Pulmonary nocardiosis: a comparative analysis of Nocardia asteroides and non- asteroides species

Introduction

While not a common disease, there are estimated to be 500–1000 cases of Nocardia in the USA each year. ¹ It most commonly presents as a pulmonary infection, usually in the background of a compromised immune status. ² Unfortunately, diagnosis of Nocardia is difficult due to a lack of distinctive clinical features and the slow growth of the organism often leads to delays in identifying the species and obtaining susceptibility results. We aimed to elucidate the differences in the risk factors, clinical presentations and outcomes of Nocardia asteroides and non-asteroides pulmonary nocardiosis presenting to our tertiary care hospital during a 10-year period.

Materials and methods

We performed a retrospective cohort study comparing pulmonary infections by N. asteroides with the other Nocardia species.

All adult patients (over 18 years of age) presenting to the Aga Khan University Hospital, Karachi, Pakistan, between January 2000 and December 2010 with pulmonary nocardiosis were selected. The patients were identified using cultural data and a chart review was performed in order to identify their demographics, co-morbidities, clinical presentations, radiological and biopsy findings and treatment outcomes.

Immunosuppression was defined as: a known history of HIV infection; organ transplantation; any haematological malignancy or autoimmune disorder; an absolute neutrophil count of <500 cells/cm;³ or a history of steroid or immunomodulatory drug use within 30 days of onset of symptoms. Outcomes were categorized as recovery (improvement in the patient's presenting clinical signs and symptoms) or death (all causes during the time period of infection with Nocardia). However, long-term outcomes were not assessed due to a high attrition rate.

Data was entered on an SPSS version 16.0 (SPSS Inc., Chicago, IL, USA) and analysed for frequencies and cross-tabulations. Chi-squared test was used with a significance of α = 0.05.

Results

A total of 41 patients with pulmonary nocardiosis were identified, of whom half had infections with N. asteroides complex (58.5%, n = 24). Infections by Nocardia other than asteroides were predominantly Nocardia species that could not be further speciated (NOS) (29.3%, n = 12) followed by Nocardia otitidiscaviarum (12.2%, n = 5).

The diagnosis of pulmonary nocardiosis was made on the basis of sputum cultures alone in a third of the patients in both groups (31% versus 36%). Of the remaining 21 patients, diagnosis was made solely on a pleural fluid culture (N. asteroids, n = 4; Nocardia species, n = 4), a BAL culture (N. asteroids, n = 6; Nocardia species, n = 5) or a blood culture (N. asteroids, n = 1; Nocardia species, n = 1).

There was no difference between the two groups in the demographics or risk factors for developing N. asteroides versus a non-N. asteroides infection (Table 1). Radiological findings were also similar in both groups. Infiltrates (usually lobar) were the most commonly seen manifestation in both groups (64% and 68.8%) with almost half (43.8% and 45.5%) having a concomitant pleural effusion. The radiological data was missing for one patient with Nocardia species.

Although the duration of hospital stay for patients infected with N. asteroides was longer (18 days versus 9 days), this was not statistically significant. Most patients (n = 23) in both groups were treated with trimethroprim-sulfamethoxazole, usually in combination with other drugs. The antibiotics included a fluorquinolone (n = 9), amoxicillin-clavulanate (n = 4) and imipenem (n = 4). Ten patients died – Nocardia was named as the primary cause of mortality in six of them. In both groups, immunocompromised patients had a higher mortality rate (30%, n = 6 versus 25%, n = 3) compared to the non-immunocompromised (20%, n = 1 versus 0%, n = 0) although this did not achieve statistical significance (P = 0.66 versus P = 0.27). Most deaths occurred within nine days of diagnosis. The remainder were primarily sent home on trimethoprim-sulfamethoxazole (84.6%, n = 11) along with a flouroquinolone (53.8%; n = 7). Data regarding the discharge medication for four patients was not available.

Discussion

Although most Nocardia species are capable of infecting the lungs, ³ our study found a relatively higher proportion of infections by Nocardia species other than asteroides especially with the relatively uncommon N. otididiscavarium.

As with other studies, risk factors leading up to the infection were similar between the species with steroid use being the most frequent, followed by diabetes mellitus. ⁴ While HIV, organ transplantation and malignancies have also been identified as major risk factors in previous studies, ⁵ none of our patients suffered from these. This is probably reflective of the low rate of HIV in the general population ⁶ as well as the limited number of transplants performed in this country.

Early diagnosis of infections due to Nocardia is often difficult due to non-specific clinical manifestations. ^7,8 Both study groups presented with symptoms of pneumonia, which included fever, cough and dyspnea, and radiological findings did not vary significantly between the two groups.

In agreement with other studies, the in vitro susceptibility patterns indicated that both N. asteroides and N. otitidiscavarium were susceptible to imipenem and amikacin (Table 2). ^9,10 Although other studies have shown that up to half of the strains tested as being resistant to cotrimoxazole, ^9,10 our findings showed that almost all strains were susceptible to cotrimoxazole: 92% of N. asteroids; 80% of N. otitidiscavarium; and 100% for the other Nocardia species.

Most patients with N. asteroides and non-asteroides infection did well and recovered. Interestingly, despite being resistant to antibiotics routinely given for empiric therapy, infections with N. otitidiscavarium and other species had better outcomes. This may be due to low virulence of N. otitidiscavarium compared with other species. ⁴ Our study also found immunosuppression to be the single most important factor leading to a poor outcome. This is similar to another retrospective analysis conducted in France in 1987 that showed an overall mortality rate of 29.2% with immunosupressed patients.

Conclusion

Our study was limited by its small sample size, especially for the non-asteroides strains, which may have prevented some of the differences in the groups from reaching a statistical significance. The retrospective nature of the data also precluded close follow-up after hospital discharge and, therefore, information of long-term follow-up is unavailable.

Despite these limitations, we found that the clinical presentations, risk factors and outcomes for pulmonary infections by the various Nocardia species is similar, although N. asteroides may cause a slightly more severe disease compared to the non-asteroides species.

Conflicts of interest: There was no conflict of interest for any of the authors.

Authors' declaration: There were no financial relationships relevant to this article to disclose.