Do High Doses of Multiple Antibiotics Loaded into Bone Cement Spacers Improve the Success Rate in Staphylococcal Periprosthetic Joint Infection When Rifampicin Cannot Be Employed?

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10-147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.

Validation of the antibacterial effect of topically applied tranexamic acid using in vitro and in vivo models.

Background: Several studies have shown that tranexamic acid (TXA), an antifibrinolytic, reduces postoperative infection rates. Recent in vitro research showed that TXA alone and in combination with vancomycin and gentamicin had a synergistic effect against some staphylococcal strains. In the present study, this synergistic effect was validated in samples from patients with staphylococcal periprosthetic infection (PPI) and in an in vivo model. Methods: We tested 19 clinical strains (5 Staphylococcus aureus and 14 coagulase-negative staphylococci [CoNS]) against 10 mg/ml TXA alone and in combination with serial dilutions of vancomycin and gentamicin. The standardized microtiter plate method was used. The minimal inhibitory concentration (MIC) were calculated using standard visualization of well turbidity. We also used an S. aureus (ATCC29213) murine subcranial PPI model to compare the synergistic effect of TXA and gentamicin with that of TXA or gentamicin alone after 4 days of monitoring. The mice were euthanized, and disks were removed for analysis of cfu/ml counts and cell viability rate. Biofilm structure of both in vitro and in vivo samples was also analyzed using scanning electron microscopy (SEM). Results: When TXA was combined with vancomycin or gentamicin, the MIC decreased in 30% of the strains studied. According to species, the MIC50 for vancomycin and gentamicin alone and in combination with TXA against S. aureus strains was the same. This was also the case for CoNS with vancomycin and its corresponding combination, whereas with gentamicin and TXA, a reduction in MIC50 was observed (2 dilutions). In addition, in the in vivo model, the mean (SD) log cfu/ml and cell viability rate obtained from the implant was lower in the group of mice treated with TXA and gentamicin than in those treated only with TXA or gentamicin. SEM images also corroborated our findings in strains in which the MIC was reduced, as well as the in the mice implants, with the area occupied by biofilm being greater in samples treated only with gentamicin or TXA than in those treated with TXA+gentamicin. Conclusion: We confirm that combining TXA with vancomycin or gentamicin exerts a synergistic effect. However, this only occurs in selected strains.

Corrigendum: Tranexamic acid in combination with vancomycin or gentamicin has a synergistic effect against staphylococci.

[This corrects the article DOI: 10.3389/fmicb.2022.935646.].

In Vitro Efficacy of Dalbavancin as a Long-Acting Anti-Biofilm Agent Loaded in Bone Cement.

Based on previous studies by our group in which we demonstrated that dalbavancin loaded in bone cement had good elution capacity for the treatment of biofilm-related periprosthetic infections, we now assess the anti-biofilm activity of dalbavancin and compare it with that of vancomycin over a 3-month period. We designed an in vitro model in which we calculated the percentage reduction in log cfu/mL counts of sonicated steel discs contaminated with staphylococci and further exposed to bone cement discs loaded with 2.5% or 5% vancomycin and dalbavancin at various timepoints (24 h, 48 h, 1 week, 2 weeks, 6 weeks, and 3 months). In addition, we tested the anti-biofilm activity of eluted vancomycin and dalbavancin at each timepoint based on a 96-well plate model in which we assessed the percentage reduction in metabolic activity. We observed a significant decrease in the dalbavancin concentration from 2 weeks of incubation, with sustained anti-biofilm activity up to 3 months. In the case of vancomycin, we observed a significant decrease at 1 week. The concentration gradually increased, leading to significantly lower anti-biofilm activity. The percentage reduction in cfu/mL counts was higher for dalbavancin than for vancomycin at both the 2.5% and the 5% concentrations. The reduction in log cfu/mL counts was higher for S. epidermidis than for S. aureus and was particularly more notable for 5% dalbavancin at 3 months. In addition, the percentage reduction in metabolic activity also decreased at 3 months in 5% dalbavancin and 5% vancomycin, with more notable values recorded for the latter.

