Vaginosis citolítica: actualización diagnóstica y terapéutica / Cytolytic vaginosis: diagnostic and therapeutic update

El objetivo es conocer el abordaje diagnóstico y terapéutico de la vaginosis citolítica. Para ello se hizo una búsqueda sistemática de la literatura médica mediante las bases de datos: PubMed, Central, etc. Se limitó a ensayos clínicos aleatorizados, metaanálisis y revisiones bibliográficas, con disponibilidad del texto completo para evaluarlos en su totalidad e incluirlos en la revisión; publicados entre 1980 y 2021. Se incluyeron 27 publicaciones. La vaginosis citolítica es un trastorno infradiagnosticado. En mujeres con síntomas y signos de candidiasis vulvovaginal, que no responden a la terapia, se debe considerar la probabilidad de estar en presencia de una vaginosis citolítica. El tratamiento obliga a elevar el pH vaginal a valores básicos y a disminuir el número excesivo de Lactobacillus, resultando de utilidad las duchas vaginales con bicarbonato de sodio y/o un tratamiento con antibióticos derivados de la penicilina junto a un inhibidor de ß-lactamasas o doxiciclina en las pacientes alérgicas a la penicilina. Finalmente, se concluye que la vaginosis citolítica es una afección común, frecuentemente se diagnostica de forma errónea porque se confunde con la candidiasis vulvovaginal; se caracteriza por producir un cuadro clínico similar. El tratamiento se enfoca en disminuir el número de Lactobacillus y la elevación del pH vaginal.

The objective is to know the diagnostic and therapeutic approach of cytolytic vaginosis. A systematic search of the medical literature was carried out using the following databases: Medline via PubMed, Central, and Cochrane Database of Systematic Reviews, among others. The search was limited to randomized clinical trials, meta-analyses, and literature reviews that had the full text available for full evaluation and inclusion in the review; published between 1980 and 2021. Twenty-seven publications were included. Cytolytic vaginosis is a frequently underdiagnosed disorder, which mimics Candida vaginitis. In women with symptoms and signs of vulvovaginal candidiasis who do not respond to antifungal therapy, the possibility of cytolytic vaginosis should be considered. The treatment of this condition requires raising the vaginal pH to basic values and reducing the excessive number of Lactobacillus, resulting in useful vaginal douches with sodium bicarbonate and/or treatment with antibiotics derived from penicillin together with a ß-lactamases inhibitor or doxycycline in patients allergic to penicillin. Finally, we conclude that cytolytic vaginosis is a common condition, frequently misdiagnosed because it is confused with vulvovaginal candidiasis, since it is characterized by producing a similar clinical picture. Treatment focuses on reducing the number of Lactobacillus and raising vaginal pH.

Prescription of antibiotics after tooth extraction in adults: a nationwide study in Korea

OBJECTIVES: This study aimed to understand the nationwide patterns of antibiotic prescription after tooth extraction in adult patients.MATERIALS AND METHODS: This study analyzed dental records from the National Health Insurance Service–National Sample Cohort (NHIS–NSC) database on 503,725 tooth extractions performed in adults (≥19 years) during 2011–2015. Patient sex, age, household income, systemic disease (diabetes mellitus and hypertension), type of dental institution, region of dental institution, year of prescription, and type of tooth extraction procedure were considered. The antibiotic prescription rate and broad-spectrum antibiotic prescription frequency were analyzed using chi-squared tests. Factors affecting the prescription of broad-spectrum antibiotics were evaluated using multivariate logistic regression analysis.RESULTS: The rate of antibiotic prescription after tooth extraction was 81.85%. Penicillin was most commonly prescribed (45.25%), followed by penicillin with beta-lactamase inhibitors (18.76%), metronidazole (12.29%), and second- to fourth-generation cephalosporins (11.52%). The proportion of broad-spectrum antibiotics used among all prescribed antibiotics was 45.88%.CONCLUSION: The findings of this study demonstrate that the rate of antibiotic prescription after tooth extraction is higher in Korea than in other countries. Furthermore, broad-spectrum antibiotics are used more frequently, which may indicate unnecessary drug prescription, an important contributor to antibiotic resistance.

