Infective Endocarditis Empirical therapy Antibiotic Guidelines Classification: Clinical Guideline Lead Author: Antibiotic Steering Group Additional author(s): as above Authors Division: Division of Clinical Support Services & Tertiary Medicine Unique ID: 144TD(C)25(C4) Issue number: 4 Expiry Date: November 2018 Contents Who should read this document?... 2 Key Practice Points... 2 Background/ Scope/ Definitions... 2 What is new in this version?... 3 Guideline... 3 Endocarditis, Infective Empirical treatment of... 3 1. Initial Investigations... 3 2. Diagnosis... 5 3. Treatment... 6 3.1 Native valve endocarditis indolent presentation... 6 3.2 Native valve endocarditis severe sepsis... 6 3.3 Native valve endocarditis severe sepsis AND risk factors... 7 3.4 Prosthetic valve endocarditis... 7 3.5 Therapeutic drug monitoring... 8 Standards... 8 Explanation of terms & Definitions... 8 References and Supporting Documents... 9 Roles and responsibilities... 9 Appendices... 9 Document Control Information... Error! Bookmark not defined. Policy Implementation Plan... Error! Bookmark not defined. Monitoring and Review... Error! Bookmark not defined. Endorsement... Error! Bookmark not defined. Screening Equality Analysis Outcomes... Error! Bookmark not defined. Page 1 of 9
Who should read this document? This policy applies to all clinical staff involved the prescribing of antimicrobials. Key Practice Points This policy highlights the roles and responsibilities of clinical staff involved in prescribing empirical antimicrobials for infective endocarditis. These guidelines are empiric. For organism specific advice and information about duration, refer to UK guidelines or discuss with microbiology. Background/ Scope/ Definitions Antimicrobial agents are among the most commonly prescribed drugs and account for 20% of the hospital pharmacy budget. Unfortunately, the benefits of antibiotics to individual patients are compromised by the development of bacterial drug resistance. Resistance is a natural and inevitable result of exposing bacteria to antimicrobials. Good antimicrobial prescribing will help to reduce the rate at which antibiotic resistance emerges and spreads. It will also minimise the many side effects associated with antibiotic prescribing, such as Clostridium difficile infection. It should be borne in mind that antibiotics are not needed for simple coughs and colds. In some clinical situations, where infection is one of several possibilities and the patient is not showing signs of systemic sepsis, a wait and see approach to antibiotic prescribing is often justified while relevant cultures are performed. This document provides treatment guidelines for the most common situations in which antibiotic treatment is required. The products and regimens listed here have been selected by the Trust's Medicines Management Group on the basis of published evidence. Doses assume a weight of 60-80kg with normal renal and hepatic function. Adjustments may be needed for the treatment of some patients. This document provides treatment guidelines for the appropriate use of antibiotics. The recommendations that follow are for empirical therapy and do not cover all clinical circumstances. Alternative antimicrobial therapy may be needed in up to 20% of cases. Alternative recommendations will be made by the microbiologist in consultation with the clinical team. This document refers to the treatment of adult patients (unless otherwise stated). Refer to up to date BNF/SPC for information on interactions, side effects, cautions and contraindications for individual drugs. In the case where an antibiotic prescription is necessary, probiotic therapy should be considered in order to reduce the risk of C. difficile infection Page 2 of 9