Ruminococcus gnavus, an unusual cause of surgical site infection following vertebral posterior instrumentation: a case report.

Background: Ruminococcus gnavus (R. Gnavus) is an anaerobic Gram-positive coccus, common commensal of the gastrointestinal tract of animals and humans. Anaerobic organisms as etiologic agents of bone and joint infections (BJI) are uncommon and frequently underestimated. New technologies, such as mass spectrometry techniques and molecular techniques like 16S rRNA, allow for more efficient diagnosis of these anaerobic bacteria. We present the first case report of deep surgical site infection (SSI) due to R. Gnavus, following spinal surgery. Case Description: We report the case of a deep SSI caused by R. Gnavus following posterior spinal instrumentation in an 81-year-old woman. The patient underwent extension of her previous fusion L2-L5, due to adjacent segment disease (ASD). We performed a T10 to S2-alar-iliac instrumentation. During the postoperative period, the patient presented with a paralytic ileus that required the placement of a nasogastric tube followed by gastrointestinal bleeding and two gastroscopies. Subsequently the patient showed signs of deep SSI. We performed surgical irrigation and debridement. All six cultures in anaerobic media showed short Gram-positive diplococci, using matrix-assisted laser desorption/ionization time of flight mass spectrometry (Maldi-TOF MS) all six strains were identified as R. Gnavus. The patient was treated with amoxicilin 1 g/8 h and ciprofloxacin 750 mg/12 h for 4 weeks. Six months postoperative, she was asymptomatic. Conclusions: As is the case with our patient, all previously described cases of R. Gnavus infection had a history of intestinal disease or immunosupression. We believe the isolation of R. Gnavus should raise the possibility of intestinal injury. Immunosuppression is also an important risk factor for the development of R. Gnavus infection.

Cost analysis of disease including treatment with dalbavancin in a Spanish hospital: ECODAL ANALYSIS.

INTRODUCTION AND AIM: Dalbavancin is an antibiotic with activity against gram-positive bacteria that allows early discharge of patients requiring intravenous therapy. Outpatient treatment helps offset hospitalisation costs associated with standard intravenous treatment. Our objective was to assess the cost of disease management, including treatment with dalbavancin, in a Spanish hospital for 1 year, and the hypothetical costs associated with treatment with other therapeutic alternatives to dalbavancin. METHODS: A single-centre, observational, retrospective post-hoc analysis was conducted based on electronic medical records analysing all patients who received dalbavancin treatment throughout 1 year; cost analysis was performed for the whole process. In addition, three scenarios designed on the basis of real clinical practice by clinical experts were hypothesised: (i) individual therapeutic alternative to dalbavancin, (ii) all patients treated with daptomycin, and (iii) all days of dalbavancin as outpatient treatment transformed into hospital stay. Costs were obtained from the hospital. RESULTS: Thirty-four patients were treated with dalbavancin; their mean age was 57.9 years, and 70.6% were men. The main reasons for dalbavancin use were outpatient management (61.7%, n = 21) and ensuring treatment adherence (26.5%, n = 9). The main indications were: osteoarticular infection (32.4%) and infective endocarditis (29.4%). One-half (50%) of the infections were due to Staphylococcus aureus (23.5% were methicillin resistant). All patients achieved clinical resolution, and no costs associated with dalbavancin-associated adverse events or re-admissions were reported. The mean total cost of treatment was 22,738€ per patient, with the greatest expenditures in interventions (8,413€) and hospital stay (6,885€). The mean cost of dalbavancin treatment was 3,936€; without dalbavancin, this cost could have been increased to 3,324-11,038€ depending on the scenario, mainly due to hospital stays. MAIN LIMITATION: Limited sample size obtained from a single centre. CONCLUSION: The economic impact of the management of these infections is high. The cost of dalbavancin is offset by the decreased length of stay.

