Tolerability of High Doses of Daptomycin in the Treatment of Prosthetic Vascular Graft Infection: A Retrospective Study.

INTRODUCTION: In treatment of prosthetic vascular graft infection (PVGI), appropriate antimicrobial treatment is crucial for controlling the septic process and preventing re-infection of the new graft. Glycopeptides are the mainstay of treatment for device-related infections by methicillin-resistant Staphylococcus aureus strains, but with some limitations, especially concerning vancomycin-intermediate and glycopeptide-intermediate S. aureus. We report our experience using a high dose of daptomycin (DAP) for treatment of PVGI. METHODS: We reviewed medical reports of 26 patients treated with high doses of DAP (>8 mg/kg) and beta-lactams/aminosides for PVGI, defined as positive bacterial culture of intraoperative specimens or blood samples and/or clinical, biological, and radiological signs of infection. Clinical success was defined by resolution of all clinical signs at the end of follow-up, without the need for additional antibiotic therapy, and/or negative culture in case of new surgery. RESULTS: Cultures of intraoperative samples were positive in 21 patients (80.8%). Blood and intraoperative cultures were concomitantly positive in 10 patients. The main microorganism identified in microbiological samples was S. aureus (n = 18). Surgery was performed in 23 patients (88.4%). The mean duration of the DAP regimen was 12.3 ± 11.9 days. DAP was discontinued in 26 patients [need to switch to microbiological results (n = 19), bacterial pneumonia (n = 2), and increased creatine phosphokinase levels (n = 4)]. One patient had myalgia, while 9 received concomitant statins. CONCLUSION: High-dose DAP therapy shows a satisfactory toxicity profile even in severely ill patients with multiple comorbidities, and may favorably compete with vancomycin, especially concerning the risk of induced nephrotoxicity.

Factors predictive of treatment failure in staphylococcal prosthetic vascular graft infections: a prospective observational cohort study: impact of rifampin.

BACKGROUND: There exists considerable debate concerning management of prosthetic vascular graft infection (PVGI), especially in terms of antimicrobial treatment. This report studies factors associated with treatment failure in a cohort of patients with staphylococcal PVGI, along with the impact of rifampin (RIF). METHODS: All data on patients with PVGI between 2006 and 2010 were reviewed. Cure was defined as the absence of evidence of infection during the entire post-treatment follow-up for a minimum of one year. Failure was defined as any other outcome. RESULTS: 84 patients (72 M/12 F, median age 64.5 ± 11 y) with diabetes mellitus (n = 25), obesity (n = 48), coronary artery disease (n = 48), renal failure (n = 24) or COPD (n = 22) were treated for PVGI (median follow-up was 470 ± 469 d). PVGI was primarily intracavitary (n = 47). Staphylococcus aureus (n = 65; including 17 methicillin-resistant S. aureus) and coagulase-negative Staphylocococcus (n = 22) were identified. Surgical treatment was performed in 71 patients. In univariate analysis, significant risk factors associated with failure were renal failure (p = 0.04), aortic aneurysm (p = 0.03), fever (p = 0.009), aneurysm disruption (p = 0.02), septic shock in the peri-operative period (p = 0.005) and antibiotic treatment containing RIF (p = 0.03). In multivariate analysis, 2 variables were independently associated with failure:septic shock [OR 4.98: CI 95% 1.45-16.99; p=0.01] and antibiotic containing rifampin [OR: 0.32: CI95% 0.10-0.96; p=0.04]. CONCLUSION: Results of the present study suggest that fever, septic shock and non-use of antibiotic treatment containing RIF are associated with poor outcome.

Periprosthetic joint infections: clinical and bench research.

Prosthetic joint infection is a devastating complication with high morbidity and substantial cost. The incidence is low but probably underestimated. Despite a significant basic and clinical research in this field, many questions concerning the definition of prosthetic infection as well the diagnosis and the management of these infections remained unanswered. We review the current literature about the new diagnostic methods, the management and the prevention of prosthetic joint infections.

