Nuevas cefalosporinas / New cephalosporins

Resumen La resistencia bacteriana se ha incrementado en América Latina y el mundo, por lo que se requiere investigación y creación de nuevos antimicrobianos capaces de erradicar a los microorganismos resistentes. Se realizó una revisión acerca de nuevas cefalosporinas y sus combinaciones con un inhibidor de β-lactamasas, recopilando información de espectro, farmacocinética, farmacodinamia y estudios clínicos de las indicaciones actuales para ceftarolina, ceftazidima/avibactam y ceftolozano/tazobactam. La primera, con actividad frente a Staphylococcus aureus y Staphylococcus coagulasa negativa sensibles y resistentes a meticilina, y contra Streptococcus pneumoniae resistente a penicilina; por lo tanto, aprobada para uso en neumonía bacteriana adquirida en comunidad e infecciones bacterianas de piel y tejidos blandos. Entre las nuevas combinaciones, ceftazidima, una cefalosporina de tercera generación con actividad anti-pseudomonas, asociada a avibactam, un inhibidor de β-lactamasas, ha demostrado efectividad en el tratamiento de infecciones abdominales e infecciones urinarias complicadas. Por último, la combinación ceftolozano y el conocido tazobactam presenta acción comparable a la combinación de ceftazidima y avibactam por su actividad contra bacilos gramnegativos y, en combinación con metronidazol no presenta inferioridad a meropenem en infecciones intra-abdominales. Se presentan los estudios clínicos y las potenciales indicaciones y escenarios de uso de estas cefalosporinas.

Bacterial resistance has increased in Latin America and the world, making research and creation of new antimicrobials capable of eradicating resistant microorganisms essential. A review of new cephalosporins and their combinations with a beta-lactamase inhibitor was conducted, collecting data on the spectrum, pharmacokinetic and pharmacodynamic profile and clinical studies of the current indications for ceftaroline, and the combinations ceftazidime with avibactam and ceftolozane with tazobactam. The first one has activity against methicillin-resistant Staphylococcus aureus and coagulase negative Staphylococcus (SCoN) and against penicillin-resistant Streptococcus pneumoniae, therefore approved for use in community-acquired pneumonia and acute bacterial skin and skin structure infections. Among the new combinations, ceftazidime, a third generation cephalosporin with antipseudomonal activity, associated with avibactam, a betalactamase inhibitor, has been shown to be effective in the treatment of abdominal infections and complicated urinary infections. Finally, the combination of ceftolozane with tazobactam has comparable action to ceftazidime with avibactam due to its activity against Gram negative rods, and in combination with metronidazole they do not present inferiority to meropenem in intra-abdominal infections. The clinical studies are presented, as well as the potential indications and clinical scenarios for their use of this cephalosporins.

Sepsis neonatal tardía nosocomial en una unidad de terapia intensiva: agentes etiológicos y localización más frecuente / Late onset neonatal sepsis in an intensive care neonatal unit: etiological agents and most frequent location

Resumen Introducción: La sepsis neonatal nosocomial (SNN) es una entidad frecuente en las unidades de cuidados intensivos, donde causa una gran morbimortalidad. La ubicación más frecuente es bacteriemia, seguido de neumonía asociada a ventilador mecánico y vía urinaria. Objetivo: Conocer la etiología y localización más frecuente de la infección en el SNN. Población, Material y Métodos: Estudio retrospectivo, de prevalencias de enero a diciembre de 2015, realizado en la Unidad de Cuidados Intensivos Neonatal de un hospital de alta complejidad. Fueron incluidos todos los neonatos. Resultados: Se incluyeron 70 pacientes, se analizaron 88 episodios de SNN. La localización más frecuente fue sangre 40% de los casos, seguido de orina y aspirado traqueal en 25% respectivamente. Los microorganismos más frecuentemente aislados fueron Staphylococcus de diferentes tipos, seguido de Acinetobacter baumannii multi-resistente. La afectación del SNC fue de 32%. La mortalidad fue de 34%, elevándose a 50% ante un segundo episodio de SNN. La terapia empírica de elección fue vancomicina y carbapenem, ajustándose a antibiograma. Conclusiones: La infección más frecuente fue la bacteremia, principalmente por Staphylococcus resistentes a meticilina. La afectación del SNC fue elevada, lo mismo que la mortalidad.

