Antimicrobial evaluation of new metallic complexes with xylitol active against P. aeruginosa and C. albicans: MIC determination, post-agent effect and Zn-uptake.

Xylitol (xylH5) is metabolized via the pentose pathway in humans, but it is unsuitable as an energy source for many microorganisms where it produces a xylitol-induced growth inhibition and disturbance in protein synthesis. For this reason, xylitol is used in the prophylaxis of several infections. In the search of better antimicrobial agents, new copper and zinc complexes with xylitol were synthesized and characterized by analytical and spectrosco pic methods: Na2[Cu3(xylH−4)2]·NaCl·4.5H2O (Cu-xyl) and [Zn4(xylH−4)2(H2O)2]·NaCl·3H2O (Zn-xyl). Both copper and zinc complexes presented higher MIC against Pseudomona aeruginosa than the free xylitol while two different behaviors were found against Candida albicans depending on the complex. The growth curves showed that Cu-xyl presented lower activity than the free ligand during all the studied period. In the case of Znxyl the growth curves showed that the inhibition of the microorganism growth in the first stage was equivalent to that of xylitol but in the second stage (after 18 h) Zn-xyl inhibited more. Besides, the PAE (post agent effect)obtained for Zn-xyl and xyl showed that the recovery from the damage of microbial cells had a delay of 14 and 13 h respectively. This behavior could be useful in prophylaxis treatments for infectious diseases where it is important that the antimicrobial effect lasts longer. With the aim to understand the microbiological activities the analysis of the particle size, lipophilicity and Zn uptake was performed.

Emergence of KPC-producing Klebsiella pneumoniae in Uruguay: infection control and molecular characterization.

We describe the first outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP), the infection control measures adopted and the shift in resistance patterns of isolates during antibiotic treatment. The ST258 KPC-KP strain exhibited a multiresistant antibiotic phenotype including co-resistance to gentamycin, colistin and tigecycline intermediate susceptibility. Isolates before and after treatment had different behaviour concerning their antibiotic susceptibility and the population analysis profile study. A progressive increase in the aminoglycosides (acquiring amicacin resistance) and ß-lactam MICs, and a decreased susceptibility to fosfomycin was observed throughout the administration of combined antimicrobial regimens including meropenem. A high meropenem resistance KPC-KP homogeneous population (MIC 256 Jg/mL), could arise from the meropenem heterogeneous low-level resistance KPC-KP population (MIC 8 Jg/mL), by the selective pressure of the prolonged meropenem therapy. The kpc gene was inserted in a Tn4401 isoform a, and no transconjugants were detected. The core measures adopted were successful to prevent evolution towards resistance dissemination.

Decreased susceptibility to azithromycin and erythromycin mediated by a novel mtr(R) promoter mutation in Neisseria gonorrhoeae.

During a screen of Neisseria gonorrhoeae clinical isolates obtained in Uruguay for susceptibility to azithromycin, we noticed that approximately 10% of the strains examined displayed decreased susceptibility to azithromycin and erythromycin due to the mtr(CDE)-encoded efflux pump system, but remained susceptible to Triton X-100. We now report that the mtr(R) promoter region of one of these isolates contains a dinucleotide insertion (TT) that mediates this resistance phenotype.

Decreased azithromycin susceptibility of Neisseria gonorrhoeae due to mtrR mutations.

Single-dose azithromycin therapy has recently been used in Uruguay for the treatment of uncomplicated gonococcal infections. As part of an active surveillance study to monitor the emergence of antibiotic resistance in gonococcal isolates, we examined the levels of azithromycin susceptibility in 51 consecutive isolates obtained from males with uncomplicated gonococcal urethritis. Isolates with decreased susceptibility to azithromycin (MICs, 0.25 to 0.5 microg/ml) were common, and these isolates often displayed cross-resistance to hydrophobic antimicrobial agents (erythromycin and Triton X-100). Resistance to erythromycin and Triton X-100 is frequently due to overexpression of the mtrCDE-encoded efflux pump mediated by mutations in the mtrR gene, which encodes a transcriptional repressor that modulates expression of the mtrCDE operon. Accordingly, we questioned whether clinical isolates that express decreased azithromycin susceptibility harbor mtrR mutations. Promoter mutations that would decrease the level of expression of mtrR as well as a missense mutation at codon 45 in the mtrR-coding region that would result in a radical amino acid replacement within the DNA-binding motif of MtrR were found in these strains. When these mutations were transferred into azithromycin-susceptible strain FA19 by transformation, the susceptibility of gonococci to azithromycin was decreased by nearly 10-fold. The mtrCDE-encoded efflux pump system was responsible for this property since insertional inactivation of the mtrC gene resulted in enhanced susceptibility of gonococci to azithromycin. We conclude that the mtrCDE-encoded efflux pump can recognize azithromycin and that the emergence of gonococcal strains with decreased susceptibility to azithromycin can, in part, be explained by mtrR mutations.

