUVmax showed a sensitivity of 82 \% and a specificity of 82 \% with a cut-off of 34 \%. ROC curves for SUV2 showed a sensitivity of 83 \% and a specificity of 46 \% with a cut-off of 6.4. ROC curves for delta-CRP showed a sensitivity of 67 \% and a specificity of 89 \% with a cut-off of 74 \%. ROC curves for CRP2 showed a sensitivity of 65 \% and a specificity of 70 \% with a cut-off of 0.7 mg/dl. No statistically significant difference was found between delta-SUVmax AUC and delta-CRP AUC (p = 0.5).Delta-SUVmax provided a higher sensitivity and specificity for identifying responders. SUV2 provided comparable sensitivity, but significantly lower specificity. CRP level performed less well for identifying responders. There was no significant difference in the global performance of the two tests (delta-SUVmax AUC and delta-CRP AUC). However, the higher sensitivity of delta-SUVmax for the early identification of responders may have an important clinical impact in guiding antibiotic therapy especially in patients with a noninformative CRP test at diagnosis.

Spine infections require a multidisciplinary approach to be treated and solved. A guide line to drive physicians in the deep complexity of such a disease is extremely helpful. SIMP suggests a flow-chart built up on clear concepts such as right and well managed antibiotic therapy, sound stability of the spine, correct and smart use of the standard and functional imaging techniques, such as f18 FDG PET/CT. In 16 months a total of 41 patients have been treated for spondylodiscitis, discitis and vertebral osteomyelitis by our team of physicians and 25 patients have been enrolled in a prospective study whose target is the assessment of the SIMP flow-chart and of every single aspect that characterize it.

The objective of the present retrospective observational study carried out in patients receiving a standard dosage of linezolid and undergoing routine therapeutic drug monitoring (TDM) was to assess the interindividual variability in plasma exposure, to identify the prevalence of attainment of optimal pharmacodynamics, and to define if an intensive program of TDM may be warranted in some categories of patients. Linezolid plasma concentrations (trough [ C min ] and peak [ C max ] levels) were analyzed by means of a high-performance liquid chromatography (HPLC) method, and daily drug exposure was estimated (daily area under the plasma concentration-time curve [AUC 24 ]). The final database included 280 C min and 223 C max measurements performed in 92 patients who were treated with the fixed 600-mg dose every 12 h (q12h) intravenously ( n = 58) or orally ( n = 34). A wide variability was observed (median values [interquartile range]: 3.80 mg/liter [1.75 to 7.53 mg/liter] for C min , 14.70 mg/liter [10.57 to 19.64] for C max , and 196.08 mg·h/liter [144.02 to 312.10 mg·h/liter] for estimated AUC 24 ). Linezolid C min was linearly correlated with estimated AUC 24 ( r 2 = 0.85). Optimal pharmacodynamic target attainment (defined as C min of ≥2 mg/liter and/or AUC 24 /MIC 90 ratio of >80) was obtained in about 60 to 70% of cases, but potential overexposure (defined as C min of ≥10 mg/liter and/or AUC 24 of ≥400 mg·h/liter) was documented in about 12% of cases. A significantly higher proportion of cases with potential overexposure received cotreatment with omeprazole, amiodarone, or amlodipine. Our study suggests that the application of TDM might be especially worthwhile in about 30% of cases with the intent of avoiding either the risk of dose-dependent toxicity or that of treatment failure.

The purpose of this study was to assess the clinical efficacy of high-dose levofloxacin plus rifampicin in the empirical treatment of non-tuberculous spondylodiscitis in an epidemiological context of low incidence of staphylococcal fluoroquinolone resistance. All consecutive adult patients with spondylodiscitis (January 2003 to December 2006) were empirically treated with high-dose levofloxacin (500 mg every 12 h normalised to renal function and optimised by means of therapeutic drug monitoring whenever feasible) plus rifampicin 600 mg every 24 h. Trough and peak plasma concentrations were targeted at 1-3 mg/L and 6-9 mg/L, respectively, to maximise the concentration-dependent activity of levofloxacin in bone. Follow-up was performed until 9 months after the end of therapy. Forty-eight patients were included. Eleven patients underwent a surgical approach for spine stabilisation. Among the 29 bacterial isolates, Staphylococcus aureus was the most frequent (65.5%) (all meticillin-susceptible strains). Tailored levofloxacin plasma exposure over time was ensured in most cases. Median treatment duration was 15.1 weeks. Overall response rates were: 77.1% at the intent-to-treat analysis; 84.1% among patients who completed therapy (N = 44); and 96.3% among those receiving targeted therapy against documented levofloxacin-susceptible isolates (N = 27). No patient had evidence of disease relapse at follow-up. Our findings suggest that high-dose levofloxacin regimens may be highly effective in the treatment of non-tuberculous spondylodiscitis and support its putative role in combination with rifampicin against S. aureus. © 2008 Elsevier B.V. and the International Society of Chemotherapy.