Nocardiosis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

severe nocardiosis: disseminated disease, CNS involvement, cavitary pulmonary lesions, or immunocompromise

1st line – empiric antibiotic therapy

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1st line –

empiric antibiotic therapy

Although treatment should be guided by Nocardia speciation and susceptibility testing, clinicians usually start treatment empirically, when the results are still not available.

Initial aggressive treatment with combination therapy is advised to ensure a wide coverage of all the possible species involved and because of possible synergy between antibiotics.[62] For the treatment of severe disease, some experts recommend a triple regimen consisting of trimethoprim/sulfamethoxazole, amikacin, and a carbapenem (e.g., imipenem/cilastatin).[5][8][73][86] Alternatively, a two-drug regimen may be advised for severe disease not involving the central nervous system (CNS), such as trimethoprim/sulfamethoxazole plus amikacin or imipenem/cilastatin, or imipenem/cilastatin plus amikacin.[43]

Amkacin is often included in initial empiric treatment regimens due to high susceptibility rates across Nocardia species, however, its use is associated with potential nephrotoxicity and ototoxicity. Careful monitoring of serum amikacin levels and for signs of these complications is advised, particularly if treatment duration is prolonged. As amikacin achieves poor CNS penetration, a two-drug regimen containing this treatment may be insufficient for the treatment of CNS disease which is why treatment with triple therapy is recommended in such cases.

Linezolid is another option to include in an initial regimen for severe disease (e.g., trimethoprim/sulfamethoxazole plus linezolid plus a carbapenem).[43] Linezolid has shown strong in-vitro activity against most of the Nocardia species and strains tested.[64] Additionally, linezolid has high oral bioavailability and can penetrate the CNS.[65][66] There is growing evidence to support the use of linezolid in the treatment of nocardiosis, including among patients with CNS involvement, although some clinicians have raised concerns that the range of serious adverse effects might limit its widespread use.[62][67][68] One 2019 retrospective study of 20 patients with moderate-to-severe nocardiosis found that initial empiric treatment with a linezolid-containing regimen was at least as safe and effective as other first-line agents.[70] The risk of hematologic and neurologic complications might limit its use to monitored hospital settings and for initial, empiric treatment. Careful monitoring of these complications is recommended with treatment.

When the results of typing and sensitivity tests are available, treatment can be adjusted and oral agents can be considered for follow-up therapy.[43] Because resistance patterns within the same species may differ, treatment will be individual to each patient and cannot be standardized. The choice of agent(s) is individualized based on culture and sensitivity.

Duration of therapy is variable and depends on the location of the lesions and the immune status of the patient.

Primary options

Three-drug regimen

sulfamethoxazole/trimethoprim: 15 mg/kg/day intravenously/orally given in divided doses every 6-12 hours

and

amikacin: 15 mg/kg/day intravenously given in divided doses every 12 hours

and

imipenem/cilastatin: 500 mg intravenously every 6 hours, or 1000 mg intravenously every 6-8 hours

Three-drug regimen

sulfamethoxazole/trimethoprim: 15 mg/kg/day orally/intravenously given in divided doses every 6-12 hours

and

linezolid: 600 mg intravenously/orally every 12 hours

and

imipenem/cilastatin: 500 mg intravenously every 6 hours, or 1000 mg intravenously every 6-8 hours

Two-drug regimen

sulfamethoxazole/trimethoprim: 15 mg/kg/day orally/intravenously given in divided doses every 6-12 hours

-- AND --

amikacin: 15 mg/kg/day intravenously given in divided doses every 12 hours

imipenem/cilastatin: 500 mg intravenously every 6 hours, or 1000 mg intravenously every 6-8 hours

Two-drug regimen

imipenem/cilastatin: 500 mg intravenously every 6 hours, or 1000 mg intravenously every 6-8 hours

and

amikacin: 15 mg/kg/day intravenously given in divided doses every 12 hour

Consider – surgery

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Consider –

surgery

Treatment recommended for SOME patients in selected patient group

May be necessary for draining or removing central nervous system, pulmonary, or cutaneous abscesses or empyemas not responding to medication.

nonsevere nocardiosis: immunocompetent, nondisseminated, no CNS involvement, no pulmonary cavitary lesions

pulmonary disease

1st line – empiric antibiotic therapy

Back

1st line –

empiric antibiotic therapy

Although treatment should be guided by Nocardia speciation and susceptibility testing, clinicians usually start treatment empirically, when the results are still not available.