Tailoring antimicrobials in febrile neutropenia: using faster diagnostic and communication tools to improve treatment in the era of extensively resistant pathogens

ABSTRACT Febrile Neutropenia represents a medical emergency and the use of appropriate antimicrobial therapy is essential for a better outcome. Although being time-consuming, conventional cultures and antimicrobial susceptibility tests remain the golden standard practices for microbiology identification. Final reports are typically available within several days. Faster diagnostic tools, such as species identification trough Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) and molecular techniques might help to shorten time to diagnostic and also guide definitive therapy in this scenario. Here we present a case in which the use of a diagnostic molecular workflow combining MALDI-TOF and real-time PCR for relevant genes codifying antibiotic resistant integrated with instant communication report, led to a tailored and more appropriate treatment in a patient presenting with febrile neutropenia.

Nueva Delhi metalo--ß--lactamasa en especies de Enterobacteriaceae aisladas de pacientes hospitalizados, Managua, Nicaragua / New Delhi Metallo--ß-lactamase in Enterobacteriaceae species isolated from hospitalized patients, Managua Nicaragua

Resumen Objetivo: determinar la frecuencia de metalo-β lactamasa tipo Nueva Delhi (NDM), en aislados de enterobacterias provenientes de pacientes hospitalizados con diferentes procesos infecciosos. Método: se realizó una investigación descriptiva transversal, agosto 2015 - octubre 2016, en el Hospital Alemán Nicaragüense. Se estudiaron 249 cepas en vigilancia activa a los carbapenémicos. La identificación y perfil de resistencia se efectuó en Vitek2; la sospecha de resistencia a los carbapenémicos se tomó cuando la CMI de Imipenem y Meropenem 2-4 μg/mL y Ertapenem 2 μg/mL, se determinó mediante Kirby Bauer, el test de sinergia triple disco (carbapenémicos y EDTA 10µg); se hizo la reacción en cadena de la polimerasa para metalo-β-lactamasa Nueva Delhi. Resultados: se analizaron 249 cepas, entre estas se identificó 45 cepas resistentes a los carbapenémicos, correspondiendo al 18%. De estas cepas, 43 dieron positivo para el test de sinergia con EDTA; 21 portaban el gen de Nueva Delhi. El 66% de metalo-β-lactamasa Nueva Delhi se encontró en aislamientos de Klebsiella pneumoniae, seguida de Escherichia vulneris en un 14%, Escherichia coli en un 5%, Providencia rettgeri en un 5%, Pantoea agglomerans en un 5% y Kluyvera cryocrescens en un 5%.19 Conclusiones: el hallazgo del presente estudio es una advertencia clara sobre la circulación de cepas de metalo-β-lactamasa tipo Nueva Delhi que codifican la resistencia a los carbapenémicos en el hospital analizado.

Abstract Objective: to determine the frequency of New Delhi-type metallo-β-lactamase (NDM) in isolates of enterobacteria from patients hospitalized with different infectious processes. Method: a cross-sectional descriptive study was carried out between August 2015 and October 2016 at Alemán Nicaragüense Hospital. A total of 249 strains were studied in active surveillance of carbapenems resistance. The identification and resistance profile was carried out in Vitek2. Suspected resistance to carbapenems was considered when the MIC of Imipenem and Meropenem was 2-4 μg/mL and for Ertapenem of 2 μg/mL, determined by Kirby Bauer, the triple disc synergy test (carbapenems and EDTA 10μg). A polymerase chain reaction test was made to determinate New Delhi metallo-β lactamase. Results: a total of 249 strains were analyzed, among which 45 strains resistant to carbapenems were identified, corresponding to 18%. Of these strains, 43 were positive for the synergy test with EDTA; 21 carried the New Delhi gene. Of the New Delhi metallo-β lactamase. 66% were found in isolates of Klebsiella pneumoniae, followed by Escherichia vulneris in 6 isolates, Escherichia coli in 2, Providencia rettgeri in 2, Pantoea agglomerans in 2 and Kluyvera cryocrescens by 2. Conclusions: the results of the present study are a clear warning about the circulation of New Delhi-type metallo-β-lactamase strains that codify for the resistance to carbapenems in the hospital analyzed.

