The diary in the intensive care unit: Concept analysis.

INTRODUCTION: Admission to an intensive care unit can cause sequelae to both patients and family members. In some countries, the use of diaries is a preventive action. AIM: This research proposes to critically examine the concept of 'Intensive Care Unit Diary' by analysing the current state of the scientific literature to develop a precise conception of this phenomenon in nursing practice, since there are multiple unknowns regarding its use and content. METHOD: A bibliographic search was carried out in the PubMed, Cochrane Library, Scopus and CINAHL databases in January 2023. The terms used to search for their use and definitions in the databases included Nurse, Concept analysis, Family, Uci Diary, Patient Critical, Intensive Care Unit. We use Wilson's concept analysis, later developed by Walker and Avant. RESULTS: The concept analysis shows that the 'ICU Diary' is a record made in colloquial language by health workers and relatives of the patient admitted to the intensive care unit. Aimed at the patient, with an empathic and reflective style, which offers a narrative of the process, daily life and the conduct or behaviour of the patient during his stay. It is a therapeutic tool led by nurses accepted by patients, families and professionals. Its use benefits the recovery process, reducing post-traumatic stress in family members and patients. It favours communication and the bond between nurses, family members and patients, helping to express feelings and emotions. CONCLUSIONS: The concept of 'UCI Diary' is complex. Through Wilson's model, a clarification of the concept has been achieved, creating a starting point for more precise research on this phenomenon and its effects on patients, family members, professionals and the health system.

Relación entre dismenorrea y síndrome de dolor miofascial. Perspectiva desde la fisioterapia. Estudio piloto aleatorizado / Relationship between dysmenorrhoea and Myofascial Pain Syndrome. A physiotherapist perspective. Pilot randomized trial

La dismenorrea es el conjunto de síntomas que se pueden padecer durante la menstruación, siendo el más característico un dolor intenso. El síndrome de dolor miofascial es el conjunto de signos y síntomas que producen los puntos gatillo miofasciales (PGM) tanto en su localización como a distancia, entre otros el dolor. Por lo tanto, el objetivo del estudio es estudiar la eficacia del tratamiento fisioterápico de los PGM en musculatura abdominal, aductora y del suelo pélvico para con la afectación de las variables de dolor, función sexual, calidad de vida, fuerza y movimiento en pacientes con dismenorrea. MATERIAL Y MÉTODOS: Estudio piloto aleatorizado. Se dividió a las participantes entre un grupo A (n = 6) donde se aplicó punción seca y terapia manual en musculatura abdominal, aductora de la cadera y suelo pélvico y grupo B (n = 7) donde se aplicó termoterapia y estiramientos en la misma musculatura. Las variables estudiadas fueron: dolor menstrual, función sexual, calidad de vida, rango de abducción de cadera, fuerza muscular, resistencia del suelo pélvico y existencia de puntos gatillo miofasciales. Una fisioterapeuta realizó los tratamientos y otra las valoraciones, estando cegada la segunda. RESULTADOS: el grupo A obtuvo una diferencia clínica (1,6 puntos menos en EVA) y estadísticamente significativa del dolor (p = 0,018), frente al otro grupo (0,4 puntos, p > 0,05), así como una mejora en la calidad de vida (p < 0,05) del grupo A. No se hallaron cambios significativos en el resto de las variables. CONCLUSIÓN: existe un alivio significativo del dolor y mejora de la calidad de vida del grupo A. Se considera así que el tratamiento específico del síndrome de dolor miofascial puede presentar mayor eficacia clínica. Se concluye la necesidad de continuar esta investigación con una mayor muestra de participantes, con el fin de esclarecer la eficacia del tratamiento de fisioterapia para el resto de las variables estudiadas

