A Rare Presentation of Q Fever Endocarditis

Abstract

Q fever endocarditis is caused by the bacteria Coxiella burnetii which primarily spreads via aerosol. It has a higher incidence in males, those with negative blood cultures, animal contact, and preexisting valvular heart disease. Herein, we present an atypical case of culture-negative Q fever endocarditis in a 73-year-old female without a history of valvular heart disease or known animal exposures. Two months prior to this presentation, she was hospitalized for acute hypoxic respiratory failure due to community acquired pneumonia and was recovering well from previous infection until she suddenly developed increased shortness of breath requiring oxygen supplementation, and she was found to have a new murmur during her clinical exam. Her diagnosis of Q fever endocarditis was confirmed, and she required transfer to a tertiary care center for higher level of care. This case stresses the importance of early detection and initiation of treatment through an interdisciplinary approach to reduce the high mortality rates of Q fever endocarditis.

Introduction

Q fever is a zoonotic infection caused by Coxiella burnetii, an obligate intracellular Gram-negative bacterium primarily transmitted via aerosol routes. Previous studies have shown an increased incidence of Q fever endocarditis in male patients, individuals with negative blood cultures, animal contact including exposure to cats, dogs, and rarely to ticks, consumption of raw milk products, and preexisting valvular heart disease. ¹ Herein, we report a case of culture-negative Q fever endocarditis in a female patient with no history of valvular heart disease.

Case Presentation

A 73-year-old female with a medical history of coronary artery disease, heart failure with preserved ejection fraction (HFpEF), chronic obstructive pulmonary disease, chronic kidney disease (CKD), and a history of pulmonary embolism (PE) presented with progressively worsening shortness of breath.

Leading up to her current presentation, the patient had required 3 hospitalizations for pneumonia. During the first admission, she was treated with levofloxacin for 10 days and discharged without oxygen. Five days later, she was readmitted with dyspnea and found to have a positive V/Q scan for PE (computed tomography [CT] angiography of the Chest deferred due to CKD/patient preference). Her WBC was 20 000, improving to 15 000 on empiric clindamycin and cefepime. Her course was attributed more to PE than pneumonia, and she was discharged on apixaban, supplemental oxygen (3-4 L), and oral antibiotics.

Two weeks later, she returned with worsening dyspnea and a large left pleural effusion, complicated by acute hypoxemic/hypercapnic respiratory failure requiring ICU care and Bilevel Positive Airway Pressure (BiPAP). Thoracentesis revealed an exudative effusion, and she subsequently required chest tube drainage. She improved on broad-spectrum antibiotics (WBC 21 000-13 000) and was discharged on cefpodoxime and metronidazole.

At pulmonary follow-up, she remained oxygen-dependent (3 L at rest, 4 L with exertion) but denied systemic symptoms. She reported lower extremity edema thought to represent HFpEF exacerbation, though diuretics were deferred to cardiology/Primary Care Physician (PCP). Bedside thoracic ultrasound showed only mild bilateral effusions. Plans were made for pulmonary function tests and CT chest in 4 to 6 weeks, but she was re-hospitalized within a month for worsening respiratory failure.

Upon admission, she required 4 L of oxygen to maintain a saturation of 98%. She was afebrile, and her electrocardiogram revealed sinus rhythm without ST segment changes. Notably, she had a grade 3 diastolic murmur in the aortic region, not present during prior admission. Laboratories revealed an elevated troponin (normal <14 pg/mL) at 434 ng/L at admission, down-trending to 379 ng/L in 2 hours, brain natriuretic peptide of 369 pg/mL (1.0-100.0 pg/mL), mild leukocytosis of 11.9 M/µL (3.8-10.8 M/µL), microcytic anemia with hemoglobin of 10 g/dL (12.0-16.0 g/dL), and normal electrolytes and renal function. A chest X-ray revealed bilateral pleural effusions, and a CT chest without contrast showed moderate right pleural effusion, multifocal consolidation, and mild cardiomegaly. The patient was admitted for further evaluation and management.

She denied current pet exposure (her daughter had a dog 2 years prior). She denied exposure to birds, cats, or farm animals, as well as ingestion of raw milk, recent travel, or environmental exposures such as hiking, gardening, spelunking, swimming in lakes, or barefoot walking. She reported that she had quit smoking, with a 30 pack-year history, and continued to use smokeless tobacco. She denied alcohol or illicit drug use.

Cardiology service was consulted, and the patient underwent a transthoracic echocardiogram (TTE). The patient’s previous TTE performed a year prior illustrated no valvular abnormalities. Her TTE during this hospitalization revealed: ejection fraction: 65% to 70%, moderate-to-severe aortic stenosis (peak aortic velocity of 372 cm/second, mean gradient 32 mmHg) and mild pulmonary hypertension (right ventricle systolic pressure 40 mmHg).

