Cardiovascular Infections

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Empiric Treatment for Native Valve Endocarditis (not in septic shock)

Infective endocarditis is diagnosed based on Modified Duke Criteria.

Empiric antibiotics should be given to all patients who are haemodynamically unstable or who have an acute presentation, after blood cultures are taken.

In patients who are haemodynamically stable, with a subacute, indolent presentation, delay antibiotics until culture results are available.

Antimicrobial

Benzylpenicillin 3 million IU (1.8g) (child 80 000 IU (50mg)/kg) IV Q4H

PLUS

Cloxacillin 2g (child 50mg/kg) IV Q4H

PLUS

Gentamicin 4-5mg/kg (child <10 years old: 7.5mg/kg) IV OD

Alternative:

If benzylpenicillin is not available replace this with:

Ampicillin 2g (child 50mg/kg) IV Q4H

For severe penicillin allergy or if cloxacillin is not available use:

Vancomycin IV 25-30mg/kg loading dose then dose according to Vancomycin dosing section

PLUS

Gentamicin 4-5mg/kg (child <10 years old: 7.5mg/kg) IV OD

Comments and Duration of Therapy 

If bacterial endocarditis is suspected it is recommended that at least 3 set of blood cultures be taken, before initiating therapy. If culture is positive, direct antibiotics to treat specific pathogen (see below).

Seek review by Cardiology and Infectious Diseases where available.

Important principles of management include:

  • Treatment must be given IV
  • Treatment is usually 4-6 weeks in duration
  • Adequate drug concentrations and duration are essential

Empiric Treatment for Prosthetic Valve Endocarditis, Endocarditis- associated Septic shock, Healthcare-associated Endocarditis, OR where MRSA is suspected.

Antimicrobial 

Vancomycin IV 25-30mg/kg loading dose, then dose according to Vancomycin dosing section

PLUS

Cloxacillin 2g (child 50mg/kg) IV Q4H

PLUS

Gentamicin 4-5mg/kg (child <10 years old: 7.5mg/kg) IV OD

If patient is in septic shock replace Gentamicin with:

Amikacin 28mg/kg IV OD as single dose in patients with creatinine clearance >60ml/minute. Use 16-20mg/kg if creatinine clearance <60ml/minute. For subsequent dosing see Aminoglycoside dosing section.

Child 15mg/kg IV OD

If amikacin is not available and patient is likely to have normal renal function give above regime but increase Gentamicin dose to 7mg/kg IV for first dose.

Comments and Duration of Therapy 

Cloxacillin is used in addition to vancomycin as it is more effective than vancomycin for methicillin-sensitive Staphylococcus aureus.

Seek review by Cardiology and Infectious Diseases where available.

Streptococcus viridans and bovis group Endocarditis

Antimicrobial 

Benzylpenicillin 3 million IU (1.8g) (child 80 000 IU (50mg)/kg) Q4H

PLUS

If gentamicin dose monitoring is available and there no contraindications to use. Gentamicin 1mg/kg IV TID or 3mg/kg (child 5mg/kg) IV OD for 2 weeks then stop.

See Aminoglycoside dosing section.

Alternative:

If benzylpenicillin is not available replace with:

Ampicillin 2g (child 50mg/kg) IV Q4H

OR

Ceftriaxone 2g (child 50mg/kg) IV OD

For patients with severe allergy to penicillin use:

Vancomycin IV, dose according to Vancomycin dosing section

Comments and Duration of Therapy 

Patients treated with long term gentamicin should have renal function monitored every two days and should be asked regularly about symptoms of ototoxicity such as vertigo or hearing loss. If symptoms occur cease gentamicin.

Duration:

For uncomplicated native valve disease, with MIC of 0.125mg/L or lower, in which gentamicin is used for two weeks, treat for a total of 2 weeks.

For patients with complicated disease (large vegetation, slow response to treatment, extra-cardiac infection), MIC of >0.125mg/L, OR where 2 weeks of gentamicin cannot be used, treat for a total of 4 weeks.