The term dysmenorrhoea defines different symptoms that women can feel during menstruation, the most common being intense pain. Myofascial pain syndrome (MPS) is the combination of signs and symptoms caused by myofascial trigger points (MTP), at their site or at a distance. Therefore, the objective of this study is to evaluate the efficacy of a treatment for MTP in the abdominal, hip adductor and pelvic floor muscles, from a physiotherapeutic approach, regarding the following outcome measures: pain, sexual function, quality of life, strength and mobility in patients suffering from dysmenorrhoea. MATERIALS AND METHODS: Randomized pilot study. Participants were divided into two groups: A (n = 6), where dry needling and manual therapy was applied to the abdominal, hip adductor and pelvic floor muscles; and B (n = 7), where the participants received thermotherapy and stretching of these muscles. The outcome measures studied were menstrual pain, sexual function, quality of life, hip abduction range of motion, strength of the affected muscles, pelvic floor muscle endurance and finding myofascial trigger points. All the treatments were provided by the same physiotherapist, while a different physiotherapist carried out the evaluations blinded to each patient's group. RESULTS: in group A, a clinically (1.6 less in VAS) and statistically significant reduction (p = 0.018) in pain was observed in comparison with group B (.4 in VAS, p > 0.05). Quality of life also improved in the first group (p< 0.05). No further significant differences were found in the remaining outcome measures. CONCLUSIONS: a significant improvement was observed with regards to pain and quality of life in group A. Thus, we consider that specific treatment for MPS could be more clinically effective. We conclude that this research should be continued with a larger sample of participants, in order to clarify the efficacy of the physiotherapy treatment suggested for the remaining outcome measures

Staphylococcus aureus meningitis in adults: A comparative cohort study of infections caused by meticillin-resistant and meticillin-susceptible strains.

BACKGROUND: Staphylococcus aureus meningitis is an uncommon nosocomial infection usually associated with neurosurgical procedures, but spontaneous infections may occasionally appear. AIMS: To compare the features of meningitis caused by meticillin-resistant (MRSA) and meticillin-susceptible (MSSA) S. aureus and examine the prognostic factors for mortality, including MRSA infection and combined antimicrobial therapy. METHODS: Retrospective cohort study of 350 adults with S. aureus meningitis admitted to 11 hospitals in Spain (1981-2015). Logistic regression and propensity score matching were used to analyse prognostic factors. RESULTS: There were 118 patients (34%) with MRSA and 232 (66%) with MSSA. Postoperative infection (91% vs 73%) and nosocomial acquisition (93% vs 74%) were significantly more frequent in MRSA than in MSSA meningitis (P < 0.001). Combined therapy was given to 118 (34%) patients. Overall 30-day mortality rate was 23%. On multivariate analysis, mortality was associated with severe sepsis or shock (odds ratio (OR) 9.9, 95% confidence interval (CI) 4.5-22.0, P < 0.001), spontaneous meningitis (OR 4.2, 95% CI 1.9-9.1, P < 0.001), McCabe-Jackson score rapidly or ultimately fatal (OR 2.8, 95% CI 1.4-5.4, P = 0.002), MRSA infection (OR 2.6, 95% CI 1.3-5.3, P = 0.006), and coma (OR 2.6, 95% CI 1.1-6.1, P < 0.029). In postoperative cases, mortality was related to retention of cerebrospinal devices (OR 7.9, 95% CI 3.1-20.3, P < 0.001). CONCLUSIONS: Clinical and epidemiological differences between MRSA and MSSA meningitis may be explained by the different pathogenesis of postoperative and spontaneous infection. In addition to the severity of meningitis and underlying diseases, MRSA infection was associated with increased mortality. Combined antimicrobial therapy was not associated with increased survival.

Experimental study of cerebrospinal fluid tumor necrosis factor-alpha release in penicillin- and cephalosporin-resistant pneumococcal meningitis treated with different antibiotic schedules.