Pathogen-driven decision for implant retention in the management of infected total knee prostheses.

PURPOSE: In prosthetic joint infections (PJIs) of the knee, debridement with implant retention is associated with a high risk of recurrence. METHODS: A single-centre cohort study was performed with extensive analysis of the literature covering 1980-2012. RESULTS: In 21 patients (mean age 80.4 years, 19 immunosuppressed), in association with 1.5-three months of antibiotic treatment, an attempt was made to salvage the prosthesis by open (11 patients) or arthroscopic (ten patients) debridement. After a mean follow-up of seven years (range four-20 years), patients were in remission in seven cases (33 %). Remission was achieved in 0 % of all methicillin-resistant Staphylococcus aureus (MRSA) infections (zero/three), in 0 % (zero/three) of methicillin-resistant coagulase-negative staphylococcal infections, in 29 % (two/seven) of methicillin-sensitive S. aureus infections and in 75 % (three/four) of infections due to streptococci. The literature review focused on implant preserving approaches yielded 599 cases with an overall success rate of 47 % (284/599) and significantly more remissions in streptococcal vs staphylococcal knee PJIs (43/54 vs 144/324; p < 0.01, odds ratio 4.9, 95 % confidence interval 2.4-10.9). CONCLUSIONS: In addition to established indications for explantation such as implant loosening, sinus tract or methicillin resistance, the decision for debridement and retention of knee PJIs should also depend on the pathogen. Implant preservation is futile with methicillin-resistant staphylococci, but seems to be a valid option for streptococcal PJIs.

Evaluation of rapid mecA gene detection versus standard culture in staphylococcal chronic prosthetic joint infections.

In case of periprosthetic joint infections, the antibiotic treatment administered intraoperatively entails consequences on bacterial ecology with potential secondary effects. This study evaluates the rapid detection of methicillin-resistant staphylococci (MRS) by Xpert® technology directly on intraoperative samples. Xpert® technology was compared to conventional culture for 104 clinical specimens performed on 30 patients. The performance of the test expressed in terms of sensitivity, specificity, positive predictive value, and negative predictive value was, respectively, 87.1%, 100%, 100%, and 94.5% for the 104 specimens, and 92.3%, 100%, 100%, and 94.4% for the 30 patients. With the rapid detection of MRS, the use of vancomycin was limited for 17 of these 30 patients. In conclusion, this technique would allow the implementation of first-line antibiotic treatment adapted to the presence of MRS or not within approximately 1 h and would strongly reduce the use of broad-spectrum antibiotics.

First initial community-acquired meningitis due to extended-spectrum beta-lactamase producing Escherichia coli complicated with multiple aortic mycotic aneurysms.

We report the first case of extended-spectrum beta-lactamase producing E. coli community-acquired meningitis complicated with multiple aortic mycotic aneurysms. Because of the acute aneurysm expansion with possible impending rupture on 2 abdominal CT scan, the patient underwent prompt vascular surgery and broad spectrum antibiotic therapy but he died of a hemorrhagic shock. Extended-spectrum beta-lactamase producing E. coli was identified from both blood and cerebrospinal fluid culture before vascular treatment. The present case report does not however change the guidelines of Gram negative bacteria meningitis in adults.

Vascular graft infections.

PURPOSE OF REVIEW: This review provides a focus on infections of prosthetic vascular grafts used to treat peripheral arterial diseases. RECENT FINDINGS: The incidence of infections varies between 1 and 6%. Risk factors of infection are not well identified. Main causative pathogens are Gram-negative bacilli, Staphylococcus aureus, and coagulase-negative staphylococci, without clear differences according to location of graft and time of onset of infection. There is no consensual diagnostic criterion. The basic principles for management of graft infections have been known for many years. A surgical approach combining graft excision, complete debridement, and maintaining distal vascular flow is required. Antimicrobial therapy is always instituted to reduce sepsis and prevent secondary graft infection, but there are no evidence-based data to recommend any regimen. However, antibiotics should have bactericidal activity whatever the bacteria growth phase, reduce the microbial burden, penetrate within the biofilm, and prevent further biofilm formation. Mortality and morbidity from these infections remain significant. SUMMARY: A multidisciplinary approach with a limited number of reference centres, recruiting sufficient numbers of patients to perform controlled trials, and to provide expert recommendations, could be the best way to answer unresolved questions and improve the prognosis.

