Ceftazidime-Avibactam/Aztreonam Combination for the Treatment of Carbapenem-resistant Klebsiella pneumoniae-induced Osteomyelitis: A Case Series with Review of Literature

Introduction: Osteomyelitis secondary to multi-drug resistant (MDR) gram-negative bacteria (GNB), especially Carbapenem-resistant Klebsiella pneumoniae (CRKP), is a rare occurrence. These are difficult to treat micro-organisms and their presence within the host bone tissue makes them inherently resistant to most standard antimicrobials. Although a number of drugs have been described in the literature, there are no standardized guidelines as to the ideal drug of choice effective against CRKP-induced bone and joint infections (BJIs). In this context, we have described our experience in treating three cases of CRKP osteomyelitis secondary to an open fracture, who presented to us following a road-traffic accident (RTA). Case Report: Three patients of polytrauma presented to the emergency room of a tertiary care institute following RTA. All of them were primarily resuscitated, following which fixation of the fractures was undertaken. In the post-operative period, surgical site infection was seen in all three at specific locations. These were thoroughly debrided, and intraoperative samples sent for culture analyses. The latter revealed isolates of CRKP. Accordingly, a multidisciplinary approach was followed, combining inputs from the surgical team, clinical microbiologist, as well as an infectious disease specialist. Infected implants were removed, and a plastic surgery consult sought for wound coverage. Ceftazidime-Avibactam (CAZ-AVI) in conjunction with Aztreonam (ATM) was started after synergy testing. This was continued for a duration of 4-6 weeks. In two patients, the fracture had successfully united, whereas in one, a definitive fixation is still pending. Soft-tissue envelope healing was achieved in all cases. No adverse effects were reported. Conclusion: Cases of BJI secondary to CRKP necessitate a combined approach which includes prompt surgical debridement with/without implant removal and culture-specific antimicrobial therapy. Although experience is limited, CAZ-AVI/ATM combination has shown promising results.