Antibiotic prophylaxis for urinary catheter manipulation following arthroplasty: a systematic review.

BACKGROUND: Urinary catheter use in the peri- and post-operative phase following arthroplasty may be associated with urinary tract infection (UTI) and deep prosthetic joint infection (PJI). These can be catastrophic complications in joint arthroplasty. We performed a systematic review of the evidence on use of antibiotics for urinary catheter insertion and removal following arthroplasty. METHODS: Electronic databases were searched using the Healthcare Databases Advanced Search interface. Grey literature was searched. From 219 citations, six studies were deemed eligible for review. Due to study heterogeneity, a narrative approach was adopted. Methodological quality of each study was assessed using the Critical Appraisal Skills Programme appraisal tool. RESULTS: A total of 4696 hip and knee arthroplasties were performed on 4578 participants across all studies. Of these, 1475 (31%) were on men and 3189 (68%) on women. The mean age of study participants was 69 years. Three thousand four hundred and eighty-nine cases (74.3%) were related to hip arthroplasty and 629 (13.4%) to knee arthroplasty. Five hundred and seventy-eight (12.3%) were either hip or knee arthroplasty. Forty-five PJIs were reported across all studies (0.96%). Two studies found either no PJI or no statistical difference in the rate of PJI when no antibiotic prophylaxis was used for catheter manipulation. Another study found no statistical difference in PJI rates between patients with or without preoperative bacteriuria. Where studies report potential haematogenous spread from UTIs, this association can only be assumed. Increased duration of urinary catheterization is positively associated with UTI. CONCLUSION: It remains difficult to justify the use of prophylactic antibiotics for catheter manipulation in well patients. Their use is not recommended for this indication.

Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins.

Using a high throughput screening methodology we surveyed a collection of largely uncharacterized validated or suspected kinase inhibitors for anti-human cytomegalovirus (HCMV) activity. From this screen we identified three structurally related 5-aminopyrazine compounds (XMD7-1, -2 and -27) that inhibited HCMV replication in virus yield reduction assays at low micromolar concentrations. Kinase selectivity assays indicated that each compound was a kinase inhibitor capable of inhibiting a range of cellular protein kinases. Western blotting and RNA sequencing demonstrated that treatment of infected cells with XMD7 compounds resulted in a defect in the production of the major HCMV transcriptional transactivator IE2 proteins (IE2-86, IE2-60 and IE2-40) and an overall reduction in transcription from the viral genome. However, production of certain viral proteins was not compromised by treatment with XMD7 compounds. Thus, these novel anti-HCMV compounds likely inhibited transcription from the viral genome and suppressed production of a subset of viral proteins by inhibiting IE2 protein production.