Amikacin therapy for urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli

BACKGROUND/AIMS: The number of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is increasing. In an outpatient setting, there are limited therapeutic options to treat ESBL-producing pathogens. We evaluated the outcomes of amikacin outpatient parenteral antibiotic therapy (OPAT) for UTIs caused by ESBL-EC in patients not pre-treated with carbapenem. METHODS: We retrospectively evaluated the outcomes of amikacin OPAT for UTIs caused by ESBL-EC. RESULTS: From November 2011 to October 2012, eight females, who could not be hospitalized for carbapenem treatment, were treated with amikacin OPAT for nine episodes of non-bacteremic ESBL-EC UTIs. Seven of the eight patients had one or more comorbidities. Of the nine UTI cases, three had symptomatic lower UTIs and six had non-bacteremic upper UTIs. In all of the cases, symptomatic and laboratory improvements were observed following amikacin OPAT. One patient showed a delayed relapse with bilateral microabscesses 3 weeks after treatment cessation; however, a clinical and microbiological cure was eventually reached. All of the patients were able to tolerate amikacin OPAT without any significant nephrotoxicity or ototoxicity. CONCLUSIONS: Amikacin OPAT represents a feasible therapeutic option for non-bacteremic UTIs caused by ESBL-EC in settings with limited resources.

Meningitis por Listeria monocytogenes en niñas inmunocompetentes: queso no pasteurizado como probable causa de infección / Listeria monocytogenes meningitis in immunocompetent children: unpasteurized cheese likely cause of infection

Listeria meningoencephalitis is a rare condition, occurring mainly in immunocompromised patients. We present two cases of Listeria monocytogenes meningoencephalitis in immunocompetent children, with successful treatment with betalactam/aminoglycoside combination. Unpasteurized cheese was postulated as the source of infection.

La meningoencefalitis por Listeria spp. es una infección infrecuente, principalmente en pacientes con algún tipo de inmunosupresión. Presentamos dos casos clínicos de meningitis por Listeria monocytogenes en niñas inmunocompetentes con tratamiento exitoso con β lactámicos combinados con aminoglucósidos; se identificó la ingesta de queso no pasteurizado como probable fuente de infección.

Overproduction of clavulanic acid by extractive fermentation

Background Clavulanic acid is an important beta-lactamase inhibitor produced as a secondary metabolite by the actinomycete Streptomyces clavuligerus. Clavulanic acid is chemically unstable; therefore, it is degraded during bacterial cultivation. In this work, the adsorbents clinoptilolite, activated carbon, calcined hydrotalcite, and Amberlite IRA 400 anionic exchange resin were studied in terms of their ability to adsorb clavulanic acid during extractive fermentation, in order to prevent product degradation and avoid product concentrations reaching inhibitory levels. Adsorption assays were used to investigate the effect of pH, and the decrease in the clavulanic acid concentration in the culture broth was measured for each adsorbent. Results IRA 400 was found to be most effective, with 78% adsorption of clavulanic acid. The maximum production of clavulanic acid in Erlenmeyer flask cultures increased 86% in terms of mass of CA, and 248% in cumulative CA concentration, with the use of Amberlite IRA 400 as adsorbent in extractive fermentation, compared to control fermentation performed without product removal. Conclusions The results indicated that extractive fermentation using a solid phase could be an important way of enhancing clavulanic acid titers. It was also possible to show that clavulanic acid acts as an inhibitor of its own synthesis.

Actividad inhibitoria de dihidroxifenil propenona sobre betalactamasas de Enterobacter cloacae: estudio preliminar en el desarrollo de fármacos para enfrentar la resistencia bacteriana / Inhibitory activity of dihydroxy-phenyl-propenone on betalactamase of Enterobacter cloacae : Preliminary study for drug development to overcome bacterial resistance

Introducción . Los microorganismos patógenos como Enterobacter cloacae producen betalactamasas que les confieren resistencia frente a los antibióticos betalactámicos; se ha identificado, además, la actividad limitada de los inhibidores enzimáticos, de modo que la única posibilidad de enfrentar la resistencia es el diseño de nuevos fármacos y su uso racional. Objetivo. Evaluar el efecto de la chalcona dihidroxifenil propenona sobre un aislamiento clínico de E. cloacae y sobre la betalactamasa aislada a partir de este microorganismo resistente como un aporte en la búsqueda de compuestos inhibidores de las betalactamasas. Materiales y métodos. Se sintetizó la chalcona dihidroxifenil propenona y se evaluó su efecto sobre el aislamiento clínico de E. cloacae para determinar la concentración inhibitoria mínima mediante el método de microdilución en caldo y con la betalactamasa purificada mediante cromatografía de afinidad se realizaron estudios espectrofotométricos de cinética enzimática. Resultados. La concentración inhibitoria mínima de la dihidroxifenil propenona sobre E. cloacae fue de 35 µg/ml; el porcentaje de recuperación de la betalactamasa a partir del microorganismo fue de 31,75 %; en el estudio cinético se evidenció actividad inhibitoria de acuerdo con los parámetros cinéticos de V max =1,7 x 10 -3 µM/minuto y K M´ =2330 µM. Conclusión. La chalcona dihidroxifenil propenona ejerce su actividad inhibitoria por medio de la interacción con la betalactamasa y, de esta manera, protege la integridad estructural de los antibióticos betalactámicos; dicho efecto sinérgico la convierte en un compuesto promisorio en la búsqueda de alternativas para enfrentar la resistencia bacteriana.

