A Case of Disseminated Nocardia farcinica Presenting as Fever of Unknown Origin in a Transplant Patient

Closing Prognosis: Nocardia farcinica

HISTORY OF THE PRESENT ILLNESS
A 44-year-old girl with a medical historical past vital for end-stage renal illness underwent a deceased-donor kidney transplant. 9 months later, she offered to her nephrolo­gist within the fall with fevers and chills, 2 days after getting back from a visit to China. She was prescribed a course of azithromycin and had a chest x-ray and urine tradition carried out. The chest x-ray was unremarkable, and the urine tradition grew Proteus mirabilis. She was then prescribed a course of levofloxacin. She continued to have fevers at residence, so she was instructed to current to the hospital for additional testing. On admission, she reported having had right-side flank ache, pleuritic chest ache, nonproductive cough, and myalgias for about 1 week.

PAST MEDICAL HISTORY

The affected person had a historical past of end-stage renal illness attributable to presumed immunoglobulin A nephropathy. She had been receiving hemodialysis for a number of months by way of tunneled catheter adopted by peritoneal dialysis for Three years previous to her transplant. On the time of transplant, she demonstrated prior publicity to Epstein-Barr virus and cytomegalovirus (CMV). Her donor additionally demonstrated prior publicity to CMV. Her postoperative course was difficult by leukopenia, which required adjustment of her immune suppression, momentary cessation of Pneumocystis prophylaxis with trimethoprim/sulfamethoxazole (TMP-SMX), and administration of colony-stimulating components.

She additionally had low-level CMV DNAemia, with out proof of organ involvement, handled with valganciclovir about 5 months after transplant. This situation, a type of leukopenia, was attributed to a mixture of CMV and medicines and resolved about Three months previous to presentation.

She additionally had a historical past of hypertension, hypothyroidism, hyper­parathyroidism, and gastroesophageal reflux illness.

KEY MEDICATIONS

At presentation, the affected person was taking cyclosporine, myco­phenolate mofetil, and prednisone for immunosuppression. She was additionally taking prophylactic TMP-SMX and lately accomplished a course of valganciclovir. As well as, she took amlodipine, levothyroxine, famotidine, aspirin, atorvastatin, and ferrous sulfate.

EPIDEMIOLOGICAL HISTORY

The affected person was born in China and grew up in Brazil. She spent Three weeks within the area of Canton in southern China and returned 2 days previous to symptom onset. Whereas in China, she visited household and traveled to rural areas however denied outside actions, contact with animals, and bug bites. She did bear a dental extraction throughout her journey. Usually, she lived at residence in the US along with her husband and a couple of grownup youngsters, none of whom had any current sicknesses. She was not employed. She had no historical past of alcohol, tobacco, or illicit drug use.

PHYSICAL EXAMINATION

On preliminary presentation, the affected person was febrile with a tempera­ture of 101.9° F. Her very important indicators had been in any other case inside regular limits. She appeared nicely and in no misery. She was famous to have a grade 3/6 systolic murmur on the proper higher sternal border that was not beforehand famous. Her examination was in any other case unremarkable.

STUDIES

Preliminary labs revealed a leukocytosis of 15.Zero ok/ mm3 with a excessive absolute neutrophil rely of 14.1 ok/mm3 and low absolute lymphocyte rely of 0.2 ok/mm3. A complete metabolic panel was unremarkable. Her cyclosporine stage was elevated at 725 ng/mL (objective: 100-150 ng/mL). A D-dimer was elevated to 3468 ng/mL. An inter­feron-gamma launch assay was detrimental. The rest of her preliminary labs, together with lactic acid, routine blood cultures, urinalysis, respiratory viral panel, CMV viral load, and peripheral blood smear, had been unrevealing.

A computed tomography (CT) scan of the chest was carried out confirmed a brand new subpleural consolidative opacity within the anterior proper center lobe (Determine 1). A transthoracic echocar­diogram confirmed gentle aortic regurgitation, not considerably modified from prior research. Decrease extremity Doppler ultrasound didn’t present deep venous thrombosis. She couldn’t get intravenous distinction attributable to baseline continual kidney operate and refused a air flow/perfusion scan.

CLINICAL COURSE

Through the affected person’s preliminary hospitalization, a definitive supply of her fever was not discovered. She continued to have fevers regardless of therapy with vancomycin and cefepime. She declined a bron­choscopy and a biopsy of the suitable center lobe consolidation and was began on isavuconazole for suspected fungal an infection. She left towards medical recommendation on hospital day Three and was provided with a brief course of amoxicillin/clavulanate, which she accomplished. Because of intolerance she didn’t proceed isavuconazole.

She was afebrile for about 2 weeks after her discharge, then developed nightly fevers once more, in addition to evening sweats and unintentional 5-pound weight reduction. Twenty-five days after her preliminary discharge, she was readmitted to the hospital. She was discovered to have an elevated CMV viral load of 2150 IU/mL (regular: <137) and was began on ganciclovir, though this was not thought to clarify her whole presentation. A CT scan of the chest on admission confirmed innumerable new nodular densities all through the lungs, with speedy improvement from prior scan (Figures 2 and three).

Infectious illness specialists had been consulted; the affected person’s fungal and acid-fast bacilli blood and sputum cultures had been despatched, and serologic testing was carried out for Bartonella, Brucella, and Coxiella. She additionally had routine blood cultures that had been held for 14 days per request.

