Early in vitro development of daptomycin non-susceptibility in high-level aminoglycoside-resistant Enterococcus faecalis predicts the efficacy of the combination of high-dose daptomycin plus ampicillin in an in vivo model of experimental endocarditis.

Background: Previous studies showed development of daptomycin non-susceptibility (DNS: MIC >4 mg/L) in Enterococcus faecalis infections. However, no studies have assessed the efficacy of the combination of daptomycin/ampicillin against E. faecalis strains developing DNS in the experimental endocarditis (EE) model. Objectives: To assess the in vitro and in vivo efficacy of daptomycin at 10 mg/kg/day, daptomycin/ampicillin and ampicillin/ceftriaxone against two high-level aminoglycoside-resistant E. faecalis strains, one developing DNS after in vitro exposure to daptomycin and another that did not (DS). Methods: Subculture of 82 E. faecalis strains from patients with endocarditis with daptomycin MICs, time-kill and in vivo experiments using the EE model. Results: 33% of the strains (27 of 82) displayed DNS after subculture with daptomycin. Daptomycin MIC rose from 0.5-2 to 8-16 mg/L. In time-kill experiments, when using a high inoculum (10 8 cfu/mL), daptomycin/ampicillin was synergistic for one-third of DS strains and none of DNS strains, while ampicillin/ceftriaxone retained synergy in all cases. In the EE model, daptomycin did not significantly reduce cfu/g from vegetations compared with control against either strain, while daptomycin/ampicillin reduced significantly more cfu/g than daptomycin against the DS strain, but not against the DNS strain [2.9 (2.0-4.1) versus 6.1 (4.5-8.0); P = 0.002]. Ampicillin/ceftriaxone was synergistic and bactericidal against both strains, displaying the same activity as daptomycin/ampicillin against the DS strain. Conclusions: Performance of an Etest for daptomycin MIC after subculture with daptomycin inhibitory doses on strains of high-level aminoglycoside-resistant E. faecalis endocarditis may be an easy test to predict the in vivo efficacy of daptomycin/ampicillin.

Fosfomycin plus ß-Lactams as Synergistic Bactericidal Combinations for Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus.

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.

Daptomycin is effective for treatment of experimental endocarditis due to methicillin-resistant and glycopeptide-intermediate Staphylococcus epidermidis.

This study evaluated the daptomycin activity against two methicillin-resistant Staphylococcus epidermidis (MRSE) clinical isolates with different vancomycin susceptibilities: MRSE-375, with a vancomycin MIC of 2 microg/ml, and NRS6, a glycopeptide-intermediate S. epidermidis (GISE) strain with a vancomycin MIC of 8 microg/ml. The in vivo activity of daptomycin at two different doses (standard dose [SD-daptomycin], 6 mg/kg of body weight/day intravenously [i.v.]; high dose [HD-daptomycin], 10 mg/kg/day i.v.) was evaluated in a rabbit model of infective endocarditis and compared with that of a standard dose of vancomycin (SD-vancomycin; 1 g i.v. every 12 h) for 2 days. For the MRSE-375 strain, high-dose vancomycin (HD-vancomycin; 1 g i.v. every 6 h) was also studied. For MRSE-375, SD- and HD-daptomycin therapy sterilized significantly more vegetations than SD-vancomycin therapy (9/15 [60%] and 11/15 [73%] vegetations, respectively, versus 3/16 [19%] vegetations; P = 0.02 and P = 0.002, respectively). HD-daptomycin sterilized more vegetations than HD-vancomycin (11/15 [73%] versus 5/15 [33%] vegetations; P = 0.03) and was more effective than SD- and HD-vancomycin in reducing the density of bacteria in valve vegetations (0 log(10) CFU/g vegetation [interquartile range {IQR}, 0 to 1 log(10) CFU/g vegetation] versus 2 log(10) CFU/g vegetation [IQR, 2 to 2 log(10) CFU/g vegetation] and 2 log(10) CFU/g vegetation [IQR, 0 to 2.8 log(10) CFU/g vegetation]; P = 0.002 and P = 0.01, respectively). For the NRS6 strain, SD- and HD-daptomycin were significantly more effective than vancomycin in reducing the density of bacteria in valve vegetations (3.7 log(10) CFU/g vegetation [IQR, 2 to 6 log(10) CFU/g vegetation] versus 7.1 log(10) CFU/g vegetation [IQR, 5.2 to 8.5 log(10) CFU/g vegetation]; P = 0.02). In all treatment arms, isolates recovered from vegetations remained susceptible to daptomycin and vancomycin and had the same MICs. In conclusion, daptomycin at doses of 6 mg/kg/day or 10 mg/kg/day is more effective than vancomycin for the treatment of experimental endocarditis due to MRSE and GISE.

