The original version of this article unfortunately contained a mistake. The family name of author “Jaime Jose Morales de Cano” was incorrect.

A 60-year-old woman presented to the emergency department with a two-day history of black discharge through the skin over the right hip and a fever of 39ºC. Physical examination revealed a spontaneous flow of black discharge from the right hip area, which intensified when pressure was applied (Figure 1a). Blood tests showed raised c-reactive protein (171.5mg/L; <5mg/L) and leukocytosis (24x10e9/L) with neutrophilia. Swab cultures from the fistula showed S. epidermidis.

One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6–20.7) and 32.3 (95% CI 27.3–38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58–5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip.

Using a tissue cage infection rat model, we test the anti-biofilm effect of clarithromycin on the efficacy of daptomycin and a daptomycin + rifampicin combination against methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). In vitro: kill curves, daptomycin exposure studies and clarithromycin activity against biofilm were studied. In vivo: the efficacies of clarithromycin, daptomycin or daptomycin + clarithromycin, daptomycin + rifampicin and daptomycin + rifampicin + clarithromycin combinations were evaluated. In vitro: the addition of clarithromycin to daptomycin improved its activity only against one MRSA strain. Changes in daptomycin MIC values appeared more quickly in MSSA than in MRSA strain, and this was not modified by clarithromycin. Clarithromycin prevented biofilm formation but did not eradicate it. In vivo: the daptomycin + rifampicin combination was the most effective treatment and was not improved by the addition of clarithromycin. Daptomycin and daptomycin + clarithromycin had similar effectiveness; the combination protected against the appearance of daptomycin resistance only in one MRSA strain. Using a staphylococcal foreign-body infection model, we observed a slight effect with the addition of clarithromycin to daptomycin, which resulted in protection against the appearance of daptomycin-resistant strains. However, efficacy was not improved. Overall, our findings do not support a relevant clinical role for macrolides in treating device-related staphylococcal infections based on their anti-biofilm effect.

The incidence of prosthetic joint infection (PJI) is expected to increase in the coming years. PJI has serious consequences for patients, and high costs for the health system. The complexity of these infections makes it necessary to organize the vast quantity of information published in the last several years. The indications for the choice of a given surgical strategy and the corresponding antimicrobial therapy are specifically reviewed.

Pyogenic arthritis of native joints due to Bacteroides fragilis seems to be an infrequent disease. We analyzed the cases diagnosed in a tertiary hospital during a 22-year period and reviewed the literature to summarize the experience with this infectious entity.In our institution, of 308 patients with pyogenic arthritis of native joints, B fragilis was the causative organism in 2 (0.6%) cases. A MEDLINE search (1981-2015) identified 19 additional cases.Of the 21 patients available for review (13 men and 8 women, with a mean age, of 54.417 years), 19 (90%) presented a systemic predisposing factor for infection; the most common associated illness was rheumatoid arthritis (8 patients). Bacteremia was documented in 65% (13/20) of cases. In 5 patients (24%), 1 or more concomitant infectious process was found. Metronidazole was the most frequently used antibiotic. Surgical drainage was performed in 11 cases (52%). The overall mortality rate was 5%.Pyogenic arthritis of native joints due to B fragilis is an infrequent disease that mainly affects elderly patients with underlying medical illnesses and in whom bacteremia and the presence of a concomitant infectious process are frequent conditions.

