Linezolid Effective for Gram-Positive Bacterial Infections in ICU

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, wrote Aijia Ma, MD, of West China Hospital of Sichuan University, Sichuan, China, and colleagues.

Linezolid has demonstrated effectiveness against methicillin-resistant Staphylococcus aureus (MRSA) and skin and soft tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018, and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S aureus [MSSA]) followed by Enterococci (6.7% vancomycin-resistant; 9.2% vancomycin-susceptible) and Streptococcus pneumoniae (3.4% multidrug-resistant; 1.7% non–multidrug-resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line vs. first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1109 mg, and the mean treatment time was 5.1 days.

A total of 8 patients (2.2%) reported linezolid-related adverse events, and 4 patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (2 patients) compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote in their discussion.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events, they said.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

J Intensive Med. Published online July 5, 2022. Full text

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