Nonsevere pulmonary disease may be treated with trimethoprim/sulfamethoxazole monotherapy, or with a two-drug regimen consisting of trimethoprim/sulfamethoxazole plus another agent such as ceftriaxone, ciprofloxacin, moxifloxacin, linezolid, or minocycline.[21][43] Choice of antibiotic therapy is guided by the treating clinician and depends on whether the infection is mild or moderate.

The hematologic and neurologic complications associated with linezolid might limit its use to monitored hospital settings and for initial, empiric treatment.

Fluoroquinolones (e.g., ciprofloxacin, moxifloxacin) have been associated with serious, disabling, and potentially irreversible adverse effects, including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[87] Warnings have also been issued about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[88][89]

Duration of therapy is variable and depends on the location of the lesions and the immune status of the patient.

Primary options

One-drug regimen

sulfamethoxazole/trimethoprim: 15 mg/kg/day orally/intravenously given in divided doses every 6-12 hours

Two-drug regimen

sulfamethoxazole/trimethoprim: 15 mg/kg/day orally/intravenously given in divided doses every 6-12 hours

-- AND --

ceftriaxone: 2 g intravenously every 24 hours

ciprofloxacin: 400 mg intravenously every 12 hours; 500-750 mg orally twice daily

moxifloxacin: 400 mg intravenously/orally every 24 hours

linezolid: 600 mg intravenously/orally every 12 hours

minocycline: 100 mg orally twice daily

cutaneous: no mycetoma or bone or joint involvement

1st line – empiric antibiotic therapy

Back

1st line –

empiric antibiotic therapy

Although treatment should be guided by Nocardia speciation and susceptibility testing, clinicians usually start treatment empirically, when the results are still not available.

Most frequently seen in immunocompetent agricultural workers.

Duration of therapy is variable and depends on the location of the lesions and the immune status of the patient.

Primary options

sulfamethoxazole/trimethoprim: 15 mg/kg/day orally/intravenously given in divided doses every 6-12 hours

Consider – surgery

Back

Consider –

surgery

Treatment recommended for SOME patients in selected patient group

Subcutaneous abscesses may occasionally need to be drained.

cutaneous: with mycetoma, bone or joint involvement

1st line – empiric antibiotic therapy

Back

1st line –

empiric antibiotic therapy

Although treatment should be guided by Nocardia speciation and susceptibility testing, clinicians usually start treatment empirically, when the results are still not available.

Most frequently seen in immunocompetent agricultural workers.

Combination therapy with two antibiotics is advised for mycetoma, or if there is deep tissue involvement or extension to the bone.[12][43][73][74]

Trimethoprim/sulfamethoxazole may be combined with several agents (e.g., moxifloxacin, ciprofloxacin, imipenem/cilastatin, linezolid).

The hematologic and neurologic complications associated with linezolid might limit its use to monitored hospital settings and for initial, empiric treatment.

Warnings have also been issued about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[88][89]

Duration of therapy is variable and depends on the location of the lesions and the immune status of the patient.

Primary options

Two-drug regimen

sulfamethoxazole/trimethoprim: 15 mg/kg/day orally/intravenously given in divided doses every 6-12 hours

-- AND --

ciprofloxacin: 400 mg intravenously every 8-12 hours; 500-750 mg orally twice daily

moxifloxacin: 400 mg intravenously/orally every 24 hours

imipenem/cilastatin: 500 mg intravenously every 6 hours, or 1000 mg intravenously every 6-8 hours

linezolid: 600 mg intravenously/orally every 12 hours

Consider – surgery

Back

Consider –

surgery

Treatment recommended for SOME patients in selected patient group

Subcutaneous abscesses may occasionally need to be drained.

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Nocardiosis

Treatment algorithm

severe nocardiosis: disseminated disease, CNS involvement, cavitary pulmonary lesions, or immunocompromise

empiric antibiotic therapy

Primary options

Three-drug regimen

Three-drug regimen

Two-drug regimen

Two-drug regimen

surgery

nonsevere nocardiosis: immunocompetent, nondisseminated, no CNS involvement, no pulmonary cavitary lesions

empiric antibiotic therapy

Primary options

One-drug regimen

Two-drug regimen

empiric antibiotic therapy

Primary options

surgery

empiric antibiotic therapy

Primary options

Two-drug regimen

surgery