Outcome and predictors of treatment failure in total hip/knee prosthetic joint infections due to Staphylococcus aureus.

BACKGROUND: Variables associated with the outcome of patients treated for prosthetic joint infections (PJIs) due to Staphylococcus aureus are not well known. METHODS: The medical records of patients treated surgically for total hip or knee prosthesis infection due to S. aureus were reviewed. Remission was defined by the absence of local or systemic signs of implant-related infection assessed during the most recent contact with the patient. RESULTS: After a mean posttreatment follow-up period of 43.6 ± 32.1 months, 77 (78.6%) of 98 patients were in remission. Retention of the infected implants was not associated with a worse outcome than was their removal. Methicillin-resistant S. aureus (MRSA)-related PJIs were not associated with worse outcome, compared with methicillin-susceptible S. aureus (MSSA)-related PJIs. Pathogens identified during revision for failure exhibited no acquired resistance to antibiotics used as definitive therapy, in particular rifampin. In univariate analysis, parameters that differed between patients whose treatment did or did not fail were: American Society of Anesthesiologists (ASA) score, prescription of adequate empirical postsurgical antibiotic therapy, and use of rifampin combination therapy upon discharge from hospital. In multivariate analysis, ASA score ≤2 (odds ratio [OR], 6.87 [95% confidence interval {CI}, 1.45-32.45]; P = .04) and rifampin-fluoroquinolone combination therapy (OR, 0.40 [95% CI, 0.17-0.97]; P = .01) were 2 independent variables associated with remission. CONCLUSIONS: The results of the present study suggest that the ASA score significantly affects the outcome of patients treated for total hip and knee prosthetic infections due to MSSA or MRSA and that rifampin combination therapy is associated with a better outcome for these patients when compared with other antibiotic regimens.

Vascular graft infections in the intensive care unit: clinical spectrum and prognostic factors.

OBJECTIVES: To report clinical characteristics and prognosis of vascular graft infections in Intensive Care Unit (ICU). METHODS: Thirty seven patients consecutively admitted in ICU for suspected or definite vascular graft infection between January 2006 and June 2009 were included. RESULTS: Staphylococcus species (n = 18) and enterobacteriae (n = 16) were the most frequent causative organisms. Twenty six patients (70%) needed mechanical ventilation. Further surgical procedures were performed in 7 patients (19%). In case of definite infection, mortality in ICU was 33%. In non survivors, shock (92% vs 42%, p = 0.01), age > 70 years (73% vs 27%, p = 0.04), POSSUM score > 45 (73% vs 27%, p = 0.04) and extra-anatomic bypass (45% vs 14%, p = 0.05) were more frequent, intra-operative volume of red cells transfusion (6 ± 3 vs 3 ± 2 units, p = 0.006) and of fresh frozen plasma (2.8 ± 2.8 vs 0.7 ± 1.2 units, p = 0.02), and SAPS II score (58 ± 26 vs 38 ± 17, p = 0.03) were higher. Proportion of adequate initial antibiotic therapy was similar in survivors and non survivors (91% vs 100%, p = 0.4). Proportion of patients treated with an aminoglycoside tended to be higher in survivors (59% vs 27%, p = 0.07). By multivariate analysis, only shock was associated with death in ICU (AOR: 16.3; 95% CI: 1.7-152.1; p = 0.01). CONCLUSIONS: Vascular graft infection carries high morbidity and mortality rates in ICU. Extra-anatomic bypass might be associated with higher mortality. Early aminoglycoside prescription might be protective.

Brain abscesses during Proteus vulgaris bacteremia.

