(2/23) Glowacki Lecture: Infective Endocarditis (IE) and Central Venous Catheter Infections Bacterial Endocarditis: A microbial infection of a platelet-fibrin vegetation on the endothelial surface of the heart. The infective organism adheres to the platelet-fibrin scab on the heart valve. Heart valves: Tricuspid, Pulmonic, Mitral, Aortic. The most commonly infected heart valve is the mitral valve

- Pathophysiology: Insult to the valvular or endocardial endothelium allows for the deposition of platelet-fibrin aggregates. A thrombotic vegetative source, it serves as an ideal location for bacteria to adhere to following episodes of transient bacteremia

- Risk Factors: Prosthetic Valves, previous endocarditis, indwelling catheters, patent ductus. Rheumatic Heart Disease, intravenous drug abuse (IVDA), dental or surgical procedures

- S/Sx: Fever, chills, weakness, dyspnea, night sweats, weight loss, malaise – quite non-specific o Physical: Splinter hemorrhages, painful lesions, Osular nodes, Janeway lesions o Labs: WBC ~/Ý, Anemia, Thrombocytopenia, ESRÝ, CRPÝ - all non-specific o Culture: HALLMARK lab finding is continuous bacteremia

- Diagnostic Tests o Blood Cultures: 3 sets over the course of 24 hours. Perform 1-2 sets daily until negative.

§ They should be at different sites to *decrease the chance of contamination § They should be at different times of the day to *increase the likelihood of isolating the organism. § What? à The thrombus will be intermittently releasing parts of the growing infection

o Echocardiography helps determine valvular vegetation. Should always be performed § Trans-thoracic: Less invasive, quicker, and preferred by cardiologists § Trans-esophageal: More sensitive, but requires the patient to be IPO for like 6 hours. This can be

the more cost-effective echo for patients with: prosthetic valves, previous cardiothoracic surgery, COPD, and morbid obesity

- Etiology: The most common infective organism of IE is Staph Aureus o Coagulase(+) staphylococci are the dominating infective species

§ How gram(+)? Central Line… Chemo…. TPN o *Known epidemiological features can help aid our dx of alternate

infective species, such as IVDA, presence of an indwelling device, dental procedures (HACEK organisms), etc.

o Orgs of the mouth- HACEK: Haemophilus sp, Aggregatibacter, Cardiobacterium, Eikenella, Kingella § Responsible for 5-10% of Community-acquired NVE. There has been an increased incidence of

strains producing b-lactamase, making ceftriaxone an attractive option. Fluoroquinolones have also been shown to be effective, making them useful for patients unable to tolerate b-lactams

Treatment of Bacterial IE - Drug-Regimen selection considerations: sensitivities/MIC, hepatic/renal function, location of infection, DDI

o Presence of a Biofilm: Biofilms are the scourge of S aureus, and they are impenetrable to abx - S. aureus, and Coagulase(-) staphylococci are the most common cause of infective endocarditis. The MIC has

been getting higher over the years, such that the required higher aminoglycoside (AG) dose has been associated with worse clinical outcomes.

o AG are no longer recommended for NVE to be used in synergy, though for Prosthetic they still find application. Uncomplicated cases of NVE require 6 weeks of therapy.

o Daptomycin is an alternative to Vancomycin for MRSA and for high dose cases. - Community-Acquired Native Valve Endocarditis (NVE) in non-IVDA patients

o Bug: V. streptococci, S. gallolyticus, A. defective, Granulicatella species o PCN Sensitive (low MIC) à PCN 12-18 million units daily x4w o PCN Sensitive, PCN-ALL à Vancomycin 30mg/kg DIV 2 doses x4w o PCN Intermediate (int. MIC) à PCN 24 million units daily x4 weeks + Gentamicin 3mg/kg x2w

- Prosthetic Valve Bacterial Endocarditis (PVE) High-dose PCN required o Prosthetic Valve à PCN 24million units DIV 4-6daily doses x6w + Gentamicin x2w o Prosthetic Valve, PCN-ALL à Vancomycin 30mg/kg DIV 2 doses x6w

- MSSA NVE Endocarditis o Ox-Susceptible (MSSA): Nafcillin/Oxacillin 12g/q24 DIV 4-6 doses x6w o PCN-ALL: Cefazolin 6g/q24 DIV 3 doses x6w o Ox-Resistance (MRSA): Vancomycin 30mg/kg/q24 DIV 2 doses x6w

- MSSA Prosthetic Valve Endocarditis (PVE) - Requires 3 drugs o Ox-Susceptible (MSSA): Nafcillin/Oxacillin 12g/q24 DIV 6 doses ³ 6w + Gentamicin + Rifampin

