Nocardia species are found worldwide and are opportunistic pathogens of both immunocompromised and immunocompetent hosts. Recent updates to the taxonomy of this genus have indicated that there are more than 90 recognized species of Nocardia with 54 species reported to be clinically relevant.
KEYWORDS: Nocardia, antimicrobial agents, epidemiology
ABSTRACT
Nocardia species are found worldwide and are opportunistic pathogens of both immunocompromised and immunocompetent hosts. Recent updates to the taxonomy of this genus have indicated that there are more than 90 recognized species of Nocardia with 54 species reported to be clinically relevant. In this paper, we report the species distribution, specimen source distribution, and antimicrobial susceptibility profiles of 2,091 clinical isolates recovered for the years 2011 to 2017 using the updated taxonomy. The most commonly isolated species included Nocardia nova complex, Nocardia cyriacigeorgica, and Nocardia farcinica complex, with an additional 25 species or species complexes recovered from clinical specimens. The antimicrobial susceptibility profile was highly variable between the species, but in general, amikacin, linezolid, and trimethoprim-sulfamethoxazole demonstrated good in vitro activity against most species.
INTRODUCTION
Nocardia species are found throughout the world in water, soil, and other organic matter. Although these are generally considered opportunistic pathogens that cause disease in immunocompromised patients, approximately one-third of cases involve immunocompetent hosts (1, 2).
The data available on the incidence of nocardiosis are limited, but it is estimated that there are 500 to 1,000 new cases annually in the United States (3). Nocardia is usually acquired through inhalation of the organism, but traumatic inoculation into the skin also occurs, and the organism has been reported to be nosocomially acquired through direct inoculation of the skin by contaminated catheters or surgical equipment. Nocardia infections are not thought to be transmitted from person to person (4, 5).
Nocardia species can cause a wide variety of clinical syndromes, with pulmonary infections being the most common manifestation. Nocardia species are also responsible for extrapulmonary infections with a predilection for the central nervous system, skin, and subcutaneous tissue. Nocardia bacteremia is extremely rare, even in an immunocompromised population (6).
Since first being identified in 1889, Nocardia taxonomy has been challenging and has continued to evolve, with more than 90 currently recognized species (7). Differences in susceptibility profiles, clinical presentation, and treatment options necessitate the identification of Nocardia to species level in order to provide optimal patient care.
In the laboratory, Nocardia species are slow-growing, aerobic, weakly acid-fast, Gram-positive, branching bacteria that are classically described as having a beaded appearance on Gram stain. Phenotypic and biochemical identification methods are not able to sufficiently discriminate between the species, so currently, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) or DNA sequencing are the methods of choice for identification to the species or species complex level (8).
The available data on Nocardia species drug susceptibilities are limited, often lack supportive prospective clinical outcomes data, and are usually highly individualized (2). The aim of this work was to perform a retrospective evaluation of Nocardia species identified at a tertiary medical center with a reference laboratory over a 6-year period and to provide antimicrobial susceptibility data for the identified Nocardia species.
RESULTS
Description of Nocardia species isolated.
A total of 2,091 cultures were positive for Nocardia species from 1 August 2011 through 31 August 2017. Of these, 1,891 (90.4%) were identified to the species level, and 200 (9.5%) were able to be identified only to the genus level as Nocardia species. Of the 200 isolates identified only to the genus level, 95 (48%) were identified by partial 16S rRNA gene sequencing, and 105 (52%) were identified by MALDI-TOF MS.
General characteristics of the samples submitted are shown in Table 1. Our sample population included 1,175 (56.2%) men and 916 (43.8%) women. The median age was 66 years (interquartile range, 55 to 76 years). We excluded pediatric samples (any patients 18 years or younger).
TABLE 1.