Introduction: Enterobacter cloacae is a pathogenic microorganism with the ability to produce betalactamase enzymes, which makes them resistant to betalactamic antibiotics. Additionally, the limited activity of enzymatic inhibitors has been identified, and, therefore, the design of new drugs and the promotion of their rational use are the only possibilities to overcome this problem. Objective: The aim of this research was to evaluate the effect of dihydroxy-phenyl-propenone on a clinical isolate of E. cloacae , as well as its activity on a betalactamase isolated from this resistant microorganism in order to contribute to the search for new betalactamase inhibitors. Materials and methods: Dihydroxy-phenyl-propenone chalcone was synthesized and evaluated on a clinical isolate of E. cloacae to determine the minimum inhibitory concentration by broth microdilution; once the betalactamase enzyme was purified by affinity chromatography, a spectrophotometric analysis was done to evaluate its kinetic activity. Results: The minimum inhibitory concentration value of dihydroxy-phenyl-propenone on E. cloacae was 35 µg/ml; the recovery percentage of the betalactamase from the microorganism was 31.75% and the kinetic parameters were V max =1.7 x 10 -3 µM/min and K M = 2330 µM, which show an important inhibitory activity. Conclusion: Dihydroxy-phenyl-propenone has shown inhibitory activity on betalactamase enzymes and the ability to protect the chemical integrity of betalactamic antibiotics; this synergistic effect turns it into a promising compound in the search for new alternatives to overcome bacterial resistance.

Mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii and the application of a combination of drugs in vitro / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii (CRAB) in burn patients and the antimicrobial activity of a combination of drugs against this bacteria in vitro.</p><p><b>METHODS</b>A total of 135 strains of Acinetobacter baumannii (AB) from wound excretion, sputum, and venous catheter wall of patients hospitalized in our department from January 2011 to July 2013 were collected individually. Drug resistance of 135 strains of AB to 12 antibiotics commonly-used in clinic was detected using K-B paper diffusion method. Among the CRAB strains, double-disk synergy test was used to screen metallo-β-lactamase (MBL)-producing strains, and the drug resistance rates between MBL-producing strains and non-MBL-producing strains were compared. Minimal inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of cefoperazone/sulbactam, imipenem, cefepime, ampicillin/sulbactam, and amikacin used alone against MBL-producing CRAB were determined by broth microdilution method. MIC, MIC50, and MIC90 of amikacin respectively combined with imipenem, cefoperazone/sulbactam, cefepime, or ampicillin/sulbactam against MBL-producing CRAB were determined by checkerboard method with diluted agar. Fractional inhibitory concentration (FIC) index was calculated to determine the antibacterial effect of each combination of two antibiotics. Synergy with FIC lower than or equal to 0.5, or additivity with FIC higher than 0.5 and lower than or equal to 1.0 was regarded as effective, and indifference with FIC higher than 1.0 and lower than or equal to 2.0 or antagonism with FIC higher than 2.0 was regarded as ineffective. The effective rate was calculated. Data were processed with Chi-square test.</p><p><b>RESULTS</b>The resistant rates of the 135 strains of AB to imipenem, meropenem, and ceftazidime were high, and those of piperacillin/tazobactam and ampicillin/sulbactam were low. A total of 120 strains of CRAB was screened, accounting for 88.89%, among which the MBL-producing strains accounted for 78.33% (94/120). The resistant rates of MBL-producing strains to piperacillin/tazobactam, imipenem, meropenem, piperacillin, and cefepime were respectively 59.5%, 87.2%, 93.5%, 87.0%, 86.0%, and they were significantly higher than those of non-MBL-producing strains (respectively 43.0%, 81.3%, 87.5%, 78.4%, 64.0%, with χ(2) values from 4.571 to 8.260, P < 0.05 or P < 0.01). Among the inhibition concentrations of each of the 5 antibiotics used alone against MBL-producing strains, MIC, MIC50, and MIC90 of ampicillin/sulbactam were the lowest, respectively 4.00, 16, 64 µg/mL, while those of cefepime were high, respectively 32.00, 128, 512 µg/mL. MIC, MIC50, and MIC90 of amikacin combined with each of the other 4 antibiotics were decreased from 50.00% to 98.44% as compared with that of single administration of each antibiotic. Among the 94 strains of MBL-producing CRAB, the synergic, additive, indifferent, and antagonistic effects were respectively observed in 40, 33, 6, and 15 strains applied with combination of amikacin and ampicillin/sulbactam; 42, 30, 5, 17 strains applied with combination of amikacin and cefoperazone/sulbactam; 38, 15, 19, 22 strains applied with combination of amikacin and cefepime; 34, 2, 37, 21 strains applied with combination of amikacin and imipenem, among which the antibacterial effective rates decreased successively, respectively 77.7%, 76.6%, 56.4%, and 38.3%. The former two rates were respectively significantly higher than the latter two rates (with χ(2) values from 8.618 to 29.889, P values below 0.01).</p><p><b>CONCLUSIONS</b>Production of MBL is the main mechanism of resistance of the CRAB isolated from burn patients hospitalized in our department against carbapenems in about 3 years. The antibacterial effects of amikacin combined with each of the former-mentioned 4 agents are better than those of each of the five antibiotics used singly, and the effects are particularly obvious when combining amikacin with compound agent containing enzyme inhibitors.</p>

