Case 7

A 56-Year-Old Male With 3 Weeks of Fever

Arthur Jeng, Arzhang Cyrus Javan

A 56-year-old male presents to the emergency room with complaints of fevers and chills for the past 3 weeks. Otherwise, his review of systems is negative for headache, cough, shortness of breath, abdominal pain, dysuria, urinary frequency or urgency, or back/flank pain. Vital signs reveal his temperature is 39.1 °C (102.4 °F), pulse rate is 118/min, blood pressure is 154/80 mm Hg, and respiration rate is 17/min. Physical exam is normal, with a cardiac exam showing tachycardia but otherwise regular rhythm and no rubs or murmurs. His laboratory data are shown in Table 7.1. The emergency room physician admits the patient for pyelonephritis based on the abnormal urinalysis (UA).

TABLE 7.1

Initial Laboratory Tests

Leukocyte count	9000/µL
Hemoglobin	14.2 g/dL
Platelet count	476,000/µL
Leukocyte differential	75% neutrophils, 20% lymphocytes, 5% monocytes
Serum creatinine	0.6 mg/dL
Liver function tests	Normal
Sedimentation rate	78 (elevated)
Urinalysis	pH 6.5, 1+leukocyte esterase, 10 white blood cells

What do you think about his admission diagnosis?

This patient has fevers but a paucity of other symptoms. Although pyelonephritis can cause fevers, he does not have any symptoms of either pyelonephritis (flank pain, nausea) or lower urinary tract infection (UTI) (dysuria, urinary frequency/urgency). Additionally, the UA does not demonstrate significant pyuria. Therefore, despite being labeled with the diagnosis of pyelonephritis, it is unlikely the reason for his fevers, and additional investigation needs to be performed.

What is the differential diagnosis?

The differential diagnoses should include causes of subacute chronic fevers with a paucity of symptoms. This would include subacute bacterial endocarditis, indolent infections such as extrapulmonary tuberculosis, brucellosis (undulant fever), Q fever, typhoid fever, typhus (from Rickettsia), certain cancers (especially lymphoma, leukemia, and renal cell carcinoma), and autoimmune diseases. Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can allow opportunistic organisms, such as Cryptococcus, cytomegalovirus (CMV), and Mycobacterium avium complex to cause fever with no localizing symptoms. It may also predispose patients to febrile noninfectious processes such as multicentric Castleman’s disease and lymphoma.

Which other tests should be ordered?

• Blood culture: Two or more sets of blood cultures are essential for the initial evaluation of fever of uncertain origin. Blood cultures are the key diagnostic study for infective endocarditis, and they can also diagnose less common infections that one may not be considering, such as Brucella and Cryptococcus.

• Computed tomography (CT) scans: If all workup, including cultures, have been unrevealing, CT scans of the body (chest, abdomen, pelvis) are indicated, as these scans can evaluate for occult infections (e.g., abscesses of the liver, intestinal region, adnexa in women and prostate in men, evidence of tuberculosis), masses concerning for malignancy (lymph node enlargement, liver/kidney masses, bony metastases), and signs of collagen vascular diseases (inflammation of the lungs and serosal linings).

• HIV test: The Centers for Disease Control and Prevention (CDC) recommends that all patients in the health care system have an HIV screen. This screening test is even more critical in patients who have fever of uncertain origin, as opportunistic infections need to be evaluated if they are found to have HIV.

On hospital day 2, the urine culture demonstrates 50,000 colony forming units (cfu)/mL of Streptococcus viridans group. Someone from your team sees this result and comments that your patient has a UTI with S. viridans as the pathogen.

What do you think about this diagnosis?

To diagnose a UTI, three factors need to be satisfied:

1. Symptoms consistent with a UTI

2. Significant pyuria

3. Significant bacteriuria with a bacteria that causes UTIs

Because S. viridans does not cause UTIs and the patient does not have UTI symptoms, this is not the diagnosis. The bacteriuria is either a contaminant, or it is reflecting bacteremia (the nephrons filter the blood, often leading to pathogens leaking from blood into the urine).

STEP 2/3

Clinical Pearl

The other bacteria where this mistake is commonly made is Staphylococcus aureus (S. aureus). When S. aureus is found in the urine, it is unlikely to represent an S. aureus UTI, as these bacteria do not commonly cause UTIs (in the absence of a urinary catheter or other prostheses in the urinary tract). It should prompt the clinician to evaluate for bacteremia with S. aureus, with subsequent leakage from blood to urine, as in this case.

Later that day, the microbiology lab technician calls you and reports that four of four blood culture bottles are growing gram-positive cocci in chains. The bacteria are subsequently identified as being in the S. viridans group.

What is the likely diagnosis now, and what other tests should you order?

The microbiology data show significant bacteremia within S. viridans group, making subacute bacterial endocarditis the most likely diagnosis.

