Isolation and characterization of lytic phage TUN1 specific for Klebsiella pneumoniae K64 clinical isolates from Tunisia.

BACKGROUND: Multidrug-resistant Klebsiella pneumoniae spp. (kp) are emerging agents of severe infections of the respiratory, urinary tract and wounds that can progress to fatal septicemia. The use of bacteriophages is currently being considered as an effective alternative or adjuvant to antibiotic therapy. RESULTS: In this study, we report capsule (K)-typing of 163 carbapenem-resistant Kp (CRKP) isolated 2014-2018 at the Military Hospital of Instruction of Tunis (MHT), Tunisia, by partial amplification and sequencing of the Kp wzi gene. The most prevalent K-type overall was K64 with 50.3% followed by K17 and K27 (22.7 and 11.0%, respectively). K64 Kp strains were most common and associated with increased case/fatality rates, especially at the intensive care unit (ICU). Using a K64 Kp strain we isolated and characterized a lytic Kp phage, vB_KpP_TUN1 (phage TUN1), from wastewater samples of the ICU at the MHT. TUN1 belongs to the Autographiviridae family and specifically digests K64 Kp capsules most probably via a depolymerase encoded by gp47. Furthermore, we successfully assembled phage TUN1 in a non-replicative host (E. coli) raising the possibility of in vitro assembly in the absence of live bacterial hosts. We propose that phage TUN1 is a promising candidate to be used as an adjuvant or an alternative to antibiotic therapy in CRKP infections, facilitating regulatory approval of phage therapy. CONCLUSIONS: K64, K17 and K27 are the most common wzi capsule types in this geographical location in Northern Africa. The lytic phage TUN1 efficiently lyses K64 Kp strains associated with increased case/fatality rates at body temperature. Together with its ability to be rescued in a non-replicative host these features enhance the utility of this phage as an antibacterial agent.

Urinary tract infections following renal transplantation: a single-center experience.

Urinary tract infection (UTI) is the most frequent infectious complication among renal transplant recipients and a frequent cause of bacteremia, sepsis and acute graft failure. To evaluate the incidence, risk factors, type of pathogens and long-term effect of UTIs on graft and patient survivals in our center, we performed a retrospective cohort study reviewing the medical records of patients who received a renal transplant at our center from June 1986 to December 2009, excluding patients who lost their grafts in the first month due to arterial or veins thrombosis and acute antibody-mediated rejection. We studied 393 kidney-transplanted recipients; at least one UTI occurred in 221 (53.69%) patients during the follow-up period. The most frequent pathogens isolated in urine culture were Escherichia coli (n = 39, 18.4%) and Klebsiella pneumonia (n = 31, 14.6%). When patients with UTIs were compared with those without UTIs, female gender and use of mycophenolate mofetil or azathioprine seemed to be risk factors for UTIs on univariate analysis. However, female gender was the only independent risk factor on multivariate analysis RR = 1.964 (1.202-3.207), P = 0.007. This study confirmed that UTIs remain a major problem in renal transplant recipients, and female gender was the only independent risk factor.