Introduction: Nosocomial neonatal sepsis (NNS) is a frequent entity in intensive care units, causing great morbidity and mortality. The most frequent site is blood, followed by lungs and urine. Objective: To know the etiology and most frequent localization of infection in the NNS. Population, Material and Methods: Cross sectional study, from January to December 2015, performed in a teaching hospital. All newborns infants were included. Results: 70 patients were included, 88 episodes of NNS were analyzed. The most frequent localization was bacteremia in 40% of cases, followed by urinary tract infection and VAP in 25% respectively. The bacteria most frequently isolated were staphylococci of different types, followed by multiresistant Acinetobacter. The CNS involvement was 32%. Mortality was 34%, rising up to 50% with a second episode of NNS. The empirical therapy of choice was vancomycin and carbapenem, adjusting to antibiogram. Conclusions: The most frequent infection was bacteremia, mainly by staphylococci resistant to methicillin. CNS involvement was elevated, as well as mortality.

Epidemiología de las infecciones urinarias asociadas a catéter y no asociadas a catéter en un hospital universitario de tercer nivel / Nosocomial urinary tract infection: an analysis beyond urinary catheterization

Resumen Introducción: Las infecciones urinarias asociadas a la atención de la salud (ITU-AAS) representan un importante problema sanitario, siendo poco conocidas sus características cuando no están asociadas a cateterización urinaria u ocurren fuera de unidades de cuidados intensivos (UCI). Objetivos: Determinar las características de los pacientes con ITU-AAS, etiología y susceptibilidad antimicrobiana de las mismas, tanto asociadas a catéter (ITU-C) como no asociadas a catéter (ITU-noC), en UCI y en sala general. Materiales y Métodos: Se realizó un estudio analítico retrospectivo de corte transversal entre 2009 y 2013 en un hospital universitario de tercer nivel. Se identificaron todos los episodios de ITU-AAS, diferenciándolas en ITU-C e ITU-noC. Resultados: Se incluyeron 253 episodios de ITU-AAS, siendo más frecuentes las ITU-C (60,9%) respecto a ITU-noC. Un 37,4% de ITU-noC y 59,7% de ITU-C ocurrieron en UCI. Los microorganismos aislados más frecuentemente fueron Escherichia coli, Klebsiella pneumoniae y Enterococcus sp. El 19% de los bacilos gramnegativos fueron productores de β-lactamasa de espectro extendido, siendo su frecuencia similar en ambos grupos. Conclusión: Las co-morbilidades de los pacientes con ITU-AAS, los agentes etiológicos responsables y sus correspondientes espectros de sensibilidad, fueron similares en los grupos de ITU-C e ITU-noC, tanto en sala general como en UCI.

Introduction: Nosocomially acquired urinary tract infections (NAUTI) represent an important public health issue, but its characteristics when they are not catheter associated (CA-UTI) or when they take place outside intensive care units (ICU) are poorly understood. Objectives: To determine the patients' characteristics, etiology and antimicrobial susceptibility of NAUTI, both CA-UTI and no CA-UTI, in general ward and ICU. Methods: We conducted a retrospective analytic cross-sectional study, between 2009 and 2013, in a third level universitary hospital. All NAUTI episodes were identified, classifying them as CA-UTI and no CA-UTI. Results: We included 253 episodes of NAUTI, being CA-UTI (60,9%) more frequent than no CA-UTI. A 37,4% of no CA-UTI and 59,7% of CA-UTI were identified in ICU. The most frequently isolated microorganisms were Escherichia coli, Klebsiella pneumoniae and Enterococcus sp. A 19% of extended spectrum betalactamase producing gram negative bacilli were found, without differences between groups. Conclusion: Patients's comorbidities, microorganisms associated to NAUTI and its antimicrobial susceptibility were similar in CA-UTI and no CA-UTI, as in general ward and ICU.

