Linezolid- and Multidrug-Resistant Enterococci in Raw Commercial Dog Food,Europe, 2019–2020

We describe enterococci in raw-frozen dog food commercialized in Europe as a source of genes encoding resistance to the antibiotic drug linezolid and of strains and plasmids enriched in antibiotic-resistance and virulence genes in hospitalized patients. Whole-genome sequencing was fundamental to linking isolates from dog food to human cases across Europe.     

A toxicogenomic approach for identifying biomarkers for myelosuppressive anemia in rats

Myelosuppressive anemia is a serious side effect associated with several drugs. Thus, there is an increasing demand for sensitive biomarkers for the early detection of myelosuppressive anemia during toxicological studies. We applied a toxicogenomic approach to identify useful biomarker genes reflecting myelosuppressive anemia in the rat liver. Expression of the hemoglobin beta chain complex (Hbb), aminolevulinic acid synthase 2 (Alas2), and cell division cycle 25 homolog B (Cdc25b) genes changed as a result of anemia induced by the myelosuppressive agents linezolid, cisplatin, and carboplatin, suggesting that these genes may be suitable biomarkers. Moreover, evaluation of perfused and unperfused livers indicated that changes in the expression of these genes originate in circulating reticulocytes in the liver. Erythroid differentiation-associated changes in expression of the Hbb, Alas2, and Cdc25b genes were confirmed in vitro using Friend leukemia cells. In conclusion, our current research provides novel evidence that gene expression in circulating reticulocytes contained in the liver changes dramatically under myelosuppressive conditions. While further large-scale validation studies are needed, our results indicate that the genes we identified might be useful biomarkers for the sensitive detection of myelosuppressive anemia in rats.     

Mitochondrial loss indicates early axonal damage in small fiber neuropathies

Evaluation of nerve fibers in the skin provides a useful tool for the diagnosis of small fiber neuropathies (SFNs). Our aim was to determine whether mitochondria are involved in SFN, indicating early axonal damage. We quantified mitochondrial respiratory chain complex IV (OXPHOS) and axonal (PGP 9.5) fluorescence on skin sections from 32 SFN patients and 14 healthy controls. Also, a group of six patients were recruited before and after 30-day treatment with the mitotoxic antibiotic linezolid. We measured the co-localization of OXPHOS within the intraepidermal and subpapillary dermal axons (PGP-immunoreactive [PGP-ir]). SFN patients with relatively preserved intraepidermal nerve fibers (SFN borderline) showed statistically significant reduction of OXPHOS (50.5 ± 33.9 μm(2) vs. 107.6 ± 81 μm(2) in controls, p < 0.02). A positive correlation was found between both PGP-ir and OXPHOS in controls (Pearson's coefficient r = 0.59, p < 0.001), whereas such correlation was absent in SFN. With respect to baseline measurements, linezolid therapy increased both PGP-ir and OXPHOS, which could be considered an initial compensatory toxic-induced response. This study set out to identify a possible marker of axonal pre-degenerative state in SFN borderline patients.     

Efficacy and safety of linezolid in immunocompromised children with cancer

Background: The aim of this study was to determine the safety, tolerance and efficacy of linezolid for the treatment of infections from Gram‐positive bacteria in immunocompromised children with cancer. Methods: This was a prospective non‐comparative unblinded study in the Hematology/Oncology Unit over a two‐year period, administering linezolid as monotherapy in children with cancer. Results: Seventeen children received linezolid (30 mg/kgr: 3 i.v. per day). Mean duration of linezolid administration was 12.2 days (range, 6–38 days), while the median age of the evaluable patients was 2.2 years (range, 6 months–11.2 years). Primary diagnosis was acute lymphoblastic leukemia (nine patients), brain tumor (three patients), multi‐organ Langerhans cell histiocytosis (two patients), rhabdomyosarcoma, Burkitt's lymphoma and ovarian tumor (one patient each). All patients were in the midst of chemotherapy cycles. Ten out of 17 children had positive blood cultures (methicillin‐resistant Staphylococcus aureus, four patients; vancomycin‐resistant Enterococcus, three patients; penicillin‐resistant Streptococcus pneumoniae, three patients), while seven of the 17 had fever and vancomycin‐resistant Enterococcus in stool cultures. All patients were considered clinically cured after the end of the linezolid regimen (100% efficacy). The main adverse events were thrombocytopenia grade 1–3 and anemia grade 2–3 (four and two patients, respectively). Chemotherapy‐induced myelotoxicity (six patients) was not worsened during linezolid therapy. No bleeding episodes were presented. Self‐limited diarrhea grade 1–2 was presented in four patients (mean duration 2 days). The total adverse event rate was 23.5%; however, there was no premature cessation of linezolid in any patient. Conclusions: Linezolid may be another effective and safe therapy to treat infections from resistant Gram‐positive bacteria in immunocompromised children, even in young ages.     

Linezolid: pharmacokinetic characteristics and clinical studies

Linezolid is an oxazolidinone indicated in the treatment of nosocomial and community-acquired pneumonia, complicated and uncomplicated skin and skin structure infections and vancomycin-resistant Enterococcus infections. The drug is also approved for use in complicated skin infections and nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus , concurrent bacteremia associated with vancomycin-resistant Enterococcus faecium and concurrent bacteremia associated with community-acquired pneumonia caused by penicillin-susceptible Streptococcus pneumoniae .     

Efficacy and safety of linezolid in liver transplant patients

S. Radunz, B. Juntermanns, G.M. Kaiser, J. Treckmann, Z. Mathe, A. Paul, F.H. Saner. Efficacy and safety of linezolid in liver transplant patients
Transpl Infect Dis 2011: 13: 353–358. All rights reserved Abstract: Bacterial infections are the main cause of death within the first year after liver transplantation, and the increased incidence of multidrug‐resistant gram‐positive pathogens has created a major challenge in the treatment of these patients. Linezolid, the first US Food & Drug Administration‐approved oxazolidinone, offers a valuable novel treatment option for serious gram‐positive infections. Linezolid is relatively non‐toxic but prolonged treatment with linezolid was associated with thrombocytopenia. Here we report on the experience of linezolid treatment in adult liver transplant patients, who are at an increased risk for thrombocytopenia because of hypersplenism. From November 2003 until December 2009, we evaluated the clinical course of 46 liver transplant patients (27 male/19 female) in our surgical intensive care unit. For proven or probable gram‐positive infection, all patients received linezolid 600 mg intravenously every 12 h. On clinical improvement, treatment was changed to oral linezolid 600 mg twice daily. Treatment duration was 11 ± 7 days. Treatment indications were pneumonia (n=8), blood stream infection (n=30), and surgical site/abdominal infection (n=3). Clinical cure was achieved in 43 out of 46 patients. During the course of treatment, no cases of severe thrombocytopenia occurred and a statistically significant platelet count increase was seen from day 1 (110 ± 73/nL) to day 7 (165 ± 116/nL) and day 14 (180 ± 140/nL). We did not observe any further adverse events, especially no severe neurological complications (e.g., serotonin syndrome) or signs of lactate acidosis. Two patients died from uncontrolled vancomycin‐resistant Enterococcus faecium sepsis with septic shock and one due to uncontrolled methicillin‐resistant Staphylococcus aureus pneumonia. These deaths were considered to be unrelated to linezolid treatment, and linezolid was regarded as the optimal treatment choice in these patients. A subgroup analysis of patients treated for >14 days revealed no statistically significant differences when compared with patients on shorter treatment. In particular, no cases of thrombocytopenia occurred during longer treatment. In conclusion, linezolid is a safe and effective treatment for adult liver transplant patients with gram‐positive infections.