Background—Despite advances in medical, surgical, and critical care interventions, infective endocarditis remains a disease that is associated with considerable morbidity and mortality. The continuing evolution of antimicrobial resistance among common pathogens that cause infective endocarditis creates additional therapeutic issues for physicians to manage in this potentially life-threatening illness. Methods and Results—This work represents the third iteration of an infective endocarditis “treatment” document developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It updates recommendations for diagnosis, treatment, and management of complications of infective endocarditis. A multidisciplinary committee of experts drafted this document to assist physicians in the evolving care of patients with infective endocarditis in the new millennium. This extensive document is accompanied by an executive summary that covers the key points of the diagnosis, antimicrobial therapy, and management of infective endocarditis. For the first time, an evidence-based scoring system that is used by the American College of Cardiology and the American Heart Association was applied to treatment recommendations. Tables also have been included that provide input on the use of echocardiography during diagnosis and treatment of infective endocarditis, evaluation and treatment of culture-negative endocarditis, and short-term and long-term management of patients during and after completion of antimicrobial treatment. To assist physicians who care for children, pediatric dosing was added to each treatment regimen. Conclusions—The recommendations outlined in this update should assist physicians in all aspects of patient care in the diagnosis, medical and surgical treatment, and follow-up of infective endocarditis, as well as management of associated complications. Clinical variability and complexity in infective endocarditis, however, dictate that these guidelines be used to support and not supplant physician-directed decisions in individual patient management. (Circulation. 2005; 111:e394-e433.)

http://www.endocardites-aquitaine.fr/fileadmin/documents/documents/2005BADDOUR.pdf

Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America

The BSAC Guidelines on Endocarditis were last published in 1998. The Guidelines presented here have been updated and extended to reflect changes in both the antibiotic resistance characteristics of causative organisms and the availability of new antibiotics. Randomized, controlled trials suitable for the development of evidenced-based guidelines in this area are still lacking, and therefore a consensus approach has again been adopted. The Guidelines cover diagnosis and laboratory testing, suitable antibiotic regimens and causative organisms. Special emphasis is placed on common causes of endocarditis, such as streptococci and staphylococci, however, other bacterial causes (such as enterococci, HACEK organisms, Coxiella and Bartonella) and fungi are considered. The special circumstances of prosthetic endocarditis are discussed.

/pdf/guidelines-for-the-diagnosis-and-antibiotic-treatment-of-16q5icln36.pdf

Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy

Objective To compare β lactam monotherapy with β lactam-aminoglycoside combination therapy for severe infections. Data sources Medline, Embase, Lilacs, Cochrane Library, and conference proceedings, to 2003; references of included studies; contact with all authors. No restrictions, such as language, year of publication, or publication status. Study selection All randomised trials of β lactam monotherapy compared with β lactam-aminoglycoside combination therapy for patients without neutropenia who fulfilled criteria for sepsis. Data selection Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary outcome assessed was all cause fatality by intention to treat. Relative risks were pooled with the random effect model (relative risk Results 64 trials with 7586 patients were included. There was no difference in all cause fatality (relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared the same β lactam (1.02, 0.76 to 1.38), and 31 studies compared different β lactams (0.85, 0.69 to 1.05). Clinical failure was more common with combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing different β lactams (0.76, 0.68 to 0.86). There was no advantage to combination therapy among patients with Gram negative infections (1835 patients) or Pseudomonas aeruginosa infections (426 patients). There was no difference in the rate of development of resistance. Nephrotoxicity was significantly more common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not significant for these comparisons. Conclusions In the treatment of sepsis the addition of an aminoglycoside to β lactams should be discouraged. Fatality remains unchanged, while the risk for adverse events is increased.

https://www.bmj.com/content/bmj/328/7441/668.full.pdf

β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials

The clinical courses of 13 consecutive intravenous drug users with Staphylococcus aureus endocarditis treated principally with vancomycin were reviewed. Two patients, one with only right-sided endocarditis and the other with tricuspid and mitral valve endocarditis, had recurrences of positive blood cultures 2 days after completing a 4-week course of vancomycin. Two patients, both of whom eventually were cured, had modifications of therapy because of bacteremia persisting 7 and 16 days into therapy. One patient required an operation for recurrent fevers, and the resected vegetation showed evidence of active infection. Time-kill studies performed with nafcillin and vancomycin for 10 isolates of S. aureus showed that vancomycin was less rapidly bactericidal than nafcillin. Although vancomycin is used as an alternative to penicillinase-resistant penicillins for treatment of staphylococcal endocarditis, these findings raise the question of whether it is equivalent to these drugs in efficacy.