Antimycobacterial and antimalarial activities of endophytic fungi associated with the ancient and narrowly endemic neotropical plant Vellozia gigantea from Brazil

BACKGROUND Endophytic fungi, present mainly in the Ascomycota and Basidiomycota phyla, are associated with different plants and represent important producers of bioactive natural products. Brazil has a rich biodiversity of plant species, including those reported as being endemic. Among the endemic Brazilian plant species, Vellozia gigantea (Velloziaceae) is threatened by extinction and is a promising target to recover endophytic fungi. OBJECTIVE The present study focused on bioprospecting of bioactive compounds of the endophytic fungi associated with V. gigantea, an endemic, ancient, and endangered plant species that occurs only in the rupestrian grasslands of Brazil. METHODS The capability of 285 fungal isolates to produce antimicrobial and antimalarial activities was examined. Fungi were grown at solid-state fermentation to recover their crude extracts in dichloromethane. Bioactive extracts were analysed by chromatographic fractionation and NMR and displayed compounds with antimicrobial, antimycobacterial, and antimalarial activities. FINDINGS Five fungi produced antimicrobial and antimalarial compounds. Extracts of Diaporthe miriciae showed antifungal, antibacterial, and antimalarial activities; Trichoderma effusum displayed selective antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare; and three Penicillium species showed antibacterial activity. D. miriciae extract contained highly functionalised secondary metabolites, yielding the compound epoxycytochalasin H with high antimalarial activity against the chloroquine-resistant strain of Plasmodium falciparum, with an IC50 approximately 3.5-fold lower than that with chloroquine. MAIN CONCLUSION Our results indicate that V. gigantea may represent a microhabitat repository hotspot of potential fungi producers of bioactive compounds and suggest that endophytic fungal communities might be an important biological component contributing to the fitness of the plants living in the rupestrian grassland.

Evaluación de test rápidos y diseño de una estrategia para la detección y caracterización de carbapenemasas en cepas de bacilos gramnegativos / Test evaluation and strategy proposal to detect and to characterize carbapenemase-producing gram negative bacilli

Resumen Introducción: La detección de bacilos gramnegativos productores de carbapenemasas es compleja, existiendo actualmente varios test disponibles. La confirmación mediante la caracterización molecular de la enzima no está disponible en todos los laboratorios del país. Objetivo: Plantear una estrategia rápida, eficiente y sencilla para la detección y confirmación de carbapenemasas en cepas de bacilos gramnegativos. Material y Métodos: Se utilizaron 39 aislados productores y ocho no productores de carbapenemasas para evaluar los test fenotípicos Carba NP, CarbAcineto NP, Blue-Carba y validar el test molecular Xpert® Carba-R directo de la colonia en comparación con RPC convencional. Resultados: La sensibilidad para Carba NP, CarbAcineto NP y Blue-Carba fue de 79,5; 87,2 y 84,6%, respectivamente; mientras que la especificidad fue de 100; 100 y 87,5%, respectivamente. La concordancia entre RPC convencional y Xpert® Carba-R fue de 100%. El límite de detección para Xpert® Carba-R fue diferente según el tipo de carbapenemasa: 40,8 ufc/reacción par KPC y NDM y 30,6 ufc/reacción para VIM. Discusión: En aislados con susceptibilidad disminuida a carbapenémicos se propone realizar un tamizaje con CarbAcineto NP, para luego caracterizar la carbapenemasa con Xpert® Carba-R y adoptar las medidas de contención específica: para cada caso.