Whilst levofloxacin (LVX) in combination with rifampicin (RIF) is considered the optimal treatment for prosthetic joint infection (PJI) caused by meticillin-susceptible Staphylococcus aureus (MSSA), no therapeutic alternatives have been accurately evaluated. Based on the high effectiveness of the combination of daptomycin (DAP) plus RIF against meticillin-resistant S. aureus (MRSA) in this setting, in this study the efficacy of DAP+RIF and DAP+LVX combinations was tested as alternative therapies for foreign-body infections (FBIs) caused by MSSA. A tissue-cage infection model was performed using an MSSA strain. Male Wistar rats were treated for 7 days with LVX, DAP, RIF or the combinations LVX+RIF, DAP+RIF and DAP+LVX. Antibiotic efficacy was evaluated by bacterial counts from tissue cage fluid (TCF) and the cure rate was determined from adhered bacteria. Resistance was screened. Monotherapies were less effective than combinations (P < 0.05), and resistance to DAP and RIF emerged. DAP+RIF (decrease in bacterial counts in TCF, −4.9 log CFU/mL; cure rate, 92%) was the most effective therapy (P < 0.05). There were no differences between LVX+RIF (−3.4 log CFU/mL; 11%) and DAP+LVX (−3.3 log CFU/mL; 47%). No resistant strains appeared with combined therapies. In conclusion, the combinations DAP+RIF and DAP+LVX showed good efficacy and prevented resistance. DAP+RIF provided higher efficacy than LVX+RIF. These DAP combinations were efficacious alternatives therapies for MSSA FBI. Further studies should confirm whether DAP+RIF may be useful as a first-line therapy in the setting of PJI caused by MSSA.

Objective: To analyze the clinical features, microbiological spectrum, diagnostic procedures and outcomes in native joint pyogenic arthritis among non-intravenous drug users.Methods: We collected all microbiologically proved cases of infectious arthritis at our hospital between 1992 and 2013. Patients with prosthetic joint infection were excluded, as were patients with non-pyogenic arthritis and intravenous drug users.Results: We identified 268 patients; the mean age was 61 +/- 14.7 years and 62% were men. The incidence increased over the period of study. In 188 patients (70%), one or more underlying medical illnesses were found. The mean symptom duration was 8.9 +/- 9.5 days. Globally, 311 affected joints were found, 232 (75%) involving peripheral joints and 79 (25%) axial joints. Staphylococci (55%) and Streptococci (29%) were the predominant microorganisms. Blood cultures were positive in 78% (173/223) of the cases. In 81 patients (30%), one or more concomitant infectious processes were found. Antimicrobial therapy was prescribed 4-8 weeks in most cases, and surgical drainage was performed in 65% of patients. Four patients relapsed and 23 (8%) died.Conclusions: The prevalence of pyogenic native joint arthritis in non-intravenous drug users is increasing, frequently affecting old patients with underlying medical conditions. Although large joints are the most frequently compromised, the involvement of axial joints is a relevant feature that has not been recognized in other series. Staphylococci and Streptococci are the main causative agents. Bacteremia and concomitant infectious processes are frequent complications. Diagnostic delay and mortality continue to be important concerns. (C) 2015 Elsevier Inc. All rights reserved.

Objectives: A role for microorganisms in aseptic prosthetic loosening (AL) is postulated. We analyse the microbiological and clinical findings of patients with suspected AL, and compare them with patients with chronic prosthetic joint infection (PJI).Methods: Prospective study (2011-2012) of patients with presumed AL. Evaluation of tissue samples (>= 5; TS) at the time of surgery and sonication fluid (SF) of prosthesis.Results: According to positive culture in TS/SF, 89 patients were divided into: Group 1: (>= 2 positive-TS; n = 12); Group 2: single positive-TS and concordant SF (n = 10); Group 3: one positive or non-concordant TS or SF (n = 38); and Group 4: cultures negative (n = 29). Positive-SF was always concordant with TS in Group 1 (75%); it was positive in 74% in Group 3. Median months (prosthesis-age: implantation to revision arthroplasty) for PJI and Group 1-4 was 21, 46, 65, 63 and 81, respectively (P < 0.001); they also had a different dynamic trend in prosthesis failure (P < 0.001).Conclusions: Several patients with suspected AL are misdiagnosed PJI. Results from SF correlated well with TS in Group 1, led us to consider single positive-TS as significant (Group 2) and to suggest that microorganisms were on the prosthesis (Group 3). We observed a correlation between microbiology and prosthesis-age, which supports that early loosening is more often caused by hidden PJI than late loosening. (C) 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