Determination of the Elution Capacity of Dalbavancin in Bone Cements: New Alternative for the Treatment of Biofilm-Related Peri-Prosthetic Joint Infections Based on an In Vitro Study.

Antibiotic-loaded bone cement is the most widely used approach for the treatment of biofilm-induced septic sequelae in orthopedic surgery. Dalbavancin is a lipoglycopeptide that acts against Gram-positive bacteria and has a long half-life, so we aimed to assess whether it could be a new alternative drug in antibiotic-loaded bone cement for the treatment of periprosthetic joint infections. We assessed the elution capacity of dalbavancin and compared it with that of vancomycin in bone cement. Palacos®R (Heraeus Medical GmbH, Wehrheim, Germany) bone cement was manually mixed with each of the antibiotics studied at 2.5% and 5%. Three cylinders were obtained from each of the mixtures; these were weighed and incubated in 5 mL phosphate-buffered saline at 37°C under shaking for 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 168 h, and 336 h. PBS was replenished at each time point. The samples were analyzed using high-performance liquid chromatography (vancomycin) and mass cytometry (dalbavancin). Elution was higher than the minimum inhibitory concentration (MIC)90 for both antibiotics after 14 days of study. The release of vancomycin at 14 days was higher than of dalbavancin at each concentration tested (p = 0.05, both). However, the cumulative release of 5% dalbavancin was similar to that of 2.5% vancomycin (p = 0.513). The elution capacity of dalbavancin reached a cumulative concentration similar to that of vancomycin. Moreover, considering that the MIC90 of dalbavancin is one third that of vancomycin (0.06 mg/L and 2 mg/L, respectively) and given the long half-life of dalbavancin, it may be a new alternative for the treatment of biofilm-related periprosthetic infections when loaded in bone cement.

Tranexamic Acid in Combination With Vancomycin or Gentamicin Has a Synergistic Effect Against Staphylococci.

Background: Tranexamic acid (TXA) is an antifibrinolytic agent applied in orthopedic surgery and has been proven to reduce post-surgery infection rates. We previously showed that TXA also had an additional direct antimicrobial effect against planktonic bacteria. Therefore, we aimed to evaluate whether it has a synergistic effect if in combination with antibiotics. Materials and Methods: Three ATCC and seven clinical strains of staphylococci were tested against serial dilutions of vancomycin and gentamicin alone and in combination with TXA at 10 and 50 mg/ml. The standardized microtiter plate method was used. Minimal inhibitory concentrations (MICs) were calculated by standard visualization of well turbidity (the lowest concentration at which complete absence of well bacterial growth was observed by the researcher) and using the automated method (the lowest concentration at which ≥80% reduction in well bacterial growth was measured using a spectrophotometer). Results: Tranexamic acid-10 mg/ml reduced the MIC of vancomycin and gentamicin with both the standard method (V: 1-fold dilution, G: 4-fold dilutions) and the automated turbidity method (vancomycin: 8-fold dilutions, gentamicin: 8-fold dilutions). TXA-50 mg/ml reduced the MIC of gentamicin with both the standard turbidity method (6-fold dilutions) and the automated turbidity method (1-fold dilutions). In contrast, for vancomycin, the MIC remained the same using the standard method, and only a 1-fold dilution was reduced using the automated method. Conclusion: Ours was a proof-of-concept study in which we suggest that TXA may have a synergistic effect when combined with both vancomycin and gentamicin, especially at 10 mg/ml, which is the concentration generally used in clinical practice.

Effect of Tranexamic Acid against Staphylococcus spp. and Cutibacterium acnes Associated with Peri-Implant Infection: Results from an In Vitro Study.

