CSF from the external ventricular drain and blood were sent for analysis. CSF samples were cultured an additional seven times during the admission and were negative. On day 14, the patient developed Serratia marcescens line-related bacteraemia with a ceftaroline MIC ¼ 1.5 mg/L by Etest w . Gentamicin and meropenem were started empirically and streamlined to ciprofloxacin after final susceptibilities were reported. Repeat blood cultures were negative. On day 23 a new VP shunt was placed. The patient received ceftaroline and ciprofloxacin until discharge on day 27, at which point oral linezolid and ciprofloxacin were prescribed for an additional 7 days.Simultaneous ceftaroline blood and CSF samples were collected 6 and 7 days into therapy. The blood samples were centrifuged and CSF and blood samples were frozen at 2708C. The samples were mailed on dry ice to Keystone Bioanalyticals, which analysed them by liquid chromatography-MS. All storage and handling instructions were strictly followed. Results are shown in Table 1.By the time of CSF analysis, the patient's symptoms of infection had abated and it is likely that little-to-no meningeal inflammation remained. Thus, the CSF:plasma ratios of 0.035 and 0.041 are consistent with those of other b-lactams in this clinical situation. 8 Although the patient's clinical picture resolved while receiving ceftaroline, we cannot be sure that ceftaroline was the reason since the patient's CSF cultures cleared before it was initiated. While the drug levels from this patient help assess ceftaroline CSF penetration, we believe that ceftaroline levels collected during acute meningitis should be measured to determine the likely role of ceftaroline in the treatment of CNS infections. FundingThis study was carried out as part of our routine work. Transparency declarationsJ. C. G. is a speaker for Forest, Cubist and Astellas, he is a consultant for Forest and Pfizer, and he has received grant funding from Merck. S. S. K. and M. R.: none to declare.

Restriction of HIV-1 in myeloid-lineage cells is attributed in part to the nucleotidase activity of the SAM-domain and HD-domain containing protein (SAMHD1), which depletes free nucleotides, blocking reverse transcription. In the same cells, the Vpx protein of HIV-2 and most SIVs counteracts SAMHD1. Both Type I and II interferons may stimulate SAMHD1 transcription. The contributions of SAMHD1 to retroviral restriction in the central nervous system (CNS) have been the subject of limited study. We hypothesized that SAMHD1 would respond to interferon in the SIV-infected CNS but would not control virus due to SIV Vpx. Accordingly, we investigated SAMHD1 transcript abundance and association with the Type I interferon response in an SIV model. SAMHD1 transcript levels were IFN responsive, increasing during acute phase infection and decreasing during a more quiescent phase, but generally remaining elevated at all post-infection time points. In vitro, SAMHD1 transcript was abundant in macaque astrocytes and further induced by Type I interferon, while IFN produced a weaker response in the more permissive environment of the macrophage. We cannot rule out a contribution of SAMHD1 to retroviral restriction in relatively non-permissive CNS cell types. We encourage additional research in this area, particularly in the context of HIV-1 infection.

Pilakka-Kanthikeel et al. recently reported higher levels of the retroviral restriction factor sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) in astrocytes than in microglia, suggesting that SAMHD1 levels might explain in part the relatively refractory nature of astrocytes to retroviral replication. These findings are consistent with our studies of simian and human immunodeficiency virus infection of astrocytes and macrophages. Similarly, a role for two host microRNAs in post-transcriptional regulation of SAMHD1 agrees with our in vitro results and those of others. However, data from an animal model of HIV neurologic disorders may not be consistent with robust miRNA-mediated regulation of SAMHD1 in vivo.