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.

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Rev Esp Quimioter 2015:28(3):132-138

A practice-based observational study on the use of micafungin in Surgical Critical Care Units                                 
 


EMILIO MASEDA, CARLOS A. GARCÍA-BERNEDO, ISABEL FRÍAS, JOSÉ-ALEJANDRO NAVARRO, JESÚS RICO, REYES IRANZO, JUAN-JOSÉ GRANIZO, MARÍA-JOSÉ VILLAGRÁN, ENRIC SAMSÓ, FERNANDO GILSANZ ON BEHALF OF THE MYCREA STUDY GROUP              

 

Introduction. Echinocandins are first-line therapy in critically ill patients with invasive Candida infection (ICI). This study describes our experience with micafungin at Surgical Critical Care Units (SCCUs).
Methods. A multicenter, observational, retrospective study was performed (12 SCCUs) by reviewing all adult patients receiving 100 mg/24h micafungin for ≥72h during ad-mission (April 2011-July 2013). Patients were divided by ICI category (possible, probable + proven), 24h-SOFA (<7, ≥7) and outcome.
Results. 72 patients were included (29 possible, 13 probable, 30 proven ICI). Forty patients (55.6%) presented SOFA ≥7. Up to 78.0% patients were admitted after urgent surgery (64.3% with SOFA <7 vs. 90.3% with SOFA ≥7, p=0.016), and 84.7% presented septic shock. In 66.7% the site of infection was intraabdominal. Forty-nine isolates were recovered (51.0% C. albicans). Treatment was empirical (59.7%), microbiologically directed (19.4%), rescue therapy (15.3%), or anticipated therapy and prophylaxis (2.8% each). Empirical treatment was more frequent (p<0.001) in possible versus probable + proven ICI (86.2% vs. 41.9%). Treatment (median) was longer (p=0.002) in probable + proven versus possible ICI (13.0 vs. 8.0 days). Favorable response was 86.1%, without differences by group. Age, blood Candida isolation, rescue therapy, final MELD value and %MELD variation were significantly higher in patients with non-favorable response. In the multivariate analysis (R2=0.246, p<0.001) non-favorable response was associated with positive %MELD variations (OR=15.445, 95%CI= 2.529-94.308, p=0.003) and blood Candida isolation (OR=11.409, 95%CI=1.843-70.634, p=0.009).
Conclusion. High favorable response was obtained, with blood Candida isolation associated with non-favorable response, in this series with high percentage of patients with intraabdominal ICI, septic shock and microbiological criteria for ICI.

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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.

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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.

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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.

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Rev Esp Quimioter 2016, 29(4):206-213

Changes in the epidemiology of Clostridium difficile infection during 2005-2014 in Salamanca, Spain                    

OLAIA CORES-CALVO, ENRIQUE GARCÍA-SÁNCHEZ, LUIS FÉLIX VALERO-JUAN, JOSÉ ELÍAS GARCÍA-SÁNCHEZ, MARÍA INMACULADA GARCÍA-GARCÍA          

Background. To know the most relevant epidemiological features of Clostridium difficile infection (CDI) between 2005- 2014 in the province of Salamanca (Spain).
Methods. Descriptive cross-sectional study carried out through review of the clinical microbiologic records at Complejo Asistencial Universitario de Salamanca. Detection was performed according to standard methodology.
Results. 2.6% of stool samples analyzed for detection of C. difficile toxins (9,103) were positive. The average prevalence was 6.8 cases per 100,000 people per year. The mean age was 65 ± 21.4 years and the median 70 years. 59% of cases occurred in patients over 64 years, with an average prevalence of 16.5 (4 times higher than the 15-64 group). Most cases (86.4%) occurred in hospitalized patients, and the group of over 64 had the highest percentage of hospital CDI, with 55%.
Conclusions. A significant increase in the number of requests and in the prevalence of CDI over the decade studied is observed, and prevalence rates were significantly lower than those of other studies. The percentage of CDI increased significantly in both inpatient and community. Age and hospitaliza-tion were risk factors for developing CDI. After the introduc-ion of a molecular detection technique in 2014, the prevalence increased, being 2.5 times higher than 2013.

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Rev Esp Quimioter 2016, 29(Suppl. 1):35-38

Multidrug-resistant tuberculosis: current epidemiology, therapeutic regimens, new drugs                     

CRISTINA GÓMEZ-AYERBE, MARÍA JESÚS VIVANCOS, SANTIAGO MORENO          

Multidrug and extensively resistant tuberculosis are especially severe forms of the disease for which no efficacious therapy exists in many cases. All the countries in the world have registered cases, although most of them are diagnosed in resource-limited countries from Asia, Africa and South America. For adequate treatment, first- and second-line antituberculosis drugs have to be judiciously used, but the development of new drugs with full activity, good tolerability and little toxicity is urgently needed. There are some drugs in development, some of which are already available through expanded-access programs.

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Rev Esp Quimioter 2016, 29(6):318-327

Key issues in the infected patient care in the Emergency Department                     

FLAVIA CHIARELLA, JUAN GONZÁLEZ-DEL CASTILLO, FRANCISCO JAVIER CANDEL, ERIC JORGE GARCÍA- LAMBERECHTS, MARÍA JOSÉ NÚÑEZ-ORANTOS, FRANCISCO JAVIER MARTÍN-SÁNCHEZ REPRESENTING THE INFECTIOUS DISEASE GROUP OF SPANISH EMERGENCY MEDICINE SOCIETY          

Objective. To develop a set of recommendations, by consensus of Emergency Medicine experts, on key aspects related to the care of adult patients with acute infection attended in Spanish emergency departments (ED).    
Methodology. The study was divided into three phases: 1) To design a questionnaire by a coordinating group; 2) To conduct a survey in ED physicians in order to know their opinion on the issues raised by the coordinating group; 3) To develop a number of recommendations based on the responses to the questionnaire and their subsequent discussion.
Results. A group of 28 experts from different Spanish ED, as well as 5 members of the coordinating group, with knowledge and experience in the management of infectious diseases in ED, conducted a round of voting to a questionnaire of 18 issues grouped into three sections: 1) identification and stratification of the severity; 2) diagnosis and treatment; 3) management.   
Conclusions. A monitoring system and proper training of the entire healthcare team are required, as well as extensive knowledge on these issues, to ensure adequate and effective care for these patients. It is essential to educate and train all health staff, especially in the ED, because it is the initial point of contact for most patients with an infection. The experts established proposals based on survey questions and the discussion.

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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.

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