Gentamicin: 3mg/kg/24h, div 2-3 Rifampin: 900mg/24h, div 3

§ Rifampin shows efficacy in the sterilization of foreign bodies infected by MRSA. Caution DDI o Ox-Resistance (MRSA): Vancomycin + Rifampin + Gentamicin

- NVE+PVE, Enterococci IE: Sensitivities should be tested for PCN, Vanco, and Gentamicin. AG pay a key role in the combined treatment with PCN, Ampicillin, or Vanco. Vancomycin-resistant enterococcus (VRE) should be managed by an infectious disease specialist. Sometimes use double b-laxctam coverage (add ceftriaxone)

o Sensitive: Ampicillin + Gentamicin Alternatively, PCN + Gentamicin o VRE: Linezolid or Daptomycin @10-12mg/kg/day >6w

- HACEK PVE/NVE: Ceftriaxone - Miscellaneous Gram(-) Bacilli, like Pseudomonas: b-lactam + AG x6w, likely will need a valve replacement.

o Fungi: Amphoterrible ± flucytosine, likely getting a valve replacement IE Prevention via Prophylactic Abx Tx: Certain patients should receive prophylactic treatment – best categorized as any type of surgery on the heart. This includes patients with: Prosthetic Valves or valve repair, previous hx of endocarditis, and congenital heart disease (CHD). They should receive preventative therapy when:

- All dental procedures involving manipulation of gingival tissue PREVENTATIVE THERAPY FOR ADULTS – if indicated – see risks above

PO NPO PCN-ALL PCN-ALL NPO

Amoxicillin 2g Ampicillin/Cefazolin/Ceftriaxone Keflex/Clindamycin/Azithromycin Cefazolin/Ceftriaxone/Clindamycin Catheters - Safest place to install a catheter is the subclavian.

- There are short-term (peripheral, mid-line) and long-term (PICC, port-a-cath) catheters. PICC most common o Long-term access required: Poor access to short-term vessels (IVDA), Hyperosmolar (TPN), Long-term

therapy (Endocarditis), patient/physician preference, chemo, etc - Risks: Insertion site (skin flora), cutaneous vs subQ, sterilization techniques

o The longer it is in, the higher the risk of infection o The more lumens, the higher the risk of infection

Catheter Infections - Catheter-related bacteremia/sepsis: Positive cultures of the same organism in the catheter AND peripheral blood. - Localized catheter site infection: Clinically or microbiologically proved infection at the catheter exit site

o Including: Cellulitis, Purulence, Tunnelitis, Pocket Infections - Septic Thrombophlebitis: Venous thrombus on the catheter and clinical signs of sepsis - Infusate-related bacteremia: Presence of a pathogen in the blood AND infusate. Contaminated infusion.

o Such as the New England company and Medrol Pluta story - Etiology: Majority of infective agents are gram(+), as expected. The most common bacteria contributing to

infection are: Coagulase(-) Staphylococcus (37%), Staph aureus(12.6%)………enterococci, candida, gram(-) - Sx: Spiking fever, sweating/rigors, Hypotension, Septic shock, tachycardia, endocarditis, arteritis, hematogenous

lung infection, persistent bacteremia or fungemia o Catheter-Specific: Erythema, Warmth, purulent discharge, swelling at catheter exit site

- Dx: 1 entire set of cultures is needed: Catheter tip culture (> 15CFU) + 2 peripheral blood cultures o Catheter-specific and non-specific Sx o CBC with differentia o Rule out other sources of infection

Treating Catheter Infections: There are complicated and uncomplicated cases - Step 1: Whenever a catheter is not needed, PULL IT OUT - Complicated: Tunnel infection/Port Abscess (local) à Tx for 7 days - Coagulase-(-) Staphylococcus – Vancomycin 15mg/kg q12º for 10-14 days

o Alternatively – Vancomycin Lock – Vanco 2.5mg/mL + Heparin 2500units/mL *3mL to try and salvage the line - 20% chance reoccurrence if not removed

- Enterococci – Same as above o If VRE à Use Daptomycin 6mg/kg/day or Linezolid 600mg q12º x10-14d, AND PULL THE LINE

- Staph Aureus – Remove the line. Continue to treat for 2 weeks after the first set of negative blood cultures. o MSSA à Nafcillin or Oxacillin 1-2g IVPB q4-6º o MRSA à Vancomycin 15mg/kg q12º or Daptomycin 6-8mg/kg for 2-6w

- Gram(-) Bacilli – Pip/Tazo x7-14d, pull the line - Candida – Amphoterrible is the best antifungal, but they don’t call it amphoterrible for nothing

Prevention: To prevent extra-luminal contamination, use skin antimicrobials and antiseptics (chlorhexidine – Hibiclens and Peridex)