Antibiotic susceptibility and fosfomycin resistance characterization in a cohort of children older than 6 years of age with urinary tract infection / Sensibilidad antibiótica y caracterización de la resistencia a fosfomicina en una cohorte de niños mayores de 6 años con infección urinaria

Fosfomycin tromethamol (FT) was reintroduced as an option for the treatment of low urinary tract infection (UTI) in children. In this study, we described the antibiotic sensitivity and mechanisms of resistance to fosfomycin in isolates from children older than 6 years with UTI. Urine culture and antibiotic susceptibility study were performed. In fosfomycin resistant strains, PCR for fos, blaCTX-M was performed followed by classification by phylogenetic group and sequencetyping. Escherichia coli was the most frequent etiological agent (89.2%). The susceptibility percentages were: fosfomycin 97.9%; amoxicillin-clavulanate 92.7%; cefuroxime and ceftriaxone 99%; nitrofurantoin 94.4%. An E. coli strain (ST69, phylogenetic group D) was resistant to fosfomycin (MIC 256mg/l) and carried the blaCTX-M-14 and fosA3 genes in a 45kb IncN-type plasmid.

La fosfomicina-trometamol (FT) se reintrodujo como una opción para el tratamiento de la infección del tracto urinario (ITU) baja en niños. En este estudio describimos la sensibilidad antibiótica y los mecanismos de resistencia a FT en aislamientos de niños mayores de 6 anos con ITU. Se realizaron urocultivos y estudios de sensibilidad antibiótica. En las cepas resistentes a fosfomicina se realizó la técnica de PCR para fos, blaCTX-M, y su identificación según su grupo filogenéticoy secuenciotipo. Escherichiacoli fue el agente etiológico más frecuente (89,2%). Los porcentajes de sensibilidad fueron: fosfomicina 97,9%; amoxicilina-clavulánico 92,7%; cefurox-ima y ceftriaxona 99%; nitrofurantoína 94,9%. Una cepa de E. coli (ST69, grupo filogenético D) fue resistente a fosfomicina (CIM 256mg/l) y portaba los genes blaCTX-M-14 y fosA3 en un plás-mido de 45 kb del tipo IncN. Este es el primer reporte de E. coli ST69 con blaCTX-M-14/fosA3 de origen humano.

Sensibilidad a fosfomicina en Escherichia coli productoras de betalactamasas de espectro extendido / Sensitivity to Fosfomycin in Extended-spectrum Betalactamase-producing Escherichia coli

RESUMEN Las infecciones urinarias son causadas mayormente por Escherichia coli (E. coli), el uso indiscriminado de antibióticos ha originado un aumento de infecciones por cepas productoras de betalactamasas de espectro extendido (BLEE). Con el objetivo de determinar la sensibilidad a fosfomicina se realizó un estudio en cepas de E. coli productoras de BLEE aisladas de urocultivos provenientes de un hospital de Perú. Se recolectaron 266 cepas de E. coli identificadas por métodos convencionales como productoras de BLEE. Se determinó la sensibilidad de fosfomicina por concentración inhibitoria mínima mediante el método de dilución en agar y por el método de disco difusión. Se encontró 192 (72,2 %) cepas de E. coli productora de BLEE sensibles a fosfomicina. Se concluye que la fosfomicina presenta actividad antimicrobiana frente a cepas de E. coli productoras de BLEE, y podría ser considerada una buena opción terapéutica frente a cepas resistentes.

ABSTRACT Urinary infections are caused mainly by Escherichia coli (E. coli); indiscriminate use of antibiotics has caused an increase in infections due to extended-spectrum beta-lactamase (ESBL)-producing strains. Aiming to determine the sensitivity to fosfomycin, a study was conducted in ESBL-producing E. coli strains isolated from urine cultures at a hospital in Peru. Two hundred and sixty-six (266) strains of E. coli were collected, which were determined by conventional methods to be ESBL- producing. Sensitivity to fosfomycin was determined through minimum inhibitory concentration with the agar dilution method and the diffusion disc method. One hundred and ninety-two (192) (72.2%) strains of ESBL-producing E. coli strains sensitive to Fosfomycin were found. It, therefore, follows that fosfomycin exhibits antimicrobial activity against ESBL-producing E. coli strains and that it could be considered a good treatment option for resistant strains.