Tranexamic acid (TXA) is extensively used in orthopedic surgery and traumatology as an antifibrinolytic agent to control intra- and postoperative bleeding and, therefore, indirectly, to reduce postsurgery infection rates. The hypothesis of an additional antibiotic effect against microorganisms associated with periprosthetic joint infection needs to be further evaluated. We aimed to assess whether TXA could reduce bacterial growth using an in vitro model. ATCC and clinical strains of staphylococci and Cutibacterium acnes were tested against TXA in both planktonic and sessile forms. We recorded the percent reduction in the following variables: log CFU/mL by microbiological culture, percentage of live cells by confocal laser scanning microscopy, and, additionally in sessile cells, metabolic activity by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) assay. Variables were compared between groups using the Kruskal-Wallis test, and the results were reported as median (interquartile range [IQR]). Statistical significance was set at a P value of <0.05. Clinical significance was defined as a reduction of ≥25%. TXA at 50 mg/mL led to a slight reduction in CFU counts (4.5%). However, it was at 10 mg/mL that the reduction reached 27.2% and 33.0% for log CFU/mL counts and percentage of live cells, respectively. TXA was not efficacious for reducing preformed 24-h mature staphylococci and 48-h mature C. acnes biofilms, regardless of its concentration. TXA did not exert an antimicrobial effect against bacterial biofilms. However, when bacteria were in the planktonic form, it led to a clinically and statistically significant reduction in bacterial growth at 10 mg/mL. IMPORTANCE The possible use of TXA as an antibiotic agent in addition to its antifibrinolytic effect may play an important role in the prevention of prosthetic joint infection.

Implant Removal in the Management of Prosthetic Joint Infection by Staphylococcus aureus: Outcome and Predictors of Failure in a Large Retrospective Multicenter Study.

OBJECTIVES: To compare the characteristics and outcomes of cases with acute prosthetic joint infection (PJI; early post-surgical or hematogenous) by Staphylococcus aureus managed with implant removal (IRm) or debridement and retention (DAIR). To analyze the outcomes of all cases managed with IRm (initially or after DAIR failure). METHODS: Retrospective, multicenter, cohort study of PJI by S. aureus (2003-2010). Overall failure included mortality within 60 days since surgery and local failure due to staphylococcal persistence/relapse. RESULTS: 499 cases, 338 initially managed with DAIR, 161 with IRm. Mortality was higher in acute PJI managed initially with IRm compared to DAIR, but not associated with the surgical procedure, after propensity score matching. Underlying conditions, hemiarthroplasty, and methicillin-resistant S. aureus were risk factors for mortality. Finally, 249 cases underwent IRm (88 after DAIR failure); overall failure was 15.6%. Local failure (9.3%) was slightly higher in cases with several comorbidities, but independent of previous DAIR, type of IRm, and rifampin treatment. CONCLUSIONS: In a large multicenter study of S. aureus PJI managed with IRm, failure was low, but mortality significant, especially in cases with acute PJI and underlying conditions, but not associated with the IRm itself. Rifampin efficacy was limited in this setting.

Genotypic and Phenotypic Characteristics of Staphylococcus aureus Prosthetic Joint Infections: Insight on the Pathogenesis and Prognosis of a Multicenter Prospective Cohort.