Erythromycin-resistant Neisseria gonorrhoeae and oral commensal Neisseria spp. carry known rRNA methylase genes.

Two Neisseria gonorrhoeae isolates from Seattle and two isolates from Uruguay were resistant to erythromycin (MIC, 4 to 16 microg/ml) and had reduced susceptibility to azithromycin (MIC, 1 to 4 microg/ml) due to the presence of the self-mobile rRNA methylase gene(s) ermF or ermB and ermF. The two Seattle isolates and one isolate from Uruguay were multiresistant, carrying either the 25.2-MDa tetM-containing plasmid (Seattle) or a beta-lactamase plasmid (Uruguay). Sixteen commensal Neisseria isolates (10 Neisseria perflava-N. sicca, 2 N. flava, and 4 N. mucosa) for which erythromycin MICs were 4 to 16 microg/ml were shown to carry one or more known rRNA methylase genes, including ermB, ermC, and/or ermF. Many of these isolates also were multiresistant and carried the tetM gene. This is the first time that a complete transposon or a complete conjugative transposon carrying an antibiotic resistance gene has been described for the genus Neisseria.

Capsular type distribution and susceptibility to antibiotics of Streptococcus pneumoniae clinical strains isolated from Uruguayan children with systemic infections. Pneumococcus Study Group.

Children under 24 months of age are at high risk for serious infection with Streptococcus pneumoniae but they do not elicit effective immune responses to the currently available capsular polysaccharide vaccines. A polysaccharide protein conjugated vaccine involving the most frequent types has become an urgent need. To produce such a vaccine for Latin America, information on type distribution is required. Recently, Uruguay was 1 of the 6 countries in Latin America where surveillance for invasive pneumococcal infections in children under the age of 5 years was carried out. Seventy percent of the 182 invasive S. pneumoniae isolates were recovered from patients under 24 months of age, and 19% were recovered from infants under 6 months. The 7 most frequent types were 14, 5, 1, 6B, 3, 7F, and 19A; representing 80% of invasive isolates. Twenty-one types were identified, 16 in pneumonia and 14 in meningitis. Resistance to penicillin increased during the study period, from 29% in 1994, to 40% in 1995-1996, mainly because of the spread of type 14 strains resistant to penicillin and trimethoprim/sulphamethoxazol (89% of resistant isolates). The high proportion of systemic pneumococcal infections recorded in patients under 24 months of age and the increasing resistance of these agents to first-choice antibiotics point to an urgent need for a capsular polysaccharide protein conjugated vaccine.

[Application of a computer program for identifying different genera and species of the Enterobacteriaceae family in clinical bacteriology]. / Aplicación de un programa de computación para la identificación de los distintos géneros y especies de la familia Enterobacteriaceae en bacteriología clínica.

Computer programs were developed for the selection of a minimum set of biochemical tests that allow the identification of the species of Enterobacteriaceae with major clinical significance. The system proposed consists of nine conventional biochemical tests, the results of which are interpreted with the help of a numeric code. This selects the most probable species for each result and, when necessary, additional tests can be performed to confirm the identification proposed. The system (SYS9E) was used in the identification of 66 strains of nosocomial origin. The results were compared with those of commercial systems.

Contenido plasmídico de cepas de Neisseria gonorrhoeae aisladas en Uruguay / Plasmid contein in Neisseria gonorrhoeae strain isolates in Uruguay

Se analizó el contenido plasmídico de 40 cepas de Neisseria gonorrhoeae aisladas de exudados uretrales, provenientes de un solo centro asistencial de Montevideo. Se correlacionó el contenido plasmídico con la resistencia in vitro a la Penicilina G y con la producción de beta-lactamasa. De las cepas estudiadas, el 100 por ciento contiene un plásmido de 2,6 MDaltons. El 50 por ciento de las cepas posee además otros dos plásmidos de 3,2 MDal y 24,5 MDal, son resistentes a la penicilina y producen beta-lactamasa