Characteristics of 2,091 Nocardia isolates from 2011 to 2016
| Characteristic | No. (%) |
|---|---|
| Patient demographics | |
| Median age (range) (yrs) | 66 (55–76) |
| Male | 1,175 (56.2) |
| Female | 916 (43.8) |
| Year specimen submitted | |
| 2011 (August to December) | 53 (2.5) |
| 2012 | 319 (15) |
| 2013 | 325 (15.5) |
| 2014 | 348 (16.6) |
| 2015 | 403 (19) |
| 2016 | 412 (19.7) |
| 2017 (January to August) | 231 (11) |
| Specimen source | |
| Respiratory specimens | 1,295 (62) |
| Sputum | 631 (30) |
| Bronchoalveolar lavage fluid | 499 (23.8) |
| Lung tissue | 110 (5.2) |
| Pleural fluid | 42 (2) |
| Tracheal secretions | 13 (0.6) |
| Nonrespiratory specimens | 796 (38) |
| Musculoskeletal | 372 (17.8) |
| Blood | 110 (5.2) |
| Brain biopsy | 78 (3.7) |
| Cerebrospinal fluid | 10 (0.4) |
| Others | 226 (10.8) |
Our samples included 22 specimens from international countries. These included 12 samples from Saudi Arabia, 3 from Lebanon, 2 from Qatar, 2 from the United Arab Emirates, 1 from Chile, 1 from Brazil, and 1 from Italy. Among isolates from the United States, 1,056 (50.5%) of the reported specimens were from Florida, Minnesota, Texas, Arizona, Michigan, and Louisiana (300, 256, 143, 135, 114, and 108 specimens, respectively) (Fig. S1 and S2 in the supplemental material).
The number of specimens received per year has steadily increased from 319 in 2012 to 412 in 2016 (Table 1).
The majority of positive cultures were from respiratory specimens (1,295 [62%]), including 631 (30%) from sputum, 499 (23.8%) from bronchoalveolar lavage (BAL) fluid, 110 (5.2%) from lung biopsies, 42 (2%) from pleural fluid, and 13 (0.6%) specimens from tracheal secretions. Cultures from other sources included musculoskeletal in 372 (17.8%), blood cultures in 110 (5.2%), brain biopsy cultures in 78 specimens (3.7%), and cerebrospinal fluid culture from 10 samples. This is similar to what has been previously described in the literature (Table 2) (9–11).
TABLE 2.
Results of antibiotic susceptibility testing to Nocardia isolates: current study and previous similar studies
| Characteristic | Data for study |
|||
|---|---|---|---|---|
| This study | Schlaberg et al. 2014 (9) | Valdezate et al. 2017 (10) | Lebeaux et al. 2018 (11) | |
| No. of isolates | 2,091 | 1,299 | 1,119 | 736 |
| Patient age (median [IQR]) (yrs)a | 66 (55–76) | 63, DNC | DNC | 66 (4–90) |
| Sex (%) | ||||
| Male | 56.2 | 53 | DNC | 58 |
| Female | 43.8 | 47 | DNC | 42 |
| Years specimens submitted | 2011–2017 | 2006–2011 | 2005–2014 | 2010–2015 |
| Specimen source or reference (no. [%]) | ||||
| Lung | 110 (5.2) | 54% | 961 (85.9) | 427 (53.8) |
| Sputum | 631 (30) | DNC | DNC | 156 (19.7) |
| BAL | 499 (23.8) | DNC | DNC | 112 (14.1) |
| Blood | 110 (5.2) | 6% | 13 (1.3) | 39 (4.9) |
| Brain | 78 (3.7) | 3% | 27 (2.8) | 37 (4.7) |
| CSF | 10 (0.4) | DNC | DNC | 6 (0.8) |
| Others | 653 (31.2) | DNC | DNC | DNC |
| Antibiotic (% of N. nova complex, N. cyriacigeorgica, N. farcinica, N. brasiliensis, N. abscessus complex, and N. transvalensis complex isolates, respectively, susceptible) | ||||
| Amikacin | 100, 99, 100, 100, 100, 26 | 100, 100, 100, 100, 100, 28 | 100, 99, 98, 100, 100, 52 | 100, 99, 99, 100, 99, 70 |
| Amoxicillin-clavulanate | 4, 8, 96, 99, 61, 89 | 9, 3, 76, 95, 78, 57 | 32, 28, 82,92, 96, 100 | 8, 9, 80, 92, 74, 88 |
| Cefepime | 47, 24, 1 ,0, 69, 27 | DNC | DNC | 77, 65, 9, 44, 92, 83 |
| Ceftriaxone | 14, 64, 3, 2, 93, 64 | 47, 88, 3, 49, 98, 63 | DNC | 70, 96, 20, 69, 97, 96 |
| Clarithromycin | 97, 1, 0, 0, 38, 2 | 97, 1, 0.5, 3, 29, 4 | DNC | DNC |