Enterococcal endocarditis revisited.

The Enterococcus species is the third main cause of infective endocarditis (IE) worldwide, and it is gaining relevance, especially among healthcare-associated cases. Patients with enterococcal IE are older and have more comorbidities than other types of IE. Classical treatment options are limited due to the emergence of high-level aminoglycosides resistance (HLAR), vancomycin resistance and multidrug resistance in some cases. Besides, few new antimicrobial alternatives have shown real efficacy, despite some of them being recommended by major guidelines (including linezolid and daptomycin). Ampicillin plus ceftriaxone 2 g iv./12 h is a good option for Enterococcus faecalis IE caused by HLAR strains, but randomized clinical trials are essential to demonstrate its efficacy for non-HLAR EFIE and to compare it with ampicillin plus short-course gentamicin. The main mechanisms of resistance and treatment options are also reviewed for other enterococcal species.

Delayed sternal closure for life-threatening complications in cardiac operations: an update.

Over a 7-year-period, 25 patients had delayed sternal closure after open heart operations out of 34 patients whose sternum was not closed. The indications were extreme cardiac dilatation and uncontrollable mediastinal hemorrhage. This represented a 1.79% incidence in the overall open heart surgical experience at our unit. Sternal closure was performed at a mean of 2.64 days after the initial operation. Eighteen patients (52.9%) left the hospital alive and well, representing a 72% survival rate among patients undergoing delayed sternal closure. No mediastinal or fatal infection developed and only 1 patient had late superficial wound infection after delayed sternal closure. We conclude that delayed sternal closure is an effective method to treat severe complications after cardiac operations.

Open heart surgery for thrombosis of a prosthetic mitral valve during pregnancy. Fetal hydrocephalus.

Pregnant women with cardiac valvular prostheses present an important risk factor and the major complications are endocarditis and thromboembolism. Thromboembolism is determined by a hypercoagulation state. Compulsory anticoagulation treatment is an associated risk factor producing maternal and fetal complications. Different open heart surgical cases during pregnancy have been reported and a review of the literature shows favourable maternal prognosis. A 30-year-old woman with a Björk-Shiley mitral prosthesis, during the 6th week of pregnancy presented with thrombosis and embolism due to a change in anticoagulation treatment from acenocumarol to heparin. Open heart surgery was carried out and the patient's course was favourable. A fetal hydrocephaly of unknown etiology was discovered during the 18th week of pregnancy. Open heart surgery during pregnancy and the necessity of thromboembolic prophylaxis, have been analysed and revised.

Early results with intraoperative transluminal coronary artery balloon dilatation.

We used intraoperative transluminal coronary balloon dilatation, together with coronary artery bypass grafting, to obtain complete myocardial revascularization in extensively diseased coronary arteries. Our patient population consisted of ten males and two females, with a mean age of 58 years. The left anterior descending artery was dilated in five patients, the posterior descending artery was dilated in three, the obtuse marginal artery in two, the left circumflex artery in one, and the right coronary artery in one. Additionally, a mean of 2.81 grafts per patient were placed. Hospital mortality was one patient (8.33%). There was also one case of perioperative myocardial infarction. Postoperative angiography was done in seven patients: five were shown to be improved, one had a vessel that appeared unchanged, and one had an occluded vessel. We found intraoperative transluminal coronary balloon dilatation to be a simple and efficient technique that offers potential improvement in myocardial revascularization.

