Incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infection in European hospitals: the COMBACTE-NET ARTHR-IS multi-centre study.

BACKGROUND: The aim of this study was to estimate the incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infections (SA-PJI) after primary hip and knee arthroplasty in European centres. METHODS: This study was conducted in patients who underwent primary hip and knee arthroplasty in 19 European hospitals between 2014 and 2016. The global incidence of PJI and SA-PJI was calculated. The associated disease burden was measured indirectly as infection-related mortality plus loss of function. For healthcare utilization, number and duration of hospitalizations, number and type of surgical procedures, duration of antibiotic treatments, and number of outpatient visits were collected. Subgroup and regression analyses were used to evaluate the impact of SA-PJI on healthcare utilization, controlling for confounding variables. RESULTS: The incidence of PJI caused by any micro-organism was 1.41%, and 0.40% for SA-PJI. Among SA-PJI, 20.7% were due to MRSA with substantial regional differences, and were more frequent in partial hip arthroplasty (PHA). Related deaths and loss of function occurred in 7.0% and 10.2% of SA-PJI cases, respectively, and were higher in patients with PHA. Compared with patients without PJI, patients with SA-PJI had a mean of 1.4 more readmissions, 25.1 more days of hospitalization, underwent 1.8 more surgical procedures, and had 5.4 more outpatient visits, controlling for confounding variables. Healthcare utilization was higher in patients who failed surgical treatment of SA-PJI. CONCLUSIONS: This study confirmed that the SA-PJI burden is high, especially in PHA, and provided a solid basis for planning interventions to prevent SA-PJI.

Vertebral osteomyelitis after spine instrumentation surgery: risk factors and management.

BACKGROUND: Vertebral osteomyelitis after spine instrumentation surgery (pVOM) is a rare complication. Most cases of infection occur early after surgery that involve skin and soft tissue and can be managed with debridement, antibiotics, and implant retention (DAIR). AIM: To identify pVOM risk factors and evaluate management strategies. METHODS: From a multicentre cohort of deep infection after spine instrumentation (IASI) cases (2010-2016), pVOM cases were compared with those without vertebral involvement. Early and late infections were defined (<60 days and >60 days after surgery, respectively). Multivariate analysis was used to explore risk factors. FINDINGS: Among 410 IASI cases, 19 (4.6%) presented with pVOM, ranging from 2% (7/347) in early to 19.1% (12/63) in late IASIs. After multivariate analysis, age (adjusted odds ratio (aOR): 1.10; 95% confidence interval (CI): 1.03-1.18), interbody fusion (aOR: 6.96; 95% CI: 2-24.18) and coagulase-negative staphylococci (CoNS) infection (aOR: 3.83; 95% CI: 1.01-14.53) remained independent risk factors for pVOM. Cases with pVOM had worse prognoses than those without (failure rate; 26.3% vs 10.8%; P = 0.038). Material removal was the preferred strategy (57.9%), mainly in early cases, without better outcomes (failure rate; 33.3% vs 50% compared with DAIR). Late cases managed with removal had greater success compared with DAIR (failure rate; 0% vs 40%; P = 0.067). CONCLUSION: Risk factors for pVOM are old age, use of interbody fusion devices and CoNS aetiology. Although the diagnosis leads to a worse prognosis, material withdrawn should be reserved for late cases or when spinal fusion is achieved.

P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial.

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).

Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia.

BACKGROUND: The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. METHODS: We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. RESULTS: A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. CONCLUSIONS: Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).

Suppressive antibiotic therapy in prosthetic joint infections: a multicentre cohort study.

OBJECTIVES: The aim was to describe the effectiveness of suppressive antibiotic treatment (SAT) in routine clinical practice when used in situations in which removal of a prosthetic implant is considered essential for the eradication of an infection, and it cannot be performed. METHODS: This was a descriptive retrospective and multicentre cohort study of prosthetic joint infection (PJI) cases managed with SAT. SAT was considered to have failed if a fistula appeared or persisted, if debridement was necessary, if the prosthesis was removed due to persistence of the infection or if uncontrolled symptoms were present. RESULTS: In total, 302 patients were analysed. Two hundred and three of these patients (67.2%) received monotherapy. The most commonly used drugs were tetracyclines (39.7% of patients) (120/302) and cotrimoxazole (35.4% of patients) (107/302). SAT was considered successful in 58.6% (177/302) of the patients (median time administered, 36.5 months; IQR 20.75-59.25). Infection was controlled in 50% of patients at 5 years according to Kaplan-Meier analysis. Resistance development was documented in 15 of 65 (23.1%) of the microbiologically documented cases. SAT failure was associated with age <70 years (sub-hazard ratio (SHR) 1.61, 95% CI 1.1-2.33), aetiology other than Gram-positive cocci (SHR 1.56, 95% CI 1.09-2.27) and location of the prosthesis in the upper limb (SHR 2.4, 95% CI 1.5-3.84). SAT suspension was necessary due to adverse effects in 17 of 302 patients (5.6%). CONCLUSIONS: SAT offers acceptable results for patients with PJI when surgical treatment is not performed or when it fails to eradicate the infection.

