Care at Completion of Antimicrobial Therapy Short-Term Follow-Up The majority of patients with IE are cured with appro- priate medical and, if necessary, surgical treatment. Echocardiography is reasonable before or synchronous with completion of antimicrobial therapy to establish a new baseline for subsequent comparison (Table 18). A referral to a program to assist in the cessation of drug use should be made for IDUs. Patients should be educated about the signs of endocarditis and urged to seek immediate medical attention should they occur. If feasible, a thorough dental evaluation is reasonable, especially in patients deemed likely to require valve replace- ment, with all active sources of oral infection eradicated. All indwelling intravenous catheters used to infuse antimicrobial treatment should be removed promptly at the end of therapy. Routine blood cultures are no longer recommended after the completion of antimicrobial therapy because the likelihood of a positive culture result in a patient who is otherwise without evidence of active infection is low. In the short-term follow-up, patients should be moni- tored for development of several complications (Table 18). A relapse of IE is a primary concern. Patients should be aware that relapses can occur and that new onset of fever, chills, or other evidence of systemic toxicity mandates immediate eval- uation, including a thorough history and physical examination and 3 sets of blood cultures. Every effort should be made to determine the cause of signs or symptoms of infection. In addition, prescribing empirical antimicrobial therapy should be avoided for an undefined febrile illness unless the patient s clinical condition (eg, sepsis) warrants empirical therapy. It is reasonable for patients who have completed therapy to undergo an examination after completing antibiotic therapy. Developing or worsening heart failure is a second com- plication that should be considered during short-term follow- up. Although new onset of heart failure caused by valvular dysfunction is unlikely during this period, valve function can deteriorate as a result of ongoing infection or mechanical stress unrelated to infection. In addition to physical examina- tion, echocardiographic findings can support this diagnosis. If heart failure develops or worsens, the patient should be evalu- ated immediately for cardiac surgery. Antibiotic toxicity still can occur after the completion of treatment and is the third complication that should be consid- ered during short-term follow-up. Two drug-related adverse events are concerns. The first is delayed ototoxicity because of the previous use of aminoglycosides. Audiological and Table 18. Care During and After Completion of Antimicrobial Treatment Initiation before or at completion of therapy Echocardiography to establish new baseline Drug rehabilitation referral for patients who use illicit injection drugs Education on the signs of endocarditis and need for antibiotic prophylaxis for certain dental/surgical/invasive procedures Thorough dental evaluation and treatment if not performed earlier in evaluation Prompt removal of intravenous catheter at completion of antimicrobial therapy Short-term follow-up At least 3 sets of blood cultures from separate sites for any febrile illness and before initiation of antibiotic therapy Physical examination for evidence of heart failure Evaluation for toxicity resulting from current/previous antimicrobial therapy Long-term follow-up At least 3 sets of blood cultures from separate sites for any febrile illness and before initiation of antibiotic therapy Evaluation of valvular and ventricular function (echocardiography) Scrupulous oral hygiene and frequent dental professional office visits Baddour et al Infective Endocarditis in Adults 1473 vestibular toxicity can develop despite the maintenance of appropriate serum drug concentrations during treatment. For patients receiving long-term aminoglycosides, particu- larly those with underlying renal or otic disorders, serial audiograms may be considered during therapy if feasible and available. No tools are routinely available for monitor- ing vestibular function, and patients should be told to report the onset of any symptoms of vestibular toxicity during or after treatment. The second antibiotic-related adverse event is Clostridium difficile infection. Onset of diarrhea can be delayed as long as 4 weeks after the last dose of antibiotic. The hope is that prompt recognition and treatment of this infectious complica- tion will diminish the likelihood of severe complications. Recommendations 1. Echocardiography is reasonable before or synchro- nous with completion of antimicrobial therapy to establish a new baseline for subsequent compari- son (Class IIa; Level of Evidence C). 2. A referral to a program to assist in the cessation of drug use should be made for IDUs (Class I; Level of Evidence C). 3. Patients should be educated about the signs of endocarditis and urged to seek immediate medi- cal attention should they develop (Class I; Level of Evidence C). 4. A thorough dental evaluation is reasonable, espe- cially in patients deemed likely to require valve replacement, with all active sources of oral infec- tion eradicated (Class IIa; Level of Evidence C). 5. Routine blood cultures are not recommended after the completion of antimicrobial therapy because the likelihood of a positive culture result in a patient who is otherwise without evidence of active infection is low (Class III; Level of Evidence C). 