What is new in this version? Sectionn 3.2 - Native valve endocarditis severe sepsis (no risk factors for Gram-negatives*). The combination of vancomycin and gentamicin alone will not provide optimum Gram negative cover so if the source of infection remains unclear, broad spectrum cover with piperacillin/tazobactam or meropenem may be added to cover for sepsis of uncertain origin. Guideline Endocarditis, Infective Empirical treatment of These guidelines are for empiric therapy only, if the causative organism is identified, a microbiologist MUST be contacted for treatment advice. For advice on duration, refer to UK guidelines Gould et al (see references section for document details). 1. Initial Investigations A high index of suspicion and a low threshold for investigation are essential to exclude infective endocarditis in high risk patients. The British Society for Antimicrobial Chemotherapy recommends that echocardiography must be performed as soon as possible in all patients with suspected infective endocarditis, ideally within 24 hours. Transthoracic echocardiography (TTE) is the initial investigation of choice (sensitivity 70-80%). Blood cultures should be taken BEFORE starting antibiotics in ALL cases. In patients with a subacute presentation, three blood culture sets should be taken from peripheral sites at least 6 hours apart. In patients with severe sepsis/septic shock, two blood culture sets should be taken within 1 h prior to commencing empirical therapy. Blood cultures can be taken from the same site, but must be taken at different times. Empirical antibiotic treatment should be started before the results of blood cultures are known. Once the results of the blood cultures and antibiotic sensitivities are known, adjust the prescribed therapy and duration according to advice from microbiology. Repeat blood cultures are not recommended. Culture Negative Endocarditis. In patients with blood culture negative infective endocarditis, first line serological testing for Coxiella (Q fever) and Bartonella should be performed. Page 3 of 9
In cases with an initial negative TTE/TOE, repeat TTE/TOE should be performed 7-10 days later if clinical suspicion remains high. Routine repeat echocardiography whilst on treatment is not required but repeat echocardiography may be required in some cases consult with cardiology in all cases of definite or probable endocarditis. ALL patients with a Staphylococcus aureus bacteraemia or a candidaemia should have a TTE, due to the frequency of IE in this setting, the virulence of these organisms, the devastating effects once intracardiac infection is established and/or the need for surgery. Patients should have a TTE within the first week of treatment (or within 24 hours if there is other evidence to suggest IE). Unexplained fevers in a paced patient should prompt a search for pacing lead associated endocarditis. All patients with suspected or confirmed endocarditis MUST be reviewed by a cardiologist and a microbiologist to ensure optimal treatment is achieved, in terms of antimicrobial choice, dose and duration. ALL therapy MUST be given by the IV route. Page 4 of 9
2. Diagnosis Duke criteria can be used to assist in the diagnosis of IE, but are not a substitute for clinical judgement. Table 1: Modified Duke criteria for diagnosis of infective endocarditis (adapted from Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy 2011). A diagnosis of definite infective endocarditis requires: two major criteria; or one major and three minor criteria; or five minor criteria. Criterion Diagnostic Type Major criteria Positive blood culture Evidence of endocardial involvement Minor criteria Predisposition to IE Fever Vascular phenomena Immunological phenomena Microbiology phenomena Echocardiographic findings Typical organism consistent with IE from TWO separate blood cultures drawn > 6 hours apart OR drawn within 1 hour in the presence of severe sepsis/septic shock. OR C.burnetii antiphase I IgG antibody titre >1:800. Positive echocardiogram for IE OR New valvular regurgitation (worsening or changing murmur is NOT sufficient). viridans streptococci, Streptococcus bovis or HACEK group, OR community-acquired Staphylococcus aureus or enterococci (in the absence of a primary focus). Predisposing heart condition or IVDU. Temperature >38.0 C Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhages and Janeway lesions. Glomerulonephritis, Osler s nodes, Roth spots, Rheumatoid factor. Positive blood culture but does not meet a major criterion (as above). Serological evidence of active infection with an organism consistent with IE. Consistent with IE but do not met a major criterion (as above). Page 5 of 9