BACKGROUND/PURPOSE: To measure the inflammatory response in terms of tumor necrosis factor-alpha (TNF-α) levels in cerebrospinal fluid (CSF), using bacteriolytic versus nonbacteriolytic antibiotic therapy and adjunctive treatment with dexamethasone in an experimental rabbit model of pneumococcal meningitis. METHODS: In a rabbit model of pneumococcal meningitis, we tested CSF TNF-α levels in several samples from rabbits infected with the HUB 2349 strain and treated with ceftriaxone 100 mg/kg/d, ceftriaxone plus vancomycin 30 mg/kg/d, or daptomycin at 15 mg/kg or 25 mg/kg. Daptomycin schedules were compared with the same doses in combination with dexamethasone at 0.125 mg/kg every 12 hours over a 26-hour period. RESULTS: The ceftriaxone group had the highest levels of TNF-α. TNF-α levels were significantly higher after ceftriaxone administration than in both daptomycin groups. The high-dose daptomycin group presented the lowest inflammatory levels in CSF samples. Adjunctive treatment with dexamethasone in this group modulated the inflammatory response, bringing down CSF TNF-α levels. CONCLUSION: CSF TNF-α levels were significantly lower in rabbits treated with daptomycin than in rabbits treated with ceftriaxone. Daptomycin avoided the inflammatory peak after administration observed in ceftriaxone-treated rabbits. The use of daptomycin plus dexamethasone achieved a significantly larger reduction in CSF TNF-α levels.

Aplicación y evaluación del plan de cuidados en pacientes ingresados en la unidad de cuidados intensivos / Application and evalauation of care plan for patients admitted to Intensive Care Units

Objetivo: Evaluar si la utilización de un plan de cuidados (PC) mejora los resultados de los cuidados enfermeros en pacientes ingresados en la unidad de cuidados intensivos (UCI). Material y métodos: Estudio piloto pre y post. Muestra: 121 pacientes ingresados en la UCI. Sesenta y un pacientes del grupo preintervención y 55 pacientes del grupo postintervención a los cuales se les aplicó el PC. Se utilizó un mapa de indicadores de calidad (IC) específicos de una UCI médica para evaluar la práctica clínica enfermera y el test exacto de Fisher para comparar grado de asociación entre los IC en los 2 grupos. El nivel de significación estadística aceptado fue del 5% (p < 0,05). Resultados: Se evaluaron 116 registros de 121 pacientes: 61 preintervención y 55 postintervención. Test de Fisher: cumplimentación de los registros de enfermería p = 0,0003. Revisión del carro de parada cardíaca (PCR) p < 0,001. Bacteriemia relacionada con catéter venoso central (CVC) p = 0,622. Neumonía asociada a ventilación mecánica invasiva (VMI) p = 1.000. Posición semiincorporada en pacientes con VMI p = 0,049 y el manejo de la analgesia en el paciente no sedado con dolor p = 0,082. Conclusiones: La aplicación de un PC enfermero en los pacientes ingresados en la UCI puede contribuir a la mejora en los resultados de los cuidados enfermeros

Objective: Assess whether the use of the nursing care plans improves outcomes of nursing care to patients admitted to the intensive care unit (ICU). Methods: The study was conducted in a University Hospital of Barcelona in Spain, using a pre- and post-study design. A total of 61 patient records were analysed in the pre-intervention group. A care plan was applied to 55 patients in the post-intervention group. Specific quality indicators in a medical intensive care unit to assess the clinical practice of nursing were used. Fisher's exact test was used to compare the degree of association between quality indicators in the two groups. Results: A total of 116 records of 121 patients were evaluated: 61 pre-intervention and 55 post-intervention. Fisher test: The filling of nursing records, p = .0003. Checking cardiorespiratory arrest equipment, p< .001. Central vascular catheter related bacteraemia (B-CVC) p = .622. Ventilator associated pneumonia (VAP) p = .1000. Elevation of the head of the bed more than 30° p = .049, and the pain management in non-sedated patients p = .082. Conclusions: The implementation of nursing care plans in patients admitted to the intensive care area may contribute to improvement in the outcomes of nursing care

[Application and evalauation of care plan for patients admitted to Intensive Care Units]. / Aplicación y evaluación del plan de cuidados en pacientes ingresados en la unidad de cuidados intensivos.

OBJECTIVE: Assess whether the use of the nursing care plans improves outcomes of nursing care to patients admitted to the intensive care unit (ICU). METHODS: The study was conducted in a University Hospital of Barcelona in Spain, using a pre- and post-study design. A total of 61 patient records were analysed in the pre-intervention group. A care plan was applied to 55 patients in the post-intervention group. Specific quality indicators in a medical intensive care unit to assess the clinical practice of nursing were used. Fisher's exact test was used to compare the degree of association between quality indicators in the two groups. RESULTS: A total of 116 records of 121 patients were evaluated: 61 pre-intervention and 55 post-intervention. Fisher test: The filling of nursing records, p=.0003. Checking cardiorespiratory arrest equipment, p <.001. Central vascular catheter related bacteraemia (B-CVC) p=.622. Ventilator associated pneumonia (VAP) p=.1000. Elevation of the head of the bed more than 30° p=.049, and the pain management in non-sedated patients p=.082. CONCLUSIONS: The implementation of nursing care plans in patients admitted to the intensive care area may contribute to improvement in the outcomes of nursing care.

