Rev Esp Quimioter 2015:28(6):275-281

Liposomal formulations of amphotericin B: differences according to the scientific evidence     

                        
JOSÉ RAMÓN AZANZA, BELÉN SÁDABA, JOANA REIS              

This article presents an overview of the characteristics of liposomes as drug carriers, particularly in relation to liposomal formulations of amphotericin B. General features regarding structure, liposome-cell interactions, stability, encapsulation of active substances and elimination of liposomes are described. Up to the present time extensive efforts to produce similar or bioequivalent products of amphotericin B formulations, in particular in the case of liposomal amphotericin B, have been unsuccessful in spite of having a very similar composition and even an apparently identical manufacturing process. Guidelines for the development of generic liposomal formulations developed by the FDA and EMA are also summarized. Based on the available evidence of the composition of liposomes, any differences in the manufacturing process even if the same lipid composition is used may result in different final products. Therefore, it seems unreasonable to infer that all amphotericin B liposomal formulations are equal in efficacy and safety.

Rev Esp Quimioter 2015;28(6):275-281 [pdf]

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Rev Esp Quimioter 2016, 29(2):99-104

Development of a web application for recording bacterial etiologic agents and their antimicrobial susceptibility to improve the treatment of urinary tract infections and monitor resistance to antibiotics     

                        

FRANCISCO GÓMEZ-PALOMO, ANTONIO SORLÓZANO-PUERTO, CONSUELO MIRANDA-CASAS, JOSÉ MARÍA RODRÍGUEZ-RODRÍGUEZ, JOSÉ MARÍA NAVARRO-MARÍ, JOSÉ GUTIÉRREZ-FERNÁNDEZ             

Introduction. We describe the development of a web platform that provides an updated record of the etiology and antimicrobial susceptibility of the different microorganisms responsible for urinary tract infections.
Material and Methods. The MicrobDinamyc system (Francisco Soria Melguizo, SA, Madrid, Spain) is employed for the management of information derived from the urine culture results. The web application database automatically gathers the results of urine cultures conducted in the laboratory.
Results. The user can consult the distribution of bacterial etiologies and antimicrobial susceptibilities in the different clinical settings during a specific time window.
Conclusions. Using susceptibility data obtained in previous studies and stored on the web platform, it is possible to deduce the clinical activity of a given antibiotic in a specific setting.

Rev Esp Quimioter 2016; 29(2):99-104 [pdf]

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Rev Esp Quimioter 2016, 29(4):202-205

Antimicrobial susceptibility of Gram-negative bacilli of community acquired intra-abdominal infections in a hospital at Buenos Aires, Argentina                     

LAURA MORGANTI, EZEQUIEL CÓRDOVA, ELSA CASSINI, NORA GÓMEZ, LAURA LÓPEZ MORAL, MARCELA BADÍA, CLAUDIA RODRÍGUEZ          

Introduction. Community acquired complicated intra-abdominal infections (cIAI) are a common condition. Few data are available about the level of antimicrobial resistance of Gram-negative bacteria isolated from community acquired cIAIs in Argentina.
Methods. Retrospective-prospective observational study (March 2010 to February 2012). Gram-negative bacteria antimicrobial susceptibility of isolates from community acquired cIAIs were evaluated.
Results. During this period, a total of 85 patients were included and 138 pathogens were collected. Male sex: 58%. Median age: 33. Monomicrobial cultures were obtained in 49% of the cases. Ninety (65%) corresponded to Gram-negative organisms, and 48 (38%) to Gram-positive cocci. Gram-negative organisms most frequently observed were: Escherichia coli 76%, Klebsiella pneumoniae 8%, Pseudomonas aeruginosa 7% and Enterobacter spp. 6%. E. coli and K. pneumoniae showed a high percentage of strains resistance to ciprofloxacin of 37% and 29%, respectively. Similarly, resistance to ampicillin/sulbactam was observed in a 16% of the E. coli isolates. The prevalence of multiresistant Gram-negative organisms was 38%.
Conclusions. A high level of resistance to antimicrobials was observed in community acquired cIAIs, mainly to ciprofloxacin and ampicillin/sulbactam two of the most used antimicrobial for empirically treatment of cIAIs in our country. In addition a significant proportion of multiresistant Gram-negative organisms were identified.