| Imipenem | 100, 99, 83, 8, 64, 9 | 99, 43, 33, 1, 31, 6 | 98, 97, 96, 44, 88, 78 | 99, 89, 77, 15, 88, 63 |
| Linezolid | 100, 100, 100, 100, 100, 100 | 100, 100, 100, 100, 100, 100 | 99, 99, 97, 100, 100, 100 | 100, 100, 100, 100, 100, 100 |
| Minocycline | 19, 14, 7, 16, 94, 31 | 12, 6, 5, 24, 85, 15 | 11.3, 16,11, 41, 91, 30 | 93, 81, 87, 87, 98.7, 96 |
| TMP-SMX | 100, 100, 99, 100, 100, 88 | 100, 100, 99.5, 100, 100, 81 | 80.4, 96, 55, 100, 97, 60 | 91.7, 97, 96, 96, 98.7, 88 |
| Tobramycin | 3, 99, 1, 100, 100, 0 | 13, 99, 0.5, 100, 100, 4 | 52, 97, 16, 92, 99, 4 | 20, 99, 3, 100, 99, 4 |
| Study highlight | Most commonly isolated species (constituting ≈90%) included N. nova complex, N. cyriacigeorgica, N. farcinica complex, N. brasiliensis, N. abscessus complex, and N. transvalensis complex. | More than 90% of isolates belonged to N. nova complex, N. cyriacigeorgica, N. farcinica, N. brasiliensis, N. abscessus complex, N. transvalensis complex, and Nocardia beijingensis complex. | Prevalence values for different Nocardia species were similar during 2005–2009 and 2010–2014, except for those of N. abscessus, N. farcinica, and N. transvalensis, which fell significantly in the second subperiod (P < 0.05). | The most frequent species were N. farcinica (20.2%), N. abscessus complex (19.9%), and N. nova complex (19.5%). The N. farcinica proportion increased significantly over time from 13% in 2010 to 27.6% in 2014. |
Abbreviations: BAL, bronchoalveolar lavage; CSF, cerebrospinal fluid; CNS, central nervous system; DNC, data not collected; IQR, interquartile range; TMP-SMX, trimethoprim-sulfamethoxazole.
Table 3 indicates that the most commonly isolated species were N. nova complex, 452 (21.6%); Nocardia cyriacigeorgica, 352 (16.8%); N. farcinica complex, 319 (15.3%); Nocardia brasiliensis, 223 (10.7%); N. abscessus complex, 205 (9.8%); and N. transvalensis complex, 121 (5.8%). These 6 species and species complexes constituted more than 80% of all Nocardia species isolated in the study period.
TABLE 3.
Identified species for 2,091 Nocardia isolates from 2011 to 2017
| Species | No. of isolates (%) |
|---|---|
| Nocardia nova complexa | 452 (21.6) |
| Nocardia cyriacigeorgica | 352 (16.8) |
| Nocardia farcinica complexb | 319 (15.3) |
| Nocardia brasiliensis | 223 (10.7) |
| Nocardia abscessus complexc | 205 (9.8) |
| Nocardia species | 200 (9.6) |
| Nocardia transvalensis complexd | 121 (5.8) |
| Nocardia asteroides | 76 (3.6) |
| Nocardia otitidiscaviarum | 30 (1.4) |
| Nocardia pseudobrasiliensis | 21 (1) |
| Nocardia brevicatena/Nocardia paucivorans | 19 (0.9) |
| Nocardia niwae | 14 (0.7) |
| Nocardia puris | 9 (0.4) |
| Nocardia amikacinitolerans | 6 (0.3) |
| Nocardia carnea | 5 (0.2) |
| Nocardia takedensis | 5 (0.2) |
| Nocardia thailandica | 5 (0.2) |
| Nocardia araoensis | 4 (0.2) |
| Nocardia flavorosea | 3 (0.1) |
| Nocardia mexicana | 3 (0.1) |
| Nocardia exalbida | 2 (0.1) |
| Nocardia ignorata | 2 (0.1) |
| Nocardia jiangxiensis | 2 (0.1) |
| Nocardia niigatensis | 2 (0.1) |
| Nocardia testacea | 2 (0.1) |
| Nocardia amamiensis | 1 (<0.1) |
| Nocardia anaemiae | 1 (<0.1) |
| Nocardia blacklockiae | 1 (<0.1) |
| Nocardia brevicatena | 1 (<0.1) |
| Nocardia higoensis | 1 (<0.1) |
| Nocardia higoensis/shimofusensis | 1 (<0.1) |
| Nocardia rhamnosiphila | 1 (<0.1) |
| Nocardia salmonicida | 1 (<0.1) |
| Nocardia shimofusensis | 1 (<0.1) |
| Nocardia sienata | 1 (<0.1) |
| Nocardia vinacea | 1 (<0.1) |
N. nova complex includes Nocardia africana, Nocardia aobensis, Nocardia cerradoensis, Nocardia elegans, Nocardia kruczakiae, Nocardia mikamii, N. nova, Nocardia vermiculata, and Nocardia veterana.
