Endocarditis due to vancomycin-resistant Enterococcus raffinosus successfully treated with linezolid: case report and review of literature.

Enterococcus raffinosus is scarcely found in clinical samples and even less frequently as etiologic agent of endocarditis. We are herein presenting one case of mitral prosthetic-valve endocarditis in a 77-y-o male due to a vancomycin-resistant Enterococcus raffinosus isolate, successfully treated with 6 weeks of linezolid, and a two-year follow up.

Rationale for treating community-acquired lower respiratory tract infections with amoxicillin/sulbactam combination through pharmacodynamic analysis in the setting of aminopenicillin-resistant organisms.

In order to establish a rationale for treating community-acquired lower respiratory tract infections, we assess here the pharmacodynamics of amoxicillin/sulbactam, 500mg/500mg, a formulation marketed in Argentina since 1988 and currently available in 17 countries, against the major pathogens, in comparison with that of a novel formulation (875mg/125mg, see J Chemother 2000; 12: 223-227). In time-kill studies, both bactericidal and inhibitory activity were seen in the 1.5- and 6-h sera, obtained from 12 volunteers after a single oral dose, against both a penicillin-susceptible and an -intermediate Streptococcus pneumoniae strain, as well as against Moraxella catarrhalis and a beta-lactamase-negative Haemophilus influenzae strain. Only the 1.5-h sera proved bactericidal against a penicillin-resistant S. pneumoniae strain (MIC, 2 microg/ml) and a beta-lactamse-positive H. influenzae isolate. This study suggests that amoxicillin/sulbactam (500mg/500mg) is still a suitable option for treating community-acquired lower respiratory tract infections, allowing a b.i.d. dosing schedule. Caution should be taken with pneumonia caused by beta-lactamase-positive H. influenzae or penicillin-resistant (MIC > or =2 microg/ml) S. pneumoniae isolates. Either shorter dosing intervals (t.i.d.) or a higher amoxicillin content in the formulation (i.e. 875 mg) may be required in these situations.

A pharmacodynamic model to support a 12-hour dosing interval for amoxicillin/sulbactam, a novel oral combination, in the treatment of community-acquired lower respiratory tract infections.

We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sulbactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the major respiratory pathogens in 12 volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericidal or inhibitory activity against both a penicillin-susceptible and a penicillin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 and 0.25 microg/ml, respectively), as well as against a beta-lactamase-positive Moraxella catarrhalis and a beta-lactamase-negative Haemophilus influenzae strain. Both the peak samples and those corresponding to 4 h after dose (i.e. 33% of a 12-h dosing interval) proved active against both a penicillin-resistant S. pneumoniae (MIC, 2 microg/ml) and a beta-lactamase-positive H. influenzae strain. The AMX-SUL formulation evaluated in this study showed pharmacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing interval regimen.

Acute community-acquired pneumonia in adults: guidelines for initial antimicrobial therapy based on local evidence from a South American Working Group (ConsenSur).

Community-acquired pneumonia (CAP) is probably one of the infections affecting ambulatory patients for which the most diverse guidelines have been written worldwide. Most guidelines agree that antimicrobial therapy should be initially tailored according to either the severity of the infection or the presence of co-morbidity and epidemiology. Nevertheless, a great variability may be noted among different countries in the selection of first choice antimicrobial agents, even for cases considered as low-risk. This may be due to the many microbial causes of CAP and specialties involved, as well as different healthcare systems which affect the availability or cost of antibiotics. However, many countries or regions adopt some of the guidelines or design their own recommendations, regardless of the local data, probably because of the scarcity of such data. A committee composed of South American infectious diseases specialists and microbiologists, with strong interest and recognized experience in CAP, were convened to establish a working group (ConsenSur) for designing a local evidence-based practice guideline for the initial management of CAP. This supplement is intended to give a practice recommendation for the initial antimicrobial treatment of CAP upon the basis of local evidence, in the hope of procuring a suitable tool for use by the different health-care providers concerned with the management of this infection in South America or in other countries where the main considerations for CAP are comparable.

Efficacy of amoxicillin-sulbactam, given twice-a-day, for the treatment of community-acquired pneumonia: a clinical trial based on a pharmacodynamic model.