Rev Esp Quimioter 2016; 29(4):202-205 [pdf]

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Rev Esp Quimioter 2016, 29(Suppl. 1):31-34

Approach to directed therapy after knowledge of the isolate: carbapenemase-producing Enterobacteriaceae, multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii                     

JOSÉ ANTONIO MARTÍNEZ          

Directed treatment of infections due to multidrug-resistant Gram-negative bacilli is a difficult task, since it requires the use of a limited number of antibiotics that are often more toxic and possibly less efficacious than β-lactams and fluoroquinolones. Furthermore, there are very few controlled trials informing on the relative efficacy of different therapeutic strategies.  As a general rule, it is recommended to use at least two active drugs or a combination with proven synergistic activity in vitro, because several observational studies have associated this practice with better outcomes and as a measure to potentially curb the emergence of further resistance. It is already available a new cephalosporin active against most strains of Pseudomonas aeruginosa resistant to ceftazidime due to derepression of ampC and in the near future an effective inhibitor of class A, class C and OXA-48 will be available which combined with ceftazidime is expected to mean a significant addition to the armamentarium against Gram-negative bacilli with these resistance determinants.

Rev Esp Quimioter 2016; 29(Suppl. 1):31-34 [pdf]

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Rev Esp Quimioter 2016, 29(6):308-317

Darunavir/cobicistat monotherapy. Experience in a tertiary hospital                     

LUCIA YUNQUERA-ROMERO, ROCÍO ASENSI-DÍEZ, JUAN CARLOS DEL RIO-VALENCIA, ISABEL MUÑOZ-CASTILLO, MANUEL ÁNGEL CASTAÑO-CARRACEDO          

Introduction. Ritonavir-boosted protease inhibitor (IP/r) monotherapy: darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pretreated patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r monotherapy, according to GESIDA guidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/ mL for at least 6 months and absence of protease inhibitors mutations or previous virologic failures to IP/r. Currently, there are no studies that evaluate the efficacy and safety of darunavir/cobicistat (DRV/COBI) monotherapy.
Methods. This prospective study analyzed pretreated HIV patients with DRV/r monotherapy that were switched to DRV/COBI monotherapy. The aim of the study is to describe the effectiveness and safety of the DRV/COBI monotherapy.
Results. Seventy-eight patients were evaluated. Patients had a median of 31.29 months of DRV/r monotherapy before DRV/COBI monotherapy. Nine of the 78 patients developed “blips” (plasma viral load: 50-200 copies/ml) and four patients had plasma viral load ≥200 copies/mL. An 83.3% (65/78) of the patients remained with undetectable plasma viral load. As for safety, there were no significant differences in lipid profile, liver function (transaminases) and renal function between DRV/r and DRV/COBI monotherapy.
Conclusions. DRV/COBI monotherapy seems to be effective and safe (lipid profile, liver and kidney function). However, it will be necessary to design specific studies comparing DRV/r vs DRV/COBI monotherapy to confirm these results.

Rev Esp Quimioter 2016; 29(6):308-317  [pdf]

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Rev Esp Quimioter 2017, 30(2):84-89

Antibacterial effect of sevoflurane and isoflurane                     

MARÍA MARTÍNEZ-SERRANO, MANUEL GERÓNIMO-PARDO, ÁNGEL MARTÍNEZ-MONSALVE, MARÍA DOLORES CRESPO-SÁNCHEZ           

Introduction. Multidrug resistant bacteria are increasing worldwide and therapeutic options are limited. Some anaesthetics have shown antibacterial activity before. In this study, we have investigated the antibacterial effect of the halogenated anaesthetic agents sevoflurane and isoflurane against a range of resistant pathogens.
Methods. Two experiments were conducted. In the first, bacterial suspensions of both ATCC and resistant strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were exposed to liquid sevoflurane and isoflurane during 15, 30 and 60 minutes. In the second experiment clinical resistant strains of E. coli, Klebsiella pneumoniae, Enterobacter cloacae, P. aeruginosa, Acinetobacter baumannii, S. aureus, and Enterococcus faecium were studied. Previously inoculated agar plates were irrigated with the halogenated anaesthetic agents and these were left to evaporate before the plates were incubated. In both experiments colony forming units were counted in resultant plates.
Results. In the first experiment, isoflurane showed faster and higher antimicrobial effect than sevoflurane against all the strains studied. Gram-negative organisms were more susceptible. In the second experiment, E. faecium was found to be resistant to both halogenated agents; only isoflurane showed statistically significant activity against the rest of the strains studied.
Conclusions. Both halogenated agents, but particularly isoflurane, showed in vitro antibacterial activity against pathogens resistant to conventional antibiotics. Further investigation is required to determine whether or not they also exhibit this property in vivo. This might then allow these agents to be considered as rescue treatment against multidrug resistant patho-gens, including a topical use in infected wounds.