N. farcinica complex includes N. farcinica and Nocardia kroppenstedtii.
N. abscessus complex includes N. abscessus, Nocardia arthritidis, Nocardia asiatica, Nocardia beijingensis, and Nocardia pneumoniae.
N. transvalensis complex includes N. blacklockiae, N. transvalensis, and Nocardia wallacei.
Grouping the isolates according to the specimen source submitted, the most common species isolated from respiratory sources (sputum, BAL fluid, lung biopsies, pleural fluid, and tracheal secretions) were N. nova complex, 328/1,295 (25.3%); N. cyriacigeorgica, 290/1,295 (22.3%); N. farcinica complex, 151/1,295 (11.6%); and N. abscessus complex, 128/1,295 (9.8%).
The most common Nocardia species isolated from brain specimens was N. farcinica complex, 33/78 (42.3%), followed by N. abscessus complex, 20/78 (25.6%). The most common Nocardia species isolated from blood was N. farcinica complex, 39/110 (35.4%), followed by N. nova complex, 36/110 (32.7%) and N. cyriacigeorgica, 16/110 (14.5%).
Table 2 compares our results with other literature reports, and the antimicrobial susceptibility results across the 4 highlighted studies are in good agreement (9–11).
Antimicrobial susceptibility profiles.
Antimicrobials in vitro susceptibility profiles for some agents were highly variable between different Nocardia species (Table 4).
TABLE 4.
Antimicrobial susceptibility profiles by Nocardia species
| Nocardia species | n | Susceptibility (%) of indicated species to: |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Amka | Amox/clav | Cefepime | Ceftriaxone | Cip | Clr | Doxycycline | Imp | Lzd | Min | Mxf | TMP-SMX | Tob | ||
| Nocardia nova complexb | 452 | 100 | 4 | 47 | 14 | 1 | 97 | 1 | 100 | 100 | 19 | 3 | 100 | 3 |
| Nocardia cyriacigeorgica | 352 | 99 | 8 | 24 | 64 | 0 | 1 | 11 | 99 | 100 | 14 | 1 | 100 | 99 |
| Nocardia farcinica complexc | 319 | 100 | 96 | 1 | 3 | 49 | 0 | 2 | 83 | 100 | 7 | 76 | 99 | 1 |
| Nocardia brasiliensis | 223 | 100 | 99 | 0 | 2 | 0 | 0 | 5 | 8 | 100 | 16 | 40 | 100 | 100 |
| Nocardia abscessus complexd | 205 | 100 | 61 | 69 | 93 | 3 | 38 | 87 | 64 | 100 | 94 | 13 | 100 | 100 |
| Nocardia species | 200 | 93 | 37 | 33 | 40 | 14 | 42 | 25 | 76 | 100 | 39 | 39 | 99 | 60 |
| Nocardia transvalensis complexe | 121 | 26 | 89 | 27 | 64 | 49 | 2 | 10 | 9 | 100 | 31 | 72 | 88 | 0 |
| Nocardia asteroides | 76 | 99 | 26 | 51 | 49 | 21 | 51 | 29 | 88 | 100 | 43 | 25 | 100 | 58 |
| Nocardia otitidiscaviarum | 30 | 100 | 0 | 0 | 0 | 0 | 17 | 43 | 3 | 100 | 60 | 23 | 87 | 53 |
| Nocardia pseudobrasiliensis | 21 | 62 | 5 | 0 | 0 | 100 | 95 | 0 | 0 | 100 | 0 | 86 | 33 | 100 |
| Nocardia brevicatena/Nocardia paucivorans | 19 | 95 | 47 | 95 | 95 | 100 | 100 | 95 | 100 | 100 | 95 | 84 | 100 | 95 |