In vitro activity of fosfomycin tromethamine against extended spectrum beta-lactamase producing urinary tract bacteria

To determine the in vitro activity of Fosfomycin tromethamine against extended spectrum beta-lactamase producing uropathogens. Experimental study. Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from October 2011 to October 2012. A total of 381 culture positive ESBL producing isolates from 2400 urine samples submitted over a period of one year were included in this study. Identification of isolates was done by standard biochemical profile of the organisms. The antimicrobial susceptibility of culture positive isolates was performed by disk diffusion method as recommended by Clinical Laboratory Standard Institute guidelines [CLSI]. The antimicrobial activity of Fosfomycin to various isolates revealed that 93% of E. coli, 64% Klebsiella spp. 50% Proteus spp. 75% Enterobacter cloacae, 100% Citrobacter freundii, 100% Burkholderia spp. 100% Serratia spp. and 50% Stenotrophomonas maltophilia were susceptible to this chemical compound. Fosfomycin showed excellent effectiveness to most of the common ESBL producing bacteria such as E. coli, Klebsiella and Proteus spp

In vitro fosfomycin activity in vancomycin-resistant Enterococcus faecalis

Enterococci are part of the endogenous flora of human beings, are naturally resistant to several classes of antimicrobials, and are able to acquire resistance with relative ease. Currently the vancomycin-resistant enterococci are spread all over the world and treatment options for infections caused by it are often extremely limited. We assessed 193 vancomycin-resistant Enterococcus faecalis isolates collected from four different hospitals in Porto Alegre for their susceptibility to fosfomycin using the E-test and agar diffusion. Fosfomycin proved to be active in vitro against the great majority of isolates, indicating that it is a valid option in the treatment of these infections.

Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum

In Plasmodium falciparum, the formation of isopentenyl diphosphate and dimethylallyl diphosphate, central intermediates in the biosynthesis of isoprenoids, occurs via the methylerythritol phosphate (MEP) pathway. Fosmidomycin is a specific inhibitor of the second enzyme of the MEP pathway, 1-deoxy-D-xylulose-5-phosphate reductoisomerase. We analyzed the effect of fosmidomycin on the levels of each intermediate and its metabolic requirement for the isoprenoid biosynthesis, such as dolichols and ubiquinones, throughout the intraerythrocytic cycle of P. falciparum. The steady-state RNA levels of the MEP pathway-associated genes were quantified by real-time polymerase chain reaction and correlated with the related metabolite levels. Our results indicate that MEP pathway metabolite peak precede maximum transcript abundance during the intraerythrocytic cycle. Fosmidomycin-treatment resulted in a decrease of the intermediate levels in the MEP pathway as well as in ubiquinone and dolichol biosynthesis. The MEP pathway associated transcripts were modestly altered by the drug, indicating that the parasite is not strongly responsive at the transcriptional level. This is the first study that compares the effect of fosmidomycin on the metabolic and transcript profiles in P. falciparum, which has only the MEP pathway for isoprenoid biosynthesis.

In vitro activity of fosfomycin-gentamicin, fosfomycin-ceftazidime, fosfomycin-imipenem and ceftazidime-gentamicin combinations against ceftazidime-resistant Pseudomonas aeruginosa.

The effects of antimicrobial combinations against ceftazidime-resistant Pseudomonas aeruginosa strains isolated from hospitalized patients were investigated. Using the checkerboard titration method, combination of fosfomycin-gentamicin, fosfomycin-ceftazidime, fosfomycin-imipenem and ceftazidime-gentamicin was synergistic against 4, 11, 38 and 39% of 22, 18, 29 and 18 strains tested respectively and additive effect of the combinations against the strains tested was 41, 33, 14 and 44%, respectively. Antagonistic effects against the isolates were noted when fosfomycin was combined with gentamicin (27%), ceftazidime (22%) and imipenem (7%). No antagonistic effect was observed in the ceftazidime-gentamicin combination.

Antibacterianos de acción sistémica, parte II: otros grupos de antibióticos / Systemic antibacterial drugs, part II: other groups of antibiotics

Se presenta la segunda parte de una revisión bibliográfica sobre los antibacterianos de acción sistémica, la cual incluye grupos de antibióticos tan importantes como aminociclitoles, aminoglucósidos, diaminopirimidinas, estreptograminas, fosfomicinas, fusidanos, glicopéptidos, lincosamidas, macrólidos, nitrofuranos, nitroimidazoles, polipéptios, quinolonas y rifamicinas

Fosfomicina / Fosfomycin

FOM es un antibiótico único en su clase -epóxido de ácido fosfónico- que inhibe un paso precoz de la síntesis de la pared bacteriana. Carece de efectos adversos importantes. Tiene in vitro excelente actividad antiestafilocóccica (80-100%), tanto en cepas sensibles como resistentes a meticilina. In vivo, especialmente en infecciones del sistema nervioso central, su uso debe ser evaluado mediante estudios adecuadamente diseñados. No debiera usarse como droga única por el riesgo de selección de cepas resistentes. Presenta efecto sinérgico con la mayoría de los otros antimicrobianos

Censo bacteriológico e análise da sensibilidade antimicrobiana na UTI do Hospital Naval Marcílio Dias: análise de dois anos / Bacteriologic census and analysis of antimicrobian sensibility in the intensive care unit of Hospital Naval Marcilio Dias: analysis of 2 years

Os autores apresentam uma revisäo das infeçöes ocorridas na Unidade de Terapia Intensiva do hospital naval Marcílio Dias, em um período de dois anos. O artigo mostra o predomínio dos microorganismos gram-negativos e do Staphylococcus aureus na casuística, bem como a sensibilidade dos mesmos