M.L. Fernández Guerrero

Treatment of experimental endocarditis due to methicillin-susceptible or methicillin-resistant Staphylococcus aureus with trimethoprim-sulfamethoxazole and antibiotics that inhibit cell wall synthesis.

Using two strains of Staphylococcus aureus, one susceptible and one heterogeneously resistant to methicillin, for which MICs and MBCs of trimethoprim-sulfamethoxazole (TMP-SMX) were 0.06 and 0.06 micrograms/ml and 0.06 and 0.25 microgram/ml, respectively (concentrations are those of TMP), we studied the efficacies of TMP-SMX and cloxacillin, teicoplanin, and vancomycin for treatment of experimental staphylococcal endocarditis. Rabbits were treated with dosages of TMP-SMX selected to achieve concentrations in serum equivalent to that obtained in humans treated for Pneumocystis carinii pneumonia. The overall mortality rate of rabbits treated with TMP-SMX was 84% at day 3, not different from that of the control groups (P > 0.1). No sterile vegetations were observed to be present in control groups or in animals treated with TMP-SMX. However, 26, 60, and 75% of rabbits treated with teicoplanin, cloxacillin, and vancomycin, respectively, showed sterile vegetations. For methicillin-susceptible S. aureus (MSSA), the mean vegetation counts were not significantly different between the control group and the group treated with TMP-SMX (P > 0.1). For methicillin-resistant S. aureus (MRSA), treatment with TMP-SMX was more effective than no therapy, decreasing the number of organisms in vegetations (P < 0.01). For both strains, therapy with cloxacillin and therapy with teicoplanin or vancomycin were significantly more effective than therapy with TMP-SMX. Despite high concentrations of teicoplanin in serum which exceeded MBCs for staphylococci more than 50 times at the peak and 10 times at the trough, therapy with cloxacillin or vancomycin was superior to therapy with teicoplanin against both MSSA and MRSA. These data do not support the use of TMP-SMX in treatment of endocarditis and other severe staphylococcal infections with high bacterial counts.

Treatment of experimental endocarditis due to penicillin-resistant Streptococcus pneumoniae.

Using two strains of pneumococci for which MICs of penicillin were 1 and 4 micrograms/ml, those of cefotaxime were 0.01 and 0.5 micrograms/ml, and those of teicoplanin were 0.01 and 0.1 micrograms/ml, we studied the efficacy of different dosages of penicillin, cefotaxime, and teicoplanin in the treatment of experimental pneumococcal endocarditis in rabbits. Animals treated with dosages of penicillin G procaine needed to achieve levels in serum near the MIC for pneumococci showed a significant reduction in log10 CFU per gram of vegetation, as compared with the control (P < 0.001), although only 20% of the animals showed sterile vegetations. When levels of penicillin in serum were in the range of three- to fourfold the MIC, a greater reduction in log10 CFU per gram of vegetation was seen, and 88% of the animals showed sterile vegetations. Only the regimen of penicillin that provided concentrations in serum above the MIC throughout the interval between two doses provided constant sterilization of the cardiac vegetations. Dosages of cefotaxime and teicoplanin selected to achieve concentrations in serum equivalent to that obtained in humans during treatment resulted in levels of antimicrobial agents in serum hundreds or thousands of times higher than the MICs for the infecting strains. In terms of antimicrobial efficacy, cefotaxime and teicoplanin were equivalent to regimens with high dosages of penicillin.

Antimicrobial treatment of invasive non-perinatal human listeriosis and the impact of the underlying disease on prognosis

Listeriosis is a resurgent foodborne disease in European countries. Benefits of combined β-lactam-aminoglycoside treatment remain controversial and the impact of the underlying disease on prognosis has not been fully assessed. We conducted a retrospective review of cases of sporadic listeriosis in adults from 1995 to 2008 at two university-affiliated hospitals serving a population of 600,000 people in Madrid, Spain. The primary end-point was the associated in-hospital mortality. Sixty-four patients were studied. Estimated incidence of listeriosis was 0.76/100.000 persons/year. Seventy-four per cent had chronic underlying diseases; cirrhosis of the liver and haematological and solid neoplasias were the most common comorbidities. Primary bacteraemia (58%) and meningitis (42%) were the most frequent manifestations. Focal infections were seen in ten cases. In-hospital mortality was 31%. Patients treated with ampicillin or with an ampicillin-gentamicin combination did not differ in age, severity of underlying disease or type of presentation. Differences in mortality were not seen between patients treated with monotherapy and those given combined treatment (28% vs 35%; p 0.634). Ten patients were treated with trimethoprim-sulfamethozaxole alone and only one died. All patients without comorbidities survived infection but mortality of patients with cirrhosis of the liver was 21% and that of patients with haematological or solid neoplasias was 66%. Only haematological neoplasia (OR 6.67; 95% CI 1.71-26.04; p 0.006) was significantly associated with an increased risk of mortality (R(2) (Cox-Snell) = 0.262). Mortality of listeriosis mainly depended on the severity of the underlying disease. Combined ampicillin-gentamicin therapy did not improved survival. Trimethoprim-sulfamethozaxole may be an effective alternative therapy for listerial infections.

