Rev Esp Quimioter 2015:28(Suppl. 1):16-18

Usefulness of PK/PD parameters of antimicrobials in the treatment of complex and extremely-resistant infections     

                        
JUAN PABLO HORCAJADA              

Complex or difficult to treat infections should benefit from antimicrobial PK/PD data in each specific situation. In the case of multidrug resistant gram negative infections the optimized use of colistin needs the using of PK/PD indexes. Likewise, in infections of inaccessible sources, PK/PD concepts play a key role in choosing the best antimicrobial and dosage. An example would be the potential role of linezolid in CNS infections. Among fungal infections, symptomatic candiduria by fluconazole-resistant strains are a therapeutic challenge. In this context micafungin could be a good alternative, again based on PK/PD concepts.

Rev Esp Quimioter 2015:28(Suppl. 1):16-18 [pdf]

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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):103-117

Delphi-based study and analysis of key risk factors for invasive fungal infection in haematological patients                     

LOURDES VÁZQUEZ, MIGUEL SALAVERT, JORGE GAYOSO, MANUEL LIZASOAÍN, ISABEL RUIZ CAMPS, NICOLÁS DI BENEDETTO, ON BEHALF OF THE STUDY GROUP OF RISK FACTORS FOR IFI USING THE DELPHI METHOD           

Introduction. Mortality caused by invasive fungal infections due to filamentous fungi (IFI-FF) is high. Predisposing factors to IFI-FF are multiple and should be stratified. The objective of this study was to identify key risk factors for IFI-FF in onco-haematological patients in different clinical settings.
Methods. Prospective national Delphi study. Risk factors for IFI-FF in patients with onco-haematological diseases were identified by a systematic review of the literature. An anonymous survey was sent by e-mail to a panel of experts. A key risk factor was defined when at least 70% of the surveyed participants assigned a “maximal” or “high” risk.
Results. In allogenic stem cell transplantation, 18 of the 42 risk factors analyzed were classified as key risk factors, including neutropenia, previous IFI-FF, grade III/IV acute or extensive chronic graft-versus-host disease (GVHD), umbilical cord blood transplantation, HLA mismatching transplantation, graft failure, absence of HEPA filters, absence of laminar air  flow, diagnosis of acute myeloid leukaemia, haploidentical transplantation, anti-TNF-α drugs, alemtuzumab, anti-thymocyte globulin, immunosuppressive prophylaxis for GVHD, lymphocytopenia, cytomegalovirus infection, and proximity to construction areas. In acute leukaemia/myelodysplastic syndrome (AL/MDS), 7 of 25 risk factors were defined as key risk factors, including neutropenia, consolidation therapy without response, induction therapy, antifungal prophylaxis with azoles, proximity to construction areas, and absence of HEPA filters. In lymphoma/multiple myeloma (MM), the five key risk factors among 21 analyzed were use of steroids, neutropenia, progressive disease, anti-CD52 therapies, and proximity to construction areas.
Conclusions. The Delphi method was useful for the classification and stratification of risk factors for IFI-FF in patients with onco-haematological diseases. Identifying key risk factors will contribute to a better management of IFI-FF in this group of patients at high or changing risk.

Rev Esp Quimioter 2017; 30(2):103-117  [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.

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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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