We compared the efficacies of daptomycin (doses equivalent to 8 to 10 mg/kg of body weight/day in humans) and cloxacillin alone with those of cloxacillin-rifampin and cloxacillin-daptomycin combinations, using a tissue cage methicillin-susceptible Staphylococcus aureus (MSSA) infection model. Monotherapies were less effective than combinations (P < 0.05), and daptomycin resistance emerged. Cloxacillin-daptomycin proved as effective as cloxacillin-rifampin and prevented the appearance of resistance; this combination may be an alternative anti-MSSA therapy, which may offer greater benefits in the early treatment of prosthetic joint infections (PJI).

ABSTRACT Despite the use of daptomycin alone at high doses (greater than 6 mg/kg of body weight/day) against difficult-to-treat infections, clinical failures and resistance appeared. Recently, the combination daptomycin-cloxacillin showed enhanced efficacy in clearing bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to evaluate the efficacy of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg/day in humans, respectively) in combination with cloxacillin in a rat tissue cage infection model by MRSA and to compare its efficacy to that of daptomycin-rifampin. We used MRSA strain ATCC BAA-39. In the log- and stationary-phase kill curves, daptomycin-cloxacillin improved the bactericidal activity of daptomycin, especially in log phase. For in vivo studies, therapy was administered intraperitoneally for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day (daptomycin 100 and daptomycin 45), daptomycin 100-cloxacillin at 200 mg/kg/12 h, daptomycin 45-cloxacillin, and daptomycin 100-rifampin at 25 mg/kg/12 h. Daptomycin-rifampin was the best therapy ( P < 0.05). Daptomycin 45 was the least effective treatment and did not protect against the emergence of resistant strains. There were no differences between the two dosages of daptomycin plus cloxacillin in any situation, and both protected against resistance. The overall effect of the addition of cloxacillin to daptomycin was a significantly greater cure rate (against adhered bacteria) than that for daptomycin alone. In conclusion, daptomycin-cloxacillin enhanced modestly the in vivo efficacy of daptomycin alone against foreign-body infection by MRSA and was less effective than daptomycin plus rifampin. The benefits of adding cloxacillin to daptomycin should be especially evaluated against infections by rifampin-resistant MRSA and for protection against the emergence of daptomycin nonsusceptibility.

In this journal, Cataldo et al. 1 Cataldo M.A. Petrosillo N. Cipriani M. Cauda R. Tacconelli E. Prosthetic joint infection: recent developments in diagnosis and management. J Infect. 2010; 61: 443-448 Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar recently reported recent developments in management of prosthetic joint infections, which are especially difficult to treat due to the presence of bacterial biofilm and tolerance to antibiotics. 2 Zimmerli W. Trampuz A. Ochsner P.E. Prosthetic-joint infections. N Engl J Med. 2004; 351: 1645-1654 Crossref PubMed Scopus (680) Google Scholar Methicillin-resistant Staphylococcus aureus (MRSA) is often involved in these infections. Since the efficacy of anti-MRSA therapies based on antibiotics is limited, other therapeutic targets are being investigated. 3 Costerton J.W. Biofilm theory can guide the treatment of device-related orthopaedic infections. Clin Orthop Relat Res. 2005; : 7-11 Crossref PubMed Scopus (330) Google Scholar In recent years, the knowledge of the quorum-sensing systems involved in staphylococcal virulence has increased. One of them uses the inducer RNAIII-activating protein (RAP) to induce the phosphorylation of the target of RAP (TRAP) and activation of the agr-system. In a study with a laboratory mutant S. aureus strain unable to produce TRAP, Balaban et al. showed that in the absence of TRAP the strain formed little biofilm. 4 Gov Y. Bitler A. Dell'Acqua G. Torres J.V. Balaban N. RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis: structure and function analysis. Peptides. 2001; 22: 1609-1620 Crossref PubMed Scopus (108) Google Scholar Later, several in vivo studies by the same authors have shown the activity of RNAIII-inhibiting peptide (RIP) in preventing staphylococcal biofilm formation. 5 Dell'Acqua G. Giacometti A. Cirioni O. Ghiselli R. Saba V. Scalise G. et al. Suppression of drug-resistant staphylococcal infections by the quorum-sensing inhibitor RNAIII-inhibiting peptide. J Infect Dis. 2004; 190: 318-320 Crossref PubMed Scopus (71) Google Scholar , 6 Balaban N. Stoodley P. Fux C.A. Wilson S. Costerton J.W. Dell'Acqua G. Prevention of staphylococcal biofilm-associated infections by the quorum sensing inhibitor RIP. Clin Orthop Relat Res. 2005; : 48-54 Crossref PubMed Scopus (101) Google Scholar However, to date, only one study has tested the in vivo therapeutic efficacy of RIP against a biofilm infection using a rat graft infection model. 7 Balaban N. Cirioni O. Giacometti A. Ghiselli R. Braunstein J.B. Silvestri C. et al. Treatment of Staphylococcus aureus biofilm infection by the quorum-sensing inhibitor RIP. Antimicrob Agents Chemother. 2007; 51: 2226-2229 Crossref PubMed Scopus (150) Google Scholar

