Differential Proteomic and Genomic Comparison of Resistance Mechanism of Pseudomonas aeruginosa to Cefoperazone Sodium/Sulbactam Sodium.

The aim of this study was to determine the resistance mechanism of Pseudomonas aeruginosa to cefoperazone sodium/sulbactam sodium. We retrospectively analyzed the drug resistance of P.a isolated at the First Affiliated Hospital of Guangxi Medical University. Drug-resistant P.a strains were constructed, then wild-type (WT) and drug-resistant (DR) strains were compared using protein and gene microarrays to determine differences between DR and WT strains. The resistance rates of P. aeruginosa during 2013, 2014 and 2015 were 21.2%, 21.4%, and 24.6% respectively. Among 242 protein peaks of WT and DR bacteriophage proteins, 41 were differentially expressed between the two groups. The expression of 26 and 15 proteins were respectively upregulated and downregulated in the DR compared with the WT group. Gene microarray results revealed 679 mutant loci in the DR group, of which 42 with the top 50 Q values were found in the NCBI database. The rate of P.a resistance to cefoperazone sodium/sulbactam sodium remained high between 2013 and 2015. The numbers of different proteins and genetic variations in the DR strains suggested that the resistance mechanism of P.a to cefoperazone sodium/sulbactam sodium involves multiple genes and proteins that might be key to controlling P.a resistance to cefoperazone sodium/sulbactam sodium.

Aislamientos microbiológicos en el Hospital Patrocinio Peñuela Ruíz: Estado Táchira 2005 / Microbiological isolation in the Hospital Patrocinio Peñuela Ruíz: Tachira State 2005

El cultivo de microorganismos es un proceso que permite el aislamiento de los gérmenes causantes o asociados a una infección. Con el aislamiento del germen no solamente se documenta el agente etiológico, sino que éste se tiene disponible para realizar pruebas de tipificación, determinación de sensibilidad a antibióticos y capacidad bactericida de líquidos corporales. En el Hospital Patrocinio Peñuela Ruíz, durante el año 2005, se realizaron 850 aislamientos microbiológicos, por lo que se plantea realizar una investigación de tipo transversal, retrospectivo, descriptivo y observacional, que tiene como objetivo determinar la prevalencia de los microorganismos aislados, a través de los cultivos secreciones, durante enero-diciembre 2005. Los principales resultados son que el mayor porcentaje (50,42) fue realizado en mujeres. La tendencia a realizar toma de muestra para aislamiento microbiológico es en los extremos de la vida, con un 23,05 por ciento en las personas mayores de 60 años y un 11,16 por ciento en los menores de 12 años. El 43,17 por ciento resultaron positivos para algún microorganismo aislado. El principal microorganismo aislado por servicio y otros departamentos fue: en pediatría Staphylococcus aureus (8.03 por ciento), en la Emergencia pediátrica Staphylococcus aureus (8.33 por ciento). En Medicina Interna Staphylococcus aureus 11,73 por ciento, en la Emergencia de Adultos staphylococcus aureus 18,07 por ciento, en Traumatología pseudomona aeurinosa y el staphylococcus aureos con 7,69 por ciento cada una. En Cirugía pseudomona aeruginosa (17,05 por ciento), en gineco-obstetricia e.coli (23,53 por ciento), y para terminar, en la Unidad de Cuidados Intensivos, Pseudomona aeruginosa 15,97 por ciento. También gracias a esta investigación, se pudo determinar la sensibilidad o resistencia antibiótica de los principales microorganismos aislados.