BACKGROUND: Staphylococcus aureus is the leading cause of prosthetic joint infection (PJI). Beyond the antibiogram, little attention has been paid to the influence of deep microbiological characteristics on patient prognosis. Our aim was to investigate whether microbiological genotypic and phenotypic features have a significant influence on infection pathogenesis and patient outcome. METHODS: A prospective multicenter study was performed, including all S. aureus PJIs (2016-2017). Clinical data and phenotypic (agr functionality, ß-hemolysis, biofilm formation) and genotypic characteristics of the strains were collected. Biofilm susceptibility to antimicrobials was investigated (minimal biofilm eradication concentration [MBEC] assay). RESULTS: Eighty-eight patients (39.8% men, age 74.7 ±â€…14.1 years) were included. Forty-five had early postoperative infections (EPIs), 21 had chronic infections (CPIs), and 19 had hematogenous infections (HIs). Twenty (22.7%) were caused by methicillin-resistant S. aureus. High genotypic diversity was observed, including 16 clonal complexes (CCs), with CC5 being the most frequent (30.7%). agr activity was greater in EPI than CPI (55.6% vs 28.6%; P = .041). Strains causing EPI were phenotypically and genotypically similar, regardless of symptom duration. Treatment failure (36.5%) occurred less frequently among cases treated with implant removal. In cases treated with debridement and implant retention, there were fewer failures among those who received combination therapy with rifampin. No genotypic or phenotypic characteristics predicted failure, except vancomycin minimal inhibitory concentration ≥1.5 mg/L (23.1% failure vs 3.4%; P = .044). MBEC50 was >128 mg/L for all antibiotics tested and showed no association with prognosis. CONCLUSIONS: S. aureus with different genotypic backgrounds is capable of causing PJI, showing slight differences in clinical presentation and pathogenesis. No major microbiological characteristics were observed to influence the outcome, including MBEC.

Improving surgical antibiotic prophylaxis adherence and reducing hospital readmissions: a bundle of interventions including health information technologies.

OBJECTIVES: Infection following orthopaedic surgery is a feared complication and an indicator of the quality of the hospital. Surgical antibiotic prophylaxis (SAP) guidelines are not always properly followed. Our aim was to describe and evaluate the impact of a multidisciplinary intervention on antibiotic prophylaxis adherence to hospital guidelines and 30-day postoperative outcomes. METHODS: The study was carried out from January to May 2016 and consisted of creating a multidisciplinary team, updating institutional guidelines and embedding the recommendations in the computerised physician order entry system which is linked to dose and renal function alerts, educational activities and pharmaceutical bedside care of patients in the orthopaedic department. A prospective pre-post study was carried out in accordance with the Declaration of Helsinki. The following information was recorded: patient and surgery characteristics, adherence to SAP guidelines, surgical site infections, length of hospital stay and rate of readmission 30 days after discharge. Statistical analyses were performed using SPSS 18.0. RESULTS: Eighty three orthopaedic patients of mean±SD age 68.2±17.0 years (44.6% male, 40 in the pre-intervention group and 43 in the intervention group) were included. Cefazolin was the recommended and most commonly administered antibiotic agent. In the intervention group, an improvement in global adherence to guidelines was achieved (76.7% vs 89.9%; p=0.039): antibiotic duration (75.0% vs 97.7%), correct dosage post-surgery (55.0% vs 76.7%), timing of administration (57.5% vs 72.1%), antibiotic pre-surgery prescription (92.5% vs 97.7%). Three surgical site infections were detected in the pre-intervention group and none in the intervention group (p>0.05). Length of hospital stay was reduced by 1 day and readmission decreased by 15% (p=0.038). CONCLUSIONS: SAP is used in daily practice in most orthopaedic patients. The implementation of a multidisciplinary programme based on health technology improved the adherence to guidelines and appeared to reduce the readmission rate.

Current use of daptomycin and systematic therapeutic drug monitoring: Clinical experience in a tertiary care institution.

Therapeutic drug monitoring (TDM) could optimise daptomycin use. However, no validated serum target levels have been established. This prospective study at a tertiary centre including hospitalised patients receiving daptomycin aimed to evaluate the adequacy of daptomycin doses in a real-life study, assess interpatient variability in serum levels, identify predictive factors for non-adequate serum levels and assess their clinical impact. Blood samples [trough (Cmin) and peak (Cmax) levels] were drawn ≥3 days post-treatment initiation. Serum daptomycin concentrations were determined by HPLC. Outcome was classified as: (i) favourable, if clinical improvement or cure occurred with no adverse events; or (ii) poor, in the case of no clinical response, recurrence, related mortality or if adverse events were detected. Sixty-three patients (63.5% male; median age 63.0 years) were included. The most common indications for daptomycin use were bacteraemia (46.0%), complicated skin and soft-tissue infection (30.2%) and endovascular infection (15.9%). The initial dosage was adequate in 43 patients (68.3%), low in 14 (22.2%) and high in 6 (9.5%). Large interindividual variability in serum levels was observed, with a median Cmin of 10.6 mg/L (range 1.3-44.7 mg/L) and median Cmax of 44.0 mg/L (range 3.0-93.7 mg/L). Multivariate analysis showed that Cmin < 3.18 mg/L was independently related to poor outcome (OR = 6.465, 95% CI 1.032-40.087; P = 0.046). High variability in daptomycin use and serum levels was detected. Specific serum targets were identified as risk factors for poor outcome. TDM might be useful to optimise daptomycin doses and to avoid therapeutic failure.