Fiebre recurrente como primera manifestación del cáncer de colon

El cancer de colon es una causa rara y mal conocida de fiebre de origen desconocido (FOD). Se estima que menos del 1% de todos los casos de FOD son secundarios a una neoplasia de oculta de colon. Los autores presentan 4 casos de FOD como primera manifestacion de un cancer oculto del colon, haciendo enfasis en sus peculiaridades diagnosticas y patogenicas. La fiebre recurrente, sin patron definido, de breve duracion, autolimitada, imprevisible en cuanto a su aparicion, deberia hacer sospechar la existencia de un cancer de colon oculto. En ocasiones la bacteriemia por Escherichia coli es tambien primera manifestacion de esta neoplasia.

Treatment of cerebrospinal fluid shunt infections with teicoplanin

Intraventricular teicoplanin 10–15 mg was administered daily to three patients with cerebrospinal fluid (CSF) shunt infections due toStaphylococcus epidermidis andEnterococcus faecalis. Teicoplanin concentrations in CSF 24 h after intrathecal injection of the drug exceeded four- to eight-fold the MICs for the infecting microorganisms. CSF cultures rapidly became negative and shunt devices were withdrawn and replaced in the same operative procedure. Intraventricular teicoplanin was well tolerated. No relapses occurred. Teicoplanin may be an alternative to vancomycin for the antimicrobial therapy of CSF shunt infections.

Emerging infectious endocarditis due to Scedosporium prolificans : a model of therapeutic complexity

Scedosporium prolificans is an emerging agent for severe infections. Although among the dematiaceous fungi Scedosporium is the most frequently isolated in blood cultures, Scedosporium endocarditis is rarely reported. We show herein a patient with acute leukaemia who developed S. prolificans endocarditis. Twelve cases were found in an extensive review of the English literature. In six cases (46%), there was predisposing heart conditions such as a prosthetic valve or an intracavitary device. Only 4 patients (31%) were immunocompromised hosts with haematologic neoplasia, solid-organ transplantation or acquired immunodeficiency syndrome (AIDS). Exposure to Scedosporium was observed in immunocompetent patients who developed infection while in the community. Scedosporium endocarditis occurred on both sides of the heart. Systemic and pulmonary emboli and other metastatic complications were seen in all of these patients. The overall mortality was 77% and, specifically, all of the immunocompromised hosts and 6 out of 7 patients with mitral or aortic valve endocarditis died. Patients with right-sided endocarditis associated with a removable intracardiac device exhibited a better prognosis. Scedosporium endocarditis, although still rare, is an emerging infection with an ominous prognosis. At the present time, valve replacement or the removal of cardiac devices plus combined antifungal treatment may offer the best possibility of cure.

Treatment of experimental endocarditis due to ampicillin-susceptible or ampicillin-resistant Salmonella enteritidis.

Using two strains of Salmonella enteritidis, one susceptible and one resistant to ampicillin, we studied the efficacies of ampicillin, gentamicin, ampicillin plus gentamicin, ofloxacin, and cefotaxime for the treatment of experimental salmonella endocarditis. Rabbits were treated for 3 days with dosages of antibiotic selected to achieve concentrations in serum equivalent to those obtained in humans during therapy. Aortic salmonella endocarditis seemed to be very difficult to treat, and all antimicrobial regimens failed to achieve the complete sterilization of cardiac vegetations. In vitro studies did not accurately predict the in vivo response to therapy, and no correlations regarding the synergistic activity of the combination of ampicillin plus gentamicin were observed. For the ampicillin-susceptible S. enteritidis isolate, ampicillin and cefotaxime produced the greatest reduction in the number of organisms in vegetations, with no significant differences between them. For the ampicillin-resistant strain, the combination of ampicillin with gentamicin produced a synergistic effect that was not anticipated by the in vitro studies. Both cefotaxime and ofloxacin were effective in reducing the number of microorganisms in the vegetations, although the reduction produced by cefotaxime was less that that produced against the ampicillin-susceptible strain. Monotherapy with gentamicin exhibited only modest activity against the ampicillin-susceptible S. enteritidis strain.