The present multicenter study reports the results of a clinical trial, designed on the basis of a pharmacodynamic study published previously (Bantar et al., J. Chemother 2000; 12: 223-227) to assess the efficacy of amoxicillin/sulbactam (875 mg/125 mg), given orally twice-a-day for 7 days in the treatment of patients with community-acquired pneumonia (CAP). Eighty-four evaluable subjects older than 19 years with clinical symptoms and features suggestive of CAP, consulting from June 2000 to March 2002 and meeting the PORT risk class I through III, were enrolled in the study. Mean age (y +/- standard deviation) was 46.7 +/- 16.3 and 62% of the patients had some co-morbidity predisposing for CAP. Several individuals (77.4%) fell into a low-risk class (i.e. PORT I or II) and 22.6% of patients belonged to a moderate-risk class at the start of treatment. Six patients (6.45%) had pneumococcal bacteremia. Streptococcus pneumoniae was the organism most frequently isolated (61.9% of all the patients in whom an etiologic diagnosis was made), followed by Haemophilus influenzae. Clinical success was observed in 97.6% of the patients (confidence interval 95%, 94.3%-100%). Almost all the individuals with clinical success became afebrile within the first 3 days of therapy. Ten patients (11.8%) reported mild or moderate adverse events (especially diarrhea) possibly related to the antimicrobial therapy, but this did not lead to withdrawal from the trial. The results of this study suggest that amoxicillin/sulbactam (875 mg/125 mg) is an efficacious and well tolerated option for treating patients with CAP belonging to a low-moderate risk class and support the use of a short, oral (7-day) b.i.d. regimen.

Review of pharmacokinetic, pharmacodynamic and clinical studies with a modern combination of amoxicillin/sulbactam.

Amoxicillin/sulbactam is a modern antimicrobial combination. This combination proved to be useful for the treatment of several infections caused by different microorganisms, mainly with the beta-lactamase-producing species. In this review we present the most relevant pharmacokinetic, pharmacodynamic and clinical information associated with its use.

[Microbiology and conservative surgery of serious infections of the diabetic foot]. / Microbiología y cirugía conservadora en infecciones graves del pie diabético.

Between June of 1987 and August 1988 we evaluated 31 diabetic patients hospitalized for severe foot infections to determine the etiologic agents, the value of the bacteriologic samples obtained, the benefits of conservative surgery and variable predictors of a major amputation. Sixteen patients suffered from necrosis, 16 osteomyelitis, 14 ulcers, 5 cellulitis, and/or abscesses and 22 had vascular compromise. Samples were taken from these infections excluding necrotic material. We isolate 76 microorganisms (2.4/pt), 57% Gram-positive cocci (predominantly S. aureus and enterococci), and 43% Gram-negative bacilli. Anaerobes were not isolated probably secondary to the exclusion of necrotic samples. There was high incidence of skin and soft tissue sampling (79%) bone (13/16) and surgical curettage (11/11). In 9 patients the correlation of soft tissue sampling and bone sampling was assessed with a positive correlation with respect to Gram-positive cocci. Twenty-one patients required conservative surgeries of the foot (9 underwent revascularization), 67% of which avoided a mayor amputation. However no significant variables predictive of a major amputation were detected in this study. In summary, the conservative surgery allowed to 2 out of 3 patients to preserve the foot.

A multicentre, double-blind, randomised study comparing the efficacy and safety of oral levofloxacin versus ciprofloxacin in the treatment of uncomplicated skin and skin structure infections.

A multicentre, randomised, double-blind trial in Latin America compared oral levofloxacin 500 mg once daily for 7 days with oral ciprofloxacin 500 mg twice daily for 10 days in 272 patients with uncomplicated skin and skin structure infections. Among 253 subjects evaluable for clinical efficacy (129 levofloxacin, 124 ciprofloxacin), clinical success (cure and improvement) was observed in 96.1% of levofloxacin-treated patients and in 93.5% of ciprofloxacin-treated patients. Overall, bacteriological eradication rates by pathogen were 93.2% and 91.7%, respectively. Levofloxacin eradicated 94% (66/70) of Staphylococcus aureus and 94% (17/18) of Streptococcus pyogenes isolates, compared with 93% (70/75) and 92% (12/13) for ciprofloxacin. Microbiological eradication rates by subject were approximately 93% and 90% for the levofloxacin and ciprofloxacin groups, respectively. Drug-related adverse events were reported by 8.9% of those receiving levofloxacin and 8.2% of those administered ciprofloxacin. Findings support the efficacy of oral levofloxacin for uncomplicated skin and skin structure infections due to S. aureus and S. pyogenes.

Comparative clinical evaluation of imipenem/cilastatin vs. cefotaxime in treatment of severe bacterial infections.

