Dual intraventricular plus systemic antibiotic therapy for the treatment of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae ventriculitis.

OBJECTIVE: To report a case of Klebsiella pneumoniae carbapenemase (KPC)-producing K pneumoniae ventriculitis successfully treated with dual intraventricular plus systemic antibiotic therapy. CASE SUMMARY: A 43-year-old woman with a ventriculoperitoneal shunt was transferred from a nursing home with fever, altered mental status, and leukocytosis. She was found to have KPC-producing K pneumoniae ventriculitis. Combination intraventricular antibiotic therapy with colistin and gentamicin plus systemic colistin and amikacin led to the resolution of infection. DISCUSSION: Utilization of intraventricular or intrathecal antibiotics has been described in the literature for multidrug resistant (MDR) Gram-negative central nervous system (CNS) infections; however, none of the cases were caused by a KPC-producing organism. Given the pathogenicity and limited treatment options for this resistant organism, we utilized intraventricular colistin 10 mg and intraventricular gentamicin 10 mg in combination with systemic colistin and amikacin. An extensive literature search revealed several case reports and case series of documented MDR Acinetobacter baumanii CNS infections successfully treated with intraventricular colistin or aminoglycoside therapy with good tolerability. Additionally, recent pharmacokinetic analyses suggest improved cerebrospinal fluid (CSF) concentrations with direct CNS antimicrobial administration in combination with systemic therapy. Although our patient's cerebral spinal fluid cultures were cleared with dual intraventricular plus systemic therapy, she continued to deteriorate clinically because of her comorbid conditions and required hospice admission. CONCLUSIONS: This describes the first reported case of KPC-producing K pneumoniae ventriculitis microbiologically cured based on negative blood and CSF cultures with a combination of intraventricular and systemic therapy.

Mutant Huntingtin Disrupts the Nuclear Pore Complex.

Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus and cytoplasm, is tightly regulated by nuclear pore complexes (NPCs) made up of nucleoporins (NUPs). Previous studies offered clues that mHTT may disrupt nucleocytoplasmic transport and a mutation of an NUP can cause HD-like pathology. Therefore, we evaluated the NPC and nucleocytoplasmic transport in multiple models of HD, including mouse and fly models, neurons transfected with mHTT, HD iPSC-derived neurons, and human HD brain regions. These studies revealed severe mislocalization and aggregation of NUPs and defective nucleocytoplasmic transport. HD repeat-associated non-ATG (RAN) translation proteins also disrupted nucleocytoplasmic transport. Additionally, overexpression of NUPs and treatment with drugs that prevent aberrant NUP biology also mitigated this transport defect and neurotoxicity, providing future novel therapy targets.

Single-Dose Basiliximab Induction in Low-Risk Renal Transplant Recipients.

OBJECTIVES: To compare the efficacy of a single dose of basiliximab with two doses in preventing acute rejection in selected low-risk renal transplant recipients. METHODS: This observational study of 760 kidney transplant recipients considered to be at low immunologic risk (peak panel reactive antibody less than 10%) compared patient and graft outcomes following a single-dose versus a two-dose regimen of basiliximab. MAIN RESULTS: No differences were found in patient survival (92% vs 92%, p=0.6), graft survival (86% vs 83%, p=0.2), acute rejection (cellular [4% vs 7%, p=0.2], antibody-mediated rejection [19% vs 19%, p=0.9]), or opportunistic infections (34% vs 30%, p=0.3) between the single versus two-dose regimens, respectively. In multivariate analyses, the number of doses of basiliximab was not associated with acute rejection or patient/graft survival despite adjustment with Cox regression and propensity scores. However, delayed graft function (DGF), donor age older than 65 years, and human leukocyte antigen mismatch of 3 or higher were associated with acute rejection (hazard ratio [HR] 2.64, 1.91, and 1.57, respectively, p≤0.04), and DGF and diabetes were associated with death/graft loss (HR 2.56 and 1.63, respectively, p≤0.009). PRINCIPAL CONCLUSIONS: A single dose of basiliximab is safe and effective for induction in low-risk kidney transplant recipients.