Antibiotic Practice Change to Curtail Linezolid Use in Pediatric Hospitalized Patients in Hawai'i with Uncomplicated Skin and Soft Tissue Infections.

Antimicrobial resistance affects health care providers' choice of antibiotics in the treatment of skin and soft tissue infections (SSTIs). Based on local antibiotic susceptibility data showing high clindamycin resistance and high MRSA prevalence, a change in antibiotic regimen for children hospitalized for uncomplicated SSTIs was instituted in an attempt to curb the use of linezolid. A retrospective chart review was performed on 278 pediatric patients with uncomplicated SSTIs hospitalized at Kapi'olani Medical Center for Women and Children in Hawai'i from May 2014 to April 2015 and November 2015 to October 2016. Data consisted of 12 months of baseline data and 12 months of data post-implementation of an antibiotic combination regimen of 2 widely-used antibiotics: high-dose cefazolin and high-dose clindamycin. Practitioners were encouraged to use cefazolin alone if clinical suspicion was high for single-organism infection with group A streptococcus. The measured outcomes included initial antibiotic, switch in antibiotic, and length of stay. The use of the combination of cefazolin and clindamycin as the initial treatment, compared with prior practice of monotherapy with clindamycin or cephazolin, was associated with fewer patients started on linezolid (P=.03), no increase in patients switching to linezolid (P=.97), and no significant change in length of stay (P=.06). When clindamycin resistance and MRSA prevalence are both elevated, the combination of cefazolin and clindamycin is an option that can help with antibiotic stewardship to decrease the use of linezolid.

Comparative efficacy of linezolid and vancomycin for endotracheal tube MRSA biofilms from ICU patients.

PURPOSE: To compare the efficacy of systemic treatment with linezolid (LNZ) versus vancomycin (VAN) on methicillin-resistant Staphylococcus aureus (MRSA) burden and eradication in endotracheal tube (ETT) biofilm and ETT cuff from orotracheally intubated patients with MRSA respiratory infection. METHODS: Prospective observational clinical study was carried out at four European tertiary hospitals. Plasma and endotracheal aspirate (ETA) levels of LNZ and VAN were determined 72 h after treatment initiation through high-performance liquid chromatography or bioassay. LNZ or VAN concentration in the ETT biofilm and MRSA burden and eradication was determined upon extubation. The minimum inhibitory concentration (MIC) for LNZ and VAN was assessed by E-test strips (Biomerieux®). Scanning electron microscopy images were obtained, and ETT biofilm thickness was compared between groups. RESULTS: Twenty-five patients, 15 treated with LNZ and 10 with VAN, were included in the study. LNZ presented a significantly higher concentration (µg/mL) than VAN in ETT biofilm (72.8 [1.3-127.1] vs 0.4 [0.4-1.3], p < 0.001), although both drugs achieved therapeutic plasma levels 72 h after treatment initiation. Systemic treatment with LNZ achieved lower ETT cuff MRSA burdens than systemic treatment with VAN. Indeed, LNZ increased the MRSA eradication rate in ETT cuff compared with VAN (LNZ 75%, VAN 20%, p = 0.031). CONCLUSIONS: In ICU patients with MRSA respiratory infection intubated for long periods, systemic treatment with LNZ obtains a greater beneficial effect than VAN in limiting MRSA burden in ETT cuff.

Ultrahigh-throughput absolute quantitative analysis of linezolid in human plasma by direct analysis in real time mass spectrometry without chromatographic separation and its application to a pharmacokinetic study.

Therapeutic drug monitoring (TDM) is necessary in the clinical management of linezolid to improve its efficacy and reduce the risk of time- and dose-dependent toxicity. A novel and ultrahigh-throughput analytical method for the determination of linezolid in human plasma was developed based on direct analysis in real-time tandem mass spectrometry (DART-MS/MS) without chromatographic separation. After solid-phase extraction with Waters Oasis HLB, the linezolid and internal standard linezolid-d3 were detected by positive ion electrospray ionization followed by multiple reaction monitoring (MRM) of the transition at m/z 338.1 → 296.2 and 341.2 → 297.3, respectively. The use of DART-MS obviates the need for chromatographic separation and allowed determination of linezolid in a total run time of only 24 s per sample. The method was linear in the concentration range 0.20-25 µg mL-1 with intraday and interday precision <14.5% and accuracy ranging from -3.85% to 12.7%. The method was successfully applied to a pharmacokinetic study of linezolid in healthy male volunteers after oral administration of a 600 mg tablet. DART-MS/MS provides a rapid and sensitive method for the determination of linezolid that does not require chromatographic separation. It is eminently suitable to meet the high-throughput challenge of clinical TDM. Graphical abstract.