Proteus vulgaris is only rarely the cause of multiple septic metastases. We describe multiple brain abscesses due to P. vulgaris in an immunocompetent patient successfully treated by antibiotic therapy and colonectomy.

Tolerability of prolonged linezolid therapy in bone and joint infection: protective effect of rifampicin on the occurrence of anaemia?

BACKGROUND: Linezolid therapy has shown high rates of clinical success in patients with osteomyelitis and prosthetic joint infections caused by Gram-positive cocci. Recent studies have demonstrated that linezolid/rifampicin combination therapy prevents the emergence of rifampicin-resistant mutations in vitro. However, linezolid/rifampicin combination-related haematological and neurological toxicities have not been evaluated. OBJECTIVES: To assess the tolerability of prolonged linezolid/rifampicin combination therapy compared with other linezolid-containing regimens in patients with bone and joint infections. METHODS: We reviewed the medical records of 94 patients who had received linezolid for >4 weeks after bone and joint infections. Anaemia was defined as a ≥2 g/dL reduction in haemoglobin, leucopenia as a total leucocyte count <4 × 10(9)/L, and thrombocytopenia as a reduction in platelet count to <75% of baseline. RESULTS: Anaemia was less frequent among patients on linezolid/rifampicin combination therapy than among patients on linezolid alone or in combination with other drugs (9.3%, 44% and 52%, respectively; P<0.01). In multivariate analysis, age and treatment group were independently associated with anaemia. Thrombocytopenia was reported in 44% of patients on linezolid/rifampicin combination therapy, in 48% of patients on linezolid alone and in 57.7% of patients on other linezolid-containing regimens. Age was the only variable associated with thrombocytopenia (P=0.019) in univariate analysis. CONCLUSIONS: Linezolid/rifampicin combination therapy was associated with a significantly reduced incidence of anaemia among patients with bone and joint infections, but it did not have an effect on thrombocytopenia and peripheral neuropathy rates. Linezolid/rifampicin combination therapy was not associated with poor clinical outcomes.

Six weeks of antibiotic treatment is sufficient following surgery for septic arthroplasty.

OBJECTIVES: In the treatment of prosthetic joint infections (PJI), the benefit of antibiotic therapy for more than 6 weeks after surgery is uncertain. We compared PJI cure rates according to the duration of antibiotics, 6 versus 12 weeks. METHODS: A prospective observational non-randomized study in Geneva University Hospitals 1996-2007. RESULTS: A total of 144 PJI (62 hip arthroplasties, 62 knee arthroplasties, and 20 hip hemiarthroplasties) were included with a prolonged follow-up ranging from 26 to 65 months. Surgical treatment included 60 débridements with implant retention, 10 one-stage exchanges of the prosthesis, 57 two-stage exchanges, and 17 Girdlestone procedures or knee arthrodeses. Seventy episodes (49%) received 6 weeks antibiotic therapy and 74 episodes, 12 weeks. Cure was achieved in 115 episodes (80%). Cure rate did not change according to the duration of intravenous antibiotics (>8 days, 8-21 days, >21 days) (Kruskal-Wallis-test; p = 0.37). In multivariate analysis, none of the following parameters was statistically significantly associated with cure: two-stage exchange (odds ratio 1.1,95%CI 0.2-4.8); number of débridements (0.9, 0.4-1.9); six weeks antibiotherapy (2.7, 0.96-8.3); duration of intravenous course (1.0, 0.96-1.03); sinus tract (0.6, 0.2-1.7); or MRSA infection (0.5, 0.2-1.5), although implant retention showed a tendency for less cure (0.3, 0.1-1.1). CONCLUSIONS: Following surgery for treatment of PJI, antibiotic therapy appears able to be limited to a 6-week course, with one week of intravenous administration. This approach needs confirmation in randomized trials.

Needle puncture and transcutaneous bone biopsy cultures are inconsistent in patients with diabetes and suspected osteomyelitis of the foot.