Introduction: The detection of carbapenemase-producing gram negative bacilli is complicated, because there are available multiple options of test. The confirmation of the enzyme by molecular characterization is not available in all laboratories in our country. Objective: To propose a fast, efficient and simple strategy to detect and confirm CPB. Materials and Methods: 39 CPB isolates and 8 non-producing were used to evaluate the phenotypic test Carba NP, CarbAcineto NP and Blue-Carba, validating the test Xpert® Carba-R, to be used directly with bacterial colonies with conventional PCR. Results: The sensitivity of Carba NP, CarbAcineto NP and Blue-Carba was 79,5; 87,2 y 84,6%, respectively; and specificity was 79.5; 87.2 and 84.6%, respectively. The limit of detection of Xpert® Carba-R was different for each carbapenemasa: 40.8 ufc/reaction to KPC and NDM and 30.6 ufc/reaction to VIM. Discussion: On isolates with decreased susceptibility to carbapenems we propose to use as screening the test CarbAcineto NP, follow by Xpert®Carba-R to characterize the carbapenemase and adopt specific infection control measures.

Emergence of cefepime resistance in gram-negative induced nosocomial infections

The rapid emergence of antibiotic resistance, especially broad-spectrum antibiotics, resulted in the avid use of new potent antibiotics. Ceftriaxone and ceftazidime, two third-generation cephalosporin, are usually used to manage complicated and uncomplicated infections. The use of cefepime in resistant infections is increasing gradually, which put this potent antibiotic at risk of resistance. During an 18-month period, a total of 220 gram-negative bacteria including Pseudomonas spp, Serratia spp, Acinetobacter spp, Proteus spp, E-coli and Kiebsiella spp. have been isolated by standard microbiological methods from nosocomial surgical site, abscess, blood stream and urinary tract infections. MIC of antibiotics on isolated bacteria was determined by gradient concentration method. Totally, 29.4%, 19.5% and 23.3% of isolated bacteria with MIC /= 256micro g/ml to cefepime, cefiriaxone and ceftazidime was also observed in 47.1%, 70.8% and 62.5% of cases, respectively [p<0.05]. High level resistance to cefepime were more commonly observed for pseudomonas [73.1%] and Klebsiella spp. [73.5%], respectively [p<0.05]. According to CLSI criteria, 47.1% of isolated bacteria in this study showed high level of resistance [MIC >/= 256micro g/ml] to cefepime. Therefore application of cefepime, as a drug of choice, for gram-negative organisms is not reasonable. Our result demonstrated that this potent antibiotic should not be used as a choice for empiric antibiotic therapy, in the cases of nosocomial infections caused by gram-negative organisms

Carbapenem resistance in gram-negative bacilli isolates in an Iranian 1000-bed tertiary hospital

Carbapenems are beta-lactamase antibiotics, presently considered as most potent agents for treatment of infections caused by Gram-negative bacilli. The aim of this study was to determine resistance of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumonniae as prevalent nosocomial agents to commonly used antibiotics including carbapenems such as imipenem and meropenem. A total of 202 gram-negative bacilli including K. pneumoniae, P aeruginosa and A. baumannii isolated from hospitalized patients in Milad hospital of Tehran were subject for susceptibility testing. Susceptibility testing was performed by disk diffusion and MIC methods as recommended by Clinical Laboratory Standards Institute [CLSI]. All isolates of K. pneumonia were susceptible to imipenem and meropenem. Resistance in non-fermenting gram-negative bacilli [NFGB] was prevalent. P. aeruginosa isolates exhibited 7.5% and 40.2% resistance to imipenem and meropenem respectively. The majority isolates of Acinetobacter baumannii were multi-drug resistant and resistance of this organism to imipenem and meropenem was 27.7% and 38.5% respectively. Our study revealed that in spite of resistance of K. pneumoniae to commonly used antibiotics, all isolates were susceptible to imipenem and meropeem. More than 80% isolates of A. bammanni were resistant to commonly used antibiotics. About 40.2% isolates of P. aeruginosa and [38.5%] isolates of A. baumannii were resistant to meropenem respectively

Antimicrobial resistance pattern among aerobic gram-negative bacilli of lower respiratory tract specimens of intensive care unit patients in a neurocentre.