| Nocardia niwae | 14 | 100 | 0 | 7 | 100 | 21 | 100 | 36 | 100 | 100 | 86 | 86 | 100 | 100 |
| Nocardia puris | 9 | 100 | 0 | 0 | 0 | 11 | 0 | 100 | 78 | 100 | 100 | 11 | 100 | 100 |
| Nocardia amikacinitolerans | 6 | 67 | 100 | 17 | 33 | 0 | 0 | 83 | 100 | 100 | 100 | 17 | 100 | 100 |
| Nocardia carnea | 5 | 100 | 20 | 100 | 100 | 80 | 60 | 20 | 100 | 100 | 40 | 80 | 100 | 100 |
| Nocardia takedensis | 5 | 100 | 40 | 100 | 100 | 0 | 100 | 100 | 100 | 100 | 100 | 20 | 100 | 100 |
| Nocardia thailandica | 5 | 100 | 0 | 20 | 60 | 0 | 80 | 0 | 100 | 100 | 0 | 20 | 100 | 100 |
| Nocardia araoensis | 4 | 100 | 100 | 75 | 100 | 0 | 75 | 25 | 25 | 100 | 25 | 50 | 100 | 100 |
| Nocardia flavorosea | 3 | 100 | 0 | 100 | 100 | 100 | 33 | 67 | 100 | 100 | 67 | 100 | 100 | 100 |
| Nocardia mexicana | 3 | 0 | 0 | 0 | 33 | 0 | 0 | 0 | 100 | 100 | 0 | 0 | 0 | 0 |
| Nocardia exalbida | 2 | 100 | 0 | 100 | 100 | 0 | 50 | 100 | 100 | 100 | 100 | 0 | 100 | 100 |
| Nocardia ignorata | 2 | 100 | 0 | 0 | 0 | 50 | 0 | 100 | 100 | 100 | 100 | 50 | 100 | 100 |
| Nocardia jiangxiensis | 2 | 100 | 100 | 0 | 0 | 0 | 100 | 0 | 100 | 100 | 100 | 0 | 100 | 100 |
| Nocardia niigatensis | 2 | 50 | 0 | 0 | 0 | 50 | 50 | 0 | 0 | 100 | 0 | 0 | 50 | 100 |
| Nocardia testacea | 2 | 100 | 0 | 50 | 100 | 100 | 0 | 0 | 100 | 100 | 0 | 50 | 100 | 100 |
| Nocardia amamiensis | 1 | 100 | 0 | 100 | 100 | 0 | 100 | 100 | 100 | 100 | 100 | 0 | 100 | 100 |
| Nocardia anaemiae | 1 | 100 | 0 | 0 | 100 | 0 | 100 | 0 | 100 | 100 | 100 | 0 | 100 | 100 |
| Nocardia blacklockiae | 1 | 0 | 100 | 0 | 100 | 0 | 100 | 0 | 100 | 100 | 0 | 100 | 100 | 0 |
| Nocardia brevicatena | 1 | 100 | 0 | 0 | 0 | 0 | 0 | 100 | 100 | 100 | 100 | 0 | 100 | 100 |
| Nocardia higoensis | 1 | 100 | 100 | 0 | 0 | 100 | 0 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| Nocardia higoensis/shimofusensis | 1 | 100 | 0 | 0 | 0 | 0 | 0 | 0 | 100 | 100 | 0 | 0 | 100 | 100 |
| Nocardia rhamnosiphila | 1 | 100 | 0 | 0 | 0 | 100 | 0 | 0 | 100 | 100 | 0 | 100 | 100 | 100 |
| Nocardia salmonicida | 1 | 100 | 0 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| Nocardia shimofusensis | 1 | 100 | 0 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| Nocardia sienata | 1 | 100 | 0 | 0 | 100 | 100 | 0 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| Nocardia vinacea | 1 | 100 | 0 | 0 | 100 | 0 | 0 | 0 | 100 | 100 | 100 | 0 | 100 | 100 |
AMK, amikacin; Amox/clav, amoxicillin-clavulanic acid; Cip, ciprofloxacin; Clr, clarithromycin; Imp, imipenem; Lzd, linezolid; Min, minocycline; Mxf, moxifloxacin; TMP-SMX, trimethoprim-sulfamethoxazole; Tob, tobramycin.
