Severe pneumonia due to Nocardia otitidiscaviarum identified by mass spectroscopy in a cotton farmer: A case report and literature review.

RATIONALE: Nocardia species are aerobic saprophytic bacilli. Among Nocardia species, Nocardia otitidiscaviarum (N otitidiscaviarum) is rarely reported in pulmonary infection. PATIENT CONCERNS: We reported a case of N otitidiscaviarum pneumonia in a cotton farmer. DIAGNOSES: N otitidiscaviarum pneumonia was identified by mass spectroscopy.
INTERVENTIONS: Combined treatments (amikacin, imipenem and trimethoprim-sulfamethoxazole) were administered after identification of N otitidiscaviarum. OUTCOMES: The patient eventually died from severe respiratory insufficiency in the hospital. LESSONS: Early precise diagnosis and prompt combined therapy are of vital importance in severe Nocardia pulmonary infection.

Introduction

Nocardia species consist of gram-positive, variably acid-fast, strictly aerobic Saprophytic, and rod-shaped bacteria, which show branching filamentous forms and are ubiquitous in the environment, particularly in soil rich in organic matter, decaying vegetation, and standing water.[ Out of all Nocardia species, Nocardia asteroids, Nocardia farcinica, and Nocardia brasiliensis are the primarily pathogens causing nocardiosis, while other species are rarely or infrequently reported.[ As one of the less commonly isolated Nocardia species,[N otitidiscaviarum is considered to be less pathogenic than other species of Nocardia.[ Herein we present a case of N otitidiscaviarum pulmonary Infection.

Case report

A 58-year-old cotton farmer was presented to the West China Hospital of Sichuan University because of an over 1-month history of recurrent fever (between 38 and 40 °C), productive cough, and dyspnea. Prior to admission, he was diagnosed of pneumonia and treated with latamoxef, ofloxacin, vancomycin, and voriconazole at local hospital. However, no remission of symptoms was observed. Moreover, he was a hepatitis B virus carrier with a 10 pack-years smoking history. However, no history of diabetes mellitus, tuberculosis, and use of glucocorticoids in the past were informed.

On admission, blood pressure, 145/95 mm Hg; heart rate, 120 per minute; respiratory rate, 30 per minute; and temperature, 39.3 °C. Physical examination revealed diminished breath sounds, but no rales were heard, and evaluation of other systems was unremarkable except moderate edema of lower limbs. Arterial blood gases analysis showed pH 7.361, PCO2 53.5 mm Hg, and PO2 62.8 mm Hg. Laboratory data (Table 1) revealed leukocytosis of 49,500/mm3 with 97.4% neutrophils, and elevated procalcitonin of 5.16 ng/mL. Chest computed tomography, presence of nodules, masses, patchy consolidations, and bilateral pleural effusion, is noted (Fig. 1A). Meanwhile, it was soon alerted in sputum smear with presence of filamentous, gram-positive, weakly acid-fast, and beaded bacilli with possible diagnosis of Nocardia infection (Fig. 1B, C). Trimethoprim-sulfamethoxazole (3 pills per 6 hours) with noninvasive ventilation was promptly administered. Sputum culture showed growth of numerous bacteria that were precisely determined to be N otitidiscaviarum by the method of mass spectroscopy on day 6 after admission (Fig. 1D). Antibiotics were thus modified to amikacin and imipenem in addition to trimethoprim-sulfamethoxazole in accordance with the sensitivity test. However, the patient was not improved as expected and eventually died from severe respiratory insufficiency on the 13th hospital day.

Table 1

Results of laboratory tests during 13 days of disease course.

Figure 1

(A) Chest computed tomography (CT) image, (B) gram-positive staining, (C) weakly acid-fast staining, and (D) mass spectroscopy graph for Nocardia otitidiscaviarum.

This case report was approved by the Institutional Review Board of West China Hospital of Sichuan University, and the informed consent was obtained.

Discussion

N otitidiscaviarum, formerly called Nocardia caviae, was first obtained from the middle ear of an infected Sumatran guinea pig and reported by Snijders in 1924,[ while 1st report of cases of human infection by N otitidiscaviarum did not reach the literature until the mid-1960s.[

In spite of the fact that nocardiosis are being increasingly recognized, infections due to N otitidiscaviarum, comprising about only 0.3% to 2.9% of all Nocardia infections,[ remain infrequently reported.[ Beaman et al described that only 10 cases from 347 patients infected by Nocardia in United States were identified as N otitidiscaviarum infection.[ Similarly, Kageyama et al[ reported that out of more than 303 pathogenic Nocardia strains isolated from nocardiosis patients in Japan from 1992 to 2001, only 14 were identified as N otitidiscaviarum. This low incidence of N otitidiscaviarum may be attributed to its lower prevalence in the environment when compared with other Nocardia species,[ although it has been found to be native to the soil.[ In this case, the cotton farmer had intimate contact with the soil, which increased the risk for N. otitidiscaviarum infection.