ABSTRACT The efficacy of daptomycin, imipenem, or rifampin with fosfomycin was evaluated and compared with that of daptomycin-rifampin in a tissue cage model infection caused by methicillin-resistant Staphylococcus aureus (MRSA). Strain HUSA 304 was used. The study yielded the following results for MICs (in μg/ml): fosfomycin, 4; daptomycin, 1; imipenem, 0.25; and rifampin, 0.03. The study yielded the following results for minimum bactericidal concentration (MBC) (in μg/ml): fosfomycin, 8; daptomycin, 4; imipenem, 32; and rifampin, 0.5. Daptomycin-rifampin was confirmed as the most effective therapy against MRSA foreign-body infections. Fosfomycin combinations with high doses of daptomycin and rifampin were efficacious alternative therapies in this setting. Fosfomycin-imipenem was relatively ineffective and did not protect against resistance.

OBJECTIVES:Tigecycline appears as an alternative therapy against methicillin-resistant Staphylococcus aureus (MRSA) with limited clinical experience. We evaluate the efficacy of tigecycline and its combination with rifampin in comparison to that for vancomycin in a rat model of foreign-body infection by MRSA. METHODS:A tissue-cage infection model were used; therapy with tigecycline, vancomycin, rifampin, tigecycline plus rifampin and vancomycin plus rifampin was administered intraperitoneally for 7 days. The antibiotic efficacy was evaluated in the tissue-cage fluid and in the coverslips (attached bacteria); the emergence of resistance was screened. RESULTS:Among monotherapies rifampin was the best treatment (decrease in log CFU/ml of tissue-cage fluid, 2.75) (P < 0.05). The addition of rifampin improved the efficacy of vancomycin (decrease, 2.28) and tigecycline (decrease, 1.56) in solitary; there were not significantly differences between tigecycline-rifampin (decrease, 3.39) and vancomycin-rifampin (decrease, 3.70), but only the latter was better than rifampin alone (P < 0.05). Resistant strains were only detected using rifampin alone. CONCLUSIONS:tigecycline alone was the least effective treatment. Tigecycline-rifampin prevented the emergence of rifampin resistance, thus allowing the benefits of rifampin over time against staphylococcal foreign-body infections, but its efficacy needs to be evaluated in comparison with other anti-MRSA combined therapies.