N. nova complex includes Nocardia africana, Nocardia aobensis, Nocardia cerradoensis, Nocardia elegans, Nocardia kruczakiae, Nocardia mikamii, N. nova, Nocardia vermiculata, and Nocardia veterana.
N. farcinica complex includes N. farcinica and Nocardia kroppenstedtii.
N. abscessus complex includes N. abscessus, Nocardia arthritidis, Nocardia asiatica, Nocardia beijingensis, and Nocardia pneumoniae.
N. transvalensis complex includes N. blacklockiae, N. transvalensis, and Nocardia wallacei.
Antimicrobials that generally demonstrated a high level of activity (>90% susceptible [S]) against most Nocardia species include amikacin, linezolid, and trimethoprim-sulfamethoxazole (TMP-SMX). All Nocardia isolates that were tested against linezolid were susceptible using the current CLSI interpretive criteria.
In general, susceptibility to amikacin was typical. However, a high rate of resistance (R) to amikacin was noted with N. transvalensis complex (74% R) and Nocardia pseudobrasiliensis (38% R) and to TMP-SMX with N. pseudobrasiliensis (67% R), Nocardia otitidiscaviarum (13% R), and N. transvalensis complex (12% R).
Imipenem had good in vitro activity against N. cyriacigeorgica (99% S) and N. nova complex (100% S), but high rates of resistance were noted in N. brasiliensis (92% R), N. transvalensis complex (91% R), and N. abscessus complex (36% R).
Ceftriaxone had good in vitro activity against N. abscessus complex (93% S) and Nocardia paucivorans (95% S) but poor activity with N. farcinica complex (97% R) and N. brasiliensis (98% R).
Amoxicillin-clavulanic acid demonstrated a high level of in vitro activity with N. farcinica complex (96% S), N. brasiliensis (99% S), and N. transvalensis complex (∼90% S), while this agent performed poorly with N. nova complex (96% R) and N. cyriacigeorgica (92% R).
Ciprofloxacin had poor in vitro activity in general with exception of N. pseudobrasiliensis (100% S) and N. paucivorans (100% S), while clarithromycin demonstrated good in vitro susceptibility against N. nova complex (97% S), N. paucivorans (100% S), and N. pseudobrasiliensis (95% S).
The tetracyclines had good activity only against N. abscessus complex (doxycycline, 87% S; minocycline, 94% S) and N. paucivorans (doxycycline, 95% S; minocycline, 95% S). Tobramycin demonstrated high in vitro activity against N. cyriacigeorgica (99% S), N. brasiliensis (100% S), N. abscessus complex (100% S), N. pseudobrasiliensis (100% S), and N. paucivorans (95% S). In general, resistance was high for most species against cefepime and moxifloxacin.
Among our 2,091 isolates, we identified 462 isolates (22%) as MDR Nocardia species. Of those, >75% belong to N. brasiliensis (201[43.5%]), N. transvalensis complex (92 [20%]), and N. farcinica (56 [12%]).
N. brasiliensis was frequently resistant to imipenem (92% R) and ceftriaxone (98% R) but demonstrated good susceptibility to amikacin, tobramycin, and TMP-SMX.
N. transvalensis complex was frequently resistant to imipenem (91% R) and amikacin (74% R) but retained good susceptibility to amoxicillin-clavulanic acid (89% S) and TMP-SMX (88% S).
In addition, N. pseudobrasiliensis was often MDR, with resistance to imipenem (100% R), ceftriaxone (100% R), and TMP-SMX (67% R), but had good susceptibility to ciprofloxacin, clarithromycin, linezolid, and tobramycin.
DISCUSSION
As expected, the most common source for positive Nocardia cultures was respiratory sources. Nocardia species were recovered from blood cultures in about 5% and from brain biopsies in 3.7% of patients with suspected nocardiosis.
Most of our patient population were of older age with a median age of 60 years, and the highest number of specimens were sent from southern states, including Florida, Texas, Louisiana, and Arizona (with the exception of high numbers from Minnesota and Michigan). This may be a reflection of geographic differences in Nocardia distribution, or it could be due to the location of laboratories using the Mayo Clinic as a reference laboratory.
We also noted a steady increase in the number of specimens over the study time frame, which might indicate an increasing incidence or, alternatively, more awareness of the need for, and easier access to, Nocardia culture and antimicrobial susceptibility testing.
