Combination therapy for multidrug-resistant cytomegalovirus disease

Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of pet contact as a risk factor for carriage of multidrug-resistant staphylococci in nursing home residents

BACKGROUND Pets, often used as companionship and for psychological support in the therapy of nursing home residents, have been implicated as reservoirs for antibiotic-resistant bacteria. We investigated the importance of pets as reservoirs of multidrug-resistant (MDR) staphylococci in nursing homes. METHODS We assessed the carriage of MDR staphylococci in pets and in 2 groups of residents, those living in nursing homes with pets and those living without pet contacts. We collected demographic, health status, and human-pet contact data by means of questionnaires. We assessed potential bacteria transmission pathways by investigating physical resident-to-pet contact. RESULTS The observed prevalence of MDR staphylococci carriage was 84/229 (37%) in residents living with pets and 99/216 (46%) in those not living with pets (adjusted odds ratio [aOR], 0.6; 95% confidence interval [CI], 0.4-0.9). Active pet contact was associated with lower carriage of MDR staphylococci (aOR, 0.5; 95% CI, 0.4-0.8). Antibiotic treatment during the previous 3 months was associated with significantly increased risk for MDR carriage in residents (aOR, 3.1; 95% CI, 1.8-5.7). CONCLUSIONS We found no evidence that the previously reported benefits of pet contact are compromised by the increased risk of carriage of MDR staphylococci in residents associated with interaction with these animals in nursing homes. Thus, contact with pets, always under good hygiene standards, should be encouraged in these settings.

Viral escape in the CNS with multidrug-resistant HIV-1.

Introduction: HIV-1 viral escape in the cerebrospinal fluid (CSF) despite viral suppression in plasma is rare [1,2]. We describe the case of a 50-year-old HIV-1 infected patient who was diagnosed with HIV-1 in 1995. Antiretroviral therapy (ART) was started in 1998 with a CD4 T cell count of 71 cells/ìL and HIV-viremia of 46,000 copies/mL. ART with zidovudine (AZT), lamivudine (3TC) and efavirenz achieved full viral suppression. After the patient had interrupted ART for two years, treatment was re-introduced with tenofovir (TDF), emtricitabin (FTC) and ritonavir boosted atazanavir (ATVr). This regimen suppressed HIV-1 in plasma for nine years and CD4 cells stabilized around 600 cells/ìL. Since July 2013, the patient complained about severe gait ataxia and decreased concentration. Materials and Methods: Additionally to a neurological examination, two lumbar punctures, a cerebral MRI and a neuropsycological test were performed. HIV-1 viral load in plasma and in CSF was quantified using Cobas TaqMan HIV-1 version 2.0 (Cobas Ampliprep, Roche diagnostic, Basel, Switzerland) with a detection limit of 20 copies/mL. Drug resistance mutations in HIV-1 reverse transcriptase and protease were evaluated using bulk sequencing. Results: The CSF in January 2014 showed a pleocytosis with 75 cells/ìL (100% mononuclear) and 1,184 HIV-1 RNA copies/mL, while HIV-1 in plasma was below 20 copies/mL. The resistance testing of the CSF-HIV-1 RNA showed two NRTI resistance-associated mutations (M184V and K65R) and one NNRTI resistance-associated mutation (K103N). The cerebral MRI showed increased signal on T2-weighted images in the subcortical and periventricular white matter, in the basal ganglia and thalamus. Four months after ART intensification with AZT, 3TC, boosted darunavir and raltegravir, the pleocytosis in CSF cell count normalized to 1 cell/ìL and HIV viral load was suppressed. The neurological symptoms improved; however, equilibrium disturbances and impaired memory persisted. The neuro-psychological evaluation confirmed neurocognitive impairments in executive functions, attention, working and nonverbal memory, speed of information processing, visuospatial abilities and motor skills. Conclusions: HIV-1 infected patients with neurological complaints prompt further investigations of the CSF including measurement of HIV viral load and genotypic resistance testing since isolated replication of HIV with drug resistant variants can rarely occur despite viral suppression in plasma. Optimizing ART by using drugs with improved CNS penetration may achieve viral suppression in CSF with improvement of neurological symptoms.

Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1

In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms.