Management And Outcome Of Infections By Klebsiella Pneumoniae With Decreased Susceptibility To Carbapenems In Renal Transplant Patients

Introduction: Up to 20% of urinary tract infections (UTI) in renal transplant recipients (RTR) are reported to be caused by ESBL-producing bacteria. Due to their high resistance to ESBL-mediated hydrolysis, carbapenems are the treatment of choice in these cases. The occurrence of infections with carbepenem-resistant Klebsiella pneumoniae (KPC) however is a life-threatening event. Especially since optimal treatment of infections with KPC is not well defined and nephrotoxic agents seem to be required to reduce mortality rates ranging up to 57%. Methods: We report an outbreak of K. pneumoniae with resistance or decreased susceptibility to carbapenems in six RTR of our centre between 05/2010 and 01/2011. Patient age was 65.5±2.9 y. Five patients were de novo transplant recipients (index cultures (IC) 3 to 6 weeks after Tx), one patient was 5 years post transplantation. Immunosuppressive regimens consisted of Basiliximab, MMF, steroids and CsA or Tac according to the local standard protocol. All patients received perioperative antibacterial-prophylaxis with imipenem and longterm PCP-prophylaxis. Antibiotic susceptibilities of isolated K. pneumoniae were determined by Vitek2 and E-test. Genetic relatedness was investigated using Enterobacterial Repetitive Intergenic Consensus (ERIC)- and repetitive sequence based (REP)-PCR. Follow-up is 9.5±2.6 months. All values given as mean±SD. Results: Ertapenem-resistant K. pneumoniae were isolated from rectal swabs, urine or BAL-fluid. All K. pneumoniae were resistant to penicillins, cephalosporins, ertapenem, fluoroquinolones and cotrimoxazol. Some exhibited elevated MICs for meropenem, doripenem or imipenem but remained susceptible. ERIC- and REP-PCR analysis of isolates from 5 of 6 patients showed an identical profile suggesting a clonal spread. One patient was only colonized, three presented with UTI. Two patients, having been treated recently for BPAR or relapsing ITP, were severely ill suffering from pneumonia and/or sepsis due to ertapenem-resistant K. pneumoniae. Antibiotic treatment consisted of high dose meropenem, gentamicin, and inhalative colistin in case of pneumonia, for 19±9 days. In 4 of 5 patients with infection, MMF was transiently withdrawn. Trough-levels [ng/mL] for CsA ((203.3±11.4) vs (194.1±36.7) p=0.82; n=3) and Tac ((12.5±1.2) vs (8.1±0.2) p=0.07; n=2) did not differ significantly before and after IC were obtained. There is no difference in S-Creatinine [mg/dL] at date of IC and at latest follow up ((1.85±0.25) vs (2.1±0.5) p=0.67; n=6). All patients are alive with functioning grafts. Conclusion: In potentially life-threatening infections due to ertapenem resistant K. pneumoniae in RTR, excellent patient and graft survival can be achieved. Early onset combination therapy with gentamicin/high dose meropenem and transient withdrawal of MMF have proved save and efficacious in our cohort.