The Not-So-Good Prognosis of Streptococcal Periprosthetic Joint Infection Managed by Implant Retention: The Results of a Large Multicenter Study.

BACKGROUND.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. METHODS.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. RESULTS.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using ß-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with ß-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). CONCLUSIONS.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of ß-lactams are confirmed and maybe also a potential benefit from adding rifampin.

Executive summary of management of prosthetic joint infections. Clinical practice guidelines by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) / Resumen ejecutivo de tratamiento de las infecciones de prótesis articulares. Guia clínica práctica de la Sociedad Española de Enfermedades Infecciosas y Microbiologia Clínica

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. The authors selected clinically relevant questions and then reviewed the available literature in order to give recommendations according to a pre-determined level of scientific evidence. The more controversial aspects were debated, and the final composition was agreed at an ad hoc meeting. Before its final publication, the manuscript was made available online in order that all SEIMC members were able to read it and make comments and suggestions

Se prevé un incremento de la incidencia de infección de las prótesis articulares (IPA) en los próximos años. Las IPA plantean graves consecuencias para los pacientes y un alto coste el sistema sanitario. La complejidad de estas infecciones hace que sea necesario organizar la inmensa cantidad de información publicada en los últimos años. En estas guías se revisan específicamente las indicaciones para la elección de una estrategia quirúrgica dada y el tratamiento antimicrobiano correspondiente. Los autores seleccionaron las preguntas clínicamente relevantes y revisaron la literatura disponible con el fin de proporcionar recomendaciones de acuerdo con un grado de evidencia científica predeterminada. Los aspectos más controvertidos fueron debatidos y la redacción final se acordó en una reunión ad hoc. Antes de su publicación, el manuscrito estuvo abierto a comentarios y sugerencias de los miembros de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica

Executive summary of management of prosthetic joint infections. Clinical practice guidelines by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

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. The authors selected clinically relevant questions and then reviewed the available literature in order to give recommendations according to a pre-determined level of scientific evidence. The more controversial aspects were debated, and the final composition was agreed at an ad hoc meeting. Before its final publication, the manuscript was made available online in order that all SEIMC members were able to read it and make comments and suggestions.

Is the Commercial Antibiotic-Loaded Bone Cement Useful in Prophylaxis and Cost Saving After Knee and Hip Joint Arthroplasty? The Transatlantic Paradox.

BACKGROUND: The use of antibiotic-loaded bone cement (ALBC) has proven to be effective in preventing periprosthetic infection (PPI) after total hip (THA) and knee arthroplasty (TKA). However, the economic benefit of using ALBC routinely remains controversial. METHODS: A total of 2518 patients subjected to THA, partial hip arthroplasty, and TKA between 2009 and 2012 were identified in our prospectively collected registry. Two groups were defined: before (2009-2010) and after the introduction of ALBC (2011-2012). The risks of PPI associated with each type of surgery in each group were determined and compared. Patients subjected to THA without cemented implants were used as controls, and possible bias associated with changes in infection rate during the study period and other variables were controlled. The costs of the use of ALBC were calculated, along with the savings per case of PPI avoided. The minimum follow-up for discarding PPI was 2 years. RESULTS: Following the introduction of ALBC, a global decrease of 57% was observed in the risk of PPI (P = .001). By type of surgery, the decrease was 60.6% in the case of TKA (P = .019) and 72.6% in the case of cemented hip arthroplasty (partial and total; P = .009). No decrease in infection rate was noted in uncemented hip arthroplasty (P = .42). The total saving associated with the use of ALBC was €1,123,846 (€992 per patient): €440,412 after TKA (€801 per patient) and €686,644 after cemented hip arthroplasty (€2672 per patient). CONCLUSION: The use of ALBC has been found to be effective in preventing PPI after TKA and hip arthroplasty, with a favorable cost-efficiency profile using standardized cost and infection rates in our setting.