Objectives: Antibiotic-loaded spacers may improve antimicrobial efficacy in two-stage revision of prosthetic joint infections, but they may also interfere in the course of infection. This prospective study of prosthetic joint infections managed with two-stage revision and antibiotic-loaded spacers (2004-09) analyzes case outcomes and proposes a second-stage culture interpretation scheme.Methods: Second-stage infection was diagnosed upon second-stage cultures (synovial membranes, joint fluid, spacers), as either superinfection (>= 2 samples, new organism) or persistence (>= 1 samples, previously isolated organism). Isolated positive antibiotic-loaded spacers cultures were considered as colonizations.Results: Of 42 patients, two had two prosthetic infections (n = 44): 25 knees, 19 hips. Spacers contained gentamicin (33), vancomycin (10) and aztreonam (1). Three patients (7%) with wound healing impairment required debridement and spacer exchange. The remainder underwent second-stage surgery as planned: 34 (77%) new arthroplasties, five arthrodeses, one resection arthroplasty and one permanent spacer. Of 18 cases (44%) with >= 1 positive sample, only four (10%) were second-stage infections. Fourteen antibiotic-loaded spacers cultures (34%) were positive. Four new prostheses (9%) supervened further infections: one by the organism isolated in the spacer, three by new bacteria.Conclusions: The findings of second-stage cultures show that the surgical site is frequently non-sterile at reimplantation. Isolated positive antibiotic-loaded spacer cultures usually have no clinical consequences, but together with tissue cultures they help to diagnose second-stage infections when clinical signs are absent. (C) 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Successful treatment of prosthetic joint infections (PJIs) requires surgical intervention and prolonged antimicrobial therapy (AT), although the most suitable management has not been clearly defined yet. The aim of the study is to review our experience in the management of AHPJIs. From 01/01/2004 to 31/12/2006 all patients with PJIs were prospectively evaluated in 8 Spanish hospitals by the REIPI. We focused here on AHPJIs. Diagnostic of infection was based on clinical-microbiological evidence. Forty-nine patients, 30 (61.2%) women, median age: 75.35 years (range: 31–92), were diagnosed of AHPJIs: 22 (44.8%) hips, 26 (53%) knees and 1 (2%) elbow implants. Following total joint replacement our patients had a median infection-free period of 4.9 years (range 0.3 to 18.7). The comorbidities were: 9 (18.3%) rheumatoid arthritis, 7 (14.3%) diabetes, and 6 (12.2%) chronic renal failure. Clinical features were acute in all cases: pain 100%, inflammatory signs 75.5%, and fever 70%. In 27 (55%) of the cases a distant previous infection caused by the same microorganism could be identified. The etiology was: S. aureus 18 (36.7%), streptococcal infections 13 (26.5%), coagulase-negative staphylococci 2 (4%), gram-negative bacilli 11 (22.4%), anaerobes 2 (4%), and mixed infections in 3 (6.1%) cases. Thirty (61.1%) patients underwent early drainage/debridement with retention of the implant, 11 (22.4%) two-stage replacement, 6 (12.5%) arthrodesis, 1 (2.1%) resection arthroplasty, and 1 unknown. Patients were treated with specific AT (median duration of 10.6 weeks) according to the isolated microorganism. At 1 year follow-up 25 (51%) were cured, 7 (14.3%) relapsed after a conservative approach (3 required an arthrodesis and 1 a two-stage replacement), 5 (10.2 %) died and 5 (10.2%) had a re-infection; in 7 the evolution was unknown. AHPJs can be successfully treated in most cases with surgical debridement plus an antibiotic course. If a relapse is observed, removal of the prostheses could be necessary.

