Culture-negative infective endocarditis (CNE) is a diagnostic problem in spite of improved echocardiographic and blood culturing techniques. We conducted the present study to estimate the proportion of CNE in patients with infective endocarditis, to investigate data regarding risk factors, and to evaluate the Duke and the modified Beth Israel criteria in patients with CNE. We evaluated 820 consecutive suspected episodes of infective endocarditis in adults at the Departments of Infectious Diseases in Göteborg and Borås, Sweden (1984-1996). All patients were diagnosed and treated according to a protocol; 487 episodes were identified as infective endocarditis. Episodes with absence of bacterial growth at blood culture were defined as CNE and were classified with the Duke and the modified Beth Israel criteria. We identified 116 CNE episodes (median age, 67 yr). Mortality was 7%, and in 15%, cardiac surgery was performed. The Duke criteria classified 20 definite, 80 possible, and 16 reject episodes. The modified Beth Israel criteria distinguished 13 definite, 15 probable, 27 possible, and 61 reject episodes. The proportion of CNE among patients with infective endocarditis varied from 19% to 27% at the 2 departments. Antibiotic treatment preceded blood culture in 45% of the CNE episodes. About 20% in a Scandinavian population of infective endocarditis patients have CNE. Antibiotic pretreatment explains less than 50% of all CNE episodes. The Duke criteria are more sensitive but less specific than the modified Beth Israel criteria in classifying patients with CNE.

Swedish guidelines for diagnosis and treatment of infective endocarditis (IE) by consensus of experts are based on clinical experience and reports from the literature. Recommendations are evidence based. For diagnosis 3 blood cultures should be drawn; chest X-ray, electrocardiogram, and echocardiography preferably transoesophageal should be carried out. Blood cultures should be kept for 5 d and precede intravenous antibiotic therapy. In patients with native valves and suspicion of staphylococcal aetiology, cloxacillin and gentamicin should be given as empirical treatment. If non-staphylococcal etiology is most probable, penicillin G and gentamicin treatment should be started. In patients with prosthetic valves treatment with vancomycin, gentamicin and rifampicin is recommended. Patients with blood culture negative IE are recommended penicillin G (changed to cefuroxime in treatment failure) and gentamicin for native valve IE and vancomycin, gentamicin and rifampicin for prosthetic valve IE, respectively. Isolates of viridans group streptococci and enterococci should be subtyped and MIC should be determined for penicillin G and aminoglycosides. Antibiotic treatment should be chosen according to sensitivity pattern given 2-6 weeks intravenously. Cardiac valve surgery should be considered early, especially in patients with left-sided IE and/or prosthetic heart valves. Absolute indications for surgery are severe heart failure, paravalvular abscess, lack of response to antibiotic therapy, unstable prosthesis and multiple embolies. Follow-up echocardiography should be performed on clinical indications.

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The Swedish Reference Group for Antibiotics (SRGA) has carried out a risk-benefit analysis of aminoglycoside treatment based on clinical efficacy, antibacterial spectrum, and synergistic effect with beta-lactam antibiotics, endotoxin release, toxicity, and side effects. In addition, SRGA has considered optimal dosage schedules and advice on serum concentration monitoring, with respect to variability in volume of drug distribution and renal clearance. SRGA recommends that aminoglycoside therapy should be considered in the following situations: (1) progressive severe sepsis and septic shock, in combination with broad-spectrum beta-lactam antibiotics, (2) sepsis without shock, in combination with broad-spectrum beta-lactam antibiotics if the infection is suspected to be caused by multi-resistant Gram-negative pathogens, (3) pyelonephritis, in combination with a beta-lactam or quinolone until culture and susceptibility results are obtained, or as monotherapy if a serious allergy to beta-lactam or quinolone antibiotics exists, (4) serious infections caused by multi-resistant Gram-negative bacteria when other alternatives are lacking, and (5) endocarditis caused by difficult-to-treat pathogens when monotherapy with beta-lactam antibiotics is not sufficient. Amikacin is generally more active against extended-spectrum beta-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli than other aminoglycosides, making it a better option in cases of suspected infection caused by multidrug-resistant Enterobacteriaceae. Based on their resistance data, local drug committees should decide on the choice of first-line aminoglycoside. Unfortunately, aminoglycoside use is rarely followed up with audiometry, and in Sweden we currently have no systematic surveillance of adverse events after aminoglycoside treatment. We recommend routine assessment of adverse effects, including hearing loss and impairment of renal function, if possible at the start and after treatment with aminoglycosides, and that these data should be included in hospital patient safety surveillance and national quality registries.