Peptides derived from human and bovine lactoferricin were designed, synthesized, purified, and characterized using RP-HPLC and MALDI-TOF-MS. Specific changes in the sequences were designed as (i) the incorporation of unnatural amino acids in the sequence, the (ii) reduction or (iii) elongation of the peptide chain length, and (iv) synthesis of molecules with different number of branches containing the same sequence. For each peptide, the antibacterial activity against Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 29212 was evaluated. Our results showed that Peptides I.2 (RWQWRWQWR) and I.4 ((RRWQWR)4K2 Ahx 2C2) exhibit bigger or similar activity against E. coli (MIC 4–33 μM) and E. faecalis (MIC 10–33 μM) when they were compared with lactoferricin protein (LF) and some of its derivate peptides as II.1 (FKCRRWQWRMKKLGA) and IV.1 (FKCRRWQWRMKKLGAPSITCVRRAE). It should be pointed out that Peptides I.2 and I.4, containing the RWQWR motif, are short and easy to synthesize; our results demonstrate that it is possible to design and obtain synthetic peptides that exhibit enhanced antibacterial activity using a methodology that is fast and low-cost and that allows obtaining products with a high degree of purity and high yield.

Time-kill curve plot. Peptide LfcinB (20–25)4 against S. aureus ATCC 25923. The peptide was tested at concentrations corresponding to MIC (blue line), 2 MIC (pink line) and 4 MIC (orange line) values.

Chimeric peptides containing short sequences derived from bovine Lactoferricin (LfcinB) and Buforin II (BFII) were synthetized using solid‐phase peptide synthesis (SPPS) and characterized via reversed‐phase liquid chromatography and mass spectrometry. The chimeras were obtained with high purity, demonstrating their synthetic viability. The chimeras’ antibacterial activity against Gram‐positive and Gram‐negative strains was evaluated. Our results showed that all the chimeras exhibited greater antibacterial activity against the evaluated strains than the individual sequences, suggesting that chemical binding of short sequences derived from AMPs significantly increased the antibacterial activity. For each strain, the chimera with the best antibacterial activity exerted a bacteriostatic and/or bactericidal effect, which was dependent on the concentration. It was found that: (i) the antibacterial activity of a chimera is mainly influenced by the linked sequences, the palindromic motif RLLRRLLR being the most relevant one; (ii) the inclusion of a spacer between the short sequences did not significantly affect the chimera's synthesis process; however, it enhanced its antibacterial activity against Gram‐negative and Gram‐positive strains; on the other hand, (iii) the replacement of Arg with Lys in the LfcinB or BFII sequences improved the chimeras’ synthesis process without significantly affecting their antibacterial activity. These results illustrate the great importance of the synthesis of chimeric peptides for the generation of promising antibacterial peptides.

RESUMENObjetivos Describir el uso de antibióticos en infección de vías urinarias, en una unidad de primer nivel de atención en salud. Métodos Estudio observacional, descriptivo, de una cohorte histórica, basada en registros, de usuarios consultantes en la Unidad de Servicios de Salud-UNISALUD, de la Universidad Nacional de Colombia, sede Bogotá, con diagnóstico de infección de vías urinarias, entre julio de 2002 y junio de 2003. Resultados La incidencia de infección de vías urinarias fue de 6,3 %, afectando especialmente a las mujeres con 84,4 %. Los signos y síntomas son los típicamente encontrados en esta entidad: 58 % de los casos corresponde a infecciones bajas, 36 % a inespecíficas, 4 % a infecciones durante el embarazo y 2 % a infecciones altas. Los uropatógenos aislados fueron: E. coli (88,9 %), Proteus spp. Hubo una gran variabilidad en la prescripción de esquemas antibióticos. Los de mayor consumo, en dosis diaria definida, fueron: Nitrofurantoína, Trimetoprim-sulfa y Fluoroquinolonas, frente a los cuales, los uropatógenos aislados presentaron perfiles de susceptibilidad bajos. La proporción de tratamientos empíricos con respecto a los confirmados fue de 4:1. El 98 % de los casos correspondió a pacientes con un único evento, o con una o dos recurrencias. Discusión La infección de vías urinarias presentó un comportamiento acorde al perfil epidemiológico de esta entidad patológica en la población general. La baja susceptibilidad de los microorganismos a los antibióticos 170 Murillo -Uso de Antibióticos 171 prescritos, podría reflejar un uso inadecuado, a nivel de la comunidad institucional, induciendo presión selectiva sobre la resistencia bacteriana.Palabras Clave: Atención ambulatoria, antibióticos, agentes antibacterianos, infección, urinaria, resistencia bacteriana a drogas (fuente: DeCS, BI-REME). ABSTRACT Using antibiotics in urinary tract infection in a first level of attention health care unit in Bogotá, ColombiaObjectives Describing using antibiotics for urinary tract infection in a first level of attention health care unit. Methods This was an observational and descriptive study of a cohort of register-based patients attending the Universidad Nacional de Colombia's Health Service Unit (UNISALUD) diagnosed as suffering urinary tract infection between July 2002 and June 2003. Results 6,3 % urinary tract infection incidence was found, especially affecting women (84,4 %). The signs and symptoms were the same as those usually found in this disease. 58% corresponded to lower tract infection, 36 % to non-specific infection, 4 % to infection during pregnancy and 2 % to upper tract infection. The following uropathogens were isolated: E. coli (88.9%), Proteus spp. (1 %) and Staphylococcus saprophyticus (0,3 %). There was great variability in the antibiotic schemes being prescribed. Nitrofurantoin, Trimethoprim-sulfamethoxizole and Fluoroquinolones were the most prescribed, per defined daily dose; these antibiotics presented low susceptibility for the uropathogens so isolated. There was a 4:1 ratio of empi...