A transesophageal echocardiogram revealed a large mass involving the atrial and ventricular surfaces of the aortic valves noncoronary cusp, measuring 1.3 × 1.1 cm (Figure 1). Moderate aortic regurgitation, moderate-to-severe aortic stenosis, and mild thickening of the mitral valve anterior leaflet tip with <5 mm mobile mass on the atrial surface were seen. A regurgitation flow was seen through the aortic valve during diastole, which prompted concern for a perforation.

Figure 1.

TEE in parasternal long axis view showed large vegetation involving the atrial and ventricular surfaces of the aortic valve noncoronary cusp measuring 1.3 × 1.1 cm (red arrow). The aortic valve right coronary cusp illustrates normal anatomy (blue arrow). The left ventricle has normal cavity dimensions with normal systolic function with an estimated ejection fraction of 60% to 65%. TEE, transesophageal echocardiogram.

Cardiothoracic surgery was consulted due to severe aortic valve involvement; however, she was a high-risk candidate for open heart surgery. Unfortunately, in the setting of endocarditis, transcatheter aortic valve placement would not be ideal.

Infectious disease service was consulted, initiating empirical treatment with ceftriaxone and vancomycin for suspected endocarditis; however, all blood cultures remained negative. Atypical infectious disease workup was initiated due to persistent suspicion of endocarditis, which revealed a Q fever phase 1 IgG titer of 1:4096. Her treatment was modified to doxycycline and hydroxychloroquine.

Given the complexity of her case, with severe aortic valve involvement and suspected endocarditis, an interdisciplinary meeting was held. The patient was transferred to a tertiary care center for further management of her severe condition with possible aortic valve replacement.

Discussion

Q fever endocarditis is a rare but serious infection, often underdiagnosed due to its presentation as culture-negative endocarditis. It occurs most frequently in patients with preexisting valvular heart disease, but as this case demonstrates, it can also develop in patients without a history of valvulopathy. The absence of typical signs such as positive blood cultures and the small size of vegetation, which may not always be visible on echocardiography, make diagnosis particularly challenging. Therefore, a high index of suspicion is required in patients with culture-negative endocarditis.^{2 -4}

Serologic testing plays a crucial role in diagnosing Q fever endocarditis. The presence of a phase 1 IgG titer ≥1:800 serves as a major diagnostic criterion. ² In this case, the patient’s phase 1 IgG titer of 1:4096 strongly supported the diagnosis of Q fever endocarditis, even in the absence of positive blood cultures. ³

The treatment for Q fever endocarditis typically involves a combination of doxycycline and hydroxychloroquine, which has significantly improved patient outcomes. This regimen has been shown to reduce mortality compared to other antibiotic therapies. ² In this case, after identifying C. burnetii as the causative agent, the patient’s treatment was adjusted accordingly, and the interdisciplinary approach between cardiology, cardiothoracic surgery, and infectious disease teams played a pivotal role in managing the case. ⁵

Although Q fever is a rare entity, it is increasingly being recognized, particularly in the elderly population of developed countries. ⁵ Chronic Q fever infections, such as endocarditis, tend to occur in individuals with valvulopathy or immunosuppression, but exposure to animals such as cattle, sheep, and goats is another significant risk factor. ⁶ The case highlights the importance of maintaining awareness of Q fever as a potential cause of culture-negative endocarditis, especially given its rising frequency in hospitalized patients. ⁵ The patient’s prior hospitalizations for pneumonia were concerning for a possible initial presentation of Q fever. At that time, sputum and blood cultures, as well as an extended respiratory pathogen panel, were negative, raising the possibility that her pneumonia represented an undiagnosed manifestation of C. burnetii infection. Notably, she also reported lower extremity swelling at her outpatient pulmonology follow-up, which may have reflected evolving aortic regurgitation. Unfortunately, she did not have outpatient cardiology follow-up during this period.

Q fever’s natural history underscores the chronic nature of the infection, particularly its tendency to persist within host cells, evading the immune system for extended periods. This explains why endocarditis can develop months or years after the initial infection, especially in susceptible individuals, such as those with underlying cardiac conditions or immunosuppression. ⁷ In this case, although the patient had no known history of valvulopathy, her chronic comorbidities may have predisposed her to a more severe manifestation of the disease.

Early detection and timely initiation of appropriate therapy are essential to reducing the high morbidity and mortality associated with Q fever endocarditis. ⁴ Left untreated, the infection can cause severe complications such as heart failure, severe valvular damage, and an increased risk of death. ² In this case, prompt serologic testing and the initiation of targeted antibiotic therapy likely contributed to improved patient outcomes.

Conclusion

This case highlights the diagnostic challenges associated with Q fever endocarditis, particularly in culture-negative cases and patients without known risk factors such as valvulopathy. Early recognition, interdisciplinary care, and targeted antibiotic therapy are essential for reducing morbidity and improving patient outcomes.