Pulmonary Nocardiosis: Risk Factors, Clinical Features, Diagnosis and Prognosis

Raquel Martínez; Soledad Reyes; Rosario Menéndez

Disclosures

Curr Opin Pulm Med. 2008;14(3):219-227. 

In This Article

Diagnosis

The diagnosis of Nocardia requires isolation and identification of the organism from a clinical specimen. It is important that physicians notify the laboratory when Nocardia is suspected in a clinical specimen, so that measures can be taken to optimize recognition and recovery of the organism. Microscopic and macroscopic examinations of specimens submitted for culture of Nocardia are the first steps in providing a definitive diagnosis.[2**] Bronchial washings, bronchial lavage fluids, sputum samples, abscesses, wound drainages, tissues or cerebrospinal fluids are the most commonly received specimens. Stainings with modified acid-fast stains, and especially Gram stains (Figs 3a,b), are especially important to provide rapid presumptive diagnosis while awaiting the results of the culture. Cultures for Nocardiae require a minimum of 48-72 h before colonies become evident (Fig. 4).

Figure 3.

Microbiological staining

Figure 4.

Microbiological culture

The taxonomy of the genus Nocardia has been revised extensively during recent years, and a number of unnamed taxons have been delineated.[2**,40,41]

Identification of Nocardia isolates at the species level by means of routine phenotypic testing is difficult; however, a simple identification scheme, based on a panel of nine conventional phenotypic and enzymatic tests, has been developed and validated for the rapid identification of the most common Nocardia spp. found in human clinical specimens.[42] Correct identification of species is important for clinical management and treatment.[43**]

Molecular techniques, such as PCR, restriction enzyme analysis, and 16S rRNA gene sequencing, have revolutionized the identification of Nocardia spp. These techniques are, however, restricted to referral laboratories.[2**] Brown et al.,[44] used N. farcinica-specific PCR primers for identification of members of this species. As 16S rRNA gene sequencing is frequently used for species identification, recently Wauters et al.[42] studied the species distribution of the Nocardiae in a large number of clinical samples in Belgium by using 16 rRNA gene sequencing. The investigators recovered 86 strains of Nocardia species; among these, 83 (96%) strains belonged to only six Nocardia spp.: N. farcinica (44%), N. Nova (22%), N. cyriacigeorgica (15%), N. brasiliensis (6.9%), N. abscessus (5.8%) and N. paucivorans (2.3%).

Conville et al. [45*] describe a novel method for identifying Nocardia isolates by using sequence analysis of a portion of the secA1 gen, distinguishing 29 clinically relevant species or taxa of Nocardia, using sequence analysis of both a portion of the secA1 gen and the deduced amino acid and sequence.

In another recent study,[46**] DNA extracted from different Nocardia strains was used in a real-time PCR assay (of 16S rDNA) with SYBR Green and melting-curve analysis to identify Nocardia spp. All Nocardia strains were identified correctly (Nocardia farcinica, N. nova, N asteroide among others). With this method, the identification of Nocardia spp. can be completed in a few hours, which is closely related to a favourable outcome for patients.

For laboratories with molecular capabilities, gene sequencing provides rapid and usually reliable identification of most Nocardia isolates.[2**]

Regarding serological methods, a number of serologic tests have been evaluated to determine their applicability to the early diagnosis of nocardial infections. It appears that the usefulness of a single serologic methodology for the detection of nocardiosis disease may be limited by the variety of species now known to cause infections and the potential lack of sensitivity for detecting antibody response in immunocompromised patients.

Antimicrobial susceptibility testing of Nocardia isolates is recommended as a guide to therapy in cases of severe and disseminated infection, in refractory cases, or in patients who are intolerant to treatment with sulfonamides. Performance and interpretation of tests for antimicrobial susceptibility of Nocardia spp. are, however, problematic, due to the slow growth of these organisms. The Clinical and Laboratory Standard Institute (CLSI) has approved a standard susceptibility testing and interpretation method by microdilution in cation-supplemented Mueller-Hinton broth.[47] Although broth microdilution is now the CLSI recommended method for antimicrobial susceptibility testing for the Nocardiae, other methods have also been evaluated, and their tests include disk-diffusion, agar dilution, Etests and the Bactec radiometric growth index method. Few correlation studies have, however, been performed with the broth microdilution method. In a recent publication,[43**] susceptibilities to 11 antimicrobial agents were determined by Etest for 93 Nocardia isolates from clinical specimens in Belgium and 15 types of strains belonging to different Nocardia spp. All isolates were susceptible to TMP-SMX, amikacina and linezolid, but susceptibilities of the various Nocardia spp. to β-lactams, aminoglycosides, ciprofloxacin and clarithromycin varied markedly. Among the different species encountered, N. farcinica and N. brasiliensis displayed the most multiresistant profiles with resistance to imipenem occurring mainly with N. brasiliensis and N. abscessus. Table 3 shows the frequency of susceptibility of various Nocardia spp. to selected antimicrobial agents published in this article.

In another study of nocardiosis,[26*] all eight different species of Nocardia that were identified were all were found to be susceptible to co-trimoxazole, as determined by the Etest. Amikacin, linezolid and minocycline appeared to be highly effective in vitro against the eight Nocardia spp. isolated, but different patterns of susceptibility to other agents were observed. Thus, the patterns of susceptibility to B-lactam agents, ciprofloxacin, gentamicin and tobramycin varied among the species. Similar results were obtained in another review on Nocardia infection.[30**] In this case, in-vitro susceptibility testing was performed by broth microdilution according to CLSI guidelines: amikacin (97% susceptible), imipenem (94% susceptible) and sulfamethoxazole (97% susceptible) had the greatest in-vitro activity. Ceftriaxone had poor activity against N. farcinica (13% susceptible). Varied results were seen for the remaining antibiotics.

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