The susceptibility profiles of Nocardia species against the antimicrobials recommended by the CLSI for in vitro susceptibility testing were highly variable by agent and by species, demonstrating the need to routinely identify Nocardia isolates to the species level and to perform in vitro susceptibility testing for all isolates thought to be clinically significant. In general, amikacin, linezolid, and TMP-SMX demonstrated good in vitro activity against most Nocardia species, and these agents are often used in combination empirically while awaiting laboratory susceptibility testing results. Possible exceptions to this rule are N. pseudobrasiliensis and N. transvalensis complex, which can show variable susceptibility to amikacin and sometimes TMP-SMX in vitro.
To our knowledge, this report provides the largest data set to date on the epidemiology and antimicrobial susceptibility profiles of Nocardia isolates from across the United States and worldwide and is consistent in many aspects with previously published reports (Table 2) (9, 10, 12).
The time between the isolation of Nocardia species and the availability of susceptibility results can be several weeks, so the choice of empirical antibiotic regimen can be aided by the in vitro data provided in this report and in previously published reports while awaiting completion of laboratory testing.
MATERIALS AND METHODS
The study was approved by the Mayo Clinic Institutional Review Board. A retrospective review of laboratory data was conducted to identify microbiologic cultures from adult patients who were positive for Nocardia species in the period between 1 August 2011 and 31 August 2017 and for which antimicrobial susceptibility testing was performed.
The clinical microbiology laboratory at Mayo Clinic in Rochester, Minnesota, receives specimens for microbiologic culture, identification, and susceptibility testing from Mayo Clinic hospitals and from Mayo Clinic Laboratory client hospitals throughout the United States and from many countries throughout the world.
Specimens received were cultured in BD Bactec mycobacteria growth indicator tube (MGIT) 960 broth in mycobacterial growth indicator tubes (Becton, Dickinson and Company, Franklin Lakes, NJ) and on Middlebrook 7H11/7H11S agar biplates incubated at 35 to 37°C for up to 6 weeks. Positive MGIT broth was subcultured to a Middlebrook 7H11 agar plate, and isolated colony growth was identified using Sanger sequencing of a 500-bp region of the 16S rRNA gene as previously described (13). Databases used included the MicroSeq ID 16S rDNA 500 library with the current version for the year the isolate was identified from 2011 to 2017 and a Mayo Clinic custom database containing well-characterized clinical isolates and type strains with multiple strains per species in order to augment strain diversity found in the MicroSeq database, and, if neither the MicroSeq nor the Mayo database provided a match, NCBI GenBank BLAST analysis was used with the sequence required to be published in peer-reviewed literature in order to accept the result. A 100% match to the database entry was required for identification. Sequence length was required to be at least 420 bp, and the Phred quality score was required to be >30. In 2015, the use of MALDI-TOF MS was added to supplement species identification using Sanger sequencing (14).
Antimicrobial susceptibility testing was performed using CLSI guidelines current during the study period (15), and the Trek Sensititre Rapmyco plate was used for rapidly growing mycobacteria and Nocardia species. Interpretation of the minimal inhibitory concentration (MIC) as susceptible or resistant for each isolate was done using current CLSI interpretive criteria (16). MICs reported as intermediate (I) were combined with resistant (R) for this study.
Taxonomy.
A recent review by Conville et al. (7) was used to determine the most current taxonomy for Nocardia species. Thus, the Nocardia abscessus complex includes N. abscessus, Nocardia arthritidis, Nocardia asiatica, Nocardia beijingensis, and Nocardia pneumoniae. The Nocardia nova complex includes Nocardia africana, Nocardia aobensis, Nocardia cerradoensis, Nocardia elegans, Nocardia kruczakiae, Nocardia mikamii, N. nova, Nocardia vermiculata, and Nocardia veterana. The Nocardia farcinica complex includes N. farcinica and Nocardia kroppenstedtii. The Nocardia transvalensis complex includes Nocardia blacklockiae, N. transvalensis, and Nocardia wallacei.
Multidrug-resistant Nocardia.
To our knowledge, there is no current consensus for defining multidrug-resistant (MDR) Nocardia, but in this work, the definition by Schlaberg et al. (9) was followed, with MDR Nocardia species defined as an isolate that is nonsusceptible (resistant or intermediate) to 2 or more of the most commonly used empirical agents, which would currently be amikacin, ceftriaxone, imipenem, and TMP-SMX.
Supplementary Material
Footnotes
Supplemental material is available online only.
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