https://aac.asm.org/content/aac/34/6/1227.full.pdf

Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users.

http://www.endocardites-aquitaine.fr/fileadmin/documents/documents/2012THUNY.pdf

Management of infective endocarditis: challenges and perspectives

Staphylococcus aureus is the commonest cause of acute endocarditis in intravenous drug abusers. In-vitro and in-vivo animal studies have found increased killing of organisms with the combination of a beta-lactam antibiotic and an aminoglycoside. These findings have created a controversy about the use of such combination therapy. We randomly treated 25 episodes of S. aureus endocarditis in intravenous drug abusers with either single or combination antibiotic regimens. Mean days to defervescence were similar in both groups: 6.3 d (SEM, 1.49 d) for the single drug group and 6.6 d (SEM, 1.02 d) for the group treated in combination with an aminoglycoside. There were no bacteriologic failures or relapses in either group. No patients needed valvular surgery, and the mortality rate was zero. Thus, it appears that single drug therapy with an appropriate beta-lactam antibiotic is adequate and appropriate in intravenous drug abusers with S. aureus endocarditis.

Single or Combination Therapy of Staphylococcal Endocarditis in Intravenous Drug Abusers

We retrospectively reviewed 55 episodes that fulfilled criteria for Staphylococcus aureus endocarditis in 50 drug addicts. The most common presenting symptoms were fever(90%), chest pain(58%), and cough(43%). All patients had evidence of right-sided heart involvement, and a murmur of tricuspid insufficiency was noted in 42%. Evidence of left-sided heart involvement was present in only 5%. The most helpful laboratory aid in facilitating an early clinical diagnosis of endocarditis was the chest x-ray film. Roentgenographic evidence of septic pulmonary emboli was present in 67% of initial chest films and eventually in 87% of all cases. All but five patients completed at least four weeks of intravenous antibiotic therapy. No patients required cardiac surgery and there were no deaths. The apparent predilection of S aureus for the right side of the heart and infrequent left-sided involvement may explain why addicts with endocarditis have a favorable response to antibiotic therapy.

Staphylococcal endocarditis in addicts.

The therapeutic efficacy of amikacin was evaluated in patients with serious hospital-acquired infections caused by Gram-negative bacilli susceptible to amikacin, but usually resistant to kanamycin, gentamicin, and tobramycin. The infections for which amikacin was given were Gram-negative bacteremia in 15 patients and Gram-negative meningitis in two patients. Therapy with amikacin resulted in a cure in 13 patients, improvement in 1, and failure in 3. Continuous intravenous infusion of amikacin yielded a high cerebrospinal fluid to serum ratio of amikacin in one case of meningitis and intrathecally administered amikacin yielded high ventricular fluid levels in another case of meningitis. The emergence of resistance to amikacin was noted in one patient treated with amikacin in whom Serratia bacteremia persisted. Treatment with amikacin was usually tolerated well. This study indicates that amikacin is an effective antibiotic in the treatment of serious Gram-negative infections caused by gentamicin-resistant organisms. ( Arch Intern Med 138:713-716, 1978)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=intemed&articleId=587938&pdfFileName=archinte_138_5_013.pdf

Amikacin therapy of gram-negative bacteremia and meningitis. Treatment in diseases due to multiple resistant bacilli.

We evaluated clinical features of five cases of Toxoplasma encephalitis (TE) occurring in recent Haitian entrants into the United States. None of the patients had any underlying malignancy or known immunosuppressive therapy. Histopathologic findings of TE at autopsy were confirmed by peroxidase-antiperoxidase method. Four patients had an antecedent episode of disseminated tuberculosis and all five were receiving antituberculous therapy when neurologic manifestations of lethargy, seizures, and motor weakness first developed. These symptoms progressed into coma and death within 15 days. Peripheral lymphocytopenia was noted in all patients; three were anergic. Parenchymal lesions were identified by CT brain scans and total proteins were elevated in spinal fluid in all cases. TE appears to be a manifestation of the acquired immune deficiency syndrome in Haitians; it should be suspected in those with a febrile illness and multiple focal lesions of the central nervous system.

Richard L. Greenman

Papers

Single or Combination Therapy of Staphylococcal Endocarditis in Intravenous Drug Abusers

Staphylococcal endocarditis in addicts.

Amikacin therapy of gram-negative bacteremia and meningitis. Treatment in diseases due to multiple resistant bacilli.

Toxoplasma encephalitis in recent Haitian entrants.