[Prospective and comparative study of pacemaker implants carried out at the electrophysiology laboratory and the operating room]. / Estudio prospectivo, comparativo entre implantes de marcapasos realizados en el laboratorio de electrofisiología y en el quirófano.

INTRODUCTION AND OBJECTIVES: Permanent pacemaker implantation is done by different physicians with either a surgical or clinical training. Our objective was to evaluate if there were significant differences in the implantation parameters and in the complication rate among implantations performed by cardiologists in the electrophysiologic laboratory and cardiological surgeons in the operating room. MATERIAL AND METHODS: We prospectively collected those patients' data who received a first pacemaker implantation by cardiovascular surgeons and electrophysiologists during the year 1998. Data collected included demographic information, indication for pacing, surgical time, complications during procedure, stimulation and sensing thresholds as well as type of pacing. RESULTS: We first-implanted 216 pacemakers in a one year period, 101 by cardiovascular surgeons and 115 by electrophysiologists. 56% were male patients. Average age in the surgery group was 74.2 +/- 9 years and 72.09 +/- 12 in the electrophysiology group (p = NS). Main diagnoses were as follows: complete heart block in 32.9% patients, complete heart block 2. degrees 16.4%, sinus node dysfunction 12.2%, AV node ablation 12.2% and others. The complications rate for surgery group was 4% and 1.7% for electrophysiologists (p = NS). Electrophysiologists placed more bicameral devices. No clinically significant differences were found among other implant parameters. CONCLUSIONS: Pacemaker implant by cardiologists in an electrophysiologists laboratory is a safe procedure that does not have more complications when compared to the same procedure done in the operating room by surgeons. This allows hospital resource optimization and reduction of hospital stay length.

[Postinfarction ventricular septal defect. Surgical approach by right ventriculotomy in 4 patients]. / Comunicación interventricular postinfarto agudo de miocardio. Abordaje quirúrgico por ventriculotomía derecha con éxito en 4 pacientes.

Ventricular septal defect secondary to myocardial infarction still have high mortality. Early and swift surgical repair is needed to obtain adequate results. Surgical exposure of defect through the infarcted left ventricle wall is the usual technique. Nevertheless right ventricular access to the interventricular septum has given excellent results on 4 of our patients. Our results are analyzed.

[Traumatic rupture of the tricuspid valve. Its conservative surgical treatment]. / Rotura traumática de la válvula tricúspide. Tratamiento quirúrgico conservador.

Tricuspid insufficiency caused by blunt chest trauma is rare and usually unsuspected clinically, early after trauma. Cross-sectional Echocardiography and Cardiac Catheterization are essential to establish the diagnosis. Therapy applied varies from repair to valvular replacement. We describe an 18-year-old boy with traumatic tricuspid regurgitation treated by reconstruction of the attachments of the anterosuperior leaflet and annuloplasty with a Puig-Massana ring. Six month after surgery he is fully recovered, although persist a moderate degree of tricuspid insufficiency.

[Aneurysms of the abdominal aorta in patients on a permanent hemodialysis program]. / Aneurismas de aorta abdominal en pacientes en programa de hemodiálisis permanente.

Surgical approach of an aneurysm at the infrarenal aorta abdominal, in six patients with terminal renal failure and chronic hemodialysis, is presented. They were all men, and the middle age was 62 years. There were two hospital deaths and a latter death. At the moment of this report, the three survival patients are well, after a follow-time of 34.6 months. Treatment of this group of patients, as well as the literature concerning to this subject are reviewed.

[Coarctation of the abdominal aorta. Surgical treatment]. / Coartación de aorta abdominal. Tratamiento quirúrgico.

Five cases of aortic abdominal coarctation are presented, 4 of them surgically treated (by-pass). A revision of the theme, specially its etiology and surgical options, is carried out.

[Vascular injuries of the lower extremity]. / Traumatismos vasculares del miembro inferior.

Authors present their experience (32 patients affected by a traumatic femoropopliteal injury) with vascular traumatisms at the lower limb. Causes, treatment and successful results with the new technics and the early clinical management to the patients are commented.