DIAGNOSTIC PROCEDURES AND RESULTS

Because of her new murmur and a number of pulmo­nary lesions, the affected person underwent a transe­sophageal echocardiogram that confirmed “focal thickening/nonspecific focal hyperdensity on the suitable coronary cusp with central regurgita­tion.” Her routine blood cultures grew to become optimistic for Nocardia on the fourth hospital day. She was empirically began on TMP-SMX and imipenem/ cilastatin, which was later switched to mero­penem. She had a magnetic resonance imaging (MRI) scan of her mind, which didn’t present central nervous system involvement of Nocardia.

She continued to have fevers till the tenth hospital day, and linezolid was added as a 3rd empiric agent whereas additional testing of her Nocardia isolate was in course of. Repeat chest imaging confirmed bilateral pleural effusions, and he or she underwent a thoracentesis on hospital day 8. Her pleural fluid was transudative by Gentle’s standards however grew Nocardia on tradition. On imaging, she was additionally discovered to have a fluid assortment round her transplanted kidney, which was drained by interventional radiology. The fluid cultures from this assortment remained detrimental. Her blood cultures had been persistently optimistic for 11 whole days earlier than clearing.

TREATMENT AND FOLLOW-UP

The Nocardia isolate was despatched out for extra testing and returned as Nocardia farcinica. She was handled with TMP-SMX, meropenem, and linezolid whereas within the hospital. After her blood cultures cleared, she was transitioned to a 3-drug oral routine consisting of amoxicillin/clavu­lanate, moxifloxacin, and TMP-SMX primarily based on susceptibility testing (Determine 4).

Her CMV DNAemia was regarded as reac­tivation within the setting of acute sickness. Her viral load grew to become undetectable on ganciclovir, and he or she was transitioned to oral valganciclovir. She was discharged after 20 days within the hospital. She was famous to be feeling nicely at follow-up visits.

DISCUSSION
Nocardia species are cardio gram-positive branching rods that show weak acid-fast staining.¹ The taxonomy of the genus Nocardia has been quickly evolving due to improved molec­ular testing. The variety of recognized species is debatable, with some sources citing greater than 90 species, together with greater than 50 acknowledged as inflicting illness in people.²

The commonest human pathogens had been members of what was as soon as known as the Nocardia asteroides advanced, however many species that had been previously on this group have been reclassified. N nova, N farcinica, N cyriacigeorgica, N abscessus, and N brasiliensis at the moment are among the many commonest species.³ In some case opinions, N farcinica has been noticed to have increased charges of antibiotic resistance than different species.^4,5 Research in mice have additionally steered that N farcinica could also be extra virulent and more likely to trigger disseminated an infection than different species.⁶

Nocardia will not be a part of the conventional human flora, however they’re discovered within the setting worldwide and will be inhaled or straight inoculated into the pores and skin.⁷ Immunosuppression, particularly diminished cell-mediated immunity, is a well-documented danger issue for nocardiosis, with roughly two-thirds of instances occurring in sufferers with an underlying immunocompro­mised situation.⁷ Nonetheless, immunocompetent hosts can develop nocardiosis, as nicely; they have a tendency to develop localized pores and skin infections. Immune-compromised hosts usually tend to develop pulmonary or disseminated illness.⁸

Pulmonary illness can have many presenta­tions, with signs together with cough, dypsnea, hemoptysis, and weight reduction. Radiographic discover­ings are nonspecific and embrace nodules and cavitary lesions.⁹Nocardia can disseminate to just about any organ, significantly the central nervous system. Subsequently, MRI screening of all sufferers with pulmonary or disseminated illness is advisable.⁸ Bacteremia, as seen on this affected person, is comparatively uncommon.¹⁰

In sufferers with stable organ transplant, a number of affected person components have been related to the next danger of nocardiosis, together with excessive trough ranges of calcineurin inhibitors, use of high-dose corticosteroids, historical past of CMV an infection, affected person age, and size of keep within the intensive care unit after trans­plant.^11,12 Though many transplant sufferers take TMP-SMX as Pneumocystis prophylaxis and this drug is the mainstay of therapy for nocardiosis, it’s not clear if taking prophylactic doses of TMP-SMX present some safety towards creating Nocardia-related infections.11 Sufferers who developed nocardiosis whereas on prophylactic TMP-SMX haven’t been discovered to have increased charges of TMP-SMX resistance, as is the case right here.¹⁰

Nocardia is gradual rising, and routine plates and cultures are steadily discarded earlier than development is detected. If Nocardia is suspected, cultures will be held for a chronic interval of two to three weeks. Varied selective media also can assist isolate Nocardia from contaminated speci­mens, reminiscent of sputum.¹¹

Trimethoprim/sulfamethoxazole is usually used as first line-therapy for nocardiosis, however mixture remedy is usually used for extreme or disseminated illness.¹³ Susceptibility varies enormously amongst species, so susceptibility testing is advisable for all instances to information remedy.¹⁴ Antimicrobial remedy for no less than 6 to 12 months is advisable. Reducing immune suppression as a lot as attainable can be advisable.

Outcomes in disseminated nocardiosis are variable and rely on affected person components, together with variety of organs concerned, in addition to time to analysis and to initiation of applicable remedy.⁹ As a result of nocardiosis can current in a wide range of methods and be difficult to diagnose, a excessive stage of scientific suspicion is required for this more and more acknowledged pathogen as our popu­lation of immunosuppressed sufferers grows.

Spivack is a first-year infectious illness fellow at Temple College Hospital, in Philadelphia, Pennsylvania, the place she additionally accomplished her drugs residency. She is desirous about city bioethics, social determinants of well being, and all issues infectious.

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