BACKGROUND: Needle puncture has been suggested as a method for identifying bacteria in the bones in patients with diabetes with osteomyelitis of the foot. However, no studies have compared needle puncture with concomitant transcutaneous bone biopsy, which is the current standard recommended in international guidelines. METHODS: We conducted a prospective study in 2 French diabetes foot clinics. Transcutaneous bone biopsy specimens, needle puncture specimens, and swab samples were collected on the same day for each patient. RESULTS: Overall, 31 patients were included in the study from July 2006 through February 2008. Twenty-one bone biopsy specimens (67.7%), 18 needle puncture specimens (58%), and 30 swab samples (96.7%) had positive culture results. Staphylococcus aureus was the most common type of bacteria that grew from bone samples, followed by Proteus mirabilis and Morganella morganii. The mean number of bacteria types per positive sample were 1.35, 1.32, and 2.51 for bone biopsy specimens, needle puncture specimens, and swab samples, respectively. Among the 20 patients with positive bone biopsy specimens (69%), 13 had positive needle puncture samples. Overall, the correlation between microbiological results was 23.9%, with S. aureus showing the strongest correlation (46.7%). Results of cultures of bone biopsy and needle puncture specimens were identical for 10 (32.3%) of 31 patients. Bone bacteria were isolated from the needle punctures in 7 (33.3%) of the 21 patients who had positive bone biopsy specimen culture results. If the results of cultures of needle puncture specimens alone had been considered, 5 patients (16.1%) would have received unnecessary treatment, and 8 patients (38.1%) who had positive bone culture results would not have been treated at all. CONCLUSIONS: Our results suggest that needle punctures, compared with transcutaneous bone biopsies, do not identify bone bacteria reliably in patients with diabetes who have low-grade infection of the foot and suspected osteomyelitis.

Activity and impact on antibiotic use and costs of a dedicated infectious diseases consultant on a septic orthopaedic unit.

UNLABELLED: The Orthopaedic Service of the Geneva University Hospitals engages dedicated infectious disease (ID) specialists to assist in the treatment of infected patients. We investigated the daily clinical activity and the impact on antibiotic costs in the Septic Unit since 2000. METHODS: Retrospective analysis of various databases. Prospective survey of clinical activity from January 2008 to March 2008. RESULTS: According to the survey, the ID specialist performed 265 first-time and 1420 follow-up consultations (average of 11.4 consultations per working day). In 88% of cases the antibiotic regimen initiated by the surgeons was approved. When the ID specialist had to change antibiotic treatment, it was for de-escalation in 43.7%, discontinuance in 32.4%, and initiation in 24.4% of cases. From April 2007 to March 2008, the ID specialist decreased total antibiotic use by 43 DDD/100 patients-days (p=0.0006) in the Septic Unit. Direct antibiotic costs decreased by US$64,380 over the same period, equal to the annual salary of the ID specialist. There was no change in the number of recurrent infections. CONCLUSIONS: The main antibiotic-related activity of the dedicated orthopaedic ID specialist in Geneva our institution was to discontinue or adjust a pre-existing antimicrobial therapy. This activity significantly reduced antibiotic use and related costs on a septic orthopaedic unit.

First case of intrafamily transmission of a new MRSA clone with toxic shock syndrome toxin-1.

We report the first case of intrafamily transmission of a C-MRSA clone harbouring toxic shock syndrome toxin-1 (TSST-1). Because of the risk of this clone to spread in the community, family members of these patients should be screened to detect and prevent the diffusion of recurrent or new infections.

Outcome of diabetic foot osteomyelitis treated nonsurgically: a retrospective cohort study.