6. All indwelling intravenous catheters used to infuse antimicrobial treatment should be removed promptly at the end of therapy (Class I; Level of Evidence C). 7. For patients receiving long-term aminoglycosides, particularly those with underlying renal or otic disorders, serial audiograms may be considered during therapy if available (Class IIb; Level of Evidence C). 8. In the short-term follow-up, patients should be monitored for the development of several com- plications, including IE relapse and heart failure (Class I; Level of Evidence C). 9. Patients should be aware that relapses can occur and that new onset of fever, chills, or other evidence of systemic toxicity mandates immediate evalu- ation, including a thorough history and physical examination and 3 sets of blood cultures (Class I; Level of Evidence C). 10. Because of concerns for IE relapse, a thorough evalua- tion should be done to determine the cause of infection signs and symptoms (Class I; Level of Evidence C). 11. Empirical antimicrobial therapy for suspected infection should be avoided unless the patient s clinical condition (eg, sepsis) warrants it (Class III; Level of Evidence C). 12. It is reasonable to have patients who have completed therapy and do not have symptoms of systemic tox- icity undergo an examination after completing anti- biotic therapy (Class IIa; Level of Evidence C). 13. Developing or worsening heart failure is a common complication that should be monitored for during short-term follow-up (Class I; Level of Evidence C). 14. If heart failure develops or worsens, the patient should be evaluated immediately for cardiac sur- gery (Class I; Level of Evidence B). 15. Antibiotic toxicity still can occur after the comple- tion of treatment and is a complication that should be considered during short-term follow-up (Class I; Level of Evidence C). 16. No tools are routinely available for monitoring vestibular function, and patients should be told to report the onset of any symptoms of vestibular toxicity during or after treatment (Class I; Level of Evidence C). Long-Term Follow-Up Months to years after completion of medical therapy for IE, patients should have ongoing observation for and education about recurrent infection and delayed onset of worsening valve dysfunction (Table 18). Daily dental hygiene should be stressed, with serial evaluations by a dentist who is familiar with this patient population. Patients should be questioned about symptoms of heart failure, and a thorough physi- cal examination should be done. Additional evaluation with echocardiography is indicated in selected patients with posi- tive findings from history and physical examination. Patients should be instructed to seek immediate medical evaluation for persistent fever (Table 18). This is necessary because IE can mimic a variety of febrile illnesses. Blood cultures should be obtained. Antibiotic therapy should not be initiated for treat- ment of undefined febrile illnesses without blood cultures being obtained first. Antibiotics prescribed for nonspecific or unproved febrile syndromes are a major cause of (blood) culture-negative IE, and this practice should be strongly discouraged. Recommendations 1. Months to years after completion of medical ther- apy for IE, patients should have ongoing observa- tion for and education about recurrent infection and delayed onset of worsening valve dysfunction (Class I; Level of Evidence C). 2. Daily dental hygiene should be stressed, with serial evaluations by a dentist who is familiar with this patient population (Class I; Level of Evidence C). 3. Patients should be questioned about symptoms of heart failure, and a thorough physical examination should be done (Class I; Level of Evidence C). 4. Additional evaluations with echocardiography should be obtained in selected patients with posi- tive findings from history and physical examina- tion (Class I; Level of Evidence C). 5. Patients should be instructed to seek immediate medical evaluation for fever, and blood cultures should be obtained (Class I; Level of Evidence C). 6. Antimicrobial therapy should not be initiated for the treatment of undefined febrile illnesses unless the patient s condition (eg, sepsis) warrants it (Class III; Level of Evidence C). Dental Management A large, prospective study demonstrated a strong associa- tion between 3 indexes of oral hygiene and gingival disease and the incidence of bacteremia from IE-related species.327 Poor oral hygiene results in gingivitis, which often leads to periodontitis, and it is likely that these 2 periodontal dis- eases are associated with community-acquired IE. Current evidence suggests that poor oral hygiene and periodon- tal diseases, not dental office procedures, are likely to be responsible for the vast majority of cases of IE that originate in the mouth.328 Regardless of the source of infection, inpatients with IE should be thoroughly evaluated by a dentist familiar with the potential role of the mouth in these cases. The optimal timing for this evaluation may be after the patient s cardiac status has stabilized and early enough that all invasive dental procedures can be accomplished during intravenous antibiotic therapy. The clinical examination should rule out periodontal inflammation and pocketing around the teeth and caries that will eventually result in pulpal infection. A full series of intra- oral radiographs is required for the identification of caries and periodontal disease (eg, bone loss, tooth fractures). All of this is aimed at reducing the incidence and magnitude