Enfermedad de Castleman multicéntrica en sida. Su relación con el VHH-8 o virus herpes asociado al sarcoma de Kaposi. Estudio de dos casos

Castleman disease is considered a reactive lymphadenopathic picture with two clinical forms: one localized, frequent in immunocompetent patients and another multicenter one that is more characteristic in immunodepressed patients. Two cases of Castleman disease multicenter in HIV positive patients with Kaposis sarcoma are presented. Both patients have multiple adenopathies, hepatomegaly and symptoms B on diagnosis. One of them had a favorable response to chemotherapy treatment and another died. A review of the concept of multicenter Castleman disease and its pathogenic relationship to human herpes virus 8 (HHV-8) is done.

Comentarios clínicosLas infecciones del sistema nervioso central en pacientes con virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividadCentral nervous system infections in HIV patients in the era of high activity antiretroviral treatment

Aunque la incidencia de la mayoria de las infecciones del sistema nervioso central en los pacientes infectados por el virus de la inmunodeficiencia humana ha disminuido tras la introduccion de los modernos tratamientos antirretrovirales, aun siguen siendo una causa importante de morbilidad y mortalidad. Las nuevas tecnologias en biologia molecular y neurorradiologia permiten el diagnostico en muchos casos y han disminuido la necesidad de la biopsia cerebral. El pronostico ha mejorado sustancialmente tras la introduccion de la terapia antirretroviral de alta eficacia, pero, sin embargo, se precisan tratamientos mas activos para infecciones como la LMP o la encefalitis por citomegalovirus donde la mortalidad sigue siendo inaceptablemente alta.

Tolerance and safety of intravenous streptomycin therapy in patients with tuberculosis

Although the clinical use of streptomycin has declined greatly, it is still a commonly used anti-tuberculous drug [1]. Given the re-emergence of tuberculosis and the limited number of anti-tuberculous drugs, the use of streptomycin has gained renewed interest. Streptomycin is administered by deep intramuscular injections and, in both Europe and the USA, the manufacturers do not recommend intravenous administration [2]. However, repeated intramuscular injections of streptomycin produce pain and inflammation. In this investigation, we assessed the tolerance and safety of intravenous streptomycin, an off-label method of administration that could be clinically useful in patients with tuberculosis and other infectious diseases. Consecutive patients with tuberculosis who were B50 years old and had normal renal function (serum creatinine \1.2 mg/dl) were selected. The study was conducted in a university-affiliated hospital from January 2011 to March 2012. This study was approved by the local institutional committee of clinical trials. The purpose of the study was explained to the patients and those that gave written informed consent were included. Patients were empirically treated with standard doses of rifampin, isoniazid and pyrazinamide. In addition, streptomycin sulphate (Estreptomicina Normon, Madrid, Spain) 15 mg/kg/24 h in 100 ml of normal saline was administered intravenously over 45–60 min. In some patients with risk factors for multi-resistant tuberculosis, ethambutol was also added in the initial empirical regimen. Serum levels of streptomycin were measured on the third day of treatment by means of ultra-performance liquid chromatography-mass spectrometry 1 h after the end of infusion (peak level) and before the next dose (trough level), following a protocol previously detailed [3]. Patients were examined daily with bedside vestibular and Romberg tests and asked for signs of vestibular or cochlear dysfunction. Haematological testing and chemistry were recorded at baseline and every other day. Screen for hearing loss was assessed by a Rinne and Weber 256-Hz tuning fork at the bedside to avoid movements of contagious patients through the hospital. When tests were uncertain or responses difficult to reproduce, pure tone audiometry was performed. Because the study was designed to assess the tolerance of intravenous streptomycin therapy in the short term, we considered a minimum of 1 week of administration in order to include patients into the analysis. Basically, streptomycin was stopped when rapid, DNA-based, molecular tests to detect mutations associated with drug resistance indicated full susceptibility of the infecting strain to rifampin and isoniazid, when sputum acid-fast smears were negative or when the health-care provider estimated that the patient could be discharged from hospital to follow therapy on an outpatient basis. Some of these patients continued intramuscular streptomycin therapy for different periods of time. Twenty-seven patients were given intravenous streptomycin. Four of them received another course of streptomycin therapy in subsequent admissions; hence, 31 courses of streptomycin therapy were finally assessed. R. Pérez Tanoira R. Fernández Roblas J. Esteban M. L. Fernández Guerrero (&) Division of Infectious Diseases and Clinical Microbiology, Fundación Jiménez Dı́az, Universidad Autónoma de Madrid, Ave. Reyes Católicos, 2, 28040 Madrid, Spain e-mail: mlfernandez@fjd.es