Effect of dexamethasone on the efficacy of daptomycin in the therapy of experimental pneumococcal meningitis.

This study aimed to determine the effect of dexamethasone in combination with low-dose or high-dose daptomycin for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis. Efficacy (ΔCFU/mL) and cerebrospinal fluid (CSF) levels of daptomycin at 15mg/kg and 25mg/kg were studied in a rabbit model of pneumococcal meningitis, comparing them with the same doses in combination with dexamethasone at 0.125mg/kg every 12h over a 26-h period against two different Streptococcus pneumoniae strains, HUB 2349 and ATCC 51916 with daptomycin minimum inhibitory concentrations (MICs) of 0.09mg/L and 0.19mg/L, respectively. Daptomycin levels in CSF were lower when dexamethasone was given concurrently. Against strain HUB 2349, therapeutic failure occurred with daptomycin 15mg/kg+dexamethasone; daptomycin 25mg/kg+dexamethasone was better at reducing bacterial counts than the lower dose throughout treatment. Against the highly cephalosporin-resistant ATCC 51916 strain, daptomycin 15mg/kg+dexamethasone achieved a lower bacterial decrease than daptomycin 15mg/kg alone, and therapeutic failure at 24h occurred in the daptomycin 15mg/kg+dexamethasone group. Addition of dexamethasone to a 25mg/kg daptomycin dose did not affect the efficacy of daptomycin: it remained bactericidal throughout treatment. In conclusion, against the studied strains, low-dose (15mg/kg/day) daptomycin is affected by concomitant use of dexamethasone: CSF levels are reduced and its bacterial efficacy is affected. At a higher daptomycin dose (25mg/kg/day), however, the use of dexamethasone does not alter efficacy; the combination appears to be a good choice for the treatment of pneumococcal meningitis.

Experimental study of the efficacy of daptomycin for the treatment of cephalosporin-resistant pneumococcal meningitis.

OBJECTIVES: To determine the efficacy of daptomycin for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis using in vitro and in vivo methods. METHODS: In vitro killing curves were determined with clinically achievable CSF antibiotic concentrations. In a rabbit model of pneumococcal meningitis, we studied the efficacy (Δ cfu/mL) of daptomycin used at 15 and 25 mg/kg, comparing it with ceftriaxone 100 mg/kg/24 h and ceftriaxone plus vancomycin 30 mg/kg/24 h over a 26 h period against two different strains: HUB 2349 and ATCC 51916, with MICs of 2 and 32 mg/L of cefotaxime/ceftriaxone, respectively. RESULTS: The penetration of daptomycin into CSF ranged between 9% and 11%. Daptomycin therapy achieved an excellent response, being bactericidal within 2 h of antibiotic administration. Against strain HUB 2349, daptomycin at both doses was as effective as ceftriaxone plus vancomycin. Against the highly resistant strain, daptomycin 25 mg/kg was significantly better than ceftriaxone plus vancomycin at 2 and 6 h. CONCLUSIONS: Daptomycin at standard doses, and especially at high doses, may be a useful alternative for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis.

Listeria monocytogenes meningoencephalitis in adults: analysis of factors related to unfavourable outcome.