3. Treatment The empirical treatment advice is sub -divided into the following sections Section 3.1 Native valve endocarditis indolent presentation (i.e NOT acutely unwell) Section 3.2 Native valve endocarditis severe sepsis (no risk factors for Gram-negatives*) Section 3.3 Native valve endocarditis severe sepsis AND risk factors for Gram negatives* Section 3.4 Prosthetic valve endocarditis Section 3.5 Therapeutic drug monitoring for the empirical treatment management of infective endocarditis Doses quoted assume patients are of average weight with normal renal and hepatic function. If advice is required, contact the ward pharmacist or microbiologist. *Risk factors for Gram negative infection include: recurrent UTIs, biliary sepsis or intra-abdominal infection in the last 3 months 3.1 Native valve endocarditis indolent presentation (i.e NOT acutely unwell) Patients with a penicillin allergy see section 3.2 Amoxicillin 2g IV every 4 hours (if egfr<50ml/min discuss with microbiology) PLUS Gentamicin 1mg/kg (Ideal body weight) IV every 12 hours Adjust gentamicin dose appropriately if patient is elderly, has impaired renal function or is obese /underweight. This can be discussed with the ward pharmacist. For therapeutic drug monitoring of gentamicin, see section 3.5. 3.2 Native valve endocarditis severe sepsis (no risk factors for Gram-negatives*) Acutely unwell is defined as patient with embolic features, general sepsis syndrome and is haemodynamically unstable. Vancomycin IV PLUS Gentamicin 1mg/kg (Ideal body weight) IV every 12 hours Adjust vancomycin or gentamicin dose appropriately if patient is elderly, has impaired renal function or is obese /underweight. This can be discussed with the ward pharmacist. For therapeutic drug monitoring of gentamicin, see section 3.5. Page 6 of 9
This combination will not provide optimum Gram negative cover so if the source of infection remains unclear consider adding cover for sepsis of uncertain origin: Add Piperacillin/tazobactam 4.5g IV tds (bd if CrCl <20ml/min, CKD 5) Penicillin allergy without anaphylaxis/angioedema/bronchospasm: Add meropenem 1g every 8 hours Severe penicillin allergy/anaphylaxis/angioedema/bronchospasm Discuss with microbiology 3.3 Native valve endocarditis severe sepsis AND risk factors for Gram negatives* Vancomycin IV PLUS Meropenem 2g IV every 8 hours (if egfr<50ml/min discuss with microbiology) Patients with anaphylaxis, angiodema or bronchospasm to penicillins contact microbiology. Adjust vancomycin or gentamicin dose appropriately if patient is elderly, has impaired renal function or is obese /underweight. This can be discussed with the ward pharmacist. For therapeutic drug monitoring of vancomycin and gentamicin see section 3.5. 3.4 Prosthetic valve endocarditis Treat as per section 3.2 or 3.3 above depending on presence of risk factors for Gram negative infection, PLUS Rifampicin 600 mg twice daily orally/iv (use lower doses of rifampicin in severe renal impairment) Page 7 of 9
3.5 Therapeutic drug monitoring for the empirical treatment management of infective endocarditis Throughout therapy, antibiotic level monitoring must be conducted. The following table is a reference for appropriate blood levels: Antibiotic Sampling times Appropriate trough level Gentamicin Immediately 1mg/L before third dose and one hour after the end of administration Vancomycin Immediately 15-20mg/L before fourth dose or after 48hrs of therapy. Pre-dose (trough level required) Appropriate peak level 3-5mg/L n/a Standards Document the Indication/rationale for antimicrobial therapy, including clinical criteria relevant to this. Review and document the patient s allergy status Ensure the choice of antibiotic complies with the antibiotic guidelines and you have documented any clinical criteria relevant to the choice of agent. Document a management plan including a stop or review date. Where relevant, consider drainage of pus or surgical debridement/removal of foreign material. Explanation of terms & Definitions Not applicable Page 8 of 9
References and Supporting Documents Li J S, Sexton D, Mick N et al. Proposed Modifications to the Duke Criteria for the Diagnosis of Infective Endocarditis. Clinical Infect Dis 2000;30:633-638 Gould FK, Denning DW et al. Guidelines for the antibiotic treatment of endocarditis in adults: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2011; 67: 269 289. Habib G et al. 2015 ESC Guidelines for the management of infective endocarditis. European Heart Journal http://dx.doi.org/10.1093/eurheartj/ehv319 August 2015 Roles and responsibilities All clinical staff involved in the prescribing of antimicrobials to adhere to this policy including full documentation on EPMAR as detailed. Appendices Not applicable Page 9 of 9