Susceptibilidad antimicrobiana de cepas de Pseudomonas aeruginosa aisladas en el laboratorio del Hospital Regional Dr. Leonardo Guzmán de Antofagasta, Chile / In vitro antimicrobial susceptibility of Pseudomonas aeruginosa strains isolated at Hospital Dr. Leonardo Guzmán, Antofagasta, Chile

Pseudomonas aeruginosa es un patógeno nosocomial frecuente que presenta elevada resistencia a los antimicrobianos y causa infecciones graves cuando hay alteración de los mecanismos defensivos del paciente. Así, conocer los patrones locales de sensibilidad es importante para la elección del tratamiento antimicrobiano adecuado en cada institución. En este trabajo determinamos la susceptibilidad antimicrobiana de cepas de P. aeruginosa aisladas desde pacientes atendidos en el Hospital Regional de Antofagasta. La mayoría de los pacientes tenía alguna condición predisponente a la infección y 48% tenía una infección grave. Las cepas mostraron mayor resistencia a los antimicrobianos que lo reportado en trabajos nacionales previos. Las cepas fueron altamente resistentes a amikacina (36,8%), ceftazidima (36,8%) y ciprofloxacina (68,4%), moderadamente resistentes a imipenem (26,3%), mientras que eran escasamente resistentes a piperacilina/tazobactam (5,3%) y cefoperazona/sulbactam (15,8%), Este es el primer trabajo, realizado en nuestra región, que estudia la susceptibilidad de P. aeruginosa frente a distintos grupos de antimicrobianos utilizados en clínica.

Pseudomonas aeruginosa is a nosocomial pathogen that often displays a high degree of antibiotic resistance. This pathogen causes also serious infections specially in patients with severe diseases or immunodeficiency. To offer the best treatment in every institution it is necessary to know the local pattern of antimicrobial susceptibility, then we studied the antibiotic susceptibility of P. aeruginosa strains isolated from patients attended in the Regional Hospital of Antofagasta. Most of them had an underlying disease that predisposed them to the infection and 48% had a severe infection. The strains showed higher drug resistance than that reported by other chilean researchers. P. aeruginosa displayed high resistance to amikacin (36,8%), ceftazidime (36,8%) and ciprofloxacin (68,4%) intermediate resistance to imipenem (26,3%), but low resistance to piperacillin/tazobactam (5,3%) and cefoperazone/sulbactam (15,8%). This is the first drug susceptibility study conducted in the Second Region of Chile, where P. aeruginosa was assayed against those antibiotics used in the clinical practice.

Susceptibility of clinical isolates of Bacteroides fragilis group strains to cefoxitin, cefoperazone and ticarcillin/clavulanate.

A total of 40 strains of the B. fragilis group was isolated from clinical specimens in two hospital centers in Fortaleza from 1993 to 1997. The most frequently isolated species was Bacteroides fragilis (19 strains) and most isolates came from intra-abdominal and wound infections. The susceptibility profile was traced for cefoxitin, cefoperazone and ticarcillin-clavulanate by using the agar dilution reference method. All isolates were susceptible to ticarcillin-clavulanate (128/2 microg/ml). Resistance rates of 15 and 70% were detected to cefoxitin (64 microg/ml) and cefoperazone (64 microg/ml), respectively. Such regional results permit a better orientation in choosing this group of antibiotics for prophylaxis and therapy especially in relation to cefoxitin, which is frequently used in the hospital centers studied.

Susceptibility of clinical isolates of Bacteroides fragilis group strains to cefoxitin, cefoperazone and ticarcillin/clavulanate

A total of 40 strains of the B. fragilis group was isolated from clinical specimens in two hospital centers in Fortaleza from 1993 to 1997. The most frequently isolated species was Bacteroides fragilis (19 strains) and most isolates came from intra-abdominal and wound infections. The susceptibility profile was traced for cefoxitin, cefoperazone and ticarcillin-clavulanate by using the agar dilution reference method. All isolates were susceptible to ticarcillin-clavulanate (128/2mug/ml). Resistance rates of 15 and 70 percent were detected to cefoxitin (64mug/ml) and cefoperazone (64mug/ml), respectively. Such regional results permit a better orientation in choosing this group of antibiotics for prophylaxis and therapy especially in relation to cefoxitin, which is frequently used in the hospital centers studied.

Multicenter evaluation of antimicrobial resistance to six broad-spectrum beta-lactams in Colombia using the Etest method. The Colombian Antimicrobial Resistance Study Group.