PURPOSE: To analyse the short-term outcome in patients with Listeria monocytogenes meningoencephalitis (LMME) to improve management and outcome. METHODS: Observational study with adult patients with LMME between 1977 and 2009 at a tertiary hospital in Barcelona, Spain. Parameters that predicted outcome were assessed with univariate and logistic regression analysis. RESULTS: Of 59 cases of LMME, 28 occurred in the last decade. Since 1987, a new protocol has been used and 29/45 patients (64%) treated since then received adjuvant dexamethasone. In patients who received this treatment there was a trend towards fewer neurological sequelae (5 vs 33%; p = 0.052). Antiseizure prophylaxis with phenytoin was administered in 13/45 (28%) patients. Seizures occurred in 7/45 (16%) patients, all in the group who did not receive phenytoin. Hydrocephalus presented in 8/59 (14%). It was never present at admission and five patients needed neurosurgical procedures. Sequelae after 3 months were present in 8/45 (18%), mostly cranial nerve palsy. Rhombencephalitis (RE) was related to the presence of neurologic sequelae (OR: 20.4, 95% CI: 1.76-236). Overall mortality was 14/59 (24%), 9/59 (15%) due to neurological causes related to hydrocephalus or seizures. Mortality was defined as early in 36% and late in 64%. In the multivariate analysis, independent risk factors for mortality were presence of hydrocephalus (OR: 17.8, 95% CI: 2.753-114) and inappropriate empirical antibiotic therapy (OR: 6.5, 95% CI: 1.201-35). CONCLUSIONS: Outcome of LMME may be improved by appropriate empirical antibiotic therapy, suspicion and careful management of hydrocephalus. Use of adjuvant dexamethasone or phenytoin in a subgroup of these patients might have a benefit.

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.

Arthritis related to systemic meningococcal disease: 34 years' experience.

The purpose of this investigation was to assess the clinical characteristics, therapeutic aspects, and outcome of arthritis related to invasive meningococcal disease (IMD). All episodes of bacterial meningitis and IMD are recorded systematically. We selected all episodes of IMD, with or without meningitis, that presented arthritis. From 1977 to 2010, 522 episodes of IMD were treated. Thirty-nine of these (7.5 %, 26 women, mean age 33 years) presented arthritis. Of these 39, 37 (95 %) presented skin lesions and 31 (79 %) had meningitis. Twenty (51 %) had positive blood cultures and six (15 %) had shock. No differences were found in skin lesions, shock, or bacteremia compared to cases without arthritis. In contrast to other septic forms, arthritis related to IMD was cured with short antibiotic therapy and without surgical drainage. There was no mortality. All patients recovered and none presented joint sequelae; however, 13 adult patients (33 %) required long-term treatment with steroids due to persistent symptoms. Arthritis related to IMD most frequently affects the knees and ankles, and may be a cause of fever relapse. Short antibiotic therapy is enough in all cases and surgical drainage is not needed. In some adult patients, especially those over 50 years of age, evolution is torpid and steroid therapy may be required in order to achieve recovery.

Efficacy of tigecycline alone and with rifampin in foreign-body infection by methicillin-resistant Staphylococcus aureus.

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.

Disseminated adiaspiromycosis: case report of a liver transplant patient with human immunodeficiency infection, and literature review.

Disseminated adiaspiromycosis is a rare infection that is sometimes associated with immunocompromised situations. We report the case of a patient, infected with human immunodeficiency virus and receiving highly active antiretroviral therapy, who had a liver transplant for hepatocellular carcinoma. The patient presented skin and pulmonary lesions due to adiaspiromycosis during immunosuppressive therapy. A review of >60 cases in the literature shows that adiaspiromycosis is a rare infection and Emmonsia is a dimorphic fungus that is difficult to grow. It should be considered a possible diagnosis in case of fungal infection and pulmonary granulomatosis. We should be aware of emerging adiaspiromycosis in patients with risk factors of immunosuppression, particularly transplant recipients. In these patients in particular, liposomal amphotericin B therapy should be considered.

Efficacy of fosfomycin and its combination with linezolid, vancomycin and imipenem in an experimental peritonitis model caused by a Staphylococcus aureus strain with reduced susceptibility to vancomycin.