Noticeably, N otitidiscaviarum has been described as an opportunistic pathogen in human.[ However, it has been reported in both immunocompromised and immunocompetent individuals to be a cause of pulmonary, primary cutaneous, and lymphocutaneous infections.[ Individuals with weakened immune system, such as patients suffering from diabetes mellitus, chronic obstructive pulmonary disease, mixed connective tissue disorder, ulcerative colitis, cirrhosis, human immunodeficiency virus infection, malignancies, those receiving long-term or large dose of corticosteroid therapy, and bone marrow or solid organ transplant, are at higher risk.[ In this case, the patient has no immunocompromised disorders, but 10 pack-years smoking history, which could be a risk factor to weaken the defense capability in lungs.

Being relatively rarely reported, N otitidiscaviarum is postulated to be less pathogenic in human when compared with other Nocardia species.[ However, contradictory results have been yielded from animal studies of nocardial virulence.[ Smith and Hayward[ reported that N otitidiscaviarum and N asteroids were of similar virulence; Mishra et al[ confirmed that the 2 species were of equal pathogenicity and were both markedly more virulent than N brasiliensis. It is likely that the pathogenicity of N otitidiscaviarum varies due to different strain variability, inoculum size, and infection route. Moreover, human infections by N otitidiscaviarum usually occur in 2 major forms, the pulmonary form (through direct inhalation of pathogen or bacteria fragments carried in dust or spores) and the cutaneous form (following injection by a thorn prick or similar accidents).[ There has not been any case report of human-to-human or animal-to-human transmission.[ Obviously, this case prefers the pulmonary form.

With signs, symptoms, and imaging features being not pathognomonic, it is challenging to clinically diagnose N otitidiscaviarum infection.[ Conventional evaluation of specimens like sputum samples, abscesses, wound drainages, or bronchial washings by smear and culture remains the principal method of diagnosis.[ Yet, it is noteworthy that almost 1 week or even more may be needed for the presence of N otitidiscaviarum to be noted on cultures on routine bacteriologic media because of its slow growth.[ However, relative to the conventional methods, polymerase chain reaction and 16S rDNA sequencing, or mass spectroscopy used in this case are much more rapid precise, and accurate in identifying N otitidiscaviarum.

N otitidiscaviarum infection calls for long-course drug treatment, and it is suggested that antibiotic therapy should be continued for 6 months in immunocompetent patients and up to a year in immunosuppression.[ Although increasing numbers of Nocardia species including N otitidiscaviarum complex have developed increasing resistance and demonstrated inconsistent susceptibility to trimethoprim-sulfamethoxazole, sulfonamides remain the standard antimicrobial agents for the treatment of nocardiosis to date.[ Most N otitidiscaviarum isolates are also reported to be resistant to and beta-lactams like ampicillin, amoxicillin-clavulanic acid, and imipenem, but are usually susceptible to amikacin and the fluoroquinolones.[ Meanwhile, some other studies have shown that N otitidiscaviarum complex is proved to be sensitive to linezolid in vitro; however, data from in vivo studies are lacking. In addition, incidence of hematological toxicity become higher after 4 weeks of linezolid application, and clinical experience with linezolid is limited.[ Antimicrobial susceptibility testing can guide the treatment of N otitidiscaviarum, and the US National Committee for Clinical Laboratory Standards approved an antimicrobial testing of aerobic actinomycetes including Nocardia by using broth microdilution.[ Although the optimal treatment protocol of N otitidiscaviarum still unknown, a combination of sulfonamides and amikacin with a carbapenem or a 3rd-generation cephalosporin are suggested for severe or disseminated infections.[ Similarly in this case, combined therapy (amikacin, imipenem, and trimethoprim-sulfamethoxazole) was administered in accordance with the sensitivity test on the 6th hospital day after N otitidiscaviarum was identified. However, the mortality rate in pulmonary nocardiasis patients is 15% to 30%, even in severe patients up to 50%.[ So, early diagnosis and prompt initiation of treatment are of vital importance in Nocardia infection.[ In this case, overdelayed diagnosis and intervention definitely attributes to the eventual death.

In conclusion, N otitidiscaviarum infection is rarely reported and requires early diagnosis and prompt intervention. Considering the high rate of mortality, long-course treatment with optimal protocol is desperately needed.