The need for comprehensive and quantitative accurate antimicrobial resistance surveillance systems has become acute as a guide to problem recognition and to focus local interventions. A multilaboratory (10 medical centers) Colombia surveillance project was initiated in early 1997 to monitor the potency and spectrum of six (cefepime, cefotaxime, ceftazidime, cefoperazone/sulbactam, aztreonam, and imipenem) broad-spectrum antimicrobial agents tested against 100 organisms per participant center (802 strains). Ten groups of organisms were tested by a reference-quality method (Etest; AB BIODISK, Solna, Sweden) with results validated by concurrent quality control and additional challenge strain analysis. Results from nine qualifying medical centers were tabulated, and 95.7 to 96.8% of quality assurance tests were within expected ranges. Only cefepime (90.1-100.0% susceptible) and imipenem (96.3-100.0%) were active against all Enterobacteriaceae at > 90% of susceptible isolates using the breakpoint concentrations recommended by the National Committee for Clinical Laboratory Standards. Among ceftazidime- (or cefotaxime- or aztreonam-) resistant Enterobacter spp. and Citrobacter freundii, cefepime remained active, but not cefoperazone with sulbactam. Escherichia coli and Klebsiella spp. strains having resistance phenotypes consistent with extended spectrum beta-lactamase production were discovered in approximately 5 to 10% of isolates. All tested drugs except ceftazidime (31.8-57.7% susceptible) were active against > 94% of oxacillin-susceptible staphylococci. Similar rates of resistance (9.1-14.8%) were observed in Pseudomonas aeruginosa for five of six drugs (not cefotaxime; 15.9% of strains were susceptible). Acinetobacter spp. isolates were most susceptible to imipenem (95.8%), cefepime (86.1%), and cefoperazone/sulbactam (83.3%). Overall for the 1997 order of antimicrobial spectrums for these tested compounds was: imipenem (96.6%) > cefepime (93.6%) > cefoperazone/sulbactam (90.5%) > cefotaxime (74.9%) > aztreonam (74.3% for Gram-negative bacilli only) > ceftazidime (73.2%). These data should be used to guide empiric regimens in Colombia, and additionally will provide a resistance statistical baseline to which future studies in this nation can be compared.

Susceptibilidad de escherichia coli frente a 13 drogas antimicrobiana / Susceptibility of escherichia coli against 13 antimicrobial drugs

Escherichia coli es uno de los bacilos gram negativos más aislados en nuestras clínicas, provocando diversos cuadros de tipo infeccioso. Por este motivo es importante conocer la susceptibilidad antimicrobiana de esta especie, con el fin de poder administrar drogas antimicrobianas realmente efectivas. Este trabajo determina la sensibilidad cuantitativa "in vitro" de 245 cepas de Escherichia coli, aisladas de diversas muestras clínicas frente a 13 drogas antimicrobianas para lo cual se utilizó el método de dilución en agar de Ericsson y Sherris. Los resultados obtenidos muestran que alrededor del 90 por ciento de las cepas fueron sensibles a Enoxacino, Cefotaxima, Aztreonam, Gentamicina, Ceftriaxzona, Amikacina, Cefuroximo, Cefoperazona y Nitrofurantoina y alrededor del 50 por ciento de las cepas fueron sensibles a Cefradina. Frente a los restantes antimicrobianos-Cloramfenicol, Cotrimoxazol y Ampicilina- se obtuvo un alto nivel de resistencia

The effect of liposomal cefoperazone against Pseudomonas aeruginosa in a granulocytopenic mouse model of acute lung infection.

The therapeutic efficacy of liposomal cefoperazone against Pseudomonas aeruginosa was investigated in a granulocytopenic mouse model of acute lung infection. Granulocytopenia was induced in mice by intraperitoneal (i.p.) injection of 200 mg/kg cyclophosphamide. Mice were challenged by exposure to an aerosol containing P. aeruginosa and were treated i.p. with liposomal cefoperazone prepared by the dehydration-rehydration method. The half-life of free cefoperazone in the lungs following i.p. administration of the liposomal drug was significantly lengthened (13 min vs. 261 min), and the cefoperazone activity in the lungs remained above the MIC longer after administration of liposomal cefoperazone than after treatment with cefoperazone. Liposomal cefoperazone was more effective than cefoperazone alone in preventing death of granulocytopenic mice from lethal pulmonary challenge with P. aeruginosa (75% vs. 38% survival, p = 0.031). Finally, P. aeruginosa was cleared faster from the lungs of mice treated with liposomal cefoperazone when compared with those treated with cefoperazone. This study shows that incorporation of cefoperazone into liposomes enhances the activity of the antibiotic against P. aeruginosa in a granulocytopenic host.