Anthropometrical study of the human glenoid in a normal Spanish population. / Estudio antropométrico de la glena humana en una población española normal.

OBJECTIVE: To evaluate the size of the glenoid in a southern Spanish population, to compare it with previous results from other populations and determine the size of the implants that are marketed for shoulder arthroplasty. MATERIAL AND METHODS: Between January 2015 and December 2017, an anthropometrical study of the human glenoid was performed using computed axial tomography scans (CT) of 154 patients over 30 years old. The glenoid dimensions were analysed 3-dimensionally using 2mm interval thicknesses, determining the average height and width of the glenoid. The upper point of the glenoid geometry was determined as the supraglenoid tubercle of the ovoid glenoid surface, where the long head of the biceps tendon is thought to originate. The lower point was then positioned at the furthest point from the upper point on the glenoid contour. Anterior and posterior points were determined such that the 3-dimensional anterior-posterior distance was maximized on the plane perpendicular to the upper-lower axis. Sex differences and correlations between sides and among the respective parameters in the glenohumeral dimensions were also evaluated. RESULTS: The glenoid had an average height of 28.78mm and width of 20.27mm. The values were significantly different between the men and the women, being greater in the men. The glenoid size is well correlated with the patient's size. Direct correlations exist between the glenoid height and width and the glenoid size and the patient's height. The available metaglenoids currently on the market are no bigger than 25-24mm. CONCLUSION: In comparison, the southern Spanish population have a glenoid size similar to the Caucasian population, but smaller than that of the American population. The data shown could be useful to improve the design of shoulder prostheses for the southern Spanish population.

Outcomes of rotator cuff augmentation surgery with autologous fascia lata. / Resultados de la cirugía de refuerzo del manguito rotador con fascia lata autógena.

OBJECTIVE: To evaluate whether augmentation grafts using autologous fascia lata improve functional results for rotator cuff repairs and reduce the retear rate compared to those without augmentation. MATERIAL AND METHODS: This is a prospective evaluation comprising 20 patients with a complete symptomatic rotator cuff tear. The operations were carried out from a superior approach performing a total cuff repair, for 10 patients we used a suture augmented with an autologous graft taken from their own fascia lata while unaugmented sutures were used for the other 10 patients. The follow-up period lasted for one year post-intervention. We measured variables for tear type, functionality and pain, both baseline and at 6 and 12-month follow ups. We evaluated retear incidence in each group as well as each group's pain and functionality response. RESULTS: The improved pain levels in the non-graft group evolved gradually over time. Conversely, in the group with the augmentation grafts, average Constant-Murley shoulder outcome scores at six months were already above 10 and were maintained at 12 months. One retear occurred in the graft group and 2 in the group without grafts, thus presenting no significant differences. There were no significant changes in pain and function values at the one year follow up in either group. CONCLUSION: Our preliminary results regarding rotator cuff augmentation surgery with autologous fascia lata showed a significant improvement in pain levels after 6 months compared to the patients with no augmentation, who required 12 months to reach the same values. After a year of follow up, there were no differences between the mean Constant and pain scores in either intervention group The number of retears in the non-graft group was greater than that in the group with grafts although the difference was not significant.

Effect of tranexamic acid administration on bleeding in primary total hip arthroplasty. / Efecto de dosis única intravenosa de ácido tranexámico sobre el sangrado en artroplastia total de cadera. Estudio prospectivo, controlado y aleatorizado.