Short- versus long-duration levofloxacin plus rifampicin for acute staphylococcal prosthetic joint infection managed with implant retention: a randomised clinical trial.

Levofloxacin plus rifampicin (L+R) is the treatment of choice for acute staphylococcal prosthetic joint infection (PJI) managed with debridement and implant retention (DAIR). Long courses have been empirically recommended, but some studies have suggested that shorter treatments could be as effective. Our aim was to prove that a short treatment schedule was non-inferior to the standard long schedule. An open-label, multicentre, randomised clinical trial (RCT) was performed. Patients with an early post-surgical or haematogenous staphylococcal PJI, managed with DAIR and initiated on L+R were randomised to receive 8 weeks of treatment (short schedule) versus a long schedule (3 months or 6 months for hip or knee prostheses, respectively). The primary endpoint was cure rate. From 175 eligible patients, 63 were included (52% women; median age, 72 years): 33 patients (52%) received the long schedule and 30 (48%) received the short schedule. There were no differences between the two groups except for a higher rate of polymicrobial infection in the long-schedule group (27% vs. 7%; P = 0.031). Median follow-up was 540 days. In the intention-to-treat analysis, cure rates were 58% and 73% in patients receiving the long and short schedules, respectively (difference -15.7%, 95% CI -39.2% to 7.8%). Forty-four patients (70%) were evaluable per-protocol: cure rates were 95.0% and 91.7% for the long and short schedules, respectively (difference 3.3%, 95% CI -11.7% to 18.3%). This is the first RCT suggesting that 8 weeks of L+R could be non-inferior to longer standard treatments for acute staphylococcal PJI managed with DAIR.

Differences between a probable and proven BCG infection following intravesical instillations: 16 years experience in a tertiary care hospital.

BACKGROUND: Intravesical instillation of Bacillus Calmette-Guérin (BCG) is an efficient immunotherapy for superficial bladder cancer. BCG infection represents a major yet uncommon adverse event that occurs in 5-10% of the patients treated with BCG instillations, though the pathogenesis of this entity is not clear. METHODS: We report two cases of patients presented at our institution with BCG infection after instillation: one with microbiological BCG isolate and another without, and review all the medical records of patients instilled with BCG in our institution from 1996 until 2012, comparing patients with probable and proven BCG infection. RESULTS: During the study period, a total of 786 patients received BCG intravesical instillations. Of them, 31 (4%) patients had to suspend treatment because of adverse events and, specifically, 11 (1.3%) patients had to interrupt treatment because of suspected BCG infection. The incidence of BCG infection during our study period was 0.87 episodes per 1,000 instilled patients/year and 140 cases per 10,000 instilled patients. Of the 11 patients with suspected BCG infection, 7 (64%) had a probable BCG infection, while 4 (36%) patients had a proven BCG infection. All patients with a proven infection had a previous underlying condition, compared to a high proportion of patients with probable infection (57%) that did not present with underlying diseases. Common findings between both groups of patients were abnormal imaging studies and laboratory tests. Regarding treatment, 8 (73%) of the 11 patients with BCG infection received at least two first line drugs active against M. bovis (isoniazid, rifampicin or ethambutol), four patients (36%) received steroids as part of the treatment and curation was obtained in 10 (91%) patients, while 1 patient with a proven infection had a death related to BCG infection. CONCLUSIONS: We can conclude that BCG infection after intravesical instillations has a low incidence in our institution. Patients with previous underlying conditions seem to have more proven infections. A high proportion of patients do not yield positive microbiological tests; in those cases the diagnosis relies in clinical, radiological and laboratory findings. Treatment for BCG infection should include at least two active drugs against M. bovis and coadjuvant steroid treatment for systemic BCG infections.