[The arterial complications of closed injuries to the shoulder girdle]. / Complicaciones arteriales de los traumatismos cerrados de la cintura escapular.

After a period of time of 5 years, we made a review of all the patients registered at our Center. Eight cases of closed traumatism at the scapulohumeral belt, with vascular injury associated (0.2% of all closed traumatisms at this level registered in our center during this time) were reported. Six patients presented also an osteoarticular injury associated. Three different vascular injuries were showed: three cases of complete arterial section, two arterial contusions and a partial arterial section. From the two cases without osteoarticular injuries, one of them showed a complete section and the other presented an arterial contusion. Polytraumatic patients showed multiple osteoarticular injuries. We registered one fracture-luxation at the shoulder, 3 diafisaric humeral fractures, one humeral neck fracture, one clavicle fracture, one fracture-luxation at the cervical column and one simple luxation of the shoulder.

Changes in the treatment of Enterococcus faecalis infective endocarditis in Spain in the last 15 years: from ampicillin plus gentamicin to ampicillin plus ceftriaxone.

The aim of this study was to assess changes in antibiotic resistance, epidemiology and outcome among patients with Enterococcus faecalis infective endocarditis (EFIE) and to compare the efficacy and safety of the combination of ampicillin and gentamicin (A+G) with that of ampicillin plus ceftriaxone (A+C). The study was a retrospective analysis of a prospective cohort of EFIE patients treated in our centre from 1997 to 2011. Thirty patients were initially treated with A+G (ampicillin 2 g/4 h and gentamicin 3 mg/kg/day) and 39 with A+C (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) for 4-6 weeks. Increased rates of high-level aminoglycoside resistance (HLAR; gentamicin MIC ≥512 mg/L, streptomycin MIC ≥1024 mg/L or both) were observed in recent years (24% in 1997-2006 and 49% in 2007-2011; p 0.03). The use of A+C increased over time: 1997-2001, 4/18 (22%); 2002-2006, 5/16 (31%); 2007-2011, 30/35 (86%) (p <0.001). Renal failure developed in 65% of the A+G group and in 34% of the A+C group (p 0.014). Thirteen patients (43%) in the A+G group had to discontinue treatment, whereas only one patient (3%) treated with A+C had to discontinue treatment (p <0.001). Only development of heart failure and previous chronic renal failure were independently associated with 1-year mortality, while the individual antibiotic regimen (A+C vs. A+G) did not affect outcome (OR, 0.7; 95% CI, 0.2-2.2; p 0.549). Our study shows that the prevalence of HLAR EFIE has increased significantly in recent years and that alternative treatment with A+C is safer than A+G, with similar clinical outcomes, although the sample size is too small to draw firm conclusions. Randomized controlled studies are needed to confirm these results.

Complete translocation of the aortic root and coronary bypass grafting with a microporous polyurethane (Mitrathane) composite valved graft in the treatment of recurrent prosthetic valve endocarditis.

The case of a 20-year-old male patient, with a history of addiction to parenteral heroin and recurrent prosthetic valve endocarditis, is presented. In this case the final procedure consisted of a complete translocation of the aortic root and coronary bypass grafting with a composite graft made from a microporous polyurethane (Mitrathane) cardiac patch, a prosthetic valve and two Mitrathane vascular grafts for the coronaries. This is a complex operation, only indicated in cases of extensive destruction of the aortic root due to recurrent endocarditis. To our knowledge, it is the first case of this type performed using Mitrathane.

Severe fibrous epicarditis after microporous polyurethane (Mitrathane) cardiac patch implantation.

Several materials have been used for pericardial closure after open heart surgery. Mitrathane is a recently introduced material designed for use in the cardiovascular system. A case of severe epicarditis after implantation of a Mitrathane cardiac patch for pericardial closure is presented. This epicardial reaction rendered the exposure of the heart at reoperation extremely difficult. This is a complication not reported to date with this new material. Thus, careful evaluation of Mitrathane is needed before extending its use to larger series.