OBJECTIVE: The purpose of this article was to identify criteria predictive of remission in nonsurgical treatment of diabetic foot osteomyelitis. RESEARCH DESIGN AND METHODS: Diabetic patients who were initially treated without orthopedic surgery for osteomyelitis of the toe or metatarsal head of a nonischemic foot between June 2002 and June 2003 in nine French diabetic foot centers were identified, and their medical records were reviewed. Remission was defined as the absence of any sign of infection at the initial or contiguous site assessed at least 1 year after the end of treatment. A total of 24 demographic, clinical, and therapeutic variables including bone versus swab culture-based antibiotic therapy were analyzed. RESULTS: Fifty consecutive patients aged 62.2 +/- 11.1 years (mean +/- SD) with diabetes duration of 16 +/- 10.9 years were included. The mean duration of antibiotic treatment was 11.5 +/- 4.21 weeks. Bone biopsy was routinely available in four of the nine centers. Overall patient management was similar in the different centers except for the use of rifampin, which was recorded more frequently in patients from centers in which a bone biopsy was available. At the end of a 12.8-month posttreatment mean follow-up, 32 patients (64%) were in remission. Bone culture-based antibiotic therapy was the only variable associated with remission, as determined by both univariate (18 of 32 [56.3%] vs. 4 of 18 [22.2%], P = 0.02) and multivariate analyses (odds ratio 4.78 [95% CI 1.0-22.7], P = 0.04). CONCLUSIONS: Bone culture-based antibiotic therapy is a factor predictive of success in diabetic patients treated nonsurgically for osteomyelitis of the foot.

Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: a retrospective study.

BACKGROUND: Linezolid is an oxazolidinone agent which is apparently well designed for treating chronic osteomyelitis, but data on effectiveness and tolerability as prolonged therapy is currently lacking. OBJECTIVE: The purpose of this study was to assess the effectiveness and tolerability of linezolid in the treatment of chronic osteomyelitis. METHODS: The charts of hospitalized patients who had been treated with linezolid for >4 weeks because of chronic osteomyelitis and were followed up for > or =12 months after the end of treatment were retrospectively reviewed for clinical outcome and tolerability. Cure was defined as the absence of clinical, biological, or radiological evidence of infection throughout the posttreatment follow-up. Linezolid tolerability was assessed on the basis of hematologic properties during treatment. RESULTS: Of the 66 patients included, all were white (mean [SD] age, 67.7 [18.1] years; 41 men and 25 women; mean [SD] weight, 80.7 [18.6] kg). Thirty-seven (56.1%) patients had infection due to implants including 27 prosthetic joints. Pathogens were predominantly methicillin-resistant staphylococci (49/72 strains, 68.1 %). Every patient was administered N linezolid (600 mg BID) treatment for 6 to 8 days as inpatients, and then, as outpatients, they were switched to PO treatment. Fifty (75.8%) patients received a combination of linezolid and other antimicrobial agents, including rifampin (32 [48.5%]). Surgery was performed in 52 (78.8%) patients. The median hospital stay was 14 days (mean [SD], 19 [11.4] days [range, 7-70 days] ). The median duration of treatment was 13 weeks (mean [SD], 14.3 [8.2] weeks [range, 5-36 weeks]). At the end of treatment, 56 (84.8%) patients were cured, and during the post-treatment follow-up (median duration, 15 months [range, 12-36 months]), 4 relapses occurred, resulting in an overall successful cure for 52 (78.8%) patients. Reversible anemia was reported in 21 patients (31.8%), of whom 16 (24.2%) required blood transfusions. Median time from treatment initiation to anemia onset was 7.3 weeks (range, 4-12 weeks). Peripheral neuropathy was reported in 6 (9.1%) patients, of whom 4 remained symptomatic for up to 24 months after linezolid discontinuation. Other reported adverse events included nausea (6 [9.1%]), diarrhea (1 [1.5%]), and headache (2 [3.0%]), although none of these patients discontinued treatment. CONCLUSIONS: In this retrospective chart review, treatment with linezolid as monotherapy or in combination with antimicrobials and/or surgery was associated with cure of chronic osteomyelitis in 84.8% of subjects at 12 weeks after the end of treatment and 78.8% at follow-up. Adverse events were reported in 51.5% of subjects, and 34.8% of subjects discontinued the study because of adverse events. The potential for severe complications justifies close monitoring of these patients.