BACKGROUND: Analysis of the tracheal and bronchial isolates from the lower respiratory tract specimens of the intensive care unit (ICU)-admitted patients, was carried out for the year 2002 with a perspective of looking at the antibiotic resistance pattern. METHODS: Lower respiratory tract secretions (tracheal or bronchoscopic aspirates) of 370 patients were cultured, identified and antimicrobial susceptibility performed by standard methods. RESULTS: Out of samples obtained from 370 patients, 274 (74%) were culture positive. A total of 489 bacterial isolates were recovered from 270 patients; 451 were gram-negative bacilli (GNB) and 38 were Staphylococcus aureus. In four of the patients, Candida spp was isolated. The common GNB isolates were non-fermentative gram-negative bacilli (NFGNB, 31.9%), followed by Pseudomonas aeruginosa (21.5%) and Klebsiella spp (19%). Elderly (24.8%) and adults (19.2%) showed increased rate of GNB isolation. In both tracheal and bronchial GNB isolates, the highest mean resistance was to cefazolin (98.8%) and ampicillin (97.6%) while the lowest mean resistance was to amikacin (48.5%). Isolation of two organisms per specimen (41.4%) was commonly seen. Multidrug resistance to the tested antimicrobials was more frequent in NFGNB (6.6%) and Pseudomonas aeruginosa (5%). There were no remarkable differences in the overall mean drug resistance among tracheal and bronchial GNB isolates. CONCLUSIONS: Isolation practices, antibiotic policies, effective surveillance, maintenance of epidemiological trends of infections and, rapid molecular diagnosis are the need of hour in improved and speedy management of lung infections with resistant organisms.

Imipenem resistance in nonfermenters causing nosocomial urinary tract infections.

Nonfermenting gram-negative bacilli (nonfermenters) have emerged as important nosocomial pathogens causing opportunistic infections in immunocompromised hosts. These organisms show high level of resistance to b-lactam agents, fluoroquinolones and aminoglycosides. Imipenem is a carbapenem antibiotic, which can be very useful for treatment of infections caused by nonfermenters. Eighty-five nonfermenters causing nosocomial UTI were tested for MIC to imipenem by agar dilution method. Resistance to other antimicrobial agents was compared between imipenem sensitive (S) and resistance (R) groups. Overall 36.4% of nonfermenters were resistant to imipenem. Forty two percent of P. aeruginosa and 18.5% of Acinetobacter baumanii were imipenem resistant. Other nonfermenters showed variable resistance, resistance in Alcaligenes spp. being very high. More than 70% of the nonfermenters were resistant to ceftazidime, gentamicin and ciprofloxacin. Piperacillin and amikacin had the best in vitro susceptibility. No significant difference was found in the antibiotic susceptibility profile among imipenem sensitive (S) or resistant (R) strains.

Non-fermenters in human infections.

One thousand and one hundred thirty non-fermenting gram negative bacteria were isolated from various samples. Of these, Pseudomonas aeruginosa was the commonest isolate (72.83%) followed by Acinetobacter anitratus (8.4%), Alcaligenes faecalis (7.6%), Acinetobacter lwoffi (4.4%), Pseudomonas flourescens (2.4%), Schwanella putrefaciens (1.6%), Stenotrophomonas maltophilia (1.6%), Pseudomonas putida (0.4%), Bravundimonas vesicularis (0.4%) and Flavobacterium meningosepticum (0.4%). Antibiotic sensitivity pattern showed multiple drug resistance pattern with majority of the isolates being resistance to two or more drugs.

Prevalence of nonfermenters in clinical specimens.