ABSTRACT Since the currently approved dose of daptomycin (6 mg/kg of body weight/day) has been associated with clinical failures and resistance development, higher doses for some difficult-to-treat infections are being proposed. We studied the efficacy of daptomycin at high doses (equivalent to 10 mg/kg/day in humans) and compared it to that of reference and alternative treatments in a model of foreign-body infection with methicillin (meticillin)-resistant Staphylococcus aureus. In vitro studies were conducted with bacteria in the log and stationary phases. For the in vivo model, therapy with daptomycin at 100 mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin (rifampicin) at 25 mg/kg/12 h, or linezolid at 35 mg/kg/12 h was administered for 7 days. Antibiotic efficacy was evaluated using either bacteria from tissue cage fluids or those attached to coverslips. We screened for the emergence of linezolid- and rifampin-resistant strains and analyzed the surviving population from the daptomycin-treated group. Only daptomycin was bactericidal in both the log- and stationary-phase studies. Daptomycin (decrease in the log number of CFU per milliliter of tissue cage fluid, 2.57) and rifampin (decrease, 2.6 log CFU/ml) were better (P < 0.05) than vancomycin (decrease, 1.1 log CFU/ml) and linezolid (decrease, 0.9 log CFU/ml) in the animal model. Rifampin-resistant strains appeared in 60% of cases, whereas no linezolid resistance emerged. No daptomycin-resistant subpopulations were detected at frequencies of 10−7 or higher. In conclusion, daptomycin at high doses proved to be as effective as rifampin, and the two were the most active therapies for this experimental foreign-body infection. These high doses ensured a profile of safety from the development of resistance.

Oral therapies alternative to fluoroquinolones against staphylococcal chronic osteomyelitis have not been evaluated in comparative studies. Consecutive nonaxial Staphylococcus aureus chronic osteomyelitis cases were included in a comparative trial after debridement. Fifty patients were randomized: group A (n = 22) was treated with cloxacillin for 6 weeks intravenously plus 2 weeks orally (p.o.), and group B (n = 28) was treated with rifampin-cotrimoxazole for 8 weeks p.o. During follow-up (10 years), five relapses occurred: two (10%) in group A and three (11%) in group B. Foreign-body maintenance was associated with relapse (P = 0.016). Oral rifampin-cotrimoxazole treatment showed outcomes comparable to those for intravenous cloxacillin treatment.

ABSTRACT Serious Enterococcus faecalis infections usually require combination therapy to achieve a bactericidal effect. In orthopedic infections, the prognosis of enterococcal etiology is considered poor, and the use of aminoglycosides is questioned. The ampicillin-ceftriaxone combination has recently been accepted as alternative therapy for enterococcal endocarditis. After one of our patients with endocarditis and vertebral osteomyelitis was cured with ampicillin-ceftriaxone, we started a pilot study of orthopedic infections. Patients with infections due to E. faecalis (with two or more surgical samples or blood cultures) diagnosed during 2005 to 2008 were recruited. Polymicrobial infections with ampicillin- and ceftriaxone-resistant microorganisms were excluded. Patients received ampicillin (8 to 16 g/day)-ceftriaxone (2 to 4 g/day) and were followed up prospectively. Of 31 patients with E. faecalis infections, 10 received ampicillin-ceftriaxone. Including the first patient, 11 patients were treated with ampicillin-ceftriaxone: 3 with prosthetic joint infections, 3 with instrumented spine arthrodesis device infections, 2 with osteosynthesis device infections, 1 with foot osteomyelitis, and 2 with vertebral osteomyelitis and endocarditis. Six infections (55%) were polymicrobial. All cases except the vertebral osteomyelitis ones required surgery, with retention of foreign material in six cases. Ampicillin-ceftriaxone was given for 25 days (interquartile range, 15 to 34 days), followed by amoxicillin (amoxicilline) being given to seven patients (64%). One patient with endocarditis died within 2 weeks (hemorrhagic stroke) and was not evaluable. For one patient with prosthesis retention, the infection persisted; 9/10 patients (90%) were cured, but 1 patient was superinfected. Follow-up was for 21 months (interquartile range, 14 to 36 months). Ampicillin-ceftriaxone may be a reasonable synergistic combination to treat orthopedic infections due to E. faecalis . Our experience, though limited, shows good outcomes and tolerability and may provide a basis for further well-designed comparative studies.