Recent progress in development of antibiotics against Gram-negative bacteria / 药学学报

Multidrug-resistant (MDR) bacterial infections, especially those caused by Gram-negative pathogens, have emerged to be one of the world's greatest health threats. However, not only have recent decades shown a steady decline in the number of approved antimicrobial agents but a disappointing discovery also void. The development of novel antibiotics to treat MDR Gram-negative bacteria has been stagnated over the last half century. Though few compounds have shown activities in vitro, in animal models or even in clinical studies, the global antibiotic pipeline is not encouraging. There are a plethora of unexpected challenges that may arise and cannot always be solved to cause promising drugs to fail. This review intends to summarize recent research and development activities to meet the inevitable challenge in restricting the proliferation of MDR Gram-negative bacteria, with focus on compounds that have entered into clinical development stage. In addition to new analogues of existing antibiotic molecules, attention is also directed to alternative strategies to develop antibacterial agents with novel mechanisms of action.

Diversidad de ß-lactamasas en aislamientos clínicos de enterobacterias / ß-lactamases diversity in clinical isolates of enterobacterias / Diversidade de ß-lactamases em isolamentos clinicos de enterobactérias

La rápida emergencia de resistencia a antimicrobianos debida a la presencia de b-lactamasas de espectro extendido (BLEE) tiene un impacto significativo en la salud pública. Las BLEEs son enzimas producidas por bacilos gramnegativos y confieren resistencia a las penicilinas, a todas las cefalosporinas y al aztreonam, pero no a los carbapenemes ni a las cefamicinas y la mayoría son inhibidas por el ácido clavulánico. El objetivo de este trabajo fue evaluar la resistencia a antibióticos b-lactámicos en aislamientos de Klebsiella pneumoniae, Escherichia coli y Proteus mirabilis y caracterizar las b-lactamasas responsables de dicha resistencia. Se analizaron 2.030 aislamientos (362 Klebsiella pneumoniae, 1.250 Escherichia coli y 175 Proteus mirabilis) provenientes de diferentes materiales clínicos de pacientes que concurrieron al Hospital Provincial del Centenario de la ciudad de Rosario (Santa Fe) durante el período 2008-2009. Los ensayos de sensibilidad antibiótica se realizaron de acuerdo con las recomendaciones del Clinical and Laboratory Standard Institute. Se confirmó la presencia de los genes codificantes de BLEE blaTEM, blaSHV, blaCTX-M y blaPER mediante la reacción en cadena de la polimerasa (PCR) utilizando cebadores específicos. Los aislados fueron caracterizados fenotípicamente como productores de BLEE y demostraron poseer varios genes bla. Se detectaron tres diferentes b-lactamasas BLEE derivadas de SHV, TEM y CTX-M y se demostró que pueden coexistir dos o más de estos genes en una misma bacteria.