Rev Esp Quimioter 2017; 30(2):84-89  [pdf]

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Rev Esp Quimioter 2015:28(3):139-144

Role of double strand DNA break repair for quino-lone sensitivity in Escherichia coli: therapeutic implications                                 
 


ROCÍO GONZÁLEZ-SOLTERO, ANA GARCÍA-CAÑAS, ROSA B. MOHEDANO, BELÉN MENDOZA-CHAMIZO, EMILIA BOTELLO              

 

Introduction. Quinolones are one of the types of antibiotics with higher resistance rates in the last years. At molecular level, quinolones block  type II topoisomerases producing double strand breaks (DSBs). These DSBs could play a double role, as inductors of the  quinolone bactericidal effects but also as mediators of the resistance and tolerance mechanisms.
Material and methods. In this work we have studied the molecular pathways responsible for DSBs repair in the quinolone susceptibility: the stalled replication fork reversal (recombination-dependent) (RFR), the SOS response induction, the translesional DNA synthesis (TLS) and the nucleotide excision repair mechanisms (NER). For this reason, at the European University in Madrid, we analysed the minimal inhibitory concentration (MIC) to three different quinolones in Escherichia coli mutant strains coming from different type culture collections.
Results. recA, recBC, priA and lexA mutants showed a significant reduction on the MIC values for all quinolones tested. No significant changes were observed on mutant strains for TLS and NER.
Discussion. These data indicate that in the presence of quinolones, RFR mechanisms and the SOS response could be involved in the quinolone susceptibility.

Rev Esp Quimioter 2015:28(3):139-144 [pdf]

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Rev Esp Quimioter 2015:28(Suppl. 1):19-24

Inhaled medication and inhalation devices for lung disease     

                        
AMPARO SOLÉ, ROSA Mª GIRÓN              

Nebulized antibiotic therapy is an attractive therapeutic option given the high concentration obtained from the drug at the site of infection, minimizing the adverse effects and possible drug interactions. Inhalation of drugs as treatment of cystic fibrosis (CF) related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. Other limited areas of experience in this field are lung transplant recipients, immunosuppressed patients, bronchiectasis and ventilated patients. In this review document we analyse the current status of the inhaled medications, their modes of administration and indications and their results as well as side effects. Specifically we address antibiotics, and additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Several factors contribute to a highly variable pulmonary drug deposition as the devices, the physical properties of the administered antimicrobial agent, the type of respiratory disease and the inhalation technique. Despite many clinicians have obtained a valuable experience from the aerosolized administration of antimicrobials and persuaded of their efficacy and safety. However, RCTs out of CF are needed to answer important clinical questions, such as what is the appropriate dose, the optimal delivery device, the optimal way of drug administration, as well as the exact therapeutic role and pharmacokinetic profile of aerosolized drug.

Rev Esp Quimioter 2015:28(Suppl. 1):19-24 [pdf]

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Rev Esp Quimioter 2015:28(6):282-288

Potential antimicrobial drug interactions in clinical practice: consequences of polypharmacy and multidrug resistance     

                        
CRISTINA MARTÍNEZ-MÚGICA              

Background. Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the antiinfective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure.
Methods. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked.
Results. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin.
Conclusions. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.

Rev Esp Quimioter 2015;28(6):282-288 [pdf]

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Rev Esp Quimioter 2016, 29(2):86-90

Surveillance of antimicrobial susceptibility of Escherichia coli producing urinary tract infections in Galicia (Spain)     

                        

MERCEDES TREVIÑO, ISABEL LOSADA, BEGOÑA FERNÁNDEZ-PÉREZ, AMPARO COIRA, MARÍA F. PEÑA-RODRÍGUEZ, XURXO HERVADA Y GRUPO DE ESTUDIO DE LA SOGAMIC PARA EL ESTUDIO DE RESISTENCIAS EN GALICIA             


Introduction. Escherichia coli is the microorganism responsible for most of the community-acquired urinary tract infections (UTI). Our purpose was to determine the susceptibility of E. coli associated with UTI in Galicia and consider the most appropriate antibiotics for empirical treatment.
Methods. Retrospective study during the period 2011- 2012 of the isolation of E. coli in urine samples from almost all the Galician population. Demographic variables, minimum inhibitory concentration, and reading data were collected: amoxicillin-clavulanate, cefotaxime, gentamicin, amikacin, ciprofloxacin, cotrimoxazole, nitrofurantoin and fosfomycin. The identification and susceptibility studies were mainly conducted by automated systems. The interpretation of the results was performed according to CLSI criteria.
Results. During the study period 55,046 E. coli were isolated in UTI. The percentages of resistance were: cotrimoxazole, 30%; ciprofloxacin, 33%; amoxicillin-clavulanate, 23% and 10% for 3rd generation cephalosporins. Fosfomycin and nitrofurantoin showed the highest activity with more than 96% of susceptibility in our study. The linear trend of resistance regarding age was statistically significant (p <0.0001) as it was regarding males (p <0.00001) for all antibiotics.
Conclusions. In Galicia, the most active antibiotics against E. coli associated with UTI are fosfomycin and nitrofurantoin so they should be considered as empirical treatment of choice by the community-acquired UTI not complicated by E. coli.

Rev Esp Quimioter 2016; 29(2):86-90 [pdf]

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