The objective of this study was to evaluate the in vitro and in vivo efficacies of therapies including fosfomycin against clinical Staphylococcus aureus isolates with reduced susceptibility to vancomycin (hGISA). Time-kill curves were performed over 24 h. Peritonitis in C57BL/6 mice was induced by intraperitoneal inoculation of 10(8) CFU/ml. Four hours later (0 h), therapy was started and the treatment groups were: control (not treated), fosfomycin (100 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h), fosfomycin plus linezolid, fosfomycin plus vancomycin and fosfomycin plus imipenem, receiving subcutaneous therapy over 25 h. Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were determined. In vitro, fosfomycin showed a synergistic effect when combined with the other antimicrobials tested. In the animal model, fosfomycin combinations were effective and significantly reduced the bacteraemia rates achieved in the control, imipenem and vancomycin groups (p < 0.05). The best combination in vivo was fosfomycin plus imipenem. Also, fosfomycin plus linezolid was significantly better than vancomycin alone, reducing the bacterial concentration in the peritoneal fluid. In conclusion, in vitro and in vivo, fosfomycin in combination with linezolid, vancomycin or imipenem exerted a good activity. Fosfomycin plus imipenem was the most active combination, decreasing 3 log CFU/ml, and appears to be a promising combination for clinical practice.

Efficacy of usual and high doses of daptomycin in combination with rifampin versus alternative therapies in experimental foreign-body infection by methicillin-resistant Staphylococcus aureus.

The treatment of prosthetic joint infections caused by methicillin-resistant Staphylococcus aureus (MRSA) continues to be a challenge for the clinician. The aim of this study was to evaluate the efficacies of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg of body weight/day, respectively, in humans) and in combination with rifampin and to compare the activities to those of conventional anti-MRSA therapies. We used MRSA strain HUSA 304, with the following MICs and minimal bactericidal concentrations (MBCs), respectively: daptomycin, 1 µg/ml and 4 µg/ml; vancomycin, 2 µg/ml and 4 µg/ml; linezolid, 2 µg/ml and >32 µg/ml; and rifampin, 0.03 µg/ml and 0.5 µg/ml. In time-kill curves, only daptomycin and its combinations with rifampin achieved a bactericidal effect in log and stationary phases. For in vivo studies, we used a rat foreign-body infection model. Therapy was administered for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin at 25 mg/kg/12 h, and linezolid at 35 mg/kg/12 h, and each antibiotic was also combined with rifampin. Among monotherapies, daptomycin at 100 mg/kg/day and rifampin performed better than vancomycin and linezolid. In combination with rifampin, both dosages of daptomycin were significantly better than all other combinations, but daptomycin at 100 mg/kg/day plus rifampin achieved better cure rates at day 11 (P < 0.05) than daptomycin at 45 mg/kg/day plus rifampin. Resistant strains were found in monotherapies with rifampin and daptomycin at 45 mg/kg/day. In conclusion, daptomycin at high doses was the most effective monotherapy and also improved the efficacy of the combination with rifampin against foreign-body infections by MRSA. Clinical studies should confirm whether this combination may be considered the first-line treatment for foreign-body infections by MRSA in humans.

In vitro and in vivo activities of linezolid alone and combined with vancomycin and imipenem against Staphylococcus aureus with reduced susceptibility to glycopeptides.

The objective of this study was to evaluate the in vitro and in vivo efficacies of linezolid (35 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h), linezolid+imipenem, linezolid+vancomycin and vancomycin+imipenem against two clinical Staphylococcus aureus isolates with reduced susceptibility to glycopeptides using time-kill curves and the murine peritonitis model. Time-kill curves were performed over 24 h. For the murine peritonitis model, peritonitis was induced by the intraperitoneal inoculation of 10(8) CFU/ml of each bacterial strain. Four hours later (0 h), the mice were randomly assigned to a control group or to therapeutic groups receiving subcutaneous treatment for 25 h. Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were determined. The time-kill curves showed that the addition of linezolid to imipenem yielded synergistic results after 24 h. The addition of linezolid decreased vancomycin activity. In the animal model, vancomycin and linezolid monotherapies produced comparable bacterial decreases in mice infected with each strain but linezolid achieved higher rates of blood sterilisation. Linezolid tested either in monotherapy or in combination showed similar efficacy against both strains in terms of bacterial killing, number of negative blood cultures and survival. Linezolid and vancomycin were moderately bactericidal and similar in efficacy against glycopeptide-intermediate or -resistant S. aureus. Linezolid combinations, as effective as linezolid tested alone, could be considered as alternative options for the treatment of glycopeptide-intermediate S. aureus (GISA) infections.