The rapid emergence of antimicrobial resistance due to extended spectrum b-lactamases (ESBL) has a significant impact on public health. ESBL, produced by gram-negative bacilli, are enzymes that confer resistance to penicillins, cephalosporins and aztreonam, but not to carbapenems or cephamycins, and are usually inhibited by clavulanic acid. The aim of this study was to evaluate b-lactam resistance within isolates of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis and to characterize the b-lactamases responsible for this resistance. A total of 2,030 strains (362 Klebsiella pneumoniae, 1,250 Escherichia coli, and 175 Proteus mirabilis) isolated from patients at Hospital Provincial del Centenario in Rosario-Santa Fe were analyzed from 2008 to 2009. Antibiotic sensitivity tests were performed according to Clinical and Laboratory Standard Institute recommendations. Molecular detection of ESBL-related bla genes, including blaTEM, blaSHV, blaCTX-M and blaPER was performed by polymerase chain reaction (PCR) using specific primers. The strains were phenotipically confirmed as ESBL producers and the isolates carried several bla genes. Three different b-lactamases were detected: SHV-related, TEM-related and CTX-M-related, showing that two or more genes may coexist in the same bacterium.

A rápida emergência de resistência a antimicrobianos devida à presença de b lactamases de espectro estendido (BLEE) tem um impacto significativo na saúde pública. As BLEEs são enzimas produzidas por bacilos gram-negativos e conferem resistência às penicilinas, a todas as cefalosporinas e ao aztreonam, mas não aos carbapenêmicos nem às cefamicinas e a maioria são inibidas pelo ácido clavulânico. O objetivo deste trabalho foi avaliar a resistência a antibióticos b-lactâmicos em isolamentos de Klebsiella pneumoniae, Escherichia coli e Proteus mirabilis e caracterizar as b-lactamases responsáveis por tal resistência. Foram analisados 2.030 isolamentos (362 Klebsiella pneumoniae, 1.250 Escherichia coli e 175 Proteus mirabilis) provenientes de diferentes materiais clínicos de pacientes que foram ao Hospital Provincial do Centenário da cidade de Rosario (Santa Fe) durante o período 2008-2009. Os ensaios de sensibilidade antibiótica foram realizados de acordo com as recomendações do Clinical and Laboratory Standard Institute. Confirmou-se a presença dos genes codificantes de BLEE blaTEM, blaSHV, blaCTX-M e blaPER mediante a reação em cadeia da polimerase (PCR) utilizando cevadores específicos. Os isolados foram caracterizados fenotipicamente como produtores de BLEE e demonstraram possuir vários genes bla. Foram detectadas três diferentes b-lactamases derivadas de SHV, TEM e CTX-M e se demonstrou que podem coexistir dois ou mais destes genes numa mesma bactéria.

Interacción entre meropenem y ácido valproico: A propósito de dos casos pediátricos / Pharmacological interaction between meropenem and valproic acid: a report of two cases

The pharmacological interaction between meropenem and valproic acid is potentially serious, especially in critically ill patients, resulting in low plasmatic levels of the anticonvulsant. However, to our knowledge, this interaction between meropenem and reduced valproic acid plasma levels has not been reported in the pediatric chilean population. We present two clinical cases of chilean children, thus reporting that this interaction is present in our population, with an aim at educating physicians about the possibility of such interaction.

La interacción farmacológica entre meropenem y ácido valproico en pacientes críticos es potencialmente grave, reflejándose en una disminución del fármaco anticonvulsivante mayor a 70%. Se desconocen estrategias efectivas que la reviertan. Esta interacción no ha sido descrita en pacientes chilenos pediátricos. A través de la presentación de dos casos clínicos alertamos que la interacción puede suceder en nuestra población y educamos a los pediatras que indican meropenem sobre la posibilidad de este evento.

Study on water of crystallization in tazobactam / 药学学报

<p><b>AIM</b>To investigate whether tazobctam has crystallization water.</p><p><b>METHODS</b>In order to establish a method for water content determination in tazobctam, many methods including Karl Fischer titration, weight loss on drying, TGA, DSC and X-ray diffraction experiment of an orthorhombic form were studied.</p><p><b>RESULTS</b>The water content of the same batch tazobactam determined by different mthods was different.</p><p><b>CONCLUSION</b>The results showed that one mole tazobatam contains half mole water of crystallization and the strength of attraction between tazobatam molecule and water molecule is rather strong.</p>