OBJECTIVE: To study the efficacy of tranexamic acid to decrease perioperative bleeding in patients who have undergone a total hip arthroplasty operation and to evaluate drug safety. MATERIAL AND METHODS: Observational, prospective, controlled and randomized study on the efficacy of tranexamic acid as a method to reduce bleeding in primary hip replacement surgery. We included 134 patients operated during 2014 in our centre, who were divided into 2 groups according to whether or not they had received tranexamic acid. The main study variables were haemoglobin and haematocrit levels, the amount of blood collected from the post-operative drain in the first 12, 24 and 48hours and transfusion requirements. RESULTS: Post-operative haemoglobin and haematocrit levels were statistically higher (P<.001) in the group with treatment. During the first 48hours bleeding values from the group that did not receive TAX were higher compared to patients treated with tranexamic acid. Statistically significant differences (P=.001) were found as to the need for transfusion according to group, more transfusions were performed in the cohort that had not received tranexamic acid: 25.37% compared to 4.48% for the group with tranexamic acid. No adverse events related to administration of tranexamic acid were recorded. CONCLUSIONS: Administration of tranexamic acid has proved to be an effective and safe method to reduce peri-operative bleeding in patients who underwent total hip arthroplasty and avoids allogenic blood transfusion. Therefore, tranexamic acid treatment could entail a financial saving for the healthcare system and expose the patient to less risk.

Coronal patellar osteotomy of the external facet combined with the release of the lateral retinaculum improves the clinical outcomes of isolated lateral release in lateral knee compartment syndrome. / La osteotomía patelar coronal de la faceta externa asociada a liberación del retináculo lateral mejora los resultados clínicos de la liberación lateral aislada en el síndrome de compresión lateral de rótula.

OBJECTIVE: To describe a novel coronal osteotomy of the external facet of the patella, and to evaluate if the outcomes of the treatment of lateral knee compartment syndrome (LKCS) with this osteotomy, combined with the release of the external lateral retinaculum, are better than the isolated lateral retinacular release. MATERIAL AND METHODS: A prospective study with a 2 year follow up that included 70 patients diagnosed with LKCS, distributed into 2 groups. The first group included 50 patients on whom the lateral retinacular release combined with osteotomy was performed, and a second group on whom an isolated retinacular release was performed. Measurements were made using the Werner functional scale before the surgery and at 3, 12, and 24 months follow-up. RESULTS: There were significant differences in the overall functional state between the two groups after the surgery (better in the osteotomy group at all the intervals, P<.05). The improvement, which was progressive up to 12 months, was slightly less at 24 months, although the values were still better than the pre-surgical ones in both groups. Pain was the variable that showed most improvement. The patients with LKCS with degenerative signs showed a benefit in all cases. CONCLUSION: The results demonstrate that the described patellar osteotomy technique, combined with lateral retinacular release, significantly improves the pain and the functional scale score of patients with LKCS after 2 years of follow-up, to a greater extent than isolated lateral retinacular release, including those in which there was evidence of degenerative signs.

Acute Effects of Nasal CPAP in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common genetic disease that may cause left ventricular outflow tract (LVOT) obstruction, heart failure, and sudden death. Recent studies have shown a high prevalence of OSA among patients with HCM. Because the hemodynamics in patients with LVOT obstruction are unstable and depend on the loading conditions of the heart, we evaluated the acute effects of CPAP on hemodynamics and cardiac performance in patients with HCM. METHODS: We studied 26 stable patients with HCM divided into nonobstructive HCM (n = 12) and obstructive HCM (n = 14) groups (LVOT gradient pressure lower or higher than 30 mm Hg, respectively). Patients in the supine position while awake were continuously monitored with beat-to-beat BP measurements and electrocardiography. Two-dimensional echocardiography was performed at rest (baseline) and after 20 min of nasal CPAP at 1.5 cm H2O and 10 cm H2O, which was applied in a random order interposed by 10 min without CPAP. RESULTS: BP, cardiac output, stroke volume, heart rate, left ventricular ejection fraction, and LVOT gradient did not change during the study period in either group. CPAP at 10 cm H2O decreased right atrial size and right ventricular relaxation in all patients. It also decreased left atrial volume significantly and decreased right ventricular outflow acceleration time, suggesting an increase in pulmonary artery pressure in patients with obstructive HCM. CONCLUSIONS: The acute application of CPAP is apparently safe in patients with HCM, because CPAP does not lead to hemodynamic compromise. Long-term studies in patients with HCM and sleep apnea and nocturnal CPAP are warranted. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01631006; URL: www.clinicaltrials.gov.

The changing epidemiology of bacteraemic osteoarticular infections in the early 21st century.