STEP 2/3

Clinical Pearl

Subacute bacterial endocarditis, which can progress for weeks or months before the patient seeks medical care, is most commonly caused by S. viridans group, followed by Enterococcus and other streptococci (e.g., Streptococcus gallolyticus). These pathogens prefer to adhere to previously damaged or abnormal valves (e.g., rheumatic, prosthetic, congenitally or acquired abnormal valves), primarily through bacteremia from endogenous tissue disruption/manipulation (e.g., odontogenic procedures or intestinal mucosal breach). In contrast, S. aureus can cause acute infective endocarditis, with clinical progression over days, and it is associated with rapid valve destruction and/or development of complications. Although S. aureus does have a predilection to infect previously abnormal/damaged valves, it is also well known to adhere to normal valves. Especially in industrialized societies, S. aureus has become the most common cause of infective endocarditis, either as a result of intravenous drug use or through secondary bacteremia from venous catheters (e.g., central venous lines, PermCath dialysis catheters).

As such, the patient needs an echocardiogram to evaluate for cardiac vegetations and any complications, including valvular dehiscence and/or myocardial/perivalvular abscess. In most hospitals, the initial echocardiogram to obtain is the transthoracic echocardiogram (TTE), as this is a noninvasive study that can be obtained very quickly. The modified Duke criteria can be used to assist in the evaluation and diagnosis of infective endocarditis (Table 7.2). A list of typical organisms that cause infective endocarditis is shown in Table 7.3. When a patient has infective endocarditis but the blood cultures do not grow any organisms, it is called culture-negative infective endocarditis. These pathogens are uncommon causes of infective endocarditis (Table 7.4) and require further evaluation through serology or PCR to establish a microbiological diagnosis. Detailed history-taking may uncover epidemiologic risk factors for acquiring one of these pathogens.

STEP 2/3

Clinical Pearl

Culture-negative infective endocarditis is most commonly caused by antibiotic administration prior to blood culture collection, either from the patient’s self-administration or from the emergency department. True culture-negative infective endocarditis with nonculturable bacteria is not common.

A medical student who heard about the case comments that it is unbelievable that the patient may have infective endocarditis because he does not have a murmur or any signs of emboli on exam.

TABLE 7.2

Modified Duke Criteria

(Need two major criteria or one major + three minor criteria or five minor criteria)
Major Criteria	Blood Culture Criteria
	• Typical microorganisms consistent with infective endocarditis from two separate blood cultures: viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or community-acquired enterococci in the absence of a primary focus; or • Microorganisms consistent with infective endocarditis from persistently positive blood cultures defined as follows: At least two positive cultures of blood samples drawn >12 hours apart; or all of three or a majority of four or more separate blood cultures (with first and last sample drawn at least 1 hour apart); or • Single positive blood culture for Coxiella burnetii or anti–phase 1 IgG antibody titer >1: 800
	Endocardial Involvement Criteria
	Echocardiogram positive for infective endocarditis defined as follows: oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or abscess; or new partial dehiscence of prosthetic valve; new valvular regurgitation (worsening or changing or preexisting murmur not sufficient)
Minor Criteria	Predisposition, predisposing heart condition, or injection drug use
	Fever, temperature >38 °C (100.4 °F)
	Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions
	Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor
	Microbiological evidence: positive blood culture but does not meet a major criterion as noted above or serological evidence of active infection with organism consistent with infective endocarditis

TABLE 7.3

Bacteria That Cause Infective Endocarditis and Prevalence From International Collaboration on Endocarditis (ICE) Prospective Cohort Study

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Tags: Medicine Morning Report Beyond the Pearls

Jun 15, 2016 | Posted by admin in GENERAL & FAMILY MEDICINE | Comments Off

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Staphylococci	Cases (%) from ICE Cohort
Staphylococcus aureus	31.6
Coagulase-negative staphylococci	10.5
Streptococci
Viridans group streptococci	18
Streptococcus gallolyticus (bovis)	6.5
Other streptococci (β-hemolytic streptococci, nutritionally variant streptococci)	5.1
Enterococcus	10.6
HACEK Group

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7 A 56-Year-Old Male With 3 Weeks of Fever

A 56-Year-Old Male With 3 Weeks of Fever

What do you think about his admission diagnosis?

What is the differential diagnosis?

Which other tests should be ordered?

What do you think about this diagnosis?

What is the likely diagnosis now, and what other tests should you order?

Basicmedical Key

Fastest Basicmedical Insight Engine

7 A 56-Year-Old Male With 3 Weeks of Fever

What do you think about his admission diagnosis?

What is the differential diagnosis?

Which other tests should be ordered?

What do you think about this diagnosis?

What is the likely diagnosis now, and what other tests should you order?

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