First case of autochthonous Clostridium difficile PCR ribotype 027 detected in Spain / Primer caso autóctono de Clostridium difficile del ribotipo 027 detectado en España

INTRODUCTION: Clostridium difficile ribotype 027 (Cd027) has caused outbreaks in the United States, Canada, and Europe since 2001. In Spain, the importance of Cd027 is still unknown. In 2007, we began active surveillance of Cd027 to determine its incidence in our hospital. Methods From January 2007 to April 2012, isolates of C. difficile by multiplex PCR were studied to detect toxin genes. Binary toxin-positive isolates were characterized using PCR-ribotyping. Cd027 were further characterized by toxino-typing, sequencing of tcdC gene, and MLVA (multilocus-variable-number-tandem-repeat-analysis).Results Only 8 strains were Cd027 from 3666 isolates of C. difficile analyzed during the study period. These strains were isolated from 4 patients: a Spanish patient previously hospitalized in the UK, a pregnant laboratory technician, a British tourist, and a Spanish patient without epidemiological antecedents for acquiring Cd027. MLVA typing of Cd027 isolates revealed 4 different patterns. The first patient had 2 episodes of diarrhea caused by different Cd027. The strains from the first episode of patient 1 and the strain from patient 2 were grouped in the same clonal cluster (these cases were previously published as laboratory transmission), while strains from patients 3 and 4 were genetically unrelated to each other, and to the strains from patients 1 and 2.ConclusionWe report the first finding of an autochthonous case of non-severe Cd027 infection. Our results indicate that Cd027 diarrhea is uncommon in our area, and it appears mainly as imported cases. MLVA typing enables us to distinguish different genotypes among our Cd027 isolates

INTRODUCCIÓN: Clostridium difficile del ribotipo 027 (Cd027) ha causado importantes brotes en EE. UU, Canadá y Europa desde 2001. Actualmente su importancia en España es poco conocida. En 2007, nuestro grupo inició la búsqueda de Cd027 para determinar su incidencia en nuestro hospital. MÉTODOS: Desde enero de 2007 hasta abril de 2012 se estudiaron todos los aislados de C. difficile mediante PCR multiplex de los genes de las toxinas. Las cepas toxina binaria positivas se caracterizaron por PCR-ribotipado. Las cepas de Cd027 encontradas se genotiparon por toxinotipo, secuenciación del gen tcdC y MLVA. RESULTADOS: Durante el periodo de estudio se analizaron 3.666 cepas de C. difficile de las que solo 8 fueron Cd027. Estas cepas se aislaron de 4 pacientes: una paciente española previamente hospitalizada en el Reino Unido, una técnico de nuestro laboratorio, una turista británica y un paciente español sin antecedentes de riesgo para haber adquirido Cd027. Mediante MLVA obtuvimos 4 patrones de tipado diferentes. La primera paciente tuvo 2 episodios de diarrea causados por cepas diferentes de Cd027. Una de estas cepas fue la misma que la de nuestra técnico de laboratorio (este caso está publicado como una transmisión de laboratorio). Las cepas de los pacientes 3 y 4 tuvieron MLVA únicos. CONCLUSIÓN: En este trabajo describimos el primer autóctono de diarrea causada por Cd027. Nuestros resultados indican que es infrecuente en nuestro medio y que aparece principalmente como casos importados. El tipado por MLVA nos ha permitido diferenciar genotipos diferentes entre los aislados de Cd027 de nuestro hospital