For patients with prosthetic valves, treat for 6 weeks.

If vancomycin is used, treat for 6 weeks.

Staphylococcus aureus Native Valve Endocarditis

Cloxacillin is more effective than vancomycin for methicillin-sensitive Staphylococcus aureus.

Antimicrobial 

For MSSA:

Cloxacillin 2g (child 50mg/kg) IV Q4H

Alternative:

Cefazolin 2g (child 50mg/kg) IV TID

OR

Vancomycin 25-30mg/kg IV loading dose, then dose according to Vancomycin dosing section

For MRSA:

Vancomycin 25-30mg/kg IV loading dose, then dose according to Vancomycin dosing section

Comments and Duration of Therapy 

Duration:

MSSA: For uncomplicated infection treat for 4 weeks. For patients with perivalvular abscess, or septic embolic complications treat for 6 weeks.
MRSA: Treat for 6 weeks IV

See Staphylococcus aureus bacteraemia in Sepsis and Directed Therapy for Blood Stream Infections.

Prosthetic Valve Endocarditis with Staphylococcus aureus or Coagulase-negative Staphylococcus spp.

Antimicrobial 

For methicillin-sensitive Staphylococci:

Cloxacillin 2g IV Q4H

Consider ADDING:

Gentamicin 1mg/kg IV TID, or 3mg/kg OD for 2 weeks, if organism is susceptible, there are no contraindications, and gentamicin dose monitoring is available. See Aminoglycoside dosing section.

Consider ADDING:

Rifampicin 300mg PO TID after 3-5 days of cloxacillin, for 6 weeks, if organism is susceptible, drug is tolerated, and active TB has been ruled out.

For MRSA:

Replace cloxacillin with:

Vancomycin 25-30mg/kg IV loading dose, then dose according to Vancomycin dosing section. Add gentamicin and rifampicin where appropriate as described above.

Comments and Duration of Therapy 

Patients treated with long term gentamicin should have renal function monitored every two days and should be asked regularly about symptoms of ototoxicity such as vertigo or hearing loss. If symptoms occur cease gentamicin.

Delayed commencement of rifampicin is important to reduce the development of rifampicin resistance when the bacterial burden is high early in infection.

Duration:

Treat for 6 weeks IV.

If rifampicin is used, continue this for 6 weeks.

If gentamicin is used, stop this after 2 weeks.

See Staphylococcus aureus bacteraemia in Sepsis and Directed Therapy for Blood Stream Infections.

Enterococcus Endocarditis

Antimicrobial 

For beta-lactam susceptible:

Ampicillin 2g (child 50mg/kg) IV Q4H

PLUS

Gentamicin 1mg/kg IV TID, or 3mg/kg IV OD for 2 weeks, if no contraindications, and gentamicin is monitoring available. See Aminoglycoside dosing section.

If high level resistance to gentamicin, or gentamicin cannot be used ADD:

Ceftriaxone 2g (child >1 month, 50mg/kg) IV BID to ampicillin.

For beta-lactam resistant:

Vancomycin IV, dose according to Vancomycin dosing section

PLUS

Gentamicin 1mg/kg IV TID, or 3mg/kg IV OD for 6 weeks, if no contraindications, and gentamicin monitoring available. See Aminoglycoside dosing section.

Comments and Duration of Therapy 

Duration:

Beta-lactam susceptible: Treat for 4 weeks if uncomplicated native valve disease, and rapid response to therapy. Otherwise treat for 6 weeks. Stop gentamicin after 2 weeks.
Beta-lactam resistant: Treat for 6 weeks with both ampicillin and gentamicin if no contraindications.

Patients treated with long term gentamicin should have renal function monitored every two days and should be asked regularly about symptoms of ototoxicity such as vertigo or hearing loss. If symptoms occur cease gentamicin

HACEK Endocarditis

Haemophilus parainfluenzae, Aggregatibacter spp., Cardiobacterium spp., Eikenella corrodens, and Kingella spp.