Adult patients with severe bacterial infections caused by organisms susceptible to imipenem and cefotaxime were given either imipenem/cilastatin sodium (MK0787/MK0791) or cefotaxime as a part of a multiclinic randomized study to evaluate the effectiveness, safety, and tolerability of imipenem/cilastatin. Clinical diagnoses included bacteremia, urinary tract infection, osteomyelitis, mediastinitis, lower respiratory tract infection, and soft tissue infection. Efficacy was evaluated for 10 patients given imipenem/cilastatin and for 10 patients given cefotaxime. Major pathogens isolated included Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, Streptococcus pneumoniae, Bacteroides fragilis, and Peptostreptococcus species. Satisfactory clinical responses were noted in 90% of the patients in both treatment groups. Eradication of the pathogen was achieved in nine of 10 patients treated with imipenem/cilastatin and in 10 of 10 patients treated with cefotaxime. No major adverse effects were found in patients in each treatment group. The results of this study suggest that imipenem/cilastatin sodium is a relatively safe and effective antibiotic for the treatment of adult patients with severe infections caused by susceptible organisms.

[Analysis of urinary infection in the 1st month after kidney transplantation. Value of short prophylaxis with norfloxacin]. / Análisis de la infección urinaria en el primer mes postrasplante renal. Valor de la profilaxis corta con norfloxacino.

Urinary tract infection is the most common complication in the first month after renal transplant, and it is associated with rejection and relapses. In addition, it is the leading cause of gram negative bacilli bacteremia. In a program of continuous epidemiological surveillance from March 1979 to October 1988, we evaluated the urinary tract infections in the first month after renal transplant, considering the following variables: duration of bladder catheterization, urologic complications, type of immunosuppression and preoperative and postoperative antibiotic prophylaxis. There were no differences between the development of urinary tract infections in relation with the duration of bladder catheterization (7 vs 4 days), the reduction of urologic complications (21 vs 6%), or with the introduction of cyclosporin to the conventional immunosuppressive regimen. However, when the group of 46 patients receiving postoperative antibiotic prophylaxis (norfloxacin 800 mg/day every 12 h during the time of vesical catheterization less than or equal to 4 days) was compared with the 147 without postoperative antibiotic prophylaxis, the rate of urinary tract infection in the first month was 8.7% vs 32.8%, respectively (p less than 0.01). Short-term prophylaxis with norfloxacin was a useful regimen, with good oral tolerance and a similar therapeutic efficacy as the sustained regimens reported in the literature.

Pharmacokinetics and pharmacodynamics of amoxicillin-sulbactam, a novel aminopenicillin-beta-lactamase inhibitor combination, against Escherichia coli.

We evaluated the pharmacokinetics of amoxicillin-sulbactam (AMX-SUL), a novel drug combination, and its pharmacodynamics against Escherichia coli in 12 volunteers receiving a single oral dose (1, 000 mg). Peak serum bactericidal and urine inhibitory activities in most volunteers were observed against E. coli strains for which AMX-SUL MICs were low (2- to 4-mg/liter) (2 strains) and high (>/=16-mg/liter) (47 strains), respectively.

Estudio nacional multicéntrico de prevalencia de infección de la herida quirúrgica / National prevalence study of surgical wound infection

En junio de 1988, se realizó un estudio de prevalencia (de un día) de infecciones de la herida quirúrgica en centros asistenciales públicos y privados. El objetivo fue conocer la magnitud del problema como primer paso de un Programa Nacional de Control de Infecciones en cirugía. Se utilizaron las definiciones del CDC para infección de herida y tipos de herida quirúrgica. Los datos fueron incorporados a un programa de computación para su análisis estadístico. Participaron 48 centros de las distintas regiones del país. De un total de 4033 camas quirúrgicas se evaluaron 1412 pacientes operados. Presentaron infección de la herida quirúrgica 268 pacientes (19 por ciento). La prevalencia de infección de herida fue: limpia 10,5 por ciento, limpia contaminada 15 por ciento, contaminada 30 por ciento y sucia 46 por ciento. La tasa fue mayor entre los pacientes que ingresaron infectados (32 por ciento vs 15 por ciento). No se encontraron diferencias significativas en relación a características de las instituciones: públicas o privadas, número de camas, docencia y complejidad quirúrgica. El 70 por ciento de las instituciones tenía Comité de Infecciones. En síntesis: las tasas observadas superan las referidas en otros estudios. Del análisis de los resultados surge que los Comités de Infecciones deben contar con un Programa de Control y la capacidad de asegurar su ejecución