Oral versus Intravenous Antibiotics for Bone and Joint Infection.

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

A case of NDM-carbapenemase-producing hypervirulent Klebsiella pneumoniae sequence type 23 from the UK.

INTRODUCTION: Hypervirulent capsular type K1 Klebsiella pneumoniae strains of clonal complex 23 (CC23) are associated with severe community-acquired pyogenic liver abscesses, often complicated by metastatic infections and significant mortality. The majority of hypervirulent strains reported are susceptible to most antibiotics except ampicillin. To the best of our knowledge, this is the first case of New Delhi metallo-ß-lactamase (bla NDM)-producing hypervirulent K. pneumoniae from the UK. CASE PRESENTATION: We present a case of pyogenic liver abscess in a 63-year-old female of Bangladeshi origin, with a recent diagnosis of pancreatic cancer. The patient was treated with piperacillin/tazobactam and blood cultures grew a fully susceptible Escherichia coli. Despite antimicrobial therapy and drainage of the abscess, the patient continued to deteriorate and died on day seven of admission. The fluid drained from the liver abscess grew a fully susceptible E. coli and a multi-drug-resistant K. pneumoniae. Two weeks prior to admission, a rectal screening swab grew a metallo-ß-lactamase-producing K. pneumoniae. Molecular characterization revealed that both the K. pneumoniae isolates belonged to the hypervirulent K1 cluster of CC23, sequence type 23. The isolate from the rectal screen was positive for the bla NDM metallo-ß-lactamase gene. CONCLUSION: The emergence of carbapenemase-producing hypervirulent K. pneumoniae strains presents a new and significant threat to global public health. Management of these infections will be extremely challenging due to the limited treatment options available and they are likely to be associated with an even greater mortality.