of bactere- mia from any manipulation of the gingival tissues, including normal daily events such as brushing teeth and chewing food. Treatment invariably involves a thorough dental cleaning by a hygienist who will review with patients the importance of maintaining scrupulous oral hygiene. Dental disease is almost entirely preventable if patients are compliant with 4 measures. First, the cause of both peri- odontal disease and caries is bacterial plaque accumulation on teeth, and prevention is dependent on keeping teeth free of plaque. Second, patients must understand that dietary mea- sures are critically important in preventing the formation of plaque, especially in areas on the teeth that are difficult to keep clean. The degree to which sugar and other refined carbohydrates are eliminated from the diet will have a major impact on the growth of pathogenic bacterial species, some of which are responsible for IE. Third, routine follow-up with their family dentist is necessary for close monitoring of oral hygiene and the early identification and eradication of oral disease. Finally, the daily use of a high-concentration fluori- dated toothpaste will help to ensure that the acid from plaque does not decalcify tooth structures and result in caries.A focus on all 4 measures should help to reduce the incidence of bac- teremia and the risk for recurrent IE. Recommendations 1. Inpatients with IE should be thoroughly evaluated by a dentist to identify and eliminate oral diseases that predispose to bacteremia and may therefore contribute to the risk for recurrent IE (Class I; Level of Evidence C). 2. The clinical examination should focus on periodon- tal inflammation and pocketing around teeth and caries that may result in pulpal infection and subse- quent abscess (Class I; Level of Evidence C). 3. A full series of intraoral radiographs will allow the identification of caries and periodontal disease and other disease (eg, tooth fractures) not evident from the physical examination. This should occur when the patient is able to travel to a dental facility (Class I; Level of Evidence C). Baddour et al Infective Endocarditis in Adults 1475 Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other Larry M. Baddour Mayo Clinic None None None None None None None Robert S. Baltimore Yale University School of Medicine None None None None None None None Bruno Barsic Hospital for Infectious Diseases, School of Medicine Zagreb None None Astellas*; Pfizer*; MSD* None None None None Arnold S. Bayer LA Biomedical Research Institute Infectious Diseases Astellas ; Cubist ; NIH/NIAID*; Theravance* None None Johnson Graffe et al*; Morrow, Kidman, Tinker et al*; Galloway, Lucchese et al*; MES Solutions*; Hoffman, Sheffield et al*; Clifford Law* None None None Ann F. Bolger UCSF None None None None None None None Anne M. Fink University of Illinois at Chicago None None None None None None None Vance G. Fowler, Jr. Duke University CDC ; Cerexa/Forest ; MedImmune ; NIH ; FDA ; Cubist* None None Witness in case involving group B Streptococcal Vertebral osteomyelitis None MedImmune*; Novartis ; The Medicines Comapy*; Novadigm*; Debiopharm*; Cerexa*;Affinium*; Tetraphase*; Bayer*; Theravance*; Cubist*; Genetech*; Basilea* None Michael H. Gewitz New York Medical College None None None None None None None Matthew E. Levison Drexel University College of Medicine None None None None None Merck Manual None Peter B. Lockhart Carolinas Medical Center None None None None None None None Patrick O Gara Brigham and Women s Hospital None None None None None None None Michael J. Rybak Wayne State University Cubist*; Forest*; MDCH*; NIH*; Actavis*; Theravance* None Cubist*; Forest*; Novartis*; Actavis*; The Medicines Company* None None Cubist*; Forest*; Theravance*; Actavis ; The Medicines Company* None James M. Steckelberg Mayo Clinic None None None None None None None Kathryn A. Taubert American Heart Association None None None None None None None Imad M. Tleyjeh King Fahd Medical City None None None None None None None Walter R. Wilson Mayo Clinic None None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be significant if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. Disclosures References 1. Duval X, Delahaye F, Alla F, Tattevin P, Obadia JF, Le Moing V, Doco- Lecompte T, Celard M, Poyart C, Strady C, Chirouze C, Bes M, Cambau E, Iung B, Selton-Suty C, Hoen B; AEPEI Study Group. Temporal trends in infective endocarditis in the context of prophylaxis guideline modifi- cations: three successive population-based surveys. J Am Coll Cardiol. 2012;59:1968 1976. doi: 10.1016/j.jacc.2012.02.029. 2. Correa de Sa DD, Tleyjeh IM,Anavekar NS, Schultz JC, Thomas JM, Lahr BD, Bachuwar A, Pazdernik M, Steckelberg JM, Wilson WR, Baddour LM. 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Benito N, Mir JM, de Lazzari E, Cabell CH, del R o A, Altclas J, Commerford P, Delahaye F, Dragulescu S, Giamarellou H, Habib G, Reviewer Disclosures Reviewer Employment Research Grant Other Research Support Speakers Bureau/Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other Giovanni Di Salvo King Faisal Hospital and Research Center (Saudi Arabia) None None None None None None None Franklin D. Lowy Columbia University None None None None None None UptoDate* Stanford T. Shulman Lurie Children s Hospital, Children s Memorial Hospital, Northwestern University Medical School None None None None None None None This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. 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