Osteoarticular infections (OAI), which are often associated with bacteraemia, seem to be increasing. We studied all patients with bacteraemia and concomitant OAI: septic arthritis (SA), vertebral osteomyelitis (VOM) or peripheral osteomyelitis (POM), which were seen at our institution (1985-2011). Data were extracted from a prospective protocol of bacteraemia cases recorded. Trends in main findings were considered in five periods. Major antibiotic resistance patterns were studied. A total of 601 cases of bacteraemic OAI, accounting for 1.8% of total bactaeremias, were studied: SA (48%), VOM (40%) and POM (17%). When comparing the 1985-91 and 2007-11 periods, the incidence of bacteraemic OAI increased from 2.34 to 5.78 episodes/100 000 inhabitants per year (p <0.001); and nosocomial and healthcare-related cases increased from 18% to 30% (p <0.001) and from 10% to 25% (p <0.001), respectively. Also, there was an increase of age (median, from 49 to 65 years, p <0.001), patients with comorbidities (23% to 59%, p <0.001), and device-related OAI (7% to 28%, p <0.001). Patterns of OAI were changing over time. Compared with younger patients, older adults (≥ 65 years) had more VOM, prosthetic-joint infections and enterococcal OAI. The percentage of OAI caused by methicillin-susceptible Staphylococcus aureus decreased, while those caused by methicillin-resistant S. aureus, streptococci, enterococci, and Gram-negative bacilli increased. There was a link between certain microorganisms with specific OAI and age of patients. Over the past three decades, bacteraemic OAI increased in association with aging and use of orthopaedic devices. Nosocomial and healthcare-related OAI increased, with a rise in multidrug-resistant bacteria. These trends should be considered when planning diagnostic and therapeutic guidelines for OAI.

Clinical and microbiological findings in prosthetic joint replacement due to aseptic loosening.

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: Group1: (≥2 positive-TS; n = 12); Group2: single positive-TS and concordant SF (n = 10); Group3: one positive or non-concordant TS or SF (n = 38); and Group4: 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.

Streptococcal vertebral osteomyelitis: multiple faces of the same disease.

The role of Streptococcus species as an aetiological microorganism of vertebral osteomyelitis (VO) is considered to be of little relevance. We aimed to describe a large number of cases of streptococcal vertebral osteomyelitis (SVO), to analyze the clinical features associated with different Streptococcus species, and to compare them with a cohort of patients with VO caused by Staphylococcus aureus. An incidence study and a retrospective, multicenter, observational clinical study of cases of SVO (1991-2011) were performed. Statistical comparison of SVO by different species and between them and staphylococcal VO was carried out. Over the whole period there was an increasing incidence in the number of VOs and SVOs per year (p <0.05). Among 58 cases of SVO, those caused by non-viridans streptococcus (Streptococcus pneumoniae, Streptococcus agalactiae and Streptococcus pyogenes; n = 26) mimicked VO by S. aureus, and presented with more fever, neurological symptoms and paravertebral abscesses in comparison with those caused by the viridans group (remaining species). In contrast, the latter have a sub-acute clinical picture and were associated with the presence of endocarditis (p <0.05). Among non-viridans SVOs, concomitant infection was specifically related to S. pneumoniae (p <0.05). In conclusion, SVO presents a wide range of clinical patterns. The relationship between VO and diagnosis of endocarditis was established with SVO caused by the viridans group. Whereas non-viridans SVO mimics acute characteristics of VO caused by S. aureus, cases of viridans SVO are significantly more likely to have a sub-acute clinical presentation. The increased incidence of SVO during the last decades could support a new epidemiological scenario.

Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy.

OBJECTIVE: Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy. METHODS: Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth) and overnight portable monitoring. Ninety patients (males, 51%; age, 46±15 years; body mass index, 26.6±4.9 kg/m2) were included, and obstructive sleep apnea (respiratory disturbance index ≥15 events/h) was present in 37 patients (41%). RESULTS: Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale) was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis) were age ≥45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47-13.54; p = 0.008) and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43-20.12; p = 0.013]. CONCLUSION: Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation.

Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy

OBJECTIVE: Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy. METHODS: Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth) and overnight portable monitoring. Ninety patients (males, 51%; age, 46±15 years; body mass index, 26.6±4.9 kg/m2) were included, and obstructive sleep apnea (respiratory disturbance index ≥15 events/h) was present in 37 patients (41%). RESULTS: Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale) was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis) were age ≥45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47-13.54; p = 0.008) and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43-20.12; p = 0.013]. CONCLUSION: Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation. .

Fosfomycin-daptomycin and other fosfomycin combinations as alternative therapies in experimental foreign-body infection by methicillin-resistant Staphylococcus aureus.

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.

Efficacy of daptomycin-cloxacillin combination in experimental foreign-body infection due to methicillin-resistant Staphylococcus aureus.

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.