One hundred and thirty three non fermenting gram negative bacilli isolated out of 625 different clinical specimens were identified and characterised. Samples were exudate from chronic suppractive otits media (341), diabetic foot (117) wound (116) and blood (51). Of these isolates Pseudomonas aeruginosa 105(78.94%) predominated followed by Acinetobacter sp 8 [6.1%], Pseudomonas putrifaciens 6(4.5%), Flavobacterium sp 6(4.5%), Xanthomonas maltophilia 5(3.75%), Alkaligenes sp 3 (2.25). 31 (23.30%) were resistant to commonly used antibiotics. Amikacin 85 (63.90%) was found to be more effective than fluoroquinolones (27.8-48.12%).

Antimicrobial susceptibility pattern of gram-negative aerobic isolates from intensive care units in Saudi Arabia; a multicenter study

To determine the pattern and prevalence of recognized categories of resistance to broad-spectrum antibiotics in seven Intensive Care Units [ICUs] in the Kingdom. A multicenter study was established to carry out susceptibility tests on at least 100 isolates from patients admitted into ICUs of seven hospitals in various areas in the Kingdom. Tests were performed using the Microscan MIC Plus type MIC panel. Setting: Microbiology laboratories and ICUs of seven hospitals in the Kingdom. Four hundred and seventy eight patients admitted into the study provided 703 isolates, which were examined for beta-lactamase production. The dominant species isolated were Ps. aeruginosa [148], E.coli [117] and Kleb. pneumoniae [11]. In all but one center, most isolates resistant to 3rd generation cephalosporins were E. coli and Klebsiella spp. with multi-resistance pattern consistent with extended spectrum B-lactamase [ESBL]. Inducible Enterobacteriaceae [IE], with chromosomal type-1 cephalosporinases were next in importance, followed by Ps.aeruginosa. Amikacin was the most effective aminoglycoside least affected by IE, while amoxil/clavulanate had a low impact on conferring sensitivity on the isolates. Blood culture isolates showed a strong contribution of resistance from inducible Enterobacteriaceae, principally nosocomial Serratia spp. and Enterobcater spp. with linked resistance to the aminoglycosides. The superiority of imipenem and ciprofloxacin over other antibiotics for empiric therapy of bacteremia in ICU patients was evident from the susceptibility data of all isolates

Estudo comparativo entre as associaçöes aztreonam/clindamicina e tobramicina/clindamicina no tratamento de infecçöes intra-abdominais / Comparison of aztreonam plus clindamycin with tobramycin plus clindamycin in the treatment of intra-abdominal infections

Este estudo avaliou a atividade do aztreonam (um antibiótico ß-lactâmico com atividade específica contra bactérias Gram-negativas), comparando-a com a da tobramicina, em pacientes hospitalizados com infecçöes intra-abdominais severas causadas por patógenos Gram-negativos isoladamente ou associados a outras bactérias. O estudo incluiu no total 156 pacientes, dos quais 76 receberam aztreonam + clindamicina e 80 foram tratados com tobramicina + clindamicina. Os pacientes foram submetidos a diversos procedimentos cirúrgicos envolvendo a cavidade peritoneal. A avaliaçäo clínica final revelou percentagens semelhantes de resultados satisfatórios: 86,5% nos pacientes tratados com aztreonam e 86.2% no grupo tratado com tobramicina. Entre os pacientes que tiveram maus resultados observou-se que em 50% dos casos as infecçöes eram causadas por Gram-negativos isoladamente ou associados a miciroorganismos Gram-positivos, no grupo tratado com aztreonam; esta percentagem subiu para 82% quando se avaliou o mesmo subgrupo entre os pacientes tratados com tobramicina. A incidência de efeitos adversos e de alteraçöes dos parâmetros laboratoriais näo foi significante e semelhante nos dois grupos. Os resultados deste estudo sugerem que o aztreonam pode ser uma droga eficaz e segura para o tratamento de infecçöes causadas por bactérias Gram-negativas