WK, a 34 year old female with a recent history of Enterococcus faecalis bacteremia is admitted with fever, malaise, and a new heart murmur. Blood cultures remain positive, and, following a transesophageal echocardiogram, she is diagnosed with native valve endocarditis. The organism shows no resistance to standard agents including ampicillin and gentamicin synergy. 

Height: 68in

Weight: 70kg

SCr: 0.9 mg/dL

Allergies: Sulfa - mild rash approximately 10 years ago

No other significant past medical history.

What would be the most appropriate gentamicin dose and regimen to use for synergy when given with the ampicillin?

A. 60 mg IV Q8H

B. 60 mg IV daily 

C. 80 mg SQ Q12H

D. 100 mg IV Q8H

E. 420 mg IV daily

Answer with rationale:

Endocarditis is a serious infection of the inner lining of the heart chambers and heart valves. It is typically caused by Gram-positive pathogens, such as viridans group streptococci, enterococci, or S. aureus. Bacteria in the bloodstream attach to damaged areas of the heart, and can form colonies that could also cause clots, leading to other cardiovascular complications like heart failure or stroke. People with existing heart conditions, artificial (especially mechanical) heart valves, history of IV drug use, or a history of heart surgery are at higher risk. Symptoms include fever, chills, fatigue, shortness of breath, but a more distinct sign is a new or changing heart murmur. Diagnosis includes blood tests and a transesophageal echocardiogram, while treatment typically involves long-term use of IV pathogen-specific antibiotics.

Ampicillin and gentamicin work as part of a treatment strategy known as synergy, because ampicillin disrupts the bacterial cell wall, allowing gentamicin to enter the cell more easily. Once inside, gentamicin interferes with bacterial protein synthesis, leading to enhanced bacterial killing that neither drug could achieve alone.

Many drugs, especially antibiotics, require renal dose adjustment to avoid build-up and toxicities. Aminoglycosides have a very significant side-effect profile including nephrotoxicity and ototoxicity, so when doing synergy dosing, it is important to know how to appropriately calculate a creatinine clearance and make the appropriate adjustment.

IBW = 45.5 + (2.3 x inches > 60) = 63.9kg

63.9 x 1.3 = 83.07 (which is > actual body weight of 70kg) 

→ use 63.9kg for CrCl and dosing

CrCl = (140-age) x wt x 0.85) ÷ (72 x SCr) = 88.8 mL/min

→ no renal dose adjustments necessary

Answer A is correct: When gentamicin is dosed for synergy therapy for enterococcus endocarditis, it is at 1mg/kg IM or IV every 8-12 hours. After calculating an ideal body weight of 63.9kg, and a creatinine clearance of 88.8 mL/min indicating effective renal function, rounding to 60mg would be an appropriate dose.

Answer B is incorrect: If the patient had altered kidney function, considering a longer dosing interval may be appropriate, however that decision does not become relevant until a creatinine clearance of less than 60 mL/min which is not the case here. 

Answer C is incorrect: The actual body weight is generally only used for gentamicin dosing if it is less than the ideal body weight. In this case, the actual body weight is greater than the ideal body weight, but is less than 30% higher than the ideal, meaning for dosing and CrCl calculations, the ideal body weight of 63.9kg should be used, rounded to 60mg. The interval of q12h would not be appropriate as well considering her excellent renal function. In addition, no antibiotics are recommended to be given subcutaneously for the treatment of endocarditis. 

Answer D is incorrect:  The dosing is not at 1mg/kg Q8-12H recommended for synergy. This dosing regimen is more consistent with treatment of gram-negative infections and not synergy for gram-positive infections (~1.7mg/kg per dose Q8H). 

Answer E is incorrect:  This is not the correct dosing or interval for this patient. This would represent single daily dosing or "extended interval dosing" of 7mg/kg once daily which is used primarily to treat systemic gram-negative infections. When used for endocarditis, single daily dosing is reserved for certain types of streptococcal endocarditis at 3mg/kg once daily with good renal function. 

Brand/generics Covered:

Gentamicin (no active brand names), Ampicillin (no active brand names)

Naplex Content Domains Covered

1.C.2: Calculations of quantities of drugs to be administered

3.C.4: Errors and omissions in dosing