First case of ceftazidime/avibactam administration in home care. ESBL producing Klebsiella pneumoniae bacteremia

Dear Editor,

The increase in nosocomial infections caused by multi-drug resistant Gram-negative bacilli has necessitated the development of new antibiotics. In recent months, the FDA approved 2 new antibiotics, ceftolozane/tazobactam and ceftazidime/avibactam, for the treatment of intra-abdominal infections (together with metronidazole) and urinary tract infections.¹ Since June 2016, ceftazidime/avibactam has been approved in Europe for the treatment of nosocomial pneumonia, including those cases associated with mechanical ventilation and infections caused by Gram-negative aerobic microorganisms, with limited treatment options.² There is no documented evidence on the use of these drugs in the hospital at home (HAH) setting, a treatment modality that is not only less expensive, but also drastically reduces the possibility of intrahospital transmission of the bacteria.

We report the first case of ceftazidime/avibactam administration in a hospital at home programme. It discusses a 62-year-old patient with hypertension who had recently been diagnosed (February 2016) with acute myeloblastic leukaemia and was undergoing treatment with chemotherapy. He was admitted to haematology for a consolidation cycle, and had as a complication persistent bacteraemia caused by multi-drug resistant extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae secondary to sacral ulcer. Initially he received empirical treatment with imipenem/cilastatin and colistin. Given that his fever persisted and his blood cultures were positive again, the antibiogram was extended and showed sensitivity only to ceftazidime/avibactam and resistance even to ceftolozane/tazobactam (minimum inhibitory concentration of 8). Therefore, in view of the results, despite the fact that it was not among the approved indications at that time (it is now), it was decided to start treatment with ceftazidime/avibactam. Given his clinical stability, HAH services were contacted to complete treatment. They continued administering 2/0.5 g/8 h of ceftazidime/avibactam, which required pump infusion and 2 home visits (the drug is stable diluted and unrefrigerated for 12 h¹). No outstanding incidents or related side effects occurred, and his monitoring rectal swab and blood cultures became negative.

Hospital-acquired infections are the sixth leading cause of death both in the United States and in Europe.³ Those caused by Gram-negative bacteria have a special capacity for acquiring new mechanisms of resistance to antibiotics, especially if they are under antibiotic pressure. Since few new antibiotics have been developed in recent years, few treatment options are available to fight these infections. Cases of nosocomial bacteraemia caused by Gram-negative bacteria account for 30% of these infections. The most common microorganisms include species of Klebsiella, as in our case. The increase in resistance to broad-spectrum cephalosporins and carbapenems is also a particularly significant problem.³ Among cases of nosocomial bacteraemia caused by K. pneumoniae, in the United States, 27.1% were resistant to third-generation cephalosporins, and 10.8% were resistant to carbapenems, with even higher rates of resistance in Europe.³ Therefore, in this regard it is essential to have new therapeutic weapons such as ceftazidime/avibactam, an antibiotic approved on 25 February 2015. This antibiotic is active against a broad group of Gram-negative bacteria, Enterobacteriaceae and even Pseudomonas aeruginosa. However, it is minimally active against Acinectobacter, anaerobes and Gram-positive bacteria.⁴ It is well tolerated (the most common side effects reported in the REPRISE study were gastrointestinal, in the same proportion in the 2 branches of the study–with and without ceftazidime/avibactam–with no other significant side effects).⁵ In addition, it has demonstrated activity against K. pneumoniae carbapenemase, or KPC,⁶ class A carbapenemases, encoded by plasmid genes, which would explain its greater capacity for spreading. Moreover, it should be noted that the antibiotic treatment directly observed in HAH units in Spain has proven to be safe, effective and probably more economical (there are no clear data that confirm this).⁷ In addition, another advantage demonstrated in this case in particular–and to date not studied–is the potential for home administration of the antibiotic. This would significantly decrease the potential for transmission of the bacterium.

In conclusion, administration of ceftazidime/avibactam in the HAH setting in selected cases would drastically decrease costs deriving from hospital admission, as well as complications related to hospital stay; would not undermine the treatment indicated for the patient; and would help control intrahospital transmission. Therefore, we believe that its home use should be considered under suitable circumstances.

Funding

The authors declare that they did not receive funding to complete this study.