In vitro activity of ceftazidime and other antipseudomonal antibiotics against mucoid strains of pseudomonas aeruginosa

The minimum inhibitory concentration of ceftazidime, was determined for 132 mucoid strains of pseudomonas aeruginosa (MPA) isolated from patients with cystic fibrosis (CF), using an agar tube dilution method. Using strains collected over a ten-year period, we found that 98 percent were susceptible to achievable serum concentrations with MIC50 and MIC90 of 1.2 and 3.1 ug/ml, respectively. Susceptibility of 60 of these strains was also determined for cefoperazone (100 percent susceptible), tobramycin (97 percent), and carbenicillin (83 percent). Susceptibility of stored strains was similar to that of fresh isolates. We have shown that strains of MPA in a U.S. population were more susceptible to ceftazidime than those currently reported from Europe where this antibiotic was introduced earlier. Cefoperazone, another third generation cephalosporin which has received less attention in the treatment of patients with CF, is as active as ceftazidime in vitro. These data provide a basis for determining the future impact of these agents on pseudomonas susceptibility (AU)

Eficacia clínica de la cefoperazona en infecciones severas / Clinical efficacy of cefoperazone in severe infections

Se evaluó la eficacia clínica y la tolerancia de la cefoperazona (2-6 g/día por 12 días en promedio) en 14 pacientes hospitalizados con las infecciones siguientes: infección de herida operatoria, celulitis, antrax, bronconeumonía, neumonía, infeccion urinaria y osteomielitis. Se encontró un 100% de efectividad en la curación clínica de las mismas y un 92.9% de erradicación bacteriológica. Los microorganismos aislados fueron S. aureus (2), P. aeruginosa (1), S. epidermidis (1), C. diversus (1), E. agglomerans (5), E. coli (4) y dos no identificados. En dos pacientes se aislaron dos especies bacterianas del sitio de infección. Los efectos colaterales observados fueron leves y no ameritaron la suspensión del tratamiento y fueron los siguientes: elevación de fosfatasa alcalina (1), descenso de hemoglobina (1) eritema nodoso (1), en estos tres casos es difícil establecer si fueron provocados por la cefoperazona o por la enfermedad concurrente. Un leve aumento del tiempo de protrombina fue observado en dos casos. En conclusión la cefoperazona resultó un antibiótico de alta eficacia y de excelente tolerancia en infecciones severas causadas por organismos susceptibles

Evaluación del espectro y actividad in vitro de cefoperazona en relación a 9 antimicrobianos frente a diversas bacterias patógenas / Evaluation of spectrum and in vitro activity of cefoperazone in relation of 9 antimicrobial agents in different pathogenical bacteria

Se comparó la actividad in vitro de Cefoperazone en relación a Cefotaxima, Ceftriaxona, Amikacina, Gentamicina, Dibekacina, Cotrimoxazol, Cloramfenicol, Ampicilina (se incluyó en determinadas instancias Carbenicilina, Cloxacilina y Cefazolina) frente a 967 cepas de bacterias patógenas de las cuales 749 bacilos Gram negativos y 218 cocáceas en placa determinando la concentración inhibitoria mínima (CIM). Los resultados mostraron actividad similar a Cefotaxima, Ceftriaxona y Amikacina frente a E. coli, S. typhi y Pseudomonas aeruginisa; una relativa menor efectividad sobre Klebsiella, S. Typhimurium y Proteus mirabilis. En relación a S. aureus su actividad fue inferior a Cloxacilina pero con un rango de cobertura del 84 por ciento. Destaca efectividad de Cefoperazona sobre Streptococcus grupo D tipo enterococo (82,2 por ciento de cepas sensibles) significativamente superior a las otras cefalosporinas y a los aminoglicósidos