Thank you to PGY2 Shawn Shah for presenting an interesting case of a 66 year old homeless male who presented with fevers, productive cough, and chronic intermittent chest pain. The patient had a transthoracic echocardiogram done which showed an EF of 35%, as well as a 1.6×1.4cm aortic valve vegetation. The patient had repeatedly negative blood cultures and culture-negative endocarditis was suspected. 

What is culture negative endocarditis? 
-3 negative blood cultures (after 5 days of incubation) **Remember that administration of antibiotics before obtaining blood cultures decreases the recovery rate of bacteria by 35-40%!!! 
-HACEK organisms previously thought to be the most common causes, however can be easily isolated when cultured fro more than 5 days 
-Certain exposures/conditions can point to a specific diagnosis such as: farm animals (Brucella, Coxiella), homeless shelters (bartonella quintana), cats (Bartonella henselae), unpasteurized milk (Brucella/Coxiella) 
-Immunocompromised and HIV+ patients are at risk for fungal and Coxiella endocarditis 

Remember to consider causes of noninfective endocarditis as well such as anti-phospholipid antibody syndrome (sterile valvular vegetations, most commonly affecting the mitral valve), atrial myxoma, marantic endocarditis 

Empiric Therapy 
-ID consult is recommended for the empiric therapy of culture negative endocarditis. 
-For acute presentations of native valve endocarditis (NVE), coverage for Staph aureus, beta-hemolytic strep and aerobic gram negative bacilli should be initiated (vancomycin + cephalosporin)
-For subacute presentations of NVE, coverage for Staph aureus, viridans group strep, HACEK and enterococci should be initiated (vancomycin + ampicillin-sulbactam). 
**These regimens do not cover organisms for all organisms that cause culture negative endocarditis. If other organisms suspected, need additional coverage such as Doxycycline.

The patient was subsequently found to have elevated Bartonella titers and had an aortic valve replacement surgery performed, with the native valve staining positive for Warthin-Starry stain (supportive of Bartonella). 
Treatment for confirmed Bartonella endocarditis: Doxycycline + Gentamicin (Rifampin if cannot use gentamicin) for 14 days. If valve surgery is performed, doxycycline alone is continued for 6 weeks. If surgery is not performed and infected tissue is still present, doxycycline is continued for 3 months. 

On a semi-related note, check out the POET trial (https://www.nejm.org/doi/full/10.1056/NEJMoa1808312) which discusses the use of partial oral antibiotics in the treatment of left sided endocarditis. We will be discussing this in journal club on December 20th! 

Today we presented a case of a 44 year old M with no significant past medical history who reported a 3 month history of shortness of breath and abdominal pain and distension. Given the history and physical exam findings consistent with a volume overloaded state, the initial differential diagnosis included causes of heart failure, liver disease and renal disease (ESRD, nephrotic syndrome). Labs were significant for an infiltrative pattern of liver injury (significantly elevated alkaline phosphatase, minimally elevated transaminases and normal bilirubin) as well as an elevated globulin gap of 4.8. TTE showed reduced an ejection fraction of 35% and abdominal ultrasound demonstrated cirrhosis and ascites.

Work-up of an elevated globulin gap:
– An elevated globulin gap (difference between the total serum protein and serum albumin concentration) should always be evaluated. The first step in evaluation is to determine whether it represents a monoclonal or polyclonal gammopathy.
– Causes of polyclonal gammopathy include viral infections (acute HIV, hepatitis C), connective tissue disorders and other causes of persistent inflammation (acute phase reactants will cause an increase in the globulin gap).
– Causes of monoclonal gammopathy include MGUS, multiple myeloma, Waldenstrom’s macroglobulinemia, amyloidosis and lymphoma.
– An SPEP (shown below), immunofixation and free light chain assay should be ordered to help determine the etiology of the protein gap. Remember that SPEP is the initial screening test and the sensitivities of serum immunofixation and free light chain assay are higher for detecting the presence of paraproteins. An abnormal free light chain ratio indicates overproduction of either kappa or lambda light chain.

Today in Goldstein Morning Report we presented a case of a 45 year old M with no PMH who was brought in for acute encephalopathy and witnessed seizures. On exam the patient was found to have multiple cranial neuropathies and labs were significant for a positive RPR (1:32). The patient had a lumbar puncture performed which showed 4 WBCs (lymphocytes), glucose 67 and protein 54 and CSF VDRL was found to be reactive.

Neurosyphilis
– Clinical signs of neurosyphilis include meningitis, stroke, acute/chronic encephalopathy, loss of vibration sense, cranial nerve dysfunction and auditory/ophthalmic abnormalities.
– The diagnosis of neurosyphilis is based on clinical suspicion, serologic tests and CSF analysis.
– Remember that CSF abnormalities can occur in early syphilis, and may not be clinically significant in the absence of neurologic signs/symptoms.
– In early neurosyphilis, serum nontreponemal (VDRL, RPR) and treponemal tests (FTA-ABS) are generally reactive, however in late neurosyphilis VDRL and RPR may be nonreactive and FTA-ABS should always be performed.
– CSF-VDRL is highly specific and a reactive test is diagnostic for neurosyphilis, however the sensitivity is much lower.

Diagnosis of neurosyphilis in an HIV- patient
– In patients with a nonreactive CSF-VDRL, treatment depends on further CSF findings.
—> If the CSF WBC>5, treat for neurosyphilis.
—> If the CSF WBC<5 but the CSF protein >45, treat for neurosyphilis.

Diagnosis of neurosyphilis in an HIV+ patient
– Similarly to HIV- patients, further CSF studies must be used to diagnosed neurosyphilis when the CSF-VDRL is negative. However HIV can cause a mild CSF pleocytosis and protein level (especially in those with CD4>200, detectable HIV RNA and not on ART).
–> If the CSF WBC >20, treat for neurosyphilis.
–> If the CSF WBC is 6-20, treat for neurosyphilis if the CD4<200, HIV RNA<50 and on ART
–> If the CSF WBC is ≤5, do not treat.