Off-label usage of tigecycline for MDR-Acinetobacter spp

Background: Tigecycline is a new class of antibiotic named glycylcyclines. It is active in vitro against a variety of Gram + and Gram - organisms, including nosocomial resistant pathogens such as MRSA, ESBLs-producing Enterobacteriaceae, and MDR-Acinetobacter spp. It has been approved by the FDA for the treatment of complicated intraabdominal infections, complicated skin and skin structure infections and community acquired bacterial pneumonia.  Off-label indication use is defined as prescribing the drug for an indication other than the one approved by the regulatory authorities. Off-label indications of tigecycline are hospital-acquired pneumonia (HAP), blood-stream infections (BSI), urinary tract infections (UTI) and osteomyelitis. Objective: We evaluated the outcomes in patients who previosly received tigecycline with off-label indications. Methods: For the present analysis, patients who received tigecycline for off-label indications were extracted from our hospital’s and Department of Infectious Diseases databases. The hospital infections were diagnosed according to the definitions and criteria of the NNIS. The following data were analyzed for each patient:  i) admission setting [general ward or intensive care unit (ICU)]; ii) source of infection; iii) previous antibiotic therapy; iv) concurrent antibiotics; v) clinical success at the end of the treatment [defined as cure (complete resolution) or non-responce and death]. Results: Nineteen patients received tigecycline for off-labeled indications who had isolated MDR Acinetobacter spp as the infecting agent. The mean age was 57±14,8 (37-78) and 14 (73,7%) of the patients were males. Eight (%42.1) patients were already hospitalized in the ICU when the infection was diagnosed. Six (31,6%) patients had BSIs, and 13 (68,4%) had HAP.  Three patients also had UTIs. The mean duration of the treatment was 16,0±11,8 days (2-50). 94.7% have had antibiotic therapies prior to tigecycline and carbapenems had been the most frequently administered agent (63,2%). Fourteen patients were treated with concomitant antibiotics such as carbapenems, quinolons, and amikacine. The clinical success rate was only 26,3% and fourteen patients died or remained as unsuccessfully treated. Microbiological eradication data, ICU stay, prior and concomitant antibiotic usage had no direct influence on the success of off-label treatment with tigecycline (P>0.05).

Conclusions: Due to lack of another potent antibiotic for the use in the presence of MDR Acinetobacter spp in our country tigecycline was the last chance of the patients with this infection. BSIs and HAP are serious infections with high mortalitiy rates hence treatment with tigecycline, which is a bacteriostatic agent, will not be that reliable in the treatment of such clinical presentations. Our study is a preliminary evaluation for the success of off-label treatment of tigecyline. More experience and case-control studies are needed.