Antimicrobial 

Ceftriaxone 2g (child >1 month 50mg/kg) IV OD

Comments and Duration of Therapy

Duration:

Treat for 4-6 weeks IV

Culture Negative Endocarditis

Culture negative endocarditis is commonly due to prior antibiotic therapy, but can also be caused by unusual pathogens including Bartonella, Brucella, Coxiella burnetii, Legionella, Mycoplasma and Tropheryma whipplei, however these cannot currently be diagnosed in Timor-Leste.

Where possible seek review by Infectious Diseases.

Antimicrobial

Brucella spp.:

Doxycycline 100mg PO BID

PLUS

Cotrimoxazole 160/800mg PO BID

PLUS

Rifampicin 300mg PO BID, or 600mg PO OD

Coxiella burnetii (Q fever):

Doxycycline 100mg PO BID

PLUS

Hydroxychloroquine 600mg PO OD orally

Bartonella:

Doxycycline 100 mg PO BID

PLUS

Gentamicin 1mg/kg TID, or 3mg/kg OD for 2 weeks

Legionella spp.:

Levofloxacin 500mg IV/PO BID

PLUS

Rifampicin 300mg PO BID

Mycoplasma spp:

Levofloxacin 500mg IV/PO BID

Tropheryma whipplei:

Doxycycline 100mg PO BID

PLUS

Hydroxychloroquine 600mg PO OD

Comments and Duration of Therapy 

Duration:

Brucella: Treat for 3-6 months

Coxiella burnetii (Q fever): Treat for at least 18 months

Bartonella: Treat for 6 weeks. Stop gentamicin after 2 weeks.

Legionella: Treat for at least 6 weeks

Mycoplasma: Treat for at least 6 months

Tropheryma whipplei: Treat for at least 18 months

See Aminoglycoside dosing section where relevant.

Bacterial Pericarditis

Bacterial pericarditis may occur as a consequence of direct spread from an intrathoracic focus, haematogenous spread or extension from a subdiaphragmatic focus. Prior to widespread antibiotic use bacterial pericarditis was a frequent complication of pneumococcal pneumonia. Where antibiotic use is common, bacterial pericarditis is most often associated with nosocomial bacteraemia, thoracic surgery, or immunosuppression, and Staphylococcus aureus is the most common cause. Tuberculosis is the most common cause of subacute or chronic purulent pericarditis.

Antimicrobial 

Pericardial drainage should be performed in all patients.

Ceftriaxone 2g (child 50mg/kg) IV OD

PLUS

Vancomycin 25-30mg/kg loading dose, then dose according to Vancomycin dosing section.

Change to oral antibiotics when clinical signs of infection have resolved, and white cell count has normalized, according to susceptibility results. If susceptibility results are not available use:

Amoxicillin/Clavulanic acid 500/125mg (child 25/6.25 mg/kg) PO TID

Comments and Duration of Therapy 

Perform echocardiography in all patients with suspected pericardial disease. Send blood cultures. Send pericardial fluid for protein, glucose, cell count, gram stain and culture, AFB and mycobacterial cultures, TB GeneXpert, and cytology. Pericardial biopsy should be considered if there is ongoing diagnostic uncertainty.

Seek review by Cardiology and Infectious Diseases where available.

Duration:

Treat for a total of 2-4 weeks depending on clinical response and adequacy of drainage.

References

eTG complete. Cardiovascular System Infections. In: Therapeutic Guidelines [digital]. Melbourne: Therapeutic Guidelines Limited; 2019. http://www.tg.org.au

Gusmao dos Santos C, Francis J, Guterres J, Janson S, Lopes N, Marr I, et al. HNGV Antibiotic guidelines writing group. Antibiotic guidelines Hospital Nacional Guido Valadares. Timor-Leste; 2016

Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta J-P, Del Zotti F, et al., ESC Scientific Document Group, 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC) Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM), Eur Heart J 2015; 36 (44): 3075–3128. https://doi.org/10.1093/eurheartj/ehv319