Linezolid use in combination antibiotic therapy is effective and as safe as other firstline treatments for moderate to severe nocardiosis, according to results of a large case series study published in Open Forum Infectious Diseases.
Although cases of infection with Nocardia spp have increased in the past 2 decades, specifically in tropical regions like northern Australia, there are no optimal treatment regimens and there have been no randomized controlled trials of firstline agents. Because linezolid is the only antimicrobial to which all Nocardia species are susceptible, researchers assessed the safety and outcomes of its use in combination therapy. They identified cases through a retrospective review of all moderate to severe nocardiosis infections at Royal Darwin Hospital in the Northern Territory of Australia from December 2014 to August 2018.
Isolates from 35 individuals were identified: 28 patients were considered to have a clinically significant infection and 23 patients received treatment. Five additional linezolid-treated cases were included from a previous cohort. All isolates were susceptible to linezolid. Thus, the study included 20 patients receiving linezolid-containing regimens and 8 receiving non-linezolid-regimens.
The most common species identified were Nocardia beijingensis (19%) and Nocardia cyriacigeorgica (16%). Antimicrobial susceptibility testing results were available for 30 patients. Overall, 100% of isolates were susceptible to linezolid as well as to amikacin; 93% were susceptible to trimethoprim-sulfamethoxazole; 60% of isolates were susceptible to ceftriaxone and 45% to imipenem.
The median age was 62 years (interquartile range [IQR], 52-68 years) in the linezolid group and 67 years (IQR, 56-74 years) in the non-linezolid group. Chronic lung disease was the most common underlying risk factor (60% in linezolid group vs 63% in non-linezolid group). Pulmonary infection was the most common presentation in both groups (80% in linezolid group vs 88% in non-linezolid group). None of the patients who received linezolid had baseline thrombocytopenia, compared with 30% of those who received an alternative regimen. Five patients were immunosuppressed and none were receiving prophylaxis with trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia or melioidosis at diagnosis.
The median duration of linezolid use was 28 days. Of the patients who received linezolid, 90% were also concurrently treated with trimethoprim-sulfamethoxazole; 40% of patients in the cotreated group required prompted discontinuation of trimethoprim-sulfamethoxazole due to adverse events, compared with 20% of patients who received linezolid only. There were no relapses in the linezolid-treated patients and 1 relapse in the nonlinezolid group, in a patient treated with 3 months of combination therapy with ceftriaxone, meropenem, and amikacin—despite antimicrobial susceptibility tests indicating bacterial susceptibility to both antibiotics.
Common adverse effects in patients who received linezolid were thrombocytopenia (45%) and anemia (40%) developing at a median time of approximately 3 weeks. Acute kidney injury was also common in both groups, attributed solely to trimethoprim-sulfamethoxazole, and improved in all cases with cessation of this antibiotic.
Linezolid therapeutic drug monitoring was used in 1 patient, with successful dose reduction and outcome. “For patients who develop dose-dependent toxicity, [therapeutic drug monitoring] should be considered to reduce linezolid doses while ensuring efficacy,” noted the researchers.
There 30-day and 1-year survival between those treated with linezolid (90%, and 85%, respectively) and those who received alternative treatment was comparable. One Nocardia-attributed death occurred during linezolid therapy.
Study results “support the empirical use of linezolid for the treatment of moderate to severe nocardiosis and have informed and support the 2019 Australian Therapeutic Guidelines recommendations for empirical treatment of Nocardia infections,” concluded the researchers.
Davidson N, Grigg MJ, Mcguinness SL, Baird RJ, Anstey NM. Safety and outcomes of linezolid use for nocardiosis. Open Forum Infect Dis. 2020;7(4):ofaa090.